Abstract and case study poster sessions will be conducted during the 2011 College of American Pathologists Annual Meeting, which is scheduled for September 11 to 14, 2011. The meeting will take place at the Gaylord Texan, Grapevine, Texas. The poster sessions will occur in the Connection Café and Exhibits Hall. Specific dates and times for each poster session are listed below. Also shown below each poster session listing are the subject areas that will be presented during that session.

Melanoma of the anus is uncommon. We report a case of melanoma of the anus that presented in a 71-year-old woman with 5-year history of rectal mass, which was clinically diagnosed as hemorrhoids. During this time, the patient had intermittent mild hematochezia leading to chronic normocytic-normochromic anemia. The patient consulted to the emergency department owing to a 3-day history of moderate hematochezia. A polypoid formation at the distal rectum was felt on rectal examination. The patient underwent resection of the sigmoid and rectum. This case broadens the differential diagnosis of hematochezia, and nodular lesions of the anal region mimicking hemorrhoids, to include anorectal melanoma. Grossly, the specimen consisted of a 2.5 × 1.5 × 1.2-cm brown nodule and a 6 × 2.5 × 0.4-cm membranous fragment of tissue. The microscopic examination showed anaplastic cells originating in the epithelium of the anus, invading submucosa and lamina propria. Immunohistochemistry was positive for S100, MART1, HMB-45, CD10, CD117, and Ki-67. Lower gastrointestinal bleeding in an elderly patient with chronic anemia is highly suggestive of colon cancer. Spindle cell tumors positive for MART1 are suggestive of melanoma. Melanoma is also known to stain positively for CD117, making gastrointestinal stromal tumor its main differential diagnosis (Figure 1).

Context: Studies have been done on the expression of mucin gene products in various carcinomas (CAs). However, the data are inconsistent and may not be entirely reproducible. In this study, we reevaluate the expression of MUC1, MUC2, MUC4, MUC5AC, and MUC6 in a large series of CAs from various organs, using a single staining system (Ventana XT, Tucson, Arizona).

Design: Immunohistochemical evaluation of the expression of MUC1, MUC2, MUC4, MUC5AC, and MUC6 in 838 cases of CAs from various organs, using tissue microarray sections, were performed. The staining intensity and distribution were recorded.

Results: The positive staining results (%) and the number of cases for each entity (n) are summarized in the Table. MUC1 is expressed in the most CAs and not expressed in hepatocellular CA. MUC2 is expressed in colonic adenocarcinoma (ADC) (55%), with low or no expression in others. MUC4 is expressed in colonic, endocervical ADCs and ovarian serous CA, and is not expressed in breast CA and prostatic ADC. MUC5AC is expressed in pancreatic (67%) and esophageal (43%) ADCs and has low or no expression in others. MUC6 is expressed in esophageal ADC (40%), with low expression (12%–17%) in pancreatic, breast, and endocervical ADC, and nearly no expression in others.

Conclusions: These data provide an important reference for the utilization of mucin gene product markers. There is a tendency for each organ system to express particular mucin gene products; however, a significant overlapping of expression is demonstrated. Therefore, caution should be taken when using these markers in making a diagnosis and differential diagnosis.

Summary of Immunostaining Results

Summary of Immunostaining Results
Summary of Immunostaining Results

Context: When working on tumors of unknown origin, metastatic adenocarcinomas from upper gastrointestinal tract often present a diagnostic challenge owing to their complicated immunostaining profiles and inconsistent data in the literature. In this study, we reevaluate the expression of an extensive panel of biomarkers in esophageal adenocarcinoma (EADC) and gastric adenocarcinoma (GADC), using a single immunostaining system (Ventana XT, Tucson, Arizona).

Design: We immunohistochemically evaluated the expression of (1) epithelial markers; (2) mucin gene products; (3) tumor suppressor genes and transcription factors; and (4) tumor-associated proteins in 30 cases of EADC and 18 cases of GADC on tissue microarray sections. The positive cases (>5% of tumor cells stained) are recorded.

Results: The results (% of positive cases) are summarized in the Table. Both EADC and GADC are positive for CK7. EADCs are positive for CK19 (63%), MUC5AC (43%), and MUC6 (40%), but GADCs are negative for these markers. Most EADCs (73%) are positive for P504S, while only 39% of the GADCs are reactive. Strong nuclear positivity for SALL4 was noted in 1 case of EADC. Nuclear and membranous staining for β-catenin was seen in EADC (13%) and GADC (6%).

Conclusions: These data demonstrate that (1) many tumor/organ-specific markers, including HepPar1, napsin A, P504S, pVHL, can be positive in EADC and GADC; (2) markers for breast carcinoma (ER, PR, GCDFP15, and mammaglobin), TTF-1, RCC, and OCT4 are negative in both; (3) maspin and P504S can be potentially used as diagnostic markers for EADC; and (4) CK19, MUC5AC, and MUC6 may aid in the differential diagnosis of EADC versus GADC.

Summary of Immunostaining Results

Summary of Immunostaining Results
Summary of Immunostaining Results

We present the case of a 50-year-old white man with a history of diabetes mellitus type 1 and recent pancreatorenal transplant. Fourteen years before receiving a transplant he had lived for 1 year in rural Mexico. Two months after surgery, he was seen for nausea, vomiting, and diarrhea. His esophagogastroduodenoscopy and colonoscopy were nondiagnostic. A duodenal biopsy revealed mild duodenitis and edematous changes in the colon. He was readmitted a month later with worsening abdominal pain. Esophagogastroduodenoscopy and colonoscopy were performed, and duodenal and gastric biopsy specimens were submitted for pathologic review (hematoxylin-eosin staining). Subsequently, sputum and stool samples were analyzed with Gram and iodine staining, respectively. Diffuse duodenal mucosal ulcerations with exudates were found during colonoscopy. The duodenal biopsy revealed that the lamina propria was heavily infected with Strongyloides stercoralis larvae and eggs (Figure 2, A). No pathologic change was identified within the gastric fundic mucosa. The sputum (Figure 2, B) and stool (Figure 2, C) examinations revealed S. stercoralis larvae. Strongyloides stercoralis can manifest subclinically in humans for years after the initial infection. In immunosuppressed hosts, such as transplant patients, disseminated infections may occur owing to autoinfection, leading to a hyperinfection syndrome in which larvae increase reproduction in the duodenum and disseminate to the lungs, causing both pulmonary and gastrointestinal symptoms. The incidence of this rare syndrome in transplant patients is not well elucidated. The initial diagnosis is usually made via stool culture. Thus, the initial diagnosis by duodenal biopsy was unusual in our patient.

We report 2 cases of polypoid neural proliferations within the colonic lamina propria, composed entirely of Wagner-Meissner corpuscles, a Schwann cell–derived neurosensory unit typically found in glabrous skin. This morphology has not previously been reported in colonic polyps. Given that Wagner-Meissner corpuscles are not normally found within the gastrointestinal tract and have an unusual morphology, difficulty in characterizing these lesions may occur. Both of our cases occurred in adult males: one was undergoing routine screening colonoscopy and the other presented with blood per rectum. The pathologic lesion in both cases was identical and displayed discrete, compact aggregates of plump cells within the lamina propria, which displayed abundant eosinophilic cytoplasm composed of lamellated fibrillar structures (Figure 3). This unusual morphology caused diagnostic confusion, resulting in consultation referral to our institution. Further investigation revealed that the aggregates displayed strong immunoreactivity for S100 and negativity for CD68 and amyloid stains. No ganglion cells were identified. In both cases these neural proliferations were isolated, and patient follow-up has revealed no additional lesions, recurrence, or clinical concern for an underlying syndrome. We believe that these lesions represent a unique and previously unreported morphologic subset of the “Schwann cell hamartoma” described by Gibson et al. Recognition of Wagner-Meissner corpuscle differentiation allows for appropriate characterization of these lesions and prevents undue concern for a syndromic association or confusion with a granulomatous process.

Context: Ulcerative colitis (UC) predisposes to colorectal carcinoma (CRC). Nondysplastic colonic epithelium in UC colons harboring distant neoplasia has prominent genomic alterations relative to UC colons without neoplasia. In particular, increased chromosomal fluorescence in situ hybridization (FISH) alterations involving p53 and cyclin D1 have been demonstrated in epithelial cells specifically. Corresponding lamina propria cells, however, have not been investigated and form the subject of this report.

Design: A total of 15 fresh, nondysplastic mucosal samples remote from tumor in surgical resections were analyzed from 11 patients with UC and 4 with Crohn disease. Ten had cancer/dysplasia (progressors) and 5 were without dysplasia/cancer (nonprogressors). Seven had active inflammation and 8, inactive disease. Lamina propria cells were isolated by EDTA washing and collagenase type III and DNAse I digestion in HEPES. Mononuclear lamina propria cells were purified with Ficoll-Hypaque gradient. FISH was performed with dual-color arm and matched centromere probes for cyclin D1/CEP11 and p53/CEP17. The proportion of cells with normal 2 arm and 2 centromere signals was determined and differences assessed by t tests according to progressor status, IBD type, and activity.

Results: The proportion of cells with normal 2/2 dual-probe FISH counts for both sets of FISH probes did not differ in lamina propria mononuclear cells by progressor status, IBD type, or inflammatory activity levels (see Table).

Conclusions: These findings support that lamina propria cells of nondysplastic UC mucosa from progressors and nonprogressors do not contain the same genomic changes reported in neighboring epithelial cells, indicating the importance of epithelial cell isolation in genomic biomarker studies of UC neoplasia.

A 72-year-old woman presented to her primary care physician with nausea, vomiting, and epigastric pain. On radiographic evaluation, a partially solid and partially cystic hepatic lesion, measuring 10 cm in greatest dimension, was identified. Upon complete resection by hepatic trisegmentectomy, the cystic component was predominately smooth walled, with small papillary excrescences projecting into the cyst cavity, while the solid component was found to be tan-pink and friable, with no gross invasion into surrounding hepatic parenchyma. Microscopically, the cystic component was lined by simple columnar epithelium with bland, basally located nuclei, reminiscent of bile duct epithelium. Abrupt zones of transition from simple columnar epithelium (indistinguishable from hepatobiliary cystadenoma) to pseudostratified dysplastic epithelium were apparent (Figure 4, A). The solid component of the tumor (cystadenocarcinoma) demonstrated several different architectural patterns including tubulopapillary, cribriform, and focal solid growth. Focal intestinal metaplasia, in the form of goblet cells, was present. Although focal microscopic capsular infiltration was present, no complete capsular penetration or lymphovascular invasion was identified. Subepithelial “mesenchymal stroma” was conspicuously absent. Immunohistochemical staining for Hep Par1 revealed an interesting pattern in which the cystadenoma component of the tumor was negative, while the dysplastic and frankly carcinomatous components showed diffusely strong cytoplasmic staining (Figure 4, B). These findings support the previously reported hypothesis that this group of tumors is histogenically foregut derived, as opposed to an ovarian origin. We review previous series and case reports with emphasis and discussion on histogenesis and prognosis.

Context: Fibroblastic polyps (FPs) are described as benign lesions characterized by a proliferation of bland spindled cells separating and distorting mucosal crypts that occur in the distal colon and are commonly associated with hyperplastic polyps. Sessile serrated adenomas (SSAs) are polyps that occur throughout the colon and are thought to comprise most polyps found on the right side; however they have not been described as occurring with FP.

Design: We aim to describe the clinical and pathologic features of 11 cases with mixed SSAs/FPs collected prospectively during several months.

Results: The patients were 7 females and 4 males with ages ranging from 35 to 87 years. The indications for colonoscopy varied from screening, abdominal pain, and a history of polyps requiring follow-up. The lesions ranged in size from 6 to 12 mm and were located in the ascending colon, transverse colon, and sigmoid. Histologically, the mucosal crypts showed the classic features of an SSA, including serrated epithelium with dilated basal crypts. The fibroblastic component showed bland, plump spindle cells with oval nuclei arranged either haphazardly or in bundles parallel to the surface (Figure 5). Immunohistochemically, all cases were positive for vimentin and negative for desmin, smooth-muscle actin, S100, c-Kit, epithelial membrane antigen, cytokeratin AE1/3, CD34, and factor XIIIa.

Conclusions: Mixed SSAs/FPs are colon polyps showing the distinct features of both SSAs and FPs. Awareness of this type of polyp is important to convey the benignity of the diagnosis and avoid confusion with other epithelial and mesenchymal lesions of the colon.

Context: Autoimmune pancreatitis (AIP) is currently considered the pancreatic manifestation of IgG4-related systemic sclerosing disease. The aim of this retrospective review is to evaluate the frequency of the hallmark histologic features previously described in the literature, IgG4-positive plasma cell count, and the peripancreatic mucosal involvement of AIP.

Design: We reviewed slides from pancreatic specimens obtained from our institutional archives between 2003 and 2010 and diagnosed as AIP. Selected sections were stained for anti-IgG4 antibody (Invitrogen, 1∶100, mouse). IgG4-positive plasma cells were quantified in pancreatic and peripancreatic tissue. The presence of venulitis, granulocytic epithelial lesions, ampullary mucosal involvement, and Brunner gland involvement were evaluated.

Results: Nine of 628 pancreatic specimens (1.4%) diagnosed as AIP were retrieved. All 9 cases showed a ductocentric lymphoplasmacytic infiltrate with varying degrees of stromal sclerosis. The next most frequent findings were involvement of ampullary mucosa (5 of 9) and Brunner glands (3 of 9), followed by granulocytic epithelial lesions and venulitis (2 of 9 each). IgG4-positive plasma cell infiltration, greater than 50/HPF (high-power field), was observed in 8 sections from pancreas (mean, 128/HPF), 4 from ampulla (Figure 6, a and b; mean, 111/HPF), and 3 from Brunner glands (Figure 6, c and d; mean, 131/HPF).

Conclusions: In addition to histologically prominent pancreatic lymphoplasmacytic infiltrates, venulitis, and granulocytic lesions, some patients had peripancreatic mucosal (ampullary and Brunner glands) plasma cell infiltrates. Dense IgG4 immunostaining (>50 positive cells/HPF) had a high sensitivity (89%) for the diagnosis of AIP in our series.

Mixed endocrine-exocrine tumors display histologic features of both endocrine and glandular differentiation in which the endocrine component constitutes at least one-third of the tumor. The current understanding is that unlike collision tumors, these 2 components arise from 1 precursor (monoclonal). Molecular testing provides evidence of the monoclonal origin theory and also suggests that the endocrine component can arise, usually at an early stage, from the exocrine tumor, but not vice versa. We report a case of a colonic adenomatous polyp that has groups of endocrine cells arising from the crypt bases of the adenomatous (exocrine) epithelium. A gradual shift from adenomatous epithelium to endocrine nests is obvious in Figure 7, both with conventional histology and immunohistochemistry (inset: synaptophysin). There is only 1 article reporting this entity in which these groups of endocrine cells were called microcarcinoid; however, the histogenesis and fate of these polyps were not discussed. The histologic findings in our case correlate well with the molecular/genetic findings described in mixed endocrine-exocrine tumors, that is, endocrine component arises from exocrine at a relatively early stage. This led us to believe that it could represent an early precursor of such lesions. If a similar case is left untreated, the adenoma component could remain as an adenoma or undergo malignant transformation into invasive adenocarcinoma. The “microcarcinoid” component would possibly grow into an endocrine neoplasm, and once it formed at least one-third of the entire tumor, the lesion would meet the criteria for a mixed endocrine-exocrine tumor.

Context: Reactive oxygen species in human tissue can damage DNA and proteins. Oxidative marker 8-OHdG is a byproduct of DNA lesions. Our goal was to establish levels of 8-OHdG in human liver tissues ranging from normal to cirrhosis to dysplasia to hepatocellular carcinoma (HCC) and to determine if expression is associated with any tumor characteristics.

Design: We designed and analyzed a liver tissue array derived from 158 subjects with cirrhosis (107 without HCC + 43 with HCC) and 8 with normal liver, for expression of 8-OHdG by standard immunohistochemistry. Nuclear 8-OHdG positivity was quantified by Aperio image analysis software (Aperio, Vista, California). Nonparametric statistical tests were used with SPSS Statistics 17.0 (IBM, Armonk, New York).

Results: The 8-OHdG median level in normal liver was 32.350 (n  =  8); cirrhosis, 51.750 (n  =  106); dysplasia, 60.800 (n  =  141); and HCC, 76.400 (n  =  43). In subjects with HCC, 8-OHdG levels in HCC areas increased from well-differentiated (40.500) to moderately (63.400) to poorly differentiated tumors (115.700) (P  =  .001). In subjects without HCC, 8-OHdG levels increased from cirrhosis (54.350) to dysplasia (69.900) (P < .01). In subjects with HCC, 8-OHdG levels increased from cirrhosis (28.100) to dysplasia (36.700) to HCC (76.400) (P  =  .02) (Figure 8).

Conclusions: This study shows that immunoexpression of oxidative damage marker 8-OhdG increases with worsening disease progression and tumor differentiation. 8-OHdG may be a useful biomarker to monitor progression of HCC. Verification in a larger cohort could determine if 8-OHdG is a marker for hepatocarcinogenesis.

Context: Esophagitis dissecans superficialis (EDS) is an unusual pattern of injury characterized by sloughing of the superficial squamous epithelium with necrosis, parakeratosis, and intraepithelial abscesses. This study describes clinicopathologic aspects of EDS (Figure 9).

Design: Patients with EDS were selected from the database of Caris Life Sciences, a specialized gastrointestinal pathology group receiving specimens from community-based gastroenterologists in 42 states; Washington, District of Columbia; and Puerto Rico. The database includes demographic and clinical information, summary of the endoscopic report, biopsy location, and the histopathologic report for each biopsy specimen. Cases of EDS with a report date from November 1, 2009, to February 28, 2011, were extracted from the database.

Results: Sixty-eight patients with EDS from 25 states were recovered. Fifteen presented with dysphagia, 33 with epigastric pain/dyspepsia, and an additional 9 patients presented with both. Esophageal location was specified for 57 patients (upper, 5.3%; middle, 36.8%; and lower, 57.9%) with 11 cases unspecified. There were 12 males (17.6%) and 56 females (82.4%). The mean age at diagnosis was 63.8 years (median, 64.5 years; SD, 14.2 years; range, 18–90 years). Fungal stain results were negative in 41 cases (97.6%) and showed Candida in 1 case (2.4%). One case showed iron pill fragments.

Conclusions: EDS was most common in an older age group and showed a strong predominance in females. Most patients presented with dyspepsia and/or dysphagia. Most cases occurred in the lower or middle esophagus. There was no distinct regional pattern of prevalence. EDS was not reliably related to fungal infection or observed pill fragments. The pathogenesis of EDS remains unexplained in this series.

Context: Histologic assessment plays an important role in the diagnosis and management of liver allograft rejection. Recurrent hepatitis C infection and other causes are common findings in allograft liver rejection biopsies. Hepatitis C infection is characterized by accelerated progression toward cirrhosis and hepatic failure due to the lack of effective immunoprophylaxis with specific antiviral therapy. In contrast, recurrence of hepatitis B is uncommon. In this study, we retrospectively evaluated and compared the influence of hepatitis C infection versus other causes in transplant rejections.

Design: We included 143 patients who underwent liver transplants at our institution from January 2007 to December 2010. Various causes of transplant rejections were reviewed and evaluated. Statistical analysis was performed by using ANOVA in SPSS and was correlated with overall outcome.

Result: Transplant rejection causes included recurrent hepatitis C, hepatitis B, autoimmune, cholestasis, and nonspecific acute and chronic rejections (Figure 10). Hepatitis C–associated rejection was most frequent, 65% (94 of 143), and mean interval between transplant and rejection was 733.01 days (SD, 743.84 days), with hepatitis B, 0.02%; other viral causes, 0.4%; autoimmune, 0.2%; cholestasis, 0.03%; nonspecific acute and chronic rejection, 17%; and other factors, 0.03%. Results between hepatitis C versus other causes were statistically significant (P < .01).

Conclusion: Viral hepatitis is the most common indication of liver transplantation in United States. In our experience, recurrence of hepatitis C infection is associated with decreased long-term survival and increased rejections. This emphasizes the need for careful risk stratification for selection of transplant recipients among various infectious and noninfectious transplant candidates.

A 54-year-old-man presented with abdominal pain; endoscopy, ultrasonography, and computed tomography revealed a cystic, multiseptate, nearly circumferential mass involving the duodenal wall with likely extension into the pancreas. Owing to these findings and presentation, a Whipple-type pancreaticoduodenectomy was performed. The patient tolerated the procedure well and remained well at follow-up. Grossly, there was a 5.5-cm, circumferential, broad-based mass lesion of the duodenal mucosa (Figure 11, A, inset). Sections revealed an aggregate of cysts underlying the mucosa, which appeared to extend into the pancreas (Figure 11, A). Microscopically, the cysts, which were centered at the ampulla of Vater, had features of dilated vaterian ducts (Figure 11, B, thin arrows). In addition, there was extensive Brunner gland hyperplasia (Figure 11, B, thick arrows) confined to the mucosal level, but not associated with the cysts. No malignant features were found and a diagnosis of adenomatous hyperplasia of the vaterian ducts associated with Brunner gland hyperplasia was made. Adenomatous hyperplasia of the vaterian duct system is rare, described in the literature as benign with symptoms including abdominal pain and jaundice. Diagnostic difficulties are also noted in the literature and a radical resection is considered a valid, effective treatment. Large areas of Brunner gland hyperplasia can also resemble malignancy, both endoscopically and on imaging. In conclusion, the combination of these 2 benign entities, which has not been previously reported, caused the radiologic and endoscopic imaging to appear ominous. However, owing to symptoms and the diagnostic difficulty of ruling out malignancy, pancreaticoduodenectomy was an appropriate therapy for these benign processes.

Sarcomatoid carcinoma is an uncommon biphasic tumor with mixed malignant epithelial and mesenchymal features. We report here an unusual clinical presentation of a case of colonic sarcomatoid carcinoma. An 84-year-old man was identified by computed tomography scan as having a rapidly enlarging left-sided lung mass measuring up to 7.9 cm and focal “masslike” thickening in the colonic hepatic flexure. An open lung biopsy was performed and showed an infiltrating malignant spindle cell neoplasm (Figure 12, A) that stained positively for vimentin, weakly positive for cytokeratins, and negatively for thyroid transcription factor 1 in immunohistochemical studies. Two days later, a hemicolectomy was also performed that revealed a 5.4-cm mass in the colon, which was predominantly composed of moderately differentiated adenocarcinoma. In focal areas of this tumor, however, malignant spindle cells admixed with carcinoma component were identified (Figure 12, B). The spindle tumor cells had similar morphologic and immunostaining features as the lesion identified in the lung. The findings are consistent with a colonic sarcomatoid carcinoma with metastasis of its sarcomatoid component into the lung. The pathologic diagnosis of the lung lesion for this patient could have been very challenging because colonic sarcomatoid carcinoma is very rare, and in this case only the sarcomatoid component of the tumor metastasized to the lung. To our best knowledge, this is the first reported case of colonic sarcomatoid carcinoma with the primary clinical presentation as a malignant spindle cell lung neoplasm.

We report a case of microcystic/reticular schwannoma (Figure 13) of the proximal sigmoid colon in a 61-year-old man who presented with a 12-mm polyp while undergoing screening for colorectal neoplasm. This entity was first described in 2008 and is a rare variant of schwannoma, with a predilection for the visceral organs, predominantly the gastrointestinal tract. We also review the other 9 cases of microcystic/reticular schwannomas in the gastrointestinal tract that have been described in literature. Unlike other conventional gastrointestinal schwannomas, which are more common in the stomach, this variant appears to be more common in the large intestine. It is important to recognize this entity as it can be mistaken for a signet ring carcinoma or a myxoid gastrointestinal stromal tumor, particularly on small biopsy specimens. Conventional schwannomas occur most frequently in the stomach, and colorectal locations are uncommon. The microcystic/reticular variant appears to be more common within the colorectal region. The first series of 10 cases of microcystic/reticular schwannomas was first presented by Liegl et al in 2008. Subsequently, 4 more cases of this variant, involving the gastrointestinal tract, have been described. Adding to these recent publications, we report another example of this rare variant, which was identified in our department before the 2008 series publication, and describe for the first time the ultrastructure findings and the significant differential diagnosis considerations.

Primary rectal melanoma comprises less than 1% of all anorectal cancers and rarely presents as a rectal polyp. Most cases present in the fifth to seventh decade of life, with a female predominance of nearly 2 to 1. Initial symptoms are often nonspecific and include pain, hematochezia, and changes in bowel habits, leading to delayed medical attention and intervention. Diagnosis is often complicated by the fact that 30% of these lesions are amelanotic with varying histologic presentations. Metastasis is common, with 61% of patients demonstrating regional lymph node involvement and approximately 29% showing distant disease at initial presentation. Additional factors contributing to increased mortality are overall tumor size, perineural invasion, and loss of c-KIT expression. Despite advances in surgical and adjuvant treatments, prognosis remains dismal, with a 5-year survival rate of only 10%. We present a case of a 72-year-old white woman who experienced small-caliber stools and rectal bleeding for 1 week. Colonoscopy demonstrated a friable 3.0 × 3.0-cm polypoid mass at the distal rectum. Histologic examination showed a rectal polyp with extensive replacement by discohesive, large cells, with prominent nucleoli and an increased mitotic rate (Figure 14). The neoplastic cells displayed strong positivity for S100, HMB-45, and melanoma-associated antigen immunohistochemical stains, confirming the diagnosis of melanoma. We report this case owing to its rarity and as a reminder to consider melanoma when evaluating rectal specimens, including polyps.

Cytomegalovirus (CMV) intranuclear and intracytoplasmic inclusions are occasionally identified within endothelial, stromal, and more rarely, epithelial cells of the colonic mucosa of immunosuppressed patients. We report the first case of classic CMV inclusions within the colonic epithelium of a tubular adenoma. The patient is a 92-year-old woman with a past medical history of altered mental status and a recently diagnosed cranial meningioma being treated with 4 mg of dexamethasone 3 times a day. She presented to the emergency department with bright red blood per rectum. Flexible sigmoidoscopy revealed a 1-cm ulcer within the distal rectum and a 1-cm flat polyp at 30 cm. Microscopically, the polyp is a tubular adenoma with numerous epithelial intranuclear and intracytoplasmic inclusions within the adenomatous glands (Figure 15). These inclusions are strongly positive for CMV immunostain. Interestingly, no such inclusions were noted on hematoxylin-eosin stain or CMV immunostain within the underlying endothelial or stromal cells. The rectal ulcer biopsy specimen displayed ulcerated colonic mucosa and failed to reveal histologic evidence of CMV, and the CMV immunostaining results were negative. There are no prior reports of CMV inclusions within preneoplastic or neoplastic colonic epithelium. The significance of this unusual finding is unclear. It is possible that mutations acquired in the neoplastic epithelial cells make them more susceptible to infection by CMV, particularly in the setting of immunosuppression. Although the ulcer failed to reveal evidence of CMV, given the presence of the inclusions elsewhere, the patient was treated with valganciclovir and has remained asymptomatic.

Context: Fewer than 50 cases of metastatic carcinoma to percutaneous endoscopic gastrostomy (PEG) tube sites have been reported. The largest series included 2 patients. We report for 4 patients the clinical and pathologic characteristics of metastatic squamous cell carcinoma (SCC) to PEG tube sites.

Design: A retrospective review of our database (2002–2011) and medical records for metastatic malignancy to PEG tube sites was done.

Results: Four patients were identified (Table), each with at least moderately differentiated primary head and neck keratinizing SCC (tongue, 3; posterior pharyngeal wall, 1), and treated with postoperative chemoradiation. Two patients were assigned T2 N2 M0 cancer and 2 had unresectable tumors. The average patient age was 70 years (SD  =  10 years). All PEG tubes were placed by using the pull-string method. The metastases had a mean size of 5.4 cm (SD  =  1.0 cm) and were morphologically similar to the primary tumors. The mean time from PEG tube placement to metastasis was 10.3 months (SD  =  2.8 months). The mean postmetastasis overall survival was 16.6 months (SD  = 14.3 months), while it was 22.0 months (SD  =  11.5 months) in 3 patients treated with partial gastrectomy. The PEG tube site was the only site of metastasis in 3 cases; 1 patient had an intra-abdominal lymph node metastasis.

Conclusions: The survival of our patients with metastatic SCC to PEG tube site was significantly longer than that reported by a meta-analysis (4.3 months [SD  =  3.8 months)]). Chemoradiation therapy to primary tumor and/or postmetastasis partial gastrectomy may contribute to longer survival in our patients. PEG tube insertion, using the pull-string method, should be considered a risk factor for metastatic SCC to the insertion site in patients with head and neck SCC.

Metastatic Head and Neck SCC to Percutaneous Endoscopic Gastrostomy (PEG) Tube Site

Metastatic Head and Neck SCC to Percutaneous Endoscopic Gastrostomy (PEG) Tube Site
Metastatic Head and Neck SCC to Percutaneous Endoscopic Gastrostomy (PEG) Tube Site

Primary biliary cirrhosis (PBC) is a chronic disease that is characterized by bile duct damage, portal lymphocyte infiltration and epithelioid cells centered around septal and interlobular bile ducts. Granulomas are usually present within portal lymphocytic infiltrates and less commonly in the hepatic lobules. Intravesical instillation of immunotherapeutic bacille Calmette-Guérin (BCG) is an important and safe adjunct treatment to bladder cancer, but its use can cause granulomatous cystitis. Our patient is a 74-year-old man with a history of bladder cancer. He has been treated with monthly intravesicular BCG and interferon for 1 year. Shortly after his last dose, he presented with fever, chills, confusion, and moderately elevated liver function tests, which led to a liver biopsy. The biopsy demonstrated multiple poorly circumscribed epithelioid granulomas in both portal and lobular area. Together with positive antimitochondrial antibody E2 and ductal destruction, a diagnosis of PBC was rendered. However, since lobular granuloma is rare in PBC, we suspected an infectious cause. Indeed, these granulomas contained numerous acid-fast–positive bacilli, most likely secondary to the BCG therapy (Figure 16). Thus, a dual diagnosis of PBC and systemic bacillus Calmette-Guérinosis infection (BCGosis) was made. In patients under BCG treatment, the presence of granulomas should raise the possibility of disseminating BCGosis. These granulomas can appear anywhere and must be differentiated from those in PBC.

Context: Gastrointestinal stromal tumors (GISTs) are rare tumors of the gastrointestinal tract, with an estimated annual incidence of 6.8 per million. The risk of recurrence after surgery is related to the tumor size, site, and mitotic rate, which has been recently stratified by the National Comprehensive Cancer Network (NCCN). The impact of race on recurrence risk has not been studied.

Design: The clinicopathologic features of 32 GISTs diagnosed between 2005 and 2010 were reviewed. Recurrence risk for each tumor was determined as per NCCN criteria based on tumor site, size, and mitotic index. Racial differences were accessed by comparing recurrence risk in each racial group.

Results: The mean age of patients was 63.3 years (range, 29–86 years), with equal sex distribution. Of those diagnosed, 19 were white (59%); 9, African American (28%); and 4, Hispanic (12%). Twenty-five GISTs (78%) were located in the stomach, 5 (16%) in the small intestine, and 2 (6%) in other sites, with no significant racial differences. Overall, 13 of 32 GISTs (41%) had no recurrence risk, with very low to moderate risk in 12 of 32 (37%) and high risk in 7 of 32 (22%). Most cases with a recurrence risk of <25% were asymptomatic and incidental findings. Risk stratification based on race is shown in the Table. High-risk GISTs were more frequent in African Americans and 2 of 3 (66%) had recurrence after 18 and 31 months of primary resection.

Conclusions: This study directs that African Americans have numerically higher recurrence rates in comparison to whites and that NCCN criteria should be appropriately modified to include the impact of race on calculation of the recurrence risk.

Risk Stratification Based on Race

Risk Stratification Based on Race
Risk Stratification Based on Race

Hepatocellular adenomas are benign lesions that often share histologic features with hepatocellular carcinoma or focal nodular hyperplasia. We report a case of a 50-year-old woman who was diagnosed with hepatic adenomatosis after a computed tomography scan revealed numerous nodules (2–5 cm) in her liver. The diagnoses of hepatocellular adenomas were made on subsequent biopsy. The patient underwent embolization. A recent scan revealed that 2 of the adenomas had increased in size with hypervascular changes. Right lobectomy was performed. Microscopically, the nodules contain areas with disrupted hepatic architectures, scattered unpaired arteries, and an absence of portal tracts. Adjacent to these are other areas that range from small foci to large areas of prominent ductular proliferation intermixed with fibrosis and occasional large vessels. Reticulin staining showed focal marked loss of reticulin. This histologic finding caused initial confusion. Loss of reticulin staining raised the question of hepatocellular carcinoma, while the finding of ductular proliferation and fibrosis necessitated the entry of focal nodular hyperplasia into the differential. Only after a clinical discussion with surgeons, immunostaining for CD34 and glypican-3, and further scrutiny of the slide, which revealed intravascular emboli, was the correct diagnosis of “therapy-associated reactive changes in hepatocellular adenomas” made. It is important to recognize that therapeutic changes in hepatocellular adenomas can mimic focal nodular hyperplasia and hepatocellular carcinoma. Clinical correlation is paramount in making correct diagnoses in such events. Figure 17 shows hepatocellular adenoma with marked ductular proliferation and fibrosis mimicking focal nodular hyperplasia.

A 53-year-old woman presented to an outside hospital with right upper quadrant pain. An ultrasonography demonstrated cholelithiasis as well as fatty infiltration of the liver. Laboratory test results included elevated liver enzyme levels with a nonreactive hepatitis panel. After a 1-year delay due to uncontrolled hyperglycemia, the patient underwent laparoscopic cholecystectomy with a liver wedge biopsy. Pathology specimens revealed macrovesicular steatosis, with clusters of vessellike spaces with an appearance similar to lymphangioma (Figure 18). However, on close inspection there was no endothelial layer. CD31 staining was negative, confirming lack of an endothelium. A Hep Par stain showed hepatocytes directly surrounding these spaces. Additional staining results with HMB-45, HHF35, and S100 were negative. The appearance of lymphangioma was simulated by artifactual spaces combined with the fatty infiltrate. Such artifacts can be frequently seen in cauterized liver. Lymphangiomas consist of overgrowths of thin-walled vascular channels. The inner layer is an endothelium that should stain positive for endothelial markers such as CD31. Theories of origin include sequestration of lymphatic tissue, abnormal budding of lymph vessels, nonfusion of lymph sacs with the venous system, and lymphatic obstruction. In adults, sudden appearance is thought to be caused by delayed proliferation of cell rests, followed by triggers such as trauma. Lymphangiomas are traditionally categorized as capillary, cavernous, or cystic. The liver is often involved in lymphangiomatosis. Solitary hepatic lymphangioma is extremely rare but several case reports do exist. They typically appear as cystic masses in the liver on computed tomography scan.

Russell body gastritis is characterized by localized accumulation of plasma cells filled with Russell bodies, along with inflammatory infiltrate. Twelve cases have been reported in the English-language medical literature previously. Association with Helicobacter pylori gastritis or immunosuppression is known. The present case is the third to be reported in association with HIV infection and the first to be associated with collagenous colitis. An 82-year-old man presented with dyspepsia, loose stools, weight loss, and loss of appetite. Past medical history was significant for HIV infection, cerebrovascular accident, chronic kidney disease, peripheral vascular disease, hypertension, depression, and diabetes mellitus type 2. Computed tomography scan showed esophageal and gastric wall thickening. Gastrointestinal endoscopy revealed gastritis. Microscopic examination of the biopsy specimen revealed fragments of gastric mucosa with diffuse plasma cell infiltration in the lamina propria associated with large eosinophilic Russell bodies (Figure, 19, left). Immunoperoxidase stains revealed positivity for CD138 (Figure 19, right middle) and λ and κ chains (Figure 19, right top and bottom), implying polyclonality. Results with special stain for H. pylori and immunostain for CD68 were negative. The differential diagnoses include plasmacytoma and mucosa-associated lymphoid tissue lymphoma with plasmacytic differentiation. Human immunodeficiency virus causes polyclonal B-cell activation, plasmacytosis, hypergammaglobulinemia, and formation of circulating immune complexes. Accumulation of immunoglobulins in Russell body gastritis may be a manifestation of the immunologic abnormality. The association with collagenous colitis may be coincidental. Awareness of this entity is important to prevent confusion with neoplasia.

Context: Eosinophilic infiltrates in gastrointestinal (GI) biopsy specimens are a nonspecific finding commonly described in association with allergies, drug reactions, or parasitic infestations. We aim to evaluate the causes of increased eosinophils in GI biopsy specimens seen in our institution, which provides health care to patients from different parts of the world.

Design: We retrospectively analyzed 39 patients' GI biopsy specimens for which the final diagnosis included “increased eosinophils.” Eosinophil quantification was done manually on the H&E-stained sections. Clinical data for correlation were obtained from patient medical records.

Results: The most common diagnosis associated with increased eosinophils in GI biopsy specimens was inflammatory bowel disease, ulcerative colitis being more common than Crohn disease (Table). Other diagnoses included diverticulosis, Helicobacter pylori gastritis, nonspecific gastritis, colonic adenocarcinoma, and peripheral eosinophilia, not otherwise specified. One patient was later diagnosed with hyperthyroidism, who initially underwent biopsy for intractable vomiting and diarrhea. The eosinophilic infiltrate was most prominent in ulcerative colitis, with a count of more than 100 eosinophils per high-power field in several cases. However, the 2 peripheral eosinophilia cases had a higher average of eosinophils per high-power field.

Conclusions: In evaluating eosinophilic infiltrates in GI biopsy specimens, we found inflammatory bowel disease to be the most common cause. Ulcerative colitis was more commonly observed than Crohn disease. Several cases had increased eosinophils before the subsequent diagnosis of inflammatory bowel disease. This raises the importance of recognizing the more common associations of the nonspecific finding of eosinophilic infiltrates in GI specimens.

Most Common Diagnosis Associated With Increased Eosinophils

Most Common Diagnosis Associated With Increased Eosinophils
Most Common Diagnosis Associated With Increased Eosinophils

There is evidence that some bacterial and parasitic infections are associated with cancer development. A high level of evidence exists for the association of Schistosoma haematobium with bladder cancer. The inflammation associated to schistosomiasis can be aggressive and mimic bladder cancer under cystoscopic examination. Interestingly, in our case, the microscopic examination showed Schistosoma organisms with lateral spur, which are characteristic of Schistosoma mansoni. We present the case of a 52-year-old African man who consulted owing to several months of gross hematuria. The patient reported no other associated symptom. The physical examination results were normal except for mild abdominal defense by palpation of the hypogastria. A urinalysis revealed microscopic hematuria. A cystoscopy showed multiple intracystic lesions. Several small ulcerative and 1 large lesion were also seen. Several bladder tumor chips were submitted for microscopic examination. The specimen consisted of a friable, brown-black tissue. The microscopic examination showed intensely inflamed, eosinophil-laden granulation tissue heaps, bearing numberless parasites with a lateral spur (Figure 20). Reactive urothelial changes were predominant. The present case permits one to broaden the differential diagnoses of tumoral and ulcerative lesions in the urinary bladder. Schistosomiasis can mimic malignancy at cystoscopy. Microscopic examination is a fundamental part to rule out malignancy. Interestingly, in our case, the microscopic examination showed schistosomes with lateral spur, which are characteristic of S. mansoni.

Carcinosarcomas arising in the bladder are very rare. The exact incidence is unknown, but it is estimated at 1 per 5 000 000, with a male predominance and a mean age of 75 years. The risk factors are similar to those for urothelial carcinoma and include smoking, male sex, sixth to seventh decade of life, prior cyclophosphamide therapy, and pelvic radiation. Carcinosarcomas usually present at an advanced stage and have a worse prognosis than conventional urothelial carcinomas owing to their aggressive behavior. Given the low incidence of primary carcinosarcoma of the bladder, well-established treatment protocols are lacking. In most cases, radical cystectomy is the only treatment; however, prolonged survival has been documented with adjuvant radiotherapy. Grossly, the tumors typically demonstrate a single, exophytic, polypoid, necrotic, ulcerating mass. Microscopically, they show intimately admixed malignant epithelial and mesenchymal components. The most common epithelial components are urothelial carcinoma, squamous cell carcinoma, adenocarcinoma, and small cell carcinoma. The mesenchymal components are usually an undifferentiated, high-grade spindle cell neoplasm, osteosarcoma, chondrosarcoma, leiomyosarcoma, rhabdomyosarcoma, liposarcoma, or angiosarcoma. Our case is that of an 80-year-old woman with a history of smoking 15 packs per year, presenting with recurrent urinary tract infections and 1 episode of gross hematuria. Cystoscopy showed an exophytic tumor along the bladder dome and wall. The cystectomy specimen demonstrated a 3.0-cm, ulcerated, fungating mass extending through the muscularis propria to abut the overlying adipose tissue. Microscopically, the mass demonstrated a mitotically active, pleomorphic, vimentin+, p63+, undifferentiated, high-grade spindle cell neoplasm with foci of CK7+/CK20−/villin− adenocarcinoma (Figure 21).

Renal replacement lipomatosis (RRL) is a rare benign condition in which renal parenchyma is replaced by mature adipose tissue owing to marked renal atrophy from various causes including inflammation and nephrolithiasis. RRL may present as a unilateral renal mass mimicking a tumor on radiology. We report a case of a 61-year-old man with a growing left-sided renal mass, hematuria, and flank pain. Imaging studies (magnetic resonance imaging, computed tomography, and MAG3 Lasix renogram) revealed bilateral nephrolithiasis and an enhancing soft-tissue mass infiltrating the left renal pelvis (Figure 22, A) and collecting system, with filling defect suggesting a neoplastic versus inflammatory mass. The function of the left kidney was poor and left radical nephrectomy was performed. Grossly, the kidney was atrophic with mildly dilated pelvis and calyces. The renal pelvis and parenchyma were replaced by an irregular mass (5 × 4 × 3.5 cm) of adipose tissue (Figure 22, B) containing areas of chronic inflammation and fibrosis (Figure 22, C) with severe chronic and acute pyelonephritis and marked vascular nephrosclerosis (Figure 22, D). No tumor or stones were present (possibility that stones are being passed in urine). RRL may clinically present as a renal mass and the main radiographic differential considerations include malakoplakia, xanthogranulomatous pyelonephritis, fat-containing tumors (liposarcoma, lipoma, and angiomyolipoma), and carcinoma of renal parenchyma or pelvis. This case is presented to increase the awareness of this rare benign lesion among radiologists and surgeons in the differential diagnosis of renal masses with lipomatous radiographic features and to plan treatment according to the functional capacity of the affected kidney.

Nephroblastoma (Wilms tumor) arises from metanephric blastema, which differentiates into triphasic or sometimes biphasic or monophasic patterns including blastemal, epithelial, and stromal lineages. Overall a rare neoplasm, it represents <10% of all cancers in children but is the most common pediatric genitourinary cancer. Nephroblastoma is extremely rare in adults, with an incidence of only approximately 0.2 cases/million/year, and most cases are diagnosed before the age of 6. We report the case of a 24-year-old white man who presented with abdominal pain on the left side of increasing intensity of 6 to 7 months' duration. A computed tomography scan demonstrated a large 17.2-cm, left-sided, enhancing, renal mass with periaortic lymphadenopathy. Subsequent computed tomography scans revealed bilateral, peripheral, uncalcified, pulmonary nodules, suggestive of metastasis. A radical nephrectomy was performed; a large polypoid tumor protruded into a dilated pelvicalyceal system and extensively invaded perinephric adipose tissue, the adrenal gland, and the renal vein. Histologically, the tumor had a biphasic morphology consisting of blastemal and stroma components with diffuse anaplasia. The patient was additionally treated with chemotherapy and radiation, but persistence of the pulmonary metastases resulted in bilateral metastasectomies (Figure 23). Unfavorable prognostic factors include unfavorable histology (anaplasia), adult age at diagnosis, and high-stage tumor. Anaplasia is not sine qua non for aggressive neoplastic behavior, but these cases tend to be resistant to chemotherapy. In general, adults tend to have a poorer outcome stage for stage as compared to children. Furthermore, hematogenous metastasis, including the lungs, confers stage IV disease, for which the prognosis is grim in adults.

Ewing sarcoma/primitive neuroectodermal tumor (EWS/PNET) of the kidney is a rare entity with poor prognosis. It poses a diagnostic challenge with fine-needle aspiration (FNA) specimens. There are only 4 reported renal EWS/PNET cases with FNA findings. We present the fifth case with both cytologic and histologic findings. A 32-year-old man presented with a large renal mass on the right side. Computed tomography–guided FNA showed aggregates of loosely cohesive small-sized tumor cells with scant cytoplasm, round to oval nuclei, and inconspicuous nucleoli. Possible rosette-like architecture was noted. Nephrectomy specimen revealed sheets and nests of small-sized monotonous tumor cells with occasional Homer-Wright rosettes. The neoplastic cells showed strong expression of CD99 and vimentin and were negative for AE1/AE3 and chromogranin. The diagnosis of renal EWS/PNET is substantiated by the presence of EWSR1 translocation detected by fluorescence in situ hybridization. Preoperative FNA of renal mass plays an important role in tissue triage and therapeutic decisions. Potential pitfalls associated with renal mass FNA include lack of onsite evaluation by pathologists, inexperienced FNA performer, sampling of necrotic foci, and inadequate sampling precluding tissue triage for ancillary studies. Owing to the morphologic and immunophenotypic resemblance with other small blue cell tumors, detection of EWSR1 translocation is now considered as the gold standard for diagnosing EWS/PNET. However, nearly half of reported renal EWS/PNET cases lack this type of study. To address this crucial issue, we reviewed 30 renal EWS/PNET cases with explicit evidence of EWS translocation (Table). In summary, EWS/PNET needs to be considered in the differential diagnosis for young patients with a large renal mass.

Clinicopathologic Features of Renal EWS/PNET Cases With the EWSR1 Gene Translocation

Clinicopathologic Features of Renal EWS/PNET Cases With the EWSR1 Gene Translocation
Clinicopathologic Features of Renal EWS/PNET Cases With the EWSR1 Gene Translocation

Context: Cutting fresh prostate for tissue procurement, while maintaining the quality of sections for histologic diagnosis, can be challenging.

Design: The prostate-cutting apparatus includes a prostate slicer and a tissue clamp. The prostate slicer is fabricated out of AISI-SAE 6061 aluminum, featuring a 1.5-in-long sliding side that moves along a t-track in the base, as seen in the final design (Figure 24). The sliding side can be locked in place. On either side of the base, the 2 sides have slits spaced 3 mm apart, allowing a prostate to be sliced at 3-mm intervals. A tissue clamp consisting of 2 porous polycarbonate plates (8 × 5 × 0.093 in.) and steel clips secures the prostate tissue slices so that formalin can permeate the specimen and fixation is attained without distortion.

Results: After inking and shaving bladder neck and apical margins, a prostate is loaded onto the slicer, with the apical plane aligned with the stationary side of the slicer (Figure 24) and cut into 5 to 7 slices with a Sadie-Riggs tissue blade. The slices produced are ideal for histologic assessment: flat and well fixed with an intact capsule (Figure 24, A: prostate loaded onto the slicer; B, fresh slices; C, slices in the clamp; and D, fixed slices).

Conclusions: The prostate-cutting apparatus is safe and easy to use and cuts fresh prostate slices in a standardized fashion, enabling us to meet the demand of procuring quality fresh prostate tissue and producing quality sections for histologic assessment of prostatectomy specimens.

We present a case of a 56-year-old woman with a 7-year history of vulvar intraepithelial neoplasia (VIN) 1 that progressed within 3 years to VIN 3 and currently VIN 2, anal intraepithelial neoplasia (AIN) 1, and a remote history of cervical intraepithelial neoplasia (CIN) 1. She had no known history of asbestos exposure. Two months before diagnosis, the patient presented with a mass on cystoscopy with vesicovaginal fistula. The cytoscopic biopsy specimens were CK7+ and CK5/6+ and were interpreted as sarcomatoid carcinoma of the bladder. The radical cystectomy specimen revealed diffusely thickened bladder wall, with an exophytic mass at the posterior dome and associated serosal perforation. On histology, the tumor was composed of a biphasic proliferation of spindled cells admixed with hobnail-shaped cells forming sharply angulated glands; a diagnosis of primary peritoneal mesothelioma was rendered (PPM) (Figure 25). A broad panel of immunohistochemical stains was performed in support of the diagnosis, with results as follow: CK7+, CK5/6+, D2-40+, calretinin (focally +), WT-1−, CK20−, TTF-1−, CDX2, CD31, CD34, p53−, and mucicarmine−. This case highlights the diagnostic dilemma of rendering a diagnosis of PPM when it presents in an unusual manner and location, such as in our case. This challenge is further complicated by the histologic features of PPM when a sarcomatoid, spindle cell, or glandular pattern is prominent. In addition, this case serves as a reminder that mesothelioma is not solely associated with asbestos exposure but also with various other conditions.

Context: Tocopherol-associated protein (TAP) has been reported to act as a tumor suppressor in prostate cancer. We investigated the correlation between TAP immunohistochemical staining of prostate cancer and clinicopathologic features in patients who had undergone radical retropubic prostatectomy.

Design: Retrospective review was performed on 114 patients undergoing radical retropubic prostatectomy between 1997 and 2003. Immunohistochemical stains were performed on prostatic adenocarcinoma and benign glands from each specimen with a TAP monoclonal antibody. Seven patients were excluded owing to failed staining controls. Analysis of stain intensity was evaluated by a single pathologist. Intensity scores (1+, 2+, 3+) were correlated with clinical (PSA recurrence) and pathologic features (Gleason score, extraprostatic extension, seminal vesicle invasion, lymph node metastasis, surgical margin status).

Results: One hundred seven patients were evaluated with a mean follow-up of 86.5 months (range, 4–154 months). There was a down regulation of TAP staining in prostate cancer compared to benign prostatic glands (P < .001). Kaplan-Meier analysis revealed a relationship between the intensity of TAP staining and recurrence-free survival, as defined by biochemical recurrence PSA ≥ 0.2 (P  =  .03) (Figure 26). Fisher exact probability tests showed no statistically significant correlations between the intensity of TAP staining and pathologic features.

Conclusions: TAP immunohistochemical staining revealed a down-regulation of intensity in prostate cancer compared to benign glands in radical prostatectomy specimens. This supports the role of TAP as a tumor suppressor in prostate cancer. Loss of TAP expression was associated with a risk of biochemical recurrence. Further investigation of a larger series is required to assess its role as a prognostic marker.

Desmoplastic melanoma is a rare type of spindled cell melanoma associated with prominent collagen production and most common on the sun-exposed skin. We report a case of primary penile desmoplastic melanoma, initially misdiagnosed as squamous cell carcinoma. A 72-year-old white man with neonatal circumcision presented with progressive urinary obstruction and acute kidney injury. Meatal stenosis was noted clinically with firm glans penis. A biopsy of the meatus was performed at an outside hospital and a diagnosis of squamous cell carcinoma was made. The patient was referred to UCIMC for distal penectomy. Gross examination revealed scattered, flat, dark-brown discoloration of the skin and ill-defined firmness of the entire glans. Cross sections showed a poorly circumscribed, white firm tumor measuring 1.5 × 1.3 cm. Microscopically, the tumor is composed of haphazardly arranged spindle cells infiltrating the dermis and corpus spongiosum (Figure 27). Moderate nuclear pleomorphism, rare mitosis, and abundant collagen were present with evident neurotropism. The overlying skin showed focal atypical melanocytic proliferation and pseudoepitheliomatous hyperplasia. The differential diagnosis includes spindle cell carcinoma, leiomyosarcoma, and desmoplastic melanoma. The tumor cells were positive for S100 protein and vimentin, negative for AE1/AE3, HMB-45, Melan-A, and smooth muscle actin (SMA). The atypical melanocytic cells at the epidermal-dermal junction were positive for HMB-45 and Melan-A. A diagnosis of desmoplastic melanoma of the penis was made. Review of the previous biopsy specimen showed similar morphology with pseudoepitheliomatous hyperplasia of overlying skin. Given the high recurrence rate of desmoplastic melanoma if not adequately excised, making an accurate diagnosis would lead to appropriate management.

Context: In 2010, there were 217 730 new cases of prostate cancer in the United States. Gleason grading has been established as a reliable score for prostate cancer prognosis and is achieved using fixation and staining of tissue. We present a method in which we use the optical properties of the tissue to determine the Gleason grade.

Design: We perform label-free imaging of cancer tissue microarrays by using spatial light interference microscopy (SLIM), which quantitatively maps the refractive index of the tissue. With this spatially resolved map, different cell types and their arrangement can be distinguished, and we can identify cancerous areas from benign areas and state the Gleason grade of cancerous areas.

Results: The imaging time for a slide with 30 cores at ×10 magnification with SLIM was 8 minutes. From the 30 cases presented to us, we identified 9 cores as benign and identified areas of Gleason grade 3 in 10 cores, grade 4 in 10 cores, and grade 5 in 4 cores. The SLIM images compare very well with hematoxylin-eosin–stained tissue, as seen in Figure 28, in which Gleason grade 5 and grade 4 areas from a core are magnified on the left and right, respectively.

Conclusions: The preliminary results for the use of SLIM for label-free imaging look promising. However, our method is still subjective. We are working on using statistical measures from scattering mean free path and anisotropy maps to reduce interobserver and intraobserver variability in Gleason grading.

Yolk sac tumors are rare malignant tumors of germ cell origin that recapitulate the primary, embryonal, yolk sac tissue and most commonly arise from the gonads. Primary extragonadal germ cell tumors are very rare. The main distribution of extragonadal yolk sac tumors is located along the midline of the body in the mediastinum, central nervous system, or retroperitoneum. This is a case of a 58-year-old white man with an underlying stage 4, intra-abdominal germ cell tumor with metastasis and bowel obstruction. There was no clinical evidence of testicular involvement at the time of presentation. The pathology laboratory received a segment of small intestine with attached mesentery and a tumor mass. The tumor grossly arose from the retroperitoneum, extended into the mesenteric region beside the small intestine, but had no continuity with the small intestinal wall. Microscopic evaluation suggested a pure yolk sac tumor (Figure 29). Later, clinical testicular evaluation was undertaken and a right testicle was received and revealed a firm, tan nodule at the lower pole of the testicle. Microscopic evaluation revealed a small, 1-mm focus of atypical cells with morphology resembling that of the previous tumor with a nearby focus of neoplastic, mature cartilage. The presence of atypical cells and neoplastic cartilage in the testicle may have represented a malignant mixed germ cell tumor that presented as a retroperitoneal, pure, yolk sac tumor with no obvious clinical evidence of testicular involvement at the time of presentation. This case represents a very uncommon presentation of a yolk sac tumor in an adult.

Context: The condyloma acuminata (CAs) are lesions produced by human papilloma virus (HPV). CA is the most frequent STD worldwide and affects mainly young people. The purpose of this study is to determine the HPV genotype among the patients with genital warts (CAs) and its correlation with several epidemiologic, clinical, histopathologic, and molecular parameters.

Design: We conducted a noncomparative prospective study of 181 lesions with the clinical diagnostic of CA. Diagnostics included histopathology, HPV type by polymerase chain reaction (real-time polymerase chain reaction; Figure 30), and direct sequencing.

Results: Of the cases, 51% occur during the third decade of life and the most frequent locations are vulva, penis, and perianal zone (Figure 30). Twenty-four percent of the cases with the diagnostic of CA were not histologically diagnosed. Only in 1 of 181 cases was HPV not found. Twenty-two percent of the cases showed high-risk HPV genotypes. Seven percent of the patients showed HIV infection. The manifestation of a high-risk HPV genotype among these patients was statistically significant. Fifty-seven percent of the patients had more than 3 different sexual partners per year.

Conclusions: There is a correlation between the clinical diagnostic and the molecular findings of HPV. The histology does not support the diagnostic in a significant number of cases. In a considerable number of cases, a high-risk HPV genotype was found. However, most of the cases showed low-risk HPV genotypes as well (Figure 30). The HIV patients presented mainly high-risk HPV genotypes.

We describe a case of primary cutaneous MEC in a 52-year-old man who presented with a swelling on his back of 2 months' duration. The salivary glands were normal. The excisional biopsy specimen measured 2.5 × 2 × 2 cm in size. Cut section showed a solid grayish-white neoplasm with a slimy or mucoid feel. There was no gross involvement of the attached eclipse of skin. Histopathology showed, subjacent to an unremarkable epidermis (Figure 31), a solid, circumscribed, unencapsulated neoplasm occupying the mid and lower dermis. The neoplasm was composed of lobules of polygonal (epidermoid) cells with vesicular, slightly hyperchromatic, irregular nuclei and prominent nucleoli. Admixed with the epidermoid cells were clusters or scattered mucin-producing cells having abundant vacuolated cytoplasm and eccentrically compressed hyperchromatic nuclei. Dense fibrosis between the tumor cell lobules and occasional glandular structures were present. Transitions between the 2 cell populations were present. Frequent mitoses were encountered. Necrosis and neural and/or vascular invasion were absent. Epidermal attachment could not be demonstrated in the several sections studied. Mucin stains highlighted the mucigenic cells and immunohistochemistry revealed positivity for epithelial membrane antigen, pan-cytokeratin, and polyclonal carcinoembryonic antigen. These features were similar to MEC of salivary gland. We believe that cutaneous adenosquamous carcinoma represents a separate entity and MEC of the skin should be regarded as a tumor of cutaneous appendages. We would recommend that pathologic distinction should be made between these 2 neoplasms for prognostic purposes.

Mast cell disorders encompass a wide variety of clinical features ranging from cutaneous lesions to accumulation of neoplastic mast cells within several organs, signifying aggressive multisystem involvement. Mast cell sarcoma is a rare entity, which is usually distinguished by localized, yet destructive neoplastic mast cell expansion. Point mutations in KIT proto-oncogene have been detected in most cases of mast cell disorders. We report a case of a 1-year-old male infant who presented with a right-sided ear mass at 8 months of age. The mass was initially diagnosed as mastocytoma. Subsequent imaging showed a large, locally aggressive right temporal bone tumor. Biopsy specimen demonstrated infiltrating sheets and clusters of medium-sized to large atypical histiocytoid cells, with nuclear contour irregularity, many of which exhibited prominent nuclear clefting and hyperlobation and abundant, lightly eosinophilic cytoplasm (Figure 32). These atypical cells were positive for CD25, CD117, CD68, and tryptase and were nonreactive for CD1a and S100. Furthermore, flow cytometry revealed presence of an atypical mast cell population. However, molecular analysis of the tumor did not show the characteristic KIT mutation. Nevertheless, the clinical, radiographic, morphologic, and immunophenotypic features were most consistent with mast cell sarcoma. To our knowledge, only 4 cases of mast cell sarcoma have been reported in the literature thus far, and unlike our case, none of the documented cases occurred in infancy. Thorough clinical follow-up and multimodal approach are imperative in accurately diagnosing this rare entity, particularly in differentiating it from benign lesions, or other neoplasms presenting in this age group.

A 49-year-old black woman without any significant past history was found to have chronic myeloid leukemia in chronic phase. At presentation she demonstrated the classic Philadelphia chromosome t(9;22) in all 20 metaphases examined, with BCR-ABL rearrangement by fluorescence in situ hybridization (FISH) in 96.3% of nuclei. No other karyotypic abnormality was identified. The BCR-ABL transcript was identified as b2a2 and quantitated pretreatment. The patient received hydroxyurea transiently, followed by imatinib 400 mg daily, with sporadic compliance. A good hematologic response and 1.2 log reduction of fusion transcripts in the peripheral blood was noted. Nine months after initial diagnosis the patient developed neutropenia with 11% peripheral blasts. A bone marrow biopsy revealed 56% blasts with monocytoid features by differential. Flow cytometry studies demonstrated 35%–45% blasts with myeloid phenotype expressing CD34, CD33, HLA-DR, and partial CD64. Chromosome analysis of 20 bone marrow metaphases revealed t(9;22) in all 20 and an additional translocation between the long arm of chromosome 20 and long arm of chromosome 21 at bands 20q11.2 and 21q22, respectively, in 12 of 20 metaphases. FISH studies using the AML1 gene probe, which maps to chromosome 21q22, confirmed an AML1 gene rearrangement. Although in this patient a kinase domain mutation assay has confirmed the 35-nucleotide insertion mutation in the BCR kinase with no other mutations, this has never been implicated in CML transformation to blast crisis. These findings implicate t(20;21) involving AML1 gene in the progression of CML to myeloid blast crisis, a phenomenon that has been reported only twice previously (Figure 33).

Mantle cell lymphoma (MCL) is a mature B-cell lymphoma with 4 morphologic variants recognized by the current World Health Organization classification. Marginal zone-like MCL (MZ-MCL) is the rarest variant, which could be a potential diagnostic pitfall owing to its deceiving “monocytoid” appearance. We report a case of MZ-MCL in a 70-year-old man with a past history of squamous cell carcinoma of the lip, presenting with a mass at tongue base and lymphadenopathy on imaging. Oropharyngeal biopsy was done to rule out possible metastatic squamous cell carcinoma. However, there were diffuse submucosal lymphoid infiltrates of small to medium-sized lymphocytes with a monocytoid appearance (Figure 34, A). The neoplastic cells were κ-restricted B cells without expression of CD5 and CD10 but showed diffuse nuclear positivity for BCL-1 (Figure 34, B and C). The diagnosis of MCL was further substantiated by the presence of t(11;14)(q13;q32) involving BCL1 and IgH by fluorescence in situ hybridization. SOX11 is a new immunohistochemical marker highly specific for classic MCL, but negative in the indolent form of MCL. Interestingly, our case showed rare (<5%) weak nuclear expression of SOX11 (Figure 34, D, arrowheads), a feature associated with an indolent clinical course in MCL. In agreement with the SOX11 result, the Ki-67 proliferation index of our case is also low (approximately 10%). In summary, we, for the first time, report the negative expression of SOX11, which may support the notion that MZ-MCL is an indolent form of MCL. More cases are needed to investigate the clinical behavior of MZ-MCL.

Intravascular lymphoma (IVL), first reported in 1959 as “angioendotheliomatosis proliferans systemisata” and considered to be a neoplasm of endothelial cells, is now defined as the proliferation of clonal lymphocytes mainly lodged in the lumina of small or intermediate-sized vessels with little or no involvement of the organ parenchyma. Most cases are of B-cell origin; however, rare cases of T-cell or NK-cell lineage have also been reported in the literature, of which extremely rare cases show anaplastic morphology and cytotoxic phenotype. We report the case of a 69-year-old man with a 5-month history of a 1.8-cm, dark-purple, indurated skin lesion on right cheek, with no lymphadenopathy, hepatosplenomegaly, fever, weight loss, or mental status changes. His past medical history was significant for a remote stroke, atrial fibrillation, and warfarin therapy. Skin biopsy revealed highly pleomorphic large atypical lymphoid cells with irregular nuclear contour, conspicuous nucleoli, and abundant cytoplasm located within and confined to the lumina of intradermal vessels. Some cells showed features of hallmark cells with eccentric horseshoe-shaped nuclei. Immunophenotypic study (Table) was consistent with T-cell or NK-cell origin of the tumor cells, with cytotoxic features. T-cell receptor (TCR) β gene was clonally rearranged, consistent with a monoclonal T cell population. Further laboratory, radiographic, and bone marrow evaluations were negative for involvement by lymphoma. This is a report of an extremely rare case of cutaneous intravascular T-cell lymphoma with anaplastic large cell morphology and phenotype, a different entity not considered a subtype of intravascular lymphoma by World Health Organization classification.

Immunophenotypic Study Results

Immunophenotypic Study Results
Immunophenotypic Study Results

Context: The diagnosis of T-cell lymphoma can be challenging. Immunohistochemical stains have often been used to support a diagnosis. There have been anecdotal reports in the past about the loss of bcl-2 as a supportive finding in T-cell lymphoma diagnosis. We evaluated bcl-2 expression in 125 well-characterized T-cell lymphomas. In addition, we evaluated expression of CD25, the IL-2 receptor, and PD1, a relatively new marker that is positive in T cells of follicular helper origin.

Design: We selected 125 cases of T-cell lymphoma with slides available for immunohistochemical staining. We performed staining for bcl-2, PD1, and CD25 in these cases by using standard methods. Included in the study were peripheral T-cell lymphoma (PTCL; 41); angioimmunoblastic T-cell lymphoma (AITL; 24); anaplastic large cell lymphoma (ALCL), ALK1 positive (21); ALCL, ALK1 negative (28); and small numbers of other types.

Results: Results are summarized in the Table.

Conclusions: We found that a significant percentage of T-cell lymphomas had loss of bcl-2 expression (48%). Further, there were important differences in the frequency in different subtypes. We also found significant variation of PD1 expression and CD25 within subtypes. This study supports the finding that loss of bcl-2 expression is an important ancillary tool in the diagnosis of T-cell lymphomas.

Acute promyelocytic leukemia (APL) is associated with reciprocal translocation of chromosomes (15;17)(q22;q21), resulting in the fusion of the PML and RARA genes. We describe a case of a 67-year-old man with APL carrying a novel variant of (15;17) translocation. The marrow showed typical APL morphology except for absence of Auer rods. Flow cytometry analysis was consistent with APL. Reverse transcription-polymerase chain reaction confirmed the PML/RARA transcripts. Standard G-banding analysis on marrow cells demonstrated a karyotype of 46,XY,del(17)(q12q21.1)ins(15;17)(q22;q21.2q25.3)[18]/46,XY[2]. Fluorescence in situ hybridization using the dual-color, dual-fusion PML (15q22, orange)/RARA(17q21, green) probe also showed a variant abnormal pattern (Figure 35).The cells of typical patients with APL have 1R (red), 1G (green), and 2F (fusion or yellow) signals. Our patient had 1.5% of cells with the typical abnormal pattern; however, 85% of the cells had 2O∶1G∶1F signals. The results demonstrated that the RARA/PML fusion was absent from chromosome 17. PML remained on the der(15) and PML/RARA was inserted or translocated into the der(15). To our knowledge this abnormality has not been described before. The patient was treated with the Cancer and Leukemia Group B (CALGB) protocol 9710 regimen. His response to ATRA has been slow. The patient will be closely monitored. His clinical progress should add to our knowledge of the prognostic significance of this novel variant rearrangement.

Spontaneous regression is rare in malignant lymphomas and particularly so in high-grade lymphomas such as diffuse large B-cell lymphoma (DLBCL). Here we report the case of a previously healthy 50-year-old woman who presented with a 2-week history of a right breast lump. Ultrasonography showed a multilobulated solid mass measuring at least 4.4 cm. Fine-needle aspiration biopsy showed only normal breast tissue. A simultaneous core biopsy revealed DLBCL invading breast tissue in 1 core and normal breast tissue in another core (Figure 36). The tumor cells had centroblast-like morphology and were positive for CD45, CD20, CD10 (weak), Bcl-6, MUM1, and Bcl-2 and negative for CD5, CD3, and keratin. The MIB1 index was 80%–90%. Fluorescence in situ hybridization analysis was negative for MYC gene rearrangement. MRI and PET scans carried out within 2 months after the biopsy showed no residual tumor. Results of blood counts, bone marrow biopsy, and blood chemistry, including LDH, were all normal. Owing to the negative findings, the possibility of a specimen mix-up with the initial biopsy was raised. DNA analysis performed on the bone marrow biopsy specimen and the lymphoma showed identical DNA short-tandem-repeat profiles. The patient declined treatment, and at 5 months, MRI results continued to be negative. DLBCL is an aggressive lymphoma, and spontaneous regression has been reported only rarely. This case is an example of spontaneous regression occurring within weeks of a biopsy procedure, and it raises important questions regarding the mechanism and permanence of regression.

A 70-year-old healthy man presented with abdominal pain. A complete blood cell count revealed increased white cells with circulating blasts (22%), moderate anemia, and a normal platelet count. Fibrinogen levels were elevated (570 mg/dL). A bone marrow biopsy revealed a markedly hypercellular bone marrow with trilineage dysplasia and increased number of myeloblasts (58%). In addition to abundant cytoplasmic eosinophilic granules and globules, the myeloblasts also contained eosinophilic square (Figure 37), rhomboid, and rectangular crystals. Occasional Auer rods were also seen. On immunohistochemistry, the blasts were strongly positive for myeloperoxidase and CD33 and negative for CD34. The myeloperoxidase staining was noted in the cytoplasmic granules, globules, as well as in the crystalline inclusions. Flow cytometric analysis demonstrated that the blasts were weakly positive for HLA-DR and negative for CD34 and CD13. Chromosomal analysis revealed an abnormal male karyotype; however, results of fluorescence in situ hybridization for PML-RARa t(15;17) and myelodysplastic syndrome panel, including probes for t(8;21), were negative. While cytoplasmic eosinophilic granules are characteristically seen in acute myeloid leukemias with recurrent genetic abnormalities, specifically t(15;17) and t(8;21), these leukemias were ruled out by molecular studies. According to the World Health Organization classification (2008), this leukemia would be best classified as “acute myeloid leukemia with myelodysplasia-related changes.” Although rhomboid inclusions consisting of immunoglobulin have been described in plasma cell myeloma, to the best of our knowledge, they have not been reported in myeloblasts. In our opinion, these inclusions are related to Auer rod–like material and probably represent a manifestation of myelodysplastic syndrome/neoplasm.

Context: Plasma cell leukemia (PCL) is a rare disorder of clonal plasma cells in the peripheral blood that is considered primary if present at the time of diagnosis and secondary if seen in the course of plasma cell myeloma. A small subset displays plasmablastic morphology, the significance of which has not been elucidated in the literature to our knowledge. Here we compare the clinical outcomes, and morphologic and immunophenotypic features, of 5 PCL cases with and without plasmablasts.

Design: We conducted a computerized search for pathology cases with a diagnosis of PCL and/or with the terms “plasmablasts” or “plasmablastic” within the pathology report in our institution during the past 11 years.

Results: Five PCL cases were found, 3 primary and 2 secondary. Two of the primary and 1 of the secondary PCLs displayed plasmablastic morphology. The 2 patients with primary PCL with plasmablastic morphology had the shortest survival times after initial diagnosis. The 3 cases with plasmablastic morphology showed plasma cells with immature features including basophilic cytoplasm, dispersed chromatin, and prominent nucleoli. All cases were positive for CD38 and/or CD138 and negative for CD20. Two of the cases with plasmablastic morphology were negative for CD56 (Table).

Conclusions: PCL with plasmablastic morphology can be associated with a rapidly fatal disease course, especially if primary. Prior studies have suggested that secondary PCL is associated with a worse prognosis than its primary counterpart, but in our series, survival times were shorter in primary PCL. Cases of PCL can be negative for CD20 and have aberrant expression of CD56.

Summary of Results

Summary of Results
Summary of Results

Lymphomatoid granulomatosis (LyG) is a rare extranodal Epstein-Barr virus (EBV)–related lymphoproliferative disorder characterized by angiocentric, angiodestructive growth. LyG commonly involves the lungs, brain, kidneys, liver, and skin. The bone marrow, gastrointestinal tract, and lymph nodes are rarely involved. Our patient is a 19-year-old HIV-negative man who presented with hematemesis and hematochezia. Imaging revealed bilateral pulmonary masses without lymphadenopathy. Papulonodular skin lesions were noted on the abdomen and ulcerative lesions were seen on colonoscopy. Quantitative EBV DNA analysis revealed 3.9 million copies/mL in serum. Sections of lung showed centrally necrotic nodules surrounded by large lymphocytes with immunoblastic or plasmacytoid morphology and angiocentric growth (Figure 38). A variable inflammatory background was also present. The infiltrate was immunoreactive for CD45, CD20 (subset), CD79a, CD138 (subset), bcl-2, and CD30 (focal) by immunohistochemistry. λ Light-chain restriction was demonstrated and numerous large cells were EBV positive by in situ hybridization (>50 cells/high-power field) (Figure 38, inset). Skin and colon biopsies showed a similar polymorphous infiltrate with occasional EBV-positive cells. The bone marrow demonstrated a predominantly plasmacytoid infiltrate with scattered EBV-positive large cells. The findings were that of LyG with possible transformation to EBV-positive diffuse large B-cell lymphoma. Chemotherapy was initiated; however, the patient died of his disease 19 days after diagnosis. This case of LyG demonstrates the histologic spectrum, need for extensive immunophenotypic studies, and importance of clinicopathologic correlation to establish this challenging diagnosis. The atypical presentation, including bone marrow and gastrointestinal involvement, may further suggest histologic progression and poor prognosis.

Mixed phenotype acute leukemias (MPALs), as defined in the 2008 World Health Organization (WHO) classification of hematopoietic tumors, include bilineal and biphenotypic leukemias. The diagnosis is established by flow cytometric immunophenotyping. Cases that qualify as MPAL include myeloid/T-lymphoid or myeloid/B-lymphoid leukemias. To date, cases of MPAL with a B/T-lymphoid mixed phenotype have not been reported. We report a first such case of MPAL with mixed B/T phenotype in an 82-year-old man who presented with pancytopenia. Clinically, the patient was stable with no symptoms. The aspirate smears showed a single population of 66% blasts with lymphoblastic cytomorphology (Figure 39, B). Flow cytometric immunophenotyping revealed a homogeneous blast population expressing CD45, CD34, CD10, HLA Dr, and TdT. The blasts coexpressed T-lymphoid lineage markers (cytoplasmic CD3 and CD7), B-lymphoid lineage markers (CD19 and CD22), and myeloid markers (CD13, CD117, and CD15). Staining results with CD5, CD11b, CD14, CD33, CD56, CD61, CD79a, CD235a, and myeloperoxidase were negative (Figure 39, A). Based on the revised criteria proposed in the 2008 WHO classification for lineage assignment to single blast population, our case has strong evidence of T (cyto CD3) as well as B (CD19, CD22, and CD10) markers on the blasts, thus consistent with MPAL, B/T phenotype. With lack of myeloperoxidase, expression of other myeloid markers is less specific for designation of myeloid lineage. Alternatively, considering the complex immunophenotype with B/T and some myeloid marker expression, this may also represent trilineage acute leukemia. In summary, we report a unique case of mixed phenotype leukemia. Interestingly, cytogenetics did not reveal any abnormalities.

Chronic leukemias can arise from either myeloid or lymphoid lineage. However, it is rare to have both lineages in 1 patient. We report a case in which a patient was diagnosed with chronic myelogenous leukemia and chronic lymphocytic leukemia. A 66-year-old man was referred to our hospital for evaluation of asymptomatic persistent lymphocytosis of 12 years and new onset neutrophilia, eosinophilia, and basophilia. Peripheral blood flow cytometry was ordered, which confirmed the diagnosis of B-cell chronic lymphocytic leukemia (Rai stage 0), CD38. The patient was not treated at this time. At the 1 month follow-up, in order to rule out concurrent myeloproliferative disorder, Jak-2 mutation evaluation was ordered and results were negative. Three months later, when the patient was reevaluated, the peripheral smear was highly suggestive of chronic myeloid leukemia. Fluorescence in situ hybridization analysis for 9;22 translocation was positive. Bone marrow showed myeloid hyperplasia on the smear (Figure 40, A) and lymphoid aggregates in the bone biopsy (Figure 40, B). Molecular testing for BCR-ABL fusion protein confirmed chronic myeloid leukemia, chronic phase. Flow cytometry confirmed chronic lymphocytic leukemia. The patient was treated with imatinib mesylate and had morphologic, cytogenetic, and molecular remission of chronic myelogenous leukemia within 6 months. The B-cell chronic lymphocytic leukemia is in chronic phase and is being monitored without any therapeutic intervention. To our knowledge, this is only the 11th case of chronic lymphocytic leukemia and sequential chronic myelogenous leukemia. It is the fourth case occurring without previous chronic lymphocytic leukemia treatment. However, this is the first case with chronic myelogenous leukemia treated with imatinib mesylate with complete remission.

Context: Although the mechanism of neoplastic transformation is not clear, hepatitis C virus (HCV) infection reportedly carries increased risk for non-Hodgkin lymphoma (NHL). Our institution has a patient population that includes many patients infected with human immunodeficiency virus (HIV) and HCV. We conducted this retrospective study to investigate the distinctive clinical presentations and classifications of lymphomas occurring in HCV-infected, HIV-infected, and uninfected patients.

Design: Medical records of patients with lymphoma diagnosed from 2001–2010 were reviewed to identify those diagnosed by cytology and/or biopsy in conjunction with flow cytometry and immunohistochemistry. Patients were stratified into 3 groups: HCV positive, HIV positive, and control (HCV negative, HIV negative). Lymphomas were classified, within certain limitations, using the World Health Organization classification system. Age, sex, site of presentation (nodal versus extranodal), and stage were compared for the 3 groups.

Results: Patients in the HCV and the HIV group were similar with respect to sex, extranodal occurrences, percentage of high-grade B-cell NHLs, and a higher stage at diagnosis (Table). Interestingly, the control group had only 1 case (5%) that primarily involved the liver in comparison to 2 (11%) cases in the HCV-positive group and 3 (19%) cases in the HIV-positive group.

Conclusions: Our findings suggest that, similar to HIV, HCV-associated lymphomas present at a higher stage, have increased incidence of extranodal involvement, and a male predilection. In addition, our research suggests that there may be a higher frequency of NHL liver involvement in both HCV- and HIV-infected patients than in uninfected patients.

Study Results

Study Results
Study Results

Epstein Barr Virus (EBV)–positive, diffuse large B-cell lymphoma (EBV+ DLBCL) in the elderly is an EBV-driven B-cell neoplasm related to age-associated debility in immunity. The clinical course is aggressive, with median survival of 24 months. We report a case of EBV+ DLBCL in a 59-year-old woman who presented with a catastrophic clinical course and fulminant dissemination of lymphoma cells to visceral organs resulting in multiorgan failure and a precipitous death. The patient, who had an unremarkable past medical history, presented with fever, fatigue, malaise, and weight loss during a 1 week period. After unsuccessful treatment with antibiotics, she was admitted and found to have elevated liver function test results. A viral infection with septic shock was considered, and she was treated with antibiotics and antiviral medications. Radiographic imaging revealed hepatomegaly, splenomegaly, and mild pleural effusion and ascites, but the results of serologic tests for viruses were negative. During a short hospital course, she developed cardiac and renal failure, coagulopathy, and metabolic acidosis. Her complete blood cell count showed marked leukocytosis, anemia, and thrombocytopenia. Examination of a blood smear demonstrated a monotonous population of abnormal lymphocytes with plasmacytoid morphology (Figure 41), which was confirmed by flow cytometry. High copies of EBV genome were detected in the blood by polymerase chain reaction. A diagnosis of EBV+ DLBCL, leukemic phase, was made. Despite treatment with high-dose dexamethasone plus supportive care, our patient's condition deteriorated, and she eventually succumbed to multiorgan failure 1 week after initial presentation. Autopsy demonstrated EBV+ neoplastic infiltration in all the tissues examined.

Anaplastic large cell lymphoma, ALK+, is a T-cell lymphoma that expresses the ALK protein and contains hallmark cells—large lymphoid cells with abundant cytoplasm and pleomorphic, horseshoe-shaped nuclei. We present a case of a 43-year-old man with human immunodeficiency virus/AIDS (CD4 count of 99) who presented with a 1 month history of fever, chills, and myalgias with rapid decompensation. During exploratory laparotomy, he was found to have massive hepatosplenomegaly and generalized lymphadenopathy. A mesenteric lymph node biopsy was received in the pathology department to rule out lymphoma. Hematoxylin-eosin and immunohistochemical stains were evaluated. Additionally, flow cytometry was performed. Histology from the lymph node biopsy showed intermediate to large cells with round, vesicular nuclei with fine chromatin and one to several nucleoli. There were no multinucleated cells or hallmark cells seen (Figure 42). Flow cytometry revealed a predominant population of lymphocytes that expressed CD2, CD3 (cytoplasmic), and CD4, with partial loss of CD7 and CD3 (surface), and complete loss of CD5 and CD8. These findings were consistent with peripheral T-cell lymphoma. Because of the morphology of the cells, it was not until immunohistochemical stains showing positivity for CD4, CD30, and ALK-1 were reviewed that the diagnosis of anaplastic large cell lymphoma, ALK+ was entertained. This case reinforces the understanding that anaplastic large cell lymphoma, ALK+, has a highly variable morphologic appearance. In cases in which the diagnosis may be peripheral T-cell lymphoma, not otherwise specified, ALK-1 should always be performed to rule out anaplastic large cell lymphoma, ALK+, which has a different treatment plan and better prognosis.

Context: The analysis for immunophenotypic abnormalities by flow cytometry in myelodysplastic syndrome (MDS) may offer a valuable tool for its classification and prognosis. Unlike peripheral blood platelets, there are no established immunophenotypic abnormalities for megakaryocytes or platelets in bone marrow evaluations.

Design: We performed GPIIb (CD41) staining during a 26-month period on 159 bone marrow biopsies submitted for unexplained anemia at our institution. The history and follow-up of these patients was reviewed.

Results: Of 159 biopsies, MDS was diagnosed in 62 (39%), and of these, 36 (58%) were negative for CD41 staining. Of the remaining 26 biopsies, 17 (65%) had positive CD41 staining as an ill-defined, small population, whereas 9 of 26 (35%) showed positivity as a homogeneous cluster that stained bright. CD41 expression has a sensitivity of 41.9% and specificity of 100% for MDS. The positive predictive value is 100% with a risk ratio of 3.69. Abnormal karyotype was noted in 8 of 26 patients, 5 with a homogenous CD41 staining pattern. Moderate to severe anemia was seen in the 26 cases. Most (23 of 26; 88%) had thrombocytopenia, whereas 3 (12%) showed thrombocytosis. Megakaryocytic dysplasia was present in the biopsy of 26 patients. On follow-up, 4 of 26 patients died after transformation to acute leukemia (Figure 43).

Conclusions: We propose that positive CD41 staining pattern in bone marrow flow cytometry is associated with MDS and may serve as immunophenotypic criteria for the diagnosis. The presence of a homogenous CD41 staining population is associated with thrombocytopenia and the presence of a cytogenetically identifiable clone.

Splenic diffuse red pulp small B-cell lymphoma is a provisional entity in the World Health Organization classification. Morphologically, this hematopoietic malignancy diffusely involves the red pulp of the spleen, sparing the white pulp. The neoplastic lymphocytes are monotonous, small to medium in size, with round vesicular nuclei, and occasional distinct nucleoli. Bone marrow findings include intrasinusoidal infiltration and possible interstitial/nodular infiltration patterns. Lymphocytes within the peripheral blood often have short cytoplasmic villi. Characteristic immunophenotype results are as follows: positive for CD11c, CD22, DBA.44, and immunoglobulin (Ig) G, and negative for CD5, CD10, CD23, CD25, CD103, CD123, IgD, annexin A1, cyclin D1, and tartrate-resistant acid phosphatase. This entity generally has an indolent course with a 93% 5-year survival rate. We present a 62-year-old man with a history of polycythemia vera who was found to have a low-grade B-cell lymphoproliferative disorder with characteristics of a variant hairy cell leukemia or marginal zone lymphoma (including splenic). Two years later, he developed marked splenomegaly (3975 g) and was ultimately diagnosed with splenic diffuse red pulp small B-cell lymphoma. Two months after diagnosis, the patient had escalating liver enzymes. Subsequent computed tomography scan showed extensive bilateral pulmonary nodules, 2 nodules in the liver (3 and 15 cm), mesenteric nodularity suggestive of lymphoma, and bilateral renal masses. A liver biopsy showed involvement by diffuse large B-cell lymphoma. Currently, less than 10 total cases have been described to undergo transformation. Transformation to diffuse large B-cell lymphoma has only been reported in one other case (Figure 44).

Context: Quantitative phase imaging (QPI) is capable of providing detailed morphologic analysis as well as several novel, clinically relevant parameters for red blood cells. However, because the optical phase shift through a red blood cell is a function of both thickness and refractive index, a priori knowledge of the hemoglobin concentration has, so far, been necessary for QPI techniques. This limits the reliability, accuracy, and scope of single-cell analysis using such technologies.

Design: By combining the quantitative phase information measured using a spatial light interference microscope with bright field absorption measurements, it is possible to quantitatively determine single-cell hemoglobin concentration, oxygenation state, and cell morphology.

Results: It is possible to use QPI in combination with absorption measurements as a label-free smear analysis technique that provides more information than current automated analyzers. Figure 45 shows an absorption measurement of a typical smear at (a) 430 nm and (b) a quantitative phase map.

Conclusions: Such an instrument may be deployed as a standalone blood smear analyzer in a clinical setting without relying on external measurements of hemoglobin concentrations as in previous blood-screening QPI instruments. The additional set of parameters measured may offer the ability for earlier diagnosis and could lead to the automated detection of conditions that currently require manual smear analysis.

We describe a 46-year-old woman who presented with chronic refractory anemia and a prior history of gastric bypass surgery for controlling obesity-related comorbidities. She was treated with iron supplementation and multiple blood transfusions, without sustained response. The bone marrow biopsy showed dysplastic erythroid and myeloid precursors and adequate marrow iron stores with 15% abnormal ringed sideroblasts. Bone marrow karyotype was normal. Evaluations of her nutritional status revealed borderline-low, normal serum iron with serum copper in the reference range (Table). The patient received oral iron and copper supplements and also provided a prior history of Chinese herbal medication (a mixture of different minerals and multiple vitamins) use. However, her hematologic abnormalities persisted. Additional laboratory studies found an increased antinuclear antibody concentration (1∶160, homogeneous pattern), normal serum transferrin, ferritin, and total iron-binding capacity, vitamin B12, folate, and vitamin B6 levels. One month after treatment with erythropoietin, the blood count and bone marrow findings were within reference range. Anemia of chronic disease related to chronic inflammation associated with an underlying connective tissue disorder was identified as the underlying etiology via suppression of erythropoiesis by interference with storage iron release. In addition, in the current case, concurrent morbid obesity may have contributed to the inflammatory state. We recommend serum erythropoietin as well as iron and copper determination in the diagnostic workup of patients with suspected myelodysplastic syndrome, including those with a history of gastric bypass surgery associated with obesity-related comorbidities.

Pure erythroid leukemia (M6b by the French-American-British classification) is a rare subtype of acute myeloid leukemia with an aggressive clinical course. It is defined by more than 80% of the marrow cells being composed of immature erythroid elements with an undifferentiated or proerythroblastic appearance and no significant myeloblastic component. We report a case of a 4-month-old, male infant who presented with multifocal extramedullary myeloid sarcomas (intratemporal orbital and testicular masses) concurrent with a pure erythroid leukemia. To our knowledge, this is only the second pure erythroid leukemia presenting as a myeloid sarcoma described in the English-language literature. The patient initially presented with an intratemporal orbital mass. An incisional biopsy revealed a poorly differentiated malignancy most consistent with a myeloid sarcoma (positive findings for CD43, CD33, and CD4 by immunohistochemistry; negative results for B-cell and T-cell markers, MPO, CD34, ALK, CD42, CD61, AE1/3, MyoD1, and desmin). A bone marrow biopsy, complete blood cell count, and biopsy of a previously unmentioned testicular mass were subsequently performed. The bone marrow studies revealed a prominent erythroblast population (CD45 dim, glycophorin A+) representing more than 85% of all nucleated elements. Peripheral smear examination revealed 19% erythroblasts. The testicular mass revealed an infiltrative population of blasts that expressed CD117 and CD235a (glycophorin A) by immunohistochemistry (Figure 46). This case highlights the importance of careful morphologic and flow cytometric analysis and expands the spectrum of presentations for pure erythroid leukemias. The young age of this patient adds to the rarity of this presentation.

Systemic lupus erythematosus is associated with a broad spectrum of clinical manifestations affecting virtually every organ system. Although lymphadenopathy is a common finding in lupus, it is rarely the primary presenting manifestation. We report the case of a 33-year-old, Hispanic woman with an unremarkable past medical history who originally presented with a 6-week history of fever, fatigue, and weight loss. Her initial laboratory results showed pancytopenia, and physical examination revealed axillary, cervical, and supraclavicular lymphadenopathy. Ehrlichia immunoglobulin M was weakly positive, whereas results for other infectious disease serologies were negative. She was started on doxycycline without improvement in her symptoms. Fine-needle aspiration of a right supraclavicular lymph node was consistent with reactive lymphoid hyperplasia. A bone marrow evaluation showed no evidence of a neoplastic or infectious process. Because a positron emission tomography-computed tomography scan showed extensive lymphadenopathy, which was highly concerning for lymphoma, 2 right axillary lymph nodes were excised. One of the lymph nodes was largely necrotic, whereas the other was partially necrotic. The viable areas exhibited hyperplastic features, including paracortical hyperplasia, sinus histiocytosis, and scattered secondary follicles. Both lymph nodes contained prominent, subcapsular, and perivascular hematoxylin bodies (Figure 47), which strongly suggested lupus lymphadenitis. Special staining for fungi and acid-fast bacteria was negative. Subsequently, a high-titer ANA and antidouble-stranded DNA were identified. The patient was started on methylprednisolone and hydroxychloroquine with rapid clinical improvement. In patients presenting with necrotizing lymphadenitis, the differential diagnosis should include systemic lupus erythematosus in addition to Kikuchi disease, infection, and neoplastic diseases.

Context: The long-term management of anticoagulation with warfarin requires reliable measurements of prothrombin time–international normalized ratio (PT-INR) for maintenance of patients within therapeutic ranges. The Geisinger Health System multisite, pharmacy-managed anticoagulation clinic has 8143 patients at 16 sites where routine fingerstick PT-INR, patient evaluation, and Coumadin dose adjustments are performed by a doctor of pharmacy (PharmD). The laboratory medicine point-of-care testing (POCT) section is responsible for instrument selection, method validation, personnel training, and proficiency testing. Recent occurrences of unexpectedly high results with the i-STAT (Abbott Laboratories, Abbott Park, Illinois) led us to perform a comparison of the i-STATs, first with simultaneous venipuncture samples on Stago instruments (Diagnostica Stago, Parsippany, New Jersey) and then with the CoaguChek (Roche Diagnostics, Indianapolis, Indiana) device.

Design: In the first phase, 38 samples were analyzed by i-STAT versus Stago throughout a range of 1.01 to 5.18 INR. Deming regression yielded Y  =  1.51 × X − 0.705, where Y  =  INR i-STAT and X  =  INR Stago. The second phase was performed with 78 patients at 3 clinic locations, and patients had 2 fingersticks for POCT and venipuncture for PT-INR by Stago instrument.

Results: Our results are shown in the Table. Because both methods showed a high bias, the data were further analyzed in the clinical context of whether dosage adjustment would have been affected. Such analysis indicated that 27 of 78 i-STAT results (34.6%) and 7 of 76 CoaguChek results (9.2%) would have led to an inappropriate reduction in warfarin dose.

Conclusions: Although neither method is ideal, the CoaguChek yielded less bias and fewer potential problems. These results point out that the clinical correlation of results is just as important as the method evaluation statistics in determining proper POCT instrument selection.

Context: Anemia is very common in the geriatric population. The definition of anemia relies heavily on the complete blood cell (CBC) count and specifically hemoglobin and hematocrit, which are affected by several factors: ethnic background, sex, altitude, and physiologic fluctuation of plasma volume. It has been shown that posture can cause change in the results for some blood indices.

Design: The CBC specimens were collected from residents in long-term care facilities early in the morning when the patients were still in bed. Another set of CBC specimens were collected from the same patients in the afternoon. The patients' position was noted, and CBC results were collected using Coulter LH 780 impedance/cell sizing counter (Beckman Coulter, Fullerton, California). Statistic calculations were performed using Statistica (StatSoft, Tulsa, Oklahoma). We considered any P < .05 to be statistically different.

Results: All the samples showed an increase in CBC values between early morning (patient in bed) and afternoon (patient has been moving). The most statistically significant difference was with hemoglobin followed by hematocrit, red blood cells, platelets, and white blood cells.

Conclusion: Our results confirm the notion that a change in posture causes changes in some of the blood indices; posture changes the hydrostatic pressure that leads to a change in the movement of fluid between interstitial space and intravascular space and causes physiologic fluctuations in blood volume. Physicians should give more attention to this fact, especially in severely anemic patients, where the difference in posture may alter the hemoglobin result or indicate a need for more aggressive treatment (blood transfusion).

Sézary syndrome (SS) is a rare disease primarily affecting the middle-aged and elderly with a male predominance. It is defined by the triad of circulating Sézary cells (clonally related neoplastic T cells with characteristic cerebriform nuclei), erythroderma, and lymphadenopathy. Bone marrow (BM) involvement is uncommon, and, when present, the infiltrates are often sparse. This is a report of a case of SS “incidentally” identified by BM examination. An 82-year-old, white man had persistent monoclonal gammopathy of undetermined significance. He also had superficial maculopapular rash that exhibited mixed inflammatory infiltrate and mild spongiosis, with drug eruption as the main histologic differential diagnosis. The patient presented with decreasing hemoglobin/hematocrit, platelets, and fibrinogen levels. Peripheral blood smear demonstrated atypical lymphocytes with convoluted nuclei. Fluorescence in situ hybridization of the BM aspiration, to rule out plasma cell dyscrasia, revealed trisomy 1; 1q duplication; hyperdiploidy of chromosomes 3, 5, and 9; and multiple unusual patterns. Flow cytometry of the BM aspiration revealed 12% CD4+ CD7 T cells. The BM morphology review demonstrated hypercellular (>90%) marrow largely effaced by a T-cell lymphoproliferative disorder, with intermediate to large cells exhibiting highly convoluted nuclei and abundant cytoplasm (Figure 48). These cells were uniformly CD3+ with strong coexpression of CD4 (Figure 48, inset) and CD5, and loss of CD7 expression. The CD4∶CD8 ratio was elevated to more than 10, with CD8 highlighting small, scattered T cells only. There was no expression of ALK-1, CD30, or CD25. Given the poor prognosis of SS, high surveillance and good workup strategy are desirable, especially for cases with “atypical” presentations.

von Willebrand disease (vWD) is an inherited qualitative or quantitative abnormality of von Willebrand factor (vWF), a multimeric glycoprotein serving as the carrier protein of coagulation factor VIII. Type IIA vWD, an autosomal-dominant trait, is characterized by a deficiency of high molecular weight vWF multimers with a decreased vWF activity to antigen ratio in spite of factor VIII and vWF antigen levels within reference range. We report a case of a 47-year-old, African-American man with a history of heart failure because of severe aortic stenosis. He presented with persistent bleeding after tooth extractions in preparation for aortic valve replacement. Laboratory studies revealed a normal platelet count, platelet morphology, prothrombin time, international normalized ratio, fibrinogen, and coagulation factor assays. Platelet aggregation assays in response to thrombin, collagen, arachidonic acid, and ristocetin were normal. The platelet function assay closure times in response to both epinephrine and ADP were markedly prolonged. The vWF activity and antigen were within reference range, but the ratio was markedly decreased, a finding typically associated with type II vWD. The vWF activity to antigen ratio normalized within 48 hours after valve replacement, confirming the diagnosis of acquired type IIA vWD (Table). Increased shear stress in aortic stenosis may enhance the direct cleavage of vWF, resulting in a loss of high molecular weight vWF multimers. This condition is known as acquired type IIA vWD because it mimics the inherited disorder. Recognition of this rare, acquired coagulation abnormality in patients with valvular stenosis is critical to prevent misdiagnosis and establish appropriate treatment.

Context: The quantitative D-dimer test has largely supplanted the semiquantitative fibrin(ogen) degradation products (FDP) test because of the greater sensitivity and specificity of D-dimer in disseminated intravascular coagulation and venous thromboembolism, but FDP continues to be ordered by physicians affiliated with Intermountain Healthcare. The frequency and concordance of concurrent tests for D-dimer and FDP and the influence of positive FDP results on clinical decisions in real-world medical practice were retrospectively evaluated.

Design: Instances of concurrent measurement of FDP (FDP Plasma, Diagnostica Stago, Inc., Parsippany, New Jersey) and D-dimer (STA Liatest D-Di, Diagnostica Stago) during 2009–2010 were identified in the enterprise data warehouse. Test results were extracted and classified as negative or positive. Concordance was assessed using the McNemar test for correlated proportions. Electronic medical records were reviewed to assess the effect of positive FDP results on clinical decision-making when D-dimer was negative.

Results: In 521 of 713 orders (73.1%) for FDP, D-dimer was also ordered. As shown in the Table, FDP and D-dimer values were concordant in 424 of 521 pairs (81.4%). In the 97 discordant pairs, D-dimer was positive in 86 (88.7%) and FDP was positive in 11 (11.3%) (P < .001. Chart reviews did not identify any instances where a positive FDP value overrode a negative D-dimer value in diagnostic or therapeutic decisions.

Conclusions: Concurrent measurement of FDP and D-dimer adds little, if any, value over D-dimer alone.

Comparison of FDP and D-Dimer Results

Comparison of FDP and D-Dimer Results
Comparison of FDP and D-Dimer Results

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. It arises from an unknown progenitor cell, usually from a gain-of-function mutation of the tyrosine kinase receptor, Kit. The GISTs are most common in middle-aged to older adults and are rare in young adults and children. The GISTs rarely spread outside the abdomen. To date, there are only 3 confirmed reports of intracranial GIST metastases, to our knowledge, and none involving the dura. A 27-year-old man with a 9-year history of a primary gastric GIST with previous lung and liver metastases presented with a well-circumscribed, dural-based mass. The mass was composed of packets of spindled to epithelioid cells with a whorled appearance, high mitotic rate, and necrosis. These features combined with the location of the mass were suggestive of an atypical meningioma (Figure 49, A). Immunohistochemical stains were negative for epithelial membrane antigen (Figure 49, B). c-Kit and DOG-1 immunostains were positive (Figure 49, C and D), consistent with a metastatic GIST. We present a unique case of metastatic GIST to the brain, which has rarely been reported and has never, to our knowledge, been reported to be associated with the dura. The patient was 18 years old when he presented with the primary gastric GIST, a tumor that rarely occurs in young adults. Furthermore, primary gastric GISTs tend to be less aggressive than those arising in the small intestine. In this rare case, a uniquely aggressive GIST, mimicking a meningioma, metastasized to the brain; this rare occurrence has not, to our knowledge, been previously reported.

Spindle cell oncocytoma of the adenohypophysis is a nonendocrine, benign neoplasm, although recurrent, aggressive forms have been described. Little is known about the pathogenesis of this tumor. It is believed to arise from the folliculostellate cells of the adenohypophysis. We describe the case of a 24-year-old woman diagnosed with this tumor and provide insight into the pathogenic mechanisms of this disease. Hematoxylin-eosin–stained slides, along with immunohistochemical preparations, with adequate controls, for S100, SMI-311, neurofilament, epithelial membrane antigen (EMA), CD68, P53, pankeratin, GFAP, chromogranin, synaptophysin, and Ki-67 were examined by 3 pathologists at the University of Texas Medical School at Houston. Antibodies against CD44, CD56, and CD133, nestin, Gli-2, p-Akt, and p-mTOR were applied, and the results were described with respect to each probe's cellular compartmental distribution and intensity. Hematoxylin-eosin stain showed a proliferation of spindle and polygonal cells arranged in a fascicular pattern, without mitoses, and with a proliferation index of less than 5%. There was patchy reactivity for SMI-311, nestin, CD56, S100, and vimentin, but neurofilament was not present. Both cell types were positive for EMA. CAM 5.2 stained few of the polygonal cells. No reactivity for CD68, chromogranin, synaptophysin, GFAP, and S100 was seen. The Table lists results for stem cells and cell signaling markers. These findings suggest that the cells in spindle cell oncocytoma of adenohypophysis are neuronlike precursor cells with possible aggressive behavior. Sonic hedgehog and mTOR (predominantly mTOR complex 2) pathways were activated; these observations might have therapeutic implications.

Stem Cell and Cell Signaling Marker Results

Stem Cell and Cell Signaling Marker Results
Stem Cell and Cell Signaling Marker Results

Dural metastasis from medullary carcinoma thyroid (MTC) has not, to our knowledge, been reported in the English literature. We present the first case report involving a 39-year-old man with headache and right eye proptosis. Magnetic resonance imaging showed extra-axial mass in the right frontal calvarium measuring 7.2 × 6.5 × 6.0-cm with soft tissue extension to the right superior orbit (Figure 50, A). Differential diagnosis included meningioma, hemangiopericytoma, or metastases. Histopathology showed solid nests of metastatic tumor exhibiting several morphologic features, including spindle cells (Figure 50, B), epithelial cells (Figure 50, C), clear cells, and pseudoglandular formation. Immunohistochemistry showed carcinoma cells positive for calcitonin (Figure 50, D), synaptophysin, pancytokeratin AE1/AE3, CAM 5.2, CEA, CK7, and TTF-1 but negative for progesterone receptor, CDX-2, CK20, vimentin, and thyroglobulin. The Ki-67 labeling index was 3% to 4%. Postoperative computed tomography scan of the chest and pelvis showed a 3.6 × 2.7-cm, low-density mass in the right thyroid lobe; innumerable pulmonary nodules; and lytic bone lesions in the ribs, bilateral acetabulum, iliac bone, vertebral bodies, left clavicle, and right humerus. Such clinical presentation of medullary carcinoma has never been reported, to our knowledge. There is single case report of metastasis to an orbit presenting with unilateral proptosis. Intracranial metastasis of MTC has been reported in the sellar region, cerebral hemispheres, and cerebellum. Cases with intracranial metastasis have higher age, poor prognosis, and associated widespread metastasis. The primary management is palliative therapy in the form of metastasectomy and radiotherapy. Data on treatment and survival are debatable and elusive given the rarity of the lesion.

Tumors of the sellar region consist largely of pituitary tumors, which comprise 90% of the neoplastic lesions in this area of the brain. Pituitary adenomas are typically easy to recognize; however, several uncommon variants may take more time and effort to diagnose. We report a case of a nonfunctioning pituitary tumor from a 57-year-old woman with chromophobic cells and striking perivascular pseudorosette architecture pathognomonic for ependymoma. However, the tumor demonstrated only focal staining with glial fibrillary acid protein (Dako, Carpinteria, California) and S100 (Dako), whereas it showed diffuse, strong positivity with AE1/AE3 (Dako). Rather than confirming the diagnosis of ependymoma, the staining pattern suggested the tumor might be of epithelial origin. Additional immunohistochemical studies were performed, including glycoprotein α-subunit (Mayo Clinic Medical Laboratory, Rochester, Minnesota), and proved diagnostic of pituitary adenoma, null-cell type. This case is an excellent reminder to exercise prudent restraint and consider the entire case rather than being drawn in by a pathognomonic morphology. When encountering a tumor with an instantly recognizable pattern in an unusual location, the most common entities of that site must be definitively excluded. Clinical history, tumor size, and location are often of great value. Immunohistochemistry or electron microscopy may be critical to confirm the correct diagnosis (Figure 51).

Angiocentric glioma (World Health Organization [WHO] grade 1) is a recently described, low-grade glioma characterized by a prominent, perivascular arrangement of monomorphous bipolar cells with features of ependymal differentiation. Here, we report a case of a glioblastoma (WHO grade 4) with an angiocentric glioma-like growth pattern. A 66-year-old man was incidentally found to have a 4.2-cm, mild T2 signal abnormality in the right frontal lobe on a magnetic resonance imaging study. A diagnosis of diffuse astrocytoma (WHO grade 2) was made on the resection specimen. He did well after surgery. However, 7 months later, a new mass (3.3 cm) with peripheral enhancement in the right temporal lobe was detected on a follow-up magnetic resonance imaging study. Surgical resection was subsequently performed. Microscopically, a significant portion of the tumor (60%) showed an angiocentric, glioma-like growth pattern, in which bipolar spindle cells were oriented around blood vessels and arranged in pseudorosettes in an ependymomatous patterns (Figure 52). The remaining tumor had characteristic features of glioblastoma, including marked nuclear atypia, frequent mitoses, prominent microvascular proliferation, and necrosis. Immunohistochemically, the tumor cells were positive for GFAP, S100, vimentin, and Ki-67 (10%) but were negative for synaptophysin, NeuN, and EMA. To our knowledge, an angiocentric, glioma-like growth pattern in a high-grade glioma has not been previously reported. This case implies a potential pitfall in an intraoperative consultation if only angiocentric growth-pattern areas in a high-grade lesion are sampled. Awareness of the existence of an angiocentric growth pattern within an otherwise characteristic glioblastoma could avoid a potential diagnostic error.

Meningiomas are neoplasms arising from leptomeninges or dura mater. They are more common in women and are dura-based within the cranium, although some are intraspinal. There is an increased prevalence in patients with breast carcinoma. Metaplastic changes show bone, cartilage, or fat. This is a case of an intraspinal meningioma with osseous metaplasia in a 75-year-old woman with a history of right breast carcinoma, mastectomy, axillary node dissection, and lung nodules. She had a history of gradually increasing pain in the mid thoracic area and lower back with radiation down the right leg. Chest computed tomography showed a right upper lobe lung nodule with focal calcification (differential included granuloma, primary lung tumor, or metastatic carcinoma). Magnetic resonance imaging showed a T6 to T7, focally enhancing, intradural extramedullary lesion, measuring 1.1 cm, pressing against the spinal cord. Pathologic examination revealed a grey-tan, gritty tumor with osseous metaplasia and trabecular bone formation (Figure 53). The patient did well following surgery. Cranial irradiation has an increased risk of developing meningiomas. Osseous metaplasia is relatively rare in the spinal cord. Psammomatous meningiomas, however, have an increased predilection for the intraspinal compartment. Meningiomas are EMA+, regardless of histologic subtypes, and are also positive for progesterone. A nearly 7-year follow-up showed high-grade malignant cells, nonspecific, in pleural effusion and bronchial washings. There was immunoreactivity for CK7 and EMA and focal reactivity for CEA and CA 125. No recurrence of meningiomas was noted in the thoracic spinal cord area. The histogenesis of this relatively rare tumor could be the postradiation effect of right breast carcinoma.

We report a unique case of a ganglioneuroma maturing subtype in a 40-year-old woman who presented with a painful skull mass in the left temporal region. Preoperative magnetic resonance imaging showed a heterogeneous, enhancing mass lesion, measuring 3.2 × 2.0 cm, in the left squamosal temporal bone (Figure 54, A). There was epidural extension with a mild mass effect on the left temporal lobe. There was no intracranial parenchymal edema or adjacent extracranial soft tissue edema. Differential diagnosis included primary osseous tumor and hemangioma. Histopathology showed features consistent with ganglioneuroma, maturing subtype, according to the International Neuroblastoma Pathology Classification. The tumor had plexiform growth pattern and spindle cells with elongated and wavy nuclei in myxoid and collagenous background (Figure 54, B). There were scattered ganglion-like cells, maturing ganglion cells, and small, round cells resembling neuroblasts (Figure 54, C). Involvement of bone, fibroconnective tissue, and skeletal muscle was evident. Immunohistochemistry showed mature ganglion cells, maturing ganglion cells, and neuroblast-like cells positive for synaptophysin (Figure 54, D). Spindle cells were positive for vimentin and S100. Ganglioneuroma is most common in the pediatric population. Our case is unique because of the extremely rare occurrence of ganglioneuroma involving skull bone in an adult patient. To date, there is only one case report, to our knowledge, of ganglioneuroma involving the external auditory canal and zygomatic bone. Our case is further unique because of epidural extension of tumor with mass effect on the left temporal lobe.

Cirrhotic cardiomyopathy is a recently recognized form of cardiac dysfunction in cirrhotic patients characterized by contractile, electrophysiologic, cardiac chamber structural, and serum marker abnormalities. Contractile dysfunction is often latent and usually unmasked by various stressors including liver transplantation. We report a case of a 54-year-old man who developed dilated cardiomyopathy following liver transplantation for alcoholic/hepatitis C cirrhosis. The patient had no history of cardiac disease or alcohol use for the past 10 years. Pretransplant workup results, including a dobutamine stress echocardiogram, were normal. The patient underwent liver transplantation without complications. Five days after the transplant, he complained of chest pain. Echocardiography showed multichamber dilatation and severe left ventricular systolic dysfunction with 15% ejection fraction. Serum pro-B type natriuretic factor was markedly elevated at 69 940 pg/mL. The patient remained hemodynamically unstable despite pharmacologic intervention and dialysis. He expired 24 days after transplantation. Limited autopsy showed cardiomegaly (620 g) with multichamber dilatation (Figure 55, top). Only focal, moderate coronary artery disease was present. Histology revealed cardiomyocyte hypertrophy and cytoplasmic vacuolation (Figure 55, bottom). No myocarditis or fatty changes were seen. The transplanted liver showed centriacinar necrosis consistent with congestive cardiac failure. In a recently transplanted cirrhotic patient with no prior cardiac disease, the combination of acute, nonischemic, dilated cardiomyopathy; systolic dysfunction with remarkably decreased ejection fraction; and markedly elevated serum pro-B type natriuretic factor, is most consistent with cirrhotic cardiomyopathy. Recognition of this entity is important because it may contribute to poor outcome following liver transplantation. Although associated with a high mortality rate, cirrhotic cardiomyopathy may be reversible with early recognition and intervention.

Postpartum cerebral angiopathy is a rare cause of death among childbearing females with 34 cases reported in the English literature, of which, there were 2 brain biopsies and 2 reported fatalities with brain-only autopsies. We present the youngest known fatal case of postpartum cerebral angiopathy with brain autopsy findings. The decedent was a 25-year-old African American woman who presented initially for cesarean section for the delivery of twins after 2 prior cesarean sections. Her medical records indicated predelivery treatment with ceftriaxone for gonorrhea. She was a smoker with an intrauterine growth restriction of twin B but had no other significant past medical history. Her screening urine toxicology study was negative. Her surgery proceeded with no noted complications, and she was accordingly discharged. Two weeks after the delivery, the patient presented with headaches considered to be migraines, which were treated symptomatically. A computed tomography scan of her brain was normal at this time. She subsequently developed acute neurologic deterioration, vomiting, loss continence of her urine, and began posturing. She was unresponsive and intubated at this time. A repeat brain computed tomography showed a large intraventricular hemorrhage with acute hydrocephalus and associated herniations. Subsequent autopsy revealed a hemorrhage originating from the left putamen with interventricular hemorrhage and tonsillar herniation of the cerebellum (Figure 56). A microscopic examination of the medium-sized arterioles revealed hypertensive changes and an undulating, internal elastic lamina with changes consistent with vasospasm.

Budd-Chiari syndrome is a rare condition commonly referred to as thrombosis of the hepatic veins and/or inferior vena cava, where the etiology is frequently unknown. We present a case of Budd-Chiari syndrome with associated massive intracardiac thrombosis demonstrated only at autopsy. The patient, a 36-year-old man, presented with hematemesis, 1 week of melena, and a 1.5-month history of increasing abdominal girth. He had a fever of unknown origin for 2 years, the etiology of which was never identified. The patient underwent upper endoscopy and clotted blood was noted in the stomach. After suctioning, a source of active bleeding was not identified. The patient was admitted to the intensive care unit; however, he rapidly deteriorated and expired. Autopsy revealed massive right ventricular intracardiac thrombosis with complete occlusion of the intrahepatic and suprahepatic inferior vena cavae extending to the right atrium (Figure 57). The endocardium underlying the clots showed marked fibrosis. There were diffuse, vascular intrahepatic organizing, fresh clots with congestive hepatomegaly, and extensive centrilobular necrosis. In more than 80% of patients with Budd-Chiari syndrome, an underlying condition can be identified with thrombotic risk factors present in many of the disorders. These include myeloproliferative disorders, mass lesions, infections of the liver, and many others, none of which were identified in our patient. Our case demonstrates endomyocardial fibrosis as a currently rarely recognized cause of Budd-Chiari syndrome. Only one case with this finding has been reported in the literature, to our knowledge.

Context: Intravascular talcosis is a granulomatous reaction to foreign material in intravenously injected drugs that causes pulmonary hypertension, cor pulmonale, and sudden death. This diagnosis is easily missed if unsuspected, and in a famous case involving a World Trade Center September 11, 2001 worker, it was misinterpreted as inhalational talc pneumoconiosis.

Design: The electronic database of autopsy and surgical pathology diagnoses was searched for the years 2000 through 2010 to identify cases.

Results: Four autopsy and 4 surgical lung biopsy cases met inclusion criteria. All were male with an average age of 44 years. None were suspected of having intravascular talcosis on clinical grounds. Of the cases for which data were available, 5 of 7 cases (71%) had admitted intravenous drug use. Other clinical features were tobacco smoking (5 of 7; 71%), hepatitis C (5 of 6; 83%), and pulmonary hypertension (4 of 8; 50%). Computed tomography showed severe panlobular emphysema, diffuse centrilobular and interstitial nodules, or bibasilar atelectasis and pneumonia. All autopsy cases showed pulmonary edema with an average lung weight of 1930 g; 3 of 4 cases (75%) had cardiomegaly, and 2 of 4 (50%) had hepatosplenomegaly. All showed right and left heart dilation. Extrapulmonary talc deposition was present in bone marrow, lymph nodes, kidney, spleen, liver, myocardium, and a portal venous thromboembolus. An interstitial granulomatous reaction to polarizable, needlelike foreign material was found in all cases. The intravascular and/or perivascular distribution of the foreign material confirmed pulmonary intravascular talcosis (Figure 58).

Conclusions: In a forensic pathology context or in a hospital with many intravenous drug users, the diagnosis of intravascular talcosis is likely to be familiar, but pathologists and clinicians in other contexts could benefit from greater familiarity with this condition.

Context: Healthy umbilical cord (UC) coiling index is 0.2 coils/cm. Hypercoiled cords (coiling index > 90th percentile) and hypocoiled cords (coiling index < 10th percentile) have been associated with adverse perinatal outcome, including intrauterine growth restriction, fetal distress, and intrauterine fetal demise.

Design: We conducted a retrospective study of 245 fetal autopsies performed at our institution from January 1999 to January 2011. Postmortem and placenta reports were reviewed for gestational age and maternal factors, including history of diabetes mellitus, asthma, hypertension, smoking, drugs, and alcohol use.

Results: Of the 245 fetal autopsies, 217 (89%) had placentas for review. Of these, 142 (65%) had a placental cause of death, with acute chorioamnionitis (35%) and placental vascular disease/placental abruption (23%) as the major findings. Abnormal torsion of the UC occurred in 6 cases (2.8%): 1 in the second trimester with hypocoiled cords and 5 in the third trimester with hypercoiled cords (Table). Three of 6 cases (50%) also had infarcts and placental vascular disease/placental abruption. Maternal history was relevant in 5 of the 6 cases (83%) for diabetes mellitus type II (n  =  1), asthma (n  =  1), hypertension (n  =  1), and severe preeclampsia (n  =  2). No history of smoking, alcohol, or drug use was reported.

Conclusions: Our study highlights that careful examination of the UC with isolated finding of abnormal torsion in the absence of other placental pathologies can contribute to intrauterine fetal demise and help reduce the rate of indeterminate/unexplained fetal deaths. In cases with underlying risk factors such as acute chorioamnionitis, infarcts, placental vascular disease, and placental abruption, the associated finding of abnormal UC torsion can contribute to the final diagnostic cause of death.

Study Findings

Study Findings
Study Findings

Paradoxical air emboli occur when air within the venous system enters the arterial system, usually due to air-shunting across cardiac septal defects. Rare cases have been attributed to shunting across a physiologically closed, but probe-patent foramen ovale. We describe the autopsy findings of a fatal paradoxical coronary air embolism during surgery. A 31-year-old man underwent a thoracotomy for resection of a 12-cm mediastinal mass. During the procedure, the left subclavian vein was lacerated. Although it was repaired, the patient went into asystole. Air bubbles were seen within the coronary veins. Attempts to remove air from the right ventricle were unsuccessful, and the patient expired. Autopsy revealed coronary veins beaded with air bubbles (Figure 59, A). A needle with a water-filled syringe inserted into the right ventricle and atrium failed to reveal the presence of air in either chamber. All vessels of the heart were securely clamped. The heart was removed and submerged in water, and the coronary arteries were then individually cut. As the right coronary artery was cut, abundant amounts of air bubbles escaped through the defect, indicating the presence of air within the artery (Figure 59, B). Endocardial hemorrhages were seen in the superior septum (Figure 59, C). The foramen ovale was easily probe-patent (Figure 59, D). Air emboli are uncommon yet potentially fatal. At autopsy, it is crucial to recognize the subtle presence of air within the coronary vessels as a sign of air embolism. This will ensure proper handling of the heart to demonstrate the presence of air emboli.

Foreign body type granulomatous vasculitis has been reported in blood vessels of the brain, lungs, and skin of the foot following intravascular instrumentation with devices coated with hydrophilic polymer gel. We report a case of a 77-year-old woman who suffered an acute myocardial infarction. Cardiac catheterization revealed occlusive disease involving the right coronary artery and the circumflex artery. Coronary stenting was performed for both arteries using bare metal stents. Two weeks after the procedure, the patient presented with a large pseudoaneurysm at the site of catheterization. Shortly after admission, the patient suffered a fatal arrhythmia. Autopsy revealed a ruptured left femoral artery pseudoaneurysm at the site of catheterization with fresh blood within the thigh soft tissues. The coronary stents were in place, and a left ventricular infarct in various degrees of organization was seen. Microscopically, multiple small vessels within the cardiac muscle were noted to contain a basophilic, amorphous, focally lamellated, focally granular material. An inflammatory component was noted in the vessels containing the foreign material, consisting of giant cells and lymphocytes (Figure 60). This basophilic substance was seen in vessels throughout the heart, including the right ventricle, left ventricle, and septum. The material was nonrefractile, nonpolarizable, and negative with calcium stains. Our case is the first, to our knowledge, to document intramyocardial vessel gel emboli following a cardiac catheterization with stenting. Although the microscopic finding of emboli within vessels does not seem to be the immediate cause of death in our case, it possibly contributed to the patient's demise.

Context: Cardiac noncompaction, a rarely diagnosed, congenital disease, features numerous large ventricular apical trabeculae that project into the lumen. These ventricular apical trabeculae create deep intertrabecular recesses and subtrabecular channels of potentially slowed blood flow, causing a predisposition toward mural thrombus formation. Other complications include heart failure, arrhythmias, and possibly infarction.

Design: We analyzed these complications in 8 cases.

Results: A 5-month-old boy, also with a ventricular septal defect, had heart failure. A 1.5-year-old girl had heart failure. A 1-year-old boy, 1-year-old girl, and 2-year-old girl all had additional cardiac abnormalities with no complications attributable to the noncompaction. An 11-year-old girl had mitral regurgitation and suffered a sudden cardiac arrest in the outpatient department, presumably due to an arrhythmia. A 45-year-old man with heart failure and a large apical thrombus was started on an anticoagulant but took cocaine and not the anticoagulant. This patient had recurrent heart failure, followed by an embolic stroke and severe cerebral edema. Autopsy revealed extensive, primarily subacute myocardial infarction of both ventricular apices, only moderate coronary atherosclerosis, mural thrombi in both ventricular apices, and biventricular noncompaction (Figure 61). A 55-year-old man died 10 days after a 3-vessel coronary bypass grafting, and autopsy revealed noncompaction along with multiple microinfarcts.

Conclusions: Myocardial infarction may represent a complication of left ventricular noncompaction and add to the risk of mural thrombus formation. Increasing recognition of cardiac noncompaction suggests that it may not be as rare as previously thought. Fully understanding this disease and its complications is important because it may be familial, and its recognition should prompt screening of family members for the disease.

A 36-year-old woman presented with stillbirth at 21 weeks' gestation. Autopsy revealed a macerated, small-for-gestation, female fetus with a large right upper abdominal wall defect, with herniation of the intestinal loops and liver (Figure 62, A and B). The placenta was small, with massive perivillous fibrin deposition (Figure 62, C). The obstetric history included 2 term deliveries followed by 4 prior pregnancy losses. The first 2 stillborn fetuses (24 and 30 weeks, respectively) were grossly normal, and the placentas showed variably increased perivillous fibrin (slides were unavailable for review). The third fetus (14 weeks) had an abdominal wall defect with herniation of contents, very similar to that seen in our case, and a microscopic appearance identical to the current placenta (Figure 62, D). The fourth loss occurred in the first trimester with no recognizable fetus and only hemorrhagic decidua on microscopy. Thrombophilia workup results were normal. Massive perivillous fibrin deposition is a lesion of unknown pathogenesis that is associated with recurrent fetal growth restriction and death. Some reports suggest an association with fetal deficiency of long-chain-3-hydroxyacyl-CoA-dehydrogenase. There is no previously reported association with fetal abdominal-wall defects of any type. This defect mimics that of gastroschisis but is distinguishable by a more superolateral location and an absence of amnion vacuolation typically observed in gastroschisis. One explanation for the defect could be an unusual form of disruption related to a hardened and fibrinous placenta. However, familial occurrence of the defect in siblings raises the possibility of an underlying pleiotropic genetic cause or predisposition that merits further investigation.

We present a 64-year-old woman with a complicated medical history, including diabetes and congestive heart failure, who was hospitalized for Wegener granulomatosis (WG). Shortly after dismissal, she was readmitted and hospitalized for several weeks. Near the end of her illness, she was referred to hospice and expired shortly thereafter. At autopsy, multiple organ systems were involved by disseminated zygomycosis, including the right lung (Figure 63), right kidney, and brain. Stigmata of shock included multiple serous effusions, lymphadenopathy, and congestion of both liver and spleen. Evidence of treated WG was identified in both kidneys. No evidence of WG, active or posttreatment, was noted in either lung. The findings are consistent with renal-limited WG. The cause of death was septic shock due to disseminated zygomycosis, itself a consequence of an immunocompromised status (diabetes, long-term steroid treatment, and recent immunosuppressive treatment for WG). Zygomycosis is relatively rare and associated with a mortality rate between 70% and 100%. An opportunistic infection by “bread mold” fungi from the class Zygomycetes, its primary sites of invasion include the nasal sinuses, lungs, and gastrointestinal tract. In diabetics, the fungus spreads from the sinuses to the orbit and brain. Primary lung involvement is seen in the severely immunocompromised. Predisposing factors include corticosteroid use, diabetes mellitus, neutropenia, iron overload, and recent trauma or surgery. The diagnosis of zygomycosis is rarely suspected; antemortem diagnosis is made in 23% to 50% of cases. A high degree of clinical suspicion is needed to diagnose this condition, because delay in diagnosis results in treatment failure.

Sickle cell disease is a hemoglobinopathy with a significant impact on public health. In the United States, the median survival age was estimated in 1994 to be 42 years for men and 48 years for women. We present the autopsy findings of a 32-year-old, African American man with homozygous sickle cell anemia. He was reported in the literature for presenting renal medullary carcinoma at age 21, a rare neoplasia occurring almost exclusively in patients having a sickle gene. He survived for 10 years and 4 months after having radical nephrectomy and chemotherapy. To our knowledge, this is the longest survival reported for this tumor. The objective of this report is to highlight the spectrum of autopsy findings in this patient, related to sickle cell disease. The clinical course of this patient was relevant for numerous hospitalizations because of vaso-occlusive and thromboembolic complications (bone infarcts, pulmonary embolisms, and acute chest syndrome); numerous transfusions, including full exchanges; and chronic renal insufficiency. The patient presented to the emergency department with acute dyspnea and chest pain. His status worsened, and he expired shortly thereafter. The relevant autopsy findings included the following: evidence of remote and recent pulmonary emboli despite appropriate, long-term anticoagulation; vascular changes of pulmonary hypertension, including plexiform lesions; transfusional liver hemochromatosis; Gamna-Gandy bodies in an unexpectedly enlarged spleen (250 g); an incidental pericaval paraganglioma; and no evidence of recurrence of renal medullary carcinoma. The anatomic and histologic findings correlate very well with the clinical presentation seen in this entity (Figure 64).

Paraneoplastic necrotizing myelopathy is a rare disorder associated with malignancies. Fewer than 40 cases have been reported; 13 of these were linked to lymphoma, mostly Hodgkin lymphoma (9 cases). Most affected patients have a spectrum of findings that include ascending sensory and motor deficits, progressive gait disturbances, flaccid or spastic paraplegia with sphincteric involvement, and lower back pain. Cerebrospinal fluid examination reveals elevated protein. We present a case of a 39-year-old man with obstructive sleep apnea, hypertension, and bipolar disorder who initially complained of worsening bilateral lower extremity weakness and sensory loss for 1 month, followed by paraplegia and urinary incontinence. Cerebrospinal fluid protein was markedly elevated. Magnetic resonance imaging showed signal enhancement of the spinal cord from the medulla to T10, along with an 8.2-cm, enhancing mass involving the right psoas muscle. Biopsy of the psoas mass showed diffuse large B-cell lymphoma. The day these findings were reported, the patient developed sudden respiratory failure and expired. Autopsy revealed diffuse necrosis of the cervical spinal cord; the upper thoracic spinal cord showed patchy necrosis along with axonal degeneration and focal demyelination of the posterior columns. No lymphoma was present in the leptomeninges or parenchyma of the spinal cord. This patient's obesity and obstructive sleep apnea likely contributed to his demise, but his death was directly due to neurologic dysfunction from this unusual paraneoplastic syndrome. Figure 65 shows extensive neuronal necrosis in the lower cervical cord and the inset photomicrograph shows neuronophagia.

Although secondary lymphomas occurring in the setting of angioimmunoblastic T-cell lymphoma (AITL) are considered rare, it is a well-described phenomenon seen in association with profound immune dysfunction and Epstein-Barr virus infection. We present a case of concurrent AITL and Epstein-Barr virus–associated B-cell lymphoma, uniquely associated with acute kidney injury, secondary to cast nephropathy. The patient was a 65-year-old woman diagnosed with AITL 7 months before autopsy. One week following the ninth cycle of chemotherapy, she developed acute kidney injury. Serum electrophoresis identified monoclonal immunoglobulin G λ immunoglobulins and free serum λ light chains; however, urine electrophoresis results were negative. Subsequent flow cytometric analysis revealed a peripheral B-cell lymphoproliferative disorder with lack of light chain expression by the B cells. The patient's renal function declined, and she expired a week later. Autopsy examination revealed multisystemic involvement by the previously diagnosed AITL (Figure 66, a and b). Additionally, there was extensive nodal involvement by a B-cell lymphoproliferative disorder, morphologically consistent with diffuse large B-cell lymphoma (Figure 66, c and d), and Epstein-Barr virus was positive by in situ hybridization (Figure 66, e) and polymerase chain reaction. Microscopy of the kidney revealed changes of cast nephropathy, including extensive acute tubular injury associated with periodic acid–Schiff-negative cracked casts (Figure 66, f). Of the limited published reports of AITL associated with renal failure, most are secondary to glomerular pathology. Our case demonstrates the unique coexistence of AITL, secondary B-cell lymphoma, and serum monoclonal gammopathy, with subsequent cast nephropathy in the absence of Bence Jones proteinuria.

Abdominal cocoon, sclerosing encapsulated peritonitis, and peritoneal encapsulation are 3 entities describing encapsulation of the small intestine within a membranous sac. Abdominal cocoon and sclerosing encapsulated peritonitis both refer to small-bowel encapsulation secondary to obstruction from chronic inflammation, whereas peritoneal encapsulation refers to developmental malformations found incidentally during laparotomies or autopsies. We report autopsy findings of abdominal cocoon and meconium peritonitis in a fetus with hydrops. The patient was a female infant delivered vaginally at 27 5/7 weeks gestation. Prenatal history was significant for fetal ascites that progressed to fetal hydrops and oligohydramnios. Ultrasound-guided paracentesis attempted at 27 5/7 weeks with 380 cc of fluid extracted. At autopsy, the body weight and measurements were lower than that expected for gestational age. The abdomen was markedly distended and contained 250 ml of ascites fluid. The lungs were hypoplastic as reflected by a decreased lung to body ratio (0.012). Examination of the digestive system was significant for extensive encasement of the duodenum, jejunum, and ileum by a thin, glistening encapsulating membrane (Figure 67). Microscopically, there were abundant amniotic squamous cells with fibrosis, mononuclear cell infiltrate, and mineralization in the serosa of intestine and other abdominal organs. Other causes of fetal hydrops, such as viral infection or storage disease, were not identified. Cytogenetics studies revealed a normal female karyotype. This case demonstrates that abdominal cocoon or sclerosing encapsulating peritonitis may occur in a fetus or infant as a result of chronic inflammation and not necessarily as a developmental abnormality.