Pulmonary Pathology Society 6th Biennial Meeting Abstracts

Farnaz Hasteh¹; Grace Lin²; Claire Michael³. ¹University of California at San Diego; ²University of California San Diego Medical Center, San Diego; ³University of Michigan Medical Center, Ann Arbor.

Context: Differentiating between malignant and reactive mesothelial proliferations in cytologic effusions can be challenging. The literature suggests that desmin, epithelial membrane antigen (EMA), Glut-1, Ki-67, and p53 are useful in this differential diagnosis; however, these studies have been performed mainly on tissue specimens. This study investigates the utility of these immunohistochemical markers to differentiate reactive from malignant mesothelial cells in cytologic effusions.

Design: Archival cell blocks of pleural and peritoneal fluids from 52 cases of malignant mesothelioma (epithelioid type) and 80 cases of benign mesothelial cells were stained with desmin, EMA, and Ki-67 markers; a subset were stained for Glut-1 and p53.

Results: Desmin was positive in 69 of 80 (sensitivity, 86%) cases of benign mesothelial cells and 6 of 52 (specificity, 89%) cases of malignant mesothelioma. EMA was positive in 52 of 52 (sensitivity, 100%) malignant cases and 12 of 80 (specificity, 85%) benign cases. The proliferation marker Ki-67 showed strong and diffuse positivity in 50% of cells in 8 of 49 (sensitivity, 16%) malignant cases and 3 of 77 (specificity, 96%) benign cases. Glut-1 was positive in 6 of 15 (sensitivity, 40%) malignant cases and 7 of 46 (specificity, 85%) benign cases. p53 was strongly positive in 8 of 14 (sensitivity, 57%) malignant cases and 1 of 46 (specificity, 98%) benign cases.

Conclusions: In this immunohistochemical study of cytologic effusions, positive EMA and negative desmin stains favor a diagnosis of malignant mesothelioma, while negative EMA and positive desmin stains favor a reactive process. Strong and diffuse positivity for Glut-1 and p53 argue against a benign process. Ki-67 was not helpful in separating florid hyperplasia from malignant mesothelioma, as both could be highly proliferative.

William Funkhouser¹; Juneko Grilley-Olson¹; William Travis²; Kevin Leslie³; David Hayes¹. ¹University of North Carolina at Chapel Hill; ²Memorial Sloan-Kettering Cancer Center, New York, New York; ³Mayo Clinic Arizona, Scottsdale, Arizona.

Context: Accurate diagnosis of non–small cell lung cancer type is important because pemetrexed and bevacizumab are not approved for treating lung squamous cell carcinoma (SqCa). Interobserver reproducibility (IOR) studies of hematoxylin-eosin–only diagnoses (Burnett RA, et al. J Clin Path. 1994;47:711–713) showed a κ statistic of 0.37 for SqCa and κ of 0.58 for adenocarcinoma (ACa). We measured the IOR for the 2004 World Health Organization classifications, focusing on type (SqCa, ACa), grade (PD, non-PD), and lung pathology expertise (expert, community).

Design: Twelve expert pathologists (EPs) and 12 community pathologists (CPs) participated. Pathologists made diagnoses based on the World Health Organization's classifications (44 categories) using virtual hematoxylin-eosin slides from 96 lung tumors. κ was measured for all 44 diagnostic categories, the 10 major categories, and 2 class systems (SqCa/non-SqCa, ACa/non-ACa, PD/non-PD, EP/CP). Grades were based on the original diagnoses.

Results: There were 222 pathologist pairs and 7130 slide pairs. κ for distinguishing SqCa from non-SqCa (all grades) were 0.55, 0.64, and 0.41 (all, EP, CP, respectively). κ for non-PD SqCa/non-SqCa were 0.60, 0.68, and 0.46. κ for PD SqCa/non-SqCa were 0.46, 0.53, and 0.32. κ for distinguishing ACa from non-ACa (all grades) were 0.59, 0.69, and 0.46 (all, EP, CP, respectively). κ for non-PD ACa/non-ACa were 0.64, 0.70, and 0.55, and κ for PD ACa/non-ACa were 0.48, 0.60, and 0.30.

Conclusions: Best IOR for hematoxylin-eosin–only diagnoses of SqCa or ACa was seen when EPs reviewed non-PD SqCa (κ  =  0.68) and ACa (κ  =  0.70). IOR was lower for PD than for non-PD carcinomas for both expertise levels and for both SqCa and ACa types. IOR improvement may be possible with reflex screening for mucin and type-specific immunophenotypes.

Ilyssa O. Gordon; Jerry Krishnan; D. Kyle Hogarth; Jeffery Charbeneau; Antoinette Mazurek; Thomas Krausz; Aliya N. Husain. University of Chicago, Chicago, Illinois.

Context: The classic definitions of asthma and chronic obstructive pulmonary disease emphasize a difference in smoking history. However, there is substantial histologic and clinical overlap between these disease entities. The objective of this study was to determine if smoking history correlated with noninvasive (exhaled nitric oxide) and invasive measures of airway inflammation obtained through bronchoscopy (bronchoalveolar lavage and endobronchial biopsies) in patients with obstructive lung disease refractory to optimal therapy.

Design: We prospectively enrolled 27 adults with a clinical diagnosis of asthma or chronic obstructive pulmonary disease with inadequate symptom control despite optimal therapy. Patients were grouped into past smokers (n  =  9) and never smokers (n  =  18). Standard spirometry studies and exhaled nitric oxide analysis were performed. Eosinophil and neutrophil percentages in bronchoalveolar lavage, counts in epithelium, and grade in submucosa of endobronchial biopsy specimens were determined, as was the presence of any epithelial reactive/reparative changes. Significant differences were defined as 2-tailed P < .05 on the SAS System 9.1.3 (SAS Institute, Inc, Cary, North Carolina).

Results: There were no differences in exhaled nitric oxide (P  =  .70), eosinophil or neutrophil percentages in bronchoalveolar lavage (P  =  .26 and P  =  .21, respectively), counts in epithelium (P  =  .60 and P  =  .77, respectively), or grade in submucosa (P  =  .51 and P  =  .62, respectively) between past smokers and never smokers. In addition, no difference was found in the presence of goblet cell hyperplasia (P  =  .51), reserve cell and squamous metaplasia (P > .99 and P  =  .68, respectively), and epithelial denudation (P  =  .45) between the 2 groups.

Conclusions: Classic clinical definitions of asthma and chronic obstructive pulmonary disease that stratify patients based on smoking history do not correlate with invasive and noninvasive measures of airway inflammation or with reactive/reparative changes in airway epithelium.

Monica Ruiz¹; Hanan Abdel-Monem¹; Linda Green². ¹Baylor College of Medicine, Houston, Texas; ²Michael E. Debakey VA Medical Center, Houston, Texas.

Context: Mediastinal lymphadenopathy may be related to neoplasms (primary or metastatic), reactive conditions, or infections. The evaluation of mediastinal lymph nodes is essential for staging non–small cell lung cancer and for planning treatment. There may be false-positive or false-negative imaging in mediastinal lymphadenopathy, thus requiring surgical or cytologic sampling. We designed a study to evaluate the etiology and diseases associated with granulomatous inflammation found in mediastinal lymph nodes that were sampled surgically and by transbronchial fine-needle aspiration.

Design: We searched the surgical and cytologic files of our institution from the last 18 years for the use of SNOMED coding for granulomatous inflammation. For identified patients, we reviewed the clinical records for clinical and radiographic findings, special stains, cultures, and surgical resection follow-up.

Results: We identified 108 patients (4 females and 104 males). There were 13 cases with associated caseous necrosis. The final diagnoses included the following: 36 non–small cell lung cancers with no lymph node metastases, 8 non–small cell lung cancers with concomitant metastases, 7 non–small cell lung cancer with infections (4 Histoplasma capsulatum, 1 tuberculosis, and 2 Cryptococcus), 5 other associated nonlung malignancies, 17 infections (6 H capsulatum, 4 tuberculosis, 3 Mycobacterium avium-intracellulare, 1 Actinomyces, 1 Moraxella, and 2 M avium-intracellulare and H capsulatum), 29 sarcoidosis, 5 unknown, and 1 rheumatoid arthritis.

Conclusions: Mediastinal granulomatous inflammation can be seen in lymph nodes sampled by mediastinoscopy and transbronchial fine-needle aspiration. Etiologies may include reaction to a lung neoplasm, sarcoidosis, infections, or other systemic diseases. Infections are common and should not be overlooked. Cultures and special stains (acid-fast bacillus, Grocott-Gomori methenamine silver stain, and Gram stain) are indicated.

Jeffrey Baliff; Leslie Litzky; Kathleen Montone. Hospital of the University of Pennsylvania, Philadelphia.

Context: Fungal infections in lung tissue can be detected histologically by silver or periodic acid–Schiff stains; however, the identification of these infections is presumptive based on organism morphology. To make a definitive identification, pathologists must await culture results, which may be unavailable if fungal infection was not suspected. Even if cultures were ordered, doctors may have to wait days or weeks for results. Such delays affect patient treatment as well as possible exposure of hospital personnel to infection. Locked nucleic acid (LNA) probes offer a rapid alternative for fungal identification. LNAs are modified nucleotides with increased thermal stability, and they make excellent probes for in situ hybridization (ISH). We describe a rapid ISH method for fungal identification in pulmonary formalin-fixed, paraffin-embedded tissue.

Design: Patients with histopathologic confirmation of fungal organisms in lung tissue by silver stain were included with a presumptive identification made by morphology. LNA oligonucleotide probes targeting rRNA sequences specific for Aspergillus sp, Candida sp, Coccidioides sp, and Histoplasma sp were commercially synthesized and 3′ terminally biotin labeled. ISH was performed using modified capillary action technology. Tissues were rapidly dewaxed, cleared, rehydrated, and digested with pepsin. Hybridization was carried out at 50°C for 1 hour. After posthybridization washing, hybrids were detected using streptavidin–alkaline phosphatase and nitroblue tetrazolium. All slides were examined by light microscopy.

Results: ISH with LNA probes confirmed the histopathologic impression of fungal infection in cases of Aspergillus sp, Candida sp, Coccidioides immitis, and Histoplasma sp in lung tissue. Positive and negative controls stained appropriately. The entire procedure took less than 2.5 hours.

Conclusions: ISH with LNA oligonucleotide probes can provide rapid, tissue-based detection of various fungal pathogens in pulmonary formalin-fixed, paraffin-embedded tissue.

Andre Moreira; Natasha Rekhtman; Robert Downey. Memorial Sloan-Kettering Cancer Center, New York, New York.

Context: Stem cells may give rise to carcinomas, as has been described for lymphoma/leukemias. We hypothesize that there is a differential distribution of progenitor cell markers among the different histologic types of lung cancer.

Design: Sections of paraffin-embedded tissue of resected pulmonary carcinomas including adenocarcinoma (n  =  51), squamous cell carcinoma (n  =  11), large cell carcinoma (n  =  11), and small cell carcinoma (n  =  10) were stained for putative stem cells markers (Musashi-1, Musashi-2, CD34, c-kit, CD133, p63, and OCT-4).

Results: Musashi-1 is an RNA-binding protein involved in the regulation of precursor cells asymmetric division and differentiation. Musashi-1 was positive in 100% of small cell carcinomas, 27% of large cell carcinomas, and 4% of adenocarcinomas (primarily in solid-type adenocarcinomas). No diffuse stain was seen in squamous cell carcinoma (P < .001). There was a significant difference in the expression of progenitor cell markers among the 4 groups of pulmonary carcinoma for c-kit (P  =  .002) and for p63 (P < .001). Similar to Musashi-1, c-kit positivity was seen in solid-type adenocarcinoma. The distribution of Musashi-2 and CD133 was marginally significant (P  =  .008). No staining for OCT-4 and CD34 was seen in any of the tumor types studied. Hierarchical clustering based on marker expression separated tumors into 2 clusters. The cluster marked by high expression of Musashi-1 and c-kit contained most of the poorly differentiated adenocarcinomas and small cell carcinomas.

Conclusions: Pulmonary carcinomas can express stem cell markers, which are differentially expressed among histologic type and degree of differentiation.

Alì Greta; Boldrini Laura; Lucchi Marco; Picchi Alessandro; Mussi Alfredo; Fontanini Gabriella. University of Pisa, Pisa, Italy.

Context: Malignant pleural mesothelioma (MPM) is an immunogenic tumor, but the immune response is normally weak and unable to destroy the neoplasm. Intravenous, subcutaneous, or intrapleural administration of interleukin 2 (IL-2) has shown some effects on tumor regression in MPM; however, the mechanism underlying the biologic effects of IL-2 on tumor growth is still largely unknown.

Design: The purpose of this study was to evaluate the effect of IL-2 on the MPM microenvironment and to investigate the ability of IL-2 to modify immunologic effector cells and angiogenesis in patients with MPM. CD8⁺, CD4⁺, and foxp3⁺ tumor-infiltrating lymphocytes and tryptase and chymase mast cells were determined by immunohistochemistry in 2 distinct series of MPM patients: 60 patients who were treated preoperatively with intrapleural IL-2 (18 × 106 IU/day for 3 days) and 33 patients who were untreated. Moreover, CD34 and vascular endothelial growth factor immunostains were also performed.

Results: Tryptase mast cells and CD8⁺ and foxp3⁺ lymphocytes were significantly increased in the IL-2 preoperatively treated group. Moreover, the number of microvessels was significantly lower in IL-2 preoperatively treated patients. There were no significant differences between the 2 patient groups regarding the other analyzed factors.

Conclusions: This study indicates that intrapleural preoperative IL-2 treatment for patients with MPM leads to an increase in cytotoxic CD8⁺ lymphocytes and tryptase mast cells concomitant with reduced vasculature. IL-2 also enhances the number of foxp3⁺ T cells, which may limit the efficacy of anticancer therapy. These findings give more insight into the cancer mechanisms mediated by IL-2; however, the immune changes in the MPM microenvironment need to be examined in the context of clinical outcome.

Yiqing Chi; Yi Zhou; Ronald Angeles; Grace Guzman; Sujata Gaitonde. University of Illinois at Chicago.

Intravascular large B-cell lymphoma is a rare and aggressive subtype of extranodal diffuse large B-cell lymphoma. It is characterized by disseminated proliferation of neoplastic lymphocytes within vascular spaces. Occlusion of small- and medium-sized blood vessels by malignant lymphoma cells in a variety of organs can cause various clinical presentations, which most commonly include skin lesions and neurologic symptoms. Most cases are not diagnosed prior to death due to the variable clinical presentations and the nonspecific laboratory findings. A 55-year-old Hispanic man presented with influenza-like symptoms and progressive ascending weakness in lower extremities. Radiology findings were suggestive of adult respiratory distress syndrome with diffuse patchy lung infiltrates. Transbronchial biopsy of right lung middle lobe showed atypical bronchial epithelial cells with features suggestive of but not conclusive for an in situ epithelial neoplastic process. The patient developed tachypnea and subsequently died of respiratory failure. Postmortem examination revealed that both lungs were consolidated (left lung, 1100 g; right lung, 1350 g). Microscopically, marked intravascular large hematopoietic tumor cells with irregular nuclear contours and prominent nucleoli were present throughout the lungs. Immunohistochemically, the tumor cells were CD20⁺ and CD79a⁺ but were negative for CD3, CD34, and CD117. We made a diagnosis of intravascular large B-cell lymphoma. Retrospectively, a previous transbronchial biopsy showed similar tumor cells, which were confined to the vascular spaces. Here, we report a rare case of intravascular large B-cell lymphoma presenting with respiratory and neurologic symptoms. A high index of clinical suspicion and careful interpretation of biopsy results may allow for premortem diagnosis and early intervention in cases of this often-missed disease.

Izidor Kern¹; Andreja Beden²; Marija Dolenšek³. ¹University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia; ²University Children's Hospital, Ljubljana, Slovenia; ³University Medical Centre, Ljubljana, Slovenia.

Necrotizing sarcoid granulomatosis is a very rare, distinct, pulmonary sarcoidlike vasculitic entity that occurs in the pediatric population. A previously healthy 13-year-old adolescent girl presented with symptoms of respiratory tract infection after spending time at a spa resort. Pulmonary function tests disclosed airway obstruction with normal diffusing capacity. A chest x-ray and computed tomography scan showed multiple bilateral nodular noncavitated opacities measuring up to 5 cm in diameter and located in peribronchovascular and subpleural areas. No hilar lymphadenopathy was seen. Radiographic follow-up showed resolution and reappearance of nodular lesions. Antineutrophil cytoplasmic antibodies and serologic markers for autoimmune disorders were negative. Infectious etiology was ruled out, and various antibiotic treatment regimens were unsuccessful. Ultrasound-guided fine-needle aspiration biopsy of one of the lung nodules revealed necrosis. In a transbronchial biopsy, sarcoid granulomas were observed. In bronchoalveolar lavage fluid, the lymphocytic count was elevated with a normal CD4∶CD8 ratio. Many confluent epithelioid granulomas in lymphangitic distribution, including some with central necrosis, were present in the surgical lung biopsy specimen. There were focal areas of necrosis and necrotizing, giant-cell vasculitis. Results of microbiology and molecular biology tests and special stains for microorganisms were all negative. Therefore, the findings were consistent with a diagnosis of necrotizing sarcoid granulomatosis. The patient responded well to systemic corticosteroid treatment. All lung nodules gradually disappeared, and pulmonary function normalized. Necrotizing sarcoid granulomatosis is most often characterized by pulmonary nodular opacities, sarcoid granulomas, necrosis, and vasculitis. The disease has a benign clinical course; however, it presents a diagnostic challenge in a child, and only a few such cases have been reported.

Marcio Gomes; M.S. Amin; Harman Sekhon. University of Ottawa-The Ottawa Hospital, Ottawa, Ontario, Canada.

Context: For many years, the World Health Organization's classification system has defined bronchioloalveolar adenocarcinoma (BAC) as a noninvasive neoplasia. Additionally, when the strict criteria are followed, Japanese studies have shown that these lesions have no metastatic potential and that the 5-year survival rate is 100%. Therefore, among lung pathologists, there is a growing consensus that regardless of lesion size, BAC should be considered an in situ lesion in the TNM staging system. This reclassification would result in major therapeutic and prognostic implications for patients. However, if the strict criteria are not observed, this change could result in the undertreatment of an invasive disease.

Design: All cases diagnosed as BAC at our institution during the last 7 years were reviewed and reclassified as pure BAC, predominant BAC with minimal invasion, or invasive adenocarcinoma. Invasive adenocarcinomas included BAC cases with more than 10% invasive areas and other subtypes of adenocarcinoma.

Results: Of 73 lesions previously diagnosed as BAC, 13 (18%) were pure BAC, 8 (11%) showed minimal invasion, and 52 (71%) were reclassified as invasive adenocarcinoma. Diagnostic difficulty was most common in adenocarcinomas with a papillary phenotype and predominant BAC with invasive acinar foci. Mucinous BACs were correctly diagnosed more often than nonmucinous BACs.

Conclusions: The strict criteria for diagnosing BAC are not consistently applied by general surgical pathologists who are responsible for diagnosing most lung cancers in North America. Thus, staging these tumors as in situ lesions might sometimes preclude optimal treatment for an invasive disease.

Lynette Sholl¹; Glenda Trujillo²; Alessia Meneghin²; Fernando Martinez²; Cory Hogaboam²; Jeffrey Myers². ¹Brigham and Women's Hospital, Boston, Massachusetts; ²University of Michigan, Ann Arbor.

Context: Idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia shows variable disease progression. The pathobiology of rapid progression is unclear; however, infection, genetics, and disease severity may contribute. The toll-like receptors (TLRs) are immune regulators that perform microbial detection; TLR9 is upregulated in IPF.

Design: We examined pathology and TLR expression in patients with suspected stable or rapidly progressive IPF. Patients with suspected IPF were defined as rapid progressors if they had a >10% decline in forced vital capacity within 1 year of diagnosis. We studied 15 patients: 6 rapid progressors and 9 with stable disease. RNA isolated from discarded fresh lung tissue underwent quantitative real-time polymerase chain reaction for TLRs 1 to 9. The corresponding diagnostic slides were reviewed. Honeycomb change was scored as follows: 1, <25%; 2, 25% to 75%; 3, >75% lung tissue affected in each biopsy site.

Results: High TLR9 expression–only was detected in 6 of 6 rapid progressors and 2 of 9 stable disease patients (P  =  .007). Four rapid progressors had usual interstitial pneumonia, and 2 had nonclassifiable interstitial pneumonia. Seven stable patients had usual interstitial pneumonia, one had nonclassifiable interstitial pneumonia, and one had hypersensitivity pneumonitis. Extent of honeycomb change was similar in the stable and rapidly progressing patients. There was a trend toward more honeycomb change in patients with increased TLR9 expression (average score of 2.1 in TLR9-high vs 1.7 in TLR9-low tissue).

Conclusions: TLR9 overexpression is significantly associated with rapid progression of IPF. The pathology of stable and rapidly progressing IPF is identical. High TLR expression is associated with increased honeycomb change, suggesting that TLR9 may influence the pathogenesis of IPF.

David Hwang; Kristopher Cunningham; Sarah James; Ming Tsao. University Health Network, Toronto, Ontario, Canada.

A 45-year-old man with severe panacinar emphysema underwent bilateral lung transplantation. Past medical history included α₁-antitrypsin deficiency and 30 pack-years of tobacco smoking, as well as a history of smoking several “joints” of marijuana or hash oil mixed with tobacco per day. The explanted lungs showed extensive emphysematous changes with multiple large bullae measuring up to 12 cm in greatest dimension. In addition to the emphysematous background, histologic examination found prominent collections of interstitial and intraalveolar macrophages containing coarse brown pigment that was negative for Prussian blue, melanin, Gomori methenamine silver, and periodic acid–Schiff stains. In many cells, this pigment was admixed with well-delineated, clear vacuoles of varying sizes, the appearance of which was consistent with exogenous lipid material. The peribronchial lymph nodes showed numerous macrophages demonstrating similar features. These findings are in keeping with so-called bong lung. Also in support of this diagnosis, the patient had a known α₁-antitrypsin deficiency, with superimposed exogenous lipid pneumonia most likely due to smoking hash oil joints.

Yiqing Chi; Gregorio Chejfec. University of Illinois at Chicago.

Congenital cystic adenomatoid malformation of the lung is a congenital abnormality characterized by malformed bronchopulmonary tissue and multiple cysts. There are 5 subtypes (types 0–4). These lesions occur predominantly in stillborn infants or neonates and represent 25% of congenital lung malformations; adult presentation is rare. A 40-year-old Caucasian woman presented with recurrent respiratory tract infection. A computed tomography scan of the chest showed a mass lesion in the left lower lobe of the lung that was suspicious for a focus of active infection or tumor. The patient elected to proceed with a video-assisted thoracoscopic wedge resection of left lower lobe of the lung. Pathologic examination revealed multiple cysts measuring <1 cm and lined with ciliated cuboidal or columnar cells. The final diagnosis was congenital cystic adenomatoid malformation. We describe the clinical presentation, radiologic findings, and histopathologic characteristics of a rare case of congenital cystic adenomatoid malformation of the lung diagnosed during adulthood.

Robert J. Cabay; Michael A. Havens; Eva M. Wojcik; Razan Massarani-Wafai. Loyola University Medical Center, Maywood, Illinois.

Context: Mediastinoscopy is the gold standard for lung cancer staging. Various biopsy methods are used for staging, including a recently introduced method, endobronchial ultrasound-guided transbronchial fine-needle aspiration (EBUS-FNA). In this study, we characterize the experience of our department with this modality.

Design: We completed a search for EBUS-FNA cases received during 31 consecutive months. Specimen adequacy and cytologic interpretations were reviewed and were correlated with available histologic data.

Results: The search identified 48 EBUS-FNA specimens from 41 patients. Physician A (>10 years posttraining, surgical specialty) and Physician B (<10 years posttraining, nonsurgical specialty) performed the procedures. The mean number of slides prepared for each case was 10 (9 by A, 12 by B). Of the specimens submitted, 32 (67%) were satisfactory, including 21 of 28 (75%) from Physician A and 11 of 20 (55%) from Physician B. Satisfactory specimens were negative for malignancy in 17 (53%) cases, atypical in 3 (9%) cases, and positive for malignancy in 12 (38%) cases. Corresponding surgical specimens were available for 13 (41%) of the satisfactory specimens. Upon review, 2 cases were false negative due to sampling error. Sensitivity and specificity of EBUS-FNA were 85% and 100%, respectively.

Conclusions: EBUS-FNA is an effective technique for mediastinal and hilar lymph node sampling. Cytologic-histologic concordance is present in 11 of 13 (85%) satisfactory aspirates. Our institution's EBUS-FNA experience is similar to that of other institutions for sensitivity and specificity. The aspirator's surgical experience seems to correspond to a higher adequacy rate for the technique and a lower mean number of slides prepared.

Junya Fukuoka¹; Mitsuo Kishimoto²; Tomonori Tanaka¹; Ryoko Egashira¹; Shinichiro Hayashi³; Hidehiko Harada². ¹Toyama University Hospital, Toyama, Japan; ²Otsu Municipal Hospital, Otsu, Shiga, Japan; ³Saga University School of Medicine, Saga, Japan.

We have identified 2 cases of a unique lung disease characterized by marked pleural thickening and parenchymal fibroelastosis with strong upper lobe predominance. The first patient was a 63-year-old woman, and the second patient was a 66-year-old woman. They presented with progressive dyspnea and recurrent pneumothorax, respectively. In both cases, a chest x-ray revealed progressive severe upper lobe loss of volume and elevation of the hilum. On high-resolution computed tomography, there were subpleural sclerotic changes and reticulolinear shadows with traction bronchiectasis. The findings in the lower lung area were subtle. No evidence of collagen vascular disease was found. One patient died of progressive respiratory failure 1 year after a lung biopsy. Both lung biopsies showed fibrous thickening of the visceral pleura with prominent, homogenous and subpleural fibroelastosis without honeycombing, which were similar to apical cap. The border of the fibroelastosis was clearly demarcated. The adjacent lung parenchyma was mostly normal. In the area of fibroelastosis, gradual increase of elastic fiberdensity toward the pleura was observed. The areas of subpleural fibroelastosis showed no asbestos bodies, and the inflammation was inconspicuous. These cases did not fit within the 2002 American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. Neither patient showed evidence of collagen vascular disease, hypersensitivity pneumonitis, asbestosis, or other pneumoconiosis. The histologic appearance in both cases was similar to apical cap; however, pulmonary apical cap is typically asymptomatic and nonprogressive. Recently, a few reports have described similar cases, but presently, the etiology and pathophysiology of this entity are unknown.

Ryoko Egashira; Tomonori Tanaka; Junya Fukuoka. Toyama University Hospital, Toyama, Japan.

Context: Craniocaudal distribution is important for the diagnosis of lung disease. The importance of disease distribution in relation to lymphatic clearance is also recognized. However, histologic differences in secondary lobules between upper and lower lung levels are insufficiently defined. We analyzed the route of dust clearance, representing the lymphatic route, in normal lung tissue.

Design: We analyzed distribution of carbon dust deposition (CDD) in 86 sections from 61 lung cancer lobectomy cases. We excluded cases with cancer stages T3 or T4, prior radiotherapy, or secondary changes caused by cancer. Tissue was obtained from pathologically and radiologically normal lung areas. CDDs in secondary lobules were divided into bronchiolovascular areas and subpleural/septal areas, and the intensity of CDD in each area was separately recorded for upper and lower levels. The association between areas of CDD and levels of carbon dust was statistically analyzed (χ² test).

Results: In the upper level, predominance of CDD in bronchiolovascular areas was found in 31 of 44 cases (70.5%), and predominance in subpleural/septal areas was found in 7 of 44 cases (15.9%). We observed no difference in 6 of 44 cases (13.6%). In the lower level, predominance of CDD in bronchiolovascular areas was found in 13 of 42 cases (31%), and predominance in subpleural/septal areas was found in 25 of 42 cases (59.5%). We observed no difference in 4 of 42 cases (9.5%). The difference between upper and lower levels was statistically significant (P < .001).

Conclusions: We found that the lymphatic clearance in upper lung levels is predominantly bronchiolocentric, whereas in lower lung levels, it is predominantly peripheral. These findings may help our understanding of the discordant distribution in secondary lobules between upper and lower lung fields in a single disease, such as hypersensitivity pneumonitis.

Andrea Arrossi¹; Cesar Moran². ¹The Cleveland Clinic Foundation, Cleveland, Ohio; ²M. D. Anderson Cancer Center, Houston, Texas.

Context: Malignant pleural mesotheliomas are characterized by their histologic architectural heterogeneity. However, they are usually cytologically monotonous tumors with low-grade nuclear features, which helps to differentiate them from metastatic adenocarcinoma. Although numerous morphologic variants of mesothelioma have been recognized, tumors with high-grade or anaplastic nuclear features have not yet been properly addressed in the literature.

Design: Eight cases of mesothelioma with areas of anaplastic features were identified in a systematic review of 56 extrapleural pneumonectomies. The clinical and pathologic features of these tumors were evaluated.

Results: All patients were men with a mean age of 59 years. Four tumors were biphasic mesotheliomas, 2 were epithelioid-type mesotheliomas, and 2 were sarcomatoid-type mesotheliomas. One of the biphasic tumors had anaplastic features in both the sarcomatoid and epithelioid components. One of them had anaplastic features only in the sarcomatoid areas, and the other 2 had anaplastic features only in the epithelioid areas. The areas with anaplastic or high nuclear grade were difficult to distinguish from other sarcomas or from metastatic high-grade carcinomas. Treatment included extrapleural pneumonectomy with postoperative radiotherapy in 4 cases. The mean follow-up time was 9.3 months (range, 3.23–27.2 months). The presence of anaplastic features did not correlate with a difference in disease-specific survival when compared with mesotheliomas without anaplastic features.

Conclusions: The presence of high-grade or anaplastic features in either sarcomatoid or epithelioid tumors of the pleura should not prompt a diagnosis of sarcoma or carcinoma or discourage a diagnosis of malignant mesothelioma.

Andras Khoor. Mayo Clinic Florida, Jacksonville.

Glandular papillomas are exceedingly rare benign tumors of the lung. I discuss the case of a 62-year-old man and former heavy smoker who presented with occasional wheezing. A chest x-ray and a subsequent computed tomography scan uncovered a 15-mm pulmonary nodule with mild peripheral stranding in the right lower lobe. The computed tomography scan also revealed a 5-cm heterogeneous mass in the right kidney. Based on radiographic criteria, both lesions were suspicious for primary malignancies. The patient underwent laparoscopic radical nephrectomy for the renal lesion, as well as right thoracotomy and wedge resection of the pulmonary nodule. The kidney was involved by renal cell carcinoma, clear cell type with sarcomatoid elements (Fuhrman grade IV). Sections of the pulmonary wedge resection specimen showed a partially endobronchial, arborizing papillary lesion with stromal hyalinization. The papillary cores were covered by ciliated epithelium and interspersed mucin-producing cells. Focal squamous differentiation was also seen, and the possibility of low-grade mucoepidermoid carcinoma was considered. However, the overall structural organization and the prominence of ciliated cells favored a benign process that fit most comfortably in the category of glandular papilloma. Seven months after surgery, the patient developed metastatic renal cell carcinoma in the left clavicle, but he had no recurrence of the pulmonary nodule. Glandular papillomas may exhibit unusual features and may mimic low-grade malignancy.

Anatoly Urisman; Kirk Jones. University of California at San Francisco.

We present the case of a 67-year-old Caucasian woman with insidious onset of dyspnea and declining pulmonary function. The referring pulmonologist suspected hypersensitivity pneumonitis because of the patient's occupation as a librarian and had a low clinical suspicion for sarcoidosis. The patient underwent thoracoscopic wedge biopsies of the left upper and lower lobes. The biopsies showed prominent nonnecrotizing granulomas in a “lymphangitic pattern,” with focal calcifications, moderate to marked subpleural fibrosis, and absence of acid-fast bacilli and fungal microorganisms. The features were compatible with sarcoidosis; however, given the low clinical suspicion for this entity, the case was sent to our department for a second opinion. Review of histology confirmed the presence of nonnecrotizing granulomatous inflammation. The differential diagnosis included sarcoidosis, infection, chronic beryllium disease, or other metal-related reactions. Further review of the patient's demographic information revealed that she lived near a government facility where multiple cases of beryllium lung disease had been previously reported. Additional history confirmed she was employed as a librarian at the facility in question, and, thus, we were able to establish the correct diagnosis. This case illustrates the importance of considering the location or site of employment in addition to job-related activities when obtaining a history of occupational risks.

Thomas Sporn; Elizabeth Pavlisko. Duke University Medical Center, Durham, North Carolina.

A 50-year-old woman with a history of menorrhagia presented to her orthopedist with clavicular pain. A chest x-ray was obtained and revealed multiple lung nodules. A chest computed tomography scan confirmed multiple pulmonary nodules, the largest of which was in the right lower lobe. A subsequent positron emission tomography scan showed no significant hypermetabolic activity in the lung nodules but showed moderate activity in the uterus. She was referred for a diagnostic wedge resection. The surgical specimen consisted of a 21-g wedge of lung with a 1.6-cm firm white mass and smaller nodules ranging from 0.1 to 0.6 cm. Microscopic examination demonstrated nodular, low-grade epitheloid and spindled cell proliferations without mitoses or necrosis. Immunohistochemical stains for smooth muscle and muscle-specific actin, BCL-2, desmin, and vimentin were positive. Negative staining was observed for antikeratins, CD10, CD34, CD45, S100, and MART-1/HMB-45. Image cytometric analysis showed estrogen and progesterone receptor expression. A diagnosis of atypical smooth muscle proliferations, consistent with benign metastasizing leiomyomata, was rendered. The patient later underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Gross examination demonstrated a uterus with an 8-cm white whorled tumor. Microscopic examination showed a cellular epitheloid leiomyoma with marked cytologic atypia, rare mitoses (<1 per 10 high-power fields), no necrosis, and an immunohistochemical profile identical to the pulmonary nodules. The diagnostic entity “benign metastasizing leiomyoma” has sparked controversy since first being reported in the late 1970s. Some suggest benign metastasizing leiomyomas are truly low-grade leiomyosarcomas, while others have made headway using cytogenetics to prove that uterine leiomyoma, benign metastasizing leiomyoma, and leiomyosarcoma are a spectrum of distinct entities.

Ulrike Gruber-Moesenbacher. University-Associated Teaching Hospital Feldkirch, Feldkirch, Austria.

A 49-year-old woman presented with chills, fatigue, cough, and lack of appetite lasting 3 months. On chest x-ray, bilateral pulmonary infiltrates were seen in both upper lobes. Bronchoscopy and fluorodeoxyglucose F 18 positron emission tomography provided no further information; C-reactive protein and lactate dehydrogenase levels increased during hospitalization. The patient suffered from anemia and partial respiratory insufficiency. Results of tuberculosis tests were negative. The infiltrates persisted despite administration of oral corticosteroids. A videothoracoscopy-resection of segment R1 was performed. The patient died 9 days later of multiorgan failure; no autopsy was performed. Histologically, there was nodular and diffuse infiltration of the lung by large atypical cells. Because of the association of the infiltrate with blood vessels, the differential diagnosis of angiosarcoma was raised. Immunohistochemical investigations showed tumor cells negative for cytokeratin, CD31, HMB-45, neural cell adhesion molecule, CD14, CD1a, and smooth muscle actin antibodies. The tumor cells stained positively for antibodies against CD20, CD79a, and vascular endothelial growth factor receptor 3. The reaction for Epstein-Barr virus–encoded antibodies, CD3, CD68, and CD163 were also negative. Using CD31 stains, the exclusive intravascular location of tumor cells could be demonstrated in the nodular and diffuse infiltrations. The diagnosis was intravascular diffuse large B-cell lymphoma in the lung. Noncharacteristic symptoms, such as subfebrile temperatures, hypoxia, and diffuse and nodular infiltrates of the lung, warrants inclusion of lymphomas in the differential diagnosis. The patient's life might be saved by an early diagnosis and initiation of chemotherapy (R-CHOP) against this aggressive and poorly responding neoplasm.

This activity (“2009 Pulmonary Pathology Society (PPS) Biennial Meeting”) has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the Federation of American Societies for Experimental Biology (FASEB) and the American Society for Investigative Pathology (ASIP). FASEB is accredited by the ACCME to provide continuing medical education for physicians.

FASEB designates this educational activity (“2009 PPS Biennial Meeting”) for a maximum of 18.75 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

The objective of the (“2009 PPS Biennial Meeting”) is to provide a forum for the exchange of new research by scientists and investigators and to facilitate knowledge acquisition regarding issues and challenges related to care and prevention. At the completion of this activity, participants should be able to: 1) discuss the research underway and/or current diagnostic approaches to neoplastic and non-neoplastic pulmonary diseases; 2) demonstrate a gained level of knowledge of the methods and techniques being used by researchers and practitioners; and 3) utilize information and data that lead to improvements in human health.

The 2009 PPS Biennial Meeting is especially targeted to clinical practitioners (including community pathologists and academic pulmonary pathologists, radiologists, clinicians who emphasize lung disease among their patient population), research scientists, medical education professionals, pathology residents and postdoctoral fellows with an interest in gaining a basic and/or advanced understanding of diagnostic, prognostic, and therapeutic approaches in the areas of pulmonary diseases, including lung cancers, pulmonary vasculitis, interstitial pneumonias, respiratory bronchiolitis, fibrotic disorders of the lung, pediatric lung disease, and mesothelioma.

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