A 48-year-old African American man was initially seen at another institution because of hypertension. A screening serum prostate-specific antigen (PSA) was 5.24 ng/mL (normal range, 0–2.00 ng/mL). He stated that he had no nocturia, hematuria, frequency, hesitation, or dribbling. A digital rectal examination revealed a normal-sized prostate that was firm to rubbery without nodularity on palpation. Results of needle biopsies showed adenocarcinoma, and he was referred for evaluation and therapy. He elected to undergo radical prostatectomy with pelvic lymph node dissection.
We received a 36-g radical prostatectomy specimen that included a 4.5 × 3.7 × 3.5-cm firm to rubbery prostate with no areas of induration. Sectioning after overnight fixation showed a spongy cut surface without discrete nodules. Hematoxylin-eosin–stained slides showed variably sized glands in a fibromuscular stroma that was distended by cystlike spaces that formed a mass (Figure 1, arrowheads). On closer examination, the spaces were devoid of any epithelial or endothelial lining. They contained blue-tinged mucin, with clusters of small tubules and cords of epithelial cells floating within the mucin (Figure 2). Rare signet ring cells were present. The mucin lakes comprised half of the tumor volume. Within and adjacent to this mass were groups of smaller tubuloacinar glands that infiltrated the stroma and surrounded the larger prostatic glands. Higher power examination showed an intimate association of the tubuloacinar glands with the mucin lakes. The smaller glands were lined by single-layered cuboidal epithelium without a basal layer (Figure 3). The cytoplasm was amphophilic, and the nuclei were large with irregular membranes, coarse granular chromatin, and prominent nucleoli. The mucinous nature of this tumor was highlighted by a periodic acid–Shiff stain with diastase digestion, which stained the abundant mucin bright magenta (Figure 4). Both lobes of the prostate showed tumor, and perineural invasion was present. The surgical margins and 5 submitted lymph nodes were free of tumor. The prostatic urethra was unremarkable. An extensive radiographic and endoscopic metastatic workup was negative.
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Pathologic Diagnosis: Primary Mucinous Adenocarcinoma of the Prostate With Rare Signet Ring Cells
Abstract
Elevated serum prostate-specific antigen was detected in a 48-year-old man who then underwent needle biopsy and radical prostatectomy. Histopathologic evaluation revealed small tubules and cords of epithelial cells floating in mucin, with few signet ring cells and conventional prostatic adenocarcinoma in approximately equal proportions. These findings are diagnostic of mucinous adenocarcinoma of the prostate with rare signet ring cells. This uncommon diagnosis requires that the mucinous component comprise at least 25% of the tumor. The differential diagnosis includes metastatic mucinous tumors and primary mucinous adenocarcinoma arising from the prostatic urethra. Immunohistochemical studies can confirm the diagnosis. Patients are usually symptomatic on presentation, and the prognosis generally is poor. Little is known of the pathogenesis of this tumor, but it has been found to contain abnormal extracellular mucin, and a case report demonstrated a high frequency of microsatellite instability.
Mucinous adenocarcinoma is a rare variant of acinar adenocarcinoma of the prostate. Approximately 60 cases have been reported.1–3 The correct diagnosis requires adherence to strict diagnostic criteria set forth by Epstein and Lieberman,2 namely, the tumor volume should contain at least a 25% mucinous component, and the mucin should form extracellular lakes with or without tumor clusters floating within them. This is important because intraluminal accumulation of mucin with glandular distention is not considered a feature of this tumor.3 Metastatic extraprostatic tumor must also be excluded.
Most patients are 51 to 60 years of age, although men in their 80s may be affected. Almost all patients present with urinary symptoms, abnormal findings on digital rectal examination, and elevated serum PSA. The unusual features in our case are the early age of detection, the absence of urinary symptoms, and unremarkable findings on digital rectal examination. It is important to emphasize that primary mucinous adenocarcinoma of the prostate should not be diagnosed based on results of a needle biopsy because of sampling concerns. Instead, a report noting the mucinous features and the possibility of mucinous adenocarcinoma should be issued.
Grossly, these tumors usually have cystic to partially cystic structures filled with gelatinous material. Histologically, 2 components are seen, namely, extracellular mucin lakes and conventional prostatic adenocarcinoma, commonly Gleason grade 3/4. There generally are no papillary structures, columnar cells, or goblet cells; rare signet ring cells are present.3 These tumors are immunoreactive for PSA and prostatic acid phosphatase, and they lack staining for carcinoembryonic antigen.2,3 The behavior of mucinous adenocarcinoma is similar to conventional adenocarcinoma of Gleason grade 4.4
The extracellular mucin is found to be O-acetylated, usually at the 7 through 9 carbon positions.5 This is not present in normal mucin or in mucin found in well to moderately differentiated prostate adenocarcinomas. Saez and colleagues5 reported that this finding is an adverse prognostic marker. There is also a reported case with a high frequency of microsatellite instability.6 Those authors found a lack of 6 of 7 markers by polymerase chain reaction and an absence of hMSH2 protein by immunohistochemistry, which is rare for prostate cancers. In contrast to mucinous adenocarcinomas of the colon in hereditary nonpolyposis colon cancer, microsatellite instability is not associated with a favorable outcome.
The differential diagnosis includes primary mucinous adenocarcinoma arising from the prostatic urethra and metastatic mucinous adenocarcinoma, especially from the urinary bladder and colon, as these entail different treatments and prognoses. Tran and Epstein7 first described primary mucinous adenocarcinoma arising from the prostatic urethra. This tumor is also characterized by extracellular mucin lakes; however, the cells within and adjacent to the mucin lakes are of the intestinal type, with glandular spaces lined by atypical pseudostratified columnar epithelium. In addition, abundant signet ring or goblet cells are present, floating within extracellular mucin and infiltrating the stroma. The prostatic urethra may demonstrate changes of colonic metaplasia or in situ adenocarcinoma.
Saito and Iwaki1 reviewed all the mucin-producing adenocarcinomas of the prostate reported in the English literature. They described the following 3 subtypes: (1) mucinous carcinoma; (2) signet-ring cell carcinoma, defined as having signet ring morphologic structure in at least 25% of the tumor volume; and (3) mucinous carcinoma with signet ring cells, defined as having extracellular mucin in at least 25% of the tumor volume and having signet ring morphologic structure in less than 25% of the tumor volume. Similar findings in the 3 subtypes include age at presentation, urinary symptoms, hard nodules on digital rectal examination, immunohistochemical staining with antiPSA, and advanced stage at manifestation. The differences are that mucinous carcinoma has a higher rate of elevated serum PSA (77.8%) and a better response to hormonal therapy (77.8%); none of the signet-ring cell carcinoma or mucinous carcinoma with signet ring cells respond to hormonal therapy.
The treatment of prostatic mucinous adenocarcinoma includes surgery and hormonal treatment. The prognosis is poor; the 3- and 5-year survival rates are 50% and 25%, respectively. This is related to the propensity of the tumor to have bone and visceral metastases early in the disease. However, there are isolated case reports of long survival with this type of tumor.8,9
On follow-up, our patient had an uneventful recovery from surgery. Bone scans and radiographs revealed lesions consistent with known prior trauma, with metastasis not excluded. Biopsy was not performed.
References
The authors have no relevant financial interest in the products or companies described in this article.