The Squamous Cells of Adenosquamous Carcinoma (ASCC) of the Prostate Might Represent a Terminally Differentiated Quiescent Component: Immunohistochemical Evidence From a Case of ASCC With Pleomorphic Giant Tumor Cells

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Adenosquamous carcinoma (ASCC) of the prostate is an exceedingly rare variant of prostate cancer, accounting for 0.00003% of cases registered in the Surveillance, Epidemiology and End Results (SEER) database from 1973 to 2008.1 The largest series published to date—resulting from a joint review of cases seen at Johns Hopkins Hospital and Memorial Sloan Kettering Cancer Center—counts with 25 ASCCs, 9 of which show additional histologic components of sarcoma (6 cases) or urothelial carcinoma (3 cases).2 Here we present a case of ASCC with glandular elements of a high histologic grade and abundant scattered pleomorphic giant tumor cells.
A 57 year-old African American male presented to the urology clinic of our institution with irritative lower urinary symptoms and a prostate specific antigen of 21.5 ng/dL, but absence of significant obstructive symptoms. An extended biopsy protocol demonstrated acinar adenocarcinoma Gleason score 4+3=7 (grade group 2) with tertiary pattern 5 involving all 6 cores corresponding to the right prostatic lobe, and 2 cores corresponding to the mid left prostatic lobe and left prostatic base, respectively. The prostatectomy specimen showed a bulky tumor that involved >50% of the gland volume, and consisted of 2 predominant architectural patterns. The most abundant one was composed of malignant cribriform glands that contained cells with moderate cytologic atypia, and comprised 70% of the lesional volume. The second most frequent pattern showed solid islands of cells with central tumor-type necrosis akin to the comedo-necrosis of breast carcinomas, and severe cytologic atypia (Fig. 1A). Most of the tumor islands that lacked comedo-necrosis, showed a central component of malignant squamous cells with abrupt keratinization and dyskeratosis instead (Fig. 1B). Overall, the squamous elements accounted for approximately 5% to 10% of the neoplasm. Also, abundant mononucleated and multinucleated pleomorphic giant tumor cells, as well as bizarre atypical mitosis, were scattered throughout the higher grade components of the lesion (Figs. 1C, D). Interestingly, there were multiple areas of the tumor where a smooth, progressive transition between the 2 aforementioned patterns could be readily appreciated. By immunohistochemistry, the lower grade components showed expression of prostate specific antigen and prostate specific acid phosphatase, which was completely lost in both the solid and squamous elements of the tumor. All histologic elements but the pleomorphic giant tumor cells were positive for pan-cytokeratin, while vimentin and urothelial markers were negative throughout the tumor. The high proliferative rate of the nonsquamous elements was evident with Ki-67 immunohistochemical stain, which highlighted more than 80% of the cancer cells and showed a characteristic marginal nuclear plus nucleolar staining pattern in the pleomorphic giant tumor cells. Interestingly, the squamous foci—sharply demarcated by high-molecular weight cytokeratin and cytokeratin 5/6—were negative for Ki-67 (Figs. 2A, B). After a complete examination of the hematoxylin and eosin and immunohistochemically stained sections, the final diagnosis was that of ASCC of the prostate, with a high grade glandular component and scattered pleomorphic giant tumor cells. With regard to the stage, the presence of multifocal extraprostatic extension and absence of lymph node metastases corresponded to a pT3a, pN0 disease.
ASCC of the prostate is thought to arise from divergent differentiation of basal cells or transdifferentiation of adenocarcinoma.3 Unlike acinar adenocarcinoma, it usually presents with obstructive symptoms due to bulky local disease, showing direct extension beyond the prostate as well as dissemination to regional lymph nodes and distant metastases at initial diagnosis.2,3 The case presented above provides immunohistochemical evidence suggesting that the squamous elements might represent a quiescent, terminally differentiated component, which is also supported by the finding of numerous individual dyskeratotic (apoptotic) cells on the sections stained with hematoxylin and eosin.
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