Subtypes Of Prostate Adenocarcinoma

Even in ordinary adenocarcinomas of the prostate without light microscopic evidence of neuroendocrine differentiation, almost half show neuroendocrine differentiation when evaluated with immunohistochemistry for multiple neuroendocrine markers (^[116] diSantagnese, 1992). Most of these neuroendocrine cells contain serotonin and, less frequently, calcitonin, somatostatin, or human chorionic gonadotropin. Most of these cases have no evidence of ectopic hormonal secretion clinically. It is controversial whether the extent of neuroendocrine differentiation in ordinary prostate cancer affects prognosis. Small-cell carcinomas of the prostate are identical to small-cell carcinomas of the lung. In approximately 50% of the cases, the tumors are mixed small-cell carcinoma and adenocarcinoma of the prostate. Although most small-cell tumors of the prostate lack clinically evident hormone production, they account for the majority of prostatic tumors with clinically evident adrenocorticotropic hormone or antidiuretic hormone production. The average survival of patients with small-cell carcinoma of the prostate is less than a year. There is no difference in prognosis between patients with pure small-cell carcinoma and those with mixed glandular and small-cell carcinomas.

Between 0.4% and 0.8% of prostatic adenocarcinomas arise from prostatic ducts. When prostatic duct adenocarcinomas arise in the large primary periurethral prostatic ducts, they may grow as an exophytic lesion into the urethra, most commonly in and around the verumontanum, and give rise to either obstructive symptoms or hematuria. Tumors arising in the more peripheral prostatic ducts may present like ordinary (acinar) adenocarcinoma of the prostate and may be diagnosed on needle biopsy. Tumors are often underestimated clinically because rectal examination and serum PSA levels may be normal. Most prostatic duct adenocarcinomas are in advanced stage at presentation and have an aggressive course.

Pure primary squamous carcinoma of the prostate is rare and is associated with poor survival. These tumors develop osteolytic metastases, do not respond to estrogen therapy, and do not develop elevated serum acid phosphatase levels with metastatic disease. More commonly, squamous differentiation occurs in the primary and metastatic deposits of adenocarcinomas that have been treated with estrogen therapy.

Mesenchymal Tumors

Sarcomas of the prostate account for 0.1% to 0.2% of all malignant prostatic tumors. Rhabdomyosarcoma is the most frequent mesenchymal tumor within the prostate and is seen almost exclusively in childhood. Leiomyosarcomas are the most common sarcomas involving the prostate in adults. There are two benign reactive spindle-cell lesions that may simulate a leiomyosarcoma. One may occur, although rarely, soon after TUR, and the other occurs without a history of TUR. There are also mesenchymal tumors of the prostate arising from the unique prostatic specialized stroma. These lesions range from prostatic stromal tumors of uncertain malignant potential to prostatic sarcomas. Histologically, these lesions are variable; one subtype resembles a tumor seen in the breast and is termed phyllodes tumor of the prostate. Carcinosarcomas have also been reported within the prostate and have a dismal prognosis.

Transitional Cell Carcinoma

Primary transitional cell carcinoma of the prostate without bladder involvement accounts for 1% to 4% of all prostate carcinomas. In cases of primary transitional cell carcinoma of the prostate, stromal invasion is almost always identified. Primary transitional cell carcinomas of the prostate show a propensity to infiltrate the bladder neck and the surrounding soft tissue such that more than 50% of the patients present with stage T3 or T4 tumors. Twenty percent of the patients present with distant metastases, with bone, lung, and liver being the most common sites. In contrast to adenocarcinoma of the prostate, bone metastases tend to be osteolytic. Treatment of stage T3 disease with radiation results in a 5-year survival of approximately 34%. In the minority of cases with tumor localized to the prostate (T2), radical surgery has resulted in long-term disease-free survival in several patients.

More commonly, transitional cell carcinoma involves prostatic ducts and acini in patients with a history of flat transitional cell carcinoma in situ of the bladder who have been treated over a period of months to years with intravesical topical chemotherapy. Between 35% and 45% of cystoprostatectomies performed for transitional cell carcinoma contain prostatic involvement. However, this number is dependent on the amount of histologic sampling of the prostate tissue and may be much higher in completely mapped specimens. If cystoprostatectomy is performed and only intraductal transitional cell carcinoma is present, the prostatic involvement does not worsen the prognosis, which is determined by the stage of the bladder tumor. Intraductal transitional cell carcinoma of the prostate appears to involve the prostate via direct extension from the overlying urethra, which is usually involved by carcinoma in situ. Intraductal and infiltrating transitional cell carcinoma involving the prostate tends to be seen in higher-stage bladder tumors, in which the patients have a poor prognosis attributable to either advanced bladder or prostatic disease. A minority of these cases will have low-stage bladder tumor and a poorer prognosis, demonstrating the adverse effect of prostatic stromal infiltration. It is, therefore, prognostically important to identify prostatic stromal invasion in cases of intraductal transitional cell carcinoma, especially in patients with low-stage bladder tumor. Extensive sampling of the periurethral area in cystoprostatectomy specimens performed for transitional cell carcinoma is necessary to identify and evaluate the prostate for transitional cell carcinoma. Finally, one may find direct invasion from bladder transitional cell carcinoma into the stroma of the prostate. The distinction between poorly differentiated transitional cell carcinoma and poorly differentiated adenocarcinoma of the prostate can be difficult. There are numerous studies demonstrating that even for high-grade adenocarcinomas of the prostate, immunohistochemical stains for PSA and prostate-specific acid phosphatase (PSAP) are usually positive. Because antisera to PSA is more sensitive in identifying prostatic tumors in some cases and because PSAP gives superior results in other cases, both antisera should be used in establishing if the tumor is of prostatic origin. With only a few exceptions, immunoperoxidase staining for PSA and PSAP is very specific for prostatic tissue. However, in a small fraction of cases, which may vary depending on the amount of tumor available for examination, stains may be negative for both antigens and still represent prostate adenocarcinoma. More recently, several studies have explored the use of other markers that may be expressed preferentially in transitional cell carcinoma. The most specific is high-molecular-weight cytokeratin (34βE12), which is negative in prostate adenocarcinoma. Transitional cell carcinomas express this antigen in 57% to 70% of cases. The other two markers sometimes used are cytokeratins 7 and 20 (CK7 and CK20). CK7 and CK20 positivity in transitional cell carcinoma is 70% to 100% and 15% to 71%, respectively. The problem with these markers is that they are not specific. CK20 is seen in 2% to 72% and CK7 is seen in 19% to 35% of prostate adenocarcinomas. Consequently, the author uses only a combination of PSA, PSAP, and 34βE12, in conjunction with routine light microscopic findings, to differentiate transitional cell carcinoma from adenocarcinoma of the prostate. Newer markers that may also be specific for transitional cell carcinoma are uroplakin and thrombomodulin.

Miscellaneous Malignant Tumors

Primary prostatic lymphoma without lymph node involvement appears to be much less common than secondary infiltration of the prostate. The most common form of leukemic involvement of the prostate is that of chronic lymphocytic leukemia, although monocytic, granulocytic, and lymphoblastic leukemias have also been found in the prostate.