Small Cell Carcinoma of the Prostate

Abstract

Pure small-cell carcinoma (SCC) of the prostate is a rare entity and one of the most aggressive malignancies of the prostate. Histologically, prostatic SCCs of the prostate are part of a spectrum of anaplastic tumours of the prostate and are similar to SCCs of the lungs. In most cases, SCC of the prostate is associated with conventional prostatic adenocarcinoma. Both components of these mixed tumours frequently share molecular alterations such as ERG gene rearrangements or AURKA and MYCN amplifications, suggesting a common clonal origin. The clinical behaviour of small-cell prostate carcinomas is characterized by extensive local disease, visceral disease, and low PSA levels despite large metastatic burden. Commonly, the emergence of the SCC occurs in patients with high-grade adenocarcinoma who are often treated with androgen deprivation treatment (ADT). However, SCCs do not usually benefit from ADT. A biopsy of accessible lesions is strongly recommended to identify those with SCC pathological features, as management is undoubtedly affected by this finding. Chemotherapy is the standard approach for treating patients with either localized or advanced prostatic SCC. Despite the emergence of moreaggressive treatment modalities, the prognosis of men with prostatic SCC remains dismal.

High frequency of TERT promoter mutation in small cell carcinoma of bladder, but not in small cell carcinoma of other origins

“…A series 44 cases of SCC of the urinary bladder cases study also showed: TTF-1+, 11 (25%); synaptophysin+, 22 (50%) [[8]]. TTF-1 is often positive in prostate small cell carcinomas [[9],[10]]. Prostate-specific immunostains (such as PSA, p501s and PSMA) are positive in only a minority of small cell carcinoma (approximately 20–25%) [[10],[11]] AR and NKX3-1 were not expressed in the majority of small cell carcinoma, although the majority of the concurrent acinar foci were positive for these markers [[2]].…”

TMPRSS2-ERG gene fusion in small cell carcinoma of the prostate☆

“…Although prostatic markers such as prostatic acid phosphatase, PSA, prostate-specific membrane antigen, and prostein may be helpful in establishing the prostatic origin, the majority of prostatic SCCs are negative for these markers. 5 Prostatic SCC was initially reported to be negative for thyroid transcription factor-1, 18 nonetheless subsequent studies have found that most prostatic SCCs express TTF-1. 6 A recent study found that CD44 may be a unique feature of prostatic SCC, but a substantial number of lung SCCs are also positive for CD44.…”

“…2–3 Although lung SCC is far more common than prostatic SCC, in the absence of a lung primary, the presence of SCC in a prostate specimen is most likely to be a prostatic primary. 5 The involvement of prostate by lung SCC is rare and only occurs in the setting of widespread metastases. Hence, the distinction of prostatic SCC from non-prostatic origin has limited value in the prognosis and treatment of SCC patients.…”

“…4–6 Furthermore, most prostatic SCC lose the prostate-specific immunohistochemical markers, such as prostatic acid phosphatase, PSA, prostate-specific membrane antigen, and prostein. 5 Therefore, a specific molecular marker is needed to help establish the prostatic origin of SCC.…”

SOX2 expression in the developing, adult, as well as, diseased prostate

“…Because it is androgen receptor (AR) negative, NE PCa is naturally androgen independent. Although the vast majority of primary human PCa are adenocarcinomas, immunohistochemical evidence of NE differentiation (NED) can be often found in human PCa, and PCa exhibiting NED is associated with poor prognosis (19, 20). Rapid autopsy of hormone-refractory metastatic PCa has shown NED in most cases (21), and patients that fail androgen deprivation therapy can develop NE cancer and adenocarcinoma with NED (22).…”