UROLOGICAL SURVEY   ( Download pdf )

 

PATHOLOGY

Small cell carcinoma of the prostate. A morphologic and immunohistochemical study of 95 cases
Wang W, Epstein JI
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA
Am J Surg Pathol. 2008; 32: 65-71

  • Small cell carcinoma of prostate is rare, with the literature consisting of case reports and small series. The current work analyzes the morphology and immunohistochemistry of 95 cases of prostatic small cell carcinoma diagnosed at our institution. Specimens included 55 needle biopsies, 27 transurethral resections, 4 radical prostatectomies, and 9 biopsies from metastatic sites (some patients with > 1 procedure). Patients ranged in age from 44 to 92 years old (mean: 69 y). Although serum prostate-specific antigen (PSA) in some cases was very high (up to 1896 ng/mL), the median value was only 4.0 ng/mL. Of cases with available information, 33/78 (42%) had a history of usual prostatic adenocarcinoma. The interval between the diagnosis of small cell carcinoma and prior usual prostatic cancer ranged from 1 to 300 months (median 25 mo). Pure small cell carcinoma was seen in 54/95 (57%) of cases with the remaining cases admixed with prostate adenocarcinoma. In cases with adenocarcinoma, there was a sharp demarcation between small cell carcinoma and adenocarcinoma in 20.5% of cases; in the remaining cases there was gradual merging of the 2 components. In mixed cases, small cell carcinoma predominated (median: 80% of the tumor); the Gleason score of the adenocarcinoma was > or = 8 in 85% of these cases. In 61 cases (64%), small cell carcinoma was classic “oat cell” morphology with remaining the “intermediate cell” variant. Of the 95 cases: necrosis was seen in 40% (2% to 95% of the tumor); giant bizarre cells in 19%; Indian filing in 21%; rosette formation in 29%; focal vacuolated cytoplasm in 18%; and desmoplasia in 20%. Most (88%) of small cell carcinoma were positive for at least 1 neuroendocrine marker. In the small cell carcinoma component, 14/73 (19%) were positive for PSA, 17/61 (28%) positive for prostein (P501S), and 15/59 (25%) positive for prostate-specific membrane antigen, although often very focally. Stains for thyroid transcription factor-1 were positive in 23/44 (52.3%) cases. In this, the largest study of prostatic small cell carcinoma, we highlight the presence of morphologic features that may result in its underdiagnosis. Other more classic histologic features of small cell carcinoma along with rosettes are critical for its accurate diagnosis. P501S and prostate-specific membrane antigen were better in identifying the prostatic origin of small cell carcinoma than PSA, although the majority (60%) of prostatic small cell carcinomas were negative for all 3 markers.

  • Editorial Comment
    The variant small cell carcinoma of the prostate must be recognized by the pathologist. These rare tumors have an aggressive course and the average survival of patients is less than a year. Most of these tumors show neuroendocrine differentiation demonstrated by immunohistochemistry with markers like NSE, synaptophysin, or chromogranin. Due to these unique features small cell carcinomas are not histologically graded.
    Approximately half of the tumors are associated with conventional prostate adenocarcinoma. It is important to note that neuroendocrine differentiation may occur during progression of prostate conventional carcinomas. Therefore, the tumor may be a conventional adenocarcinoma in the prostate and small cell carcinoma in a metastatic site. In this very large series of Wang and Epstein’s the median value of serum prostate-specific antigen was 4.0 ng/mL. In mixed cases, small cells predominate and the Gleason score of the conventional component is high (> or = 8 in 85% of the cases).
    A review of the literature of genitourinary small cell carcinoma, Mackey et al. (1) found cisplatin chemotherapy to be beneficial for bladder tumors but only surgery was prognostic for prostate small cell carcinomas. Others suggest treating small cell carcinoma of the prostate with the same combination chemotherapy used to treat small cell carcinoma in other sites like, for example, “oat cell carcinoma” of the lung (2-4).

References
1. Mackey JR, Au HJ, Hugh J, Venner P: Genitourinary small cell carcinoma: determination of clinical and therapeutic factors associated with survival. J Urol. 1998; 159: 1624-9.
2. Yao JL, Madeb R, Bourne P, Lei J, Yang X, Tickoo S, et al.: Small cell carcinoma of the prostate: an immunohistochemical study. Am J Surg Pathol. 2006; 30: 705-12.
3. Amato RJ, Logothetis CJ, Hallinan R, Ro JY, Sella A, Dexeus FH: Chemotherapy for small cell carcinoma of prostatic origin. J Urol. 1992; 147: 935-7.
4. Rubenstein JH, Katin MJ, Mangano MM, Dauphin J, Salenius SA, Dosoretz DE, et al.: Small cell anaplastic carcinoma of the prostate: seven new cases, review of the literature, and discussion of a therapeutic strategy. Am J Clin Oncol. 1997; 20: 376-80.

Dr. Athanase Billis
Full-Professor of Pathology
State University of Campinas, Unicamp
Campinas, São Paulo, Brazil