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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 |