SMALL-CELL CARCINOMA OF PROSTATE

DEBA P SARMA, M.D. THOMAS G. WEILBAECHER, M.D.

From the Department of Pathology, Veterans Administration Medical Center, and the Louisiana State University Medical School, New Orleans, Louisiana

ABSTRACT-Small-cell carcinoma of the prostate is rare, but lethal. We report on 2 cases and review another 6 cases reported in the English literature. Microscopically the tumor may be pure small-cell carcinoma like that seen in the lung or may have a mixed pattern of adenocarcinoma with small-cell carcinoma. This tumor most probably arises from the basal or reserve cells of the prostatic acini. The totipotential basal cells have dual capacity for differentiation into adenocar- cinema and small-cell carcinoma.

Most carcinomas of the prostate are adenocar- cinemas. Small-cell carcinoma (oat-cell car- cinoma) occurring as a primary tumor in the prostate is rare. Only a few well-documented cases have been reported in the English litera- ture.rm4

We report 2 cases of small-cell carcinoma of the prostate and review the previously reported cases.

Case Reports

Case 1 A seventy-two-year-old man with a com-

plaint of difficulty on urination was admitted to the hospital. Physical examination revealed a fixed, hard, multinodular prostate. Small-cell carcinoma was diagnosed on needle biopsy. A transurethral prostatectomy was done. Serum acid phosphatase level was 24 IU/L (normal l- 9 IUIL). Bone scan revealed multiple metas- tases involving spine, ribs, and femur. The pa- tient was given a course of stilbestrol. He remained asymptomatic until three months la- ter when leg edema, dyspnea, and orthopnea developed. He was admitted because of decom- pensated congestive heart failure and died shortly thereafter.

A complete autopsy revealed a small-cell un- differentiated carcinoma involving the entire

prostate with tumor extension into periprostatic adipose tissue and adjacent bladder with an ob- struction of the left ureteric orifice. Metastases were present in the liver and lungs. The pulmo- nary metastases consisted of small foci of neo- plastic cells in the subpleural lymphatic spaces. No large bronchial or parenchymal tumor mass was present in the lung.

Pathologic findings. Initial needle biopsy showed sheets of pleomorphic anaplastic cells with intensely hyperchromatic nuclei and little cytoplasm within a fibromuscular prostatic stroma. Some spindling of the nuclei and many mitoses were present. Sections from the tissue of transurethral prostatic resection and from the prostate tumor at autopsy revealed diffuse in- filtration of the prostatic stroma by anaplastic small cells and focal differentiation into small poorly formed glands with slight alveolar ar- rangements (Fig. 1A). Several prostatic acini were noted to have intraluminal infiltration by the anaplastic cells (Fig. 1B). The low cuboidal epithelium lining the gland was intact in part. The neoplastic cells appeared to have arisen in the basal layer of the epithelial lining lifting up the single cuboidal layer toward the lumen. These acini with in situ pattern of anaplastic carcinoma along with the diffusely infiltrating pattern suggested that the small-cell carcinoma probably started from the basal or reserve cells

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of the prostatic acini. The metastatic deposits in various tissues had an appearance of typical small-cell carcinoma without any differentia- tion (Fig. 1C).

Immunoperoxidase studies did not show prostate-specific antigen in the neoplastic cells. Ultrastructural study did not disclose presence of any specific neurosecretory or other type of granules in the cytoplasm of the neoplastic cells.

Case 2 A sixty-four-year-old black man was admit-

ted to the hospital for evaluation of intermittent seizure episodes that he had been suffering from for the last ten years. Neurologic examination was normal. An enlarged prostate with a firm nodule was detected on physical examination.

A small-cell undifferentiated carcinoma was diagnosed on needle biopsy of the prostate (Fig. 2A). Substernal chest pain developed with sub- sequent cardiac failure and anuria. He died one month after admission.

At autopsy, a 7 x 5-cm, partly necrotic tu- mor involved the entire prostate with extension into prostatic urethra and bladder neck. Metas- tases were present in the pelvic lymph nodes, pancreas, and brain. There was no tumor in the lungs.

FIGURE 1. Case 1. (A) Undijjerentiated small-cell carcinoma of prostate; note focal dijjerentiation into poorly formed glands. (B) Anaplastic cells occu- pying basal zone of prostatic gland with intact over- lying cuboidal cells; intTalumina1 infiltration present. (C) Metastatic small-cell carcinoma in liver. (Hematoxylin and eosin; original magnijications [A] x 120, [B] x 280, and [C] x 120.)

FIGURE 2. Case 2. (A) Needle biopsy of prostate showing small-cell carcinoma; inset shows undij- jerentiated small cells with dark nuclei and very lit- tle cytoplasm. (B) Metastatic small-cell carcinoma in brain. (Hematoxylin and eosin, original magniji- cations [A] x 210, inset x 100, and [B] x 180.)

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Pathologic findings. Sections of the pros- tate showed a diffusely infiltrating anaplastic carcinoma composed of cells with scanty cyto- plasm and small- and medium-sized markedly hyperchromatic nuclei. No glandular differen- tiation was present. Metastatic tumor nodules had an identical histologic appearance (Fig. 2B).

Immunoperoxidase studies did not reveal prostate-specific antigen in the neoplastic cells.

Review cases Wise et al. 5 have described a fifty-eight-year-

old man with a prostatic carcinoma and hy- peradenocorticism and left pleural effusion. A needle biopsy of the prostate had revealed adenocarcinoma. A bilateral adrenalectomy re- vealed diffuse cortical hyperplasia with a single me&static tumor nodule in the left adrenal. Mi- croscopic illustration shows a small-cell car- cinoma. The authors have suggested that the primary site was the prostate. In the presence of pleural effusion, no evidence of exclusion of lung primary tumor, and no autopsy study, we believe that this case does not qualify as a small- cell carcinoma of the prostate.

Wenk et al.’ have reported a well-docu- mented oat-cell carcinoma of the prostate in a sixty-two-year-old white man. The patient came with dysuria, and there were clinical and laboratory features of ectopic ACTH syndrome. The patient received external irradiation. At autopsy, the entire prostate was infiltrated by oat-cell carcinoma. Tumor extended into blad- der and metastasized to the pelvic lymph nodes. Lungs were free of tumor.

Vuitch and Mendelsohr? have described a seventy-year-old man with an adenocarcinoma of the prostate that responded to oral estrogen therapy. Twenty months later urinary retention developed. Prostatic biopsy revealed a mixed adenocarcinoma and small-cell carcinoma. The patient underwent bilateral orchiectomy and received radiotherapy. Three months later Cushing syndrome developed due to ectopic ACTH production by the prostatic cancer. The patient died two months later. At autopsy small-cell carcinoma was present in the prostate and pelvic soft tissue with metatases to liver, vertebrae, and retroperitoneal lymph nodes.

Fer et aLs have briefly mentioned a case of small-cell carcinoma of the prostate with me- tastasis to bone in a sixty-one-year-old man. There was partial response to estrogen and Cy- toxan therapy. The patient was alive six months

after diagnosis. No description of the tumor or histologic illustrations were provided.

Schron, Gipson, and Mendelsohn3 have described 2 patients with small-cell carcinoma of the prostate. One eighty-year-old man with urinary obstruction was noted to have adeno- carcinoma on transurethral prostatectomy. He was treated by orchiectomy and oral estrogens. Fifteen months later, metastases to vetebrae, pelvis, and ribs developed. There was no re- sponse to chemotherapy. He died three months later. Autopsy revealed a mixed adenocar- cinema and small-cell carcinoma of the pros- tate with involvement of the seminal vesicles, pelvic soft tissue, pelvic and para-aortic lymph nodes, and bones.

The other patient was a sixty-seven-year-old man with a Stage IV prostatic adenocarcinoma. He died eight months later of widespread me- tastases. At autopsy, a mixed adenocarcinoma and small-cell carcinoma of the prostate was noted to have extensively metastasized to ab- dominal and mediastinal lymph nodes, liver, bones, lungs, and pericardium.

Hindson, Knight, and 0cker4 have reported a case of a sixty-one-year-old white man with a small-cell carcinoma of the prostate with exten- sive bone and lymph node metastasis. There was a complete but transient remission on chemotherapy (cyclophosphamide, doxorubicin hydrochloride, vincristine). The patient died eight months after diagnosis. At autopsy, small- cell carcinoma had involved the entire prostate with metastases to brain, lungs, liver, spleen, adrenals, bone, and lymph nodes. There was no primary lung tumor.

Comment

Microscopically small-cell carcinoma of the prostate may show a pattern of either (1) small- cell carcinoma in which the primary as well as the metastases show morphologic features like that of small-cell carcinoma of lung, or (2) small-cell carcinoma mixed with adenocar- cinema. We noted pure small-cell carcinoma pattern in our Case 2, as was described in 3 other cases.1.4,e Mixed small-cell carcinoma and adenocarcinoma pattern was noted in 3 cases2J as well as in our Case 1.

Histogenesis of small-cell carcinoma of the prostate remains debatable. Because of the his- tologic similarity between small-cell carcinoma of the prostate and that of the lung, the pres- ence of clinical ectopic endocrine syndromes

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due to ACTH production in a few cases, and observation of the presence of dense-core secre- tory granules in the tumor on electron micros- copy, it has been suggested that small-cell car- cinoma of the prostate originates from the neuroendocrine cells of the prostate. ls2

Argentaffin and argyrophil cells are present in the prostatic ducts and acini of normal pros- tate7.s as well as in the hyperplastic and carci- nomatous prostates. 9~10 These cells have been claimed to represent the neuroendocrine type of cells capable of giving rise to hormone-produc- ing tumors such as carcinoid or small-cell car- cinoma. However, regular adenocarcinomas of the prostate have been known to produce ecto- pit ACTH. 11-13

In several reported cases2.3 small-cell car- cinoma had developed in association with or during the course of progression of usual pros- tatic adenocarcinoma. In our Case 1 we have noted what appeared to be small-cell car- cinoma in situ arising in the basal zone of several prostatic acini. In agreement with other authors,3.14-1a we believe that the small-cell car- cinomas of the prostate like other argyrophilic prostatic carcinomas, are not necessarily neu- roendocrine in origin. They probably arise in the totipotential reserve or basal cells of the prostatic glands with the dual capacity for dif- ferentiation into adenocarcinoma and small- cell carcinoma.

Prostatic small-cell carcinoma is a highly ag- gressive tumor causing widespread metastases and early death. One patient had responded to combination chemotherapy.4

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