1992, The British Journal of Radiology, 65, 726-728

Case reports

Small cell carcinoma of the prostate By J . Sule-Suso, LMC and A. M. Brunt, M B , MRCP, FRCR Department of Clinical Oncology, North Staffordshire Royal Infirmary, Princes Road, Hartshill, Stoke-on-Trent, Staffs ST4 7LN, UK (Received 12 June 1991 and in revised form 21 October 1991, accepted 14 January 1992) Keywords: Small cell carcinoma, Prostate gland

Primary small cell carcinoma of the prostate gland is a rare disease entity with a poor prognosis. Even more unusual than primary disease is a metastasis from a lung primary (Johnson et al, 1974; Hodge & Carson, 1985). We confine ourselves in this paper to primary disease, which has to be differentiated clinically from a pulmonary metastasis. Primary small cell carcinoma of the prostate has been described as occurring after a diagnosis of adenocarcinoma of the prostate (Schron et al, 1984), as a combination of the two histologies at the time of initial diagnosis (Tetu et al, 1987) or on its own (Sarma & Weilbaecher, 1989). Though it has been suggested that small cell carcinoma of the prostate reflects a terminal aggressive phase of adenocarcinomatous disease (Schron et al, 1984), the occurrence of "pure" small cell carcinoma presents an argument against this in at least a proportion of cases (Tetu et al, 1987; Sarma & Weilbaecher, 1989). The origin of small cell carcinoma of the prostate is not clear. It has been suggested that this malignancy derives from the argyrophil and argentaffin cells found in the normal prostatic epithelium (Wenk et al, 1977). However, Schron et al (1984) noted that the small cell carcinoma in their three patients developed in association with, and during the course of progression of, "normal" prostatic adenocarcinoma. It, therefore, appeared to represent the emergence of a different clone manifesting the differentiation characteristics of small cell carcinoma rather than an entirely separate tumour.

This theory of divergent differentiation is an alternative explanation of aetiology which has other supporters (Vuitch & Mendelsohn, 1981; Jelbart et al, 1988). It is possible that both explanations are correct in a proportion of cases. We report a further case of small cell carcinoma of the prostate, the first to emanate from the UK. Case report A 62-year-old man presented in May 1990 with acute urinary retention. There were no other significant symptoms except for suprapubic pain and dysuria for the prior 2 to 3 weeks. Rectal examination revealed an irregular hard enlarged prostate. A full haematological and biochemical screen was normal except for a mildly lowered serum calcium. It was noted that prostatic specific antigen (PSA) and acid phosphatase (PAP) were normal. 2 days after admission the patient underwent transurethral resection of his prostate gland. Histologically there was fibromyoepithelial hyperplasia, acute and chronic inflammatory foci of prostatitis and no evidence of neoplasia. He was readmitted 2 months later with a large smooth swelling apparently arising from the prostate and extending to the left pararectal region. His only symptom at the time was a mild degree of tenesmus. He had a further transurethral resection, histological examination of the prostatic tissue revealed a poorly differentiated small cell tumour with hyperchromatic pleomorphic nuclei and little cytoplasm (Figs la & b). Immunohistochemistry was weakly positive for neurone specific enolase and negative for PSA and leukocyte common antigen. Appearances were those of a small cell carcinoma. A chest radiograph performed at this time was normal. The alkaline phosphatase and aspartate transaminase levels were

Figure 1. Biopsy sample from a TURP; (a) x 20 magnification, (b) x 100 magnification.

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Case reports slighly raised above the upper end of the normal range, but all other routine blood tests were normal. We looked for evidence of peptide hormone secretion, but the adrenocorticotrophic hormone (ACTH), antidiuretic hormone (ADH) and plasma and urine osmolality were normal. He was commenced on Vincristine, Adriamycin and Cyclophosphamide (VAC) chemotherapy at 3 weekly intervals with the intention of consolidating any response with radiotherapy. 9 days after the second course of VAC he was admitted with a deep venous thrombosis in his left calf. A minimal clinical response to the chemotherapy was observed. Computed tomographic (CT) scanning of his abdomen and pelvis confirmed the presence of a 11x12 cm mass involving the prostate and rectum. Irregular extraperitoneal extension towards the inferior aspect of the right sacro-iliac joint was seen, as was the presence of enlarged left iliac nodes. Chest radiographic appearances remained normal. A month after his second course of VAC he commenced radiotherapy. A large pelvic and perineal field was treated with an anterior and posterior opposed pair to 4500 cGy mid-plane dose in 25 fractions over 5 weeks. Within 10 days of starting radiotherapy a partial response was noted clinically. During treatment he became jaundiced and an ultrasound scan identified multiple enlarged lymph nodes around the head of the pancreas, with common bile duct dilatation. Para-aortic nodes were also seen to be enlarged; all these areas had been normal on the CT scan a month previously. He received palliative radiotherapy of 3000 cGy in 10 fractions to his porta hepatis. The radiotherapy to his pelvis was completed to try and gain local control. Clinically there was a complete response of the primary at the end of the 5 weeks of radiotherapy. A follow-up CT scan was arranged but the patient deteriorated rapidly. He died at home 18 days after completing radiotherapy and 3^ months after initial presentation with small cell carcinoma of the prostate. A request for a postmortem examination was declined.

Discussion The main presenting symptoms of small cell carcinoma of the prostate are often those of the local disease; dysuria, hesitancy of micturition and then urinary retention (Wenk et al, 1977; Schron et al, 1984; Tetu et al, 1987; Manson et al, 1989; Sarma & Weilbaecher, 1989). Symptoms of systemic disease, such as weakness and weight loss, may also be present (Wenk et al, 1977; Hindson et al, 1985; Hodge & Carson, 1985; Manson et al, 1989). Our patient presented with dysuria, suprapubic pain and then urinary retention, but no systemic symptoms. Serum PAP levels have been reported as increased, even in patients with pure small cell carcinoma (Tetu et al, 1987; Sarma & Weilbaecher, 1989). PSA is a more recently available serum marker. In the literature we have not identified a pure small cell carcinoma of the prostate with a raised value. Neither marker was raised in our patient. In our patient the serum ACTH was normal, less than 10 pmol/1 (normal range 3.3-15.4 pmol/1). ACTH has been reported as raised in the serum and found to be present at biopsy in tissue of a patient with pure small cell carcinoma (Wenk et al, 1977). A case of Cushing's syndrome has been reported in a patient with mixed Wol. 65, No. 776

disease (Schron et al, 1984) but has also been recorded in pure adenocarcinoma of the prostate (Hall, 1967; Lovern et al, 1975). In our patient ADH was also normal, 1.9 pmol/1 (range 0.9-4.6 pmol/1). Calcitonin, parathormone and bombesin have been raised in some cases of small cell carcinoma of the prostrate. It has been suggested that assays for these should be carried out, if possible, to see if the presence of small cell carcinoma of the prostate is suspected (Jelbart et al, 1988). These findings indicate that neither the usual serum markers for adenocarcinoma (PAP, PSA) nor the evidence of ectopic production of ACTH can be used to differentiate absolutely between adenocarcinoma or small cell carcinoma of the prostate. The prognosis of patients with small cell carcinoma of the prostate is poor. In the largest reported series of 20 cases, the longest survivors were two patients alive with disease at 18 months (Tetu et al, 1987). In nine other reported cases the mean survival from diagnosis of the small cell component was 3 months, range 0-8 months (Wenk et al, 1977; Vuitch & Mendelsohn, 1981; Schron et al, 1984; Hindson et al, 1985; Manson et al, 1989; Sarma & Weilbaecher, 1989). From the available data it is difficult to form a definite treatment strategy and one could question whether treatment is justified in some patients. It would be reasonable to base a treatment strategy around the same principles used to manage small cell carcinoma of the lung. We attempted this in our patient with initial chemotherapy followed by consolidative radiotherapy. This was the intention even though the disease appeared limited at presentation. More extensive staging, such as a CT scan of abdomen and pelvis, bone scan and bone marrow aspirate and trephine, could also be performed. These investigations are not mandatory, but can be performed both as a baseline for future comparison and as a way of planning treatment strategy. Unfortunately our patient had only a minimal response to chemotherapy, a response that is assessed as static disease. The responsiveness to radiotherapy was encouraging and it suggests that if effective chemotherapy could be found there may be a role for consolidative radiotherapy. Responses to chemotherapy have been noted (Tetu et al, 1987). One patient has had a documented complete response (Hindson et al, 1985), but with a duration of only 2 months. He was treated with VAC. It is possible that improved response rates may be achieved with other agents, e.g. etoposide and cisplatinum, and it may be reasonable to adopt this approach for treatment of this rare and aggressive tumour. The only reported use of radiotherapy in the literature is from the M. D. Anderson Hospital, where this modality was used in the treatment of 6 out of 20 cases (Tetu et al, 1987). The precise details and response was not documented. The use of a high dose (60-70 Gy) radiotherapy has been recommended because of the possible admixture of small cell carcinoma and adenocarcinoma (Jelbert et al, 1988). Hormonal manipulation, as used for treatment of adenocarcinoma of the prostate, cannot 727

Case reports

be expected to produce a worthwhile response, except possibly to an adenocarcinomatous element if present. It is not feasible to treat patients with such rare tumours on study protocols. However, results of treatment should be reported to enable clinicians seeing isolated cases to try and form a strategy for the individual patient. We believe that it is reasonable to adopt whatever approach would be offered to a patient with a similar stage of disease and primary tumour in the lung. The grim prognosis cannot be overemphasized. Acknowledgments We would like to thank Dr J. E. Scoble for allowing us to report on this case and his helpful comments, Dr S. C. Harris for reviewing the histopathology, providing the photographs and for his constructive comments and Miss A. W. Littler for typing the manuscript.

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The British Journal of Radiology, August 1992

Small cell carcinoma of the prostate.

1992, The British Journal of Radiology, 65, 726-728 Case reports Small cell carcinoma of the prostate By J . Sule-Suso, LMC and A. M. Brunt, M B , M...
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