Stesura Seveso Archivio Italiano di Urologia e Andrologia 2020; 92, 4390 CASE REPORT No conflict of interest declared. DOI: 10.4081/aiua.2020.4.390 Primitive small cell carcinoma of the prostate. Case report and revision of the literature Pietro Pepe 1, Ludovica Pepe 1, Mara Curdman 2, Michele Pennisi 1, Filippo Fraggetta 2 1 Urology Unit - Cannizzaro Hospital, Catania, Italy; 2 Pathology Unit - Cannizzaro Hospital, Catania, Italy. inguinal hernia repair. The patient had not familiarity for prostate cancer (PCa) and assumed antihypertensive and alfa-blocker drugs. At admission, the patient referred chronic fatigue and was anuric from two days, serum creatinine and PSA values were equal to 9.6 mg/dl and 4.8 ng/ml, respectively; moreover, digital rectal exami- nation was highly suspicious for PCa. In emergency, the patient underwent bilateral application of percutaneous renal nephrostomies to restore kidney function. After three day the patient was submitted to ultrasound-guid- ed extended transperineal biopsy (6); the histology showed the presence of a prostatic SCC fulfilling the World Health Organization criteria that involved all the 12 needle cores (Figure 1). The immunohistochemical analysis was positive for chromogranin, synaptophysin and focally for thyroid transcriptation factor 1 (TTF-1); Ki67 expression was equal to 85% (Figure 2), converse- ly, CK7 and p63 were negative (7). The patient under- went clinical staging including chest and abdominal computed tomography (CT); evaluation and total body scan those did not demonstrated distant metastases and/or others primitive tumors; in addition, cystoscopy and urinary cytology were negative. The patient under- went multidisciplinary evaluation, but he died 20 days from the diagnosis for progressive clinical worsening (physical and cognitive impairments) before beginning oncological treatment. Autopsy was not performed. DISCUSSION Primitive SCC of the prostate is a rare entity and has a presentation that is distinct from its adenocarcinoma counterparts (8); unique features include an unrespon- siveness to hormonal therapy, rapid progression, increased risk of lytic bone lesions, presence of visceral metastases, and low PSA in relation to disease burden. On the other hand, the majority of prostate SCC are diagnosed in men with castration-resistant prostate cancer (CRPC) and are often characterized by the presence of neuroendocrine (NE) cancer differentiation. The median time to development of SCC in patients with a history of prostatic adenocarcinoma is approxi- mately 18-24 months from diagnosis, but ranges widely from few months to several years. Primitive prostate SCC was first described by Wenk et al. (3) and, recently, Zhang et al. (4) reported 8 cases of pure SCC; autopsy studies of men who have died from CRPC A Caucasian man 84 years old was admit- ted to our Department for acute renal fail- ure secondary to severe bilateral hydronephrosis; moreover, the patient referred chronic fatigue and was anuric from two days. Serum creatinine and PSA values were equal to 9.6 mg/dl and 4.8 ng/ml and digital rectal examination was highly suspicious for prostate cancer. In emergency, the patient underwent bilateral application of percutaneous renal nephrostomies to restore kidney function and, after three days, was submitted to ultrasound-guided extended transperineal biopsy; the histology showed the presence of a prostatic small cell carcinoma (SCC) fulfilling the World Health Organization criteria. The patient underwent clinical staging including chest and abdominal computed tomography evaluation and total body scan that did not demonstrated distant metastases and/or others primitive tumors; in addition, cystoscopy and urinary cytology were negative. The patient underwent multidiscipli- nary evaluation, but he died 20 days from the diagnosis for progressive clinical worsening (physical and cognitive impair- ments) before beginning oncological treatment. In conclusion, primitive SCC represents a very rare cancer provided of poor prognosis; only the execution of prostate biopsy combined with an accurate specimen analysis allow to make the correct diagnosis and therapeutic treatment. KEY WORDS: Prostate cancer; Small cell cancer; Prostate small cell cancer; Neuroendocrine small cell prostate cancer. Submitted 17 July 2020; Accepted 30 September 2020 INTRODUCTION Primitive small cell carcinoma (SCC) of the prostate is a very rare (0.5% of the cases) and aggressive type of pro- static cancer and often is diagnosed at advanced stage due to early metastasis (1-5); most frequently, SCC is associat- ed to progressive hormone-refractory prostate cancer. The biology of SCC is poorly understood but it is always implicated in the lethal progression secondary to visceral metastases and lytic bones lesions. In this study, a case of primitive prostate SCC has been reported. CASE REPORT A Caucasian 84 years old man was admitted to our Department for acute renal failure secondary to severe bilateral hydronephrosis; the patient suffered from blood hypertension and was previously submitted to right Summary 391Archivio Italiano di Urologia e Andrologia 2020; 92, 4 Primitive small cell carcinoma of the prostate have reported the presence of SCC in up 10-20% of cases. The histological diagnosis of SCC is reached based on the presence of morphological features similar to those found in SCC of the lung; using immunohisto- chemical techniques, the small-cell component could be positive for one or more neuroendocrine markers (i.e., neuron-specific enolase, synapthosiphysin, chromo- granin, and CD56) in almost 90% of the cases. Studies have demonstrated thyroid transcriptation factor 1 (TYF-1) expression in over 50% of SCCs of the prostate, 85-90% loss rate of tumor suppressor retinoblastoma protein (RB1), and 50-60% mutation rate of TP53, limiting its utility in distinguishing primary prostate SCC from metastases of other small cell cancers. Therefore, in the absence of a primary SCC at another site (for example, the lung), the finding of SCC on prostate biopsy is almost undoubtedly an indication of prostatic origin. In the last years, gene expression in metastatic CRPC neu- roendocrine SCC prostate has been tested confirming sim- ilar molecular profile with small cell lung carcinoma (8). In addition, molecular studies have reported an increased expression of gene involved in cellular proliferation, cell cycle, neuroendocrine differentiation and mitosis. Metzger et al. (5) reported on 657 men with neuroen- docrine SCC an overall survival of 12 months. Wang et al. (9) on 260 patients selected from Surveillance, Epidemiology, and End Results (SEER) database showed an increased inci- dence of prostate SCC over time that was characterized by presence of high stage (stage IV in 77.7%), nodes involve- ment (49%) and distant metastases (68%) with PSA values greater than 10 ng/ml only in 23% of the cases; although patients underwent chemotherapy (58.8%), surgery (25.4%) and, radiotherapy (31.9%) the observed survival rates of 1-year, 2-year, and 5-year were 42.1%, 22.1%, and 12.5%, respectively. Although the poor prognosis, it is important to make dis- tinction between primitive prostate SCC and NE-CRPC because therapeutic strategy changes and should be managed similarly to other non-prostatic SCC. Rarely prostatectomy or radiotherapy alone have been shown to be curative because the tumor, in the majority of the cases, is metastatic (5), moreover, prostate SCC is usual- ly not responsive to androgen deprivation and disease progression is not associated with rises in serum PSA val- ues. In definitive, the best treatment remains the multi- disciplinary approach by chemotherapy alone or com- bined with local therapy that could offer local palliation of clinical symptoms (5, 10). In our case, the patient had a primitive prostate SCC characterized as locally advanced cancer involving blad- der and kidney function in absence of documented dis- tant metastases; therefore, we don’t know if the patient died from prostate SCC or from concomitant onset sys- temic pathologies. 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Results of a phase II study with doxorubicin, etoposide, and cisplatin in patients with fully characterized small-cell carcinoma of the prostate. J Clin Oncol. 2002; 20:3072-3080. Figure 1. Tumour was composed of undifferentiated cells with scant cytoplasm, infiltrating fatty tissue. Figure 2. Neoplastic cells showed a high proliferative fraction as highlighted by Ki67. Correspondence Pietro Pepe, MD (Corresponding Author) piepepe@hotmail.com Michele Pennisi, MD Ludovica Pepe Urology Unit - Cannizzaro Hospital, Catania Via Messina 829, Catania (Italy) Mara Curdman, MD Filippo Fraggetta, MD Pathology Unit - Cannizzaro Hospital, Catania (Italy)