Image Quizzes

Reports of dysuria and nocturia

Reviewed by Chad R. Tracy, MD

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A 69-year-old nonsmoking African American man presents with reports of dysuria, nocturia, and unintentional weight loss. He reveals no other lower urinary tract symptoms, pelvic pain, night sweats, back pain, or excessive fatigue. Digital rectal exam reveals an enlarged prostate with a firm, irregular nodule at the right side of the gland. Laboratory tests reveal a prostate-specific antigen (PSA) level of 2.22 ng/mL; a comprehensive metabolic panel and CBC are within normal limits. The patient is 6 ft 1 in and weighs 187 lb.

A transrectal ultrasound-guided prostate biopsy is performed. Histologic examination reveals immunoreactivity for the neuroendocrine markers synaptophysin, chromogranin A, and expression of transcription factor 1. A proliferation of small cells (> 4 lymphocytes in diameter) is noted, with scant cytoplasm, poorly defined borders, finely granular salt-and-pepper chromatin, inconspicuous nucleoli, and a high mitotic count. Evidence of perineural invasion is noted.

What is the likely diagnosis?

Prostate adenocarcinoma

Small cell carcinoma of the prostate

Benign prostatic hyperplasia

Large cell neuroendocrine carcinoma

The history and findings in this case are suggestive of small cell carcinoma of the prostate (SCCP).

SCCP is a rare and aggressive cancer that comprises 1%–5% of all prostate cancers (if mixed cases with adenocarcinoma are included). Similar to small cell carcinoma of the lung or other small cell primaries, SCCP is characterized by a primary tumor of the prostate gland that expresses small cell morphology and high-grade features, including minimal cytoplasm, nuclear molding, fine chromatin pattern, extensive tumor necrosis and apoptosis, variable tumor giant cells, and a high mitotic rate. Patients often have disproportionally low PSA levels despite having large metastatic burden and visceral disease. Pathologic diagnosis is made on the basis of prostate biopsy using characteristics of small cell tumors and immunohistochemical staining for neuroendocrine markers, such as CD56, chromogranin A, synaptophysin, and neuron-specific enolase.

SCCP arises de novo in approximately 50% of cases; it also occurs in patients with previous or concomitant prostate adenocarcinoma. Patients are often symptomatic at diagnosis because of the extent of the tumor. The aggressive nature and high proliferation rate associated with SCCP result in an increased risk for lytic or blastic bone, visceral, and brain metastases. In addition, paraneoplastic syndromes (eg, the syndrome of inappropriate antidiuretic hormone secretion, Cushing syndrome, and hypercalcemia) frequently occur as a result of the release of peptides.

SCCP metastasizes early in its course and is associated with a poor prognosis. It has a median survival of < 1 year. Fluorodeoxyglucose PET-CT are useful for staging and monitoring treatment response; in addition, given the disease's predilection for brain metastases, MRI of the brain should be considered.

The optimal treatment for patients with metastatic SCCP has not yet been determined. Localized SCCP is treated aggressively, typically with a multimodality approach involving chemotherapy with concurrent or consolidative radiotherapy.

According to 2023 guidelines from the National Comprehensive Cancer Network (NCCN), platinum-based combination chemotherapy (cisplatin-etoposide, carboplatin-etoposide, docetaxel-carboplatin, cabazitaxel-carboplatin) is the first-line approach for patients with metastatic disease.

Physicians are also advised to consult the NCCN guidelines for small cell lung cancer because the behavior of SCCP is similar to that of small cell carcinoma of the lung. Immunotherapy with pembrolizumab may be used for platinum-resistant extrapulmonary small cell carcinoma. However, sipuleucel-T is not recommended for patients with SCCP.

Chad R. Tracy, MD, Professor; Director, Minimally Invasive Surgery, Department of Urology, University of Iowa Hospitals and Clinics, Iowa City, Iowa

Chad R. Tracy, MD, has disclosed the following relevant financial relationships:

Serve(d) as a consultant for: CVICO Medical Solutions.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

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