De novo small cell neuroendocrine prostate cancer: An atypical case presentation

Abstract

Small cell neuroendocrine carcinoma comprises less than 1 % of all prostate cancers. We report a case of a 62-year-old male who presented acutely with severe lower urinary tract symptoms (LUTS), including nocturia, but with normal prostate-specific antigen (PSA) levels. A tender, stony-hard prostate on digital rectal examination (DRE) led to prostate biopsy and imaging. The biopsy confirmed neuroendocrine carcinoma, and chemotherapy was initiated. This case emphasizes the atypical presentation of neuroendocrine prostate cancer with acute, severe LUTS and rapid progression, underscoring the potential for missed diagnoses when PSA levels are normal.

1 Introduction

Primary neuroendocrine prostate cancer is a rare entity, representing less than 1 % of all prostate cancers, with an annual incidence of 35 per 10,000. This aggressive malignancy carries a poor prognosis, with an average survival time of 1–2 years post-diagnosis. Small cell carcinoma, a subset of neuroendocrine prostate cancer (NEPC), typically presents with advanced symptoms, including local or distant metastases. Diagnosis is confirmed histopathologically via biopsy, often after androgen receptor-targeting treatments in cases where NEPC develops from adenocarcinoma. This report presents an unusual case of de novo small cell carcinoma in a patient with normal PSA levels, highlighting the diagnostic challenges of this rare presentation.

2 Case presentation

A 62-year-old male presented with acute LUTS, including severe nocturia (six times per night) and burning micturition lasting two weeks. Physical examination showed tenderness in the bilateral testes and epididymis without abscess or scrotal discoloration. Initial diagnosis included prostatitis and epididymo-orchitis. Conservative management with alpha-blockers, antibiotics, anti-inflammatory agents, and herbal medications was initiated, with laboratory work-up—including PSA, serum creatinine, FBC, CRP, urinalysis, and urine culture—collected. Results revealed normal parameters, with PSA at 1 ng/mL (later declining to 0.8 ng/mL). However, symptoms persisted.

A digital rectal examination (DRE) was performed, revealing a stony-hard, tender prostate with an irregular and asymmetric surface. Prostate MRI demonstrated a large, irregular mass on the right side of the prostate with capsular infiltration and bilateral lymphadenopathy, rated PI-RADS 5. This unusual presentation, despite a normal PSA level, raised suspicion of a rare prostate malignancy.

A trans-perineal biopsy guided by MRI-fusion transrectal ultrasound was performed. Initial histopathology showed high-grade adenocarcinoma (Gleason 5 + 4); however, slide re-evaluation confirmed small cell neuroendocrine carcinoma involving 85–90 % of the prostate tissue cores bilaterally ( Fig. 1 ). Immunohistochemical staining was positive for racemase, chromogranin, CD56, and synaptophysin, while PSA, CK7, CK20, and GATA3 were negative, excluding gastrointestinal origin. TTF-1 positivity was noted, which, although often seen in lung origin, can occur in urogenital neuroendocrine carcinoma.

An F-18 PSMA PET scan demonstrated moderate PSMA avidity in the prostate with focal intense avidity in the mid-prostate (SUVmax 11.6) and mildly avid iliac lymph nodes (SUVmax 3.2), with no evidence of metastasis to bone or lungs. CT imaging confirmed prostate enlargement, seminal vesicle involvement, and lymphadenopathy ( Fig. 2 ). The patient began treatment with Bicalutamide (50 mg OD) and was subsequently admitted to oncology for first-line chemotherapy (Cisplatin/Etoposide) and immunotherapy (Durvalumab).