轉移性攝護腺癌同時伴生膀胱小細胞神經內分泌腫瘤 – 病例報告

蘇楷森¹、黃子豪^1,2、黃志賢^1,2 

¹臺北榮總泌尿部；²國立陽明交通大學書田泌尿科學研究中心

Metastatic Prostate Adenocarcinoma with Metachronous

Bladder Small Cell Neuroendocrine Carcinoma – A Case Report

Kai-Sen Su¹, Tzu-Hao Huang^1,2, William J. Huang^1,2

¹ Department of Urology, Taipei Veterans General Hospital;

² Department of Urology, School of Medicine and Shu-Tien Urological Science Research Center, National Yang Ming Chiao Tung University

Introduction:

Bladder small cell neuroendocrine carcinoma is extremely rare, accounting for merely 0.5~1% of all primary bladder malignancy. Due to obscured clinical symptoms, early diagnosis is difficult. Such histology indicates aggressive biological behavior and poor prognosis. We hereby present a case of metastatic prostate adenocarcinoma with metachronous diagnosis of bladder small cell neuroendocrine carcinoma.

Case report:

This is a 73-year-old male with a history of hypertension under regular medication. He was sent to our emergency department in 2022/5 due to urinary tract infection. Computed tomography (CT) revealed heterogeneous enhancement of enlarged prostate with nodular lesions at perivesical space, involving bilateral seminal vesicles and right posterior wall of urinary bladder, with resulting right hydroureteronephrosis. CT image also revealed suspected metastatic lymphadenopathy over right iliac region, peritoneal seeding at omentum, and bony metastasis at T-L spines, right 10th rib, bilateral pelvic bones and bilateral femurs, metastases considered.

Transrectal ultrasound (TRUS) prostate biopsy confirmed prostate adenocarcinoma, Gleason score 4+5. Prostate-specific antigen (PSA) level was 1006.70 ng/ml at initial diagnosis. Under the impression of metastatic prostate cancer, androgen deprivation therapy (ADT) was initiated. Leuprorelin and androgen receptor targeted agent (ARTA) with Apalutamide were administered under the diagnosis of metastatic hormone sensitive prostate cancer. The patient responded well to hormonal therapy and the PSA level dropped to nadir of 0.73 after 2 months of treatment in 2022/7, with CT follow-up in 2022/8 showed disease regression, as well as improved right hydronephrosis.

Prostate cancer condition remained stable on follow-up CT image in 2022/11 , while a 3.7cm mass noted at subcutaneous layer of right urinary bladder dome, with upstream hydroureter and mild hydronephrosis, suggesting the possibility of tumor seeding or other tumor growth. Thus we performed transurethral resection of bladder tumor (TURBT) for tissue sampling in Dec 2022, and pathology revealed small cell neuroendocrine carcinoma. The tumor cells are immunoreactive for synaptophysin and insulinoma-associated protein 1 (INSM1), but are negative for GATA3 and NKX3.1, which were distinct from previous prostate cancer.

This case was presented at multidisciplinary teams (MDT) tumor boards, surgery followed by chemotherapy for small cell neuroendocrine carcinoma of urinary bladder was concluded. Partial cystectomy was arranged on 2023/1/11 with uneventful recovery. Final pathology confirmed small cell neuroendocrine carcinoma of urinary bladder. Further 3 courses of chemotherapy with Cisplatin-based regimen was given and later withheld due to septic shock and poor condition. The patient expired in April 2023.

Conclusions:

Aggressive prostate cancer cells may transdifferentiate into neuroendocrine-like (NE-like) cells, which lack the expression of androgen receptor and prostate specific antigen, and are resistant to traditional hormonal treatments. Neuroendocrine prostate cancer (NEPC) may arise de novo or in patients previously treated with hormonal therapies for prostate adenocarcinoma as a mechanism of resistance.

Distinct pathological markers were observed between the prostate and bladder specimen of our case. However, one of the key shortcomings is that the diagnosis of prostate cancer was made through a random biopsy, which could probably overlook the neuroendocrine differentiated component present in the prostate, despite its small volume. Therefore, we are unable to deduce whether the source of this bladder tumor was due to transdifferentiation from prostate cancer, selection following hormonal therapy, or a spontaneous metachronous growth. Such case reminds us the necessity of frequent image follow-up and obtaining tissue proof when clinically indicated in advanced diseases. Precise pathological diagnosis could aid in judicious treatment planning.