Primary Neuroendocrine Tumors of the Genitourinary System: Two Rare Examples of Testicular and Renal Neuroendocrine Tumors with Clinicopathologic and Molecular Findings.

Primary neuroendocrine tumors (NETs) of the genitourinary tract are rare entities encountered in the kidneys, bladder, prostate, testes, and ovaries. Information on grading, biologic behavior, molecular characteristics, and treatment options is lacking. We present two patients with primary NETs which include one lesion involving the testis and one lesion involving the kidney. The testicular NET was incidentally discovered and clinically thought to be a conventional germ cell tumor. Histologically, the tumor was low-grade with pure carcinoid morphology, and did not demonstrate a concurrent teratoma or germ cell neoplasia in situ. Other differential diagnoses like metastasis from an extratesticular primary and sex cord-stromal tumors were argued against. Pure testicular NET is thought to be a prepubertal-type monodermal teratoma that generally lacks isochromosome 12p. Secondly, we report a primary renal NET which metastasized to the liver, lymph node, and bone. No other primary site of origin was identified. The tumor had atypical features including 6 mitotic figures/10 high-power field, Ki67 index of 4%, and resistance to chemotherapy. Prior reports have shown loss of heterozygosity on chromosome 3p21, with mutations in CDH1, TET2 and other genes in a subset of these tumors. However, our molecular assessment showed an alteration involving the ERCC2 gene in this tumor that has been described as a pathogenic variant in autosomally recessive conditions. These lesions highlight the need for urologists and pathologists to recognize and include NETs at unusual locations in their diagnostic consideration.