Primary testicular neuroendocrine tumor: Diagnostic challenges and WHO 2022 classification insights

Primary testicular neuroendocrine tumors are exceedingly rare, comprising less than 1% of testicular neoplasms. Their nonspecific presentation and overlap with other testicular tumors make diagnosis challenging. We report the case of a 21-year-old male with a painless left testicular mass. Imaging revealed a hypervascular lesion with calcifications, while serum markers (alpha-fetoprotein, beta-human chorionic gonadotropin, and lactate dehydrogenase) were normal. Radical orchiectomy demonstrated a 3-cm well-circumscribed tumor composed of monotonous cells with “salt-and-pepper” chromatin and low mitotic activity. Immunohistochemistry confirmed neuroendocrine differentiation (synaptophysin, chromogranin, INSM1 positive; Ki-67 < 1%). This profile established the diagnosis of a well-differentiated testicular neuroendocrine tumor, classified under the 2022 WHO framework as “prepubertal-type.” Although indolent, these tumors require long-term follow-up due to the risk of late metastasis. Radical orchiectomy remains the treatment of choice. This case emphasizes the critical role of histopathology and immunoprofiling in diagnosis and contributes to refining the clinical understanding of this rare entity.