Primary Testicular Neuroendocrine Tumor: Diagnostic Challenges and WHO 2022 Classification Insights

A 21-year-old's painless testicular mass turned out to be a tumor type so rare it accounts for under 1% of testicular neoplasms — and all standard tumor markers came back normal.

Journal: The Journal of International Medical Research | Published: 2026-06-19 | Type: Case Report | PMID: 42319038 Authors: Garousi V, Khalaj F, Mirzaian E (Department of Pathology, Shariati Hospital, Tehran University of Medical Sciences, Iran) Funding/COI: Neither disclosed

Summary

Primary testicular neuroendocrine tumors (TNETs) are so uncommon — under 1% of testicular malignancies — that each documented case is its own contribution to the clinical record. This report describes a 21-year-old with a 3-cm painless left testicular mass whose AFP, β-HCG, and LDH were all normal, illustrating the core diagnostic trap: the standard tumor marker panel is useless here. Diagnosis required radical orchiectomy with histopathology and immunohistochemistry (synaptophysin, chromogranin, and INSM1 positive; Ki-67 <1%), ultimately classified under the 2022 WHO framework as a well-differentiated "prepubertal-type" TNET.

Claims

• Primary TNETs represent less than 1% of all testicular neoplasms
• A meta-analysis by Amine et al. found mean diagnosis age of ~41 years for pure primary TNETs and ~55 years for secondary TNETs — this patient at 21 falls well below both
• Approximately 75% of TNETs are pure, with 25% arising in association with teratomatous components
• Standard serum markers (AFP, β-HCG, LDH) are characteristically normal; elevated NSE, vanillylmandelic acid, serum serotonin, or urinary 5-HIAA may occur instead
• Somatostatin receptor scintigraphy with octreotide has 70–90% sensitivity for detecting primary neuroendocrine tumors
• Ki-67 <1% in this case indicates very low proliferative activity
• Despite generally indolent behavior, late metastasis is a recognized risk requiring long-term surveillance

Study Quality

This is a single case report — the lowest tier of clinical evidence. It is inherently descriptive: one patient, one outcome, no comparison group, no follow-up data reported. The value of a case report in a genuinely rare entity is real (each case adds to the global case series), but no clinical inferences about prognosis, treatment efficacy, or incidence can be drawn from n=1. The histopathological workup is thorough and the application of the 2022 WHO classification framework is the paper's primary contribution, situating this case within an updated diagnostic taxonomy.

The authors do not disclose funding or conflicts of interest, which is a basic transparency failure regardless of how low-stakes a case report seems.

Red Flags

• N=1 — all observations are anecdotal by definition
• No funding or COI disclosure
• No follow-up data: we don't know the outcome beyond the orchiectomy
• All three authors are from the same department; no external pathology review mentioned
• Journal (JIMR) is mid-tier; not a specialist oncology or urology publication

Strengths

• Applies 2022 WHO classification, which is genuinely useful for documenting how the updated taxonomy handles rare entities
• Detailed immunohistochemical panel reported (synaptophysin, chromogranin, INSM1, Ki-67, plus a long list of negative markers)
• Highlights the standard-marker blind spot — a practically important point for clinicians encountering a testicular mass with normal AFP/β-HCG/LDH
• References a relevant meta-analysis (Amine et al.) for epidemiological context

Verdict

A well-executed case report for a legitimately rare tumor. The diagnostic workup is solid and the WHO 2022 classification framing is useful. But this is still n=1, and the complete absence of funding and COI disclosure is a mark against basic reporting standards. Read it if you're building familiarity with TNETs or the updated WHO taxonomy; don't cite it as evidence of anything about treatment outcomes or prognosis.