Diagnostic pitfalls and unmet needs in neuroendocrine neoplasms: The added value of collegial expert pathology review through the national TENpath network.

PURPOSE: In some situations, the pathological diagnosis of neuroendocrine neoplasms (NEN) remains challenging, with direct consequences for treatment decisions. ENDOCAN-TENpath, the French national expert network for NEN pathology, established monthly virtual "third-reading" sessions for collegial review of difficult cases. We evaluated the diagnostic outcomes and clinical impact of this process.

METHODS

All cases submitted to third-reading sessions from March 2022 to December 2023 were retrospectively reviewed. We analyzed diagnostic difficulties, diagnostic modifications, and their expected therapeutic impact.

RESULTS

Of 3239 cases received by ENDOCAN-TENpath, 126 (3.9%) were submitted to third-reading by 22 of 33 network pathologists (median turnaround: 20 days). Diagnostic difficulties fell into four categories: high-grade NEN classification (33.3%), mixed neuroendocrine/non-neuroendocrine neoplasm diagnosis (36.5%), incomplete neuroendocrine phenotypes (23.0%), and unfamiliar entities (7.1%). Consensus or majority diagnosis was reached in 102 cases (81%). Unresolved cases were due to lack of consensus (n = 13) or insufficient material (n = 10). Critically, the process yielded decisions with major therapeutic consequences: 20/46 presumed NENs were reclassified as non-neuroendocrine malignancies and 5/25 presumed adenocarcinomas as NENs, fundamentally altering treatment strategy. Furthermore, 32/42 ambiguous high-grade NENs were definitively classified as tumor or carcinoma, directly determining first-line chemotherapy regimen. These findings also prompted internal guidelines to reduce diagnostic variability.

CONCLUSION

The ENDOCAN-TENpath third-reading process yields a high rate of clinically actionable diagnostic decisions directly altering treatment strategy, while identifying unmet needs and providing a framework for reducing diagnostic variability in complex NEN cases.