A 55-year-old man presents with hypercalcemia without bony metastases. His tumor is found to secrete a protein that binds to both PTH and PTH-related receptors. Immunohistochemistry of the resected lung mass shows cells positive for chromogranin A, synaptophysin, and a proliferation index (Ki-67) of 22%. Which WHO 2021 classification grade applies to this tumor?
- A Well-differentiated neuroendocrine tumor Grade 3 (NET G3) ✓
- B Well-differentiated neuroendocrine tumor Grade 2 (NET G2)
- C Poorly differentiated large cell neuroendocrine carcinoma (LCNEC)
- D Well-differentiated neuroendocrine tumor Grade 1 (NET G1)
Correct answer: A. Well-differentiated neuroendocrine tumor Grade 3 (NET G3)
Explanation
In the WHO 2021 classification of thoracic NENs, well-differentiated tumors with Ki-67 >20% but retained well-differentiated morphology are classified as NET G3 — a separate category from large cell neuroendocrine carcinoma (LCNEC), which is poorly differentiated. Ki-67 2–20% corresponds to G2, and <2% to G1. LCNEC has necrosis, high mitoses, and lacks the granular chromatin of well-differentiated NETs; this morphological distinction is essential.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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