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April 3, 2026Endocrine Pathology2 citationsOpen Access

Well-Differentiated Neuroendocrine Tumors of Lung: A Case Series Supporting the IARC/WHO Common Classification of Neuroendocrine Tumor Nomenclature and Grading

EAEren AltunOSOmid SavariMMMart Andrew Maravillas

Key Points

  • The study aims to evaluate the appropriateness of a new classification system for pulmonary neuroendocrine tumors using Ki67 proliferation index.
  • Reviewed 124 cases of pulmonary neuroendocrine tumors from 2019 to 2025.
  • Collected data on demographics, clinical characteristics, and pathology.
  • Graded tumors based on Ki67 proliferation index and compared with traditional classifications.
  • Ki67 grading showed significant correlation with lymphatic invasion, lymph node and liver metastasis.
  • Higher Ki67 grades (G3) were linked to worse patient outcomes compared to lower grades (G1, G2).
  • A three-tiered Ki67-based grading system provides better clinical information for tumor progression and survival.

Abstract

The aim of this study was to assess whether there is sufficient evidence to recommend a change in the classification of pulmonary tumors currently classified as “carcinoid” tumors to instead apply a system similar to that used for well-differentiated gastrointestinal and pancreatic neuroendocrine tumors (NETs) using the Ki67 proliferation index (PI). We retrospectively reviewed 124 cases of pulmonary NETs (“typical carcinoids” (TC) and “atypical carcinoids” (AC)) diagnosed at the University Hospitals Cleveland Medical Center between 2019 and 2025. Demographic, clinical, and pathology data were collected, including mitotic counts, necrosis, and Ki67 PI assessed in biopsy, resection, and metastatic specimens. Tumors were graded as G1 (≤ 3%), G2 (3–20%), and G3 (> 20%) according to the 5th edition WHO criteria for gastroenteropancreatic NETs. Grading based on Ki67 PI was significantly associated with lymphatic invasion (p = 0.007), lymph node metastasis (p = 0.016), liver metastasis (p = 0.047), AJCC stage at diagnosis (p < 0.001), and patient mortality (p = 0.047). This approach provided better correlation than necrosis for liver metastasis and mortality, better than mitoses for all negative outcomes than other than liver metastasis, and better than TC/AC classification for mortality. Tumors classified as G3 had significantly worse patient outcomes than those classified as G1 or G2. Incorporating Ki67 PI into the classification provides clinically important information regarding tumor progression, staging, and survival. These findings support the adoption of a three-tiered Ki67-based grading system (G1–G3) for pulmonary NETs, ​​similar to gastroenteropancreatic NETs.

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Cite This Study

Altun et al. (2026) studied this question.

synapsesocial.com/papers/69cf5e745a333a821460cde7https://doi.org/10.1007/s12022-026-09914-2
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