Although most patients with pulmonary carcinoid (PC) can be cured by surgery, relapse may occur until 15 years after resection in up to 10% of patients. This is unpredictable at the outset, necessitating extensive follow-up (FU). We sought to determine whether an immunohistochemical marker panel (OTP, CD44, and Ki-67) could better indicate relapse-free survival (RFS) and increase uniformity among pathologists regarding carcinoid classification. To this purpose, all surgically resected PC (2003-2012) were identified in the Dutch cancer/pathology registry, and a matched relapse vs nonrelapse cohort (ratio 1:2, N = 161) was created. Cases were revised by 4 pathologists and additionally for immunohistochemistry (IHC) markers. The marker panel was applied to the complete population-based cohort (N = 536) to investigate the negative predictive value (NPV) of relapse. Median FU was 86.7 months. WHO classification among pathologists revealed poor overall agreement (mitotic count: 0.380, necrosis: 0.476) compared with IHC markers (Ki-67: 0.917, OTP: 0.984, CD44: 0.976). The mean NPV of all pathologists increased from 0.74 (World Health Organization, WHO) to 0.85 (IHC marker panel). IHC risk stratification of the complete cohort, regardless of subtype, showed a statistically significant difference in RFS between patients with high risk (n = 222) and low risk (n = 314), with an NPV of 95.9%. In conclusion, our results support the use of biomarker-driven FU management for patients with PC as the OTP/CD44/KI-67 marker panel can reliably predict which patients will probably not develop relapse over time and may benefit from a more limited postoperative follow-up. Furthermore, IHC marker assessment by pathologists for PC stratification is superior to traditional WHO typing.
Keywords: biomarker; neuroendocrine; prognosis; pulmonary carcinoid; relapse.
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