OTP, CD44 and Ki-67 on biopsy identified low-risk lung carcinoids better than WHO subtyping

Design

Retrospective registry cohort with matched biopsy and resection specimens

Population

98 patients with resected stage I–III lung carcinoid, the Netherlands, 2003–2021

Primary outcome

Relapse; biopsy risk classification accuracy and agreement

Effect

High risk in 17/19 relapses (89%) vs 2/19 (11%) by WHO; NPV 0.96 vs 0.82

This Modern Pathology study, published on 21 September, took 98 patients from the Dutch national pathology registry with resected stage I to III lung carcinoids and matched preoperative biopsies. Three pathologists reviewed all cases against the WHO 2021 criteria. Biopsies were stained for OTP, CD44 and Ki-67 and called low risk if OTP H-score was 50 or more, CD44 30 or more and Ki-67 under 5%.

Over a median of 83 months, 19 patients relapsed. The panel had classed 17 of them (89%) as high risk; WHO subtyping on biopsy had called only 2 (11%) atypical. Negative predictive value was 0.96 for the panel and 0.82 for WHO. Interobserver agreement was higher for the panel (kappa 0.67 vs 0.28), and biopsy-resection agreement was better (0.58 vs 0.17).

Typical versus atypical carcinoid depends on mitotic count and necrosis, which small biopsies often cannot assess. This panel works on the biopsy and may help thoracic teams judge who is suitable for a lung-sparing resection. The numbers are small, so it is a strong candidate for adoption rather than settled standard.

• On lung carcinoid biopsies, consider adding OTP, CD44 and Ki-67 when the result will inform resection extent.
• Report carcinoid, not otherwise specified, on biopsy rather than forcing typical or atypical.
• Use the thresholds from this study: OTP H-score ≥50, CD44 ≥30, Ki-67 <5% for low risk.
• Loss of OTP or CD44 should prompt discussion with the thoracic team.
• Keep WHO classification on the resection specimen; the panel adds to it.

Why it matters

WHO subtyping on a biopsy missed almost every relapse; the panel caught nearly all of them.

Don't overread it

Based on 19 relapses in 98 patients; the thresholds need validation in another cohort.

The statistics, in plain English

A negative predictive value of 0.96 means that when the panel called a tumour low risk, it did not relapse 96% of the time. Kappa measures agreement beyond chance: 0.67 is substantial, 0.28 only fair.

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