OTP, CD44 and Ki-67 on preoperative biopsy flagged most lung carcinoid relapses that WHO grade missed

Design

Retrospective registry cohort with matched biopsy and resection immunohistochemistry

Population

98 patients with stage I to III lung neuroendocrine tumours resected 2003 to 2021; 19 relapses, median follow-up 83 months

Primary outcome

Identification of relapse by biomarker panel vs WHO 2021 classification on biopsy

Effect

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

WHO grading of lung neuroendocrine tumours separates typical from atypical carcinoid, but on a small biopsy the call is hard and unreliable. This study used the Dutch pathology registry to select 98 patients with stage I to III lung neuroendocrine tumours resected between 2003 and 2021, with matched biopsy and resection specimens. Immunohistochemistry for OTP, CD44 and Ki-67 was scored on both. Low risk was defined as OTP of 50 or more, CD44 of 30 or more and Ki-67 below 5%; everything else was high risk. Nineteen relapses occurred over a median follow-up of 83 months.

The panel classed 17 of 19 relapses (89%) as high risk, whereas the WHO label of atypical carcinoid on biopsy captured 2 of 19 (11%). Negative predictive value was 0.96 against 0.82. Interobserver agreement was higher for the panel (kappa 0.673) than for WHO classification (0.276), and concordance between biopsy and resection was better (0.584 against 0.169).

The authors suggest it may help when sublobar resection is being considered. With 98 patients and 19 events, it is a retrospective single-registry study that needs validation before changing management.

• The panel flagged 17 of 19 relapses as high risk; biopsy WHO grade flagged 2 of 19.
• Negative predictive value was 0.96 for the panel and 0.82 for WHO grading.
• Interobserver agreement was kappa 0.673 against 0.276.
• Consider piloting the panel with validation before using it to guide sublobar resection.
• H-score and Ki-67 hot-spot scoring need standardised protocols.

Why it matters

It targets the exact decision where biopsy grading is weakest: whether a lung carcinoid is safe to treat with a limited resection.

Don't overread it

A retrospective registry cohort of 98 patients supports the idea but does not show that panel-guided surgery improves outcomes.

The statistics, in plain English

Negative predictive value of 0.96 means that of patients called low risk by the panel, 96% did not relapse in this cohort. With only 19 relapses, small changes in a few cases would shift these percentages noticeably, and the cut-offs were chosen from earlier work on the same disease.

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