Pathological & radiological variables in the diagnosis of bronchopulmonary carcinoids (BPCs) with a focus on Antigen Kiel 67 (Ki-67) proliferation index.

Background: Bronchopulmonary carcinoids (BPCs) are classified into typical carcinoids (TC) and atypical carcinoids (AC), based on the mitotic count and absence/presence of necrosis on pathology specimens. There are limitations to accurate measurement of these criteria. It important to study other markers like Ki-67, to enhance the diagnostic accuracy of lung carcinoids.

Objective And Methodology: Retrospective analysis of BPCs treated with surgery between 2012-2022, to examine the accuracy of Ki-67 on the diagnostic specimen, concordance of diagnostic and resection specimens, diagnostic accuracy of Positron Emission Tomography (PET) and concordance of clinical and pathological staging.

Results: 205 patients were included in the analysis (final diagnosis TC 180, AC 25). Mean age 60.5 years and 68 % female. Ki-67 (<5% vs. 5-30 %) on diagnostic biopsy, available in 64 % (n = 131) of the cohort, had specificity (diagnose TC correctly) of 89.4 % (95 %CI 80.4 %-94.7 %) and sensitivity (diagnose AC correctly) of 77.8 % (40.2 %-96.1 %). This compared to 97.5 % (90.3 %-99.6 %) and 36.4 % (12.4 %-68.4 %) for mitotic count (<2mitoses/2mm vs. 2-10mitoses/2mm) and 100 % (94.4 %-100 %) and 21.4 % (5.7 %-51.2 %) for necrosis (absence vs. presence). A pre-resection diagnosis of TC (including surgical biopsy) shows better concordance with final diagnosis on resection specimen (94.9 %, 95 %CI 88.7 %-97.9 %, n = 117) as compared to the diagnosis of AC 83.3 % (95 %CI 50.9 %-97.1 %, n = 12). Concordance for AC appears higher with image guided lung biopsy 80 % (95 % CI, 29.9 %-98.9 %) than bronchoscopy 50 % (9.5 %-90.5 %). SUVmax on 18FDG-PET was a modest predictor of BPC sub-type with an AUC of 0.684 (95 % CI: 0.545,0.823). The clinical and pathological staging were concordant in 46 % (85/184) cases. However, 27 % (50/184) were upstaged and 13 % (23/172) found to have occult nodal metastases on pathology review of the surgical specimens.

Conclusion: The diagnosis and sub-typing of BPCs on diagnostic specimens is challenging. Our data suggest Ki-67 could increase diagnostic accuracy, but further research is needed to confirm this.