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

Abstract

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/2mm² vs. 2-10mitoses/2mm²) 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.