Ki-67 Labeling Index in Pulmonary Carcinoid Tumors: Comparison Between Small Biopsy and Resection Using Tumor Tracing and Hot Spot Methods

Context.--Pulmonary carcinoids are classified as typical or atypical by assessing necrosis and mitoses, which usually cannot be adequately assessed on small biopsies. Ki-67 is not currently used to grade pulmonary carcinoids, but it may be helpful to determine preliminary grade in biopsies. However, the rate at which Ki-67 could underestimate or overestimate grade on small biopsies has not been well studied. Objective.--To compare Ki-67 labeling obtained on small biopsies to subsequent resection. Design.--Ki-67 was performed on paired biopsy and resection specimens from 55 patients. Slides were scanned using Aperio ScanScope. Labeling index was determined using automated hot spot and tumor tracing methods. Results.--The study included 41 typical and 14 atypical carcinoids. Atypical carcinoids were larger and had more distant metastases. Death from disease occurred in 3 patients (all had atypical carcinoids). Median hot spot Ki67 labeling index was greater in resection compared with biopsy by 0.7% (P = .02). Median tumor tracing Ki-67 was lower in resection compared with biopsy by 0.5% (P < .001). Receiver-operating characteristic analysis showed similar hot spot Ki-67 cutoffs to predict atypical histology (3.5% for biopsy, 3.6% for resection; area under the curve [AUC], 0.75 and 0.74, respectively). Different optimal cutoffs were needed for tracing method based on biopsy (2.1%; AUC, 0.75) compared with resection (1.0%; AUC, 0.67). Conclusions.--Hot spot Ki-67 tends to underestimate grade on small biopsies, whereas grade is overestimated by tumor tracing. Hot spot Ki-67 cutoff of 3.5% predicted atypical histology for both biopsy and resection. Different biopsy and resection cutoffs were necessary for tumor tracing, which would make clinical implementation more difficult. doi: 10.5858/arpa.2019-0374-OA
Pulmonary neuroendocrine tumors are a heterogeneous group of neoplasms that includes carcinoid tumors, which have somewhat unpredictable but relatively indolent behavior, as well as small cell and large cell neuroendocrine [...]