Automated quantification of Ki-67 proliferative index of excised neuroendocrine tumors of the lung

Sandy Z Liu,Lindsay Goicochea,Paul N Staats,Renee Dixon,Nirav Shah,Allen P Burke,Borislav A Alexiev

doi:10.1186/s13000-014-0174-z

Sandy Z Liu, Lindsay Goicochea + Show 5 more

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https://doi.org/10.1186/s13000-014-0174-z

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Journal: Diagnostic Pathology	Publication Date: Oct 16, 2014
Citations: 51	License type: CC BY 4.0

Affiliation: University of Maryland, Baltimore

Abstract

BackgroundThe histopathologic distinction between typical carcinoid (TC) and atypical carcinoid (AC) of the lung is based largely on mitotic index. Ki-67 may aid in separation of these tumors, as well as the distinction from large cell neuroendocrine carcinoma (LCNEC).MethodsWe identified 55 surgically resected primary neuroendocrine lung tumors (39 TC, 7 AC, 9 LCNEC) based on mitotic rate and histologic features. Ki-67 proliferative index based on automated image analysis, tumor necrosis, nodal metastases, local or distant recurrence, and survival were compared across groups.ResultsThe mean mitotic count and Ki-67 index for TC, AC, and LCNEC were 0.1 and 2.3%, 3.4 and 16.8%, and 56.1 and 81.3% respectively. The Ki-67 index did not overlap among groups, with ranges of 0–6.7% for TC, 9.9-25.7% for AC, and 63.2-91.9% for LCNEC. Nodal metastases were identified in 4/39 (10%) TC, 2/7 (22%) AC, and 2/8 (25%) LCNEC. There was no survival difference between TC and AC, but there was a significant survival difference between LCNEC and TC and AC combined (p < 0.001). There was a step-wise increase in disease free survival with tumor grade: no TC recurred, 2/7 AC recurred or progressed (median interval 35.5 months), and all LCNEC recurred or progressed (median interval 10.1 months). No patient with TC or AC died of disease, compared to 7/8 LCNEC with follow-up data.ConclusionsWe conclude that Ki-67 index is a useful diagnostic marker for neuroendocrine tumors, with 7% a divider between AC and TC, and 50% a divider between LCNEC and AC. LCNEC is biologically different from AC and TC, with a much more aggressive course, and a high Ki-67 index.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_174

Highlights

The histopathologic distinction between typical carcinoid (TC) and atypical carcinoid (AC) of the lung is based largely on mitotic index
Other than small cell carcinomas, neuroendocrine tumors are typically initially treated by surgical excision
Mitotic figures are important in separating AC from TC (0–1 mitotic figures in 10 high-power microscopic fields (HPF) for TC, 1–10 mitotic figures/10 HPF for AC, and >10/10 mitotic figures/10 HPF for large cell neuroendocrine carcinoma (LCNEC))

Summary

Introduction

The histopathologic distinction between typical carcinoid (TC) and atypical carcinoid (AC) of the lung is based largely on mitotic index. The most common type is small cell carcinoma, accounting for 15-20%, followed by large cell neuroendocrine carcinoma (LCNEC) (~3%), typical carcinoid (TC), and atypical carcinoid (AC) tumors (~1-2%). Other than small cell carcinomas, neuroendocrine tumors are typically initially treated by surgical excision The distinction between these four tumor types is based on histologic features, mitotic index, and presence or absence of necrosis [1,2]. Of these features, mitotic figures are important in separating AC from TC (0–1 mitotic figures in 10 high-power microscopic fields (HPF) for TC, 1–10 mitotic figures/10 HPF for AC, and >10/10 mitotic figures/10 HPF for LCNEC). A very high Ki-67 index can help distinguish LCNEC from AC when classification is doubt

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