Analysis of lung biopsies using the 2015 WHO criteria and detection of sensitizing mutations——a single-institution experience of 5032 cases

Abstract

Background: A specialized classification for small biopsies was added to the 2015 WHO classification of lung tumors. The purpose of this study is to explore and summarize the experience of applying the newly proposed classifications and criteria to clinical practice. Methods: We used the 2015 WHO criteria to sort out 5032 small lung biopsies from a group of Chinese patients, and demonstrated their clinicopathological features, mutational status and the relationship between these factors. Results: The most common diagnosis was primary lung carcinoma (3130, 62.2%), among which adenocarcinoma (1421, 28.2%) was the most frequent histological type. The mutational assays using ARMS-PCR technology demonstrated that EGFR was positive in 56.1% cases(499/889, from adenocarcinoma and NSCC, favor adenocarcinoma), ALK in 5.7% cases(12/211, from NSCC, which comprised all the primary lung carcinomas except small cell carcinomas), and ROS1 in 0.9% cases(2/211, from NSCC). Another 898 NSCC specimens went through an immunohistochemical (IHC) examination for ALK (D5F3) and 38 of them were positive (4.2%). The overall mutation rate of ALK was 4.5% (50/1119). There was no significant difference between ARMS-PCR and immunohistochemistry in the positive rate of ALK mutation detection (P = 0.359). EGFR mutations (P = 0.02) and ALK mutations (P < 0.001) both decreased with an increasing patient age. Furthermore, the amount of EGFR mutations was higher in adenocarcinoma (64.1% vs 34.1%, P < 0.001) than in NSCC, favor adenocarcinoma. In contrast, ALK mutations were more common in NSCC, favor adenocarcinoma (4.2% vs 8.4%, P = 0.021). Conclusions: This single-center study exhibited a large subset of small lung biopsies from a Chinese institution and demonstrated that applying the 2015 WHO classification for small lung biopsies can help predict the mutational status of primary lung carcinomas.

Prognostic value of the immunohistochemistry markers CD56, TTF‑1, synaptophysin, CEA, EMA and NSE in surgically resected lung carcinoid tumors

“…The categorization into TCs and ACs is based on the rate of mitosis and the presence of necrosis. Immunohistochemistry is essential for diagnosis, with an antibody panel consisting of chromogranin A, synaptophysin and CD56 being recommended ( 5 , 6 ). In addition, certain carcinoids exhibit staining for thyroid transcription factor 1 (TTF-1).…”

“…In addition, certain carcinoids exhibit staining for thyroid transcription factor 1 (TTF-1). The Ki67 labeling index is utilized in order to avoid misdiagnosis of high-grade neuroendocrine carcinomas ( 5 , 6 ). Furthermore, neuron-specific enolase (NSE) is a highly specific marker for neuroendocrine cells and is expressed in lung carcinoids ( 7 ).…”