A Case of Atypical Carcinoid: Harboring Variant 3a/b EML4–ALK Rearrangement

Abstract

FIGURE 1. Panels A, C, and E show one case of epithelioid mesothelioma with MET gene amplification. A, hematoxylin and eosin-stained sections (magnification 10×); C, interphase fluorescence in situ hybridization (FISH) analysis showing amplification of MET (white arrows indicate spots of MET red* signal points) with a MET/ CEP7 ratio of 4.0 (approximately eight red signals vs. two green signals; magnification 100×); E, immunohistochemistry (IHC) staining with anti-c-MET antibody showing overexpression on cytoplasm and membrane of MET protein (magnification 40×). Panels B, D and F show one case of epithelioid mesothelioma with wild-type gene status and negative expression of MET protein. B, hematoxylin and eosin 10×; D, FISH for MET gene 100×; F: IHC for MET protein 40×. MET gene amplification was investigated by FISH using the probe MET/CEP7 cocktail (Vysis MET Spectrum Red FISH Probe Kit reagent/ Vysis CEP 7 [D7Z1] SpectrumGreen Probe, both reagents from Abbott Molecular, Des Plaines, IL). IHC staining of MET was performed by Antic-Met Antibody IHC-plus LS-B2812

New Insights into the Molecular Characteristics of Pulmonary Carcinoids and Large Cell Neuroendocrine Carcinomas, and the Impact on Their Clinical Management

“…65 Thus far, two case reports have reported echinoderm microtubule-associated protein like 4 gene (EML4)-ALK receptor tyrosine kinase gene (ALK) rearrangements in patients with ACs, but only one of them responded to crizotinib (ALK receptor tyrosine kinase [first-generation]) treatment. 66,67 The data generated in the available genomic studies suggest that a successful treatment of carcinoids with small molecule inhibitors is rather unlikely; however, further studies on larger series are warranted.…”

Large Cell Neuroendocrine Carcinoma Harboring an Anaplastic Lymphoma Kinase (ALK) Rearrangement with Response to Alectinib

“…These cases were those of a 72-year-old woman and a 43-year-old woman had who received no ALK inhibitors. Three atypical carcinoid tumors harboring the EML4-ALK fusion gene have been reported to date ( 11 - 13 ). The first case was of a 54-year-old woman who exhibited resistance to crizotinib ( 11 ).…”

“…Three atypical carcinoid tumors harboring the EML4-ALK fusion gene have been reported to date ( 11 - 13 ). The first case was of a 54-year-old woman who exhibited resistance to crizotinib ( 11 ). The second case was of a 70-year-old man who was successfully treated with cizotinib ( 12 ), and the third case was of a 52-year-old man who was successfully treated with alectinib ( 13 ).…”

Molecular alterations of neuroendocrine tumours of the lung

“…Among ‘druggable’ molecular targets, recent reports have demonstrated the expression of ALK, a tyrosine kinase receptor activated aberrantly in approximately 5% of NSCLC, in metastatic AC of the lung . ALK overexpression was associated with ALK rearrangement, and ALK gene alteration was detected both in tumour tissue and in circulating tumour DNA.…”

“…ALK overexpression was associated with ALK rearrangement, and ALK gene alteration was detected both in tumour tissue and in circulating tumour DNA. The tumours did not respond to chemotherapy, but ALK inhibitor crizotinib reduced tumour growth successfully . Although intriguing, a word of caution has to be voiced, as these findings are based on single case reports whose diagnoses were made on biopsy specimens only; therefore, further validation is needed.…”