Atypical Carcinoid Tumor with Anaplastic Lymphoma Kinase (ALK) Rearrangement Successfully Treated by an ALK Inhibitor

Abstract

This is the first report in which crizotinib, an anaplastic lymphoma kinase (ALK) inhibitor, reduced an atypical carcinoid tumor with ALK rearrangement. A 70-year-old man developed a tumor in the left lung and multiple metastases to the lung and brain. The pathology of transbronchial biopsied specimens demonstrated an atypical carcinoid pattern. Combined with immunohistochemical findings, we diagnosed the tumor as atypical carcinoid. ALK gene rearrangement was observed by both immunohistochemical (IHC) and fluorescence in situ hybridization. He was treated with chemotherapy as first-line therapy, however, the tumor did not respond to chemotherapy. Thereafter, he was treated with crizotinib, which successfully reduced the tumors.

Figure 1.

Biopsied specimens stained with Hematoxylin and Eosin staining show small necrotic foci (inset) and tumor cells with fine nuclear chromatin and moderate eosinophilic cytoplasm growing in a trabecular pattern and organoid nesting arrangement. Only one mitosis was found in 10 high-power fields.

Figure 2.

HC for (A) synaptophysin and (B) ALK. (C) FISH analysis of the ALK locus using a break-apart probe strategy. Strongly positive staining for synaptophysin (Bb) (A) and ALK (5A4, Nichirei Biosciences, Tokyo) (B) was observed in tumor cells. (C) Approximately 74% of the tumor cells showed rearrangement at the ALK locus.

Figure 3.

A chest CT scan and brain MRI before and during treatment with crizotinib (A and C: May 2015, B and D: Aug 2015). Crizotinib reduced the primary mass (arrows) from 26 mm (A) to 15 mm (B), and the multiple lung metastases (arrowheads) disappeared. Crizotinib also reduced the brain metastasis (arrows) from 13.3 mm (C) to 6.2 mm (D).