PMC5140865_01
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.
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The pathology of transbronchial biopsied specimens demonstrated acidophilic tumor cells showing a cord-like distribution with small necrosis and one mitosis in 10 high-power fields (Fig. 1).
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.
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Combined with immunohistochemical (IHC) findings of CD56+/chromogranin A+/synaptophysin+ (Fig. 2A) and a low Ki-67 labeling index (<20%), we diagnosed the tumor as atypical carcinoid. Further analyses revealed that anaplastic lymphoma kinase (ALK) gene rearrangement was observed by both IHC (Fig. 2B) and fluorescence in situ hybridization (FISH) (Fig. 2C).
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).
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Thereafter, he was treated with an ALK inhibitor, crizotinib (Pfizer, Tokyo, Japan) 250 mg PO twice daily, which reduced the tumors in the lung (Fig. 3A and B) and the brain (Fig. 3C and D) by 42% and 53%, respectively, over 3 months.