PMC6103612_01
PMC6103612_02
Contrast CT scan showed a 4.5 cm lobulated mass in the right upper lobe and multiple enlarged mediastinal lymph nodes (A). The lung lesions regressed dramatically with administration of crizotinib for 1 month (B) and 12 months (C). Brain MRI revealed multiple metastases in the cerebral hemispheres and cerebellum bilaterally (not shown) (D). However, the intracranial lesions progressed 12 months later (E). A core needle lung biopsy specimen revealed trabecular and solid nests with moderately abundant eosinophilic cytoplasm, and was positive for neuroendocrine markers (F, H&E x200).
ott-11-4991Fig1.jpg
PMC6103612_02_ott-11-4991Fig1.jpg
f1-ott-11-4991
TTF-1 and neuroendocrine markers, including synaptophysin, chromogranin, and CD56. The Ki-67 index was low (10%) (Figure 1).
PMC6103612_03
PMC6103612_04
At low power, the neuroendocrine carcinoma (right) and adenocarcinoma component (left) were clearly separated (A, H&E x20). At high-power magnification, necrosis and mitotic figures were frequently seen in adenocarcinoma (B) and neuroendocrine carcinoma (C, H&E x400). Synaptophysin was positive only in the NEC component (D, IHC x40). NapsinA was only positive in the adenocarcinoma area (E, IHC x40). Both components showed immunoreactivity to CK7 (F, IHC x40). FISH for ALK gene revealed that split signals and isolated 3' signals were observed in adenocarcinoma and neuroendocrine carcinoma components, respectively (G and H). ALK rearrangement was also confirmed by ALK (D5F3) immunostaining (I, IHC x40).. Abbreviations: ALK, anaplastic lymphoma kinase; FISH, fluorescence in situ hybridization; IHC, immunohistochemistry.
ott-11-4991Fig2.jpg
PMC6103612_04_ott-11-4991Fig2.jpg
f2-ott-11-4991
Both components showed diffuse and strong immunoreactivity to ALK protein by high-sensitivity immunohistochemistry (Figure 2).