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Computed tomography (CT) scans obtained in 2010. (A) A chest CT scan revealed intrapulmonary metastases in both lungs. (B, C) An abdominal CT scan revealed a huge right adrenal metastasis (arrowheads).
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In 2010, a CT scan revealed that her intrapulmonary metastases had progressed (Fig. 1A). Although she was administered docetaxel while receiving gefitinib treatment, a right adrenal metastasis was detected (Fig. 1B and C).
Microscopic findings of the resected right adrenal metastasis. (A) Hematoxylin and Eosin staining of the adrenal specimen showed that the tumor was poorly to moderately differentiated adenocarcinoma. (B) Immunohistochemical staining revealed that the specimen was positive for thyroid transcription factor-1, suggesting that these were metastases from the primary lung adenocarcinoma.
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The immunohistochemical results revealed that it was a metastasis from the lung (Fig. 2), and a fragment analysis detected an EGFR exon 19 deletion.
Computed tomography (CT) scans obtained in 2013. The largest mass in the right lower lobe of the lung (A) and the liver metastases (B) grew more rapidly than the other metastases, which was consistent with the emergence of a tumor with higher-grade morphology.
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Notably, the metastases in the right lower lobe of lung and liver progressed rapidly in comparison to other metastases (Fig. 3).
Autopsy specimen of the largest mass in the right lower lobe of the lung. (A) Hematoxylin and Eosin (H&E) staining of the largest mass in the right lower lobe of the lung showed a transitional zone of well-to-moderately differentiated adenocarcinoma and neuroendocrine morphology. (B) H&E staining of the neuroendocrine tumor portion revealed that the tumor grew in sheets and rosette-like structures and exhibited necrosis. The tumor cells were large and had abundant cytoplasm and prominent nucleoli. The neuroendocrine tumor portion was positive for neural cell adhesion molecule (C) and synaptophysin (D), supporting a diagnosis of large-cell neuroendocrine carcinoma (LCNEC). Both the LCNEC (E) and adenocarcinoma portions (F) of the lesion expressed an EGFR mutation with an exon 19 deletion.
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Surprisingly, these two morphologies and the transitional zone were both found in the largest lung mass (Fig. 4A). The tumor cells were large and had abundant cytoplasm and prominent nucleoli (Fig. 4B). An immunohistochemical analysis revealed that the neuroendocrine component was positive for neural cell adhesion molecule (NCAM), synaptophysin, and Ki-67 (Fig. 4C and D). Notably, the EGFR mutation from the antecedent adenocarcinoma was retained in both components (Fig. 4E and F).