A case of combined-histology lung carcinoma (adenocarcinoma plus small cell carcinoma) presenting with changes in the tumor marker profile and histological findings during the clinical course

Background. Ten percent of small cell carcinomas are reported to show mixed histological features. Case. A 68-year-old man presenting with a pulmonary nodule in the right upper lobe was diagnosed with lung adenocarcinoma based on the detection of tumor cells arranged in gland-like structures in a biopsy specimen. However, combined small cell lung cancer was also suspected, because a few tumor cells showed high nuclear-cytoplasmic ratios. Immunohistochemistry was positive for TTF-1, but negative staining for a host of neuroendocrine markers. The plasma CEA level was elevated, while the plasma pro-GRP level was within the normal range. During treatment with a pemetrexed-containing regimen, plasma pro-GRP elevation and liver metastasis were detected. A liver biopsy revealed tumor cells with a high nuclear-cytoplasmic ratio. Immunohistochemistry revealed that the tumor cells were positive for TTF-1 as well as several neuroendocrine tumor markers. Based on these findings, treatment with carboplatin plus etoposide was initiated. Conclusion. In the present case, a repeat tumor biopsy was performed as the patient newly showed the elevation of a plasma neuroendocrine marker, which contributed to the decision on the most appropriate therapeutic regimen.