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Lung hepatoid adenocarcinoma (HAC) is a rare primary lung carcinoma pathologically characterized by hepatocellular carcinoma-like tumor cells, the majority of which produce alpha-fetoprotein (AFP). The clinical prognosis of lung HAC is generally poor, and effective therapeutic regimens for inoperable or recurrent cases have not been established. Here, we report a case of AFP-producing lung HAC with brain metastasis with long-term disease control, treated with the 5-fluorouracil-derived regimen S-1. The patient was a 66-year-old male admitted to the hospital with alexia. Chest X-ray revealed a massive tumor in the left upper lobe, and a head CT scan revealed a metastasis in the left parietal lobe. The laboratory data showed a remarkably elevated AFP level (97,561 ng/mL). Pathological assessment of the resected brain tumor revealed HAC, which was compatible with the lung biopsies. Together with the absence of other metastatic lesions, a final diagnosis of primary lung HAC, stage IV T4N3M1b, was given. The patient first underwent non-small cell lung cancer chemotherapy regimens (carboplatin and paclitaxel as the first line, and pemetrexed as the second line), but had clinical progression. After third-line oral S-1 (tegafur/gimeracil/oteracil) administration, the serum AFP level significantly dropped and the patient achieved long-term disease control without relapse, surviving more than 19 months after disease presentation. The autopsy result was consistent with the diagnosis of primary lung HAC, and immunohistochemical staining was AFP+, glypican 3+, and spalt-like transcription factor 4+. Here, we report the case of a rare primary lung HAC with apparent disease control on S-1 therapy, together with a literature review.

BackgroundChronic obstructive pulmonary disease is caused mainly by habitual smoking and is common among elderly individuals. It involves not only airflow limitation but also metabolic disorders, leading to increased cardiovascular morbidity and mortality.ObjectiveWe evaluated relationships among smoking habits, airflow limitation, and metabolic abnormalities.MethodsBetween 2001 and 2008, 15,324 school workers (9700 males, 5624 females; age: ≥30 years) underwent medical checkups, including blood tests and spirometry. They also responded to a questionnaire on smoking habits and medical history.ResultsAirflow limitation was more prevalent in current smokers than in ex-smokers and never-smokers in men and women. The frequency of hypertriglyceridemia was higher in current smokers in all age groups, and those of low high-density-lipoprotein cholesterolemia and diabetes mellitus were higher in current smokers in age groups ≥ 40 s in men, but not in women. There were significant differences in the frequencies of metabolic abnormalities between subjects with airflow limitations and those without in women, but not in men. Smoking index was an independent factor associated with increased frequencies of hypertriglyceridemia (OR 1.015; 95% CI: 1.012–1.018; p<0.0001) and low high-density-lipoprotein cholesterolemia (1.013; 1.010–1.016; p<0.0001) in men. Length of smoking cessation was an independent factor associated with a decreased frequency of hypertriglyceridemia (0.984; 0.975–0.994; p = 0.007).ConclusionsHabitual smoking causes high incidences of airflow limitation and metabolic abnormalities. Women, but not men, with airflow limitation had higher frequencies of metabolic abnormalities.

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