INTRODUCTION:Hepatoid adenocarcinoma of the lung (HAL) is a rare form of malignancy defined as an alpha-fetoprotein (AFP)-producing primary lung carcinoma with specific morphological features resembling hepatocellular carcinoma (HCC). Only 10 cases of HAL have been described in the literature to our knowledge. We present a case of stage IV primary lung cancer with highly elevated AFP levels and morphological and immunohistochemical characteristics for HAL.
CASE PRESENTATION:A 54-year-old African-American male with a 40 pack-year history of smoking presented with hemoptysis and left-sided chest pain. After left lung opacities were discovered on chest x-ray, a CT scan was performed and revealed a large left upper lobe mass (13 × 11 cm) invading the mediastinum and encasing the left main pulmonary artery, a right upper lobe mass (3.3 × 2.6 cm), and multiple left lung nodules. Lesions were also noted on MRI of the brain. However, no other sites of metastasis were found on abdominal-pelvic CT, double-helical liver CT, testicular ultrasound, and technetium-99m bone scan. Biopsy of the left lung mass revealed cuboidal cells with prominent nucleoli and moderate eosinophilic cytoplasm arranged in an organoid nested fashion resembling liver tissue. Immunohistochemical stains showed the tumor cells to be strongly positive for CK 20 and pCEA, and focally positive for AFP and CD10. In contrast, stains for CK7, TTF-1, PLAP, CD34 and CD30 were all negative. Subsequently, serum AFP was noted to be elevated to 14,540 ng/mL, and a diagnosis of hepatoid adenocarcinoma of the lung was made.
DISCUSSIONS:Hepatoid adenocarcinoma was first described by Ishikura et al in 1985 as an AFP-producing tubular or papillary adenocarcinoma with abundant eosinophilic cytoplasm and centrally located nuclei, proliferating in a sheet-like or trabecular pattern. It primarily affects organs which develop from the primitive foregut, the most frequent site being the stomach and less often the esophagus, pancreas, ovaries, urinary bladder, and the lung. The diagnosis of HAL is based on findings of hepatoid histopathology in lung tissue and high levels of AFP in the absence of liver disease. The elevated AFP levels correlate with disease activity and often decline after surgical resection of the primary tumor. Since HAL can also spread to the liver, differentiating metastatic HCC from metastatic HAL can be quite difficult. Immunohistochemical stains may be helpful in this regard. While all forms of hepatoid adenocarcinomas are usually positive for AFP, CK8, CK18 and polyclonal CEA, only HCC is positive for HepPar1 and CK7.1 Clinically, the cases of HAL described in the literature appear to have several common features: male predominance, large tumor size at presentation (average 9 cm), and poor prognosis. The prognosis correlates with the stage at presentation, which is most often advanced, as was the case in our patient. If complete surgical resection is performed however, prognosis may be improved in select cases.2 Therefore, early recognition, staging, and timely intervention is key.
CONCLUSION:Our patient represents the 11th case of HAL reported in the literature. Due to his advanced stage, he was not a candidate for surgery but instead, received palliative whole brain irradiation and chemotherapy consisting of methotrexate, leucovorin, vincristine, bleomycin and cisplatin. However, a poor prognosis is expected given his rising AFP levels and enlarging tumor burden despite therapy.
DISCLOSURE:Michaela Ivan, No Financial Disclosure Information; No Product/Research Disclosure Information