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Gynecomastia in a Patient With Lung Cancer

Geoffrey Liu, Marla L. Rosenfield Darling, Jennifer Chan, Michael T. Jaklitsch, Arthur T. Skarin

Department of Adult Oncology, Dana-Farber Cancer Institute; Departments of Medicine, Surgery, Radiology, and Pathology, Brigham and Women's Hospital; and Harvard Medical School, Boston, MA

A 45-year-old man presented with bilateral gynecomastia and galactorrhea. He was a 65 pack-year tobacco smoker, smoked half a joint of marijuana per day chronically, and used crack cocaine twice per week on average. He denied use of other medications, supplements, or hormones. Physical examination showed slightly enlarged breasts with a milky discharge from both nipples. There was no adenopathy, and testicular examination was normal. The patient had a serum beta-human chorionic gonadotropin (ßHCG) level of 8609 ng/mL (normally undetectable) and a prolactin level of 68 µg/L (normal, < 25 µg/L). A preoperative chest computed tomography (CT) scan showed a 2.5-cm mass posteriorly in the right upper lobe (Fig 1). A right upper lobectomy was performed. Pathology revealed a poorly differentiated large-cell carcinoma, with extensive necrosis and hemorrhage (Fig 2A and 2B). The tumor cells stained positive for LeuM1 and focally positive for carcinoembryonic antigen (CEA), but they were negative for alpha-fetoprotein. Scattered large, anaplastic, multinucleated cells showed ßHCG and placental alkaline phosphatase positivity on immunoperoxidase staining (Fig 2C). One month after surgery, the ßHCG level was 247 ng/mL and the prolactin level was normal. The nipple discharge was now watery. Four months later, the patient presented with increasing dyspnea and hemoptysis. Innumerable bilateral pulmonary nodules were present on follow-up CT scan of the chest, ranging in size from 0.5 to 1.5 cm (Fig 3A). Many of the nodules were surrounded by a halo of ground-glass opacity consistent with hemorrhage (Fig 3A, arrow). On an abdominal CT scan, a right adrenal mass was present that was consistent with metastatic disease. The ßHCG level was 5,878 ng/mL, and he had a normal prolactin level. One week later, he developed excruciating right upper quadrant abdominal pain with a benign physical examination. A repeat noncontrast CT scan of the abdomen showed heterogenous enlargement of the right adrenal mass (increased to 5.9 x 5 cm), with new regions of high attenuation peripherally consistent with hemorrhage (Fig 3B, arrow). Against medical advice, the patient left the hospital and refused systemic treatment.

View larger version (74K): [in this window] [in a new window]   Fig 1.

View larger version (87K): [in this window] [in a new window]   Fig 2.

View larger version (49K): [in this window] [in a new window]   Fig 3.

In this patient, hemorrhagic metastases, an elevated serum ßHCG level, and positive ßHCG in multinucleated tumor cells are compatible with choriocarcinomatous differentiation. In addition, a single large adrenal metastasis, positive CEA and LeuM1 immunostaining, and histology showing a continuum of cell sizes and degrees of anaplasia (as opposed to a two-cell population of cyto- and syncytiotrophoblastic cells) favor a primary lung cancer over a primary germ cell tumor.

Although gynecomastia has been documented in non–small-cell lung cancers (NSCLC), variably elevated ßHCG levels are detected in up to half of patients with NSCLC in either serum or urine using sensitive assays and may be a poor prognostic marker.^1,2 It is unusual for these elevations to result in clinical features. Large-cell lung carcinomas immunostain for ßHCG more frequently than other NSCLCs.³ ßHCG mRNA transcripts are demonstrated in some NSCLCs and not in controls.⁴ Of note, elevated ßHCG levels and gynecomastia have been documented with marijuana use.⁵ In this patient, the primary tumor contained ßHCG immunoreactivity, and ßHCG level fluctuations corresponded closely to the tumor burden and not to his marijuana use. Galactorrhea is extremely rare in NSCLC. Subclinical elevations in prolactin have been described in a minority of NSCLCs.⁶ Modest elevations in prolactin levels (< 100 µg/mL) have been associated with chronic cocaine use and cocaine withdrawal in addicts,⁷ and may have contributed to this unusual presentation of lung cancer.

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