Human chorionic gonadotropin production by a benign lung nodule

Abstract

Ectopic hormone production by a neoplasm is defined as secretion of a hormone by cells not normally a source of that hormone. This relationship is a recognized phenomenon that assists in diagnosis of disease and provides a marker for monitoring treatments. Ectopic human chorionic gonadotropin (hCG) is associated with neoplasms originating in the lungs, gastrointestinal tract, cervix, and bladder. Recent evidence recognizes 3 variants of hCG, with nontrophoblastic tumors producing the free beta-subunit variant. This variant influences cancer cell growth andmay be valuable as a poor prognostic marker [1]. Approximately 15%of lung tumorsdemonstrate detectable hormone [2], and evidence suggests that paraneoplastic lung tumors are often more resistant to treatment, have a poor prognosis, and are rapidly fatal [3]. This report presents an individual with a benign indolent lung nodule secreting beta-hCG. Final pathology revealed an inflammatory myofibroblastic tumor (IMT). This type of tumor is rare, accounting for 0.4%–1.0% of all lung tumors; they are often asymptomatic, but may present with cough, hemoptysis, or dyspnea. IMTs are low-grade tumors, histologically composedof inflammatoryspindle cells thatoftengrowlocallyandslowly [4]. A 42-year-old patient (para 0) presented after a positive homepregnancy test. Medical history was significant for an incidental lung lesion detected in 1989bychestX-ray followingapositivePPD.At that time, evaluation revealed a 2-cm, well-rounded, noncalcified lesion in the right lower lobe with no associated adenopathy. A biopsy (with preoperative evaluation showing negative hCG) was consistent with pseudotumor; no further treatment was advised. Several chest X-rays since 1989 showed a stable lesion. Obstetricgynecology history was noncontributory, with menarche at 13 years, regular periods, and no history of infertility. Upon presentation after positive pregnancy test, the patient reported only fatigue and shortness of breath upon exertion; she denied cough, sputum production, chest pain, fever, chills, or vaginal bleeding. Her last menstrual period was 51/2 weeks prior, and beta-hCG quantitative value (beta-quant) was 8961 mIU/mL. Multiple ultrasounds showed no intrauterine, molar, or ectopic pregnancy. Diagnostic laparoscopy confirmed no ectopic pregnancy; dilation and curettage revealed no gestational trophoblastic disease. The patient was given methotrexate; however, beta-quant continued to rise to 20 648mIU/mL over 5 days, and shewas referred togynecologic oncology.Gynecologic oncologyevaluated and referred her to thoracic surgery for assessment of her lung nodule. Lung exam was normal, and chest CT and positron emission tomography (PET) demonstrated a solitary, round, noncalcified right lower lobe nodule 1.2 cm (Fig. 1) with moderate uptake on PET. The patient underwent fiberoptic bronchoscopy and right thoracoscopic lower lobe wedge resection revealing a solitary, firm, solid lesion within the right lower lobe. Pathology revealed a noninvasive, 1-cm spindle cell lesion consistent with IMT. Postoperative beta-quant decreased steadily reaching zero approximately 3 weeks postoperatively, and the patient resumed regular periods. Beta-hCG secreting lung cancer is too rare to be a useful tumor marker by pulmonologists; however, it is critical that obstetriciangynecologists recognize the wide range of sources of beta-hCG production and refer patients for further evaluation after excluding common obstetric etiologies. The present case demonstrates the importance of considering all lung nodules as a source of ectopic betahCG; however, it is unclearwhether this case signifies a change in nature of the tumor, or a newfindingnot previously clinically evident. Given the recent evidence on multiple variants of hCG, further detailed analysis of hCG may be warranted in determining malignant potential of nontrophoblastic tumors. Physicians should be aware of the malignant nature ofmost beta-hCG secreting tumors and consider the potential for transformation of benign appearing nodules to more aggressive tumors.