A paraneoplastic syndrome mimicking extrauterine pregnancy
P. Sagaster1,+,
N. Zojer1,
G. Dekan2 and
H. Ludwig1
1First Department of Medicine and Medical Oncology, Wilhelminenspital Montleartstrasse 37, 1160 Vienna; 2Institute of Clinical Pathology, University of Vienna, Vienna, Austria
Received 20 April 2001; accepted 3 May 2001.
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Abstract
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We report on a 30-year-old female patient with a ß-human chorionic gonadotropin (ß-HCG)-producing lung tumour. Abdominal discomfort and vaginal bleeding were the presenting symptoms and, in conjunction with elevated ß-HCG levels, initially led to the diagnosis of extrauterine pregnancy. Bilateral ovarian cysts were detected on further diagnostic workup. Ultimately, a chest X-ray revealed a lung tumour. The paraneoplastic symptoms were completely reversible after resection of the lung lesion, and the ovarian cysts disappeared.
Key words: human chorionic gonadotropin, lung cancer, paraneoplastic
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Introduction
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Human chorionic gonadotropin (HCG) production is frequently detected in lung tumours, using immunohistochemical methods. Eventually, elevated serum levels of the ß-subunit of HCG (ß-HCG) lead to paraneoplastic symptoms, e.g. gynecomastia in male lung cancer patients. In this report we describe an HCG-related syndrome in a 30-year-old female patient mimicking extrauterine pregnancy.
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Case report
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A 30-year-old woman was admitted to the department of gynaecology with a 2-week history of abdominal discomfort and vaginal bleeding. A pregnancy test performed 3 months before had been positive. The level of ß-HCG in the serum was 428 U/l at presentation; other routine laboratory tests (including complete blood count, and tests of liver and renal function) were unremarkable. The size of the uterus was within normal limits on palpation, and extrauterine pregnancy was suspected. However, the Fallopian tubes were regular, as shown by diagnostic laparoscopy, and hysteroscopy and curretage did not reveal placental elements in the endometrium. On routine chest X-ray, a lesion in the right upper lobe of the lung was detected. At this time, primary choriocarcinoma of the lung was strongly suspected, and therapy with methotrexate 25 mg i.v. was initiated. Further diagnostic work included a computed tomography (CT) scan of the chest, which showed a 3 x 2 cm mass in the upper lobe of the right lung and a CT scan of the abdomen showing bilateral ovarian cysts. Magnetic resonance tomography showed that the largest cyst had a diameter of 4.1 x 2.5 cm (right ovary). Evaluation of thyroid function showed totally suppressed thyroid-stimulatory hormone (TSH) and fT4 just above the upper limit of normal (0.0022 mg/100 ml). A CT-guided biopsy of the chest lesion did not yield diagnostic material.
Four weeks after the initial cycle of methotrexate, the serum ß-HCG level increased to 449 U/l. At this time the patient presented at our department. A mediastinoscopy was performed at the department of surgery (AKH, Vienna) and material obtained from the lung lesion. Histological examination revealed large eosinophilic oval and polygonal tumour cells, predominantly in solid arrangement with areas of necrosis (Figure 1). More than 10% mononuclear and multinucleated giant cells were present. Additional immunohistochemical studies using antibodies against ß-HCG yielded strong staining of tumour cells (Figure 2). After resection of the upper lobe of the lung, a 1.8 cm tumour without pleural invasion was found. The regional lymph nodes sampled were negative for metastatis. Histological examination was consistent with the diagnosis of pleomorphic carcinoma with giant cells. Consequently, serum ß-HCG fell to a very low level (9 U/l) and remained at this level for the duration of an 8-month follow up without further therapy. A CT scan of the chest could not detect residual tumour in the lung; neither did a positron emission tomography show any suspect hypermetabolic lesions in the lung or another organ. A magnetic resonance tomography scan of the adrenal glands was unremarkable, and there was a complete disappearance of the ovarian cysts as shown by CT scan.

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Figure 1. Pleomorphic carcinoma with tumour giant cells, syncytiotrophoblast-like giant cells and necrosis (haematoxylineosin, magnification x100).
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Figure 2. Anti-ß-HCG immunostaining of mononuclear and multinucleated tumour giant cells of pleomorphic carcinoma (avidinbiotin complex peroxidase, magnification x100).
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Discussion
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HCG is detectable in the serum of ~15% of lung cancer patients [1]. However, only a few reports have been published on cases with ectopic secretion of HCG leading to clinically evident symptoms. Mostly, male lung cancer patients with HCG-induced gynecomastia have been reported [2, 3]. In the present case, ectopic secretion of ß-HCG led to a syndrome of ovarian hyperstimulation, which may well explain the abdominal discomfort initially reported by the patient. Theca-lutein cysts are a common feature in women with hydatidiform moles or choriocarcinoma, but have not been reported to date in lung cancer patients with excess production of HCG. Vaginal bleeding may have been due to the stimulatory effects of HCG on the endometrium. Subclinical hyperthyroidism, as present in our patient, is an effect of a TSH-like action of HCG. As shown by this case, paraneoplastic symptoms may lead to unusual clinical presentation and confound initial diagnosis.
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Footnotes
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+ Correspondence to: Montleart strasse 37, 1171 Vienna, Austria. Tel: +43-1-49150-2108; Fax: +43-1-49150-2109; E-mail: peter.sagaster@1me.wil.magwien.gv.at 
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References
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1.
Marcillac I, Troalen F, Bidart JM et al. Free human chorionic gonadotropin beta subunit in gonadal and nongonadal neoplasms. Cancer Res 1992; 52: 39013907.[Abstract]
2.
Rosen SW, Becker CE, Schlaff S et al. Ectopic gonadotropin production before clinical recognition of bronchogenic carcinoma. N Engl J Med 1968; 279: 640641.[ISI][Medline]
3.
Metz SA, Weintraub B, Rosen SW et al. Ectopic secretion of chorionic gonadotropin by a lung carcinoma. Am J Med 1973; 65: 325333.