Metastatic Choriocarcinoma to the Pancreas
Gestational choriocarcinoma is a highly metastatic neoplasm derived from placental tissue, occurring in approximately 1:20,000- 40,000 pregnancies. Although gestational choriocarcinoma may follow any gestational event, it most commonly follows molar pregnancies. We report a case of a 24-year-old Hispanic woman with persistent trophoblastic disease who, after failing to respond to chemotherapy, was found to have metastasis to the liver and pancreas. The patient underwent successful distal pancreatectomy and splenectomy to be followed by salvage chemotherapy. Strong risk factors for choriocarcinoma include previous molar pregnancy or spontaneous abortion and increased maternal age. Gestational choriocarcinoma is classically responsive to chemotherapy; surgical excision is reserved for acute emergencies and is an acceptable option for patients with persistent disease in need of palliative treatment and tissue diagnosis.
CHORIOCARCINOMA IS A WIDELY METASTATIC invasive tumor deriving from trophoblastic epithelium with a predilection for highly vascularized organs. The most common sites of metastases are the lung, vagina, pelvis, liver, and brain. Gestational choriocarcinoma occurs most commonly after molar pregnancy but may follow any gestational event. We report the case of a woman with choriocarcinoma metastatic to the lungs, liver, and pancreas. To the best of our knowledge there have been only two reported cases in the English literature of choriocarcinoma metastatic to the pancreas.1, 2
Case Report
The patient is a 24-year-old Hispanic female with a past medical history of a spontaneous abortion in 1999 and a molar pregnancy in 2000. She received chemotherapy and did not follow up with her physicians in Honduras. When she first presented to the gynecologic oncology clinic in January of 2003, she knew very little about her medical history but denied any vaginal bleeding, pulmonary, or neurological symptoms. Her serum βhuman chorionic gonadotropin (BhCG) level was 9073 mlU/mL and a computed tomography (CT) scan of the chest revealed a 3-cm noncalcified soft tissue mass in the left lower lobe (Fig. 1). Physical examination, gynecologic ultrasound, ultrasound of the liver, CT of the head, and cervical cytology were all within normal limits. In view of a persistently elevated serum BhCG, no evidence of pregnancy, and a suspicious mass on CT scan of the chest, a diagnosis of persistent gestational trophoblastic disease was made. The patient was begun on Depo-provera injections for contraception and offered weekly treatments of single-agent methotrexate 50 mg/m^sup 2^ intramuscularly. After four treatments and a partial response, chemotherapy was changed to actinomycin-D secondary to a plateau in BhCG. After five cycles of actinomycin-D, the patient received multiagent chemotherapy including EMA-CO (etoposide, methotrexate, actinomycinD, cytotoxin, vincristin) secondary to a plateau of BhCG. Post-chemotherapy imaging revealed no evidence of disease with complete resolution of the lung nodule by CT scan. Serial BhCG levels in the months after chemotherapy declined to a low of 25 mIU/mL, but the patient was again lost to follow-up.
Approximately 4 months later, she presented to the emergency room complaining of a 6-day history of vaginal bleeding, lower abdominal pain, nausea, and vomiting. Serum BhCG was 323 mlU/mL, chest X-ray and liver function tests were normal and gynecologic ultrasound demonstrated normal pelvic anatomy. CT scan revealed no evidence of disease. Dilatation and curettage was performed, and tissue samples revealed no evidence of trophoblastic tissue. The patient was offered further chemotherapy because of the persistently elevated serum BhCG, but she declined. Several months later, serum BhCG levels continued to rise, and the patient began complaining of early satiety and epigastric abdominal pain. A positron emission tomography (PET) scan showed a metabolically active mass in the tail of the pancreas and a punctuate focus of increased activity in the right hepatic lobe. A CT scan of the abdomen revealed a 6-cm cystic pancreatic tail mass and no liver lesions (Fig. 2). The patient was counseled on the risks and benefits of surgical treatment and further chemotherapy and was taken to the operating room for distal pancreatectomy and possible liver resection. Exploration of the abdomen revealed several palpable liver lesions and a large mass in the lesser sac arising from the tail of the pancreas and invading the splenic vein. En bloc distal pancreatectomy/splenectomy and adrenalectomy were performed. The removal of the hepatic lesions would have required an extended right hepatectomy, and it was determined that this was too great a risk for the patient. If necessary, this procedure would be undertaken after further courses of chemotherapy. Pathology showed a 9.3-cm mass in the tail of the pancreas, invading and thrombosing the splenic vein with highly atypical mononucleated trophoblastic cells and indistinct cytotrophoblast. This altered morphology of classic choriocarcinoma is most likely due to the effects of chemotherapy. Her postoperative course was uncomplicated, and she was discharged with plans to begin further chemotherapy.
FIG. 1. Computed tomography scan of the chest showing a 3-cm noncalcified soft tissue mass in the left lower lobe.
FIG. 2. A computed tomography scan of the abdomen revealed a 6- cm cystic pancreatic tail mass and no liver lesions.
Discussion
Gestational trophoblastic disease (GTD) is composed of a group of aggressive, highly invasive neoplasms derived from the placenta. The classification of GTD according to the World Health Organization (WHO) includes placental site trophoblastic tumor, hydatidiform mole (HM), choriocarcinoma, and miscellaneous and unclassified moles.3 The case reported here is of a young Hispanic women with persistent gestational trophoblastic disease found to be metastatic choriocarcinoma to the pancreas after surgical excision. Gestational choriocarcinoma occurs in approximately 1 in 20,000-40,000 pregnancies, most commonly after molar pregnancy but may follow any gestational event.4 Maternal age and a previous history of molar pregnancy or spontaneous abortion are considered the strongest risk factors for choriocarcinoma. The risk of choriocarcinoma increased progressively in women older than 25 years (relative risk 1.4) and even more so in those older than 39 years (relative risk 10.8). A large proportion of choriocarcinoma are preceded by a molar pregnancy and have been associated with a 1000-2000 times increased risk.3 Other risk factors include the use of oral contraceptives, maternal blood group, and environmental factors such as smoking or viral infections.
Hydatidiform moles, which are most commonly diagnosed during the first trimester, are often present with abnormal vaginal bleeding, absent fetal heart tones, enlarged ovaries, hyperemesis gravidarum, abnormally high level of human chorionic gonadotropin (hCG), and uterine enlargement greater than expected for gestational age.4 Postmolar gestational trophoblastic disease is most commonly diagnosed by increase or plateau in hCG levels after pregnancy or therapy for HM. The most common sites of metastasis are the lungs (80%), vagina (30%), pelvis (20%), liver (10%), and brain (10%). The pancreas is rarely the site of primary choriocarcinoma, and secondary has only been reported in two cases in the literature. Brain metastasis may present with focal neuralgic symptoms, cerebral mass, or intracranial hemorrhage.4 Patients with pulmonary metastasic lesions on chest radiograph may present with dyspnea, cough, hemoptysis, or may actually be asymptomatic.5 One review article suggested that the histopathologic features of choriocarcinoma can be found in virtually every case of hepatic metastasis with coexisting lung or vaginal tumors.5 Choriocarcinoma is composed of avillous invasive cytotrophoblast and syncitiotrophoblast surrounded by necrosis and hemorrhage. According to the new 2000 International Federation of Obstetrics and Gynecology (FIGO) anatomic staging and risk factor scoring system, to diagnose a gestational trophoblastic neoplasm after HM evacuation requires the persistence for greater than 6 months of plateaued values of BhCG, with a ≥10 per cent rise over 3 weeks, as well as the presence of histologic choriocarcinoma.6 The combined anatomic and staging/scoring allows physicians to make more accurate description of disease in order to correctly report and treat trophoblastic neoplasm. If the risk factor score is greater than 7, a patient is considered to have high risk of chemotherapy-resistant disease.5 Our patient can be categorized as stage IV, 12 persistent trophoblastic neoplasm.6
Treatment of stage IV persistent disease consists of combination chemotherapy, surgery, and radiation therapy. Surgery is an accepted modality of treatment of acute complications of metastatic sites such as intracranial or hepatic bleeding.5 Surgical resection of persistent GTD may not only be a therapeutic option but also help to provide a tissue diagnosis. In this case report, persistent gestational trophoblastic disease with cystic lesions in the pancreas and liver were found, and surgical resection was performed only afte\r the patient had failed to respond to multiple chemotherapy, was lost to follow up on several occasions, and presented with vaginal bleeding, early satiety, and abdominal pain. Although removal of the cystic lesion in the tail of the pancreas and involving the spleen may alleviate these symptoms and provide a tissue diagnosis, resection of the liver lesions would have required an extended right hepatic lobectomy. Metastatic choriocarcinoma in the liver are classically sensitive to chemotherapy, and it is our opinion that the patient was better served by foregoing this option due to the risk of bleeding and the clear benefits of subsequent salvage chemotherapy.
Multidrug chemotherapy have been shown to be superior over single agent in women with high-risk GTD.7 MAC (methotrexate, actinomycin- D, cyclophosphamide) is the first multidrug regimen to be extensively studied and has shown cure rates up to 96 per cent in some studies when used as the primary chemotherapy.7 Seventeen per cent to 30 per cent of patients who undergo primary multidrug combination inadequately respond or relapse, requiring subsequent therapy. Salvage chemotherapy most commonly includes EMA-EP (etoposide, cisplatin, methotrexate, actinomycin) with an overall survival rate of 88 per cent in patients with high-risk persistent disease. Myelosuppression is a well-documented complication requiring treatment delay and dose reduction in 88 per cent and 36 per cent of patients, respectively. Close follow-up is extremely important in order to detect recurrence and initiate secondary therapy. Many institutions will continue chemotherapy for three to four cycles after 3 consecutive weekly hCG assays are normal and there is no clinical evidence of disease.7 Cure for these women may inevitably depend on further chemotherapy and adjunctive surgical resection of persistent tumors.
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NICOLAS R. ALVAREZ, B.S.,* NICHOLAS LAMBROU, M.D.,[dagger] CARMEN C. SOLORZANO, M.D.*
From the * Dewitt Daughtry Family Department of Surgery and the [dagger] Department of Gynecologic Oncology, University of Miami/ Jackson Memorial Medical Center, Miami, Florida
Address correspondence and reprint requests to Carmen C. Solorzano, M.D., Department of Surgery, University of Miami School of Medicine, P.O. Box 016310 (M-875), Miami, FL 33101.
Copyright The Southeastern Surgical Congress Apr 2005