This lady's history has two key symptoms : vaginal bleeding and a chronic cough. Note that the first involves the genital tract, while the second involves the respiratory system. Very few pathologies are likely to involve both systems simultaneously - mainly malignancies of the genital tract (with metastasis), or rarely, disseminated tuberculosis. The malignancies of the genital tract which most often give rise to vaginal bleeding are cervical carcinoma, endometrial carcinoma and less often, ovarian carcinoma. However, metastasis to the lung is rare and is almost always a feature of advanced disease. One would expect her to be far more debilitated if that were the case. Choriocarcinoma is a rare malignancy of the genital tract which metastasizes early - especially to the lung, liver and brain. While many choriocarcinomas follow a molar pregnancy, these may also arise following a normal pregnancy - even after many years have passed. In addition, many of these patients appear relatively well at presentation. Disseminated tuberculosis is also a possibility. However, many of these patients are systemically unwell, demonstrate constitutional symptoms and give a history of significant weight loss. The absence of these features while in no way excluding this diagnosis, do make it less likely. The last possibility to be kept in mind is that the respiratory and genital tract symptoms might be due to two different pathologies. Thus, the respiratory symptoms might be due to asthma, allergy or infection, while those of the genital tract might very well be due to a benign lesion such as endometrial polyps or endometritis. A pelvic ultrasound scan is a suitable first-line investigation, and demonstrates an ill-defined intrauterine mass. Unfortunately, this is too non-specific a finding - it might be a choriocarcinoma, or even a uterine malignancy. A chest x-ray is also important - but this too is non-specific. However, the negative tuberculin test and sputum smears make tuberculosis unlikely. Estimation of serum beta-hCG levels helps clinch the diagnosis - this degree of elevation is rare and almost exclusive to gestational trophoblastic disease (of which choriocarcinoma is a part). This also explains the cystic appearance of the ovaries - those are likely theca-lutein cysts secondary to high beta-hCG levels. There also exists the rare possibility that this might be a metastasizing invasive hydatidiform mole (which is another form of gestational trophoblastic disease). It is impossible to definitively distinguish this from choriocarcinoma based on clinical or imaging characteristics alone thus she should undergo histological analysis of the primary tumor immediately. Regardless of whether the ultimate diagnosis is choriocarcinoma or a metastasizing invasive hydatidiform mole, she will require chemotherapy. While radiotherapy may be utilized for treatment of secondaries in the liver or brain, it is not used for treatment of the primary tumor. Exploratory laparotomy is not indicated currently, while there is no role for antituberculous therapy.
The spectrum of gestational trophoblastic disease (GTD) ranges from complete hydatidiform moles to partial moles and choriocarcinoma. Of these, the first two are benign, while choriocarcinoma is their malignant counterpart. Note that certain hydatidiform moles may invade surrounding structures and even metastasize without exhibiting features of true malignancy. In the United Kingdom, the incidence of complete moles is approximately 1 per 1000 pregnancies; that of partial moles is 3 per 1000 pregnancies; while that of choriocarcinoma is 1 in every 50,000 births. Note however, that the incidence varies markedly between countries, and is highest in certain parts of Asia. Approximately 50% of choriocarcinomas arise following a hydatidiform mole; 25% arise after miscarriages; while the remainder occur following a normal pregnancy. The most important risk factor for GTD is a previous molar pregnancy. In addition, the incidence of GTD is increased in teenagers and perimenopausal women; and in those living in lower socioeconomic conditions. Women of blood group A have been shown to have a slightly higher risk than those with blood group O. Choriocarcinomas typically present with irregular vaginal bleeding, pelvic pain and symptoms of metastatic disease. Pulmonary secondaries may give rise to dyspnea, cough and hemoptysis, while cerebral metastases may manifest as headache, hemiparesis and seizures. The other common sites of metastasis are the vagina and liver. Pelvic ultrasonography typically shows a heterogeneous, hypervascular mass of mixed echogenicity with areas of hemorrhage and necrosis. Note that these sonographic features are found in invasive hydatiform moles as well - it is difficult to make a definitive diagnosis of choriocarcinoma via ultrasound alone. Serum beta-hCG levels are massively elevated in these patients, with the degree of elevation used for risk stratification and staging. A chest x-ray is essential in these patients. In addition, if pulmonary lesions are present further imaging is mandatory to identify metastases in other sites such as the liver and brain. Note that if the chest x-ray is normal, CT imaging of the chest is not required, as discovery of micrometastases does not affect the outcome. Histological confirmation of the primary tumor is important in the management. Note that histologic analysis of metastatic lesions is not required. The management strategy is determined by the FIGO 2000 scoring system which is based on factors such as the patient's age, presence of metastases and serum beta-hCG level. Patients with a low risk (i.e. scores <= 6) are usually treated with a single chemotherapeutic agent such as intramuscular methotrexate. High risk patients (i.e. scores >= 7) are usually administered intravenous multi-agent chemotherapy, consisting of combinations of methotrexate, dactinomycin, etoposide, cyclophosphamide and vincristine. A hysterectomy may be performed if the patient has completed her family. This has been shown to reduce the amount of chemotherapy needed to induce remission. Otherwise, surgery might be required in patients who experience intractable bleeding. Radiotherapy (especially for brain and liver secondaries) may also be administered in patients with high-risk metastatic disease. Once remission has been achieved, patients with choriocarcinoma should be followed up via serial beta-hCG levels. The duration of follow up depends on unit policy - certain units advocate lifelong follow up, while others do so only for several years. Patients may be advised that it is safe to become pregnant one year after completion of chemotherapy. Becoming pregnant prior to this may lead to diagnostic confusion, as the rise in beta-hCG levels could also be attributed to relapse or recurrence. Intrauterine contraceptive devices (IUCD) or oral contraceptive pills should also be avoided until beta-hCG levels normalize, because the resulting irregular bleeding cannot be distinguished from a relapse or recurrence. Barrier methods may be used instead. Last but not least, note that these patients have an increased risk of GTD following future pregnancies. Thus, beta-hCG levels should be measured 6 to 8 weeks following the end of all pregnancies (regardless of outcome). With treatment, non-metastatic gestational trophoblastic tumors and metastatic low-risk tumors approach cure rates of 100%; even metastatic high-risk tumors achieve cure rates of 80% to 90%.