Emily E. Landers and Warner K. Huh
History of present illness
A 38-year-old gravida 4, para 3–0–1–3 woman presents to the emergency department complaining of heavy vaginal bleeding for the past 2 days. Six months prior to presentation she had undergone a dilation and curettage (D&C) for a complete molar pregnancy. She reports that she has not kept any of her follow-up appointments since surgery. Over the past few months, she has developed irregular, heavy menses, and now reports that her bleeding is so heavy it often soaks through her clothing. She also reports nausea and mild lower abdominal cramping. She recently developed a persistent cough with blood-streaked sputum, which seems to be worsening. She otherwise denies fever, chills, dizziness, palpitations, chest pain, or shortness of breath.
She has no other medical problems and has never had abdominal surgery. She is on no medication and her husband plans a vasectomy for contraception. She is a stay-at-home mother who doesn’t smoke and reports having one glass of wine each evening.
Physical examination
General appearance:Well-nourished woman in no acute distress
Vital signs:
Temperature: 36.9°C Pulse: 102 beats/min
Blood pressure: 118/76 mmHg Respiratory rate: 18 breaths/min Oxygen saturation: 97% on room air HEENT:Unremarkable
Cardiovascular:Regular rhythm, mild tachycardia; no rubs, murmurs, or gallops
Lungs:Mild diffuse crackles bilaterally
Abdomen:Soft, nontender, nondistended, active bowel sounds present. Firm uterine fundus palpated 3–4 cm below umbilicus
Rectal:Normal tone, no masses; brown stool noted;
hemoccult negative
Pelvic:Active bleeding from the cervical os, with blood pooling in vaginal vault; cervix closed; uterus mobile and enlarged, approximately 16-weeks’size; enlarged adnexa bilaterally. No cervical motion or adnexal tenderness
Extremities:No clubbing, cyanosis, or edema Neurologic:Alert and oriented × 4. No focal deficits Laboratory studies:
Urine pregnancy test: Positive
Quantitative beta-hCG: 376 524 mIU/mL (normal nonpregnant<5 mIU/mL)
Ht: 21% (normal 34.9–44.5%) Blood type: B positive
Hepatic function panel, thyroid function tests, and metabolic panel were all within normal limits Imaging:
Transvaginal ultrasound: Demonstrated an enlarged uterus with a 5.5 cm well-circumscribed, heterogeneous mass and bilateral enlarged ovaries with multiple theca lutein cysts. There was no evidence of an intrauterine or ectopic pregnancy
Chest x-ray: Showed multiple, diffuse opacities bilaterally (Fig. 93.1)
Fig. 93.1 Chest x-ray.
Acute Care and Emergency Gynecology, ed. David Chelmow, Christine R. Isaacs and Ashley Carroll. Published by Cambridge University Press.
© Cambridge University Press 2015.
How would you manage this patient?
The patient’s diagnosis is suspicious for choriocarcinoma. Due to persistent heavy vaginal bleeding and severe anemia, the patient was counseled on the need for surgical intervention with repeat D&C versus hysterectomy. The patient had no desire for future childbearing and, thus, elected hysterectomy for definitive management.
Intraoperative findings included an enlarged uterus and enlarged multicystic ovaries bilaterally. No other abnormalities were noted in the abdomen or pelvis.
The patient had an uncomplicated postoperative course and was discharged home on postoperative day 3. Surgical pathology demonstrated abnormal trophoblastic hyperplasia and anaplasia, hemorrhage, necrosis, and no chorionic villi.
Findings were consistent with choriocarcinoma (Fig. 93.2).
Given thefindings on chest x-ray, a metastatic workup was performed with a CT scan of the head and chest. The CT scan confirmed numerous pulmonary metastases. The patient was referred to a gynecologic oncologist and was treated with adjuvant multi-agent chemotherapy. Beta-human chorionic gonadotropin (beta-hCG) levels were monitored weekly until undetectable for 3 weeks, and then followed monthly for 24 months to monitor for potential recurrence. She remains healthy to date.
Choriocarcinoma
Choriocarcinoma is a rapidly growing malignant tumor of placental origin, characterized by invasion into the myo- metrium and vasculature [1,2]. It is the most aggressive form of gestational trophoblastic neoplasia (GTN). This describes a spectrum of malignancies that arise from placental tissue, which include invasive hydatidiform mole, placental site trophoblastic tumor, epithelioid trophoblastic tumor, and choriocarcinoma [3]. Choriocarcinoma accounts for approximately 10% of all GTNs. The incidence of
choriocarcinoma is approximately 1 in 40 000 pregnancies, and 1 in 40 hydatidiform moles [2]. GTN most commonly develops following a molar pregnancy, but can occur after any type of pregnancy including a term gestation or spon- taneous miscarriage. After treatment of a molar pregnancy (partial or complete), beta-hCG levels usually normalize within two months [2]. If serum beta-hCG levels plateau, increase, or persist for more than six months after molar evacuation, persistent GTN needs to be considered [4]. Clin- ical characteristics associated with an increased risk of developing GTN after treatment of molar pregnancies includes age greater than 40 years, previous GTN, initial beta-hCG greater than 100 000 mIU/mL, and the presence of cytologic atypia or hyperplasia on histology of the evacu- ated molar tissue [5].
Patients with choriocarcinoma typically present with post- partum bleeding longer than six to eight weeks following delivery or uterine evacuation, as was the case in this patient [4]. They may also present with respiratory complaints such as cough, chest pain, hemoptysis, or signs of gastrointestinal, urologic, or intracerebral bleeding, which is likely indicative of metastatic disease. One of the hallmarks of choriocarcinoma is its ability to directly invade into the uterine myometrium and vasculature with rapid, hematogenous spread to distant sites (lungs, vagina, pelvis, liver, and brain) [3,6].
The diagnosis of choriocarcinoma is made by obtaining information regarding a patient’s pregnancy history, in addition to laboratory and radiographic studies. Beta-hCG levels can vary widely with this malignancy, though they are always elevated above normal nonpregnant levels. Transvagi- nal ultrasound images often demonstrate a uterine mass.
Bilateral enlarged ovaries with multiple theca lutein cysts are also a commonfinding with this diagnosis, which results from a hypersensitive response of the ovaries to high levels of circulating beta-hCG [3]. A chest x-ray should be performed to evaluate for evidence of pulmonary metastatic disease [3].
If there is suspicion for metastasis, a CT scan of the head, chest, abdomen and pelvis should also be obtained [3].
Choriocarcioma is generally a biopsy-proven diagnosis, in most circumstances. Treatment, however, is sometimes initiated without a definitive pathologic diagnosis given the risk of massive hemorrhage following biopsy or endometrial curettage [2]. Hysterectomy is not always necessary in the treatment of choriocarcinoma; however, it may be necessary for the management of uterine hemorrhage. Key histopatho- logic features of choriocarcinoma include abnormal tropho- blastic hyperplasia, hemorrhage, necrosis, and the absence of chorionic villi [2].
Prognosis of choriocarcinoma is good even in cases of distant metastatic disease, given the sensitivity of these tumors to chemotherapy [3]. A scoring system developed by the World Health Organization (WHO) is used to determine prognostic risk (low vs. high) of disease. This scoring system is based on patient age, ABO blood type, extent of spread, largest tumor size, beta-hCG level, duration of disease from
Fig. 93.2 Pathological specimen.
Case 93: A 38-year-old woman with heavy vaginal bleeding 6 months after D&C for complete mole
initial pregnancy event to start of treatment, number and specific sites of metastases, nature of preceding pregnancy, and extent of prior treatment [6]. Additionally, an anatomical staging system developed by the International Federation of Gynecology and Obstetrics (FIGO) is used to further categor- ize disease status and aid in determining the appropriate treat- ment and surveillance strategies. Stage I includes disease confined to the uterus, stage II includes disease extending beyond the uterus but limited to genital structures, stage III includes disease extending to the lungs, and stage IV includes metastatic disease involving other sites [6]. With low risk or stage I–III disease, single-agent chemotherapy with either methotrexate or dactinomycin is generally sufficient. With high-risk or stage IV disease, alternating cycles of etoposide, methotrexate, and dactinomycin with cyclophosphamide and vincristine are indicated [1,4,6]. Radiation therapy is a rarely used treatment option for choriocarcinoma, and is often reserved for patients with metastatic disease to the central nervous system or those who require treatment in addition to surgery for persistence of disease despite appropriate chemotherapy. Fortunately, beta-hCG levels are a highly sen- sitive marker for tracking disease progression or resolution [3].
Monitoring generally consists of weekly measurement of quan- titative beta-hCG until levels are undetectable for three con- secutive weeks. This is followed by monthly measurements for
12 months (stage I–III disease) or 24 months (stage IV disease) [6]. Overall cure rates for choriocarcinoma are greater than 90% [3].
Key teaching points
Choriocarcinoma is a rapidly growing malignant tumor of placental tissue origin, characterized by invasion into the myometrium and vasculature.
Patients most commonly present with vaginal bleeding longer than six to eight weeks after the preceding pregnancy event.
Gestational trophoblastic neoplasia (GTN) most
commonly develops following a molar pregnancy, but can occur after any type of pregnancy including a term gestation or spontaneous miscarriage.
The diagnosis of choriocarcinoma is made from the patient’s clinical history, elevated beta-human chorionic gonadotropin (beta-hCG) levels, ultrasound imaging (which confirms no identifiable current pregnancy despite a likely uterine mass), chest x-ray, and, ideally, a biopsy confirmation.
Treatment with chemotherapy is associated with an excellent prognosis and overall cure rates greater than 90%.
References
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Combination chemotherapy for primary treatment of high-risk gestational trophoblastic tumor.
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