Primary ovarian choriocarcinoma masquerading as ruptured ectopic pregnancy in an HIV positive woman

Introduction: Ovarian choriocarcinoma is a highly malignant and rare gynecologic tumor. This cancer should be considered in the differential diagnosis of women presenting with a suspected ectopic pregnancy. Case Report: A multiparous HIV positive woman presented with a suspected ruptured chronic ectopic pregnancy. Her final pathology demonstrated choriocarcinoma arising out of an ovarian ectopic pregnancy versus a primary choriocarcinoma of the ovary. Further evaluation showed metastases to her brain and lungs. Despite aggressive chemotherapy, the patient continued to have progressive physical and mental decline. She was discharged to hospice care during her last admission to our institution and subsequently died. Conclusion: Ovarian choriocarcinoma should be considered when evaluating women with a ectopic Rachel M Whynott1, Julie Vitko2, Shelly W Holmstrom3, Meredith Gray4 Affiliations: 1MD, Resident, Department of Obstetrics and Gynecology, University of South Florida, Tampa, FL, USA; 2MD, Ruffolo, Hooper & Associates MD PA, Consultants in Pathology & Laboratory Medicine, Tampa, FL, USA; 3MD, Associate Professor, The University of South Florida Morsani College of Medicine, Department of Obstetrics and Gynecology, Tampa, FL, USA; 4MD, Assistant Professor, Department of Obstetrics and Gynecology, University of Kansas, Kansas City, MO, USA. Corresponding Author: Rachel M. Whynott, MD, The University of South Florida Morsani College of Medicine, Department of Obstetrics and Gynecology, Tampa General Circle, 6th Floor STC, Tampa, FL 33606; E-mail: rachel.m.whynott@gmail.com Received: 02 December 2016 Accepted: 17 January 2017 Published: 03 February 2017 pregnancy, especially in the setting of the human immunodeficiency virus.


INTRODUCTION
Ovarian choriocarcinoma is a rare and aggressive gynecologic tumor that produces human chorionic gonadotropin (hCG) hormone and is comprised of malignant trophoblastic cells [1]. This type of choriocarcinoma is classified as either gestational or non-gestational germ cell tumor and is differentiated by genetic analysis of the tumor. Gestational ovarian choriocarcinoma can arise from an ectopic pregnancy in the ovary or as metastasis from a choriocarcinoma of uterine origin. Non-gestational ovarian choriocarcinoma is a type of germ cell tumor of ovarian origin [1,2]. These subtypes of choriocarcinoma are uncommon and the incidence of primary ovarian choriocarcinoma is estimated to be 1 in 389,000,000 [2]. Gestational and non-gestational ovarian choriocarcinomas are aggressive, tend to be invasive, and metastasize hematogenously early in the disease process. Similar to other gestational  [2,3]. This case discusses a woman with human immunodeficiency virus (HIV) and a suspected chronic ectopic pregnancy, which was later diagnosed as an ovarian choriocarcinoma. This case presentation illustrates why ovarian choriocarcinoma should be considered in the differential diagnosis of patients with ectopic pregnancy, especially in the setting of immunosuppression.

CASE REPORT
A 32-year-old gravida 6 para 4 with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), who was non-compliant with highly active antiretroviral therapy (HAART), presented to the clinic for her first prenatal visit. She reported an uncertain last menstrual cycle that would have made her gestation 13 weeks 3 days at that time. Transvaginal ultrasound revealed lack of intrauterine pregnancy at this initial visit. A beta-hCG level was ordered, however, the patient, who was non-compliant throughout her care, left prior to the blood draw.
The patient did not follow-up until approximately 1 month later at 18 weeks 2 days for a colposcopy examination secondary to a high-grade squamous intraepithelial lesion (HGSIL) Pap test at her initial prenatal visit. Cervical biopsies revealed high-grade cervical intraepithelial dysplasia and an endocervical curettage specimen was not obtained secondary to pregnancy. A serum beta-hCG level was ordered at that time, but she again left prior to her blood being drawn.
The patient presented for a follow-up visit and did allow for her blood to be drawn. Her beta-hCG level at that appointment was 10638 mIU/ml, and her initial CD4 count was 183. She was scheduled for ultrasound.
The patient presented seven days later to our institution with tachycardia, peritoneal signs, and absence of an intrauterine pregnancy on bedside transvaginal ultrasound. Her beta-hCG was 7611 mIU/ml at that time. She was rushed emergently to the operating room for a suspected ruptured ectopic pregnancy. A hydropicappearing right ovarian mass and ovary with adhesions to the pelvic sidewall, uterus, and rectum was discovered on diagnostic laparoscopy (Figure 1). A laparoscopic right salpingo-oophorectomy (RSO) was performed and required a mini-laparotomy for specimen removal. A chronic ectopic pregnancy was suspected at the time of surgery. The surgeons were concerned for decidual invasion into her bladder and rectum. Cystoscopy and proctoscopy were performed and confirmed a lack of involvement of these organs.
The specimen was read as an 18-cm choriocarcinoma arising out of an ovarian ectopic pregnancy versus a primary choriocarcinoma of the ovary (Figure 2). No clinical evidence of intrauterine disease was identified in this case, further supporting a non-gestational related choriocarcinoma. FISH testing on this specimen was abnormal, consistent with tetraploidy and an XXXX sex chromosome. She was admitted as an inpatient three days after her surgery secondary to a fever of 38.61°C, for further evaluation of her disease burden and possible complication from her laparoscopic RSO. Imaging at the time of admission revealed further abdominal disease ( Figure 3) and a 12.4x15.4x16.5 cm mass of the right upper lung, which nearly replaced the entire right upper lobe, consistent with metastatic disease ( Figure  4). Additionally, metastases in the frontal lobe of her cerebrum and cerebellum were seen on a CT scan of brain ( Figure 5). Despite her extensive metastases, she was asymptomatic. The patient was started on emergent EMA-CO chemotherapy (etoposide, methotrexate, dactinomycin followed-by cyclophosphamide and vincristine). The patient experienced continued physical decline and altered mental status despite receiving four  cycles of chemotherapy. Her CD4 count dropped as low as 79 cells/μL on highly active antiretroviral therapy (HAART) therapy while undergoing chemotherapy, and it never was greater than 200 cells/μL. Her family reported that she was non-compliant with her medications at home. The patient and her family decided to discharge her to a hospice care, and she died shortly thereafter.

DISCUSSION
Choriocarcinoma in its pure form and in the reproductive age is rare at less than 1% of ovarian germ cell tumors. As in this case, the gross appearance is a hemorrhagic friable unilateral ovarian mass, which commonly ruptures. Histopathology is imperative for proper diagnosis of choriocarcinoma [4]. An accurate diagnosis is especially important for evaluation and treatment of ovarian choriocarcinoma, such as in this case, where our patient did not exhibit any symptoms of metastatic disease, suspicion for this rare diagnosis was low [5]. In addition, DNA analysis may be useful in differentiating between gestational and non-gestational choriocarcinoma. Although DNA testing would be confirmatory of a pure form of choriocarcinoma, this   test is not readily available in the clinical practice. Gestational choriocarcinomas tend to have good response to the traditional chemotherapy regimens, while there is less data guiding the treatment of the non-gestational type [5]. Prognosis tends to be good for gestational choriocarcinoma but is poor for nongestational [5]. This information regarding prognosis may help guide families in their expectations and decisions regarding care.
Interestingly, HIV positivity and CD4 counts below 200 cells/μL have been linked to poorer prognosis in patients with choriocarcinoma and gestational trophoblastic neoplastic disease in general [6,7]. In a study by Moodley et al., mortality was significantly greater in HIV infected individuals with CD4 counts below 200 cells/μL, and the stage of the cancer was significantly greater (stage III/IV) as compared to HIV infected individuals with counts above 200 cells/μL. While further research in this area is needed, HIV status seems to have an impact on the course of disease.

CONCLUSION
Ovarian choriocarcinoma should be considered in the setting of inappropriately rising beta-hCG levels and a large ovarian mass. HIV may lead to a poorer prognosis in the setting of gestational trophoblastic disease. *********

Author Contributions
Rachel M. Whynott -Substantial contributions to conception and design, Acquisition of data, Analysis and interpretation of data, Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be published Julie Vitko -Analysis and interpretation of data, Revising it critically for important intellectual content, Final approval of the version to be published Shelly W. Holmstrom -Analysis and interpretation of data, Revising it critically for important intellectual content, Final approval of the version to be published Meredith Gray -Analysis and interpretation of data, Revising it critically for important intellectual content, Final approval of the version to be published