SUBMITTED 5 JAN 23 1 REVISION REQ. 20 FEB 23; REVISION RECD. 14 MAR 23 2 ACCEPTED 19 APR 23 3 ONLINE-FIRST: MAY 2023 4 DOI: https://doi.org/10.18295/squmj.5.2023.036 5 6 An Unusual Presentation of Choriocarcinoma in A postmenopausal woman 7 A case report 8 *Aref Zribi,1 Reem Al Mazroui,2 Raza Sayani,2 Ikram A Burney1 9 10 1Women Health Program and 2Department of Radiology, Sultan Qaboos Comprehensive Cancer 11 Care and Research Centre, Muscat, Oman. 12 *Corresponding Author’s e-mail: arefdoc@gmail.com 13 14 Abstract 15 Choriocarcinoma (CC) is a malignant neoplasm of the trophoblastic tissue, with a potential to 16 metastasize to distant organs. A limited case of gestational CC develops after a long latent 17 period. We describe the case of a 52-year-old postmenopausal woman who developed metastatic 18 choriocarcinoma presumably of gestational origin, 8 years after the last pregnancy, and 2 years 19 after the last menstrual period. The patient was diagnosed with CC metastatic to the brain, 20 spleen, lung and the kidney. The β-human chorionic gonadotrophin level was found to be raised 21 (1,292,867 mIU/mL). The International Federation of Gynecologic Oncology (FIGO) risk score 22 was calculated to be 14 (very high risk). The patient was initially treated with whole-brain 23 radiotherapy (WBRT) and splenic artery embolization because of a hemoperitoneum. Afterwards 24 the patient received systemic treatment using the standard EMA/CO regimen till complete 25 serological remission. 26 Keywords: Choriocarcinoma; Postmenopausal; Latent period; Brain; Oman. 27 28 29 30 Introduction 31 Choriocarcinoma (CC) is a malignant neoplasm of the trophoblastic tissue, with a potential to 32 metastasize to distant organs.1 There are two sorts, gestational and non-gestational CC. Majority 33 of cases of gestational CC are intra-uterine, and only 0.8-4 % develop in ectopic locations.2.3 The 34 non-gestational CC arise in the gonads, usually in the reproductive age. A limited cases of 35 gestational CC develop after a long dormant period.4.5 Gestational CC has been reported to 36 develop between 5 weeks and up to 38 years after gestation, and even after menopause.4 37 Approximately 30 % of cases of gestational CC are metastatic at the time of diagnosis.4 The 38 tumor metastasizes most commonly to the lungs (60-75%), vagina (40-50%), brain (15-20%), 39 liver (15-20%), spleen (10%), intestines (5-10%), and the heart (4%).6-9 Here, we illustrate the 40 case of metastatic CC in a 52-year-old postmenopausal lady, growing 8 years after the last 41 pregnancy, and 2 years after the last menstrual period. 42 43 Case Report 44 A 52-year-old female, menopausal for two years, was brought to the emergency room with a 45 history of headache and an episode of seizure. There was no history of loss of consciousness. 46 Past medical history revealed an episode of vaginal bleeding 8 years back, for which the patient 47 underwent dilatation and curettage, and was diagnosed to have a molar pregnancy. She had no 48 other past medical history of significance. On physical examination, the patient was conscious, 49 oriented to time, place and person, vitally stable, and had normal power and tone in both upper 50 and lower limbs. There was no facial asymmetry, and all cranial nerves were intact. 51 Gynecological exam revealed a normal vulva; cervix was irregular and the uterus was bulky. 52 There was no vaginal bleeding. 53 Magnetic resonance imaging (MRI) showed a large space occupying lesion involving the right 54 frontal lobe, measuring 36 x 33 mm, with surrounding vasogenic edema and midline shift to the 55 left, and subfalcine herniation in the frontal area. Several lesions involving the right parietal and 56 the occipital lobes, largest measuring 20 x 20 mm, were also identified (Figure 1). The CT scan 57 of the body cavity showed heterogeneous appearance of the endometrial cavity, and multiple 58 hypodense lesions in the spleen, largest measuring up to 24 mm, and a small lesion in the right 59 kidney. A soft tissue nodule in the right middle lobe of the lung and in the left lung apex were 60 also seen. MRI of the pelvis showed normal endometrial thickness and signal intensity, no 61 adnexal masses, and no enlarged pelvic lymph nodes or ascites (figure 2). 62 Other than the splenic lesion, no other lesion was large enough to biopsy. The β-human chorionic 63 gonadotrophin (β-HCG) level was found to be raised (1,292,867 mIU/mL; normal <5 mIU/mL). 64 In absence of tissue diagnosis, no mass in the adnexal region, and a very high level of β-HCG, a 65 diagnosis of gestational CC was made. The International Federation of Gynecologic Oncology 66 (FIGO) risk score was calculated to be 14 (very high risk). 67 After admission to the hospital, the patient developed fever, and was found to have 68 staphylococcus aureus bacteremia, the bacteria being sensitive to cefazolin. In addition, the 69 patient was treated with levetiracetam and dexamethasone. The case was discussed in tumor 70 board. Because of the midline shift and impending herniation, the patient was initially treated 71 with whole-brain radiotherapy (WBRT) to a dose of 25Gy in 10 fractions. After radiotherapy, 72 systemic treatment was commenced using induction chemotherapy, consisting of etoposide and 73 cisplatin. Four days after receiving the 1st dose, the patient developed tachycardia (HR 140/min, 74 regular, low volume). Electrocardiogram revealed sinus rhythm. The hemoglobin was found to 75 be very low at 3 g/dl. An urgent CT scan of the abdomen showed hemoperitoneum and a 76 significant progression in the size of the metastases to the spleen, which had breached the 77 capsule (Figure 3). Splenic artery embolization was carried out leading to a complete occlusion 78 of the artery and a rapid arrest of further bleeding (Figure 4). Systemic chemotherapy was 79 continued, as the standard EMA/CO regimen, till complete serological remission. At the time of 80 serological remission, CT scan of the body cavity revealed near complete resolution of the 81 splenic and lung lesions. End-of-treatment CT scan and MRI of the brain confirmed the 82 radiologic remission. Oral and written consent were taken from the patient for publication 83 purposes. 84 85 Discussion 86 We report the successful treatment of a post-menopausal women, diagnosed to have stage IV, 87 high risk CC, most likely of gestational origin, 8 years after the evacuation of a hydatidiform 88 mole, and managed with WBRT and splenic artery embolization, before being treated with 89 systemic chemotherapy. 90 The vast majority of cases occur in women less than 35 years of age, usually within one year 91 following the diagnosis of hydatidiform mole (60% of cases), or abortion (30%) and after a 92 normal or ectopic pregnancy (10%).10.11 A higher incidence is reported from Africa, Asia and 93 South America, with an estimated incidence of 1 in 500-3000 pregnancies in south-east Asia. 94 The occurrence in postmenopausal period is uncommon.12 Furthermore, only a countable cases 95 have been described after a long latent time from the last pregnancy. 96 The risk of hydatidiform mole raise significantly with increasing mother age.13 CC can develop 97 anytime between 5 weeks to several decades after antecedent pregnancy or even after 98 menopause.14.15 Desai published a case of CC in a 73-year-old patient, developing 38 years after 99 pregnancy and 23 years after her last menstrual menses.5 O’Neill reported the case of CC in a 57-100 year old lady, 22 years after the last known pregnancy.1 Similarly, Okamoto reported the case of 101 CC in a 53-year old lady, 23 years after an elective abortion.16 Sonobe reported the case of a 50-102 year old lady with CC 23 years after the last pregnancy.17 Ito reviewed the literature of late 103 presentation of CC. The authors noted that the latent period was more than 2 years in 7.5% of 104 patient with CC.18 A long latent period from last pregnancy can be explained by an 105 asymptomatic pregnancy. Alternatively, the trophoblastic tissue retained in the uterus following 106 the antecedent pregnancy could lie dormant for several years before transformation to 107 malignancy. 108 A limitation of this case report is the lack of tissue evidence of recurrence. A biopsy from the 109 metastatic CC is usually not carried out due to a risk of hemorrhage, However, the very high β-110 HCG level, serially increasing in presence of metastases is known to occur frequently in CC. In 111 the setting of an antecedent molar pregnancy, albeit, 8 years earlier, the patient was diagnosed to 112 have recurrence of CC. 113 114 Conclusion 115 CC is one of the most curable gynecological cancer, and should be included in the differential 116 diagnosis of cancer occurring in postmenopausal woman. A few cases of a long latent period 117 after the last pregnancy have been reported, however, the mechanism of late onset of CC is not 118 known. Retained trophoblastic tissue or an asymptomatic pregnancy between the last known 119 pregnancy and the diagnosis of CC may explain, however, the actual cause remains speculative. 120 Non-gestational CC should be considered an alternative diagnosis in such cases. 121 122 Conflicts of Interest 123 The authors declare no conflict of interests. 124 125 Funding 126 No funding was received for this study. 127 128 Authors’ Contribution 129 AZ and IAB managed the case. RAM provided the images. RS managed the splenic artery 130 embolization. AZ, RAM and RS drafted the manuscript. IAB reviewed the manuscript. All 131 authors approved the final version of the manuscript. 132 133 References 134 1. O'Neill CJ, Houghton F, Clarke J, McCluggage WG. 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Nihon Sanka Fujinka Gakkai Zasshi. 1985; 184 37(5):730-4. 185 186 187 Figure1: A) Coronal T2-weighted magnetic resonance imaging (MRI) reveals hemorrhagic 188 lesion within the subcortical region of right parietal lobe measuring 2.7 x 2.2 cm with adjacent 189 vasogenic edema; B) Axial contrast-enhanced T1-weighted MRI reveals multiple, enhanced, 190 nodular lesions; C) Susceptibility weighted imaging demonstrates multiple hypointense, 191 hemorrhagic lesions in the cortical and subcortical areas. 192 193 194 Figure2: A) Sagittal T2-weighted MR reveals normal uterus with normal endometrial stripe 195 thickness and signal. Sagittal contrast-enhanced fat-suppressed T1-weighted MR image; B) 196 demonstrates normal enhancement with no tumor seen. 197 198 199 Figure3: Contrast enhanced CT performed after 25 days from initial CT because patient showed 200 sudden drop of hemoglobin. Coronal reformat CT (a-b) reveals newly developed moderate 201 hemoperitoneum with rapid increase in size of splenic hemorrhagic masses (black arrow) that are 202 likely the cause of the retroperitoneal bleed. In addition, the right renal mass has also progressed 203 in size (white arrow) 204 205 206 207 208 209 210 211 212 213 214 Figure 4: Splenic artery embolization (distal technique). A) Celiac angiogram shows large round 215 mass medial to the spleen corresponding to the known metastatic deposit (black arrow). No 216 active extravasation; B) Distal splenic artery branches are selected. Abnormal blush with active 217 extravasation was seen from a branch of splenic artery (white arrow); C) A 2.7F Progreat 218 microcatheter was then inserted co-axially through the 5F catheter and advanced. This was super 219 selectively cannulated and embolization was then performed with PVA particles and coils. No 220 further extravasation seen (image C). 221