Gestational Choriocarcinoma Presenting with Lacrimal Gland Metastasis: A First Reported Case

Background. Gestational choriocarcinoma (GC) is a recognized clinicopathological subtype of gestational trophoblastic neoplasia that usually metastasizes hematogenously to highly vascular organs like the lung, liver, and brain. However, orbital metastasis to the choroid and lacrimal gland is a rare occurrence. Case Presentation. A 21-year-old female presented with headache and left orbital swelling one year after resection of a complete hydatidiform mole followed by adjuvant methotrexate chemotherapy. A metastatic imaging screening revealed multiple metastases in the lungs, brain, and adrenal gland, in addition to the choroid and lacrimal gland. Based on her modified WHO risk factors scoring she was started on chemotherapy and whole brain radiotherapy, which resulted in a complete response. At two-year follow-up, serum b-HCG level was with normal limits; imaging surveillance was uneventful. Conclusion. We present the first case of lacrimal gland metastasis in a young girl from GC relapse.

The term Gestational Trophoblastic Neoplasia (GTN) is reserved for the last four in this subgroup as these have a propensity for progression, invasion, and metastasis any may potentially lead to death if untreated [1]. GTN commonly develops following a hydatidiform mole and less commonly following a live birth or abortion [2].
Gestational choriocarcinoma is a malignant disease with marked trophoblastic hyperplasia resulting in direct invasion into the myometrium and endometrium. About 50% of these occur following a hydatidiform mole, with an incidence of 25% each after abortion or tubal pregnancy [3].
Metastasis of GC to the orbit is a very rare presentation in the literature, which was recently reviewed [6]. We present the first case of GC presenting with lacrimal gland metastasis. A 21-year-old female G1P0 had a termination of her first pregnancy by suction evacuation of a complete hydatidiform mole one year ago. During her preoperative and 2 Case Reports in Obstetrics and Gynecology Routine laboratory blood investigations were within normal; however, b-HCG was grossly elevated (20,165 IU/L). Metastatic work-up included computed tomographic (CT) studies of the brain, chest, abdomen, and pelvis, which showed multiple hemorrhagic brain lesions, multiple lung nodules, and a small suspected metastatic lesion in the left adrenal gland. There were endometrial infiltrating uterine mass and cystic right adnexal lesion identified as a locoregional recurrence. Magnetic resonance imaging (MRI) scan of the brain revealed multiple small hemorrhagic metastases demonstrated on susceptibility-weighted imaging (SWI) (Figure 3).

Case Report
Orbital MRI scan demonstrated a marginally exophytic lesion in the left eye at the level of choroid adjacent to the optic disc appearing hyperintense to gray matter on T1weighted images (Figure 4). There was no calcification seen in the slice-matched CT images, thus helping in distinguishing between possible synchronous choroidal pathologies like retinoblastoma. The lesion was hypointense on T2-FLAIR images ( Figure 5). The high-resolution axial 3D-constructive interference in steady state (CISS) images showed the full extent of the lesion, which was confined to the retinal choroid with normal appearances of the vitreous chamber of the globe ( Figure 6). On imaging, after intravenous gadolinium, the lesion demonstrated homogenous enhancement in keeping with a vascular tumor. Another focal lesion was seen centered in the left lacrimal gland distorting the lacrimal contour ( Figure 7). The dark periosteum of the superior orbital ridge was lost in the MRI study, which showed an amorphous enhancement, and a comparison with the CT study revealed faint periosteum thickening (Figure 8). Both findings were in keeping with bone infiltration.
Given the significant disease burden, history of GC, and uterine and systemic imaging findings, the patient was diagnosed as recurrent GC. Based on the modified WHO prognostic scoring system adopted by FIGO for GTN [7], the patient was diagnosed as a high-risk GTN with a score of >7. A multidisciplinary team was involved in management planning for this patient including gynecological oncology, radiology, ophthalmology, and radiation oncology. The patient was started on EMA-CO chemotherapy regimen (etoposide, methotrexate, folinic acid, actinomycin D, cyclophosphamide, and vincristine). Additionally, the patient was also started on high-dose dexamethasone to reduce cerebral edema exerted by the brain metastasis and received whole brain radiation. She tolerated the treatment well with eventual normalization of her b-HCG, and metastatic imaging scans surveillance was negative for 2-year followup.

Discussion
Ocular metastases, also known as uveal metastasis, occur in about 9 to 10% of all systemic cancer [7][8][9]. The most common tumors to metastasize to the retina are breast cancer, accounting for 40% of cases, and lungs cancer, particularly small cell carcinoma for about 29% of the cases [8][9][10][11][12][13]. The choroid is the most common site of such metastatic diseases due to its rich vascularity [14].
Choriocarcinoma has shown metastasis to the orbit, particularly retinal choroid predominantly reported from the Case Reports in Obstetrics and Gynecology male pathological counterparts, testicular choriocarcinoma [13,15]. A few cases of GC metastasis to the retinal choroid and extraocular muscles have also been reported [6,14,16].
Unlike metastatic ocular diseases of other primaries, choriocarcinoma has an affinity for hemorrhage and need an expedited MRI evaluation for diagnosis and management planning. One of the differential diagnoses, which were entertained, was malignant melanoma, which has similar characteristics in T1-MRI scan as a hyperintense lesion. However, they tend to show a characteristic collar button shape and are more exophytic than our study. Radiological appearances of T1-MRI scan of a hyperintense choroidal lesion in the absence of calcification, particularly in the scenarios of other metastasis, helped in the decision-making.
Lacrimal gland metastasis from malignancy is a rarity in itself. Although a site-specific percentage of lacrimal gland metastatic infiltration could not be found, even among the cases with orbital metastasis, mention of lacrimal gland involvement has been few and far between. The common primary tumors metastasizing to the lacrimal glands include 6 Case Reports in Obstetrics and Gynecology esophageal, breast, and renal malignancies [17]. To the best of our knowledge, this is the first case of GC metastasizing to the lacrimal gland.
The International Federation of Gynecology and Obstetrics (FIGO) developed an adapted staging system for GTN, which incorporated the World Health Organization risk factor scoring system for GTN and the previous FIGO anatomical scoring [18]. According to this modified riskstratification system, our patient was score >7, the highest risk category in the system, based on the number, location, and size of metastases and other prognostic factors, including the level of the serum b-HCG.
Traditionally, the treatment for metastatic GC is first and foremost chemotherapy. Patients with a low-risk disease (score <7) are treated with single-agent therapy, usually methotrexate. Patients classified as having high-risk (score >7) are treated with multiple chemotherapy agents with or without radiation or surgery [19]. Recent literature suggests that patients undergoing a multiagent regimen of EMA-CO have complete response rates of 71-78% and long-term survival rates of 85-94% [19][20][21][22][23][24]. This is the same applied to orbital GC metastases with EMA/CO chemotherapy regimen without [16] or with local radiotherapy [15]. Our patient has shown complete response to chemotherapy and whole brain radiation with good recovery from the unusual ocular as well as other metastatic lesions.

Conclusion
Visual impairment and orbital swelling due to orbital metastasis in a patient with GC are rare occurrence and require a high index of suspicion. We emphasize the need of brain and orbital MRI scan in addition to local and systemic radiological evaluation and serum level of b-HCG for assessing the disease burden in all patients with advanced GC for early diagnosis and management planning.

Consent
Written informed consent was obtained from the patient for publication of this case report and any accompanying images.