Choriocarcinoma metastatic to both kidneys presenting with spontaneous renal hemorrhage: Case report

Abstract

Introduction

Choricocarcinoma is a highly malignant tumor. It metastasize commonly to the lungs. Metastasis to the kidney is uncommon, and bilateral metastasis is described rarely. Initial presentation with spontaneous bleeding of the renal metastatic tumor is scarce in the literatures. Here we present a case report of a choriocarcinoma patient with bilateral renal metastasis, presenting with spontaneous renal hemorrhage.

Case presentation

A 22 years old female presented to our emergency department with sudden onset of left flank pain. She has history of spontaneous abortion 02 years back with biopsy from the manual vacuum aspiration (MVA) showing molar pregnancy. Up on evaluation, patient was anemic. CT scan showed left renal bleeding tumor. Exploratory laparotomy and radical nephrectomy was done with the impression of bleeding renal cell carcinoma. The biopsy revealed choriocarcinoma. On her follow up, CT scan showed right renal and brain metastasis. She was given multi agent chemotherapy and her serum beta-hCG became undetectable after 01 year.

Discussion

Choriocarcinoma can be gestational or nongestational. The commonest route of metastasis is hematogenous. Presenting symptoms of renal metastasis can be hematuria, pain or more commonly incidental finding during work up. Choriocarcinoma is highly chemo sensitive.

Conclusion

Bilateral renal metastatic choriocarcinoma is uncommon. Spontaneous renal hemorrhage as an initial presentation is even rare, and it can mimic a bleeding renal cell carcinoma. High index of suspicion is needed in a young women with recent history of spontaneous abortion.

Highlights

• •Choriocarcinoma is a highly malignant tumor.
• •Choriocarcinoma metastasis to the kidneys is uncommon.
• •Initial presentation of choriocarcinoma patients with spontaneous renal hemorrhage is rare.
• •Choriocarcinoma is highly chemo sensitive. Radical nephrectomy has a place in emergency settings.

1. Introduction

Choriocarcinoma is one of the malignant types of gestational trophoblastic tumors. It can also occur in a non-gestational form [1]. Gestational Trophoblastic tumors are known to arise from the trophoblastic elements of the placenta. It retains the invasive tendency of the normal placenta. It is also characterized by secretion of beta-hCG which serves as the tumor marker.

Gestational Choricarcinoma mainly arises from a prior molar pregnancy and rarely from a non-molar pregnancy commonly within 1 year of the pregnancy. The incidence of Gestational choriocarcinoma is reported to be approximately 1 in 20,000 to 1 in 40,000 of non-molar pregnancies and follows 2 % - 3 % of molar pregnancies. This incidence is said to be higher in Asia and Africa with about 1 in 2,500 pregnancies [2]. Hematogenous spread is the main way of distant metastasis [[3], [4], [5]]. The Lungs are the commonest site of metastasis. Renal involvement with metastasis is rare and primary renal choriocarcinoma is scarce [6].

Here we report a case of choriocarcinoma with bilateral renal metastasis and the patient presenting with spontaneous tumor hemorrhage.

This case report is written based on SCARE criteria [7].

2. Case presentation

A 22 years old female patient presented to our emergency department with a complaint of left flank pain of 15 h duration. The pain is dull aching in type and had a sudden onset. The pain had no exacerbating or relieving factors. The pain did not radiate to another site. She was a known epileptic patient for the past 07 years on phenobarbitone 100 mg po/ day. The last episode of seizure was 04 years back. She had history of molar pregnancy 02 years back which was diagnosed after presenting with vaginal bleeding on the first trimester of her pregnancy. MVA was done for the management of the molar pregnancy. On the current presentation, she had no recent history of trauma, no vomiting, no cough, no hematuria, and no vaginal bleeding. She claimed her menses was irregular.

On physical examination: her pulse rate was 120 beats per minute, respiratory rate was 26/min, blood pressure was 110/70 mmHg, axillary temperature was 37.2 degree Celsius and oxygen saturation was 92 % with atmosphere. She had pale conjunctiva and non-icteric sclera. Left costo-vertebral angel tenderness was elicited.

Laboratory and imaging investigations were performed and pertinent results were: CBC with WBC count of 13,300/ul (Neutrophil of 88 %), hemoglobin of 7.6 g/dl and Platelet count of 243,000/ul. Serum electrolyte with potassium - 4.2, Sodium - 136, Chloride - 108, RFT: Cr- 0.9 mg/dl, LFT: AST 51 u/l, ALT 36 u/l, ALP 52 u/l. Urine analysis parameters were all in the normal limits. Coagulation profile was also normal. Abdominal ultrasound showed left renal upper pole blurred outline with diffuse heterogeneous content seen with in the collecting system as well as the peri-renal space. CT urography showed left large peri renal hemorrhage compressing the left kidney with delayed contrast enhancement and excretion. Right kidney was normal (Fig. 1).

Fig. 1.

CT – scan of the abdomen (Arterial Phase) showing left peri-renal hemorrhage with no enhancing mass lesion.

Patient was started on IV antibiotics with ceftriaxone and metronidazole, IV narcotic analgesics, and she was transfused with 03 units of cross matched blood. Since Trans-arterial embolization is not available in our set up, Patient was prepared for emergency exploratory laparotomy with the impression of retroperitoneal hematoma secondary to bleeding renal tumor. Under general anesthesia through a vertical midline abdominal incision the abdomen was entered. There was around 500 cc perinephric hematoma and multiple deep lacerations of the renal parenchyma on the anterior upper pole and the interpolar region. Radical nephrectomy done and the specimen sent for histopathology examination. Post operatively, she had a smooth course in the ward. Patient was discharged after 06 days of stay.

Pathology examination was described as, gross specimen examination revealing a gray brown left nephrectomy specimen measuring 10X5X4 cm with 3 mm long attached ureteric stump. There was 4X2cm defect on the lateral aspect of the kidney breaching the capsule. Cut-section showed gray-brown hemorrhagic mass measuring 3X2cm which breached the capsule and seemed to reach the renal sinus. Hemorrhagic areas were seen. Normal tan colored renal tissue measuring 7X2cm was present. Necrotic focus was not evident grossly.

Histopathological examination showed cohesive sheets of pleomorphic trophoblasts having marked cytologic atypia with abundant pale eosinophilic to clear cytoplasm with distinct cell membranes and surrounded by multinucleated syncytiotrophoblasts (Fig. 2). There was increased mitotic activity and infiltration into the renal tissue and capsule with central hemorrhage and areas of necrosis (Fig. 3). With this histo-morphologic appearance, diagnosis of secondary Choriocarcinoma of the left kidney was made. Immunohistochemistry (IHC) was not done.

Fig. 2.

Metastatic choriocarcinoma in the left kidney: Malignant trophoblasts having marked cytologic atypia with abundant pale eosinophilic to clear cytoplasm with distinct cell membranes and surrounded by multinucleated syncytiotrophoblasts. (Hematoxylin & eosin, 200×).

Fig. 3.

Infiltration into the renal tissue with central hemorrhage and areas of necrosis.

After 04 weeks, during her follow up, patient had abdomino-pelvic CT scan which showed right renal lower pole 6.3 cm by 3.7 cm heterogeneously enhancing mass which is most likely metastasis (Fig. 4). Brain CT scan also showed 3.1 cm by 2.18 cm by 2.7 cm left Parieto-Occipital peripheral cortical based heterogeneously enhancing mass (Fig. 5). Chest CT scan didn't reveal any sign of metastasis. Serum quantitative beta-hCG was done and came back 984 IU/l. Patient was then transferred to oncology department for Methothrexate based chemotherapy. She received 06 cycles of EMA/CO regimen. The serum beta-hCG dropped to 15 IU/l after the 04th cycle. After 01 year of follow up the serum beta-hCG was undetectable.

Fig. 4.

Post Contrast CT – scan of the abdomen showing right renal heterogeneously enhancing lower pole metastasis. Empty left renal fossa.

Fig. 5.

Post Contrast CT – scan of the Brain showing left Parieto-Occipital heterogeneously enhancing mass with surrounding edema.

3. Discussion

Choriocarcinoma can be gestational or non-gestational. Gestational choriocarcinoma is a malignant form of gestational trophoblastic neoplasia (GTN), and it commonly originates from the uterus [8]. It is common in women of the age group 40–59, and it is rare in post-menopausal women [9]. Our patient is younger than the commonly described age group.

Non-gestational choriocarcinoma is usually derived from germ cells of the gonads or, rarely, from extragonadal germ cells. Prognosis and sensitivity to chemotherapy is determined by whether the tumor has a gestational or non-gestational origin. These two cannot be differentiated based on the histological, immunohistochemical, or clinical manifestations. DNA analysis is critical to determining the origin of the tumor. Identifying paternal Y chromosome in the tumor cells indicates to gestational choriocarcinoma [10].

Gestational Choriocarcinoma is preceded by a molar pregnancy, miscarriage or term pregnancy in 60 %, 23 % and 10 % of the time, respectively. It can be a primary disease in 5 % of cases [3]. Choriocarcinoma co-existing with a normal intrauterine pregnancy is rare. Our patient has a history of molar pregnancy and abortion 02 years back, which is a risk factor.

About 30 % of the patients have distant metastasis upon presentation [11]. Metastasis is commonly to the Lung, Vagina, and Brain in 50 %, 30 %, and 10 % of cases, respectively. Renal, liver, spleen, intestine, and lymph nodes metastasis are less common [4,12]. Our patient had bilateral renal and brain metastasis.

Renal metastasis is usually identified incidentally during imaging of patients with choriocarcinoma. Other patients present with abdominal pain, hematuria or oliguria. Massive retroperitoneal hemorrhage due to tumor rupture of the renal parenchyma occurs even rarely [[12], [13], [14]]. The hemorrhagic tendency appears to be related to its tendency to invade blood vessels, its rapid rate of proliferation and its vascularity [15,16]. Renal metastasis is almost always preceded by lung metastasis. Overall renal involvement is estimated to range from 7 % to 50 % based on a few large series of terminal patients and on autopsy statistics [5,17,18]. CT scan is commonly used for detecting the metastasis but MRI with IV contrast is superior in detecting metastatic sites [19]. Initial presentation from renal metastasis is uncommon and it is usually misdiagnosed as renal cell carcinoma [2].

The most common presenting symptom of choriocarcinoma is gynecologic manifestations, mainly vaginal bleeding. Sometimes, the primary uterine tumor undergoes spontaneous necrosis or complete regression and the patient presents with extra-uterine manifestations in the later period due to metastasis [1]. Overall, about one third of the patients present with non-gynecological manifestations as a result of metastases. Our patient had no history of gynecologic complaints.

Histologically these tumors show diffusely infiltrative or clusters of trimorphic malignant trophoblasts with marked central hemorrhage and necrosis. Marked cytologic atypia and numerous mitotic figures are also seen. Syncytiotrophoblasts are strongly immunoreactive for hCG and weakly immunoreactive for human placental lactogen. All trophoblastic cell types are strongly immunoreactive for Cytokeratin.

The FIGO classification system is used for staging, planning treatment and to assess prognosis. Based on the FIGO anatomical staging our patient is classified as Stage 4 with distant metastasis. Based on the FIGO modified WHO prognostic scoring system our patient has a score of 9 (greater than 7) which is evidenced by the fact our patient is less than the age of 40 years, had an antecedent pregnancy which ended in abortion, the interval between the pregnancy and the treatment given is more than 13 months, metastasis to the kidney with the largest size of metastasis being more than 5 cm and pretreatment beta-hCG is less than 1000 IU/L. Thus, the patient is classified under high risk and required a more intense treatment with multi-drug regimen [20].

Even accompanied by multiple metastases, choriocarcinoma is extremely chemosensitive and the possibility of cure remains high [12]. Cure rates of 80–90 % may be achieved when combined with adjuvant radiotherapy or surgery [1]. The options of treatment for high-risk gestational trophoblastic neoplasia with multi-agent chemotherapy include MAC (Methotrexate, Actinomycin D, Cyclophosphamide or Clorambucile) or CHAMOMA (Hydroxyurea, Actinomycin D, Methotrexate, Folinic acid, Cytoxan, Vincristine, and Adriamycin). More recently, EMA/CO (Etoposide, Methotrexate, Actinomycin D, Cyclophosphamide, Vincristine) regimen has shown increased survival rate [21]. Our patient received the EMA/CO regimen and responded very well.

Surgical interventions might be needed in case of chemotherapy-resistant gestational trophoblastic neoplasia or to control hemorrhage. These procedures include hysterectomy and pulmonary resection of metastatic foci. For renal involvement, the surgical intervention can be angioembolization for actively bleeding tumor followed by chemotherapy or radical nephrectomy as a definitive treatment [8].

4. Conclusion

Choriocarcinoma can uncommonly metastasize to the kidney and even more rarely can be the first presenting symptom. A history of previous pregnancy or abortion should be sought in any young female in her reproductive age group when presenting with vague clinical picture associated with renal mass or spontaneous renal hemorrhage.

Patient (parent's) consent

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Ethical approval

Ethical approval was provided by the author's institution.

Source of funding

N/A

Research registry

N/A

Guarantor

Andualem Deneke Beyene (MD, MSc, FCS (ECSA), Professor of Urology).

Declaration of competing interest

No competing financial interests exist.