Pretreatment of choriocarcinoma syndrome: a rare complication of metastatic germ cell tumours

Background

Choriocarcinoma syndrome is an uncommon complication of testicular non-seminomatous germ cell tumour (GCT). They often present with spontaneous haemorrhage involving extragonadal metastatic sites in patients with high-volume choriocarcinoma elements, characterised by markedly elevated serum human chorionic gonadotropin (hCG) level of over 50 000 IU/L. Despite initially considered a feature of pure choriocarcinoma subtype, choriocarcinoma syndrome has now been encountered in other histological elements but with choriocarcinoma differentiation. When left untreated, it can be associated with rapid clinical deterioration that can result in significant morbidity and mortality.1–3

We present a case of choriocarcinoma syndrome in a young male patient with metastatic testicular non-seminomatous GCT with mixed yolk sac and choriocarcinoma features with spontaneous haemorrhage of perinephric and intracranial metastatic lesions presenting before and after commencement of chemotherapy, respectively, likely exacerbated by therapeutic anticoagulation for provoked venous thromboembolism identified at time of diagnosis.

Case presentation

A 27-year-old man was presented with painless right testicular mass of approximately 20 cm in diameter with no other symptoms. Scrotal ultrasound confirmed a right heteroechoic testicular mass with central cystic components (figure 1). His tumour markers were elevated with beta-human chorionic gonadotrophin (β-hCG) level of 119 000 IU/L (normal <2 IU/L), alpha-fetoprotein (AFP) of 2030 ug/L (normal <10 ug/L) and lactate dehydrogenase (LDH) of 916 U/L (normal 120–250 U/L). Due to suspicion of advanced germ cell tumour, a staging whole body CT scan was performed, which revealed metastatic disease with bilateral frontal lobe parenchymal lesions, multiple bilateral pulmonary lesions, several hypodense liver lesions with peripheral hypervascularity, right renal and pararenal metastatic nodules, as well as right-sided hydronephrosis with filling defect in the proximal ureter likely in the setting of prominent aortocaval lymphadenopathy (figure 2). In addition to the metastatic deposits, the CT also demonstrated bilateral iliac venous thrombosis and pulmonary embolism for which he was commenced on therapeutic anticoagulation with low molecular weight heparin.

Following multidisciplinary discussion and in view of his significant burden of metastatic disease, decisions for bedside percutaneous testicular biopsy for tissue diagnosis and urgent commencement of chemotherapy were made. The decision centred around concerns regarding his overall fitness for a radical inguinal orchidectomy, especially in setting of disseminated pulmonary disease, and the need for urgent tissue diagnosis. The testicular biopsy showed nests of tumour cells set among fibromyxoid stroma, with each tumour cells possessing modest quantities of focally vacuolated eosinophilic to amphophilic cytoplasm and large pleomorphic nuclei with abundant mitotic figures. Some evidence of syncytiotrophoblastic cells were also identified. Immunostains yielded AFP (+), hCG (+), CD30 (−), c-kit (+) and PLAP (+), which supported the diagnosis of non-seminomatous testicular GCT, with yolk sac tumour and choriocarcinoma differentiations (figure 3).

The following day he developed a sudden onset, sharp and severe abdominal pain localised in the epigastrium associated with nausea and tachycardia of up to 130 beats per minute. His other vital signs included blood pressure of 158/100 mm Hg, respiratory rate of 21 breaths per minute, oxygen saturation of 99% on room air and temperature of °36°C.

Investigations

His full blood examination showed progressive decline in haemoglobin from 126 g/L on day of admission to 70 g/L. A CT angiogram highlighted a new large right perinephric sub capsular fluid-filled haematoma measuring 13.8×8.9 x 21.3 cm causing anteromedial displacement of the respective kidney with significant compression of the renal parenchyma. There was also evidence of active bleeding from multiple points along the posterolateral aspect of the renal parenchyma (figure 4). His renal function remained within normal limits with eGFR of >90 mL/min/1.73m² and creatinine of 49 μmol/L.

Treatment

Following another multidisciplinary team review, a decision for urgent embolisation of bleeding vessels prior to the commencement of chemotherapy was made. Patient underwent selective embolisation of the multiple bleeding vessels supplying the mid and lower poles of the right kidney as well as the right L2 lumbar artery.

After the procedure, the patient continued to drop his haemoglobin levels, requiring ongoing blood transfusions. A repeat CT showed a relatively stable size of the right perinephric collection, now measuring 10.1×12.9×21.2 cm, but with mild increase in hyperdense component potentially suggesting interval bleeding (figure 4). The remaining right renal parenchyma showed markedly reduced enhancement with no contrast excretion into the collecting system. In view of the continued haemoglobin drop and the ongoing requirement for blood transfusions, a decision was made for main right renal artery embolisation after appropriate discussion with the patient and his family.

Outcome and follow-up

The patient made uneventful recovery. His haemoglobin levels stabilised and he did not require any further blood transfusions. The patient was then commenced on induction chemotherapy with etoposide and cisplatin. Due to his extent of pulmonary metastatic disease burden, bleomycin was omitted in an effort to reduce his risk of pulmonary complications. There were evident biochemical improvements following completion of the first cycle with β-hCG level of 47 800 IU/L (previous 119 000 IU/L, normal <2 IU/L), AFP of 250 ug/L (previous 2030 ug/L, normal <10 ug/L) and LDH of 773 U/L (previous 916 U/L, normal 120–250 U/L).

Two weeks after, the patient represented with left flank discomfort associated with bilateral lower limb pitting oedema. His investigations showed reduced kidney function with eGFR 23 mL/min/1.73m² and creatinine 310 μmol/L. A repeat CT demonstrated new left hydroureteronephrosis likely secondary to extrinsic compression from the known pelvic lymphadenopathy. He proceeded to have left ureteric stent insertion to good effect with resolution of his symptoms, improving renal function and hydronephrosis on follow-up imaging.

Nearly 2 months following his initial diagnosis and having completed two cycles of chemotherapy with the most recent cycle including bleomycin, etoposide and cisplatin (BEP), the patient was presented to the emergency department with severe generalised pain described as involving his whole body. This was associated with projectile vomiting, increasing lethargy, loss of appetite and chills. His vital signs remained within normal limits with heart rate of 60 beats per minute, blood pressure of 144/84 mm Hg, respiratory rate of 17 breaths per minute, oxygen saturation of 99% on room air and temperature of °36.4°C. Due to his non-specific symptoms and history, a repeat CT brain, chest, abdomen and pelvis was performed, which showed progression of right frontal cerebral metastasis complicated with acute intraparenchymal haematoma leading to mass effect with leftward mediastinal shift, subfalcine herniation and likely early right uncal transtentorial herniation (figure 4). Other findings included new frontal intra-axial lesion and multiple lytic lesions along his spine, likely representing further metastatic disease. His haemoglobin remained stable at 85 g/L and his renal function remained within normal limits with eGFR >90 mL/min/1.73m² and creatinine of 91 μmol/L. A right frontal craniotomy with resection of right frontal metastatic lesions were subsequently performed, following which he made an uneventful recovery without any neurological deficits. At the time of writing this case report, the patient completed the third cycle of chemotherapy with a plan for radiotherapy to his resected cerebral metastatic site after completion of the fourth cycle of BEP.