The management of metastatic hepatic germ cell tumour in a young woman: case report and literature review

Abstract

Germ cell tumours (GCTs) have an excellent prognosis but rarely arise from the liver. Our case describes a young woman referred for urgent radiotherapy for a bone metastasis. There was also a large lesion in the liver and marked elevation of the serum α-fetoprotein (AFP) level. Liver biopsy indicated a germ cell tumour. Reduced intensity chemotherapy was commenced using the combination of etoposide, cisplatin and paclitaxel. After four cycles the AFP values had fallen, the liver function tests had normalised and the previous bone lesions had healed. The predominant lesion in the liver had also regressed. Hepatocellular carcinoma (HCC) is the main differential diagnosis. Hepatic germ cell tumours predominantly occur in young, healthy women whereas hepatocellular carcinoma occurs in cirrhotic male livers. These two malignancies are very different and accurate diagnosis is essential. Diagnosing this rare condition early allows the delivery of effective therapy and a better outcome.

BACKGROUND

We would like to highlight an important case that demonstrates the importance of early diagnosis in hepatic germ cell tumours. Germ cell tumours (GCTs) are a group of rare malignancies that generally have an excellent prognosis. The majority of GCTs arise in the testes or ovaries and with modern chemotherapy cure rates of more than 85% can be expected in patients with metastatic disease.¹ A small number of GCTs arise at extragonadal sites, most commonly the pineal gland, the mediastinum, the retroperitoneum and the sacrococcygeal region. Tumours occurring at these sites, while frequently curable, have lower overall survival rates.² Rarely, germ cell tumours arising from the liver have been described but with less than 20 cases in the literature to date. For hepatic GCTs, successful treatment of organ confined disease has been recorded,^3,4 but the scale of potential benefit from chemotherapy in advanced disease is at present less certain.^5,6

We feel that this would be of interest to clinicians specialising in the fields of oncology and hepatology. There is little literature available to guide treatment and by writing and publishing our case we would like to expand the evidence base and therefore hope that future cases can be managed more effectively having learnt from our experience.

CASE PRESENTATION

A young woman was referred for urgent radiotherapy for impending neurological impairment from a bone metastasis at L4. She had previously presented to the cardiology team with a history of abdominal discomfort and increasing shortness of breath. The initial investigations had indicated a large lesion in the left lobe of the liver along with a number of other smaller hepatic lesions, bone metastases in the spine and humerus, abnormal liver function tests and marked elevation of the serum α-fetoprotein (AFP) level. Otherwise, her medical history was unremarkable and she had been in good health, working as a full time allied medical professional in a local hospital.

On examination the patient was haemodynamically stable but had obvious abdominal distension with ascites, bilateral pleural effusions and hepatosplenomegaly. Assessment of the neurological system confirmed parasthesiae and weakness in the left leg, general hyporeflexia and weakened plantar reflexes.

INVESTIGATIONS

Laboratory analysis demonstrated a normal full blood count, mildly impaired renal function but highly abnormal liver function tests with elevated alkaline phosphatase (1019 IU/litre), alanine transaminase (41 IU/litre), bilirubin (83 uM/litre) and low albumin (23 g/litre). The AFP level was grossly elevated at 841318 ng/ml while the β-human chorionic gonadotropin (hCG) level was within the normal range.

Updated imaging investigations confirmed the presence of bilateral pleural effusions, mediastinal lymphadenopathy and multiple small volume pulmonary nodules. There were large volume ascites and a large mass in the left lobe of the liver and a number of smaller lesions in the right lobe, as shown in fig 1. A plain x ray of the right humerus revealed a large lytic lesion, which was confirmed on a bone scan. An MRI scan of the spine noted a pathological fracture and soft tissue mass at L4, but without compression of the cauda equina. Of note the imaging of the pelvis by MRI and by ultrasound did not show any abnormalities in the ovaries.

Figure 1.

CT of the abdomen showing ascites and multiple liver lesions.

The ascitic fluid cytology did not show any evidence of malignancy; however a liver biopsy indicated malignant cells consistent with a germ cell tumour.

DIFFERENTIAL DIAGNOSIS

Hepatocellular carcinoma (HCC) is the main differential diagnosis.

TREATMENT

The combination of worsening neurological damage and increasing respiratory distress mandated urgent chemotherapy treatment. As a result of the difficult clinical situation reduced intensity chemotherapy was commenced using the combination of etoposide (100 mg/m² D1 and D2) and cisplatin (20 mg/m² D1 and D2), which aimed to produce significant tumour shrinkage, but without causing extensive treatment related toxicity or fluid shifts in an acutely ill patient. Over the next 3 weeks two further doses of this relatively gentle treatment were administered and the serum AFP level fell from 900 000 to 330 000 ng/ml. With treatment the patient’s condition improved significantly, allowing removal of the ascetic drain, discontinuation of respiratory support and mobilisation around the ward. After 6 weeks in hospital she was sufficiently well to be discharged for outpatient-based care.

OUTCOME AND FOLLOW-UP

Chemotherapy treatment was continued using the paclitaxel-based doublet therapy that has previously been documented to have efficacy and good tolerability in gestational tumours and relapsed germ cell tumours.^7,8 This treatment, with carboplatin (area under the concentration versus time curve (AUC)5) substituted for cisplatin, was well tolerated and after four cycles the AFP values as shown in fig 2 had fallen to stable levels between 50 000 and 60 000 ng/ml, the liver function tests had returned to normal and the previous bone lesions had healed. The predominant lesion in the liver had also significantly regressed as seen in fig 3.

Figure 2.

Trend in α-fetoprotein (AFP) following treatment.

Figure 3.

CT of the abdomen demonstrating regression of liver lesions after treatment.

At this point a full discussion was held regarding the potential curability of this illness and the treatment path forward. Unfortunately, despite the benefits from treatment and the 90% fall in the tumour marker, patients displaying chemotherapy resistance on adequate first line treatment are very unlikely to be cured by further therapy.⁹ Treatment was discontinued and the patient managed symptomatically and, despite a significant climb in the AFP level, remained symptom free with no reaccumulation of the ascites for 4 months. Unfortunately shortly after this point the ascites returned and despite further chemotherapy given with palliative intent the patient died from her illness approximately 15 months after the original presentation.

DISCUSSION

With the introduction of curative platinum based chemotherapy for advanced germ cell tumours in the 1970s, advanced germ cell tumours arising in the testes or ovaries are now routinely curable in the majority of patients. The prognosis for the more rare extragonadal germ cell tumours is also positive, although the overall cure rates are lower.^1,2

Germ cell tumours arising in the liver are extremely rare and were only first reported in 1975.¹⁰ Since then, less than 20 cases have been described in the literature, and the most extensive experience has been summarised in 2 recent case reports and literature reviews.^4,6 Both series reported that hepatic germ cell tumours predominantly occur in young women, with cystic liver tumours and AFP values ranging from 413 ng/ml to 330 000 KU/litre at presentation. The characteristics of this young patient with an AFP value of 841 318 ng/ml at diagnosis fit well with those previously described.

The presence of a hepatic AFP producing tumour has HCC as the differential diagnosis. However the characteristic findings of HCC, occurring mainly in men as a non-cystic tumour in a cirrhotic liver with AFP levels generally less than 3000 ng/ml, contrasts with the findings in hepatic germ cell tumours that are predominantly recorded in young women with otherwise healthy livers and very high AFP levels.⁴ As these two different malignancies have very different management courses and outcomes, accurate diagnosis prior to the commencement of therapy is essential.

The management of patients with organ confined disease appears to have the potential for cure with the combination of cisplatin-based combination chemotherapy followed by surgery resulting in the apparent cure of two patients.^3,4 For patients with conventional disseminated extragonadal germ cell tumours, chemotherapy is the mainstay of treatment.² Previous analyses of GCT treatment outcomes indicate that the extragonadal origin, hepatic involvement and an elevated AFP values in excess of 10 000 ng/ml are each sufficient to place patients in the poor prognosis group, which has significantly inferior outcomes. Patients with hepatic germ cell tumours will have each of these adverse factors and in this case the difficulty delivering optimal treatment was compounded by marked, hepatic, renal and respiratory function that precluded the administration of full intensity chemotherapy treatment from the first 2–3 months.

Despite these factors, treatment was delivered safely, symptoms controlled and survival extended for over 12 months. In the management of future cases the diagnosis of this rare condition prior to the development of significant organ impairment may allow the delivery of more effective therapy and a more successful outcome.

LEARNING POINTS

• Germ cell tumours arising in ovaries and testes are potentially curable even in advanced, organ-confined disease.

• Early and accurate diagnosis allows a better outcome.

• In a young woman with a raised α-fetoprotein levels, consider hepatic germ cell tumour as well.