Medical Journal of Dr. D.Y. Patil Vidyapeeth

: 2015  |  Volume : 8  |  Issue : 3  |  Page : 407--410

Recurrent metastatic mixed germ cell tumor of central nervous system with additional seminomatous component

Shrijeet Chakraborti1, Hema Kini1, Santosh Rai2, Ashvini Kumar2,  
1 Department of Pathology, Kasturba Medical College, Mangalore, Karnataka, India
2 Department of Radiodiagnosis, Kasturba Medical College, Mangalore, Karnatak, India

Correspondence Address:
Shrijeet Chakraborti
Department of Pathology, Kasturba Medical College, Lighthouse Hill Road, Mangalore - 575 001, Karnataka


Mixed germ cell tumors (GCTs) are aggressive tumors owing to poor response to therapy, frequent recurrence and metastasis. We present here a case of 29-year-old male with recurrent metastatic mixed GCT in the left parietal lobe, with right testicular primary. Interestingly, the recurrent tumor exhibited a seminomatous component, in addition to yolk sac tumor and embryonal carcinoma. The patient was treated with surgery, cranial radiotherapy and cisplatin-based chemotherapy. The metastatic intracranial tumor recurred twice and the patient died 18 months after the first appearance of central nervous system metastasis.

How to cite this article:
Chakraborti S, Kini H, Rai S, Kumar A. Recurrent metastatic mixed germ cell tumor of central nervous system with additional seminomatous component.Med J DY Patil Univ 2015;8:407-410

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Chakraborti S, Kini H, Rai S, Kumar A. Recurrent metastatic mixed germ cell tumor of central nervous system with additional seminomatous component. Med J DY Patil Univ [serial online] 2015 [cited 2023 Dec 5 ];8:407-410
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Germ cell tumors (GCTs) account for 0.5% of primary intracranial tumors, of which approximately 3% occurs in childhood and adolescence. [1] Metastatic mixed GCTs in central nervous system (CNS) are very uncommon. [2],[3],[4],[5],[6],[7] This cases with recurrence of metastasis, which also exhibited an additional seminomatous component, apart from the yolk sac tumor and embryonal carcinoma. Definitive recognition of individual components of the mixed GCT is important as the prognosis and treatment depends on it.

 Case Report

A 29-years-old male patient presented with the right side hemiparesis and focal seizures. Magnetic resonance imaging (MRI) of the brain showed a 2.5 cm × 2 cm intra-axial lesion in the left high parietal region, which was predominantly hypointense on T1-weighted and hyperintense on T2-weighted sequences, with perilesional edema. The patient had a past history of radical inguinal orchidectomy with retroperitoneal lymph node dissection (operated elsewhere) for right testicular mass, 18 months ago. The histopathological examination of the right testicular mass revealed a nonseminomatous mixed GCT with yolk sac and embryonal carcinoma components and retroperitoneal lymph node metastasis. Serum α-fetoprotein and β-human chorionic gonadotropin (β-HCG) levels were not available. Postoperatively, he was treated with three cycles of bleomycin, etoposide and cisplatin.

At present, serum α-fetoprotein level was 405 IU/ml (reference range: 0-5.8 IU/ml) and β-HCG was 2.58 IU/ml (reference range: 0-10 IU/ml). Abdominal and chest computed tomogram did not reveal any metastatic lesions. A left occipito-parietal craniotomy and subtotal excision of the tumor was done. Histology showed grey matter infiltrated by a composite tumor comprised of reticular-microcystic pattern [Figure 1]a and b with Schiller-Duval bodies [Figure 1]c and inset. The tumor cells had round to oval nuclei with prominent nucleoli, and eosinophilic to vaculolated cytoplasm. Occasional hyaline globules [Figure 1]b inset, foci of necrosis, hemorrhage and brisk mitoses were noted. Another component of tumor exhibited medium to large-sized pleomorphic cells with round to oval nuclei, irregular nuclear membrane, fine to coarse chromatin and prominent nucleoli, arranged in solid sheets, tubular, nested and focal papillary pattern [Figure 1]d and f, with foci of necrosis [Figure 1]e. The tumor cells had moderate eosinophilic to amphophilic cytoplasm and indistinct cell borders and were immunopositive for CD30 [Figure 1]e inset. Occasional tumor giant cells, bizarre cells and numerous mitotic figures [Figure 1]f inset were seen. Hence, this composite tumor was diagnosed as metastatic nonseminomatous mixed GCT comprised of equal proportions of yolk sac tumor and embryonal carcinoma components. Postsurgery serum α-fetoprotein level was 182 IU/ml. Surgery was followed by cranial irradiation 54 Gy over 6 weeks and further chemotherapy with three cycles of bleomycin, etoposide and cisplatin.{Figure 1}

Six months later, the patient returned with sudden onset of right sided hemiparesis and right plantar extensor response. The serum α-fetoprotein level was 380 IU/ml. MRI of the brain showed a 3 cm × 2.8 cm intra-axial lesion in the left high parietal region, which was hypointense on T1 [Figure 2]a and hyperintense on T2-weighted sequences [Figure 2]b, with perilesional edema. The lesion had a central area, which was hyperintense on T1- and T2-weighted images, suggestive of intralesional bleed and also showed peripheral and central contrast enhancement [Figure 2]cwithout midline shift. The perilesional edema was better seen on the fluid attenuated inversion recovery sequence [Figure 2]d. Magnetic resonance spectroscopy showed decreased n-acetyl aspartate, high choline and lipid-lactate peaks, without any significant changes in the adjacent brain parenchyma. Left high parietal region extra-calvarial changes and fluid collection similar to cerebrospinal fluid signal intensity, were consistent with stigmata of previous surgery.{Figure 2}

Repeat left occipito-parietal craniotomy and gross total excision of the tumor was performed. Histopathologic examination showed a tumor with associated thickened meninges, gliomesenchymal scarring, calcification, lymphohistiocytic infiltrate [Figure 1]i, foreign-body giant cells, hemorrhage and fibrin, consistent with stigmata of repair after previous craniotomy and chemotherapy. The tumor exhibited similar histology of mixed GCT with embryonal carcinoma and yolk sac tumor components. However, on this occasion, a focus of seminomatous component (10% of the tumor mass) was also noted, consisting of large cells arranged in nested pattern, having round vesicular nuclei, prominent eosinophilic nucleoli and vacuolated cytoplasm. These tumor cells depicted membrane positivity for CD117 [Figure 1]h inset. The tumor cells were separated by fibrovascular septae having lymphocytic infiltrate [Figure 1]g and h positive for leukocyte common antigen [Figure 1]g inset. Immediate postoperative serum α-fetoprotein level was 115.2 IU/ml. Subsequently patient shifted to another referral center for further chemotherapy and radiotherapy, followed by recurrence and repeat surgery (details of which are not available) and later succumbed to his illness 18 months after first detection of brain metastasis.


Review of the literature shows that in the western world GCTs account for 0.5% of all primary intracranial tumors (approximately 3% in childhood and adolescence). [1] On the other hand, data from Taiwan and Japan data show that GCTs account for 2% of all primary intracranial tumors (up to 15% in the pediatric age group). [1] Primary CNS GCTs occur predominantly (80-90% cases) in males <25-years of age. [6] The sites of occurrence are neurohypophyseal axis, around 3 rd ventricle, pineal gland, intraventriclular, diffuse periventricular, basal ganglion, thalamus, cerebral hemispheres, cerebellum and intramedullary. [8]

Metastatic mixed GCTs to the brain can be both uni- or multifocal and are very uncommon with a few case report and studies in the literature. [2],[3],[4],[5],[6],[7] Recurrence of CNS metastasis of mixed GCT, as in the present case, in a rare occurrence.

Out of 190 patients with GCTs of testicular or extragonadal origin studied over a period of 30-years, five cases (2.6%) had CNS metastases, and median age was 30-years, [9] similar to the age of the patient in the present study. In 27 patients with brain metastases, 10 cases already had brain metastases at initial diagnosis, whereas remaining 17 cases developed brain metastases during treatment. Brain metastases of choriocarcinoma alone occurred in seven cases followed by two cases of teratoma, one case each of embryonal carcinoma and seminoma, and the rest of the 16 cases were mixed GCTs. [6]

Metastases containing other histologic tumor subtypes have been occasionally reported, as was the additional seminomatous focus in the recurrent metastatic CNS tumor, in the present case. A 19-years-old female had brain metastasis of only choriocarcinoma from a mixed GCT of the ovary, [10] and intracranial germinoma in a young male, with ventriculoperitoneal shunt, metastasized as intra-abdominal yolk sac tumor, have been documented. [11]

Chemotherapy in the treatment of GCTs of the CNS cannot be omitted, because many cases may have simultaneous metastases to other organs. High-dose chemotherapy is advocated to overcome blood brain barrier and ensure adequate CNS concentrations. The mode of radiotherapy, whether whole brain or stereotactic radiotherapy, doesn't affect the prognosis of patients. [7] Cisplatin-based chemotherapy in cases of brain metastases, at the time of diagnosis of mixed GCT, resulted in a 5-year survival rate of 45%. The 5-year cause specific survival rate for all patients with brain metastases after cisplatin-based chemotherapy was 12%, but was 39% in patients with an isolated brain recurrence. [12] Isolated CNS relapse in testicular nonseminomatous mixed GCT of the testis is most likely because of failure of cisplatin-based chemotherapy to reach the brain in concentrations high enough to eradicate any undetectable or clinically silent metastatic brain disease. [12] Surgery, whole brain radiotherapy and chemotherapy or various combinations of these is the treatment option in such cases. [13] In the above group of patients, Spears et al. recommended surgery for solitary lesions, followed by whole brain radiotherapy with 45-50 Gy in 25 fractions and cisplatin-based chemotherapy. [14]

The survival of cases of with synchronous CNS metastases tends to be better than that of metachronous metastases (difference was not statistically significant). The survival of patients with multiple brain metastases is however poorer than that of patients with an isolated CNS metastasis. [7] Patients with GCTs who present with brain metastases at diagnosis tend to do better than patients who develop them at relapse, [15] as was seen in the present case. Metastatic mixed GCTs have aggressive biological behavior and require multimodality treatment.


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