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|Year : 2012 | Volume
| Issue : 1 | Page : 90-93
Atypical presentation of pediatric mixed germ cell tumors in the sellar-suprasellar region
Sunil V Furtado1, Sumit Thakar1, Nandita Ghosal2, Alangar S Hegde1
1 Department of Neurosurgery, Sri Sathya Sai Institute of Higher Medical Sciences, Bangalore, India
2 Department of Pathology, Sri Sathya Sai Institute of Higher Medical Sciences, Bangalore, India
|Date of Submission||22-Sep-2011|
|Date of Decision||13-Oct-2011|
|Date of Acceptance||22-Nov-2011|
|Date of Web Publication||7-Mar-2012|
Sunil V Furtado
Department of Neurosurgery, SSSIHMS, EPIP Area, Whitefield, Bangalore - 560 066
Source of Support: None, Conflict of Interest: None
Intracranial germ cell tumors constitute a unique group of tumors, more often reported from the Asian region. Amongst them, the non-germinomatous variety occurs with a lesser frequency than the germinomatous variety. We report two children with mixed germ cell tumors with unusual clinical presentations: Central diabetes insipidus and recent-onset oculomotor palsy mimicking pituitary apoplexy. Unlike in adults, suprasellar lesions with a pituitary apoplexy-like picture in the pediatric age group may suggest a possibility of a mixed germ cell tumor.
Keywords: Diabetes insipidus, non-germinomatous germ cell tumor, oculomotor nerve, panhypopituitarism, pituitary apoplexy
|How to cite this article:|
Furtado SV, Thakar S, Ghosal N, Hegde AS. Atypical presentation of pediatric mixed germ cell tumors in the sellar-suprasellar region. Neurol India 2012;60:90-3
|How to cite this URL:|
Furtado SV, Thakar S, Ghosal N, Hegde AS. Atypical presentation of pediatric mixed germ cell tumors in the sellar-suprasellar region. Neurol India [serial online] 2012 [cited 2020 Feb 22];60:90-3. Available from: http://www.neurologyindia.com/text.asp?2012/60/1/90/93611
| » Introduction|| |
Intracranial germ cell tumors (GCTs) account for 0.5-11% and 15% of intracranial neoplasms in adults and children respectively and have been reported more frequently from Asia, particularly in Japan and Korea. , Their common location is in pineal and suprasellar regions, and they are classified into germinomatous (germinoma 65%) and non-germinomatous groups.  Non-germinomatous tumors include teratomas (18%), endodermal sinus tumors (7%), embryonal carcinomas (5%), and choriocarcinomas (5%).  The parasellar extension and rapid growth can rarely mimic pituitary apoplexy.
| » Case Reports|| |
A 13-year-old short-statured boy presented with polyuria, polydypsia and nocturia of six months' duration, headache and diplopia since two weeks and progressive drowsiness and bilateral ptosis for a week prior to admission. Neurological examination revealed a Glasgow Coma Scale (GCS) score of 14/15, bilateral primary optic atrophy, impaired visual acuity and left complete and right partial oculomotor nerve palsy. Computed tomography (CT) brain scan showed a 4 × 2.5 × 2 cm iso-to-hyperdense lesion in the sellar region with suprasellar extension [Figure 1]a. Magnetic resonance imaging (MRI) showed extension of the lesion to the cavernous sinus bilaterally and had iso-to-hyper intensities on T1-weighted images (WI) and mixed iso-to-hypo intensities on T2WI with homogenous contrast enhancement [Figure 1]b-d. At an emergent surgery via a right pterional craniotomy, a sizable suprasellar portion of the firm, rubbery, red vascular tumor compressing the optic apparatus was decompressed [Figure 2].
|Figure 1: Case 1 imaging showing: (a) a hyperdense suprasellar lesion on plain CT scan (b) iso-to-hypointense on T2WI MR images (c) isointense with a few hyperintense areas (arrow) on T1WI (d) bright contrast enhancement and left parasellar extension seen on axial contrast images|
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|Figure 2: Case 1 imaging showing (a) bilateral cavernous sinus extension and suprasellar extension on coronal contrast images (b) pre and (c) postoperative sagittal images|
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An 11-year-old girl presented with headache and vomiting of two weeks' duration and right-sided ptosis since three days. On examination her GCS was 13/15, she had bilateral primary optic atrophy and complete right third nerve palsy. MRI revealed a sellar/suprasellar lesion extending to the right cavernous sinus and interpeduncular fossa. The lesion had mixed intensities on T1WI, and intense contrast enhancement [Figure 3]. With a working diagnosis of suspected pituitary apoplexy with panhypopituitarism [Table 1], she underwent an emergent craniotomy and decompression of the lesion. The firm, grey and vascular tumor was sub-totally decompressed in view of its cavernous sinus extension. Her sensorium remained status quo in the postoperative period. She was referred for chemotherapy and radiotherapy.
|Figure 3: Case 2 imaging, (a) axial T1WI showing areas of hyperintensities within the lesion (arrow), (b) axial, (c) coronal and (d) sagittal contrast images show the lesion extending into the interpeduncular region and right cavernous sinus|
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Histopathology in the first patient demonstrated a prominent embryonal cell carcinoma component, with syncytiotrophoblastic cells and a poorly formed Schiller-Duval Body [Figure 4]. There was a predominance of large cells, arranged in a pseudopapillary and acinar configuration with occasional gland formation with coarse chromatin, prominent nucleoli, brisk mitotic activity and areas of necrosis [Figure 4]b and d. On immunohistochemistry, the tumor demonstrated focal positivity for CD30 and synaptophysin, and negativity for epithelial membrane antigen and CD20. The morphology in certain areas resembled an ependymal canal. However, immunonegativity with glial fibrillary acidic protein (GFAP) and positivity for cytokeratin (CK) rendered it a picture of gland formation [Figure 4]d. Alpha fetoprotein (AFP) immunostaining was not performed. Case 2 additionally had a prominent lymphocytic infiltrate. Raised serum AFP and beta-human chorionic gonadotropin (beta-HCG) levels obtained postoperatively corroborated the diagnosis of a mixed germ cell tumor in both the patients [Table 1].
|Figure 4: Paraffin section showing (a) tumor islands separated by spindle cells and (inset) glands with mucin lined by columnar epithelium (straight arrow), (b) large cells with coarse chromatin, prominent nucleoli, brisk mitotic activity in a pseudopapillary and acinar configuration (*), syncytiotrophoblastic cells (curved arrow) along with (inset) strong immunopositivity for CD30, [c] a poorly-formed Schiller-Duval body, [d] gland formation (curved arrow) surrounded by spindle cells with (inset) immunopositivity for CK [H and E: (a) ×100; (inset-a)(b)(c)(d) ×400][avidin biotin complex immunoperoxidase (inset b and d) ×400]|
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Hormonal evaluation revealed panhypopituitarism in both patients [Table 1], and they were accordingly started on appropriate replacements prior to surgery. Intranasal and oral desmopressin acetate (Minirin® ) was administered for diabetes insipidus. CT scan of the chest, abdomen, pelvis, and ultrasound of the scrotum did not show any primary or metastatic lesion. The pineal region was free of tumor on MRI in both cases. The first patient was referred to an oncology centre where cranial radiotherapy along with cisplatin 120 mg/m 2 , etoposide (100 mg/m 2 ), and ifosfamide (1800 mg/m 2 ) were administered. He developed recurrent disease seven months after completion of adjuvant therapy. However, the size and extent of the recurrent tumor precluded re-exploratory surgery, and he succumbed to his illness. The second patient was lost to follow-up.
| » Discussion|| |
Suprasellar tumors in the pediatric age group are distinct from their counterparts in adults as far as their pathology is concerned. Unlike in adults, with preponderance for pituitary adenomas and meningiomas, lesions in children commonly prove to be craniopharyngiomas, optic pathway gliomas and germinomas. Germinomas represent less than 1% of all intracranial neoplasms, of which mixed GCTs comprise 5-8%.  These tumors originate mainly in the pineal region and less commonly in the suprasellar or interpeduncular regions and third ventricle. In relation to suprasellar lesions, a classical triad, diabetes insipidus (DI), pan-hypopituitarism and visual disturbances has been described. Though most suprasellar GCTs conform to these findings, a few reports of mixed GCTs presenting with oculomotor or abducens palsy have been reported. ,,, Our report adds two more cases to such unusual clinical presentation.
Radiologically, GCTs are characteristically iso-to-hypointense on T1-weighted MR images, iso-to hyperintense on T2-weighted images, and enhance intensely with Gadolinium. In a series of 32 cases of GCTs, hyperintensities on T1-weighted images were seen in two cases of mixed GCTs with hemorrhage, one with fat content and three with cysts having high protein content. , Ectopic deposits and metastasis may be found anywhere in the ventricular system, a phenomenon that is not seen in any of the close differentials of a GCT.
Other pediatric suprasellar lesions can be differentiated clinico-radiologically from GCTs. The commonest pediatric sellar-suprasellar region tumor, craniopharyngioma presents with features of raised intracranial pressure (ICP), endocrine or visual disturbances. Unlike GCTs, craniopharyngiomas are often cystic masses with solid components and calcifications. Optic pathway/chiasmatic gliomas comprise 4-8% of childhood intracranial tumors. Presentation includes painless proptosis, variable degree of visual impairment, precocious puberty and diencephalic syndrome. These tumors are usually isointense to hypointense on T1-weighted images, heterogeneous on T2-weighted images, and demonstrate intense contrast enhancement. A predominance of orbital or visual symptoms and the consistent finding of hypointensity in relation to orbital fat distinguish these tumors from GCTs. Pituitary adenomas, constituting 2.7% of supratentorial tumors in childhood, are commonly functional in this age group. Pituitary dysfunction occurs to a variable degree, while the occurrence of visual symptoms and apoplexy is uncommon. On MRI, these tumors are usually hypointense to isointense on T1-weighted images and range from isointense to hyperintense on T2-weighted images. Microadenomas appear as hypo-enhancing foci on rapid-sequence contrast-enhanced T1-weighted images, while macroadenomas show a heterogeneous enhancement pattern, unlike the intense enhancement of GCTs. , Less common lesions include suprasellar arachnoid cysts (ACs), Rathke cleft cysts (RCCs) and hypothalamic hamartomas (HHs). While the ACs and RCCs may present with visual symptoms, hydrocephalus or endocrinopathies, the HHs are associated with clinically distinct features like hyperactivity syndrome, gelastic seizures, autonomic dysfunction, somnolence or precocious puberty. Imaging-wise, the cystic nature of ACs and RCCs, and the hypothalamic location of the HHs and their lack of significant enhancement are factors that help distinguish them from a GCT. 
The treatment of mixed GCTs includes a combination of chemotherapy and radiotherapy.  Serum and cerebrospinal fluid (CSF), AFP and beta-HCG levels as tumor markers can substantiate diagnosis and prognosticate response to adjuvant therapy. ,, The levels of both these markers are elevated in mixed GCTs [Table 1] and at times in embryonal carcinomas. , High AFP and beta-HCG levels in the serum or CSF would have clinched the diagnosis preoperatively in our patients. However, a working diagnosis of pituitary apoplexy necessitated an emergent surgical intervention in both our cases. The results of these serum and CSF markers could, hence, be obtained only after surgery.
The survival of patients with mixed tumors is dependent on the malignant component of the tumor, with a three-year survival rate between 9-94%. ,, Matsutani reported a poor three-year survival rate for "pure" malignant GCTs of 27.3%; the one-year survival rate was 0% for choriocarcinoma, 33.3% for yolk sac tumor, and 80% for embryonal carcinoma patients who had received chemotherapy and radiotherapy following surgery. The mixed germ cell tumor group of 39 patients consisted of patients with germinoma and teratoma, mixed tumors combined with a small portion of pure malignant tumors, or mixed tumors mainly consisting of pure malignant elements. The three- and five-year survival rates were 94.1% and 84.7% for the first group, 70% and 52.5% for the second, and 9.3% and 9.3% for the third group. 
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]