Primary human chorionic gonadotropin secreting germinoma of the corpus callosum
A 15-year-old Malay boy with no significant past medical history was referred to our institution with a 2-month history of intermittent fever, recurrent headaches, vomiting, significant weight loss, and deterioration in school performance. He did not have any significant drug, family, or developmental history.\nOn examination, he was found to be disorientated to time, place, and person. He also demonstrated terminal past-pointing bilaterally and left-sided dysdiadochokinesia.\nInitial blood investigations revealed a white blood cell count of 6.92×109/L and a C-reactive protein level of <5.0 mg/L. Serum alphafetoprotein (AFP) and human chorionic gonadotropin (b-HCG) were not elevated. Other abnormal serum biochemical parameters included free thyroxine (FT4) of 9.4 pmol/L, thyroid stimulating hormone (TSH) of 3.92 mIU/L, follicular stimulating hormone of <0.1 IU/L, luteinizing hormone of <0.07 IU/L, sodium of 155 mmol/L and serum osmolality of 323 mOSm/kg. Cerebrospinal fluid (CSF) AFP levels were normal but CSF b-HCG levels, however, were markedly elevated at 1837.01 IU/L. Contrasted computer tomographic (CT) imaging revealed a heterogenous 4 cm mass centered in the genu of the corpus callosum, filling the anterior aspect of the third ventricle and spreading along the margins of both frontal horns, causing obstruction of the Foramina of Monro and hydrocephalus. Thickening and enhancement was also noted along the margins of both lateral ventricles and a 1.3×0.9 cm enhancing nodule visualised in the 4th ventricle []. Further workup also revealed that the patient was suffering from central diabetes insipidus as well as panhypopituitarism. After neurosurgical team review, the diagnosis of GCT with extensive intraventricular CSF seeding was considered. Subsequent magnetic resonance imaging (MRI) brain reported multiple intraventricular contiguous and noncontiguous cystic masses with extension superiorly into the frontal horns, the genu of the corpus callosum and the septum pellucidum, inferiorly into the suprasellar region, as well as laterally into the right temporal horn []. Small cystic foci were also noted in the vicinity of the pineal gland. MRI attempted at this juncture was not augmented with contrasted medium due to acute kidney injury from excessive diuresis precipitated by central diabetes insipidus. No spinal drop metastases were visualized on MRI.\nThe patient underwent open craniotomy and biopsy of the intraventricular portion of the tumor. Histology revealed a germinoma composed of sheets of large primitive cells with round nuclei bearing prominent nucleoli, and ample clear cytoplasm with discrete cell membranes, interrupted by fibrous septa containing smaller reactive lymphocytes []. Immunohistochemical staining showed positive reactivity for CD117 (c-kit) and placental alkaline phosphatase, confirming the diagnosis of germinoma. Although CSF b-HCG was found to be elevated at 1837.01 IU/L, immunohistochemical staining for the same was negative.\nThe patient underwent four cycles of carboplatin, etoposide, and ifosfamide as per International Society of Pediatric Oncology Central Nervous System Germ Cell Tumor (SIOP CNS GCT) 96 protocol and subsequent craniospinal irradiation (CSI) of 54 Gray (Gy) in 32 fractions, which he tolerated well. Radiologically, his lesions remained stable despite completing treatment [] but he demonstrated good biochemical response with CSF b-HCG falling from 1837.01 IU/L to less than 2.0 IU/L. The patient had to be on permanent hormonal replacement therapy for panhypopituitarism. His last CSF b-HCG reading taken 12 months after completion of treatment remains stable at <1.2 IU/L and most recent MRI brain done 15 months after completion of treatment shows no evidence of recurrence.