Intracranial Germinoma Masquerading as Secondary Granulomatous Hypophysitis: A Case Report and Review of Literature

Abstract

Germinomas are highly immunogenic tumors eliciting a strong peri-tumoral immune response that can spillover into the surrounding healthy tissues. This phenomenon can also occur in intracranial germinomas, manifesting as secondary hypophysitis. Herein, we report a case of 12-year-old-girl presenting with polyuria and polydispsia. She had central diabetes insipidus (CDI) and panhypopituitarism. Imaging revealed a sellar-suprasellar mass with infundibular stalk thickening. Transphenoidal biopsy revealed epithelioid granulomas with immunostaining negative for germinomatous cells. Other causes of hypophysitis were ruled out. Accordingly, she was diagnosed as primary granulomatous hypophysitis and treated with high-dose corticosteroids. Three years later she again presented with headache, vomiting and diminution of vision. Imaging showed a heterogeneous, solid-cystic peripheral rim-enhancing lesion at the same location with involvement of hypothalamus, ependyma and pineal gland. Cerebrospinal fluid beta-human chorionic gonadotropin was markedly elevated, confirming the diagnosis of an intracranial germ cell tumor. She was started on chemotherapy; however, she succumbed to febrile neutropenia. We performed a literature search and found 18 anecdotal cases of secondary hypophysitis associated with intracranial germinomas. There was a slight male preponderance (male:female 5:4). Two-thirds of the cases were below 18 years of age. Polyuria was the most common presenting manifestation (83%). CDI and panhypopituitarism were seen in 89 and 78% cases, respectively. Imaging evidence of pituitary stalk thickening was seen in 12 cases (67%), while pituitary enlargement and/or sellar mass were reported in 11 cases (61%). Pineal involvement was extremely rare, being reported in only 1 case, implying the predilection of suprasellar (rather than pineal) germinomas in causing secondary hypophysitis. Histologically, 82% had lymphocytic hypophysitis, while 18% had granulomatous hypophysitis. Initially, the diagnosis of germinoma was missed in 60% of the cases who were wrongly treated with corticosteroids. To conclude, physicians should make it a dictum that all children and adolescents presenting with CDI and pituitary stalk thickening should be rigorously screened for an underlying intracranial germinoma before labeling them as primary hypophysitis.

Sellar germinoma mimicking IgG4-related hypophysitis: a case report

“…In other types of secondary hypophysitis caused by pituitary adenoma, Rathke cyst or craniopharyngioma, infiltration of IgG4-positive cells was also observed [ 13 ]. The exposure of autoantigens may also present in germinoma, which was hypothesized to be the reason for florid lymphocyte infiltration in part of germinoma cases [ 18 , 27 ]. However, no previous case of IgG4 reaction in germinoma was reported, and the current case may be the first such case.…”

“…The most common type of intracranial GCTs is germinoma, which accounts for about 70% of the cases [ 12 , 17 ]. Germinoma is so immunogenic that the tumor tissue could be infiltrated by numerous lymphocytes or plasma cells, which makes it difficult to be differentiated from hypophysitis on some occasions [ 10 , 18 , 19 ].…”

Molecular and Genetic Immune Biomarkers of Primary and Immune-Therapy Induced Hypophysitis: From Laboratories to the Clinical Practice

“…In fact, PAH is rare in the pediatric population, as the mean age at the onset of the disease is 34.5 years for women and 44.7 years for men [ 56 ]. Instead, intracranial germinoma are diagnosed in around two-thirds of cases below 18 years of age, highlighting the preponderance of this disease in the first two decades of life [ 57 ]. Similarly, Langerhans cell histiocytosis is more frequently encountered in children aged 0–15 years, with an estimated annual incidence of up to 8.9 cases per million in children younger than 15 years and a male-to-female ratio of 2:1 [ 58 ].…”

Pengelolaan Diabetes Insipidus dengan Cerebral Salt Wasting Syndrome dan Tension Pneumocephalus pada Pasien Pascabedah Eksisi Tumor Pineal

“…5 Tumor ini bersifat imunogenik dan menyebabkan respons imun yang kuat di sekitar tumor yang dapat mempengaruhi jaringan sehat yang di sekitarnya dan menyebabkan manifestasi hipofisitis sekunder. 7 Hipofisitis merupakan kondisi yang jarang terjadi, ditandai dengan inflamasi pada kelenjar dan/atau batang hipofisis yang menyebabkan pembesaran hipofisis dengan atau tanpa hipopituitarisme.7 Selain itu, germinoma juga menyebabkan reaksi granulomatosa yang dapat pula menyebabkan terjadinya hipofisitis. 8 Kondisi DI ini berlanjut sampai pasca bedah dengan kadar natrium serum tertinggi 173 mEq/L dan produksi urine terbanyak 10,5 mL/kg/jam.…”