Objective: To investigate immunohistochemical patterns of CXorf67 and H3K27me3 proteins in central nervous system germ cell tumors (GCTs) and to assess their values in both diagnosis and differential diagnosis. Methods: A total of 370 cases of central nervous system GCTs were collected from 2013 to 2020 at Huashan Hospital of Fudan University, Shanghai, China. The expression of CXorf67, H3K27me3 and commonly-used GCT markers including OCT4, PLAP, CD117, D2-40, and CD30 by immunohistochemistry (EnVision method) was examined in different subtypes of central nervous system GCTs. The sensitivity and specificity of each marker were compared by contingency table and area under receiver operating characteristic (ROC) curve. Results: Of the 370 cases there were 282 males and 88 females with a mean age of 19 years and a median age of 17 years (range, 2-57 years). Among the GCTs with germinoma, the proportions of male patients and the patients with GCT located in sellar region were both higher than those of GCTs without germinoma (P<0.05), respectively. CXorf67 was present in the nuclei of germinoma and normal germ cells, but not in other subtypes of GCT. H3K27me3 was negative in germinoma, but positive in the nuclei of surrounding normal cells and GCTs other than germinoma. In the 283 GCTs with germinoma components, the expression rate of CXorf67 was 90.5% (256/283), but no cases were positive for H3K27me3. There was also an inverse correlation between them (r²=-0.831, P<0.01). The expression rates of PLAP, OCT4, CD117 and D2-40 were 81.2% (231/283), 89.4% (253/283), 73.9% (209/283) and 88.3% (250/283), respectively. In 63 mixed GCTs with germinoma components, the expression rate of CXorf67 was 84.1% (53/63), while all cases were negative for H3K27me3. The expression rates of PLAP, OCT4, CD117 and D2-40 were 79.4% (50/63), 79.4% (50/63), 66.7% (42/63) and 87.3% (55/63), respectively. The 6 markers with largest area under ROC curve in ranking order were H3K27me3, CXorf67, D2-40, OCT4, PLAP and CD117 (P<0.05). Conclusions: CXorf67 and H3K27me3 have high sensitivity and high specificity in diagnosing germinoma. There is a significant inverse correlation between them. Therefore, they can both be used as new specific immunohistochemical markers for the diagnosis of GCTs.
Adolescent ; Adult ; Brain Neoplasms/pathology* ; Central Nervous System/pathology* ; Central Nervous System Neoplasms/metabolism* ; Child ; Child, Preschool ; China ; Female ; Germinoma/pathology* ; Histones ; Humans ; Male ; Middle Aged ; Neoplasms, Germ Cell and Embryonal/diagnosis* ; Oncogene Proteins ; Transcription Factors/metabolism* ; Young Adult

We report a case of a 24-year-old Filipino male who complained of general weakness, polydipsia, weight loss, bitemporal headaches, loss of libido and behavioral changes. Endocrine work-up revealed neurogenic diabetes insipidus and panhypopituitarism. Brain MRI showed multiple intracranial tumors in the left frontal lobe, pineal and suprasellar region with moderate non-communicating hydrocephalus. Intracranial mass biopsy with ventriculo-peritoneal shunting was done. Histopathology of the mass and CSF revealed a germinoma. He underwent chemoradiotherapy while on maintenance hormone replacement.
Neoplasms, Germ Cell and Embryonal ; Germinoma ; Hypopituitarism ; Diabetes Insipidus

OBJECTIVE: To summarize and analyze the clinical characteristics of children with basal ganglia germinoma and to improve the level of early clinical diagnosis. METHODS: The clinical data of children diagnosed with basal ganglia germinoma admitted to the Pediatric Surgery Ward of Peking University First Hospital from January 2013 to December 2020 were retrospectively analyzed, and descriptive statistics were used to analyze the clinical characteristics of children with basal ganglia germinoma. RESULTS: A total of 30 patients were included in the study, 28 were male, 2 were female, the mean age at onset was (9.7±2.2) years, the median disease duration was 7 months, 27 had unilateral disease, and 3 had bilateral disease. The clinical manifestations were decreased limb muscle strength, cognitive function disorders, polydipsia, precocious puberty, intracranial hypertension, dysphonia and swallowing dysfunction. The serum and cerebrospinal fluid tumor marker alpha-fetoprotein (AFP) were normal in the 30 patients, and the serum and cerebrospinal fluid tumor marker β-human chorionic gonadotropin (β-HCG) were normal in 8 patients.The serum β-HCG was normal in 11 patients but the cerebrospinal fluid β-HCG was slightly elevated, and the serum and cerebrospinal fluid β-HCG were slightly elevated in 11 patients. A total of 33 lesions with irregular shapes were found by imaging examination, including 15 (45.5%) patchy lesions, 10 (30.3%) patchy lesions, and 8 (24.2%) round-like high-density lesions. Tumors showed obvious high-density shadows on computed tomography (CT) scan. Magnetic resonance imaging (MRI) scan of the tumors showed low or isointensity on T1WI and isointensity on T2WI, accompanied by mild peritumoral edema, hemispheric atrophy, cerebral peduncle atrophy, calcification, cystic degeneration, ventricular dilatation and wallerian degeneration. On contrast-enhanced scans, the tumor showed no enhancement or heterogeneous enhancement. CONCLUSION The main age of onset of germ cell tumors in the basal ganglia in children is about 10 years old, and males are absolutely dominant. The clinical features and imaging manifestations have certain characteristics. With both combined, the early diagnosis of germ cell tumors in the basal ganglia can be improved.
Atrophy/pathology* ; Basal Ganglia/pathology* ; Biomarkers, Tumor ; Brain Neoplasms/diagnostic imaging* ; Child ; Chorionic Gonadotropin, beta Subunit, Human ; Female ; Germinoma/pathology* ; Humans ; Magnetic Resonance Imaging ; Male ; Neoplasms, Germ Cell and Embryonal ; Retrospective Studies

Introduction: Intratumoral calcification is a feature that is more often observed in pineal parenchymal tumour than germinoma. We describe a 13-year-old male with pineal region germinoma demonstrating extensive intratumoral calcification. Case report: He presented with worsening headache that was associated with fatigue, nausea and vomiting. Radiologic examination revealed a multilobular mass in the pineal region with internal calcifications. Biopsy showed a pure germinoma with unusually extensive calcification. Discussion: Although a diagnosis may be suggested with a careful evaluation of imaging, there is no pathognomonic pattern. Thus, histologic verification is necessary for most pineal region masses.
Germinoma

A 32-year old male came to our hospital with chief complaint of paraplegia. He had symptom of radiating pain to right leg 3 months ago before paraplegic symptom appeared. Magnetic resonance (MR) imaging from outside hospital showed intramedullary mass involving from T8 to T10 level of spinal cord. According to the imaging result, tumor removal with total laminectomy was performed between T8 and T10 level in our hospital. Pathologic result was compatible with germinoma. Spine radiation (39.6 Gy/22 fx) from T7 to T12 level without chemotherapy was performed 3 weeks later since tumor removal. Follow-up MR imaging showed no recurrence without any distant metastasis. And our patient's neurologic symptom had been improved. According to this case, postoperative radiotherapy is thought to be effective to primary spinal germinoma.
Drug Therapy ; Follow-Up Studies ; Germinoma* ; Humans ; Laminectomy ; Leg ; Magnetic Resonance Imaging ; Male ; Neoplasm Metastasis ; Neurologic Manifestations ; Paraplegia ; Radiotherapy ; Recurrence ; Spinal Cord* ; Spine

Germinoma is the most common type of intracranial germ cell tumors (GCTs). Pineal gland and suprasellar region are the most frequent sites of central nervous system (CNS) involvement. Intracranial masses caused by Langerhans cell histiocytosis (LCH) mimics features of CNS GCTs. LCH frequently involve spine and is the most common cause of vertebra plana in children. A 15-year-old boy presented with progressing symptoms of polydipsia, polyuria, general headache, nausea and severe back pain. Brain MRI showed brain tumor with simultaneous involvement of suprasellar region and pineal gland. An excisional biopsy of suprasellar mass was done. The pathologic assessment confirmed the diagnosis of germinoma. Patient's treatment continued accordingly. A spine MRI, done due to persistent backache, showed a vertebra plana. We reevaluated the primary diagnosis suspecting LCH. Germinoma of CNS was confirmed and a biopsy of vertebral lesion resulted in hemangioma. Thus we report a case of CNS germinoma with co-occurrence of vertebra plana. We emphasized the importance of histopathologic diagnosis of pineal/suprasellar masses and primary investigation of other CNS regions including spine for possible metastasis or comorbidities.
Adolescent ; Back Pain ; Biopsy ; Brain ; Brain Neoplasms ; Central Nervous System ; Child ; Comorbidity ; Diagnosis ; Germinoma* ; Headache ; Hemangioma ; Histiocytosis, Langerhans-Cell ; Humans ; Magnetic Resonance Imaging ; Male ; Nausea ; Neoplasm Metastasis ; Neoplasms, Germ Cell and Embryonal ; Pineal Gland ; Polydipsia ; Polyuria ; Spine*

Intracranial germ cell tumors (iGCTs) are a heterogeneous group of tumors with peculiar characteristics clearly distinguished from other brain tumors of neuroepithelial origin. Diverse histology, similarity to gonadal GCT, predilection to one sex, and geographic difference in incidence all present enigmas and fascinating challenges. The treatment of iGCT has advanced for germinoma to date; thus, clinical attention has shifted from survival to long-term quality of life. However, for non-germinomatous GCT, current protocols provide only modest improvement and more innovative therapies are needed. Recently, next-generation sequencing studies have revealed the genomic landscape of iGCT. Novel mutations in the KIT-RAS-MAPK and AKT-MTOR pathways were identified. More importantly, methylation profiling revealed a new method to assess the pathogenesis of iGCT. Molecular research will unleash new knowledge on the origin of iGCT and solve the many mysteries that have lingered on this peculiar neoplasm for a long time.
Brain Neoplasms ; Germ Cells ; Germinoma ; Gonads ; Incidence ; Methods ; Methylation ; Neoplasms, Germ Cell and Embryonal ; Quality of Life ; Therapies, Investigational

PURPOSE: Malignant central nervous system (CNS) germ cell tumors (GCTs), although rare, are thought to occur more frequently among Asians. However, a recent population-based study revealed no differences in GCT incidence between Asians and Caucasians. Therefore, this study was conducted to determine the incidence and survival rates of CNS GCTs using the national cancer incidence database, and to compare these rates to those in the United States and Japan. MATERIALS AND METHODS: We extracted CNS GCT patients diagnosed between 2005 and 2012 from the Korea Central Cancer Registry database. Age-standardized rates (ASRs), annual percentage change, and the male-female incidence rate ratios (IRRs) were calculated. To estimate the survival rate, we used data for patients diagnosed between 2005 and 2010 and followed their cases until December 31, 2013. RESULTS: The ASR for CNS GCT between 2005 and 2012 was 0.179 per 100,000 (95% confidence interval, 0.166 to 0.193), with an overall male-to-female (M:F) IRR of 2.95:1. However, when stratified by site, the M:F IRR was 13.62:1 for tumors of the pineal region and 1.87:1 for those located in nonpineal regions. The most frequent histologic type was germinoma (76.0%), and the most frequent location was the suprasellar region (48.5%). The 5-year survival rate of germinoma patients was 95.3%. CONCLUSION: The incidence rate of CNS GCTs in Korea during 2005-2012 was 0.179 per 100,000, which was similar to that of the Asian/Pacific Islander subpopulation in the United States. Moreover, the CNS GCT survival rate in Korea was similar to rates in Japan and the United States.
Asian Continental Ancestry Group ; Central Nervous System* ; Germ Cells* ; Germinoma ; Humans ; Incidence* ; Japan ; Korea* ; Neoplasms, Germ Cell and Embryonal* ; Survival Rate* ; United States

Langerhans cell histiocytosis (LCH) has diverse clinical manifestations, including intracranial mass lesions. We report a case of LCH that manifested as a suprasellar mass, and initially misdiagnosed as a germ cell tumor. A 29-year-old woman presented with polyuria, polydipsia and amenorrhea. Laboratory findings revealed hypopituitarism with central diabetes insipidus, and a suprasellar mass and a pineal mass were observed on magnetic resonance imaging. Under the clinical impression of a germ cell tumor, the patient was treated with germ cell tumor chemotherapy (cisplatin and etoposide) and radiation therapy without biopsy. After initial shrinkage of the lesions, further growth of the tumor was observed and a biopsy was performed. The histopathology revealed LCH. After chemotherapy according to the LCH III protocol, the tumor disappeared. She is on regular follow up for 5 years without relapse. The present findings indicate that LCH should be included in the differential diagnosis of a suprasellar mass, even in adults, especially when it manifests with diabetes insipidus. This case also underscores the importance of a histopathologic diagnosis in patients with suprasellar tumors before the initiation of a specific therapy, even if the clinical findings are highly suggestive of a specific diagnosis.
Adult ; Amenorrhea ; Biopsy ; Central Nervous System Neoplasms ; Diabetes Insipidus ; Diabetes Insipidus, Neurogenic ; Diagnosis ; Diagnosis, Differential ; Drug Therapy ; Female ; Follow-Up Studies ; Germinoma ; Histiocytosis, Langerhans-Cell* ; Humans ; Hypopituitarism ; Magnetic Resonance Imaging ; Neoplasms, Germ Cell and Embryonal ; Polydipsia ; Polyuria ; Recurrence ; Sella Turcica

Langerhans cell histiocytosis (LCH) has diverse clinical manifestations, including intracranial mass lesions. We report a case of LCH that manifested as a suprasellar mass, and initially misdiagnosed as a germ cell tumor. A 29-year-old woman presented with polyuria, polydipsia and amenorrhea. Laboratory findings revealed hypopituitarism with central diabetes insipidus, and a suprasellar mass and a pineal mass were observed on magnetic resonance imaging. Under the clinical impression of a germ cell tumor, the patient was treated with germ cell tumor chemotherapy (cisplatin and etoposide) and radiation therapy without biopsy. After initial shrinkage of the lesions, further growth of the tumor was observed and a biopsy was performed. The histopathology revealed LCH. After chemotherapy according to the LCH III protocol, the tumor disappeared. She is on regular follow up for 5 years without relapse. The present findings indicate that LCH should be included in the differential diagnosis of a suprasellar mass, even in adults, especially when it manifests with diabetes insipidus. This case also underscores the importance of a histopathologic diagnosis in patients with suprasellar tumors before the initiation of a specific therapy, even if the clinical findings are highly suggestive of a specific diagnosis.
Adult ; Amenorrhea ; Biopsy ; Central Nervous System Neoplasms ; Diabetes Insipidus ; Diabetes Insipidus, Neurogenic ; Diagnosis ; Diagnosis, Differential ; Drug Therapy ; Female ; Follow-Up Studies ; Germinoma ; Histiocytosis, Langerhans-Cell* ; Humans ; Hypopituitarism ; Magnetic Resonance Imaging ; Neoplasms, Germ Cell and Embryonal ; Polydipsia ; Polyuria ; Recurrence ; Sella Turcica