Absence of anti-rabphilin-3A antibodies in children and young adults with idiopathic central diabetes insipidus: a potential clue to elucidating a tumor etiology.

BACKGROUND: Central diabetes insipidus (CDI) is a rare condition caused by various underlying diseases, including neoplasms, autoimmune diseases, and infiltrative diseases. Differentiating between CDI etiologies is difficult. What has initially been classified as "idiopathic" central diabetes insipidus might in fact underlie various pathogenic mechanisms that are less understood to date and/or are not obvious at initial presentation. Therefore, even if idiopathic CDI is diagnosed at the time of onset, it is common for tumors such as germinoma to develop during surveillance. Crucially, a delayed diagnosis of germinoma may be associated with a worse prognosis. Recently, the presence of anti-rabphilin-3A antibodies has been found to be a highly sensitive and specific marker of lymphocytic infundibuloneurohypophysitis, an autoimmune-mediated CDI. CASE PRESENTATION: We herein present two cases, namely, a 13-year-old boy (patient 1) and a 19-year-old young man (patient 2) who were diagnosed with idiopathic CDI. In both patients, panhypopituitarism developed. Magnetic resonance imaging revealed pituitary stalk thickening and pituitary swelling approximately 1 1/2 years after the onset of CDI. Western blotting did not reveal the presence of anti-rabphilin-3A antibodies in serum in either patient, suggesting that autoimmune mechanisms might not be involved. Both patients were subsequently diagnosed with germinoma on pathological examination. They received chemotherapy, followed by radiation therapy. Notably, testosterone and insulin-like growth factor-1 levels normalized, and libido and beard growth recovered after chemoradiotherapy in patient 2. CONCLUSION: Our data suggest that the absence of anti-rabphilin-3A antibodies in young patients clinically diagnosed with idiopathic CDI may increase the probability of the development of non-lymphocytic lesions, including germinoma. We thus recommend a more attentive approach at the onset of these diseases.

Primary suprasellar germinoma: A series of 15 cases.

Primary suprasellar germinoma (PSG) is a rare malignant tumor of the central nervous system. This study aimed to explore the clinical characteristics, treatment protocol, and prognosis of patients with PSG. This case series retrospectively analyzed the clinical data of patients with PSG in Tianjin Huanhu Hospital diagnosed between January 2016 and December 2021. Fifteen patients with an average age of 19.6 years were included, in which nine of them were males. The mean duration between initial symptoms and admission was 17.0 months. The mean follow-up was 40.8 months. Ten patients had polydipsia and polyuria, visual impairments were observed in 8 patients, and 2 cases (13.3%) had symptoms both from suprasellar and pineal regions. All 15 cases were histopathologically confirmed as germinoma through craniotomy or biopsy. Most patients (80%) underwent radiotherapy combined with chemotherapy. During follow-up, all the patients showed a reduction in tumor size, especially in the bifocal cases. Symptoms of polydipsia, polyuria, and visual impairment were markedly relieved to different degrees. All patients had recovered well at discharge. Patients with polydipsia and polyuria took desmopressin daily. A histological confirmation by open biopsy through craniotomy or endoscopic biopsy might be recommended for PSG to start the appropriate treatments. Patients with PSG will usually have a good prognosis, but attention should be paid to the treatment of endocrine deficiencies.

Intracranial germinoma in the lateral ventricle with polydipsia and polyuria: a case report and literature review.

Central nervous system germ cell tumors (CNSGCTs) are rare neoplasms which usually develop in the midline structures. They are occasionally involved in off-midline structures of the brain. Here, we report an extremely rare case of an intracranial germinoma in the lateral ventricle. The patient was a 10-year-old boy with a 1-year history of polydipsia and polyuria. Brain magnetic resonance imaging (MRI) showed a relatively homogeneously enhancing lesion in the lateral ventricle, and the posterior pituitary gland was not hyperintense on T1-weighted imaging. Subependymoma was suspected, and tumor removal operation was performed; however, because the intraoperative pathological investigation revealed germinoma, we could only perform partial removal of the tumor. Postoperative histology also confirmed germinoma. Then, the patient received chemotherapy, followed by radiation therapy. MRI showed no recurrence for 6 years after treatment. Intracranial germinoma in the lateral ventricle is extremely rare. The diagnosis is occasionally challenging, especially when the tumors are located in atypical locations. This paper presents a literature review of previously described CNSGCTs of the lateral ventricle to improve awareness of CNSGCTs in atypical locations. We also consider the relationship between imaging findings and clinical manifestations.

Evaluation of the etiological and clinical characteristics of pediatric central diabetes insipidus.

OBJECTIVES: Central diabetes insipidus (CDI) is a rare but important disease of varying etiology that poses challenges in diagnosis and follow-up. Identifying diagnostic difficulties in patients with CDI will help ensure an optimal approach to their management and follow-up. This study aimed to characterize the clinical and etiological characteristics of CDI in pediatric patients. METHODS: We analyzed the admission and follow-up data of CDI patients aged 0-18 years who were followed in our center between 2010 and 2019. RESULTS: The study included 56 patients with a mean age at diagnosis of 7.92 ± 5.11 years and symptom duration of 8.65 ± 21.3 months. The patients were grouped by etiology into those with organic causes, such as structural anomalies, tumors, and trauma (group 1, n=41) and other causes (group 2, n=15). The prevalence of idiopathic CDI was 16%. At least one pituitary hormone deficiency was detected in 60.7%, the most common being thyroid stimulating hormone deficiency. Patients in group 1 had a higher mean age at diagnosis, shorter symptom duration, and higher frequency of other pituitary hormone deficiencies compared to group 2. Additionally, germinoma was detected 1 year subsequent to normal MRI findings at diagnosis and another patient was diagnosed with Langerhans cell histiocytosis (LCH) 5 years after diagnosis. All patients responded well to replacement therapies, but two patients with germinoma died during follow-up. CONCLUSIONS: In the pediatric age group, intracranial organic pathologies are an important etiology of CDI, and despite a short symptomatic period, determining the cause may be challenging and prolonged. Patients presenting at a young age with a long history of symptoms and no other pituitary hormone deficiency are unlikely to have organic CDI. However, organic causes such as LCH should be evaluated at all ages. Patients with idiopathic disease are candidates for further etiological studies, and repeated cranial imaging is important during follow-up.

Treatment Outcome of a ß-hCG Secreting Intracranial Germ Cell Tumor in an Adult Filipino Using Definitive Chemotherapy Followed by Radiotherapy: A Case Report.

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.

Diencephalic syndrome in a female child due to intracranial germinoma: a case report.

INTRODUCTION: Diencephalic syndrome (DS) is a rare syndrome with failure to thrive (FTT) as the primary manifestation, which is often associated with astrocytoma or glioma and rarely caused by germinoma. To our knowledge, there are no reports of female patients presenting with DS secondary to germinoma. CASE REPORT: we report a case (an 11-year-old girl) of diencephalic syndrome presenting with FTT. She was diagnosed with severe malnutrition in the local hospital two years before admission and still did not show normal development after long-term nutritional support. Finally, after ruling out increased metabolism, inadequate caloric intake, and nutrient absorption, intracranial MRI showed a space-occupying lesion in the suprasellar cisterna-hypothalamus area. After excluding other causes of FTT, a biopsy was performed for pathological examination and demonstrated a germinoma. An excellent therapeutic effect was achieved during the three-month follow-up after radiotherapy. CONCLUSION: This case reminds us that intracranial tumors should be considered an indispensable etiology for patients with suspicious FTT, and early diagnosis and intervention may achieve a good prognosis.

[Clinical analysis of 30 cases of basal ganglia germinoma in children].

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 ß-human chorionic gonadotropin (ß-HCG) were normal in 8 patients.The serum ß-HCG was normal in 11 patients but the cerebrospinal fluid ß-HCG was slightly elevated, and the serum and cerebrospinal fluid ß-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.

Unusual presentation of epilepsy of germinoma located in the frontal-lobe: case report and literature review.

Germinoma is rare in peripheral lobar locations in the brain, with only 10 cases of primary frontal lobe germinoma having been reported in the previous literature. Epilepsy is a rare manifestation of germinomas. We describe an unusual case of a primary frontal germinoma in a 21-year-old man who presented with epilepsy. A presumptive diagnosis of abscess or cystic glioma was made, and then, we performed microsurgery under magnetic resonance imaging (MRI) neuronavigation guidance. Postoperative histopathologic examination identified the tumour as a rare germinoma. Subsequently, adjuvant radiotherapy and chemotherapy programmes were adopted in the present case, and there were no recurrence and postoperative seizure symptoms observed in the follow-up 6 months after operation.

Characteristics of growth disturbances in patients with intracranial germinomas of different origins.

PURPOSE: To explore the characteristics of growth disturbance in patients with intracranial germinoma with different origins. METHODS: Clinical data of 151 patients with single-origin germinomas were studied retrospectively. Z-score of height (ZSOH) at both diagnosis and the last follow-up was calculated using the WHO AnthroPlus software. Linear regression was used to analyse the correlation between the absolute change in ZSOH (|ZSOH last follow-up - ZSOH diagnosis|) and clinical factors. RESULTS: The mean ZSOH decreased significantly in every origin subgroup at the last follow-up. In patients with sellar germinoma (n = 62), the mean ZSOH values at both diagnosis and the last follow-up were significantly lower than those in patients with pineal (n = 30) (p < 0.001) or basal ganglia germinomas (n = 59) (p < 0.001), respectively. In patients with basal ganglia germinoma, the mean absolute change in ZSOH decreased significantly compared to that in the patients with sellar (p = 0.006) or pineal germinomas (p = 0.04). Linear analysis revealed that sex (male vs female; p = 0.003) and age at diagnosis (≤10 years vs >10 years; p = 0.026) had negative correlations, while radiation dose at the hypothalamic-pituitary axis (HPA) (≤40 Gy vs >40 Gy; p = 0.085) had a marginally positive correlation, with absolute change in ZSOH. CONCLUSIONS: Patients with germinoma experienced growth retardation after treatments. The growth disturbance was consistent and more severe in patients with germinoma of sellar origin, while the greatest aggravation was observed in patients with germinoma of basal ganglia origin. Decreasing radiation dose to the HPA may minimize the negative impact of radiotherapy on growth.

Intracranial Germinoma Misdiagnosed as Hyperthyroidism: A Case Report and Review of the Literature.

Intracranial germ cell tumors (GCTs) are relatively rare, which account for 0.5% of all primary intracranial neoplasms. Intracranial germinomas most commonly occur in the pineal and suprasellar region, making up the majority of all intracranial GCTs. For its diversified clinical manifestations, the diagnosis is easily confused with other diseases. Here, we present a case of a 19-year-old boy with intracranial germinoma who was preliminarily misdiagnosed as hyperthyroidism for the symptoms of weight loss and thyroid dysfunction.

So-called bifocal tumors with diabetes insipidus and negative tumor markers: are they all germinoma?

BACKGROUND: The Delphi consensus statements on the management of germ cell tumors (GCTs) failed to reach agreements on the statement that the cases with (i) pineal and neurohypophyseal bifocal lesion, (ii) with diabetes insipidus, and (iii) with negative tumor markers can be diagnosed as germinoma without histological verification. To answer this, multicenter retrospective analysis was performed. METHODS: A questionnaire on clinical findings, histological diagnosis, and details of surgical procedures was sent to 86 neurosurgical and 35 pediatrics departments in Japan. RESULTS: Fifty-one institutes reported 132 cases that fulfilled the 3 criteria. Tissue sampling was performed in 91 cases from pineal (n = 44), neurohypophyseal (n = 32), both (n = 6), and distant (n = 9) lesions. Histological diagnosis was established in 89 cases: pure germinoma or germinoma with syncytiotrophoblastic giant cells in 82 (92.1%) cases, germinoma and mature teratoma in 2 cases, and granulomatous inflammation in 2 cases. Histological diagnosis was not established in 2 cases. Although no tumors other than GCTs were identified, 3 (3.4%) patients had non-germinomatous GCTs (NGGCTs). None of the patients developed permanent complications after endoscopic or stereotactic biopsy. Thirty-nine patients underwent simultaneous procedure for acute hydrocephalus without permanent complications, and hydrocephalus was controlled in 94.9% of them. CONCLUSION: All patients who fulfilled the 3 criteria had GCTs or granulomatous inflammation, but not other types of tumors. However, no fewer than 3.4% of the patients had NGGCTs. Considering the safety and the effects of simultaneous procedures for acute hydrocephalus, biopsy was recommended in such patients.

Lateral Temporal Approach for Image-Guided Stereotactic Biopsy of Pineal Region Tumors.

BACKGROUND: Biopsy of pineal region neoplasms is frequently accomplished by way of endoscopic transventricular access or using an image-guided, computer-assisted stereotactic approach. METHODS: We evaluated a nonorthogonal lateral temporal approach for stereotactic biopsy of pineal region tumors as a variation of previously described stereotactic methods. Magnetic resonance imaging-guided frameless stereotaxy was used to plan and perform biopsies of pineal region tumors using a nonorthogonal trajectory extending from the superior or middle temporal gyri through the temporal stem, anterior to the atrium of the lateral ventricle, and posterior to the corticospinal tract. RESULTS: All patients had an uncomplicated postoperative course and remained at neurologic baseline. No parenchymal or ventricular hemorrhage was present on postoperative scans. A tissue diagnosis was obtained in all patients. CONCLUSIONS: This method appears to be a safe alternative to stereotactic biopsy using other trajectories and provides adequate tissue for definitive diagnosis.

Neurological and endocrinological manifestations of 49 children with intracranial pure germinoma at initial diagnosis in Taiwan.

BACKGROUND: Intracranial pure germinoma is a rare extragonadal neoplasm. Affected patients may have motor impairment, visual disturbance, neurological signs, and endocrine disorder, depending on the size and location of the tumor. This study investigated and analyzed patients' demographic data and neuroimaging, clinical, laboratory, and endocrinological findings. METHODS: We performed a retrospective chart review of 49 children diagnosed with pure germinoma in Taiwan from 1990 to 2018. The initial clinical presentation, tumor markers (beta-hCG, alpha fetoprotein, and carcinoembryonic antigen), pituitary function, and brain images were reviewed and analyzed. RESULTS: This study included 49 patients (37 boys and 12 girls). Their ages ranged from 7.5 to 17.9 years, and the mean age at diagnosis was 13.6 years. Initial symptoms included visual disturbance (n = 23, 47.9%), motor impairment (n = 20, 40.8%), polyuria (n = 20, 40.8%), headache (n = 17, 34.7%), dizziness or vertigo (n = 14, 28.6%), nausea/vomiting (n = 13, 26.5%), and short stature (n = 8, 18.2%). Laboratory data indicated growth hormone deficiency or low IGF-1 levels (n = 18, 85.7%), adrenal insufficiency (n = 21, 77.8%), central diabetes insipidus (n = 27, 55.1%), central hypothyroidism (n = 15, 48.4%), and hypogonadotropic hypogonadism (n = 4, 44.4%). CONCLUSION: Intracranial pure germinomas may initially manifest as neurological symptoms or endocrinological findings at diagnosis. As endocrinologic presentation is related to delayed diagnosis, clinicians should be aware of patients with such complaints. Laboratory data should be surveyed carefully, and neuroimaging must be considered if the result is abnormal.