Central diabetes insipidus caused by a pituitary stalk germinoma resembling infundibuloneurohypophysitis.

We report the case of a pituitary stalk germinoma initially misdiagnosed and treated as infundibuloneurohypophysitis (INH). A 27-year-old man presented with a 1-year history of polydipsia, polyuria, nycturia consistent with central diabetes insipidus and a hyperintense pituitary stalk lesion on MRI. A possible INH diagnosis was considered, after excluding other pathologies. Lesion biopsy was discarded at that time on the ground of a small target and the high risk of added morbidity. Oral desmopressin led to initial symptoms resolution but, in the following months, an anterior panhypopituitarism developed, in spite of appropriate treatment and, by that time, the brain MRI also revealed lesion growth, which prompted a biopsy recommendation. The pathology analysis revealed a germinoma. After chemotherapy and radiotherapy, there was complete disappearance of the pituitary lesion, but the panhypopituitarism persisted. In conclusion, this case highlights the importance and difficulty of precise diagnosis in the initial assessment of pituitary stalk lesions and the need for close monitoring of treatment response. Diagnostic reassessment and biopsy in atypical cases is the only path to achieve the correct diagnosis and treatment.

Visual complaints in intracranial germinomas.

OBJECTIVE: Patients with brain tumors often report having visual complaints. This may be due to increased intracranial pressure, compression/invasion of the optic pathway or diplopia. We assessed the incidence and the etiology of visual symptoms in patients with intracranial germinoma tumors (ICGTs). METHODS AND MATERIALS: We performed a blinded retrospective review of the clinical charts and the initial magnetic resonance imaging (MRI) of 28 patients with ICGT. Thirteen tumors were pineal, five suprasellar, seven bifocal, and further three involved either the optic nerve, the corpus callosum, or the brainstem. RESULTS: Twelve patients reported visual disturbances, seven of whom mainly experienced a decrease in vision. Two of those were initially managed as "retrobulbar neuritis" when endocrinologic symptoms prompted assessment by MRI. Involvement of the optic pathway was underestimated, and both relapsed. Field deficits were definitive sequelae, whereas visual acuity was sometimes regressive in the absence of optic atrophy. CONCLUSIONS: Compression or invasion of the optic pathway by germinomas is not a rare occurrence, and this possibility should not be overlooked when thickening or contrast enhancement is detected. Radiotherapy fields should be extended accordingly.

Pineal germinoma in a child with interferon-γ receptor 1 deficiency. case report and literature review.

Interferon-γ receptor 1 (IFN-γR1) deficiency is one of the primary immunodeficiencies conferring Mendelian Susceptibility to Mycobacterial Disease (MSMD). Some cases of neoplasms have been recently reported in patients with MSMD, underlying the already known link between immunodeficiency and carcinogenesis. We report the first case of intracranial tumour, i.e. pineal germinoma, in a 11-year-old patient with complete IFN-γR1 deficiency. The first clinical presentation of the genetic immunodeficiency dates back to when the child was aged 2 y and 10 mo, when he presented a multi-focal osteomyelitis caused by Mycobacterium scrofulaceum. The diagnosis of IFN-γR1 deficiency (523delT/523delT in IFNGR1 gene) was subsequently made. The child responded to antibiotic therapy and remained in stable clinical condition until the age of 11 years, when he started complaining of frontal, chronic headache. MRI revealed a solid pineal region mass lesion measuring 20 × 29 × 36 mm. Histological findings revealed a diagnosis of pineal germinoma. The patient received chemotherapy followed by local whole ventricular irradiation with boost on pineal site, experiencing complete remission, and to date he is tumor-free at four years follow-up. Four other cases of tumors have been reported in patients affected by MSMD in our knowledge: a case of Kaposi sarcoma, a case of B-cell lymphoma, a case of cutaneous squamous cell carcinoma and a case of oesophageal squamous cell carcinoma. In conclusion, in patients with MSMD, not only the surveillance of infectious diseases, but also that of tumors is important.

Clinical profile and etiologies of children with central diabetes insipidus: a single-center experience from Turkey.

AIM: The aim of this study is to evaluate the clinical, anthropometric, hormonal, and radiological characteristics of children with central diabetes insipidus (DI). METHODS: Case records of 34 children (22 boys and 12 girls) with documented central DI referred to the Pediatric Endocrinology and Adolescent Clinic of Dokuz Eylul University Faculty of Medicine were reviewed. The mean age at diagnosis was 6.4 +/- 5.6 years (range, 0.08-16 years). All patients underwent anterior pituitary function assessment and magnetic resonance imaging of pituitary at diagnosis. The median duration of follow-up was 7.9 +/- 4.5 years. RESULTS: The etiology of central DI was organic in 22 (64.7%) patients, trauma in 2 (5.9%) patients, and idiopathic in 10 (29.4%) patients. Organic causes consisted of craniopharyngioma in 7 patients, Langerhans cell histiocytosis in 4 patients, germinoma in 4 patients, holoprosencephaly in 3 patients, astrocytoma in 1 patient, cavernous hemangioma in 1 patient, Rathke's cleft cyst in 1 patient, and autoimmune polyendocrinopathy in 1 patient. Anterior pituitary hormone deficiencies were documented in 18 (53%) patients. Organic central DI group had a greater prevalence of anterior pituitary hormone deficiency when compared with the idiopathic group (66% and 10%, respectively; p = 0.007). The final height of patients with organic etiology were significantly lower than the idiopathic group (155 and 178, cm respectively; p = 0.021). CONCLUSIONS: Etiological diagnosis is possible in a significant proportion (70.6%) of children with central DI. Findings of this study suggest that accompanying anterior pituitary hormone deficiencies and short stature may be considered as indicators of organic etiology.

Ocular manifestations of intracranial germinomas: three cases report and literature review.

Intracranial germinomas are malignant neoplasms of gonadal origin, which have some features in terms of age, sex, and clinical manifestations. They mainly occur in children and adolescents. Patients with intracranial germinomas mainly manifest with hypothalamic pituitary axis dysfunction and/or compression syndromes. Visual disturbance is one of the most significant clinical presentations, which is mainly caused by tumor cell infiltration into the optic pathway. In this article, we present three cases of patient with intracranial germinoma to analyze the ocular manifestations. All the three patients presented with endocrine symptoms in the early stage and with visual disturbances (including decreased visual acuity and visual field defects) later. In general, germinoma is diagnosed by its characteristic radiological appearance, supported by tumor markers and/or stereotactic biopsy. However, decisive diagnoses were established when ocular manifestations were presented. A suspicion for germinoma should be considered, when young patients manifest visual disturbances accompanied by endocrine symptoms.

Primary medulla oblongata germinoma in a male patient.

Germinoma mainly occurs in the pituitary stalk, pineal region, and basal ganglia. Sex predominance of the tumor in males in the pineal region and basal ganglia is well known. Primary germinoma of the medulla oblongata is rare, with only eight reports, mostly in females. We report the second male patient with primary medulla oblongata germinoma, without chromosomal abnormality, who was successfully treated with surgery, chemotherapy, and radiotherapy.

Intracranial germinoma presenting with hemiatrophy--follow-up results and literature review--two case reports.

Two boys aged 8 and 12 years presented with intracranial germinoma manifesting as cerebral hemispheric atrophy, hemiparesis, and decline in academic performance. First magnetic resonance (MR) imaging showed no enhanced lesions, but follow-up MR imaging obtained 12 or 23 months after the first visit showed new mass lesions in the temporal lobe or pituitary gland. Biopsy of these lesions resulted in a histological diagnosis of germinoma. Chemoradiation therapy produced complete remission but both patients continued to manifest mild hemiparesis and impaired cognitive function. Review of 18 previous and our 2 patients presenting with hemispheric atrophy revealed strong male predominance (18:2), mean age of 12.8 ± 5.2 (standard deviation) years, hemiparesis in all patients, and cognitive decline in 9 patients. Initial MR imaging detected mass lesions in only 9 patients, but follow-up MR imaging performed 10-38 months later detected new mass lesions in 5 patients. Radiation with/without chemotherapy provided good tumor control in all patients, but none of the 9 patients with cognitive dysfunction recovered their intellectual ability. We recommend early diagnosis based on biopsy of the atrophic site and timely treatment to improve the quality of life in these patients.

Paternity and testicular function among testicular cancer survivors treated with two to four cycles of cisplatin-based chemotherapy.

BACKGROUND: Preserved fertility is an important issue for testicular cancer (TC) survivors. OBJECTIVE: Our aim was to examine any difference regarding paternity and testicular function following two, three, or four cycles of cisplatin-based chemotherapy for TC. DESIGN, SETTING, AND PARTICIPANTS: A national multicentre follow-up survey assessing morbidity among survivors of unilateral TC diagnosed from 1980 to 1994 was conducted during the period 1998 to 2002. Of the 1814 men invited, 1462 (80.6%) participated by responding to a mailed questionnaire and/or undergoing a clinical examination including laboratory assessments. The present study includes the 316 participants up to 65 yr of age treated with two to four cycles of standard cisplatin-based chemotherapy without additional treatment beyond surgery. MEASUREMENTS: Self-reported paternity following treatment for TC according to number of cycles was assessed among men who reported antegrade ejaculation and attempts at posttreatment conception (n=106). Kaplan-Meier analysis, log-rank test, and Cox regression were applied. Gonadal hormones (n=305-314) and sperm counts (n=71) by number of cycles were assessed by linear by linear association or Mann-Whitney tests. RESULTS AND LIMITATIONS: At median 12-yr follow-up, 80% (85 of 106) had succeeded in their attempts of achieving posttreatment paternity (two cycles: 100%; three: 83%; four: 76%; p=0.022). For all patients the 15-yr actuarial paternity rate was 85%. The association between posttreatment paternity and number of cycles remained significant in the multivariate analysis (p=0.032). High serum follicle-stimulating hormone values were more common with increasing number of cycles (p=0.037), but there were no differences in serum luteinising hormone, serum testosterone, or sperm counts. Few men treated with two cycles and a limited number of sperm samples are the main limitations of this study. CONCLUSIONS: The prospects of future paternity after two to four cycles of cisplatin-based chemotherapy are good, and our data suggest that the prospects improve with decreasing number of cycles.

Quality of life of extremely long-time germinoma survivors mainly treated with radiotherapy.

PURPOSE: To assess the quality of life (QOL) of extremely long-time survivors with germinoma mainly treated with radiotherapy. PATIENTS AND METHODS: We enrolled 52 of 68 patients who received radiotherapy between 1968 and 1995 at our hospital. They were 41 males and 11 females; the tumor location was pineal in 20, neurohypophyseal in 15, pineal and neurohypophyseal in 11 patients; in 6 it was located in another region. All underwent radiotherapy; the median dose was 48.2 (range 40.0-60.2) Gy. The median follow-up period was 226 (range 0-448) months. The clinical outcome and QOL were evaluated retrospectively. RESULTS: In 6 patients, the tumor recurred; 6 other patients developed second tumors while in complete remission from the first tumor. The main cause of 12 deaths was complications due to primary tumor invasion, the initial treatment, or tumor recurrence rather than tumor progression. The 10-, 20-, and 30-year actuarial survival rate was 83.6, 77.5, and 64.2%, respectively. Of 44 patients, 6 were married and 3 males with solitary pineal tumors were fathers. Among 32 patients, 14 had, or had not, graduated from high school; the other 18 went on to higher education. Twenty-one patients had no occupation; 7 of 11 formerly employed patients had left their jobs. CONCLUSION: Radiotherapy delivered between 1968 and 1995 to patients with germinoma yielded satisfactory outcomes but a decline in the QOL.

Inherent diagnostic and treatment challenges in germinoma of the basal ganglia: a case report and review of the literature.

Among intracranial germinomas, basal ganglia germinomas represent a specific clinical and anatomical entity. Based on an unusual case of a basal ganglia germinoma in a 13-year-old Caucasian male, we highlight the diagnostic challenges and discuss treatment considerations in this disease.

Germinoma located in the basal ganglia in an 8-year-old girl.

CASE REPORT: The authors describe a unique case of an 8-year-old girl with a germinoma located in the left basal ganglia. Medical history begins 5 months before with a central diabetes insipidus, loss of weight (5 kg at admission), vomiting and asthenia. Computed tomography (CT) and cranial magnetic resonance imaging (MRI) are performed and demonstrate a left basal ganglia tumour (nucleus lentiformis). Diabetes insipidus is considered as non-visible germinoma localization on the pituitary stalk rather than as a possible consequence of peri-tumoural oedema surrounding the hypothalamus. Spinal MRI is normal. Neurological as well as general examination is normal. DISCUSSION: The first hypothesis is low-grade glioma, but pathological examination following a stereotactic biopsy of the lesion reveals a cerebral germinoma. A few days before the biopsy, the girl experienced a mild left facial palsy, and CT scans at the time of biopsy reveals an intra-tumoural haemorrhage. Alpha fetoprotein and human chorionic gonadotrophin were negative as blood and cerebrospinal fluid markers, whereas placental alkaline phosphatase was positive on immunohistochemical profile of the tumour samples. Dedicated chemotherapy, followed by focal irradiation (40 Gy, 30 sessions, 45 days; SIOP CNS GCT 93 protocol), is performed with a complete response. The outcome is good (Glasgow Outcome Scale=I), without any cognitive impairment and the persistence of a mild facial palsy and a slight right arm dystonia on last neurological examination. There is still no evidence of tumour recurrence.

Neurofiberscopic biopsy of tumors of the pineal region and posterior third ventricle: indications, technique, complications, and results.

OBJECTIVE: Evaluation of results of the neurofiberscopic biopsy of tumors of the pineal region and posterior third ventricle. METHODS: From 2001 to 2004, 23 patients (mean age, 30.6 yr) with tumors located in the pineal region or posterior third ventricle underwent neurofiberscopic biopsy with simultaneous third ventriculostomy. The procedure was indicated for verification of the histological diagnosis of the neoplasm, which was planned to be treated by radiotherapy and/or chemotherapy without open surgery (eight patients), establishment of the pathological diagnosis for further choice of the most appropriate treatment strategy (11 patients), differentiation of the recurrent neoplasm and radiation necrosis (two patients), and decompression of the large tumor-associated cyst (two patients). In six previously shunted patients, substitution of the ventriculoperitoneal shunt on the third ventricle stoma was performed. RESULTS: There was no postoperative mortality or permanent morbidity. In all cases, the obtained tissue sample was sufficient for pathological diagnosis. Transient postoperative complications included fever (15 patients), nausea and vomiting (three patients), and diplopia (one patient). On the long-term follow-up, delayed third ventricular stoma failure caused by tumor regrowth and scar formation was found in one patient, and dissemination of the malignant glioma through the subarachnoid space was found in another patient. CONCLUSION: Neurofiberscopic biopsy represents a useful method for sampling of tumors of the pineal region and posterior third ventricle, which can be effectively used in both previously shunted and shunt-free patients.

The importance of brainstem mapping in brainstem surgical anatomy before the fourth ventricle and implication for intraoperative neurophysiological mapping.

Brain stem mapping (BSM) is an intraoperative neurophysiological procedure to localize cranial motor nuclei on the floor of the fourth ventricle. BSM enables neurosurgeon to understand functional anatomy on the distorted floor of the fourth ventricle, thus, it is emerging as an indispensable tool for challenging brain stem surgery. The authors described the detail of BSM with the special emphasis on its clinical application for the brain stem lesion. Surgical implications based on the result of brains stem mapping would be also informative before planning a brain stem surgery through the floor of fourth ventricle. Despite the recent advancement of MRI to depict the lesion in the brain stem, BSM remains as the only way to provide surgical anatomy in the operative field. BSM could guide a neurosurgeon to the inside of brain stem while preventing direct damage to the cranial motor nuclei on the floor of the fourth ventricle. It is expected that understanding its advantage and limitations would help neurosurgeon to perform safer surgery to the brain stem lesion.

Regulation of Sertoli cell and germ cell differentation.

Unwanted childlessness affects approximately one in six couples worldwide. According to the World Health Organization, in nearly 40% of cases the cause can be attributed to the female, in 20% to the male, in 25% to both, and in 15% the cause remains unknown. The incidence of male factor infertility in the general population is approximately 7%. The majority of these men experience irreversible idiopathic infertility and cannot father children without some form of medical intervention. Male factor infertility, in addition, may be caused by testicular germ cell cancer, which is known to represent the most common cancer among young men in Western industrialized countries. There is growing evidence that this cancer originates from fetal germ cells exhibiting an aberrant programme of gene expression and that tumour progression may be favoured by an aberrant Sertoli cell-germ cell communication. The present monograph aims to shed more light on the regulation of Sertoli and germ cell differentiation. Involving knockout and transgenic mouse models, the authors focus on (a) male factor infertility that might be related to altered maturation of Sertoli cells, (b) male factor infertility that might be due to incorrect histone-to-protamine exchange in haploid spermatids, and (c) progression of testicular germ cell cancer that might be favoured by an aberrant Sertoli cell-germ cell communication.