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1.
BMC Endocr Disord ; 21(1): 13, 2021 Jan 11.
Article in English | MEDLINE | ID: mdl-33430828

ABSTRACT

BACKGROUND: Primary central nervous system lymphoma is a rare extra-nodal lymphoma of the central nervous system. Primary central nervous system lymphoma lesions usually appear in the vicinity of the ventricle, and there are few reports of primary central nervous system lymphoma with hypothalamic-pituitary lesions. CASE PRESENTATION: We treated a 56-year-old male with primary central nervous system lymphoma with the primary lesion in the hypothalamus, which was found by magnetic resonance imaging after sudden onset of endocrinological abnormalities. Initially, he was hospitalized to our department for hyponatremia. Endocrinological examination in conjunction with head magnetic resonance imaging and endoscopic biopsy revealed hypothalamic hypopituitarism and tertiary hypoadrenocorticism caused by a rapidly growing, diffuse large B-cell lymphoma in the hypothalamus. Remission of the tumor was achieved by high-dose methotrexate with whole brain radiotherapy, and some of the hormone responses were normalized. CONCLUSIONS: While primary central nervous system lymphoma is rare, it is important to note that hypopituitarism can result and that the endocrinological abnormalities can be partially restored by its remission.


Subject(s)
Central Nervous System Neoplasms/diagnosis , Central Nervous System Neoplasms/therapy , Hypothalamic Neoplasms/diagnosis , Hypothalamic Neoplasms/therapy , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/therapy , Adrenal Cortex Hormones/deficiency , Antimetabolites, Antineoplastic/therapeutic use , Chemoradiotherapy , Combined Modality Therapy , Endocrine System Diseases/etiology , Hormone Replacement Therapy , Humans , Hypopituitarism/etiology , Magnetic Resonance Imaging , Male , Methotrexate/therapeutic use , Middle Aged , Treatment Outcome
2.
Am J Hum Genet ; 107(4): 636-653, 2020 10 01.
Article in English | MEDLINE | ID: mdl-32946765

ABSTRACT

With mounting interest in translating genome-wide association study (GWAS) hits from large meta-analyses (meta-GWAS) in diverse clinical settings, evaluating their generalizability in target populations is crucial. Here, we consider long-term survivors of childhood cancers from the St. Jude Lifetime Cohort Study, and we show the limited generalizability of 1,376 robust SNP associations reported in the general population across 12 complex anthropometric and cardiometabolic phenotypes (n = 2,231; observed-to-expected replication ratio = 0.70, p = 6.2 × 10-8). An examination of five comparable phenotypes in a second independent cohort of survivors from the Childhood Cancer Survivor Study corroborated the overall limited generalizability of meta-GWAS hits to survivors (n = 4,212; observed-to-expected replication ratio = 0.55, p = 5.6 × 10-15). Finally, in direct comparisons of survivor samples against independent equivalently powered general population samples from the UK Biobank, we consistently observed lower meta-GWAS hit replication rates and poorer polygenic risk score predictive performance in survivor samples for multiple phenotypes. As a possible explanation, we found that meta-GWAS hits were less likely to be replicated in survivors who had been exposed to cancer therapies that are associated with phenotype risk. Examination of complementary DNA methylation data in a subset of survivors revealed that treatment-related methylation patterns at genomic sites linked to meta-GWAS hits may disrupt established genetic signals in survivors.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cancer Survivors , Epigenesis, Genetic , Gene Expression Regulation, Neoplastic , Genes, Neoplasm , Hypothalamic Neoplasms/genetics , Anthropometry/methods , Child , Cohort Studies , DNA Methylation , Female , Genome-Wide Association Study , Genotype , Humans , Hypothalamic Neoplasms/diagnosis , Hypothalamic Neoplasms/pathology , Hypothalamic Neoplasms/therapy , Male , Meta-Analysis as Topic , Metabolome/genetics , Multifactorial Inheritance , Phenotype , Predictive Value of Tests , Risk Assessment
3.
Neurol Med Chir (Tokyo) ; 60(6): 277-285, 2020 Jun 15.
Article in English | MEDLINE | ID: mdl-32404575

ABSTRACT

Most cases of optic hypothalamic pilocytic astrocytoma (OHPA) develop during childhood, so few cases of histologically verified OHPA have been described in adolescents and young adults (AYA). To elucidate the clinical features of OHPA with histological verification in AYA, we reviewed the clinical and radiological finding of OHPA treated at our institute from January 1997 and July 2017. AYA are aged between 15 and 39 years. The clinical courses of 11 AYA patients with optic hypothalamic glioma (OHG) without neurofibromatosis type 1 were retrospectively reviewed. About six patients were diagnosed in childhood and followed up after 15 years of age, and five patients developed OHPA during AYA. Histological diagnosis, verified at initial presentation or recurrence, was pilocytic astrocytoma in 10 and pilomyxoid astrocytoma in one. After initial treatment including debulking surgery and/or chemotherapy, tumor progression occurred 16 times in seven patients as cyst formation, tumor growth, and intratumoral hemorrhage. Five of 10 patients suffered deterioration of visual function during AYA. One of 10 cases had endocrinopathies requiring hormone replacement at last follow-up examination. In conclusion, histological diagnoses of OHG before and in AYA were pilocytic astrocytoma or pilomyxoid astrocytoma. Both pediatric and AYA-onset OHPA demonstrate high incidences of tumor progression and visual dysfunctions in AYA, so that long-term follow up is essential after the completion of treatment for pediatric and AYA-onset OHPA. The optimal timing of debulking surgery and radiation therapy should be established to achieve the long-term tumor control and to preserve the visual function.


Subject(s)
Astrocytoma/pathology , Hypothalamic Neoplasms/pathology , Adolescent , Adult , Age Factors , Astrocytoma/diagnostic imaging , Astrocytoma/therapy , Disease Progression , Female , Humans , Hypothalamic Neoplasms/diagnostic imaging , Hypothalamic Neoplasms/therapy , Male , Neuroradiography , Retrospective Studies , Young Adult
4.
Endocrine ; 63(2): 341-347, 2019 02.
Article in English | MEDLINE | ID: mdl-30341707

ABSTRACT

BACKGROUND: Most patients treated for hypothalamic-pituitary tumours develop GH deficiency. Long-term GH replacement treatment in adults with a previous history of hypothalamic-pituitary tumour could represent a concern about increasing the risk of tumour enlargement or recurrence. PURPOSE: To assess the progression risk of hypothalamic-pituitary tumours according to the GH secretory status (normal GH secretion, non-treated and treated GH deficiency). and determine the predictors of neoplasm recurrence. METHODS: We retrospectively reviewed 309 patients with tumours of the hypothalamic-pituitary region (294 subjects underwent neurosurgery while 81 radiotherapy) who were followed for 9.9 ± 8.3 years. RESULTS: Out of 309 patients, 200 were affected by severe GH deficiency; 90 of these underwent GH therapy. The tumour progression rate did not differ among GH-sufficient, not-treated and treated GH-deficient patients (16.5%, 16.4%. and 10.0%, respectively). In a multivariate analysis, previous radiotherapy (HR 0.12, CI 0.03-0.52, p < 0.005) and residual tumour (HR 8.20, CI 2.38-28.29, p < 0.001) were independent predictors of recurrence. After controlling for multiple covariates, the tumour recurrence risk in GH-sufficient and GH-treated patients was similar to that observed in not-treated GH-deficient patients. CONCLUSIONS: With limitations of retrospective analysis, GH therapy is not associated with an increased progression rate of tumours of the hypotalamic-pituitary region during long follow-up, thus supporting the long-term safety of GH treatment. The only predictors of tumour recurrence appear to be the presence of residual disease and the lack of radiotherapy.


Subject(s)
Hormone Replacement Therapy/adverse effects , Human Growth Hormone/metabolism , Human Growth Hormone/therapeutic use , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/etiology , Pituitary Neoplasms/diagnosis , Pituitary Neoplasms/pathology , Adult , Aged , Disease Progression , Female , Follow-Up Studies , Hormone Replacement Therapy/statistics & numerical data , Human Growth Hormone/deficiency , Humans , Hypothalamic Neoplasms/diagnosis , Hypothalamic Neoplasms/pathology , Hypothalamic Neoplasms/therapy , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasm Recurrence, Local/epidemiology , Neurosurgical Procedures/statistics & numerical data , Pituitary Neoplasms/epidemiology , Pituitary Neoplasms/therapy , Radiotherapy/statistics & numerical data , Retrospective Studies , Risk Factors , Tumor Burden/physiology
6.
Brain Tumor Pathol ; 32(4): 291-6, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26156565

ABSTRACT

Rosette-forming glioneuronal tumors (RGNT) of the fourth ventricle are slow-growing tumors that primarily involve the fourth ventricular region. We here report the first patient, an 8-year-old girl, with an RGNT originating in the hypothalamus and manifesting with precocious puberty. After partial removal, the remaining tumor showed rapid enlargement, and the pathologic diagnosis at the second surgery revealed histopathologic features similar to those found in the initial samples, including biphasic patterns of neurocytic rosettes and GFAP-stained astrocytic components. These tumor cells had mildly atypical nuclei; however, mitotic figures and necrosis were absent. Eosinophilic granular bodies and a glomeruloid vasculature were found, but Rosenthal fibers were absent. The Ki-67 proliferative index was 3.5 % (vs 1.1 % at the initial surgery). No recurrence was recorded during the 3-year period after the proton radiotherapy.


Subject(s)
Ganglioglioma/pathology , Hypothalamic Neoplasms/pathology , Rosette Formation , Child , Combined Modality Therapy , Female , Ganglioglioma/complications , Ganglioglioma/diagnosis , Ganglioglioma/therapy , Humans , Hypothalamic Neoplasms/complications , Hypothalamic Neoplasms/diagnosis , Hypothalamic Neoplasms/therapy , Neurosurgical Procedures , Proton Therapy , Puberty, Precocious/etiology , Radiotherapy
7.
Arch Argent Pediatr ; 113(1): e6-9, 2015 Jan.
Article in Spanish | MEDLINE | ID: mdl-25622177

ABSTRACT

Klinefelter Syndrome is the most frequent cause of hypergonadotropic hypogonadism in men. A flat response at luteinizing hormone releasing hormone stimulation test could be the first sign of hypothalamic tumor in these patients. We report the case of a patient diagnosed by neonatal screening with Klinefelter Syndrome, 47 XXY, that at 17 years follow-up presents analytical modification of the response to luteinizing hormone releasing hormone stimulation test with suppressed luteinizing hormone and follicle-stimulating hormone values; lately he presents with headache and loss of left eye vision. A magnetic resonance imaging of the brain showed a mixed germ cell hypothalamus tumor, requiring surgery, chemotherapy and radiotherapy with optimal response.


Subject(s)
Hypogonadism/etiology , Hypothalamic Neoplasms/complications , Klinefelter Syndrome/complications , Pituitary Neoplasms/complications , Adolescent , Humans , Hypogonadism/therapy , Hypothalamic Neoplasms/therapy , Male , Pituitary Neoplasms/therapy
8.
J Child Neurol ; 28(5): 625-32, 2013 May.
Article in English | MEDLINE | ID: mdl-23439714

ABSTRACT

Pilocytic astrocytoma, the most common pediatric brain tumor, is a clinically and molecularly heterogeneous disease that occurs most often in the cerebellum and hypothalamic and chiasmatic regions. Classically, pilocytic astrocytomas are driven by the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. Recently described genetic aberrations involving this pathway are critical for tumorigenesis. Tandem duplication of 7q34 encodes BRAF and produces several KIAA1549-BRAF novel oncogenic fusions. Activating point mutations of BRAF, such as BRAF (V600E), also lead to pilocytic astrocytoma. Loss of the NF1 gene allows hyperactivation of the oncogene KRAS. In this review, we discuss the current understanding of the novel molecular aberrations described in pilocytic astrocytomas and their clinical relevance for prognosis and treatment. The prognostic indications of these aberrations are discussed with regard to tumor location, tumor pathology, and patient age. A better understanding of the evolving molecular heterogeneity of pilocytic astrocytomas offers hope for developing molecularly targeted therapeutic armamentariums.


Subject(s)
Astrocytoma/genetics , Brain Neoplasms/genetics , Chromosome Aberrations , Genetic Heterogeneity , Astrocytoma/diagnosis , Astrocytoma/therapy , Brain Neoplasms/diagnosis , Brain Neoplasms/therapy , Cell Transformation, Neoplastic/genetics , Cerebellar Neoplasms/diagnosis , Cerebellar Neoplasms/genetics , Cerebellar Neoplasms/therapy , Child , Extracellular Signal-Regulated MAP Kinases/genetics , Genes, Neurofibromatosis 1 , Humans , Hypothalamic Neoplasms/diagnosis , Hypothalamic Neoplasms/genetics , Hypothalamic Neoplasms/therapy , Molecular Targeted Therapy , Optic Chiasm , Optic Nerve Neoplasms/diagnosis , Optic Nerve Neoplasms/genetics , Optic Nerve Neoplasms/therapy , Point Mutation/genetics , Prognosis , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins p21(ras) , Transcriptional Activation/genetics , ras Proteins/genetics
11.
J Neurosurg Pediatr ; 8(4): 353-6, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21961578

ABSTRACT

The authors report the first case of a Wilms tumor (WT) with diffuse anaplasia metastatic to the brain in a 13-year-old girl with a history of neurofibromatosis Type 1. At presentation, the metastatic tumor had radiological features that suggested a meningioma. Histologically it was characterized by striking anaplasia and features similar to the patient's previously resected WT with diffuse anaplasia.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brain Neoplasms/diagnosis , Brain Neoplasms/secondary , Kidney Neoplasms/pathology , Nephrectomy , Neurofibromatosis 1/complications , Wilms Tumor/secondary , Adolescent , Anaplasia/genetics , Astrocytoma/diagnosis , Astrocytoma/therapy , Brain Neoplasms/therapy , Chemotherapy, Adjuvant , Child , Child, Preschool , Craniotomy , Female , Humans , Hypothalamic Neoplasms/diagnosis , Hypothalamic Neoplasms/therapy , Kidney Neoplasms/genetics , Kidney Neoplasms/therapy , Magnetic Resonance Imaging/methods , Neurofibromatosis 1/genetics , Neurosurgical Procedures/methods , Phenotype , Temporal Lobe/pathology , Temporal Lobe/surgery , Wilms Tumor/genetics , Wilms Tumor/therapy
13.
Nihon Rinsho ; 69 Suppl 2: 142-5, 2011 Mar.
Article in Japanese | MEDLINE | ID: mdl-21830535
14.
Nihon Rinsho ; 69 Suppl 2: 217-20, 2011 Mar.
Article in Japanese | MEDLINE | ID: mdl-21830546
15.
Int J Radiat Oncol Biol Phys ; 81(4): e481-8, 2011 Nov 15.
Article in English | MEDLINE | ID: mdl-21470783

ABSTRACT

PURPOSE: To evaluate the outcomes in pediatric low-grade gliomas managed in a multidisciplinary setting. METHODS AND MATERIALS: We conducted a single-institution retrospective study of 181 children with Grade I-II gliomas. Log-rank and stepwise Cox proportional hazards models were used to analyze freedom from progression (FFP) and overall survival (OS). RESULTS: Median follow-up was 6.4 years. Thirty-four (19%) of patients had neurofibromatosis Type 1 (NF1) and because of their favorable prognosis were evaluated separately. In the 147 (81%) of patients without NF1, actuarial 7-year FFP and OS were 67 ± 4% (standard error) and 94 ± 2%, respectively. In this population, tumor location in the optic pathway/hypothalamus was associated with worse FFP (39% vs. 76%, p < 0.0003), but there was no difference in OS. Age ≤5 years was associated with worse FFP (52% vs. 75%, p < 0.02) but improved OS (97% vs. 92%, p < 0.05). In those with tissue diagnosis, gross total resection (GTR) was associated with improved 7-year FFP (81% vs. 56%, p < 0.02) and OS (100% vs. 90%, p < 0.03). In a multivariate model, only location in the optic pathway/hypothalamus predicted worse FFP (p < 0.01). Fifty patients received radiation therapy (RT). For those with less than GTR, adjuvant RT improved FFP (89% vs. 49%, p < 0.003) but not OS. There was no difference in OS between patient groups given RT as adjuvant vs. salvage therapy. In NF1 patients, 94% of tumors were located in the optic pathway/hypothalamus. With a conservative treatment strategy in this population, actuarial 7-year FFP and OS were 73 ± 9% and 100%, respectively. CONCLUSIONS: Low-grade gliomas in children ≤5 years old with tumors in the optic pathway/hypothalamus are more likely to progress, but this does not confer worse OS because of the success of salvage therapy. When GTR is not achieved, adjuvant RT improves FFP but not OS. Routine adjuvant RT can be avoided and instead reserved as salvage.


Subject(s)
Brain Neoplasms/therapy , Glioma/therapy , Neurofibromatosis 1/therapy , Adolescent , Age Factors , Antineoplastic Agents/therapeutic use , Brain Neoplasms/mortality , Brain Neoplasms/pathology , Child , Child, Preschool , Disease-Free Survival , Female , Follow-Up Studies , Glioma/mortality , Glioma/pathology , Humans , Hypothalamic Neoplasms/mortality , Hypothalamic Neoplasms/pathology , Hypothalamic Neoplasms/therapy , Infant , Male , Neurofibromatosis 1/mortality , Neurofibromatosis 1/pathology , Optic Nerve Neoplasms/mortality , Optic Nerve Neoplasms/pathology , Optic Nerve Neoplasms/therapy , Proportional Hazards Models , Radiotherapy Dosage , Radiotherapy, Adjuvant/methods , Retrospective Studies , Salvage Therapy/methods , Survival Analysis , Young Adult
19.
J Pediatr Hematol Oncol ; 30(3): 222-4, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18376285

ABSTRACT

The aim of this study was to present our 17-year experience (1989 to 2006) in the treatment of optic pathway/hypothalamic gliomas (OPHG) in 18 children younger than 17 years (median age, 66 mo). Only 2 of these had evidence of neurofibromatosis-1. OPHG was diagnosed using computed tomography and/or magnetic resonance imaging. Histologic studies showed low-grade astrocytoma (WHO grade I or II) in 16 cases, anaplastic astrocytoma in 1, and oligoastrocytoma (WHO grade III) in 1. Treatment included partial tumor resection in 12 patients, chemotherapy in 5, and radiotherapy in 3. Ophthalmologic and visual alterations occurred in 12 patients, endocrine alterations in 6, and neurologic signs in 5. All treatment modalities led to tumor shrinkage and stabilization for a variable period, but none of them totally eradicated the tumor. Fourteen (78%) of 18 patients had a sustained reduction of tumor size between 6 months and 17 years. The 5-year overall and progression-free survival rates were 80.0% and 63.3%, respectively. Fifty-six percent of patients had endocrinologic sequelae, with growth hormone deficiency being the most common. Two patients died, none with neurofibromatosis-1, with a hypothalamic/chiasmatic tumor with suprasellar extension and accompanying electrolyte abnormalities. Because progression of these tumors is slow and associated with endocrinopathy, we recommend chemotherapy as a primary treatment of OPHG if the disease progresses.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hypothalamic Neoplasms/therapy , Optic Nerve Glioma/therapy , Visual Pathways/pathology , Adolescent , Child , Child, Preschool , Disease Progression , Female , Follow-Up Studies , Humans , Hypothalamic Neoplasms/diagnosis , Infant , Magnetic Resonance Imaging , Male , Optic Nerve Glioma/diagnosis , Predictive Value of Tests , Retrospective Studies , Survival Rate , Treatment Outcome
20.
Pituitary ; 11(1): 85-7, 2008.
Article in English | MEDLINE | ID: mdl-17440820

ABSTRACT

The simultaneous occurrence of a hypothalamic and sellar gangliocytoma with a pituitary prolactinoma is very rare. The explanation for such an association is not known. We describe the case of a woman who had a coexisting adjacent pituitary prolactinoma and gangliocytoma within the same sellar mass. The tumor cells of the gangliocytoma demonstrated expression of enkephalin, a product of proopiomelanocortin known to be a prolactin secretagogue. We postulate that in this patient there may be a link between gangliocytoma enkephalin and prolactin hypersecretion.


Subject(s)
Ganglioneuroma/pathology , Hypothalamic Neoplasms/pathology , Neoplasms, Multiple Primary , Pituitary Neoplasms/pathology , Prolactinoma/pathology , Sella Turcica/pathology , Skull Neoplasms/pathology , Chemotherapy, Adjuvant , Dopamine Agonists/therapeutic use , Enkephalins/metabolism , Female , Ganglioneuroma/metabolism , Ganglioneuroma/therapy , Hormone Replacement Therapy , Humans , Hypothalamic Neoplasms/metabolism , Hypothalamic Neoplasms/therapy , Magnetic Resonance Imaging , Neurosurgical Procedures , Pituitary Neoplasms/metabolism , Pituitary Neoplasms/therapy , Prolactin/metabolism , Prolactinoma/metabolism , Prolactinoma/therapy , Skull Neoplasms/metabolism , Skull Neoplasms/therapy , Treatment Outcome , Young Adult
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