Hemangioblastomas and Neurogenic Polyglobulia

Abstract BACKGROUND: Neurogenic polyglobulia occurs with central nervous system hemangioblastomas. Among the suggested mechanisms are extramedullary hematopoiesis in the tumor tissue and germline mutations of the von Hippel-Lindau (VHL) tumor suppressor gene. OBJECTIVE: To determine the frequency and driving mechanisms of polyglobulia in central nervous system hemangioblastomas. METHODS: We performed a retrospective analysis of pre- and postoperative (at 3 and 12 months) hemoglobin levels in a consecutive series of patients with hemangioblastomas operated on in our institution from 1996 to 2009. We performed molecular genetic analyses for mutations of the VHL tumor suppressor gene. RESULTS: Preoperative hemoglobin levels were available from 164 patients. The average hemoglobin level (15.2 g/dL in males and 13.1 g/dL in females) was within normal range according to our standards. Of 22 patients with increased preoperative hemoglobin levels (>17 g/dL in males and >15 g/dL in females), 8 presented with pathological hemoglobin (>18.5 g/dL in males and >16.5 g/dL in females) according to World Health Organization criteria. Surgical removal of the hemangioblastoma resulted in a permanent cure of polyglobulia in all patients. Six of the 8 patients with pathological hemoglobin elevation carried a germline mutation of the VHL tumor suppressor gene. CONCLUSION: Neurogenic polyglobulia occurs in a subset of patients with hemangioblastomas. This phenomenon is mostly observed in VHL mutation carriers, but also occurs in patients with sporadic hemangioblastomas. Removal of the tumor results in the permanent cure of polyglobulia. Our observations suggest that polyglobulia is an effect by the tumor itself, either due to paraneoplasia or extramedullary hematopoiesis.

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High levels of expression of the tumor suppressor gene APC during development of the rat central nervous system

Journal of Neuroscience ◽

10.1523/jneurosci.14-05-03059.1994 ◽

1994 ◽

Vol 14 (5) ◽

pp. 3059-3071 ◽

Cited By ~ 50

Author(s):

RV Bhat ◽

JM Baraban ◽

RC Johnson ◽

BA Eipper ◽

RE Mains

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Tumor Suppressor ◽

Tumor Suppressor Gene ◽

Suppressor Gene

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Mutations and Loss of Heterozygosity of the von Hippel-Lindau Tumor Suppressor Gene in Sporadic Central Nervous System Hemangioblastomas

Brain Tumor ◽

10.1007/978-4-431-66887-9_29 ◽

1996 ◽

pp. 277-282 ◽

Cited By ~ 1

Author(s):

Susumu Ito ◽

Hiroshi Kanno ◽

Keiich Kondo ◽

Taro Shuin ◽

Masahiro Yao ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Tumor Suppressor ◽

Tumor Suppressor Gene ◽

Loss Of Heterozygosity ◽

Suppressor Gene ◽

Von Hippel Lindau

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Possible Correlation between Hypomelanosis of Ito and Wilms’ Tumor

Case Reports in Pediatrics ◽

10.1155/2018/5938120 ◽

2018 ◽

Vol 2018 ◽

pp. 1-4

Author(s):

Daniella Bello-Germino ◽

Rasmey Chhin ◽

Thu Tran ◽

Tetyana L. Vasylyeva

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Tumor Suppressor ◽

Wilms Tumor ◽

Tumor Stage ◽

Suppressor Gene ◽

Hypomelanosis Of Ito ◽

Neurocutaneous Disorder ◽

Clinical Diagnoses ◽

Organ Dysfunctions

Hypomelanosis of Ito is a neurocutaneous disorder characterized by skin manifestations in a characteristic pattern associated with musculoskeletal and central nervous system symptoms. Our patient was diagnosed with Wilms’ tumor stage I at age two and was also found to have distinct streaked areas of skin hyper- and hypopigmentation suggestive of Hypomelanosis of Ito. We believe that our patient’s clinical diagnoses of Hypomelanosis of Ito and Wilms’ tumor are interlinked. The connecting factor is yet to be identified. Our patient does not have a deletion of 11p13 associated with a defect in WT1, the Wilms’ tumor suppressor gene. As such, it is quite possible that what made her more susceptible to the development of Wilms’ tumor was her Hypomelanosis of Ito, which is implicated in a number of other organ dysfunctions.

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Mutations of thep53 tumor suppressor gene in neoplasms of the human nervous system

Molecular Carcinogenesis ◽

10.1002/mc.2940080203 ◽

1993 ◽

Vol 8 (2) ◽

pp. 74-80 ◽

Cited By ~ 157

Author(s):

Hiroko Ohgaki ◽

Robert H. Eibl ◽

Martin B. Reichel ◽

Luigi Mariani ◽

Iver Petersen ◽

...

Keyword(s):

Nervous System ◽

Tumor Suppressor ◽

Tumor Suppressor Gene ◽

Suppressor Gene ◽

Human Nervous System

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Doppler-Sonographically Guided Resection of Central Nervous System Hemangioblastomas

Operative Neurosurgery ◽

10.1227/neu.0b013e3182124677 ◽

2011 ◽

Vol 68 (suppl_2) ◽

pp. ons267-ons275 ◽

Cited By ~ 5

Author(s):

Sven Gläsker ◽

Mukesch J. Shah ◽

Beate Hippchen ◽

Hartmut P. H. Neumann ◽

Vera van Velthoven

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Power Doppler ◽

Suppressor Gene ◽

Vascular Lesions ◽

Surgical Removal ◽

Consecutive Series ◽

Benign Condition ◽

Doppler Flow ◽

Vhl Disease

Abstract Background: Central nervous system (CNS) hemangioblastomas are a benign condition, which can be permanently cured by complete surgical removal. However, the vascular nature of these lesions and difficulties in localizing the tumors account for operative morbidity and recurrence. Power Doppler flow sonography has been proven useful during surgical removal of other vascular lesions. Objective: To evaluate the usefulness of Power Doppler flow sonography for hemangioblastoma. Methods: We used the SonoWand Invite (Sonowand AS, Trondheim, Norway) intraoperative navigation system in a consecutive series of hemangioblastomas operated on at our institution. Patients with von Hippel-Lindau (VHL) disease as well as sporadic hemangioblastomas were included. Results: The system was used on n = 64 consecutive hemangioblastomas operated on at our institution from 2007 to 2009. The tumors were localized in the cerebellum (n = 26), spinal cord (n = 27), brainstem (n = 10), and supratentorial (n = 1). In VHL disease was diagnosed 53 patients, and germline mutations of the VHL tumor suppressor gene were identified in 98%. Average tumor size was 1782 mm3 and 45% of the tumors were cystic. Forty-two of 64 tumors could be localized by grayscale sonography. All tumors were visible on power Doppler flow sonography. However, in 40 cases, only the pathological vessels and not the solid tumor itself enhanced on power Doppler. Postoperative MRI follow-up revealed remnant/recurrent tumors in 2 cases. CONCLUSION: Power Doppler flow sonography is a sensitive intraoperative tool to guide the surgical approach and resection and provides reliable resection control in surgery of CNS hemangioblastoma.

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Pathomechanisms in schwannoma development and progression

Oncogene ◽

10.1038/s41388-020-1374-5 ◽

2020 ◽

Vol 39 (32) ◽

pp. 5421-5429 ◽

Cited By ~ 1

Author(s):

Dario-Lucas Helbing ◽

Alexander Schulz ◽

Helen Morrison

Keyword(s):

Extracellular Matrix ◽

T Cells ◽

Nervous System ◽

Tumor Microenvironment ◽

Tumor Suppressor ◽

Tumor Suppressor Gene ◽

Schwann Cells ◽

Cell Types ◽

Suppressor Gene ◽

Different Cell Types

Abstract Schwannomas are tumors of the peripheral nervous system, consisting of different cell types. These include tumorigenic Schwann cells, axons, macrophages, T cells, fibroblasts, blood vessels, and an extracellular matrix. All cell types involved constitute an intricate “tumor microenvironment” and play relevant roles in the development and progression of schwannomas. Although Nf2 tumor suppressor gene-deficient Schwann cells are the primary tumorigenic element and principle focus of current research efforts, evidence is accumulating regarding the contributory roles of other cell types in schwannoma pathology. In this review, we aim to provide an overview of intra- and intercellular mechanisms contributing to schwannoma formation. “Genes load the gun, environment pulls the trigger.” -George A. Bray

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Coexpression of Erythropoietin and Vascular Endothelial Growth Factor in Nervous System Tumors Associated With von Hippel-Lindau Tumor Suppressor Gene Loss of Function

Blood ◽

10.1182/blood.v92.9.3388 ◽

1998 ◽

Vol 92 (9) ◽

pp. 3388-3393 ◽

Cited By ~ 78

Author(s):

Marion Krieg ◽

Hugo H. Marti ◽

Karl H. Plate

Keyword(s):

Vascular Endothelial Growth Factor ◽

Nervous System ◽

Growth Factor ◽

Tumor Suppressor ◽

Tumor Suppressor Gene ◽

Suppressor Gene ◽

Vascular Tumors ◽

Vascular Endothelial ◽

Von Hippel Lindau ◽

Endothelial Growth Factor

Abstract Hemangioblastomas are highly vascular tumors of the central nervous system that overexpress the hypoxia-inducible gene, vascular endothelial growth factor (VEGF), as a consequence of mutational inactivation of the von Hippel-Lindau tumor suppressor gene (VHL). Previous reports showed that hemangioblastomas can also express erythropoietin (Epo), which is also hypoxia-inducible. However, Epo expression in hemangioblastomas was observed only in individual cases, and the analyses were mainly based on indirect determination of erythropoiesis-stimulating activity. Therefore, we analyzed a series of 11 hemangioblastomas for Epo, VEGF, and VHL expression by Northern blot analysis and compared the results with normal brain and glioblastomas. Surprisingly, we observed Epo mRNA expression in all hemangioblastoma specimens analyzed, but in none of four glioblastomas. In contrast, VEGF mRNA was expressed in all hemangioblastomas and all glioblastomas. In situ hybridization revealed neoplastic stromal cells as Epo- and VEGF-producing cells in hemangioblastomas. These results suggest that in the nonhypoxic microenvironment of hemangioblastoma, Epo, similar to VEGF, might be negatively regulated by the VHL gene product. © 1998 by The American Society of Hematology.

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Coexpression of Erythropoietin and Vascular Endothelial Growth Factor in Nervous System Tumors Associated With von Hippel-Lindau Tumor Suppressor Gene Loss of Function

Blood ◽

10.1182/blood.v92.9.3388.421a09_3388_3393 ◽

1998 ◽

Vol 92 (9) ◽

pp. 3388-3393 ◽

Cited By ~ 6

Author(s):

Marion Krieg ◽

Hugo H. Marti ◽

Karl H. Plate

Keyword(s):

Vascular Endothelial Growth Factor ◽

Nervous System ◽

Growth Factor ◽

Tumor Suppressor ◽

Tumor Suppressor Gene ◽

Suppressor Gene ◽

Vascular Tumors ◽

Vascular Endothelial ◽

Von Hippel Lindau ◽

Endothelial Growth Factor

Hemangioblastomas are highly vascular tumors of the central nervous system that overexpress the hypoxia-inducible gene, vascular endothelial growth factor (VEGF), as a consequence of mutational inactivation of the von Hippel-Lindau tumor suppressor gene (VHL). Previous reports showed that hemangioblastomas can also express erythropoietin (Epo), which is also hypoxia-inducible. However, Epo expression in hemangioblastomas was observed only in individual cases, and the analyses were mainly based on indirect determination of erythropoiesis-stimulating activity. Therefore, we analyzed a series of 11 hemangioblastomas for Epo, VEGF, and VHL expression by Northern blot analysis and compared the results with normal brain and glioblastomas. Surprisingly, we observed Epo mRNA expression in all hemangioblastoma specimens analyzed, but in none of four glioblastomas. In contrast, VEGF mRNA was expressed in all hemangioblastomas and all glioblastomas. In situ hybridization revealed neoplastic stromal cells as Epo- and VEGF-producing cells in hemangioblastomas. These results suggest that in the nonhypoxic microenvironment of hemangioblastoma, Epo, similar to VEGF, might be negatively regulated by the VHL gene product. © 1998 by The American Society of Hematology.

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