RESUMEN
INTRODUCTION: Hemangioblastoma (HB) is a benign tumor of the central nervous system, associated with von Hippel-Lindau disease (VHL), or sporadic. The aim of this study was to compare and examine the clinical-pathological profile of patients with spinal hemangioblastoma and YAP expression. METHODS: A retrospective, descriptive, comparative study. All patients who underwent surgery for spinal HB between 2016 and 2023 were included. Clinical and radiological data were collected and analyzed. An immunohistochemistry panel including NeuN, neurofilaments (NF), and YAP-1, was performed. RESULTS: Nine patients were studied, six women and three men. Four patients had previously diagnosed VHL. The tumor location included: four cervical (44.44%), two thoracic (22.22%), two pontine with cervical extension (22.22%) and one patient with two lesions, one cervical and one thoracic (11.11%). Non-significant clinical differences were identified between VHL and sporadic patients. Imaging evidenced seven extramedullary and three intramedullary tumors. Histologically, intra-tumoral and perivascular axonal tracts were observed in all cases. One third of the tumors (two with VHL and one sporadic) presented extramedullary hematopoiesis. Seven cases (77.8%) expressed nuclear YAP (three with VHL and four sporadic HBs). The surgical outcome was good and only one patient with VHL undergoing subtotal resection had recurrence. CONCLUSIONS: Spinal HBs can be associated with VHL or be sporadic. To the best of our knowledge, this is the first study to describe YAP expression in HB. It is important to investigate the involvement of the Hippo pathway in HBs as a possible therapeutic target.
Asunto(s)
Hemangioblastoma , Factores de Transcripción , Proteínas Señalizadoras YAP , Enfermedad de von Hippel-Lindau , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Proteínas Adaptadoras Transductoras de Señales/análisis , Hemangioblastoma/patología , Hemangioblastoma/química , Estudios Retrospectivos , Neoplasias de la Médula Espinal/patología , Neoplasias de la Médula Espinal/química , Neoplasias de la Médula Espinal/cirugía , Neoplasias de la Columna Vertebral/patología , Neoplasias de la Columna Vertebral/química , Factores de Transcripción/análisis , Enfermedad de von Hippel-Lindau/complicaciones , Enfermedad de von Hippel-Lindau/patologíaRESUMEN
Tumor-to-tumor metastasis in the central nerve system is uncommon in our routine practice. Most reports include metastatic breast cancer into meningioma. Here we report a metastatic clear cell renal cell carcinoma (ccRCC) into a cerebellar hemangioblastoma in a patient with von Hippel-Lindau (VHL) disease. Imaging cannot distinguish metastatic ccRCC from primary cerebellar hemangioblastoma. Immuno-molecular studies are proven to be diagnostic. We also reviewed previously documented tumor-to-tumor metastasis of ccRCC to cerebellar hemangioblastoma in VHL disease. Lastly, we discussed potential mechanisms involved in the metastasis of ccRCC to hemangioblastoma in the cerebellum in patients with VHL.
Asunto(s)
Carcinoma de Células Renales , Neoplasias Cerebelosas , Hemangioblastoma , Neoplasias Renales , Enfermedad de von Hippel-Lindau , Humanos , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/diagnóstico , Neoplasias Cerebelosas/patología , Neoplasias Cerebelosas/secundario , Hemangioblastoma/patología , Hemangioblastoma/diagnóstico , Neoplasias Renales/patología , Neoplasias Renales/diagnóstico , Metástasis de la Neoplasia , Enfermedad de von Hippel-Lindau/patología , Enfermedad de von Hippel-Lindau/diagnósticoRESUMEN
PURPOSE: Von Hippel-Lindau (VHL) disease is an autosomal-dominantly inherited tumor predisposition syndrome. One of the most common tumors are central nervous system (CNS) hemangioblastomas. Recommendations on the initiation and continuation of the screening and surveillance program for CNS tumors in pediatric VHL patients are based on small case series and thus low evidence level. To derive more robust screening recommendations, we report on the largest monocentric pediatric cohort of VHL patients. METHODS: We performed a retrospective analysis on a pediatric cohort of 99 VHL patients consulted at our VHL center from 1992 to 2023. Clinical, surgical, genetic, and imaging data were collected and statistically analyzed. RESULTS: 42 patients (50% male) developed CNS hemangioblastomas, of whom 18 patients (56% male) underwent hemangioblastoma surgery (mean age at first surgery: 14.9 ± 1.9 years; range 10.2-17). The first asymptomatic patient was operated on at the age of 13.2 years due to tumor progress. Truncating VHL mutation carriers had a significantly higher manifestation rate (HR = 3.7, 95% CI: 1.9-7.4, p < 0.0001) and surgery rate (HR = 3.3, 95% CI: 1.2-8.9, p = 0.02) compared with missense mutation carriers. CONCLUSION: We recommend starting MRI imaging at the age of 12 years with examination intervals every (1-) 2 years depending on CNS involvement. Special attention should be paid to patients with truncating variants. Affected families should be educated regularly on potential tumor-associated symptoms to enable timely MRI imaging and eventually intervention, as CNS hemangioblastoma may develop before screening begins. GERMAN CLINICAL TRIALS REGISTER REGISTRATION NUMBER: DRKS00029553, date of registration 08/16/2022, retrospectively registered.
Asunto(s)
Hemangioblastoma , Enfermedad de von Hippel-Lindau , Humanos , Enfermedad de von Hippel-Lindau/genética , Enfermedad de von Hippel-Lindau/complicaciones , Hemangioblastoma/cirugía , Hemangioblastoma/genética , Hemangioblastoma/patología , Masculino , Femenino , Adolescente , Niño , Estudios Retrospectivos , Neoplasias Cerebelosas/genética , Neoplasias Cerebelosas/cirugía , Neoplasias Cerebelosas/patología , Neoplasias del Sistema Nervioso Central/genética , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/cirugía , Neoplasias del Sistema Nervioso Central/patología , Estudios de Seguimiento , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/genéticaRESUMEN
ABSTRACT: Renal hemangioblastoma (HB) is a rare subset of HBs arising outside of the central nervous system (CNS), with its molecular drivers remaining entirely unknown. There were no significant alterations detected in previous studies, including von Hippel-Lindau gene alterations, which are commonly associated with CNS-HB. This study aimed to determine the real molecular identity of renal HB and better understand its relationship with CNS-HB. A cohort of 10 renal HBs was submitted for next-generation sequencing technology. As a control, 5 classic CNS-HBs were similarly analyzed. Based on the molecular results, glycoprotein nonmetastatic B (GPNMB) immunohistochemistry was further performed in the cases of renal HB and CNS-HB. Mutational analysis demonstrated that all 10 renal HBs harbored somatic mutations in tuberous sclerosis complex 1 ( TSC1 , 5 cases), TSC2 (3 cases), and mammalian target of rapamycin (2 cases), with the majority classified as pathogenic or likely pathogenic. The CNS-HB cohort uniformly demonstrated somatic mutations in the von Hippel-Lindau gene. GPNMB was strong and diffuse in all 10 renal HBs and completely negative in CNS-HBs, reinforcing the molecular findings. Our study reveals a specific molecular hallmark in renal HB, characterized by recurrent TSC/mammalian target of rapamycin mutations, which defines it as a unique entity distinct from CNS-HB. This molecular finding potentially expands the therapeutic options for patients with renal HB. GPNMB can be considered for inclusion in immunohistochemical panels to improve renal HB identification.
Asunto(s)
Hemangioblastoma , Neoplasias Renales , Mutación , Serina-Treonina Quinasas TOR , Proteína 2 del Complejo de la Esclerosis Tuberosa , Humanos , Hemangioblastoma/genética , Hemangioblastoma/patología , Hemangioblastoma/química , Neoplasias Renales/genética , Neoplasias Renales/patología , Neoplasias Renales/química , Femenino , Masculino , Proteína 2 del Complejo de la Esclerosis Tuberosa/genética , Adulto , Persona de Mediana Edad , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Análisis Mutacional de ADN , Esclerosis Tuberosa/genética , Esclerosis Tuberosa/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/análisis , Neoplasias del Sistema Nervioso Central/genética , Neoplasias del Sistema Nervioso Central/patología , Neoplasias del Sistema Nervioso Central/química , Inmunohistoquímica , Proteína 1 del Complejo de la Esclerosis Tuberosa/genética , Anciano , Predisposición Genética a la Enfermedad , Adolescente , Fenotipo , Adulto Joven , Niño , Secuenciación de Nucleótidos de Alto RendimientoAsunto(s)
Hemangioblastoma , Neoplasias Pancreáticas , Esclerosis Tuberosa , Humanos , Hemangioblastoma/cirugía , Hemangioblastoma/complicaciones , Hemangioblastoma/patología , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/complicaciones , Tomografía Computarizada por Rayos X , Esclerosis Tuberosa/complicaciones , Esclerosis Tuberosa/patologíaRESUMEN
The association between vascular tumors and thrombocytopenia is rare. Kasabach-Merritt Syndrome is seen in childhood and is characterized by hemangiomas and thrombocytopenia. A 42 years-old man with a cerebellar hemangioblastoma and thrombocytopenia, admitted with a subarachnoid hemorrhage is reported. The patient was operated and required a splenectomy to manage the thrombocytopenia. After the splenectomy the patient developed a subdural hematoma that was operated. Despite the surgical treatment, the patient died.
Asunto(s)
Humanos , Masculino , Adulto , Trombocitopenia/complicaciones , Neoplasias Cerebelosas/complicaciones , Hemangioblastoma/complicaciones , Trombocitopenia/patología , Trombocitopenia/terapia , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos X , Neoplasias Cerebelosas/patología , Neoplasias Cerebelosas/terapia , Hemangioblastoma/patología , Hemangioblastoma/terapia , Resultado Fatal , Diagnóstico Diferencial , Síndrome de Kasabach-Merritt/patología , Hematoma Subdural/complicaciones , Hematoma Subdural/patologíaRESUMEN
Relatamos os achados clínicos, epidemiológicos e anatomopatológicos de 14 casos de hemangioblastoma. Sessenta e quatro por cento ocorreram em pacientes do sexo masculino, com idades variando de 16 a 60 anos, com média de 34,4 anos. Nove localizaram-se no cerebelo. Os sintomas mais comuns foram cefaléia (n=7) e tontura (n=7), com período médio de evolução de 70 dias. O diagnóstico de síndrome de von Hippel-Lindau (vHL) foi feito em 3 pacientes. Onze pacientes foram submetidos a ressecção cirúrgica total e 3 a exérese parcial. Evidenciou-se recidiva em 28 ppor cento dos casos, em 3 anos de acompanhamento. Os pacientes com vHL apresentaram recidiva em 66 por cento dos casos. Estes achados aproximam-se dos encontrados na literatura, enfatizando a morbidade deste tumor quando associado à vHL.
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Neoplasias Cerebelosas/patología , Hemangioblastoma/patología , Neoplasias de la Médula Espinal/patología , Neoplasias Cerebelosas/cirugía , Hemangioblastoma/cirugía , Recurrencia , Neoplasias de la Médula Espinal/cirugía , Síndrome , Enfermedad de von Hippel-Lindau/complicaciones , Enfermedad de von Hippel-Lindau/diagnósticoRESUMEN
El hemangioblastoma cerebeloso es un tumor raro que tiene una incidencia de 1 a 2 por ciento entre los tumores cerebelosos. Se presenta generalmente en hombres jóvenes, de edad media entre 30 y 40 años. Es un tumor formado por numerosos vasos sanguíneos de tipo capilar con células endoteliales, pericitos y células estromales claras vacuoladas. En el Hospital Juárez de México se estudiaron cuatro casos de hemangioblastomas cerebelosos, de los cuales dos eran hombres y dos mujeres todos ellos presentaron síndrome de hipertención endocraneana y síndrome cerebeloso. El diagnóstico radiológico se dio en tres casos de cisticercosis y uno de hemangioblastoma. A todos ellos se les operó inicialmente realizándose cirugía descompresiva. El diagnóstico histológico de hemangioblastoma se realizó en el estudio definitivo. Dicho diagnóstico es de por sí difíil, por lo que requiere tinciones especiales; en tanto, el diagnóstico diferencial debe hacerse con carcinoma renal o astrocitoma pilocítico
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Enfermedades Cerebelosas/diagnóstico , Enfermedades Cerebelosas/patología , Hemangioblastoma/diagnóstico , Hemangioblastoma/patología , Hemangioblastoma/cirugía , Tomografía Computarizada por Rayos XRESUMEN
Os autores relatam os achados de autópsia de pacientes de uma mesma família e o diagnóstico por biópsia de hemangioblastoma de um terceiro membro desta mesma família. O primeiro paciente tinha 34 anos por ocasiao do óbito e os achados de necrópsia mostraram hemangioblastoma de retina, cerebelo, bulbo e medula espinhal, além de carcinoma renal, feocromocitoma, lesoes císticas de rim e pâncreas, hidromielia e meningiomas atípicos. Seu irmao morreu com 30 anos de idade e a autópsia revelou hemangioblastomas de cerebelo, carcinoma renal e cistoadenoma de células de células claras de epidídimo. A terceira paciente era filha do primeiro paciente e apresentou cefaléia e ataxia. A tomografia computadorizada mostrou lesao cerebelar cística e a biópsia confirmou tratar-se de hemangioblastoma. Sao feitas consideraçoes epidemiológicas sobre lesoes viscerais e do sistema nervoso mais comumente encontradas, além de discutir critérios diagnósticos.
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Enfermedad de von Hippel-Lindau/patología , Carcinoma de Células Renales , Neoplasias Cerebelosas/patología , Angiografía Cerebral , Hemangioblastoma/patología , Hemangioblastoma/cirugía , Neoplasias Renales , Meningioma/patología , Neoplasias Meníngeas/patología , Enfermedad de von Hippel-Lindau/genéticaRESUMEN
Os autores relatam um caso de paciente masculino, 47 anos, com hidrocefalia e malformaçao vascular da fossa posterior, indicadas por arteriografia. O paciente foi submetido à drenagem ventrículo-peritoneal em duas ocasioes, ocorrendo obstruçao da válvula em ambas. Quatro meses após o surgimento dos sintomas, o paciente faleceu, sendo demonstrada, pela autópsia, uma neoplasia cística ocupando o bulbo, cujo diagnóstico histopatológico foi hemangioblastoma. O tumor apresentou reaçoes de imuno-histoquímica positivas para vimentina, proteína S100, enolase e positividade discutível para proteína ácida fibraglial (GFAP).