Extraneuraxial hemangioblastoma: A clinicopathologic study of 10 cases with molecular analysis of the VHL gene

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11140%2F18%3A10390297" target="_blank" >RIV/00216208:11140/18:10390297 - isvavai.cz</a>

Result on the web

<a href="https://doi.org/10.1016/j.prp.2018.05.007" target="_blank" >https://doi.org/10.1016/j.prp.2018.05.007</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.prp.2018.05.007" target="_blank" >10.1016/j.prp.2018.05.007</a>

Result language

angličtina

Original language name

Extraneuraxial hemangioblastoma: A clinicopathologic study of 10 cases with molecular analysis of the VHL gene

Original language description

Less than 250 extraneuraxial hemangioblastomas occurring in paraneuraxial or peripheral sites have been reported to date, sporadically or in the setting of von Hippel-Lindau disease. Seventeen such cases underwent molecular genetic analysis, using either the patient&apos;s peripheral blood in 9 cases or paraffin embedded tumor tissue in the rest. VHL gene mutations were documented in 3/9 cases in which DNA from peripheral blood lymphocytes was used, all with clinically manifest von Hippel-Lindau disease; instead, no VHL gene alterations were found in all of the 8 cases with sporadic extraneuraxial hemangioblastoma in which DNA from tumor tissue was analyzed. Our aim is to investigate the molecular genetic profile of the VHL gene in extraneuraxial hemangioblastoma using paraffin embedded tumor tissues. The clinical features, histopathology, and molecular investigations of 10 extraneuraxial hemangioblastomas (7 females, 3 males; median age: 47 years) are presented herein. The histopathologic diagnosis was supported by immunohistochemistry (10/10) and electron microscopy (4/10). Molecular genetic analysis was conducted (10/10) for VHL gene mutations, LOH, and gene promoter methylation. Two of the present cases were already published with only limited or no molecular investigations. Four tumors of the present series were paraneuraxial, and 6 peripheral (2 involved soft tissues, and 4 the kidney). One tumor was von Hippel-Lindau disease-associated, 1 was classified as &quot;hemangioblastoma-only VHLD&quot;, 7 were sporadic, and one was unknown. All were histopathologically analogous to their counterpart located inside the central nervous system. Immunophenotypically, all tumors expressed vimentin, S-100, NSE, and alpha-inhibin (10/10). Ultrastructurally, unbound lipid droplets filled the cytoplasms of the stromal cells. Molecular analysis revealed 3 inactivating mutations (1 germline, two somatic) in the coding sequence of the VHL gene in 2 different extraneuraxial hemangioblastomas, and LOH in 4 (two as a double hit), all non-renal extraneuraxial hemangioblastomas. Methylation analysis failed to disclose promoter methylation in any case. In conclusion, we report eight new cases from the wide category of extraneuraxial hemangioblastomas (4 paraneuraxial, and 4 renal), one of which was von Hippel-Lindau disease-associated and 7 sporadic. VHL gene alterations were found not only in the von Hippel-Lindau disease-associated tumor, but for the first time also in 3 sporadic ones, two of which with novel mutations.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30109 - Pathology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Pathology: Research and Practice

ISSN

0344-0338

e-ISSN

—

Volume of the periodical

214

Issue of the periodical within the volume

8

Country of publishing house

DE - GERMANY

Number of pages

10

Pages from-to

1156-1165

UT code for WoS article

000443104700015

EID of the result in the Scopus database

2-s2.0-85048865996