Malignant Chondroblastoma: An Epigenetically Distinct Subtype of Chondroblastoma With a Predilection for the Skeletally Mature

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11140%2F25%3A10498691" target="_blank" >RIV/00216208:11140/25:10498691 - isvavai.cz</a>

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=NDDJlR546i" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=NDDJlR546i</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.modpat.2025.100790" target="_blank" >10.1016/j.modpat.2025.100790</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Malignant Chondroblastoma: An Epigenetically Distinct Subtype of Chondroblastoma With a Predilection for the Skeletally Mature

Popis výsledku v původním jazyce

Malignant chondroblastoma is a recently described variant of chondroblastoma showing a distinct age/site distribution and morphology along with the typical H3-3B p.K36M mutation. We sought to further compare conventional and malignant chondroblastoma. Malignant chondroblastomas were collected. H3-3 K36M immunohistochemistry, as well as DNA methylation and copy number profiling, were performed and compared with conventional chondroblastoma. Forty-one samples from 26 patients were identified (20 males, 6 females; age: 19-62 years; median: 39 years). Anatomical sites included rib (7), pelvis (4), acromion (4), scapula (4), spine (2), long bone (3), calcaneus (1), and talus (1). Imaging showed an expansile mass with variable cortical erosion and/or breakthrough. Most patients (n = 17) showed sheets of atypical ovoid cells deposited in a myxoid stroma. Osteoclast-like giant cells/matrix formation was scarce. Six patients had tumors with features of conventional chondroblastoma but significant cytologic atypia. Three tumors demonstrated a morphology indistinguishable from conventional chondroblastoma except for extensive permeation, and one of these cases showed a transition to high-grade sarcoma. The final case was composed only of high-grade pleomorphic sarcoma that harbored an H3F3A p.K36M mutation. When an adjacent host bone was present, permeative growth through the cortex and native trabeculae was noted. All samples tested positive for the H3-3 K36M-specific antibody (26 of 26). Methylome profiling of 28 specimens from 24 patients revealed that 26 of these specimens formed a distinct cluster on a uniform manifold approximation and projection dimension reduction plot separate from conventional chondroblastoma and high-grade osteosarcoma. Of 26 methylomes from which interpretable copy number profiles can be derived, 12 had no variations, whereas 14 had copy number changes. Of 22 patients, 11 experienced local recurrence, 8 patients developed metastasis, and 3 patients died of disease. Malignant chondroblastoma is a rare, clinically and epigentically distinct variant of chondroblastoma with a predilection for the flat bones of skeletally mature individuals and high rates of local recurrence and distant metastases. A subset transforms into high-grade pleomorphic sarcoma, either de novo or in subsequent recurrences. Malignant chondroblastoma with high-grade features and/or copy number variations appears to have a higher propensity for adverse events, including death from disease.

Název v anglickém jazyce

Malignant Chondroblastoma: An Epigenetically Distinct Subtype of Chondroblastoma With a Predilection for the Skeletally Mature

Popis výsledku anglicky

Malignant chondroblastoma is a recently described variant of chondroblastoma showing a distinct age/site distribution and morphology along with the typical H3-3B p.K36M mutation. We sought to further compare conventional and malignant chondroblastoma. Malignant chondroblastomas were collected. H3-3 K36M immunohistochemistry, as well as DNA methylation and copy number profiling, were performed and compared with conventional chondroblastoma. Forty-one samples from 26 patients were identified (20 males, 6 females; age: 19-62 years; median: 39 years). Anatomical sites included rib (7), pelvis (4), acromion (4), scapula (4), spine (2), long bone (3), calcaneus (1), and talus (1). Imaging showed an expansile mass with variable cortical erosion and/or breakthrough. Most patients (n = 17) showed sheets of atypical ovoid cells deposited in a myxoid stroma. Osteoclast-like giant cells/matrix formation was scarce. Six patients had tumors with features of conventional chondroblastoma but significant cytologic atypia. Three tumors demonstrated a morphology indistinguishable from conventional chondroblastoma except for extensive permeation, and one of these cases showed a transition to high-grade sarcoma. The final case was composed only of high-grade pleomorphic sarcoma that harbored an H3F3A p.K36M mutation. When an adjacent host bone was present, permeative growth through the cortex and native trabeculae was noted. All samples tested positive for the H3-3 K36M-specific antibody (26 of 26). Methylome profiling of 28 specimens from 24 patients revealed that 26 of these specimens formed a distinct cluster on a uniform manifold approximation and projection dimension reduction plot separate from conventional chondroblastoma and high-grade osteosarcoma. Of 26 methylomes from which interpretable copy number profiles can be derived, 12 had no variations, whereas 14 had copy number changes. Of 22 patients, 11 experienced local recurrence, 8 patients developed metastasis, and 3 patients died of disease. Malignant chondroblastoma is a rare, clinically and epigentically distinct variant of chondroblastoma with a predilection for the flat bones of skeletally mature individuals and high rates of local recurrence and distant metastases. A subset transforms into high-grade pleomorphic sarcoma, either de novo or in subsequent recurrences. Malignant chondroblastoma with high-grade features and/or copy number variations appears to have a higher propensity for adverse events, including death from disease.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30109 - Pathology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

Modern Pathology

ISSN

0893-3952

e-ISSN

1530-0285

Svazek periodika

38

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

100790

Kód UT WoS článku

001506850000001

EID výsledku v databázi Scopus

2-s2.0-105007433531