伴有 HRAS 突变的毛细血管型肌内血管瘤：扩展分子遗传谱，强调与动静脉畸形的重叠以及与婴儿血管瘤的区别。

IF 2.7 2区医学 Q2 PATHOLOGY

Human pathology Pub Date : 2024-10-24 DOI:10.1016/j.humpath.2024.105672

Shuang Xue , Mei Li , Xijun Zhang , Peigang Ning , Changxian Dong , Xiaonan Guo , Qiuyu Liu

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引用次数: 0

摘要

目的：肌内毛细血管瘤（IHCT）是一种罕见的快速流动血管病变。本研究旨在阐明 IHCT 患者的临床病理学、放射学和分子特征之间的关系：我们回顾了病理数据库中2014年至2023年所有接受手术治疗的IHCT病例。通过新一代测序（NGS）和桑格测序分析了 10 例病例。10例患者（6男4女）的中位年龄为18岁（1-37岁）。病变位于躯干（4 例）、上肢（2 例）、下肢（2 例）、肩部（1 例）和颈部（1 例）。IHCT 最常见的症状是逐渐增大的无痛性肿块。从组织病理学角度看，所有病变均表现为毛细血管的聚集、分叶和吻合索，这些血管分离或浸润骨骼肌。有四例病例的病变周围血管不规则扩张，管壁较厚，如动静脉畸形（AVM）。核磁共振成像结果通常表现为界限清晰的均质肿块。在 10 例 IHCT 病例中，有 7 例检测到了体细胞突变。其中四例携带 MAP2K1 基因突变（p.Q58_E62del、p.K57_G61del、p.K57N），两例携带 KRAS 基因突变（p.Q61R 和 p.L56V、p.G13R），一例携带 HRAS 基因突变（p.D69_Q70insRWYSAMRD）。通过测序检测到的突变等位基因频率从9.98%到15.97%不等：结论：IHCT 的血液动力学和分子遗传表型与在 AVMs 中观察到的表型非常相似。新发现的 KRAS 错义突变（包括同时存在突变类型的病例）和 HRAS 插入突变为了解血管异常的遗传基础提供了宝贵的信息。这些发现还可能成为开发新型药物治疗干预措施的潜在靶点。

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Intramuscular hemangioma capillary type with HRAS mutation: Expanding the molecular genetic spectrum with an emphasis on overlap with arteriovenous malformations and distinct from infantile hemangioma

Aims

Intramuscular hemangioma capillary type (IHCT) is a rare entity that refers to fast-flow vascular lesions. This study aims to elucidate the relationships between clinicopathological, radiological, and molecular characteristics in IHCT patients.

Methods and results

We reviewed all IHCT cases which were treated surgically in our pathology database from 2014 to 2023. Ten cases were analyzed via next-generation sequencing (NGS) and Sanger sequencing. The cohort consisted of 10 patients (6 males, 4 females) with a median age of 18 years (range: 1–37). Disease lesions were located in the trunk (n = 4), upper extremity (n = 2), lower extremity (n = 2), shoulder (n = 1), and neck (n = 1). IHCT is most commonly a progressively increasing painless mass. Histopathologically, all lesions exhibited aggregates, lobules, and anastomosing cords of capillary-type vessels separating or infiltrating the skeletal muscles. Four cases exhibited irregularly dilated vessels with thick walls, such as arteriovenous malformations (AVM) in the lesion's periphery. MRI findings commonly demonstrated a well-delineated, homogeneous mass. Somatic mutations were detected in seven of the ten IHCT cases. Four cases harbored mutations in MAP2K1 (p.Q58_E62del, p.K57_G61del, p.K57 N), two cases harbored mutations in KRAS (p.Q61R and p.L56V, p.G13R), and one case harbored a mutation in HRAS (p.D69_Q70insRWYSAMRD). Mutant allele frequencies detected by sequencing ranged from 9.98% to 15.97%.

Conclusions

The hemodynamic and molecular genetic phenotypes of IHCT closely resemble those observed in AVMs. Newly identified KRAS missense mutations, including cases with coexisting mutation types, and HRAS insertion mutations offer valuable insights into the genetic basis of vascular anomalies. These findings may also present potential targets for the development of novel pharmacotherapeutic interventions.

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来源期刊

Human pathology 医学-病理学

CiteScore

5.30

自引率

6.10%

发文量

206

审稿时长

21 days

期刊介绍： Human Pathology is designed to bring information of clinicopathologic significance to human disease to the laboratory and clinical physician. It presents information drawn from morphologic and clinical laboratory studies with direct relevance to the understanding of human diseases. Papers published concern morphologic and clinicopathologic observations, reviews of diseases, analyses of problems in pathology, significant collections of case material and advances in concepts or techniques of value in the analysis and diagnosis of disease. Theoretical and experimental pathology and molecular biology pertinent to human disease are included. This critical journal is well illustrated with exceptional reproductions of photomicrographs and microscopic anatomy.