Chen Kuang-Hua, Huang Hsuan-Ying, Chen Tse-Ching, Liu Yu-Jen, Lin I-Chieh, Ng Kwai-Fong, Chuang Huei-Chieh, Huang Shih-Chiang
Department of Anatomic Pathology, Linkou Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan, 333 Taiwan.
Department of Anatomical Pathology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Kaohsiung City, 833 Taiwan.
Hum Pathol. 2022 Dec;130:79-87. doi: 10.1016/j.humpath.2022.10.002. Epub 2022 Oct 6.
Vascular anomalies are common orbital lesions, while variations in previous nomenclature might hamper robust characterization of their clinicopathological and genetic features. We reviewed and reclassified 92 orbital vascular lesions by the modified International Society for the Study of Vascular Anomalies (ISSVA) classification with reappraising clinicopathological parameters of 4 main types of vascular malformations, including orbital venous malformation 1 (OVM1, cavernous venous malformation), OVM2 (varix), OVM3 (infiltrating venous malformation), and arteriovenous malformation (AVM). GJA4, BRAF, and KRAS mutations were assessed by Sanger sequencing. There were 90 cases of vascular malformations, consisting of 60 OVM1 (67%), 13 AVM (14%), 8 OVM2 (9%), 8 OVM3 (9%), and 1 lymphatic-venous malformation (1%). The prevailing OVM1, histologically characterized by well-delineated borders and a uniform cavernous growth pattern, predominantly occurred in intraconal space (57%, P = .019) with an older median age (49 years) and female predilection (73%). OVM2, OVM3, and AVM exhibited differences in the distributions of patients' ages and lesion locations. Sizes of lesions were significantly correlated with periorbital and intraconal/extraconal locations (P < .001). OVM1 had the lowest rate of residual and recurrent diseases (3%). GJA4 mutations were identified in 75% (44/59) of OVM1 but not in OVM2/3 and AVM. No BRAF or KRAS mutations were detected. In conclusion, the modified ISSVA scheme enables meaningful classification of orbital vascular malformations by highlighting the molecular correlation between the distinct clinicopathological features and specific GJA4 mutation in OVM1, which implies OVM1 as a unique variant of venous malformation genetically akin to cutaneous and hepatic counterparts.
血管异常是常见的眼眶病变，而以往命名的差异可能会妨碍对其临床病理和遗传特征进行准确描述。我们采用改良的国际血管异常研究学会（ISSVA）分类法，对92例眼眶血管病变进行了回顾和重新分类，并重新评估了4种主要类型血管畸形的临床病理参数，包括眼眶静脉畸形1型（OVM1，海绵状静脉畸形）、OVM2型（静脉曲张）、OVM3型（浸润性静脉畸形）和动静脉畸形（AVM）。通过桑格测序评估GJA4、BRAF和KRAS突变情况。共有90例血管畸形，其中60例为OVM1型（67%）、13例为AVM型（14%）、8例为OVM2型（9%）、8例为OVM3型（9%），1例为淋巴管静脉畸形（1%）。最常见的OVM1型，其组织学特征为边界清晰且呈均匀的海绵状生长模式，主要发生于肌锥内间隙（57%，P = 0.019），中位年龄较大（49岁），女性多见（73%）。OVM2型、OVM3型和AVM型在患者年龄分布和病变位置上存在差异。病变大小与眶周及肌锥内/肌锥外位置显著相关（P < 0.001）。OVM1型的残留和复发疾病发生率最低（3%）。在75%（44/59）的OVM1型中检测到GJA4突变，而在OVM2/3型和AVM型中未检测到。未检测到BRAF或KRAS突变。总之，改良的ISSVA方案能够对眼眶血管畸形进行有意义的分类，通过突出不同临床病理特征与OVM1型中特定GJA4突变之间的分子关联，这意味着OVM1型是一种独特的静脉畸形变体，在遗传上与皮肤和肝脏的同类病变相似。
