Flucke Uta, Hiemcke-Jiwa Laura S, van Gorp Joost M, Hayes Don, Seyger Marieke M B, Koudijs Marco J, Kester Lennart A, van Helvert Sjoerd, van Cruchten Remco T P
Department of Pathology, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Virchows Arch. 2025 May 19. doi: 10.1007/s00428-025-04128-z.
Platelet-derived growth factor receptor beta (PDGFRB) is one of the numerous members of the receptor tyrosine kinase protein family. When altered, it is known to be the driver mutation in different mesenchymal neoplasms, such as pericytic tumors, inflammatory myofibroblastic tumor, and sarcomas with myogenic differentiation. We investigated seven dermatomyofibromas for the presence of a PDGFRB mutation. Patients were 6 females and 1 male. Ages ranged from 2 to 59 years. Neoplasms were located in the shoulder (2), neck (2), upper arm (1), knee (1), and calf (1). Clinically, they appeared as ill-defined plaques. Complete excision was performed in four cases. In three cases, only a biopsy was taken. Histomorphologically, these dermal ill-defined tumors consisted of fascicles of slender myofibroblastic cells oriented often parallel to the epidermis. Their nuclei were monomorphic and elongated, and the cytoplasm was inconspicuous. Involvement of the superficial subcutis was seen in four cases. Immunohistochemically, neoplasms expressed SMA (5/7), focally desmin (1/5), and CD34 (4/6), while S100 was lacking (0/7). By DNA or RNA sequencing, PDGFRB activating mutations were identified in 6/7 tumors. Four neoplasms harbored a mutation in exon 12 encoding for the juxtamembrane domain and 2 neoplasms in exon 14 encoding for the tyrosine kinase domain. Sequencing analyses results highlight that these benign skin tumors belong to the broad spectrum of tyrosine kinase-driven neoplasms.
血小板衍生生长因子受体β（PDGFRB）是受体酪氨酸激酶蛋白家族众多成员之一。当其发生改变时，已知是不同间叶性肿瘤的驱动突变，如周皮细胞瘤、炎性肌成纤维细胞瘤以及具有肌源性分化的肉瘤。我们研究了7例皮肤肌纤维瘤中是否存在PDGFRB突变。患者为6名女性和1名男性。年龄范围为2至59岁。肿瘤位于肩部（2例）、颈部（2例）、上臂（1例）、膝部（1例）和小腿（1例）。临床上，它们表现为边界不清的斑块。4例进行了完整切除。3例仅进行了活检。组织形态学上，这些真皮内边界不清的肿瘤由细长的肌成纤维细胞束组成，这些细胞束常与表皮平行排列。它们的细胞核单一形态且细长，细胞质不明显。4例可见浅表皮下组织受累。免疫组化方面，肿瘤表达平滑肌肌动蛋白（SMA，5/7）、局灶性结蛋白（1/5）和CD34（4/6），而S100蛋白阴性（0/7）。通过DNA或RNA测序，在6/7的肿瘤中鉴定出PDGFRB激活突变。4个肿瘤在外显子12（编码近膜结构域）存在突变，2个肿瘤在外显子14（编码酪氨酸激酶结构域）存在突变。测序分析结果表明，这些良性皮肤肿瘤属于酪氨酸激酶驱动的肿瘤的广泛范畴。
