Mansour Boulos, Donati Michele, Pancsa Tamás, Grossman Petr, Šteiner Petr, Vaněček Tomáš, Comová Kateřina, Michal Michal, Michal Michael
Department of Pathology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.
Department of Pathology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200-00128, Roma, Italy.
Virchows Arch. 2025 Feb;486(2):215-223. doi: 10.1007/s00428-024-03811-x. Epub 2024 May 13.
Myoepithelial neoplasms of the skin and soft tissue still represent a confusing and somewhat controversial field in pathology as it appears that this category includes several different entities. However, recent studies have suggested that both apocrine mixed tumors (AMT) and cutaneous myoepitheliomas (CM) harbor identical chromosomal rearrangements involving the PLAG1 gene and hence may represent a morphological spectrum. The aim of the present study was to share our institutional experience with these tumors and specifically focus on studying their immunohistochemical and molecular features to further assess their relatedness. Eleven cases of AMT and 7 cases of CM were collected and analyzed using immunohistochemistry (IHC), PLAG1 FISH, and Archer FusionPlex assay. There were 14 male and 4 female patients with ages ranging from 26 to 85 years (median 55.8 years, mean 58.5 years). AMTs were mainly located in the head and neck (n = 10), while CMs were mainly located in the acral sites (n = 5). PLAG1 IHC was diffusely strongly positive in 14/17 (82%) cases, whereas a single case of AMT diffusely expressed HMGA2. Both tumor groups showed PLAG1 gene fusions which were detected in 6/13 analyzable samples (AMT, n = 4 and CM, n = 2), and included TRPS1::PLAG1 (n = 3), NDRG1::PLAG1 (n = 1), CTNNB1::PLAG1 (n = 1) and a novel PXDNL::PLAG1 fusion (n = 1). The remaining 5 cases were negative, 5 were not analyzable and the single case positive for HMGA2 by IHC revealed a potential HMGA2 gene rearrangement. The cases were further studied by FISH, with 12/17 cases showing PLAG1 gene rearrangement (AMT, n = 8 and CM, n = 4). Altogether, 14/18 cases showed PLAG1 gene rearrangement by at least one of the methods. PLAG1 immunohistochemistry had a 92% specificity and sensitivity. Our study provided additional data to suggest that AMT and CM share overlapping morphological and immunohistochemical features as well as molecular background characterized by PLAG1 gene fusions and thus represent a morphological spectrum. In addition, we identified a novel PXDNL::PLAG1 fusion and suggested that rare cases may harbor HMGA2 gene alterations which seem to be mutually exclusive with PLAG1 gene fusions. The relatedness of these tumors to salivary gland myoepithelial neoplasms and distinctness from eccrine mixed tumors and other skin and soft tissue myoepithelial neoplasms with EWSR1/FUS fusions is discussed.
皮肤和软组织的肌上皮肿瘤在病理学领域仍然是一个令人困惑且颇具争议的领域，因为这一类别似乎包含几种不同的实体。然而，最近的研究表明，大汗腺混合瘤（AMT）和皮肤肌上皮瘤（CM）都存在涉及PLAG1基因的相同染色体重排，因此可能代表一种形态学谱系。本研究的目的是分享我们机构对这些肿瘤的经验，并特别专注于研究它们的免疫组化和分子特征，以进一步评估它们的相关性。收集了11例AMT和7例CM，并使用免疫组化（IHC）、PLAG1荧光原位杂交（FISH）和Archer FusionPlex检测进行分析。患者共14名男性和4名女性，年龄范围为26至85岁（中位数55.8岁，平均58.5岁）。AMT主要位于头颈部（n = 10），而CM主要位于肢端部位（n = 5）。PLAG1免疫组化在14/17（82%）的病例中弥漫性强阳性，而1例AMT弥漫性表达HMGA2。两个肿瘤组均显示PLAG1基因融合，在6/13个可分析样本中检测到（AMT，n = 4；CM，n = 2），包括TRPS1::PLAG1（n = 3）、NDRG1::PLAG1（n = 1）、CTNNB1::PLAG1（n = 1）和一种新的PXDNL::PLAG1融合（n = 1）。其余5例为阴性，5例不可分析，免疫组化显示HMGA2阳性的单例揭示了潜在的HMGA2基因重排。通过FISH对这些病例进行进一步研究，12/17例显示PLAG1基因重排（AMT，n = 8；CM，n = 4）。总共，14/18例通过至少一种方法显示PLAG1基因重排。PLAG1免疫组化的特异性和敏感性为92%。我们的研究提供了更多数据，表明AMT和CM具有重叠的形态学和免疫组化特征以及以PLAG1基因融合为特征的分子背景，因此代表一种形态学谱系。此外，我们鉴定出一种新的PXDNL::PLAG1融合，并表明罕见病例可能存在HMGA2基因改变，这似乎与PLAG1基因融合相互排斥。讨论了这些肿瘤与涎腺肌上皮肿瘤的相关性以及与汗腺混合瘤和其他具有EWSR1/FUS融合的皮肤和软组织肌上皮肿瘤的区别。
