恶性组织细胞病(MH),或组织细胞协会分类的“M组”,其特征是肿瘤组织细胞具有大的多形性核。MH包括组织细胞肉瘤的诊断,指状树突状细胞肉瘤和朗格汉斯细胞肉瘤。我们旨在定义MH的表型谱并检查该谱的基因型特征。通过免疫组织化学,我们将22例病例分为四种亚型,分别对应于单核细胞和树突状细胞前体的分化系:i)巨噬细胞(n=5):CD68,CD163+,CD14+,因子13a+;ii)单核细胞巨噬细胞(n=5):CD68+,CD163+,CD14+,S100+,OCT2+;iii)树突状细胞(n=6):CD68+,CD11c+,S100+,溶菌酶+,ZBTB46+,CD1a/langerin<5%;iv)朗格汉斯细胞(n=6):CD68+,CD11c+,S100+,ZBTB46+,CD1a和langerin+。表型亚型与低度组织细胞肿瘤中的表型亚型一致:MH-巨噬细胞型与Erdheim-Chester疾病表型相关;MH-单核细胞-巨噬细胞型具有Rosai-Dorfman疾病表型,MH-Langerhans细胞型具有Langerhans细胞组织细胞增生症。在80%的MH病例中发现了MAPK途径基因的激活突变;29%的人在PI3k-AKT-mTOR途径中发生突变,59%的人在表观遗传调节基因中发生突变。在所有病例中都存在细胞周期蛋白D1的强表达,而p-ERK和p-AKT表达不均匀。22例MH病例中有8例(36%)被证明与先前的B细胞淋巴瘤克隆相关。定义MH的表型谱为诊断提供了指导,并允许进一步探索潜在的生物学和临床意义。
Malignant histiocytoses (MHs), or the \'M group\' of the Histiocyte Society classification, are characterized by neoplastic histiocytes with large pleomorphic nuclei. MH encompasses the diagnoses of histiocytic sarcoma, interdigitating dendritic cell sarcoma, and Langerhans cell sarcoma. We aimed to define the phenotypic spectrum of MH and examine the genotypic features across this spectrum. Using immunohistochemistry, we arranged the 22 cases into 4 subtypes that correspond to the lines of differentiation from monocytic and dendritic cell precursors as follows: (1) macrophage (n = 5): CD68+, CD163+, CD14+, and Factor 13a+; (2) monocyte-macrophage (n = 5): CD68+, CD163+, CD14+, S100+, and OCT2+; (3) dendritic cell (n = 6): CD68+, CD11c+, S100+, lysozyme+, ZBTB46+, and CD1a/langerin < 5%; and (4) Langerhans cell (n = 6): CD68+, CD11c+, S100+, ZBTB46+, CD1a+, and langerin+. The phenotypic subtypes align with those seen in low-grade histiocytic neoplasms as follows: MH-macrophage type correlates with Erdheim-Chester disease phenotype; MH-monocyte-macrophage type with Rosai-Dorfman disease phenotype, and MH-Langerhans cell type with Langerhans cell histiocytosis. Activating mutations in MAPK-pathway genes were identified in 80% of MH cases; 29% had mutations in the PI3k-AKT-mTOR pathway and 59% had mutations in epigenetic modulating genes. Strong expression of cyclin D1 was present in all cases, whereas p-ERK and p-AKT were not uniformly expressed. Eight of 22 (36%) MH cases were proven to be clonally related to a prior B-cell lymphoma. Defining the phenotypic spectrum of MH provides a guide to diagnosis and allows further exploration into the potential biological and clinical significance.