McKinney Reed A, Wang Guanghua
Head and Neck Pathology, The Joint Pathology Center, Silver Spring, MD, USA.
Molecular Diagnostics Laboratories, The Joint Pathology Center, Bethesda, MD, USA.
Head Neck Pathol. 2025 Feb 25;19(1):26. doi: 10.1007/s12105-025-01766-2.
Histiocytoses, including Langerhans cell histiocytosis (LCH), comprise a diverse group of histiocytic disorders characterized by the abnormal accumulation and proliferation of histiocytes in various tissues or organs throughout the body, ranging from benign, self-limited conditions to aggressive malignancies and systemic inflammatory syndromes. These lesions present unique diagnostic challenges due to their broad spectrum of clinical presentations, overlapping histopathological and immunophenotypical features, and genetic complexity.
This review analyzes major histiocytic lesions, focusing on their epidemiology, clinical presentations, histologic and immunophenotypic features, and genetic characteristics to facilitate accurate diagnosis and differentiation among these histiocytoses.
LCH, a well-recognized lesion, can affect various organ systems and necessitates differentiation from other types of histiocytoses such as Erdheim-Chester disease (ECD), Rosai-Dorfman-Destombes disease (RDD), and cutaneous and mucocutaneous non-Langerhans cell histiocytoses. Some histiocytic lesions, such as histiocytic sarcoma, are inherently malignant, while others, like hemophagocytic lymphohistiocytosis (HLH), manifest as severe, potentially life-threatening systemic inflammatory syndromes. Recent molecular genetic studies revealed recurrent genetic alterations in the MAPK pathway, such as BRAF V600E and MAP2K1 in LCH and ECD, and KRAS, NRAS, and MAP2K1 mutations in a subset of RDD. Malignant histiocytoses frequently show alterations in tumor suppressor genes like TP53 and CDKN2A.
Precise classification of histiocytic lesions relies on a comprehensive diagnostic approach that integrates clinical, histologic, immunophenotypic, and genetic data. Recent genetic advances shed light on these conditions' unique but occasionally overlapping pathogenic mechanisms. Molecular genetics advancements continue to refine diagnostic accuracy and present new therapeutic targets, especially for aggressive or treatment-resistant cases.
组织细胞增多症，包括朗格汉斯细胞组织细胞增多症（LCH），是一组多样的组织细胞疾病，其特征是组织细胞在全身各个组织或器官中异常积聚和增殖，范围从良性、自限性疾病到侵袭性恶性肿瘤和全身性炎症综合征。由于这些病变临床表现谱广、组织病理学和免疫表型特征重叠以及遗传复杂性，给诊断带来了独特挑战。
本综述分析主要的组织细胞病变，重点关注其流行病学、临床表现、组织学和免疫表型特征以及遗传特征，以促进这些组织细胞增多症的准确诊断和鉴别。
LCH是一种广为人知的病变，可累及多个器官系统，需要与其他类型的组织细胞增多症相鉴别，如 Erdheim-Chester病（ECD）、Rosai-Dorfman-Destombes病（RDD）以及皮肤和黏膜非朗格汉斯细胞组织细胞增多症。一些组织细胞病变，如组织细胞肉瘤，本质上是恶性的，而其他病变，如噬血细胞性淋巴组织细胞增多症（HLH），表现为严重的、可能危及生命的全身性炎症综合征。最近的分子遗传学研究揭示了丝裂原活化蛋白激酶（MAPK）通路中反复出现的基因改变，如LCH和ECD中的BRAF V600E和MAP2K1，以及部分RDD中的KRAS、NRAS和MAP2K1突变。恶性组织细胞增多症经常显示肿瘤抑制基因如TP53和CDKN2A的改变。
组织细胞病变的精确分类依赖于整合临床、组织学、免疫表型和遗传数据的综合诊断方法。最近的遗传学进展揭示了这些疾病独特但偶尔重叠的致病机制。分子遗传学进展不断提高诊断准确性，并提出新的治疗靶点，特别是对于侵袭性或难治性病例。
