Hung Yin P, Lovitch Scott B, Qian Xiaohua
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Center for Advanced Molecular Diagnostics, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Cancer Cytopathol. 2017 Aug;125(8):604-614. doi: 10.1002/cncy.21851. Epub 2017 Apr 24.
Histiocytic sarcoma (HS) is a rare malignant neoplasm showing morphologic and immunophenotypic features of histiocytes. Molecular characteristics of HS and fine-needle aspiration (FNA) criteria for its diagnosis have not been established.
A case series of HS in 8 FNA samples from 6 patients was reviewed along with histopathologic and clinical data. Immunohistochemistry was performed on cell blocks (3 cases), core biopsies (5 cases), and surgical specimens (4 cases). Targeted-exome next-generation sequencing (NGS) was performed on surgical resection specimens in 4 cases.
Four patients had a known history of hematolymphoid malignancy. Cytomorphologic features included variably cellular smears composed of large epithelioid cells with reniform nuclei and abundant vacuolated cytoplasm, in an inflammatory background, with occasional cytophagocytosis and lymphoglandular bodies. Marked pleomorphism, multinucleated monster cells, and binucleated histiocytoid cells with partially overlapping, eccentrically placed nuclei resembling Pac-Man were common. Most cases expressed histiocytic markers CD68 (6 of 7 cases), CD163 (5 of 5 cases), and PU.1 (3 of 4 cases). In 3 cases, NGS analysis revealed alterations in lysine methyltransferase 2D (KMT2D)/mixed-lineage leukemia 2 (MLL2), a gene involved in chromatin regulation and previously implicated in the pathogenesis of follicular lymphoma.
Although diagnosing HS with FNA alone is extremely challenging, the presence of pleomorphic and epithelioid large cells with binucleation and/or multinucleation in an inflammatory background should prompt the diagnosis of HS with judicious use of confirmatory histiocytic lineage markers. The detection of recurrent KMT2D/MLL2 alterations implicates epigenetic regulation in the pathogenesis of HS and supports the notion of transdifferentiation from a genetically similar but phenotypically distinct tumor of a different lineage. Cancer Cytopathol 2017;125:604-14. © 2017 American Cancer Society.
组织细胞肉瘤（HS）是一种罕见的恶性肿瘤，具有组织细胞的形态学和免疫表型特征。HS的分子特征及其细针穿刺活检（FNA）诊断标准尚未确立。
回顾了6例患者8份FNA样本中的HS病例系列，并结合组织病理学和临床数据进行分析。对细胞块（3例）、芯针活检标本（5例）和手术标本（4例）进行免疫组织化学检测。对4例手术切除标本进行靶向外显子组二代测序（NGS）。
4例患者有血液淋巴系统恶性肿瘤病史。细胞形态学特征包括涂片细胞成分多样，由大的上皮样细胞组成，细胞核呈肾形，胞质丰富且有空泡，背景为炎症细胞，偶见噬血细胞现象和淋巴腺小体。明显的多形性、多核巨细胞以及双核组织细胞样细胞较为常见，双核细胞核部分重叠、偏心分布，类似吃豆人。多数病例表达组织细胞标志物CD68（7例中的6例）、CD163（5例中的5例）和PU.1（4例中的3例）。3例经NGS分析发现赖氨酸甲基转移酶2D（KMT2D）/混合系白血病2（MLL2）基因改变，该基因参与染色质调控，先前与滤泡性淋巴瘤的发病机制有关。
尽管仅通过FNA诊断HS极具挑战性，但在炎症背景下出现多形性和上皮样大细胞，伴有双核和/或多核，应谨慎使用组织细胞系标志物进行确诊，并提示HS的诊断。复发性KMT2D/MLL2改变的检测提示表观遗传调控在HS发病机制中的作用，并支持从遗传上相似但表型不同的另一谱系肿瘤发生转分化的观点。《癌症细胞病理学》2017年；125：604 - 14。© 2017美国癌症协会
