Departments of Diagnostic Pathology.
Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Am J Surg Pathol. 2021 Mar 1;45(3):347-355. doi: 10.1097/PAS.0000000000001567.
Originally described as a systemic self-limiting disease in infancy, the spectrum of ALK-positive histiocytosis has recently been broadened to include localized diseases in older children and young adults. Despite different manifestations, these tumors share histologic characteristics and a highly recurrent KIF5B-ALK fusion. ALK-positive histiocytosis is poorly characterized in the breast. In this study, we report 3 cases of ALK-positive histiocytosis of the breast. The patients were Asian women, aged 16 to 45 years. Two patients presented with an isolated breast mass, while 1 exhibited multiorgan involvement. The latter patient received ALK inhibitor after surgery, which led to complete remission. Histologically, well-circumscribed tumors displayed fascicular and storiform growth of uniform, nonatypical spindle cells admixed with lymphocytic infiltrates. Fewer conventional epithelioid histiocytes with lobulated or clefted nuclei were observed within the same breast tumors in 2 cases or within a concomitant brain tumor in the third case. Touton-type giant cells were focally present in 2 cases. Immunohistochemically, tumor spindle, and epithelioid cells were diffusely positive for CD163 and ALK in all cases and focally positive for S100 protein in 1 of the cases. CD1a and langerin were negative. Actin-positive myofibroblasts were admixed within the tumor in 2 cases, and their reactive nature was highlighted using double immunostaining. Break-apart fluorescence in situ hybridization assay demonstrated gene rearrangements involving KIF5B and ALK in all the 3 cases. ALK-positive histiocytosis rarely occurs as a spindle cell breast tumor, and should be distinguished from other diseases such as inflammatory myofibroblastic tumors and spindled histiocytic reaction.
最初被描述为婴儿期的全身性自限性疾病，ALK 阳性组织细胞增生症的范围最近已扩大到包括年龄较大的儿童和年轻成人的局限性疾病。尽管表现不同，但这些肿瘤具有组织学特征和高度复发的 KIF5B-ALK 融合。ALK 阳性组织细胞增生症在乳房中特征较差。在这项研究中，我们报告了 3 例乳腺 ALK 阳性组织细胞增生症。患者为亚洲女性，年龄 16 至 45 岁。2 例患者表现为孤立性乳腺肿块，1 例表现为多器官受累。后者患者在手术后接受了 ALK 抑制剂治疗，导致完全缓解。组织学上，边界清楚的肿瘤显示出束状和交织状生长的均匀、非典型的梭形细胞，伴有淋巴细胞浸润。在 2 例相同的乳腺肿瘤或在第 3 例患者的同时性脑肿瘤中观察到较少的常规上皮样组织细胞，具有分叶状或裂隙状核。2 例中存在局灶性 Touton 型巨细胞。免疫组织化学染色显示，所有病例的肿瘤梭形和上皮样细胞均弥漫性表达 CD163 和 ALK，1 例局灶性表达 S100 蛋白。CD1a 和 langerin 阴性。2 例肿瘤内混合有肌成纤维细胞，并用双重免疫组化强调其反应性。3 例均通过断裂分离荧光原位杂交检测到涉及 KIF5B 和 ALK 的基因重排。ALK 阳性组织细胞增生症很少作为梭形细胞乳腺肿瘤发生，应与其他疾病如炎症性肌纤维母细胞瘤和梭形组织细胞反应相鉴别。
