Division of Pathology.
Department of Pathology.
Am J Surg Pathol. 2022 Mar 1;46(3):344-352. doi: 10.1097/PAS.0000000000001794.
Anaplastic lymphoma kinase (ALK)-positive histiocytosis is a rare emerging entity characterized by systemic or localized proliferation of histiocytes harboring ALK rearrangements. Breasts are reportedly affected by ALK-positive histiocytosis. Here, we evaluated 2 localized cases of breast ALK-positive histiocytosis through a comprehensive clinicopathologic, molecular, and genomic analysis to further delineate this entity and better understand its pathogenesis. The cases involved 2 undiagnosed ALK-positive spindle-cell breast lesions. Both cases were Asian women aged 30s to 40s who underwent excisions for asymptomatic breast masses. Macroscopically, both lesions were well-circumscribed, solid masses. Microscopically, both lesions were predominantly composed of fascicles with uniform, bland spindle cells, admixed with epithelioid histiocyte-like cells and lymphoid aggregates. Immunohistochemically, the spindle and epithelioid cells coexpressed ALK and histiocytic markers (eg, CD68, CD163). Genetically, both lesions harbored KIF5B-ALK, confirmed by fluorescence in situ hybridization and polymerase chain reaction-direct sequencing analyses. Combining these results, both cases were successfully diagnosed as ALK-positive histiocytosis. Furthermore, no common or previously annotated somatic alterations were identified by whole-exome sequencing. One case harbored clonal immunoglobulin gene rearrangements according to the polymerase chain reaction-based BIOMED-2 protocol. Therefore, ALK-positive histiocytosis can be accurately diagnosed through a combination of morphologic, immunohistochemical, and molecular analyses. In this entity, breast cases may have distinct clinicopathologic features: Asian women aged 30s to 40s, asymptomatic masses, and predominant spindled morphology. For pathogenesis, ALK rearrangements could be the driver alteration, and a subset of ALK-positive histiocytosis may harbor a lymphoid lineage. These findings can be utilized to improve the diagnosis of ALK-positive histiocytosis and better understand its pathogenesis.
间变性淋巴瘤激酶（ALK）阳性组织细胞增生症是一种罕见的新兴实体，其特征为系统性或局部性 ALK 重排的组织细胞增生。据报道，乳腺受 ALK 阳性组织细胞增生症的影响。在此，我们通过全面的临床病理、分子和基因组分析评估了 2 例局部乳腺 ALK 阳性组织细胞增生症病例，以进一步描绘该实体并更好地理解其发病机制。这 2 例病例均为未确诊的 ALK 阳性梭形细胞乳腺病变，均为 30 多岁至 40 多岁的亚裔女性，因无症状乳腺肿块而行切除术。大体上，这 2 个病变均为边界清楚的实性肿块。镜下，这 2 个病变主要由束状排列的均匀、温和梭形细胞组成，混有上皮样组织细胞样细胞和淋巴样聚集物。免疫组化染色显示，梭形和上皮样细胞共表达 ALK 和组织细胞标志物（如 CD68、CD163）。通过荧光原位杂交和聚合酶链反应-直接测序分析证实，这 2 个病变均存在 KIF5B-ALK 重排。综合这些结果，这 2 个病例均成功诊断为 ALK 阳性组织细胞增生症。此外，通过全外显子组测序未发现常见或先前注释的体细胞改变。根据 BIOMED-2 聚合酶链反应方案，1 例病例存在克隆性免疫球蛋白基因重排。因此，通过形态学、免疫组化和分子分析的结合，可以准确诊断 ALK 阳性组织细胞增生症。在该实体中，乳腺病例可能具有独特的临床病理特征：30 多岁至 40 多岁的亚裔女性、无症状肿块和主要梭形形态。就发病机制而言，ALK 重排可能是驱动改变，而一部分 ALK 阳性组织细胞增生症可能具有淋巴谱系。这些发现可用于提高 ALK 阳性组织细胞增生症的诊断准确性并更好地理解其发病机制。
