Phillips Gregory S, Knapp Maxwell, Olsen Keith C, Martin William, Hayes-Lattin Brandon, Chung Jina
Department of Dermatology, Oregon Health & Science University, Portland, Oregon, USA.
Department of Pathology, Oregon Health & Science University, Portland, Oregon, USA.
J Cutan Pathol. 2025 Jan;52(1):63-71. doi: 10.1111/cup.14732. Epub 2024 Oct 15.
Anaplastic lymphoma kinase (ALK)-positive histiocytosis has emerged as a clinically relevant diagnosis featuring a wide span of clinical presentations, which are unified by the presence of ALK-positive histiocytes on histopathology and molecular drivers involving the ALK kinase gene. This report presents an adult case of multisystem ALK-positive histiocytosis with xanthogranuloma-like features on histopathology that was responsive to ALK inhibition, and includes a review of ALK-positive histiocytoses with cutaneous involvement reported in the literature. A 56-year-old male developed a widespread eruption of red-brown papules on the face, trunk, and upper extremities. Histopathological evaluation revealed a well-circumscribed, nodular dermal infiltrate of epithelioid histiocytes with Touton giant cells, rare bizarre multinucleated cells, and focal emperipolesis. The lesional cells were positive for CD68 and ALK1 immunohistochemical stains, and negative for CD1a. Next-generation sequencing identified a DCTN1::ALK fusion. On imaging, he was found to have bone, lung, soft tissue, and salivary gland involvement. ALK inhibition was initiated with alectinib, resulting in rapid improvement of cutaneous lesions and eventual complete resolution of abnormal imaging findings, which was sustained at 24 months of follow-up. This case adds to the spectrum of ALK-positive histiocytoses and further demonstrates the positive response with targeted therapy.
间变性淋巴瘤激酶（ALK）阳性组织细胞增多症已成为一种具有临床相关性的诊断，其临床表现范围广泛，通过组织病理学上ALK阳性组织细胞的存在以及涉及ALK激酶基因的分子驱动因素而统一起来。本报告介绍了一例成人多系统ALK阳性组织细胞增多症病例，其组织病理学表现为黄瘤样特征，对ALK抑制有反应，并包括对文献中报道的伴有皮肤受累的ALK阳性组织细胞增多症的综述。一名56岁男性在面部、躯干和上肢出现广泛的红棕色丘疹皮疹。组织病理学评估显示，上皮样组织细胞呈边界清楚的结节状真皮浸润，伴有杜顿巨细胞、罕见的奇异多核细胞和局灶性血细胞吞噬现象。病变细胞CD68和ALK1免疫组化染色呈阳性，CD1a呈阴性。二代测序鉴定出DCTN1::ALK融合。影像学检查发现他有骨骼、肺部、软组织和唾液腺受累。开始使用阿来替尼进行ALK抑制治疗，导致皮肤病变迅速改善，异常影像学表现最终完全消退，在随访24个月时持续缓解。该病例增加了ALK阳性组织细胞增多症的范围，并进一步证明了靶向治疗的阳性反应。
