ALK-positive histiocytosis of external auditory canal in a 3-year-old boy.

ALK-positive histiocytosis, first described by Chan et al. in 2008,1 is a new entity in the 2022 WHO classification and 2022 ICC schemes,2, 3 and is a rare histiocytic neoplasm characterized by proliferation of bland-looking foamy histiocytes with ALK expression involving ALK rearrangements. Herein, we report a new case of 3-year-old boy in which the histiocyte-like cells show irregular nuclear contours with nuclear folding or grooving, fine chromatin, inconspicuous nucleoli, and scant cytoplasm with ALK rearrangement. Our case expands the clinical and morphologic spectrum of ALK-positive histiocytosis and alerts the clinicians to raise the possibility of this uncommon entity, especially in children. A 3-year-old boy suffered from a left ear mass for 1 year. He had visited a clinic, where folliculitis was diagnosed, but the therapeutic response to antibiotics was poor. In our hospital, an examination revealed one round, red nodule (Image 1A) over the posterosuperior aspect of the left ear opening. Laboratory data showed normal blood counts with mild eosinophilia (6%), and normal biochemical tests. Pathologically, the excised lesion showed a dense dermal infiltrate with a focal storiform arrangement (Image 1B). The infiltrating cells showed irregular nuclear contours with nuclear folding or grooving, fine chromatin, inconspicuous nucleoli, and scant cytoplasm (Image 1C). No foamy histiocyte or Touton giant cell was found. These cells were positive for CD4, CD68, CD163 (Image 1D, ×400), ALK (Image 1E, ×400) and factor XIIIa, and were negative for CD1a, CD3, CD20, CD30, MPO, and S-100 protein. Break-apart fluorescence in situ hybridization (FISH) analysis confirmed ALK rearrangement (Image 1F). The patient's postoperative course was uneventful. ALK-positive histiocytosis is a rare histiocytic neoplasm characterized by proliferation of bland-looking histiocytes with ALK expression resulting from ALK rearrangement. KIF5B is the most common fusion partner.4 The fusions lead to activation of many signaling pathways, such as mitogen-activated protein kinase (MAPK) activation. Single-system disease is the most frequent clinical presentation, accounting for around 60% cases, but multi-systemic disease and neurological involvement can occur, especially in the children.4 ALK-inhibiting therapy is usually effective in multi-systemic disease. The overall clinical outcome of patients with ALK-positive histiocytosis is typically favorable.4 Shu-hsien Wang collected clinical data and wrote the history. Hsuan-Ying Huang contributed to the FISH analysis. L. Jeffrey Medeiros critically revised the manuscript. Kung-Chao Chang supervised the report, contributed to pathologic diagnosis, and critically revised the manuscript. The authors declare no conflicts of interest.