ALK-positive histiocytosis are uncommon and often affect multiple organ systems, which pose diagnostic challenges for their rarity and the fact that the nosology of these lesions is being decide until now(4). The study of the clinicopathological features and prognosis of the disease is of great significance. Here, we reported a histiocytosis of umbilicus subcutaneous. Histomorphology showed fascicular to storiform growth of nonatypical spindle cells, admixed with lymphocytic infiltrates. The immunophenotyping and molecular findings confirmed a diagnosis of ALK-positive histiocytosis, which has described by Chang et al. in their recent series (3).
For the moment, the incidence of ALK-positive histiocytosis is relatively rare, and it needs to be differentiated from a variety of diseases. Immunohistochemistry showing negative CD207 (Langerin) can rule out Langerhans cell histiocytosis. Histiocytic cells become foamy and incorporated into Touton giant cells, which improved the differential diagnosis of juvenile xanthogranulom(JXG). JXG usually occurs in children with round or oval nuclei. Recently, few report presents ALK-positive in systemic JXG, rather than in localized lesions (8). Erdheim-Chester disease(ECD), a disease predominantly of adults with mean age of 55–60 years, but rare pediatric cases have been reported(9). Approximately 20% of patients with ECD have Langerhans cell histiocytosis lesions(10). Fibrosis in ECD is present in most cases and sometimes abandunt(11). Major showing BRAF-V600E mutation, ECD is a clonal systemic histiocytic proliferation most commonly involving bone, cardiovascular system and retroperitoneum(11). ALK-positive histiocytosis mainly occurs in young people without BRAF mutations. Epithelioid fibrous histiocytoma, often showing ALK expression, have to be distinguished from ALK-positive histiocytosis involving skin (12) (13). These cells, small or spindle shaped, have a more epithelioid form, lacking the expression of CD68 and S100(13). Differential diagnosis also including inflammatory myofibroblastoma (IMT), SMA are negative in atypical cells, and immunophenotype indicates histiocyte derived (14). Currently, ALK-positive histiocytosis has not specifically designated into the World Health Organization classification (15). Though Emile et al. in their classification included similar cases within the category of ECD, with the designation “extracutaneous or disseminated JXG with MAPK-activating mutation or ALK translocations”(12), current research suggest that ALK-positive histiocytosis differ from both ECD and JXG. The existing evidence supports that ALK-positive histiocytosis should have a separate classification, which is highly correlated with KIF5B-ALK fusion.
The literature review found that ALK-positive histiocytosis occurring in infants and young children typical features with hepatosplenomegaly and severe cytopenia (3). The tumor system affects the skin, spleen, liver, and bone marrow. On the contrary, histiocytosis occur in adults as localized lesions, such as breast, foot, nasal skin and cavernous sinus. Most infants can recover gradually or achieve complete remission with chemotherapy. All adults were completely relieved after surgical resection, and one unresectable case also achieved complete remission after crizotinib treatment. In our case, the localized ALK-positive histiocytosis harboring KIF5B-ALK has not recurred one and a half years until now, indicated a good prognosis.
In conclusion, ALK-positive histiocytosis should be distinguished from other tumors such as IMTs and spindled histiocytic reaction. The diagnosis can be critical for management, especially in systemic disorders and can be targeted using small molecule inhibitors. ALK expression or translocation testing was strongly recommend in every unusual histiocytic proliferative disorder to aid in identification of this entity. Though more localized ALK-positive histiocytosis cases showed favorable prognosis after completely resection, the long-term prognosis still needs follow-up.