Clinicopathologic features of localized ALK-positive histiocytosis: A study of three cases and review of literature

ABSTRACT: ALK-positive histiocytosis is a systemic or localized form of histiocytosis that is associated with ALK gene rearrangements. Morphological diagnosis of this entity can be challenging due to overlapping morphology and limited case reports. We describe the clinicopathological features of localized ALK-positive histiocytosis in three pediatric cases. The main features were the presence of typical histiocytes and spindle-shaped cells with varying numbers of giant cells, which can exhibit emperipolesis . Neoplastic cells lacked significant atypia, mitotic activity, or pleomorphism. Immunohistochemistry showed positivity for histiocytic markers and ALK (clone 137E9E8). Break-apart FISH confirmed ALK rearrangement. Morphological overlap with juvenile xanthogranuloma and Rosai-Dorfman disease was observed. ALK immunohistochemistry and molecular testing facilitated definitive diagnosis.