Case Report: ALK-positive histiocytosis with a novel PTRH2::ALK fusion masquerading as a liver abscess in an infant.

BACKGROUND: ALK-positive histiocytosis is a rare form of cutaneous histiocytosis and has been explicitly designated as a novel histiocytic neoplasm in recent classification systems. This disease may involve multiple organs throughout the body. Its diagnosis primarily relies on pathological confirmation, and molecular evidence of ALK rearrangement is required to establish a definitive diagnosis. For patients with unresectable or disseminated ALK-positive histiocytosis, therapy with ALK inhibitors has demonstrated considerable efficacy.

CASE PRESENTATION: An 8-month-old Chinese male infant was admitted with 1-day history of fever and newly diagnosed anemia of 0.5-day duration. Physical examination revealed chronic rashes on the bilateral lower extremities, including the plantar surfaces. Laboratory investigations demonstrated anemia (hemoglobin level: 63 g/L), elevated inflammatory markers, and an increased serum S-100 protein level (9.11 ug/L). Abdominal ultrasonography and contrast-enhanced computed tomography (CT) revealed hepatosplenomegaly and diffuse hypoechoic or cystic low-density lesions in the liver (largest approximately 7 × 8 mm), which were initially suspected to represent a liver abscess. Histopathological examination of a biopsy specimen from the lower extremity rash revealed dermal proliferation of histiocytes, foamy cells, and short spindle cells, accompanied by scattered multinucleated giant cells and lymphocytes. Immunohistochemical analysis demonstrated positivity for CD68, S100, and ALK, and negativity for CD1a, CD3, CD20, and other markers. Fluorescence in situ hybridization (FISH) confirmed ALK rearrangement, and next-generation sequencing (NGS) identified a novel PTRH2::ALK fusion. Positron emission tomography-computed tomography (PET-CT) subsequently revealed mediastinal space-occupying lesions, multiple hypermetabolic lesions in the liver, kidney, mesentery, and bones, as well as metabolically active systemic lymph nodes, findings consistent with ALK-positive histiocytosis. The patient remained clinically stable during follow-up after initiation of the ALK inhibitor crizotinib.

CONCLUSION: This study reports a rare case of infantile ALK-positive histiocytosis that was initially misdiagnosed as a liver abscess and identifies a novel PTRH2::ALK fusion gene. In addition, this study systematically summarizes, for the first time, the age, sex, lesion distribution, fusion genes, treatment strategies, and prognosis of all previously reported pediatric cases of ALK-positive histiocytosis.