15 August 2026
: Case report 
Single-Site ALK-Positive Histiocytosis With TFG-ALK Fusion: Expanding the Clinical Spectrum of This Rare Entity
Rare disease
Mona Dasgupta BCDEF 1*, David Horvath BCDE 2, Benjamin Bevill A 1, Ashley Scheiderer BCDE 2, Sean Jordan AEF 3DOI: 10.12659/AJCR.952807
Am J Case Rep 2026; 27:e952807
Table 1 Summary comparison of ALK-positive histiocytosis and key differential diagnoses.
| Disease | Clinical features | Distinguishing histologic features | Immunohistochemistry | Molecular findings |
|---|---|---|---|---|
| Affects adults and children. May present as multisystem or single-system disease. Commonly involves hematopoietic system, liver, nervous system, lungs, skin, and bone | Dense proliferation of plump to large histiocytes in a fascicular growth pattern. Fewer Touton giant cells and foamy histiocytes than in the conditions below []2 | CD4+, CD14+, CD68 +, CD163+, CD1a−, langerin− | ALK gene fusions, most commonly KIF5B-ALK. Other rearrangements include CLTC-ALK, TPM3-ALK, TFG-ALK, EML4-ALK, DCTN1-ALK, and ALK-FISH+ | |
| More common in children. Presents with bone lesions, skin rash, pulmonary nodules, and involvement of the bone marrow, liver, spleen, and CNS | Langerhans cells with prominent nuclear grooves/folds in an eosinophil-rich background []. Epidermotropism may be present []6 | CD1a+, CD68+, CD207+ (langerin), S100+, CD163- | BRAF V600E mutation is present in more than 50% of cases | |
| Typically affects children and young adults. Characterized by massive, painless bilateral cervical lymphadenopathy, lytic bone lesions, and rash []8 | Hypochromatic histiocytes with small nucleoli and abundant pale cytoplasm that may contain engulfed inflammatory cells. Prominent lymphoplasmacytic infiltrate []9 | S100+, CD68+, CD163+, CD1a− | ARAF, MAP2K1, NRAS, and KRAS mutations | |
| More common in adults. Associated with central diabetes insipidus, restrictive pericarditis, and near-universal sclerotic bone lesions | Abundant foamy histiocytes with more condensed chromatin than lesional cells in LCH and RDD []. Frequent Touton giant cells and fibrosis []10 | CD68+, CD163+, facto XIIIa+, fascia+, CD1a−, CD207- []12 | BRAF-V600E or MAPK pathway mutations | |
| Typically occurs in infancy or early childhood. Presents as solitary, well-circumscribed, firm papules or nodules with a yellow-to-orange hue on the head, neck, or upper torso []. Systemic involvement is rare []13 | Foamy histiocytes are smaller and form a denser infiltrate, typically within the dermis. Scattered Touton giant cells are present []11 | CD68+, factor XIIIa+, vimentin+, CD4+ []13 | Usually no gene fusion identified | |
| Affects children and young adults. Soft tissue tumor commonly involving the abdominal cavity, retroperitoneum, or lung | Variably cellular lesion composed of spindled myofibroblasts with a prominent mixed inflammatory infiltrate. Myxoid stroma may be present [,]14 | ALK+, SMA+, desmin+, MSA+ | ALK rearrangements | |
| Abbreviations: ALK, anaplastic lymphoma kinase; ALK-FISH+, ALK fluorescence in situ hybridization positivity; CNS, central nervous system; LCH, Langerhans cell histiocytosis; MAPK, mitogen-activated protein kinase; MSA, muscle-specific actin; RDD, Rosai-Dorfman disease; SMA, smooth muscle actin. | ||||