Submitted March 25, 2008
Accepted June 18, 2008
ALK+ histiocytosis: A novel type of systemic histiocytic proliferative disorder of early infancy
John K C Chan*, Laurence Lamant, Elizabeth Algar, Georges Delsol, William Y W Tsang, King Chung Lee, Karin Tiedemann, and Chung Wo Chow
Department of Pathology, Queen Elizabeth Hospital, Kowloon, Hong Kong
Centre de Physiopathologie de Toulouse Purpan, INSERM, U563, Universite Toulouse III Paul Sabatier, Toulouse, France
Department of Pediatrics, University of Melbourne, Melbourne, Australia
Children's Cancer Center, Royal Children's Hospital, Melbourne, Australia
Department of Anatomical Pathology, Royal Children's Hospital, Melbourne, Australia
* Corresponding author; email: jkcchan{at}ha.org.hk.
We report three cases of a previously uncharacterized form of histiocytosis presenting in early infancy and showing ALK immunoreactivity. The patients presented with pallor, massive hepatosplenomegaly, anemia and thrombocytopenia. Liver biopsy showed infiltration of the sinusoids by large histiocytes with markedly folded nuclei, fine chromatin, small nucleoli, and voluminous lightly eosinophilic cytoplasm that sometimes was vacuolated or contained phagocytosed blood cells. One patient developed cutaneous infiltrates that morphologically resembled juvenile xanthogranuloma. The histiocytes were immunoreactive for histiocytic markers (CD68, CD163, lysozyme), S100 protein, ALK (membranous and cytoplasmic pattern), and dendritic cell markers (fascin, factor XIIIa), but not CD1a and langerin. One case successfully analyzed by molecular techniques revealed TPM3-ALK fusion. Thus the spectrum of diseases exhibiting ALK translocation should be expanded to include ALK+ histiocytosis. The disease in the three patients (two having been given chemotherapy) resolved slowly over many months.
