ALK-positive histiocytosis: an expanded clinicopathologic spectrum and frequent presence of KIF5B-ALK fusion View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-12-20

AUTHORS

Kenneth Tou En Chang, Amos Zhi En Tay, Chik Hong Kuick, Huiyi Chen, Elizabeth Algar, Nadine Taubenheim, Janine Campbell, Francoise Mechinaud, Martin Campbell, Leanne Super, Chavit Chantranuwat, S. T. Yuen, John K. C. Chan, Chung W. Chow

ABSTRACT

In 2008, we presented three cases of ALK-positive histiocytosis as a novel systemic histiocytic proliferation of early infancy with hepatosplenomegaly and dramatic hematological disturbances. This series of 10 cases (including the original three cases) describes an expanded clinicopathological spectrum and the molecular findings of this histiocytic proliferation. Six patients had disseminated disease: five presented in early infancy with eventual disease resolution, and the sixth presented at 2 years of age and died of intestinal, bone marrow, and brain involvement. The other four patients had localized disease involving nasal skin, foot, breast, and intracranial cavernous sinus - the first three had no recurrence after surgical resection, while the cavernous sinus lesion showed complete resolution with crizotinib therapy. The lesional histiocytes were very large, with irregularly folded nuclei, fine chromatin, and abundant eosinophilic cytoplasm, sometimes with emperipolesis. There could be an increase in foamy histiocytes and Touton giant cells with time, resembling juvenile xanthogranuloma. Immunostaining showed that the histiocytes were positive for ALK, histiocytic markers (CD68, CD163) and variably S100, while being negative for CD1a, CD207, and BRAF-V600E. Next-generation sequencing-based anchored multiplex PCR (Archer® FusionPlex®) performed in six cases identified KIF5B-ALK gene fusion in five and COL1A2-ALK fusion in one. There was no correlation of gene fusion type with disease localization or dissemination. The clinicopathological spectrum of ALK-positive histiocytosis is broader than originally described, and this entity is characterized by frequent presence of KIF5B-ALK gene fusion. We recommend that every unusual histiocytic proliferative disorder, especially disseminated lesions, be tested for ALK expression because of the potential efficacy of ALK inhibitor therapy in unresectable or disseminated disease. More... »

PAGES

1-11

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41379-018-0168-6

DOI

http://dx.doi.org/10.1038/s41379-018-0168-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1110811049

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30573850


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