The triptych of mixed histiocytosis: a systematic review of 105 cases and proposed clinical classification

Abstract

Histiocytoses are one of the ultimate diagnostic challenges that every physician face at least once in his/her life. Giving their protean manifestation and differentiated therapeutic needs, histiocytosis requires extensive characterization and multidisciplinary management. Mixed histiocytosis is an emerging group of syndromes defined by the overlap of Langerhans cell histiocytosis and another histiocytic disorder of different type. Despite rare, it may account for up to a fifth of systemic histiocytosis patients in some series. In this work, we comprehensively review for the first time the clinical, radiological, histopathological and molecular features of mixed histiocytosis in children and adults. Moreover, we propose a clinical classification in three groups that differentiate patients with systemic involvement and worse overall survival to other groups with more localized manifestations and indolent behavior, wanting to ease their recognition and treatment. Interestingly we also found that mixed histiocytosis harbor BRAFV600E mutations with a higher frequency comparing to all other histiocytoses, and may therefore benefit of specific inhibitory drugs.

Keywords:

• Histiocytosis
• Langerhans cell histiocytosis
• Erdheim–Chester disease
• xanthogranuloma
• BRAF
• classification

Acknowledgements

The authors thank Dr. Marialuisa Bonometti for her assistance in the proofreading of the manuscript and Dr. Lucas Estevam De Oliveira for the realization of the graphic contents of the figures.

Disclosure statement

The authors have no significant relationship with, or financial interest in, any commercial companies pertaining to this article.

Data availability statement

All data reported in the present review are gathered from the scientific literature as described in the ‘Materials and Methods’ section and cited in the ‘Reference’ section. The present article also contains all the tables and figures necessary to interpret, replicate and build upon the described results.