Reticulohistiocytoses: a revision of the full spectrum

Abstract

Reticulohistiocytoses (RH) are rare and clinically heterogeneous histiocytic disorders of dermatological interest. Three clinical entities with superimposable histopathological features are currently considered, namely solitary reticulohistiocytoma, diffuse/generalized reticulohistiocytosis and multicentric reticulohistiocytosis. Although in the last decade, RH studies have only minimally progressed, histiocytosis research has advanced considerably: the prognostic and therapeutic importance of the clinical subclassification of histiocytosis patients as well as of the detection of genetic alterations in the genes of the ERK pathway has been highlighted. According to these insights, we previously reported the presence of molecular alteration RH and described a subset of patients with disseminated multisystem involvement lacking arthritis. In the present review, we aim to update and revise the knowledge regarding RH. We first reviewed their histopathological, immunophenotypical and ultrastructural features, discussed their histopathological differential diagnosis with other conditions characterized by infiltrates made of oncocytic or epithelioid cells (with special regard to Destombes-Rosai-Dorfman disease) and finally summarized the molecular landscape of RH. We therefore tried to adjust the clinical subclassification of Langerhans cell histiocytosis to the clinical phenotypes of RH, outlining five clinically different groups of patients. Finally, we reconsidered the clinical workflow to the evaluation of RH patients, in light of the 5 different clinical groups and discussed the different therapeutic approaches and the possible role of target inhibitors.

Multicentric Reticulohistiocytosis Exhibiting Positive HLA-B*07 and HLA-B*08: A Case Report

“…Sacroiliac joint involvement has previously been reported in MRH [ 3 , 5 ], yet it is not regarded as a cardinal sign of the disease [ 4 ]. Noteworthy, the majority of case reports in the currently available literature do not mention investigating the sacroiliac joints.…”

“…It has been hypothesized that patients with MRH may harbor mutations of the oncogene BRAF (B-Raf Proto-Oncogene Serine-Threonine Kinase), as well as MAP2K1 (Mitogen-Activated Protein Kinase Kinase 1), which are both involved in the RAS-MAPK (Ras/Mitogen-Activated Protein Kinase) signaling pathway and could be relevant as therapeutic targets [ 4 , 5 ]. Murakami et al examined biopsy specimens from 15 subjects with histiocytoses (two patients with MRH and 13 patients with LCH) from a genetic perspective and identified MAP2K1 mutations (similar to LCH) together with an FGFR1 (fibroblast growth factor receptor 1) tyrosine kinase fusion (which were not detected in LCH) [ 4 ].…”

“…The authors proposed that MRH be classified as a neoplastic condition, given that its pathomechanism may involve the activation of the RAS-MAPK pathway [ 6 ]. Indeed, associations between MRH and various types of neoplasia and autoimmune diseases have been reported [ 5 , 7 ]. Nevertheless, the neoplastic/paraneoplastic andautoimmune nature of the disease remains a matter of debate [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ].…”

“…The diagnosis of MRH requires a multidisciplinary clinical, pathological, and radiological approach [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. Herein, we present a case of MRH exhibiting both typical clinical changes, as well as certain distinct traits.…”

Cutaneous‐group histiocytoses associated with myeloid malignancies: A systematic review of 102 cases

“…MAP2K1, ARAF, NRAS and KRAS), and tyrosine kinase receptors or epigenetic regulators (e.g. KIT, ALK and CSF1R) 5–8 …”