The Non-Langerhans Cell Histiocytoses (Rare Histiocytoses) – Clinical Aspects and Therapeutic Approaches

Abstract

Rare histiocytoses, also called non-Langerhans cell histiocytoses, include all proliferative disorders of histiocytes, macrophages and dendritic cells that are not classified as Langerhans cell histiocytosis (LCH) and do not belong to the hemophagocytic lymphohistiocytosis (HLH) group of diseases. Thus, the term includes numerous benign or malignant, localized or systemic, adult or pediatric diseases. The classification of the histiocytic disorders has been revised several times. Here, we follow the classification recently published by Jean Francois Emile and an international expert panel, defining subgroups of histiocytoses described as L-Group, C-Group, M-Group, R-Group, and H-Group, which stands for LCH-like, cutaneous or mucocutaneous, malignant, Rosai-Dorfman-Disease like and HLH like. Some of the diseases have an excellent prognosis after resection or even disappear spontanously, others progress rapidly, requiring intensive systemic therapies. The malignant non-Langerhans cell histiocytoses in general have a poor prognosis, here, complex chemotherapy protocols are usually applied, with inconsistant results. An interesting perspective in non-malignant rare histiocytoses might be small molecular inhibitors, in particular BRAF inhibitors, since BRAF mutations have been found in some subtypes of non-Langerhans cell histiocytoses. By prospective and retrospective collection of experiences in a new registry (the "International Rare Histiocytic Disorders Registry", IRHDR), knowledge about these rare diseases might hopefully be improved.

A rare cutaneous lesion in the neonatal period: The non-Langerhans cell histiocytosis

“…Dermal dendrocyte infiltration is seen in this group of diseases, but typical Langerhans cells are absent. As reported by Classen, et al, some subtypes of these disorders typically occur early in life and tend to resolve spontaneously [3]. Our patient, also had multiple palpable lesions all over her body, with no systemic involvement.…”

“…In the follow-up, lesions can fade or they can heal with atrophic scars or hyperpigmentation in months or years. Diagnosis is made histopathologically [3]. The etiology and pathogenesis of non-LCH and its various clinical forms remain obscure.…”

Cyclin D1 expression and novel mutational findings in Rosai‐Dorfman disease

“…The identification of recurrent mutations in the mitogen‐activated protein kinase (MAPK) pathway represents an advance in our understanding and therapy of histiocytic neoplasms (Classen et al , ; Haroun et al , ; Ozkaya et al , ; Tian et al , ; Tran et al , ). For example, many Langerhans cell histiocytosis (LCH) cases harbour mutations in either BRAF or other MAPK pathway genes, which introduced the option of targeted therapy (Badalian‐Very et al , ; Brown et al , ).…”

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

“…Histiocytoses are uncommon proliferative disorders of the mononuclear phagocyte system lineage. 1,2 They are currently divided into five different groups, according to the 2016 revised classification of histiocytoses. Histiocytoses belonging to the 'cutaneous-group' (HCG) are characterised by a predominant cutaneous involvement and represent one of the widest groups of histiocytic disorders.…”