Langerhans Cell Histiocytosis Associated With Underlying Hematolymphoid Disorders in Adults: Report of 2 Cases and Review of the Literature

Abstract

Langerhans cell histiocytosis (LCH) is an uncommon disorder characterized by proliferation of abnormal LCs usually affecting children and adolescents. LCH in adults first presenting in the skin is rare. Although LCH and even LCH with a second malignancy may be more common in children, cutaneous LCH with a second hematologic malignancy has been more commonly identified in adults. The authors report 2 new cases of LCH in adult patients with underlying myelodysplasia and follicular lymphoma. The specimens were examined by routine microscopy and immunohistochemical stains for S100 protein and CD1a. Patients were elderly men with established diagnoses of follicular lymphoma and myelodysplasia, presented with follicular lesions and erythematous plaques involving intertriginous areas. Histologic examination revealed collections of mononuclear cells in upper dermis, which demonstrated strong positivity for S100 and CD1a, confirming their identity as LCs. BRAF analysis returned negative for detection of BRAF V600E mutation in both patients. The authors have recently encountered 2 cases of adult patients with skin-limited LCH predated by other lymphoproliferative disorders. The association between LCH and hematopoietic disorders may be explained by a common bone marrow precursor that is differentiating along different cell lines. Cutaneous LCH may be associated with underlying lymphoproliferative disorders and should be considered in the differential diagnosis of cutaneous eruptions in patients with hematopoietic disorders. Clinical follow-up evaluation of patients diagnosed with LCH for peripheral blood abnormalities and lymphadenopathy or "B symptoms" may be prudent in patients not already carrying a diagnosis of an underlying hematologic disorder.

Erdheim-Chester disease associated with chronic myelomonocytic leukemia harboring the same clonal mutation

“…Overall, the high prevalence of myeloid neoplasms including CMML in adults with non-Langerhans cell histiocytosis 8 as well as in patients with Langerhans cell histiocytosis may be explained by a common bone marrow precursor. 13,15 We report herein three cases of disseminated xanthelasma-like lesions of the eyelids fulfilling criteria for ECD 2 associated with CMML harboring the same mutations in skin biopsies and CMML cells. This study provides further evidence for a common progenitor cell between CMML and ECD in some cases.…”

Coexisting BRAF-Mutated Langerhans Cell Histiocytosis and Primary Myelofibrosis with Shared JAK2 Mutation

“…Some previous reports have found LCH associated with other hematopoietic disorders, including myelo-and lymphoproliferative malignancies [8,9,13,14]. It has therefore been hypothesized that mutations in common hematopoietic precursor cells may explain the development of occasional co-occurrence of two hematological diseases [8,15]. Interestingly, Milne et al found BRAF V600E mutations present both in myeloid progenitors and CD34 + cells from LCH patients [16].…”

“…LCH has previously been reported associated with other hematological disorders, including cases of myeloid proliferative neoplasia (MPN) [8,9]. Here, we present a rare case presentation of BRAF V600E -mutated LCH and coexisting primary myelofibrosis (PMF) both sharing a Janus kinase 2 (JAK2) V617F mutation.…”

Association Between High-grade Myelodysplastic Syndrome and Cutaneous Langerhans Cell Histiocytosis Suggested by Next-Generation Sequencing

“…Adult LCH is rare and can present at a single location or involve multiple end-organs with variable cutaneous involvement. The co-occurrence of AML and LCH is well documented; the LCH can be preceded by or occur synchronously with AML . Because gene expression profiling has identified the LCH cell of origin as a dendritic myeloid precursor, it is conceivable that a common clonal origin could exist between LCH and myeloid malignant neoplasms.…”

“…Although skin involvement may be the only clinical presentation in LCH, systemic involvement must be excluded; in adults, the hypothalamic-pituitary region, lungs, and bones are often affected. Occasionally this disorder occurs with leukemia or lymphoma, which may develop after the initial diagnosis of cutaneous LCH . Vemurafenib therapy can be considered in patients with BRAF variant–associated LCH who have extensive cutaneous involvement or other severe systemic complications.…”