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

Abstract

Langerhans cell histiocytosis (LCH) is an infrequent disease, characterized by oligoclonal proliferation of immature myeloid-derived cells. However, the exact pathogenesis remains unknown. In rare cases, LCH is present in patients with concomitant myeloid proliferative neoplasms. Here, we describe a 69-year-old male, who presented with a maculopapular rash covering truncus, face, and scalp. A cutaneous ulcerating lesion on the right cheek led to a biopsy showing LCH. Lesional cells were BRAFV600E and JAK2V617F mutated. A bone marrow aspirate showed no infiltration of Langerhans cells, but alterations consistent with primary myelofibrosis (PMF) and a polymerase chain reaction test were positive for JAK2V617F. Our case highlights an uncommon condition of two hematological malignancies present in the same patient. The identification of the BRAFV600E mutation supports previous findings of this mutation in LCH. Interestingly, a JAK2V617F mutation was found in both LCH and PMF cells, indicating a possible clonal relationship between the two malignancies.

Case report: Common clonal origin of concurrent langerhans cell histiocytosis and acute myeloid leukemia

“…In a review by Kemps PG et al (34), mutated genes in histiocytic disorders and myeloid neoplasms have been reported in 30 cases (29,. A total of 31 cases, including one additional case of a common mutation found in LCH and primary myelofibrosis (39), including the present case are shown in Table 2. There have been five cases, of LCH occurring concurrently with a myeloid neoplasm, including the present case.…”

Cutaneous involvement in Ph‐negative myeloproliferative neoplasms: from extramedullary hematopoiesis to myeloid metastasis with histiocytic differentiation. A systematic review of the literature

“…However, we could not have access to seven papers written in Japanese that were cited in one record 19 . Therefore, our study included 43 papers, describing 47 patients 6,9,19–59 …”

“…Histopathologically, the skin lesions revealed a picture of EMH in most cases (76.6%) and less frequently leukemic blast infiltration (LC, 12.8%), cutaneous involvement of Langerhans cell histiocytosis (LCH, 6.4%), 55,57,58 reticulohistiocytosis (2.1%), 42 or histiocytoid Sweet syndrome (2.1%) 12 . Cutaneous EMH lesions were described as dermal infiltrates composed of cells of the three hematopoietic lineages, in different stages of maturation, with occasional mitoses, megakaryocytic atypia (mononucleation, nuclear hyperchromasia, dysmorphism, and small cell size), and dermal fibrosis 6,19,34,44 .…”