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Case Reports
. 2021 Apr 16:2021:6623706.
doi: 10.1155/2021/6623706. eCollection 2021.

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

Johanne Marie Holst  1   2 , Marie Beck Enemark  1   2 , Trine Lindhardt Plesner  3 , Martin Bjerregaard Pedersen  1 , Maja Ludvigsen  1   2 , Francesco d'Amore  1   2
Affiliations
Case Reports

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

Johanne Marie Holst et al. Case Rep Hematol. .

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 BRAF V600E and JAK2 V617F 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 JAK2 V617F. Our case highlights an uncommon condition of two hematological malignancies present in the same patient. The identification of the BRAF V600E mutation supports previous findings of this mutation in LCH. Interestingly, a JAK2 V617F mutation was found in both LCH and PMF cells, indicating a possible clonal relationship between the two malignancies.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
(a) Tumor localized to the cheek of the patient. (b) Painless, nonitching maculopapular rash on the patient's truncus. (c) Normalization of the skin after BRAF-inhibitor treatment.
Figure 2
Figure 2
Skin sample at the time of diagnosis showing histopathological and immunohistochemical features consistent with Langerhans cell histiocytosis. (a) Haematoxylin and eosin staining (100x), and immunohistochemical staining for (b) S100 (100x) and (c) CD1a (100x).
Figure 3
Figure 3
Giemsa staining of the bone marrow sample showing histopathological features consistent with primary myelofibrosis (200x).
Figure 4
Figure 4
Elevated 18F-FDG uptake localized corresponding to (a) the right cheek, cutaneous portion of the back head (occipital) and in one lymph node at the neck and (b) several foci in the pelvic bones, and a soft tissue process ahead of right os pubis showing increased 18F-FDG activities. (c) The CT scan showing pathological edematous appearance of the kidney surrounded by adipose tissue.
See this image and copyright information in PMC

References

    1. Durham B. H. Molecular characterization of the histiocytoses: neoplasia of dendritic cells and macrophages. Seminars in Cell & Developmental Biology. 2019;86:62–76. doi: 10.1016/j.semcdb.2018.03.002. - DOI - PubMed
    1. Allen C. E., Merad M., McClain K. L. Langerhans-cell histiocytosis. New England Journal of Medicine. 2018;379(9):856–868. doi: 10.1056/nejmra1607548. - DOI - PMC - PubMed
    1. Emile J.-F., Abla O., Fraitag S., et al. Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages. Blood. 2016;127(22):2672–2681. doi: 10.1182/blood-2016-01-690636. - DOI - PMC - PubMed
    1. Papo M., Cohen-Aubart F., Trefond L., et al. Systemic histiocytosis (Langerhans cell histiocytosis, erdheim-chester disease, destombes-rosai-dorfman disease): from oncogenic mutations to inflammatory disorders. Current Oncology Reports. 2019;21(7):p. 62. doi: 10.1007/s11912-019-0810-6. - DOI - PubMed
    1. Tran G., Huynh T. N., Paller A. S. Langerhans cell histiocytosis: a neoplastic disorder driven by Ras-ERK pathway mutations. Journal of the American Academy of Dermatology. 2018;78(3):579–590. doi: 10.1016/j.jaad.2017.09.022. - DOI - PubMed

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