Deciphering Langerhans cell histiocytosis

Blood, Journal Year: 2025, Volume and Issue: 145(8), P. 790 - 791

Published: Feb. 20, 2025

Language: Английский

Acute myeloid leukaemia with SRSF2 and BRAF mutations preceded by histiocytic proliferation in the bone marrow

British Journal of Haematology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

BRAF p.V600E is a well-established driver mutation in various cancers, including melanoma, colorectal cancer and non-small cell lung cancer, as well haematological neoplasms hairy leukaemia, Langerhans histiocytosis (LCH) histiocytic such Erdheim–Chester disease (ECD).1 However, this exceedingly rare myeloid only approximately 10 cases of BRAF-mutant acute leukaemia (AML) have been reported to date.2-9 We report case AML with mutation, preceded by transient proliferation the bone marrow. Through immunohistochemistry genetic profiling, we investigated clonal relationship between preceding subsequent cells, revealing shared origin driven SRSF2 p.P95H mutations. A 64-year-old man no particular medical history presented our hospital because 1-week fever general malaise. Physical examination revealed hepatosplenomegaly or superficial lymphadenopathy. Haematological analysis showed white blood count (WBC) 4.1 × 109/L, 45% mature neutrophils, 21% monocytes 12% immature neutrophils; haemoglobin concentration 99 g/L; platelet 31 109/L (Table S1). Serum lactate dehydrogenase (LDH), C-reactive protein (CRP) ferritin were elevated 244 U/L, 4.91 mg/dL 1605 μg/L respectively. Bone marrow an increase large cells morphology, that is, abundant basophilic cytoplasm containing numerous vacuoles (Figure 1A). Haemophagocytes observed sporadically. Morphological dysplasia myeloid, erythroid megakaryocyte lineages was insignificant 1B). The karyotype normal. Histological clots hyperplastic marrow, 70% identified CD68-positive CD1a-negative histiocytes 1C−E). These weakly positive for myeloperoxidase (MPO) V600E staining 1F,G). patient's condition improved his test results normalized spontaneously within few weeks 2A). He subsequently followed up outpatient. 2 months later, malaise recurred, examinations WBC 17 7.5% blasts, 32 LDH level 869 U/L. His deteriorated rapidly, 4 days tests 33.7 19% blasts 1412 U/L 1H). Flow cytometric demonstrated CD13, CD33 CD56, CD10, CD14 human leukocyte antigen-DR. aspiration yielded dry tap biopsy more than 90% cellularity, MPO staining, CD68 negative CD1a 1I−N). Chromosomal peripheral complex abnormalities. patient diagnosed chemotherapy started immediately Considering poor condition, treatment 5-azacitidine venetoclax. Unfortunately, aggressive could not be controlled. Next, treated cytarabine daunorubicin, but again refractory treatment. passed away 3 after onset AML. Our targeted capture sequencing data (Supplementary Method Data S1) three somatic mutations—BRAF p.V600E, MED12 p.G44S—in sample at collected mutations, along additional p.G44C several copy number alterations, consistent findings from 2B). strongly suggest had common ancestral clone. schematic diagram evolution shown Figure 2C. Given frequency higher likely initial event, driving progression histiocytosis. acquisition alterations contributed development cannot determine point which clone diverged; it remains unclear whether clone, harbouring p.P95H, p.G44C, co-existed undetectable minor population during stage developed later through events clones mutation. key component transcriptional mediator regulates RNA polymerase II activity.10 p.G44S mutations are frequently uterine leiomyomas, breast fibroepithelial tumours chronic/small lymphocytic lymphoma.11, 12 Previous studies these activate transforming growth factor-β signalling pathway, leading resistance treatments, mitogen-activated extracellular signal-regulated kinase/BRAF inhibitors.13 To date, all exhibited monocytic phenotype, present case.3-9 frequent occurrence LCH ECD, reports ECD co-occurring p.V600E-positive AML, may play role directing haematopoietic differentiation towards lineages.6, 7, 14, 15 In fact, recent study progenitor leads differentiation.16 unsolved issue how classify diagnose presentation case. Initially, suspected haemophagocytic lymphohistiocytosis (HLH) based on clinical manifestations, fever, thrombocytopenia increased serum ferritin, CRP levels. HLH basically reactive caused inflammatory cytokines lacks characteristics current case, although cases, can develop secondary neoplasms. Moreover, did meet criteria neoplasms, chronic myelomonocytic due absence persistent monocytosis, morphological chromosomal It also align diagnostic five subgroups neoplasms—juvenile xanthogranuloma, Rosai–Dorfman disease, ALK-positive sarcoma—as described 5th edition World Health Organization classification. Retrospectively, neoplasm precursor chemotherapy-resistant Another unanswered determining optimal condition. All associated extremely prognosis, has here.3-8 Recently, MEK/BRAF inhibitors promise treating mutation-positive early application inhibitor-based allogeneic stem transplantation improve outcomes conclusion, contributes growing body evidence documenting patients coexisting share identical suggesting origin.17 Patients should undergo careful evaluation potential malignancies. M.M., T.S., T.O. H.K. analysed data. K.M. made significant contributions histological interpretation. M.S., M.I., J.T., J.K., Y.N., S.O. A.T.-K. interpreted genomic M.M. prepared manuscript. Y.N. provided important feedback authors critically reviewed approved final This research received external funding. declared conflict interest exists. institution's ethics committee study. Written informed consent obtained patient. There materials reproduced other sources. does involve trial. will available corresponding author upon reasonable request. S1. 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Language: Английский

[18F]FDG PET/CT of Langerhans Cell Histiocytosis with Vertebra Plana

Diagnostics, Journal Year: 2025, Volume and Issue: 15(7), P. 862 - 862

Published: March 28, 2025

We present an 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) scan of a 27 y/o patient with long-standing significant B symptoms, diffuse bone pain, increased inflammation parameters, and polydipsia revealing multiple FDG-avid osteolytic lesions the axial skeleton including vertebra plana T7 paraosseous soft tissue lesions. A CT-guided biopsy confirmed diagnosis Langerhans cell histiocytosis (LCH). This case highlights importance considering LCH in young patients vertebral collapse underscores role PET/CT imaging establishing accurate diagnosis.

Language: Английский