Histiocytoses encompass a wide spectrum of diseases, all characterized by tissue infiltration by CD68+ histiocytes. Most adult histiocytoses are considered clonal diseases because they highlight ...recurrent somatic mutations in the MAP-kinase pathway gene, primarily
BRAF
. The presence of
BRAF
mutation is associated with widespread disease in children with Langerhans cell histiocytosis (LCH) or cardiovascular/neurological involvement in Erdheim–Chester disease (ECD). Nevertheless, few data are available on adult clonal histiocytosis. This is why we have conducted a retrospective study of all patients with clonal histiocytosis in our institution and present the data according to the presence of
BRAF
mutation. Among 27 adult patients (10 ECD, 10 LCH, 5 Rosai–Dorfman disease (RDD), and 3 mixed ECD/LCH), 11 (39%) have
BRAF
mutation with gain of function (n = 9) and deletion (n = 2). Those patients had frequent multicentric disease with risk organ involvement, especially the brain and cardiovascular system. They had frequent associated myeloid neoplasms (mostly chronic myelomonocytic leukemia) and received more frequently targeted therapy as the front-line therapy. Nevertheless, its presence did not affect the overall survival or relapse-free survival probably due to the emergence of efficient therapies. To conclude, rapid and accurate molecular establishment in adult clonal histiocytoses is crucial because
BRAF
V600E
mutation correlates with multicentric disease with organ involvement and incomplete metabolic response.
Background: Patients with solid cancers and hematopoietic malignancy can experience systemic symptoms compatible with adult-onset Still’s disease (AOSD). The newly described VEXAS, associated with ...somatic UBA1 mutations, exhibits an overlap of clinical and/or biological pictures with auto inflammatory signs and myelodysplastic syndrome (MDS). Objectives: To describe a cohort of patients with signs of undifferentiated systemic autoinflammatory disorder (USAID) concordant with AOSD and MDS/chronic myelomonocytic leukemia (CMML) and the prevalence of VEXAS proposed management and outcome. Methods: A French multicenter retrospective study from the MINHEMON study group also used for other published works with the support of multidisciplinary and complementary networks of physicians and a control group of 104 MDS/CMML. Results: Twenty-six patients were included with a median age at first signs of USAID of 70.5 years with male predominance (4:1). Five patients met the criteria for confirmed AOSD. The most frequent subtypes were MDS with a blast excess (31%) and MDS with multilineage dysplasia (18%). Seven patients presented with acute myeloid leukemia and twelve died during a median follow-up of 2.5 years. Six out of 18 tested patients displayed a somatic UBA1 mutation concordant with VEXAS, including one woman. High-dose corticosteroids led to a response in 13/16 cases and targeted biological therapy alone or in association in 10/12 patients (anakinra, tocilizumab, and infliximab). Azacytidine resulted in complete or partial response in systemic symptoms for 10/12 (83%) patients including 3 VEXAS. Conclusions: Systemic form of VEXAS syndrome can mimic AOSD. The suspicion of USAID or AOSD in older males with atypia should prompt an evaluation of underlying MDS and assessment of somatic UBA1 mutation.
Immune thrombocytopenia (ITP) is a rare autoimmune-mediated condition characterized by isolated thrombocytopenia (<100 G/L) after exclusion of other causes. Mostly primary, it is associated with ...hematological malignancy, autoimmune disorders, or infection in 20% of patients. It is exceptionally described in patients with histiocytosis, mostly in children (seven patients in literature). We report a case of a 69-year-old man with ITP leading to the diagnosis of histiocytosis. At ITP's diagnosis, the patient had elevated gamma-globulins leading to computed tomography showing bilateral peri-renal infiltration. The biopsy showed enriched IgG-4 peri-renal Rosai Dorfman disease with
MAP2K1
mutation, although peri-renal infiltration is highly suggestive of Erdheim-Chester disease. This overlapping association was described in men with mutation in
MAP2K1
gene. Macrophages are implicated in the pathophysiology of ITP in multiple ways, notably by the phagocytosis of opsonized platelets and their function of antigen-presenting cells able to stimulate autoreactive T cells. Histiocytic cells derivate from monocyte-macrophage lineage. Activation of macrophages in active histiocytosis is responsible for consequential platelet destruction in ITP associated histiocytosis. Finally, this case highlights a rare presentation of ITP revealing histiocytosis, both being efficiently treated with rituximab.
Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs). Among them, ICIs-induced systemic sclerosis (SSc) is poorly known.
To better characterize this irAE, our ...comprehensive approach combined the description of ICIs-induced scleroderma cases, the systematic review of the literature and the analysis of VigiBase, the WHO pharmacovigilance database.
We identified two cases with underlying limited cutaneous SSc who presented a dramatic increase in the skin thickening following pembrolizumab, associated with scleroderma renal crisis in one case. In the literature, four cases of scleroderma and four cases of morphea have been reported with pembrolizumab or nivolumab. None following ipilimumab, atezolizumab or durvalumab were retrieved. Skin changes appeared or worsened more quickly with pembrolizumab than nivolumab, and had different patterns between both drugs. Patients with generalized skin changes required high-dose prednisone to improve skin thickening. Among the 2527 scleroderma cases identified in VigiBase, 35 were associated with ICIs. Nivolumab and pembrolizumab showed a disproportionality in scleroderma reporting. No disproportionality was found for ipilimumab, atezolizumab or durvalumab.
The risk of scleroderma or fibrosis extension in SSc patients should be considered when initiating anti-PD-1 agents. It suggests the role of PD-1/PD-L1 interaction in the pathophysiology of SSc.
To compare adult patients' characteristics suffering from idiopathic retroperitoneal fibrosis between "relapse-free" and relapsing patients at the diagnosis and identify factors associated with ...relapse at initial presentation.
We conducted a retrospective multicentric study in four hospitals in Eastern France, from 1993 to 2020, of adult patients suffering from idiopathic retroperitoneal fibrosis. We analyzed clinical, biological, and radiological features at diagnosis and during a forty-month follow-up.
Of 47 patients suffering from retroperitoneal fibrosis, 21 patients had idiopathic retroperitoneal fibrosis. Among them, 13 experienced one or more relapses during follow-up. At diagnosis, clinical characteristics, relevant comorbidities, biological and radiological features were similar between groups. Smoking cessation seems associated with decreased relapse risk (
: 0.0624). A total of 8 patients developed chronic renal failure during follow-up. Ureteral infiltration at diagnosis was associated with evolution to chronic renal failure (
: 0.0091).
No clinical, biological, or radiological features could predict relapse at retroperitoneal fibrosis diagnosis, but smoking cessation may prevent relapse.
A Rare Case of Chylous Ascites Razanamahery, Jérôme; Jacquier, Anthony; Humbert, Sébastien
Gastroenterology (New York, N.Y. 1943),
October 2017, 2017-Oct, 2017-10-00, 20171001, Letnik:
153, Številka:
4
Journal Article
ObjectivePeritoneal or mesenteric tumours may correspond to several tumour types or tumour-like conditions, some of them being represented by histiocytosis. This rare condition often poses diagnostic ...difficulties that can lead to important time delay in targeted therapies. Our aim was to describe main features of histiocytoses with mesenteric localisation that can improve the diagnostic process.DesignWe performed a retrospective study on 22 patients, whose peritoneal/mesenteric biopsies were infiltrated by histiocytes.ResultsAbdominal pain was the revealing symptom in 10 cases, and 19 patients underwent surgical biopsies. The diagnosis of histiocytosis was proposed by initial pathologists in 41% of patients. The other initial diagnoses were inflammation (n=7), sclerosing mesenteritis (n=4) and liposarcoma (n=1). The CD163/CD68+CD1a- histiocytes infiltrated subserosa and/or deeper adipose tissues in 16 and 14 cases, respectively. A BRAFV600E mutation was detected within the biopsies in 11 cases, and two others were MAP2K1 mutated. The final diagnosis was histiocytosis in 18 patients, 15 of whom had Erdheim-Chester disease. The median diagnostic delay of histiocytosis was 9 months. Patients treated with BRAF or MEK inhibitors showed a partial response or a stable disease. One patient died soon after surgery, and five died by the progression of the disease.ConclusionDiagnosis of masses arising in the mesentery should be carefully explored as one of the possibilities in histiocytosis. This diagnosis is frequently missed on mesenteric biopsies. Molecular biology for detecting the mutations in BRAF or in genes of the MAP kinase pathway is a critical diagnostic tool.
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