Cutaneous adult xanthogranuloma with a small portion of BRAF(V) (600E) mutated Langerhans cell histiocytosis populations: A case report and the review of published work.

Histiocytoses, including Langerhans cell histiocytosis (LCH), juvenile or adult xanthogranuloma (AXG) and Rosai-Dorfman disease (RDD), are rare disorders characterized by the proliferation of cells derived from monocyte/macrophage lineages. A few cases of LCH coexisting with xanthogranuloma or RDD have been reported. The etiology of these diseases remains unclear. However, oncogenic BRAFV 600E mutations have been identified in LCH. Here, we report the case of a 26-year-old Japanese man with a 3-month history of a solitary occipital nodule. No abnormality was detected in his other organs, and a total resection of the nodule was performed. Histopathological examination revealed the coexistence of LCH and AXG with prominent emperipolesis characteristic of RDD. Immunohistochemistry showed that most of the large histiocytes were positive for CD68, weakly positive or negative for S100, and negative for CD207 and CD1a, supporting the diagnosis of AXG. The tumor cells with emperipolesis did not show S100-positive findings characteristic of RDD. The focally aggregated oval histiocytic cells were positive for CD1a, CD207, CD68 and S100, and were compatible with the immunophenotype of LCH cells. In addition, these cells were positive for BRAFV 600E mutation. The tumor cells in our patient exhibited a cellular morphology characteristic of multiple histiocytoses in a solitary cutaneous nodule, which may imply an etiological association among LCH, AXG and RDD. To our knowledge, this is the first report of a BRAFV 600E mutation-positive case of LCH coexisting with AXG. Because patients with BRAFV 600E mutation have higher risks of multisystemic LCH and recurrence, we should carefully follow up the patient.

Ishikawa M ，Endo Y ，Uehara A ，Suto M ，Yasuda M ，Motegi SI ，Ishikawa O ... -  《-》

BRAF-mutated histiocytosis of the skull lacking the expression of Langerhans cell markers.

El Sissy FN ，Lorillon G ，Mandonnet E ，Polivka M ，Addle-Biassette H ，Emile JF ... -  《-》

[Cutaneous Rosai-Dorfman disease with lack of BRAF-V600, KRAS or NRAS mutations: A reactive or neoplastic disorder?].

Non-Langerhans cell histiocytosis, including Rosai-Dorfman disease (RDD) and xanthogranuloma are rare disorders with occasional overlapping in the histopathological and immunohistochemical (IHC) findings. We report the case of a 53-year-old woman with erythematous-violaceous plaques on the cheeks and edema in the auricular pavilions. A biopsy was performed and the histopathological examination revealed a histiocytic proliferation with emperipolesis characteristic of RDD and lymphoplasmocitic infiltrate. IHC analysis showed S100 and CD68 positivity in the histiocytes but was negative for CD1a, supporting the diagnosis of RDD. Molecular analysis failed to detect BRAF-V600, NRAS or KRAS mutation. We discuss the differential diagnosis of cutaneous non-Langerhans cell histiocytosis. Pathologist must be aware of unusual presentations of RDD and further treatment options must be explored for patients with unresectable lesions and/or resistance to the classical management of RDD.

Machado I ，Alcacer Fernández-Coronado J ，Requena C ，Través V ，Latorre Martínez N ，Ortega J ，Requena L ，Alcacer García J ... -  《-》

[Primary intraosseous Rosai-Dorfman disease: a clinicopathological analysis of fourteen cases].

Dong RF ，Gong LH ，Zhang W ，Li L ，Sun XQ ，Zhang M ，Ding Y ... -  《-》

Progress towards molecular-based management of childhood Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is characterized by inflammatory lesions containing abundant CD1a+ CD207+ histiocytes that lead to the destruction of affected tissues. This disease has a remarkable pleiotropic clinical presentation and most commonly affects young children. Although the current mortality rate is very low for childhood LCH patients (<2%), reactivation frequently occurs after a long period of disease control and the rates of permanent complications and sequelae remain high. Advances in genomic sequencing technologies in this past decade have highlighted somatic molecular alterations responsible for the disease in around 80% of childhood LCH cases. More than half of these cases harbored the BRAFV600E mutation, and most other mutations also concerned proteins involved in the MAPKinase pathway. In addition to improving what is known about the LCH pathology, this molecular knowledge provides opportunities to optimize patient management. The BRAFV600E mutation is associated with more severe presentations of the disease, a high reactivation rate, and a high permanent complication rate; this mutation therefore paves the way for future stratified management approaches. These therapies may be based on the patient's molecular status as well as other clinical characteristics of the disease that are independently associated with undesired events. Moreover, as observed in patients with solid tumors, the BRAFV600E allele can be detected in the circulating cell-free DNA of patients with severe BRAFV600E-mutated LCH. Quantification of the plasmatic BRAFV600E load for this group of patients can precisely monitor response to therapy. Finally, targeted therapies, such as BRAF inhibitors, are new therapeutic options especially designed for refractory multisystemic LCH involving risk organs. However, the long-term efficacy, long-term tolerance, optimal protocol scheme, and appropriate modalities of administration for these innovative therapies for children still need to be defined, a huge challenge.

Héritier S ，Emile JF ，Hélias-Rodzewicz Z ，Donadieu J ... -  《-》