Effective BRAF inhibitor vemurafenib therapy in a 2-year-old patient with sequentially diagnosed Langerhans cell histiocytosis and Erdheim&amp;ndash;Chester disease

Váradi, Zsófia; Bánusz, Rita; Csomor, Judit; Kállay, Krisztián; Varga, Edit; Kertész, Gabriella; Csóka, Monika

doi:10.2147/ott.s121615

Cited by 37 publications

(20 citation statements)

References 23 publications

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“…BRAF inhibitor Vemurafenib has been used for the treatment of the LCH, and some research showed that combination of Vemurafenib and MEK kinase inhibitors is effective in the treatment of melanomas. 5,31 All these manifested that RAS-RAF-MEK-ERK pathway play an important role in cancer generation.…”

Section: Discussionmentioning

confidence: 99%

A novel fusion gene PLEKHA6‐NTRK3 in langerhans cell histiocytosis

Cai

Huang

Yin

et al. 2018

Intl Journal of Cancer

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Langerhans cell histiocytosis (LCH) is the most common histiocytosis with constitutive activation of the RAS-RAF-MEK-ERK (MAPKinase) cell signaling pathway. We analyzed 89 cases of BRAF and MAP2K1 mutations by Sanger sequencing, of which 18 cases showed that these two gene mutations are negative. Whole genome sequencing of suitable specimens in these negative cases revealed a translocation from the 3 intron of PLEKHA6 to the 13 intron of NTRK3 in one case. We identified that this translocation could cause a novel fusion mutation, PLEKHA6-NTRK3. Overexpression of the PLEKHA6-NTRK3 mutant in NIH 3T3 cells enhanced MAPKinase pathway activation, promote cell growth. Our result suggested that a new mutation need be included in LCH molecular screening panel to better define its prevalence in LCH.

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Section: Discussionmentioning

confidence: 99%

A novel fusion gene PLEKHA6‐NTRK3 in langerhans cell histiocytosis

Cai

Huang

Yin

et al. 2018

Intl Journal of Cancer

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“…Hence, activating mutations in the BRAF gene have the potential to contribute to clonal cell expansion (9). Indeed, treatment of advanced PLCH with the BRAF inhibitor, vemurafenib, was reported to have resulted in a favorable outcome (10). Interestingly, the same mutation is also observed in 1-3% of non-small cell lung cancer cases, predominantly adenocarcinoma (11).…”

Section: Discussionmentioning

confidence: 99%

Development of pulmonary Langerhans cell histiocytosis in a patient with established adenocarcinoma of the lung

et al. 2017

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Newly-appearing lung nodules on surveillance imaging in patients with pre-existing lung cancer can present a diagnostic dilemma when attempting to differentiate between metastatic disease, infection, and other inflammatory conditions. Here we report a case of an // metastatic adenocarcinoma patient who underwent lung biopsy for evaluation of upper-lobe predominant lung nodules revealed to represent pulmonary Langerhans cell histiocytosis (PLCH). The patient was a heavy smoker and admitted to increase her smoking habit after initially learning about her diagnosis with lung cancer. Interestingly, despite the association of both lung adenocarcinoma and PLCH with the mutation in smokers, pyrosequencing of the patient's PLCH lesions was negative for this mutation. Co-occurrence of PLCH with lung cancer is extremely rare. While most reported cases of PLCH tend to precede the occurrence of lung cancer, a minority of cases appear after a diagnosis of lung cancer has already been established and are thought to represent a local immunologic reaction to the tumor. It is therefore postulated that the appearance of PLCH lesions in this patient's lungs is a result of her increase in cigarette smoking, possibly augmented by co-existence of adenocarcinoma.

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“…The amelioration of the PLCH phenotype was associated with a decrease of DC-related cytokine and chemokine levels in the BAL fluid, which further validates the causal role of BRAF VE DCs. Since the discovery of mutations in the RAS/MAPK pathway in LCH, multiple studies have shown that BRAF inhibitors have a beneficial effect in patients with LCH (57,58). However, BRAF inhibition can cause an alternative activation in the MAPK pathway that can lead to significant adverse effects, such as cutaneous squamous cell carcinomas and keratoacanthomas in patients with melanoma (59).…”

Section: Discussionmentioning

confidence: 99%