Langerhans cell histiocytosis and Erdheim‐Chester disease, both with cutaneous presentations, and papillary thyroid carcinoma all harboring the BRAF^V600E mutation

Abstract

Langerhans cell histocytosis (LCH) and Erdheim-Chester disease are two rare histiocytic disorders. Their occurrence in the same patient is more infrequent, but has been described. We report a case of a 38-year-old woman who presented with a diagnosis of single system cutaneous LCH. Subsequently, she developed multiple papules on her extremities consistent with a non-LCH xanthogranuloma type lesion. BRAF(V600E) mutation immunostain, VE1 was positive in the skin lesion, which was confirmed by molecular polymerase chain reaction (PCR) studies, initiating a complete systemic workup for Erdheim-Chester disease. Systemic involvement was confirmed with bilateral sclerotic bone lesions and retroperitoneal and pelvic fibrosing disease. She was also found to have a BRAF(V600E) mutation positive papillary thyroid carcinoma. New suspicious cutaneous lesions presenting in patients with a history of LCH need to be biopsied. A BRAF(V600E) mutation in a non-LCH histiocytic lesion with a xanthogranuloma phenotype (CD163/CD68/CD14/fascin/Factor 13a) should prompt an Erdheim-Chester disease workup. This is a unique case of a woman with BRAF(V600E) mutation positive Erdheim-Chester disease and cutaneous LCH, while also being, to our knowledge, the first reported case in the English literature of it occurring in a patient with a BRAF(V600E) mutation positive papillary thyroid carcinoma.

Clinical Spectrum, Quality of Life, BRAF Mutation Status and Treatment of Skin Involvement in Adult Langerhans Cell Histiocytosis

“…One patient had chronic myelomonocytic leukaemia and one had myelodysplastic syndrome, which further supports the hypothesis that a clonal abnormality on a common bone marrow precursor may be shared by LCH and myeloid disorders (33). Recently, Johnson et al (34) reported a patient with a BRAF V600E mutation in ECD skin lesions and a BRAF V600E mutation in a concomitant papillary thyroid carcinoma. The proportion of associated malignancies in our study (32%) was similar to those in a previous series of skin limited LCH (28%) (8), although higher than described previously in larger series of adult patients with LCH (6.2% in (10)).…”

Genetic mutations in accordance with a low malignant potential tumour are not demonstrated in clear cell papillary renal cell carcinoma

“…BRAF mutations are involved in tumour progression and metastasis in thyroid carcinoma,18 in colon carcinoma,19 in glioma20 and melanoma 21. It has also been reported in rare benign tumours such as metanephric adenoma of the kidney 22…”

The Non-Langerhans Cell Histiocytoses (Rare Histiocytoses) – Clinical Aspects and Therapeutic Approaches

“…The mixed histiocytoses represent disorders in which components of different histiocytoses occur in concert. This not an ununsual observation; and even BRAF mutations may be found in both components, indicating a common origin of the diseases [102,223]. Biology and treatment depend on the individual components found in the tumor, which are discussed in the specific sections.…”