Cutaneous adult xanthogranuloma with a small portion of BRAFV 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.

Cutaneous squamous cell carcinoma, thyroid cancer and Langerhans cell histiocytosis in a patient with X-linked recessive Mendelian susceptibility to mycobacterial diseases with a nuclear factor-κB essential modifier mutation.

Nuclear factor (NF)-κB essential modifier (NEMO), also known as IκB kinase subunit-γ (IKKγ), is a pivotal molecule in the NF-κB signaling pathway. Mutations of NEMO cause incontinentia pigmenti and X-linked ectodermal dysplasia with immunodeficiency. Mendelian susceptibility to mycobacterial diseases (MSMD), which confers an almost selective predisposition to mycobacterial infection, is also caused by NEMO mutations. We herein report the first case of a patient with X-linked recessive (XR) MSMD who developed cutaneous squamous cell carcinoma, thyroid cancer and Langerhans cell histiocytosis. The relationship between NEMO mutation and oncogenesis is discussed.

Primary bilateral adrenal diffuse large B-cell lymphoma demonstrating adrenal failure.

Primary adrenal lymphoma (PAL) is extremely rare although involvement of malignant lymphoma into adrenals is common. We report a case of a 58-year-old man with bilateral PAL who demonstrated adrenal insufficiency. Primary large B-cell lymphoma was proven by a computed tomography-guided needle biopsy of the adrenal tumor. Although a complete remission was once achieved by combination chemotherapy plus rituximab, a recurrence occurred with brain metastasis leading to his death. We concluded that PAL should be considered as a possible cause of bilateral adrenal incidentalomas with progressive adrenal insufficiency.

Digital gangrene in systemic lupus erythematosus.

Digital ulcers and gangrene are common skin manifestations of connective tissue diseases, especially systemic sclerosis, although they are relatively rare in systemic lupus erythematosus. We describe here three patients with digital gangrene and systemic lupus erythematosus. None of the patients showed high disease activity of systemic lupus erythematosus at the time the digital gangrene developed. Two patients were positive for anti-RNP antibodies; however, no symptoms of other collagen diseases were present. One patient had anti-phosphatidylserine/prothrombin complex antibodies, and the other had anti-cardiolipin beta2 glycoprotein I antibodies and lupus anticoagulant at low titre. All patients showed narrowing or occlusion of radial and/or ulnar arteries in addition to digital arteries. Although a complication of anti-phospholipid syndrome is considered to be a possible cause, there may be unidentified causes other than thrombosis, atherosclerosis, overlap syndrome and vasculitis.