Novel mutation in bruton's tyrosine kinase in patient with cutaneous t cell lymphoma

IntroductionX-linked Agammaglobulinemia (XLA) is a genetic disorder with mutation in Bruton's tyrosine kinase (BTK) that leads to defects in B cell development. This allows for the preponderance of recurrent respiratory tract infections. After infection, malignancy is the most prevalent cause of death in patients with congenital immunodeficiency disorders. We present the first reported case of a novel hemizygous c.1492C>G mutation in BTK in a patient with XLA and cutaneous T cell lymphoma (CTCL).Case Description55-year-old male with diagnosis of common variable immunodeficiency on immunoglobulin replacement therapy presented with erythematous papules on the nose and arms with swollen lymph nodes. Immunologic evaluation revealed IgA level 7, IgM <10, IgG 644, CD3 count 0.58, CD4 count 0.15, CD4/CD8 ratio 0.38 and absent CD19. Genetic testing revealed a novel hemizygous c.1492C>G mutation in the BTK gene leading to alternative diagnosis of XLA.Left arm biopsy showed granulomatous dermatitis with atypical CD8+ T-cell infiltrate (Figure 1). Diagnosis of cutaneous T-cell lymphoma, mycosis fungoides type, was determined. Further investigation with fluorodeoxyglucose (FDG)-PET scan revealed widespread avid skin thickening and mild FDG avid mediastinal, right hilar and bilateral inguinal nodes.DiscussionCTCL has been associated with primary immunodeficiencies such as Wiskott-Aldrich syndrome, XMEN, Hyper IgE, and RAG1 mutations as well as secondary immunodeficiencies such as HIV. CTCL has not been described in patients with XLA. In this case we report a novel hemizygous c.1492C>G mutation in the BTK gene in a patient found to have CTCL.