If At First You Don't Succeed, Trikafta Again.

Adverse reactions, including severe cutaneous reactions, to cystic fibrosis transmembrane conductance regulator (CFTR) modulators have been described in the literature. Herein we present a drug eruption in response to elexacaftor/tezcaftor/ivacaftor (brand name, Trikafta) in a 7-year-old male with cystic fibrosis, followed by desensitization and successful continuation. A review of the literature outlining similar cases is provided. Attempting to mitigate and manage drug reactions to CFTR modulators is essential because they represent vital and irreplaceable therapies for individuals with cystic fibrosis (CF).

The utility of using immunohistochemistry in the differentiation of metastatic, cutaneous clear cell renal cell carcinoma and clear cell hidradenoma.

BACKGROUND: Clear cell hidradenoma and cutaneous clear cell renal cell carcinoma (CCRCC) overlap morphologically. The distinction may be difficult in a patient with a history of CCRCC, presenting with a cutaneous nodule, potentially leading to an erroneous diagnosis. We investigated the usefulness of napsin A and paired box gene 8 (PAX-8) with previously studied markers epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), vimentin and cluster of differentiation marker 10 (CD10) in differentiating CCRCC from hidradenoma. METHODS: We evaluated hidradenomas and cutaneous CCRCCs for immunohistochemical expression of napsin A, PAX-8, EMA, CEA, vimentin and CD10. RESULTS: PAX-8 was expressed in all CCRCCs (8/8) while negative in hidradenomas. Napsin A was negative in both hidradenomas (0/12) and CCRCCs (0/10). EMA showed membranous reactivity in 11 of 12 hidradenomas and 8 of 10 CCRCCs; and highlighted ductal epithelium in 1 of 12 hidradenomas and cystic areas in 4 of 10 CCRCCs. CD10 showed ductal expression in 3 of 12 hidradenomas and membranous staining in 8 of 9 CCRCCs. CEA highlighted ductal epithelium in 11 of 12 hidradenomas while absent in CCRCCs (0/10). Vimentin highlighted neoplastic cells in 8 of 8 CCRCCs and failed to stain the hidradenomas (0/12). CONCLUSION: A conservative immunohistochemical panel including PAX-8, vimentin and CEA allow for easy distinction of CCRCC from hidradenoma, whereas napsin A added no additional value.

Cellular neurothekeoma: analysis of 37 cases emphasizing atypical histologic features.

Cellular neurothekeoma is a frequent source of diagnostic difficulty. In order to gain more insight into the range of histologic features of cellular neurothekeoma, we examined all cases from our institution, with a focus on describing atypical histologic features. Cases with sufficient histologic material for evaluation were retrieved. Cases were analyzed for demographics, growth pattern, myxoid stroma, cytologic atypia, mitotic rate, perineural invasion, and other histologic features. The 37 patients (16 M; 21 F) had a mean age of 31.0 years (range: 4-89). Tumors involved the head and neck (n=16), arms (n=11), trunk and shoulders (n=8), and foot (n=2). All cases had at least focal nesting of epithelioid to spindled tumors cells characteristic of cellular neurothekeoma. In many, alternate growth patterns were present and represented the dominant pattern in some. These patterns included fascicular (n=9), sheet-like (n=6), and corded (n=4). Myxoid stroma was present in 14 and was prominent in 5. Cytologic atypia was present in 19 patients, with 3 having severe atypia. Mean mitotic rate was 2.0/mm(2) (range 0-10 per mm(2)). Neurotropism was seen in four cases. Other unusual features included collagen trapping, giant cells, hemorrhage, lymphocytic cuffing, chondroid stroma, and cellular vacuolization. Cellular neurothekeoma has a wider range of features than is commonly recognized. The presence of nests of epithelioid tumor cells with characteristic cytologic features, no matter how focal, is a clue to the diagnosis.

Effectiveness of topical immunosuppressants in prevention and treatment of rejection in face allotransplantation.

BACKGROUND: The use of topical immunosuppressants has been anecdotally reported for the treatment of rejection in vascularized composite allotransplantation. The aim of this study was to evaluate the effectiveness of topical tacrolimus and clobetasol in the prevention and treatment of rejection. METHODS: Seventy-six hemiface allotransplants, between ACI (RT1) donors and Lewis (RT1) recipients, were performed in 11 groups and treated with topical tacrolimus or clobetasol, or in combination with systemic cyclosporine A and anti-αß-T-cell receptor antibody for 1 week. Topical treatment increased the survival of the allograft in all groups. RESULTS: Best outcomes were obtained in the groups treated with systemic therapy and topical tacrolimus. Expression of proinflammatory cytokines interleukin 2, interferon γ, tumor necrosis factor α, and transforming growth factor ß correlated with clinical signs of rejection and the final outcomes. Clobetasol application was associated with a marked depletion of lymphocytic populations, and dermal and epidermal atrophy. CONCLUSIONS: Both topical tacrolimus and clobetasol were effective in treating episodes of acute rejection, and the best outcomes were achieved when their application was initiated after systemic immunosuppression. Topical tacrolimus proved to be a preferable adjunct agent to the systemic therapy by preventing both the local and systemic complications.