Background Vismodegib is an oral hedgehog-pathway inhibitor approved for advanced basal cell carcinoma (BCC). Although most BCCs are amenable to surgery, excision of large tumors in aesthetically ...sensitive sites may compromise function or cosmesis. Objective We sought to evaluate the reduction in BCC surgical defect area after 3 to 6 months of neoadjuvant vismodegib. Methods This was an open-label, single-arm intervention trial with a primary outcome of change in target-tumor surgical defect area pre- and post-vismodegib (150 mg/d). Secondary outcomes were change in tumor area and tolerability. Results Eleven of 15 enrolled patients, aged 39 to 100 years, completed the trial. Thirteen target tumors were excised after a mean of 4 ± 2 months of vismodegib. In all, 29% (4 of 14 patients) could not complete more than 3 months because of vismodegib-related side effects. The mean baseline target-tumor diameter was 3.2 cm, and 10 of 13 tumors occurred on the face. Overall, vismodegib reduced the surgical defect area by 27% (95% confidence interval –45.7% to –7.9%; P = .006) from baseline. Vismodegib was not effective in patients who received less than 3 months. Over a mean follow-up of 11.5 (range 4-21) months for all tumors, only 1 tumor recurred at 17 months post-Mohs micrographic surgery. Limitations Short follow-up time and no placebo control are limitations. Conclusion Neoadjuvant vismodegib appears to reduce surgical defect area when taken for 3 months or longer for nonrecurrent BCCs in functionally sensitive locations. Further studies with larger sample sizes and long-term follow-up are warranted.
Abstract Background: Avanafil is a selective phosphodiesterase type 5 inhibitor being developed for the treatment of erectile dysfunction. Objective: This study was conducted to meet Korean ...regulatory requirements for the marketing of avanafil. To this end, tolerability and pharmacokinetic properties of single and multiple oral doses of avanafil in healthy Korean male volunteers were assessed. Methods: A double-blind, randomized, placebo-controlled, parallel-group, dose-escalation study was conducted at the Asan Medical Center (Seoul, Korea). Subjects were randomized to receive either drug or placebo in blocks according to each dose. Subjects were randomly allocated to receive 50-, 100-, or 200-mg tablets of avanafil or placebo once daily for 7 days (avanafil:placebo, 8:2 in each dose group). Tolerability was assessed by monitoring vital signs and results of laboratory tests, 12-lead ECGs, and color discrimination tests. Blood samples of ∼6 mL were collected in heparinized tubes before and 0.1, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours after drug administration on days 1 and 7. Plasma concentrations of avanafil were measured using LC-MS/MS. Pharmacokinetic parameters of avanafil on days 1 and 7 were determined by noncompartmental analysis and compared among the 3 dose groups. Results: Of the 32 healthy male subjects initially enrolled, 30 completed the study. The mean (SD) age, height, and weight of the participants were 23.4 (1.7) years, 175.0 (5.4) cm, and 70.3 (8.9) kg, respectively. Adverse events were reported by 20 of 25 subjects (80%) taking avanafil and by 4 of 6 (67%) taking placebo. No serious adverse events were reported, and there were no clinically relevant changes in vital signs, ECG recordings, physical examination findings, or color discrimination test results. All the adverse events resolved spontaneously. Avanafil reached a mean Tmax at 0.33 to 0.52 hour after dosing and then declined, with a mean apparent t1/2 of 5.36 to 10.66 hours. AUC and Cmax were proportional to dose, and the mean accumulation index on day 7 after a single daily dose of avanafil was 0.98. Conclusion: Avanafil was generally well tolerated and had linear pharmacokinetic properties at daily doses of 50 to 200 mg over 7 days in these healthy Korean male volunteers. Korean National Study Registration Number: 3466.
Summary Clinical management of cutaneous T-cell lymphoma (CTCL) and angioimmunoblastic T-cell lymphoma (AITL) differs markedly. Diagnostic distinction is critical. Herein, we describe a series of 4 ...patients with clinically, molecularly, and histopathologically annotated mycosis fungoides or Sézary syndrome whose nodal disease mimicked AITL. The patients otherwise exhibited classic clinical manifestations of mycosis fungoides/Sézary syndrome preceding the onset of lymphadenopathy by 1 to 5 years. Skin biopsies revealed epidermotropic infiltrates characteristic of CTCL. Lymph node biopsies revealed dense CD4+ T-cell infiltrates that coexpressed follicular helper T-cell markers and were accompanied by proliferations of high endothelial venules and arborizing CD21+ follicular dendritic cell networks. Two patients had T-cell receptor gene rearrangement studies performed on their skin, lymph node, and peripheral blood demonstrating identical polymerase chain reaction clones in all 3 tissues. A small secondary clonal B-cell population was present in 1 patient that mimicked the B-cell proliferations known to accompany AITL and persisted on successive nodal biopsies over several years. This latter phenomenon has not previously been described in CTCL. The potential for patients to be misdiagnosed with AITL for lack of consideration of advanced-stage CTCL with nodal involvement underscores the necessity of information sharing among the various pathologists and clinicians involved in the care of each patient.
Background Sox10 is a transcription factor associated with neural crest development. Its expression has been reported in melanocytes and peripheral nerve sheath cells and their associated tumors. ...Objective To assess Sox10 sensitivity in benign and malignant melanocytic neoplasms of various histologic subtypes and to discern the specificity of Sox10 in distinguishing between melanocytic neoplasms and fibrohistiocytic and histiocytic mimickers. Methods Sox10 expression was examined by immunohistochemistry in 145 cases of formalin-fixed paraffin-embedded tissue, including benign and malignant melanocytic lesions of various histologies and stages (n = 83), fibrohistiocytic and histiocytic lesions (n = 33), and peripheral nerve sheath tumors (n = 19), among others (n = 10). Results Immunoreactivity with Sox10 was observed in 100% (83/83) of benign and malignant melanocytic lesions of various subtypes, as well as in 100% (19/19) of benign and malignant peripheral nerve sheath lesions. Among the fibrohistiocytic proliferations and histiocytoses examined, Sox10 was negative in all cases (0/33). Sox10 expression did not vary by histologic subtype in nevi or melanoma; however, both the percentage of tumor nuclei demonstrating Sox10 expression and the intensity of expression were inversely correlated with malignant potential (nevi, melanoma in situ, invasive and metastatic melanoma) ( P < .001, P = .016, respectively). Malignant peripheral nerve sheath tumors also showed decreased mean Sox10 expression and decreased intensity of expression when compared with benign counterparts ( P < .001, P = .021, respectively). Limitations This is a retrospective study with 145 cases included. Conclusions Sox10 is a highly sensitive marker for melanocytic proliferations and may be useful diagnostically when the differential diagnosis includes fibrohistiocytic and histiocytic proliferations demonstrating S100 expression.
Expression of PD-L1 in mastocytosis Kuklinski, Lawrence F., BA; Kim, Jinah, MD, PhD
Journal of the American Academy of Dermatology,
05/2016, Letnik:
74, Številka:
5
Journal Article
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