Search

The combination of dabrafenib and trametinib is an important immunotherapy option for patients with BRAF V600 mutation-positive melanoma. This regimen has been reported to cause cutaneous eruptions. However, hair dysmorphology is not a reported side effect to these or any other medications to date. Herein, we highlight a case of pili multigemini formation in a patient with stage IV melanoma receiving treatment with dabrafenib and trametinib and the corresponding clinical findings.

Basal cell carcinoma (BCC) is highly curable by surgical excision or radiation. In rare cases, BCC can be locally destructive or difficult to surgically remove. Hedgehog inhibition (HHI) with vismodegib or sonidegib induces a 50–60% response rate. Long-term toxicity includes muscle spasms and weight loss leading to dose decreases. This retrospective chart review also investigates the impact of CoQ10 and calcium supplementation in patients treated with HHI drugs at a single academic medical center from 2012 to 2022. We reviewed the charts of adult patients diagnosed with locally advanced or metastatic BCC treated with vismodegib or sonidegib primarily for progression-free survival (PFS). Secondary objectives included overall survival, BCC-specific survival, time to and reasons for discontinuation, overall response rate, safety and tolerability, use of CoQ10 and calcium supplements, and insurance coverage. Of 55 patients assessable for outcome, 34 (61.8%) had an overall clinical benefit, with 25 (45.4%) having a complete response and 9 (16.3%) a partial response. Stable disease was seen in 14 (25.4%) and 7 (12.7%) progressed. Of the 34 patients who responded to treatment, 9 recurred. Patients who were rechallenged with HHI could respond again. The median overall BCC-specific survival rate at 5 years is 89%. Dose reductions or discontinuations for vismodegib and sonidegib occurred in 59% versus 24% of cases, or 30% versus 9% of cases, respectively. With CoQ10 and calcium supplementation, only 17% required a dose reduction versus 42% without. HHI is highly effective for treating advanced BCC but may require dosing decreases. Sonidegib was better tolerated than vismodegib. CoQ10 and calcium supplementation can effectively prevent muscle spasms. [ABSTRACT FROM AUTHOR]

The article presents the cases of a 71-year-old male with coronary artery disease who was presented with cutaneous squamous cell carcinoma of the left helix and an 82-year-old female with smoking history who was rushed to a clinic due to superficial and micronodular basal cell carcinoma (BCC) to discuss necrosis of the ear after skin cancer resection. Topics include the need for clinicians to account for external ear vascular arcades during Mohs micrographic surgery.

OBJECTIVE To investigate the role of potential downstream targets of HER-2/neu, including the cell-cycle regulator p27, proliferation-associated protein Ki-67, apoptosis inhibitor Bcl-2, and signal-transduction molecule Akt (which is associated with cell survival), as the development of androgen-independent prostate cancer (AIPC) in patients who are initially responsive to androgen-ablation therapy (AAT) is a significant clinical problem. PATIENTS AND METHODS Earlier studies showed that high levels of HER-2/neu tyrosine kinase receptor expression as assessed by immunohistochemistry were significantly associated with the development of AIPC, and we hypothesised that HER-2/neu overexpression provides an alternative proliferative stimulus upon androgen depletion. We established a unique clinical model system, comprising patients who received no AAT, or who had preoperative AAT, or those with advanced tumours resistant to AAT. To test our hypothesis in vitro, we stably transfected full-length HER-2/neu cDNA in androgen-responsive LNCaP cells and examined the effects of HER-2/neu overexpression on cell proliferation, apoptosis, androgen-receptor activation, and Akt phosphorylation upon androgen deprivation by using immunohistochemistry and Western blot technique. RESULTS p27 expression was initially induced on exposure to AAT, and significantly decreased in AIPC ( P < 0.001). There was also a significant increase in the Ki-67 index in AIPC ( P = 0.001). Elevated Bcl-2 expression was closely associated with AAT ( P = 0.002), suggesting that Bcl-2 expression is induced on initial exposure to AAT. Further, Bcl-2 expression was highest in hormone-resistant cancers ( P < 0.001). Using the HER-2/neu transfected cell-line model, we confirmed the mechanistic basis of the clinical observations which elucidate the pathway leading to HER-2/neu-mediated androgen independence. On androgen deprivation, the HER-2/neu transfected cells had higher proliferation rates, lower G1 arrest, inhibited p27 up-regulation, a lower apoptotic index, and higher Bcl-2, prostate-specific antigen and phosphorylated Akt expression than the mock-transfected LNCaP cells. CONCLUSION This study suggests that prostate cancer cells undergo a series of coordinated changes after exposure to AAT, which eventually result in the development of androgen independence. Further, in support of previous results, it appears that a major factor in this process is the induction of HER-2/neu overexpression, which occurs after initial exposure to AAT. HER-2/neu may contribute to the development of androgen independence through: (i) maintaining cell proliferation; (ii) inhibiting apoptosis; and/or (iii) inducing AR activation in a ligand-independent fashion. These effects may be mediated, at least in part, through activation of the PI3K/Akt pathway. [ABSTRACT FROM AUTHOR]

To examine the traditional concept that acetone or ethanol-fixed frozen tissue sections represent the "golden standard" for IHC, we have conducted a study evaluating frozen sections with various conditions of fixation and antigen retrieval (AR). Fresh human tissues were frozen in OCT. An adjacent tissue was fixed routinely in 10% neutral buffered formalin (NBF) and paraffin-embedded (FFPE). Preparations of human cell lines were processed into frozen and FFPE cell blocks to confirm the IHC results of tissues. Frozen tissue/cell sections were fixed by 6 protocols: acetone 10 min; ethanol 10 min; NBF 30 min, & 24 hrs; NBF + CaCl2 30 min, & 24 hrs. The AR technique was used for all NBF fixed tissue sections. 26 antibodies with ABC kit, DAB, were used to generate the IHC signal. Results: more than half antibodies (16/26, 61.5%) showed identical IHC staining results between acetone-fixed, and NBF-fixed tissue sections. Among the remained antibodies, 5 (19.2%) showed better IHC signals following NBF and AR, only 3 antibodies gave better IHC staining results for acetone-fixed tissue sections. Most cytoplasmic proteins (11/13) showed comparable IHC signal between acetone and NBF fixed tissue sections. For nuclear proteins, NBF-fixed tissue sections gave better IHC signals than obtained by acetone-fixed sections. In most cases NBF yielded stronger signal with less background, and better morphology. Conclusion: the data do not support the traditional use of acetone fixed frozen tissue sections as the "golden standard" for IHC. It would be prudent to employ a combination of both acetone and NBF fixed frozen sections, and FFPE tissue sections may serve as the standard for most antigens for IHC. [ABSTRACT FROM AUTHOR]

Background: In an effort to avoid numerous problems associated with narrative letters of recommendation, a dermatology standardized letter of recommendation was utilized in the 2014-2015 resident application cycle. Objective: A comparison of the standardized letter of recommendation and narrative letters of recommendation from a single institution and application cycle to determine if the standardized letter of recommendation met its original goals of efficiency, applicant stratification, and validity. Methods: Eight dermatologists assessed all standardized letters of recommendation/narrative letters of recommendation pairs received during the 2014-2015 application cycle. Five readers repeated the analysis two months later. Each letter of recommendation was evaluated based on a seven question survey. Letter analysis and survey completion for each letter was timed. Results: Compared to the narrative letters of recommendation, the standardized letter of recommendation is easier to interpret (p<0.0001), has less exaggeration of applicants' positive traits (p<0.001), and has higher inter-rater and intrarater reliability for determining applicant traits including personality, reliability, work-ethic, and global score. Standardized letters of recommendation are also faster to interpret (p<0.0001) and provide more information about the writer's background or writer-applicant relationship than narrative letters of recommendation (p<0.001). Limitations: This study was completed at a single institution. Conclusions: The standardized letter of recommendation appears to be meeting its initial goals of 1) efficiency, 2) applicant stratification, and 3) validity. (J Clin Aesthet Dermatol. 2016;9(9):36-2.). [ABSTRACT FROM AUTHOR]

Lymphangioma circumscriptum (LC) results from the development of abnormal lymphatic vasculature and is characterized by the presence of grouped vesicles filled with clear or colored fluid. Vulvar localization is uncommon. Abnormalities of the lymphatic system, such as lymphedema and cystic hygroma, are well-known features of genetic disorders such as Noonan syndrome (NS) and Turner syndrome. We report the case of a patient with NS who presented with LC of the vulva. We also discuss the expanding spectrum of clinical anomalies associated with the presentation of NS.