Efficacy, rate of tumor response, and safety of a short course (12-24 weeks) of oral vismodegib in various histologic subtypes (infiltrative, nodular, and superficial) of high-risk or locally advanced basal cell carcinoma, in an open-label, prospective case series clinical trial.

BACKGROUND: Vismodegib demonstrated 60% response rates in the ERIVANCE trial. Basal cell carcinoma has various histopathologies. Their effect on response is unclear. OBJECTIVE: The purpose of this study was to determine whether basal cell carcinoma histopathology affected vismodegib response. METHODS: This phase 2b, single-center, prospective case series study compared the efficacy of vismodegib in infiltrative, nodular, and superficial basal cell carcinomas treated for 12 or 24 weeks in 27 patients. Patients had 1 target lesion and up to 3 nontarget lesions. RESULTS: Twenty-seven patients were enrolled, with 65 tumors (27 target lesions/38 nontarget lesions). At 24 weeks, most basal cell carcinomas achieved histologic clearance, with positive biopsy results in 10.5% of target lesions, 30.4% of nontarget lesions, and 21.4% overall. No statistical differences were observed between histopathologic subtypes. One hundred percent of patients experienced an adverse event, 94% grade 1 or 2. The most common adverse events were dysgeusia/loss of taste (86%), muscle spasms (82%), and alopecia (71%). Clinically progressive disease during treatment was low (1.5%). Two patients had recurrence within 1 year of treatment. LIMITATIONS: Limitations included sample size of basal cell carcinoma histopathologic subtypes, sampling punch biopsies, and short follow-up. CONCLUSIONS: Basal cell histopathologic subtype did not significantly affect response to vismodegib. Each subtype was observed to completely respond at 12 weeks of therapy, 24 weeks, or both.

Lichenoid reaction as a potential immune response marker of intratreatment histological response during successful vismodegib treatment for a giant basal cell carcinoma.

We report an 83 year-old patient with a 13 × 7.5 cm(2) basal cell carcinoma (BCC) successfully treated with the combination of vismodegib and minimal surgery. On Day 109, a 0.9 cm papule suspicious for residual BCC was seen centrally within a large pink atrophic plaque. This lesion was excised; pathology confirmed BCC with negative surgical margins. Simultaneously, suspecting noncontiguous histologic response, we performed 21 biopsies at the periphery of the pretreatment tumor location. Seventeen (17/21, 81%) revealed lichenoid dermatitis. No tumor was seen on any. We believe the lichenoid dermatitis observed is a novel finding for two reasons. First, it may be considered a marker of a positive intratreatment response. This may help guide clinicians on the optimal treatment duration of vismodegib to maximize efficacy and mitigate side effects. Second, we think it suggests an additional mechanism of vismodegib action, possibly via local immune effects. Further investigations are warranted.

Ulcerated infantile hemangioma: novel treatment with topical brimonidine-timolol.

We report a 2-month-old boy with a painful ulcerated hemangioma on the lower mucosal lip extending to the vermillion border that caused feeding difficulty. It was successfully treated with topical brimonidine 0.2% and timolol 0.5%, a combination selective α2 -adrenergic agonist and nonselective ß-blocker. After 6 weeks of treatment, the lesion reepithelialized and the patient's symptoms and functional complications resolved. Brimonidine 0.2% timolol 0.5% ophthalmic solution is an emerging alternative treatment for hemangiomas, offering the potential to target hemangioma growth through two synergistic mechanisms (ß-inhibition and α2 -agonism) that may be especially effective for ulcerated lesions, the most common complication of infantile hemangiomas.

Evaluation of the definitions of "high-risk" cutaneous squamous cell carcinoma using the american joint committee on cancer staging criteria and national comprehensive cancer network guidelines.

Recent guidelines from the American Joint Committee on Cancer (AJCC) and National Comprehensive Cancer Network (NCCN) have been proposed for the assessment of "high-risk" cutaneous squamous cell carcinomas (cSCCs). Though different in perspective, both guidelines share the common goals of trying to identify "high-risk" cSCCs and improving patient outcomes. Thus, in theory, both definitions should identify a similar proportion of "high-risk" tumors. We sought to evaluate the AJCC and NCCN definitions of "high-risk" cSCCs and to assess their concordance. Methods. A retrospective review of head and neck cSCCs seen by an academic dermatology department from July 2010 to November 2011 was performed. Results. By AJCC criteria, most tumors (n = 211,82.1%) were of Stage 1; 46 tumors (13.9%) were of Stage 2. Almost all were of Stage 2 due to size alone (≥2 cm); one tumor was "upstaged" due to "high-risk features." Using the NCCN taxonomy, 231 (87%) of tumors were "high-risk." Discussion. This analysis demonstrates discordance between AJCC and NCCN definitions of "high-risk" cSCC. Few cSCCs are of Stage 2 by AJCC criteria, while most are "high-risk" by the NCCN guidelines. While the current guidelines represent significant progress, further studies are needed to generate a unified definition of "high-risk" cSCC to optimize management.

Coexistent dermatofibrosarcoma protuberans and anticonvulsant-induced cutaneous lymphoid hyperplasia: diagnostic challenge.

A 60-year-old African-American male patient with a history of seizures, developmental delay, long history of behavioural issues with psychotic episodes, heart, liver, thyroid and kidney diseases presented for evaluation of a right neck skin lesion. Physical examination revealed a shiny purplish-red plaque on the right neck and a thin pink plaque on the posterior neck. The lesions were similar in appearance, but different enough to warrant skin biopsy of each. Pathology demonstrated mycosis fungoides (MF) on the right neck and dermatofibrosarcoma protuberans (DFSP) on the posterior neck. The identification of two rare conditions made us reconsider our diagnosis. After further review, the right neck skin lesion was thought to be anticonvulsant-induced cutaneous lymphoid hyperplasia, not MF. This case demonstrates how insufficient skin biopsy can have significant clinical consequences. Biopsy of the right neck only would have overlooked a DFSP and incorrectly given the patient a diagnosis of MF.

High-Dose Interleukin-2 (HD IL-2) Therapy Should Be Considered for Treatment of Patients with Melanoma Brain Metastases.

A retrospective review was performed on patients with stable melanoma brain metastases treated with HD IL-2 therapy (720,000 IU/kg per dose intravenously; 14 doses, 2 cycles per course, maximum 2 courses) from January 1999 to June 2011 at Saint Louis University. There were 5 men and 3 women; median age was 52.2 years (26.8-61.1 years). One patient started treatment with lung lesions only (after resection of melanoma brain disease) and experienced partial response. Seven patients had brain metastases at treatment initiation. Median overall survival (mOS) for entire cohort (n = 8) was 8.7 months (2.1 to 19.0 months). All patients with brain metastases at first dose (n = 7) showed progressive disease; mOS was 6.7 months (range 2.1-18.2 months) for this group. Patients received radiosurgery and whole brain radiation before and after HD IL-2 therapy. One patient had symptoms suggestive of neurotoxicity. A history of alcohol abuse was revealed during admission. The patient's symptoms improved with initiation of an alcohol withdrawal protocol. In this analysis, patients with melanoma brain metastases received HD IL-2 without treatment-related mortality. We think that HD IL-2 should be considered as a treatment option in patients with melanoma brain metastases who are otherwise eligible for therapy.

Efficacy of topical brimonidine-timolol for haemangioma of infancy and perils of off-label prescribing.

We report three patients with superficial haemangiomas treated topically with Combigan ophthalmic solution (brimonidine 0.2%-timolol 0.5%), a combination selective α-2-adrenergic agonist and non-selective ß-blocker Food and Drug Administration-approved for use in glaucoma. Topical brimonidine 0.2%-timolol 0.5% therapy improved the appearance of haemangiomas in all the cases. Two patients did not experience any adverse effects. One patient had hypothermic episodes which were initially thought to be because of brimonidine 0.2%-timolol 0.5% therapy. However, an episode occurred a few weeks after discontinuation and brimonidine 0.2%-timolol 0.5% therapy was ruled out as a cause. Despite the benefit, off-label use of brimonidine 0.2%-timolol 0.5% therapy served as a pitfall in the evaluation of an unusual constellation of worrisome symptoms. In conclusion, brimonidine 0.2%-timolol 0.5% therapy is a promising alternative in the topical treatment of haemangiomas. It may have synergistic effects and increased efficacy by targeting haemangiomas via two mechanisms (α-agonism and ß-inhibition), but the risk of unforeseen adverse effects must always be considered when prescribing off-label treatment, especially in infants.

Coexistent metastatic melanoma of the kidney with unknown primary and renal cell carcinoma.

In this report, we present an African-American female patient who presented with haematuria to her primary care physician. The symptoms persisted and coexistent metastatic spindle cell-type melanoma of the kidney and renal cell carcinoma were discovered on further evaluation. No primary site for melanoma was identified. Despite aggressive treatment with ipilimumab, the patient's disease progressed quickly. The patient opted for palliative care and was referred to a hospice. Coexistent melanoma and renal cell carcinoma is exceedingly rare. Melanoma itself is rare in the African-American population. However, when it does present, it usually is at an advanced stage, as was the case in our patient. Since no primary tumour site for melanoma was found and the diagnosis was made after the tumour had metastasised, we think this case highlights the importance of cutaneous cancer surveillance in the non-Caucasian population. Earlier identification of melanoma in this population will help to improve outcomes.

Acitretin-induced poliosis with concurrent alopecia.

Acitretin, a metabolite of the aromatic retinoid etretinate, has been utilized successfully in the treatment of psoriasis since the late 1980s. Of the oral retinoids available, etretinate and acitretin are the most likely agents to induce various dose-dependent hair changes, but to our knowledge this is the first reported case of acitretin-induced poliosis. Additional cutaneous findings included skin atrophy and stickiness. Here we report a case of full body acitretin-induced poliosis with concurrent alopecia in a patient with psoriasis. A proposed mechanism for the poliosis is also presented here. Closer examination of retinoid-induced hair changes is needed in order to help physicians better counsel their patients regarding the adverse effects of acitretin and to expand the current knowledge on hair follicle biology.

Patients with drug-eluting stents and management of their anticoagulant therapy in cutaneous surgery.

Whether a patient has a drug-eluting stent (DES) implanted may not seem to be an immediate concern for a dermatologist. However, the clinician needs to consider a patient's risk of bleeding if a patient is to undergo a cutaneous surgical procedure. Patients with skin cancer are generally older with a higher risk of comorbidities such as cardiovascular disease with history of cardiac stent implantation. After DES placement, patients are typically on long-term dual antiplatelet therapy, which increases the risk of bleeding. However, stopping antiplatelet therapy prematurely can lead to serious thrombotic complications. Thus, when performing a dermatologic procedure in a patient with a DES, the physician must weigh the risks of bleeding complications with continuing antiplatelet therapy against the risk of thrombotic complications associated with stopping antiplatelet therapy. The aim of this review is to identify the issues for the dermatologist and the dermatologic surgeon surrounding the perioperative treatment of patients with a DES and to discuss the treatment of patients with an implanted DES.