Michael A. Harrington

Epidermal Anti-Programmed Cell Death-Ligand 1 Expression in TEN Associated with Nivolumab Therapy.

Nivolumab is a programmed cell death receptor‐1 (PD‐1) antibody used in the treatment of metastatic or unresectable melanoma. Cutaneous reactions are the most common adverse events reported with these agents and are rarely severe or life‐threatening. Here we present a case report describing the clinicopathological findings of a patient with a fatal toxic epidermal necrolysis (TEN) eruption associated with use of nivolumab for treatment of metastatic melanoma. The patient developed a pruritic, morbiliform eruption, which slowly progressed over 3 months to a tender, exfoliative dermatosis. Histology initially showed interface dermatitis and subsequently revealed full thickness epidermal necrosis. The diagnosis of TEN was made. From initial biopsy to TEN presentation, there was an increase in the number of CD8+ lymphocytes within the dermal–epidermal junction and an increase of programmed death ligand 1 (PD‐L1) expression in both lymphocytes and keratinocytes. Despite treatment with infliximab, high‐dose steroids and intravenous immunoglobulin, the patient expired. Herein we describe what we believe is the second case of TEN associated with anti‐PD1 therapy reported in the literature. Increased expression of PD‐L1 by immunohistochemistry was observed as the eruption progressed to TEN. Early diagnosis and treatment is necessary in these fatal TEN reactions secondary to the anti‐PD‐1 antibody therapies.

The impact of neoadjuvant hedgehog inhibitor therapy on the surgical treatment of extensive basal cell carcinoma.

BackgroundAlthough hedgehog inhibitor therapy (HHIT) is offered as isolated medical treatment for extensive basal cell carcinoma (BCC), there is little evidence on the use of HHIT before definitive surgical intervention. In order to better define the utilization of HHIT for extensive BCC, we evaluated the impact of neoadjuvant HHIT on the subsequent surgical resection and reconstruction. MethodsAn IRB-approved, retrospective chart review was performed of patients who received HHIT as initial treatment for extensive BCC. Patients who discontinued HHIT and underwent surgical resection were included. Evaluation included BCC tumor response to HHIT, operative data, pathological data, radiation requirements, and evidence of tumor recurrence. ResultsSix patients were identified with tumors of the face/scalp (n = 4), trunk (n = 1) and upper extremity (n = 1). Hedgehog inhibitor therapy continued until tumors became unresponsive (n = 3, mean = 71 weeks) or side effects became intolerable (n = 3, mean = 31 weeks). In each case, a less extensive surgery was performed than estimated before HHIT. In 3 cases, significant bone resection was avoided. All resected specimens contained BCC. Four specimens exhibited clear margins. Postoperative radiation was performed in cases with positive margins (n = 2), and 1 patient experienced local recurrence. Length of follow-up was 5.7 to 11.8 months (mean = 8.23 months). ConclusionsAlthough HHIT was not curative for extensive BCC, HHIT can decrease the morbidity of surgical treatment and increase the likelihood of curative resection. For patients with extensive BCC, a combined neoadjuvant use of HHIT and surgical treatment should be considered.

The Haitian Earthquake: a resident's reflection.

hJanuary 12th, 2010; 16:53 hours. This was the time and date that a 7.0 Mw earthquake changed the lives of the Haitian population. Thousands died, and even more survived with injuries rarely seen in any hospital in the United States. Homes and businesses were destroyed and families torn apart. The earthquake devastated the entire nation. Since that time, health care workers, including plastic surgeons, from around the globe had flocked to Haiti in hopes of assisting in any way possible. As the tragedy occurred hundreds of miles south of Tampa, Florida, I was unaware of the impact it would have on my surgical training or my personal growth as a physician.

Treatment of head and neck melanoma in situ with staged contoured marginal excisions

Abstract Staged marginal evaluation of melanoma in situ (MIS) is performed to avoid reconstruction on positive margins. Contoured marginal excision (CME) is an excision of a 2-mm wide strip of normal-appearing skin taken approximately 5 mm from the visible tumor periphery. If positive, a new CME is excised; the tumor is resected once negative margins are confirmed. The purpose of this study is to report our experience using this technique for the treatment of head/neck MIS. Clinicopathological data were abstracted for all patients who underwent staged CME followed by central tumor resection for head/neck MIS; patients with invasive melanoma were excluded. Statistical analyses included &khgr;2 test and t test. Overall, 127 patients with MIS were identified. Fifty-six percent were men; the average age was 68 years. The median number of CME procedures per patient was 1 (range, 1–4). Twenty-three percent of patients required more than 1 CME procedure to achieve negative margins. Local recurrence occurred in 3 of 127 patients after a median follow-up of 5 months. Patients requiring multiple CME procedures were more likely to experience local recurrence (P < 0.001). In conclusion, this technique is an effective method to avoid reconstruction on positive MIS margins with high local disease control rates.