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Management of lower extremity wounds following successful tumor excision presents multiple challenges. Distal lower extremity integument is highly prone to edema often lacks adequate skin laxity for standard primary closures. The closure must be resilient enough to withstand mobility. As a result, optimal reconstruction may include skin grafting, rotational flaps, free tissue transfers, healing by second intention, or some combination. These methods may involve multiple steps in reconstruction, a prolonged recovery period, increased cost, and higher infection risk. We propose a modified primary closure that takes advantage of the visco-elastic properties of the skin without introducing additional components or steps. This technique is initiated with percutaneous suture in order to intermittently stretch the skin with constant tension. This load cycling allows for lower extremity skin to stretch over time and ultimately reduce wound edge tension, allowing for ease of absorbable suture placement. The Twizzler technique is cost-effective, uses readily available supplies, and effectively closes relatively large defects on the lower extremities.

Background Dermatologists are at risk of body-fluid contamination during procedures. Objective We sought to determine the frequency of blood splash during procedural dermatology. Methods In all, 500 consecutive excisions were performed. Postoperatively, blood droplets on face shields and surgical gowns were counted. A survey regarding universal precautions during procedures was also conducted with members of the American College of Mohs Surgery (ACMS). Results Contamination from blood splashes during dermatologic procedures (Mohs micrographic surgery, excision, repair) occurred in 66.4%. Reconstruction type, anticoagulation use, wound location, and wound size correlated with a higher blood splash rate. Our survey showed that face shields and goggles are used inconsistently. Limitations The 4 participating dermatologists do not represent all practicing dermatologists. It may be possible to generalize the survey results directed at physicians in the ACMS. Conclusion Physician body-fluid contamination risk with procedural dermatology is clinically significant. Dermatologists and their assistants should wear preventive barriers during procedures to minimize the risk of viral transmission.

UV-induced pigmentation (suntanning) requires induction of alpha-melanocyte-stimulating hormone (alpha-MSH) secretion by keratinocytes. alpha-MSH and other bioactive peptides are cleavage products of pro-opiomelanocortin (POMC). Here we provide biochemical and genetic evidence demonstrating that UV induction of POMC/MSH in skin is directly controlled by p53. Whereas p53 potently stimulates the POMC promoter in response to UV, the absence of p53, as in knockout mice, is associated with absence of the UV-tanning response. The same pathway produces beta-endorphin, another POMC derivative, which potentially contributes to sun-seeking behaviors. Furthermore, several instances of UV-independent pathologic pigmentation are shown to involve p53 "mimicking" the tanning response. p53 thus functions as a sensor/effector for UV pigmentation, which is a nearly constant environmental exposure. Moreover, this pathway is activated in numerous conditions of pathologic pigmentation and thus mimics the tanning response.

background. Near-infrared reflectance-mode confocal scanning laser microscopy (RCM) represents a novel imaging technique for microscopic analysis of skin lesions and may provide a noninvasive modality for the diagnosis of basal cell carcinoma (BCC). objective. To determine the feasibility of detecting residual or clinically equivocal BCC using RCM. methods. In this pilot study, RCM was used in three cases to characterize the histologic features of index lesions in vivo. These were subsequently correlated with corresponding hematoxylin-eosin–stained sections obtained during Mohs micrographic surgery. results. Evaluation of clinically equivocal lesions by RCM revealed features characteristic of BCC, including tightly packed nests of elongated, monomorphic, polarized nuclei and subjacent ectatic blood vessels with lymphocytes undergoing margination and rolling. Conventional histology confirmed the presence of BCC in all cases. conclusion. We report the use of RCM in the confirmation of residual BCC in two cases and the tentative diagnosis with subsequent pathologic conformation of a third case in which a biopsy was previously inadequate. Our results demonstrate that confocal microscopy may facilitate diagnosis of BCC in vivo and warrant further prospective study to quantify the sensitivity and specificity of this rapidly evolving imaging modality.

Background. Imiquimod is an immune response modifier that up-regulates cytokines and has been shown in clinical studies to reduce or clear basal cell carcinoma tumors when applied topically. Objective. The objectives were to evaluate the efficacy of 5% imiquimod cream in treating basal cell carcinoma preceding excision by Mohs micrographic surgery and to determine if reflectance-mode confocal microscopy is useful to establish the need for surgical intervention after imiquimod treatment. Methods. Subjects applied study cream to one biopsy-confirmed basal cell carcinoma tumor 5 ×/week for 2, 4, or 6 weeks in this vehicle-controlled, double-blind study. Confocal microscopy was used for the 6-week treatment group to examine the target tumor area at each interval visit and immediately before Mohs micrographic surgery. After the Mohs micrographic surgery excision, the tissue was evaluated histologically, and the excision area was measured. Confocal microscopy readings were correlated to the histologic diagnosis. Results. Tumors cleared or the target tumor area was reduced in subjects in the 4- and 6-week dosing regimens. Confocal microscopy assessments correlated well with the histologic diagnosis. conclusion. Imiquimod improved excision results relative to vehicle when used for treating basal cell carcinoma before Mohs micrographic surgery. Confocal microscopy assessments correlated well with tumor response to therapy, suggesting that confocal microscopy may help determine the need for surgery.

Primary cutaneous mucinous carcinoma is a rare adnexal malignancy with a high recurrence rate following conventional excision and the potential for aggressive local invasion.To enhance the microscopic detection of mucinous carcinoma in Mohs micrographic surgical sections by incorporating rapid immunohistochemical staining.Standard Mohs micrographic surgical technique was used in conjunction with frozen section immunohistochemistry using an antibody to low-molecular-weight cytokeratin.Rapid immunoperoxidase staining using low-molecular-weight cytokeratin detected residual foci of mucinous carcinoma that were difficult to identify on routine frozen sections. Immunostaining was strongly positive in areas with clear evidence of tumor by routine histology, as well as in adjacent areas on a subsequent stage where frozen sections were equivocal or negative. Immunostaining was distinctly negative at the final surgical margin, which was shown by en face permanent sections to be free of tumor. The patient has been free of recurrence for 3 years.Immunoperoxidase-guided Mohs micrographic surgery using low-molecular-weight cytokeratin enhances the sensitivity for detection of mucinous carcinoma, and may help contribute to complete tumor removal.

Background. In the management of large facial neoplasms, the dermatologic surgeon must consider local factors affecting the success of closures. Objective. Large facial neoplasms can be removed serially with Mohs micrographic surgery. Serial excision facilitates recruitment of adjacent normal skin for replacement of lesional skin, minimizing the risks of necrosis. Methods. A large morpheaform basal cell carcinoma was excised serially. The initial defect was closed with an O to L advancement flap. The final excision and repair 2 months later consisted of a combination of primary closure with marsupialization and pursestring closure. A full-thickness skin graft was used to close the final defect. Results. The patient had optimal cosmesis at 2-year follow-up. Conclusion. Large facial neoplasms can be excised serially. This technique, performed in the setting of Mohs micrographic surgery, takes advantage of “mechanical and biologic creep,” resulting in excellent cosmesis and function.

Squamous cell carcinomas (SCCs) of the skin are sun-induced skin cancers that are particularly numerous in patients on T cell immunosuppression. We found that blood vessels in SCCs did not express E-selectin, and tumors contained few cutaneous lymphocyte antigen (CLA)+ T cells, the cell type thought to provide cutaneous immunosurveillance. Tumors treated with the Toll-like receptor (TLR)7 agonist imiquimod before excision showed induction of E-selectin on tumor vessels, recruitment of CLA+ CD8+ T cells, and histological evidence of tumor regression. SCCs treated in vitro with imiquimod also expressed vascular E-selectin. Approximately 50% of the T cells infiltrating untreated SCCs were FOXP3+ regulatory T (T reg) cells. Imiquimod-treated tumors contained a decreased percentage of T reg cells, and these cells produced less FOXP3, interleukin (IL)-10, and transforming growth factor (TGF)-β. Treatment of T reg cells in vitro with imiquimod inhibited their suppressive activity and reduced FOXP3, CD39, CD73, IL-10, and TGF-β by indirect mechanisms. In vivo and in vitro treatment with imiquimod also induced IL-6 production by effector T cells. In summary, we find that SCCs evade the immune response at least in part by down-regulating vascular E-selectin and recruiting T reg cells. TLR7 agonists neutralized both of these strategies, supporting their use in SCCs and other tumors with similar immune defects.

Objective To evaluate the demographic characteristics, clinical course, and outcome in organ transplant recipients with metastatic skin cancer. Design and Setting An international, multicenter, Internet-coordinated collaborative group retrospectively analyzed data from 68 organ transplant recipients with 73 distinct metastatic skin cancers. Main Outcome Measurements The Kaplan-Meier method was used to estimate the cumulative incidence of relapse, overall survival, and disease-specific survival after metastatic skin cancer. Univariate Cox proportional hazards models were fit to evaluate factors for an association with survival. Results Metastasis from skin cancer in organ transplant recipients most commonly consisted of squamous cell carcinoma in regional nodal basins. It was predominantly treated with a combination of surgery and irradiation. By 1 year after metastasis, the cumulative incidence of relapse was 29%, and the 3-year disease-specific survival was 56%. Patients whose initial metastases were distant or systemic had a significantly poorer disease-specific survival than those whose initial metastases were in-transit or regional (risk ratio, 6.5;P Conclusions Metastatic skin cancer in organ transplant recipients has a poor prognosis. Preventive, early, and aggressive therapeutic interventions are required to minimize this serious complication of transplant-associated immunosuppression.

Objective To describe the clinical and laboratory findings in patients with pseudoporphyria. Patients and Methods This retrospective review identified 261 patients with either porphyrin metabolism abnormalities or pseudoporphyria who were seen at the Mayo Clinic in Rochester, Minn, between 1992 and 1996. All patients with documented porphyria cutanea tarda (PCT), noncutaneous porphyrias, or variegate porphyria were excluded. Results Twenty patients had active cutaneous lesions resembling PCT with no diagnostic laboratory abnormalities. The major presenting clinical features were blistering in 19 patients (95%), scarring in 14 (70%), photosensitivity in 13 (65%), skin fragility in 13 (65%), and milia in 8 (40%). Histologically, of 17 patients tested, 12 (71%) had classic findings of subepidermal separation with festooning of dermal papillae. None of the 11 patients tested had hepatitis B or C. In all 20 patients, porphyrin profiles were nondiagnostic. Of 16 patients for whom follow-up was available, 11 reported persistent symptoms for a mean of 2.5 years after evaluation. Five patients were free of symptoms 1 week to 6 months after discontinuation of the presumed offending agent. Conclusion Pseudoporphyria mimics the cutaneous symptoms of PCT in the setting of normal or near-normal porphyrin levels in the serum, urine, or stool. Despite efforts to discontinue an offending medication, symptoms may persist indefinitely.

Background. Dermatofibrosarcoma protuberans (DFSP) is a spindle cell malignancy that has a high local recurrence rate after excision with minimal or no immediate tissue margin assessment. DFSP is exceedingly rare on the palms and soles. Objective. To report a case of a locally aggressive DFSP on the sole excised using Mohs micrographic surgery. Methods. Case report and review of the literature. Results. Mohs micrographic surgery unmasked tumor infiltration that extended around plantar aponeurosis and into underlying plantar muscle fascia. Conclusion. Mohs micrographic surgery should be considered the treatment of choice for DFSP, especially in acral locations. This technique allows the surgeon to trace out deep tumor extensions that may wrap around underlying tendon, a finding that may not be appreciated clinically.

Background. Two patients undergoing cutaneous surgery had thromboembolic strokes within 1 week after surgery. Both patients had been taking warfarin for prevention of thromboembolism and warfarin was stopped 3–7 days prior to surgery. Objective. To examine the rationale and problems associated with preoperative warfarin discontinuation. Methods. Review of the medical literature. Results. When warfarin is stopped prior to surgery and restarted soon after surgery, the patient is at increased risk for thromboembolism. Although it is commonly believed that continuing warfarin during surgery is associated with an increased bleeding risk, for cutaneous surgery, this risk is extremely low and can be easily managed. Conclusion. Warfarin should not be discontinued prior to cutaneous surgery because of the risk of thromboembolic stroke.

Background: Few case series describing Dowling-Degos disease (DDD) have been reported. Objective: Our purpose was to review the clinical and histopathologic findings in DDD. Methods: We reviewed the clinical and histopathologic findings in 6 patients with DDD who were evaluated at the Mayo Clinic. Results: In addition to the typical flexural pigmented reticulate macules, comedo-like lesions on the back or neck or both were present in all 6 patients; 3 patients had pitted perioral scars, and 3 patients reported pruritus of affected flexural areas. Five patients were female, 5 patients had onset of pigmentation before age 24 years, and 3 patients had a family history of DDD. One patient had additional pigmentation involving the dorsum of the hands and proximal nailfolds and fingernail dystrophy. Histopathologically, pigmented rete ridge elongation with thinning of suprapapillary epithelium, dermal melanosis, and perivascular lymphohistiocytic infiltration were consistently observed. Conclusion: Comedo-like lesions, pruritus, and pitted perioral scars are common features in association with the reticulate flexural pigmentation. Histopathologically, pigmented rete ridge elongation and dermal melanosis of biopsy specimens from flexural areas are seen. (J Am Acad Dermatol 1999;40:462-7.)

PREVIEWConsidering the thousands of drugs prescribed every day and the large number of over-the-counter drugs available to patients, it is not surprising that cutaneous drug eruptions are a significant problem. In this review, Drs Daoud, Schanbacher, and Dicken focus on recognition of drug reactions, analysis of the history of drug exposure, confirmation of the diagnosis, and identification of clinical entities that require dermatologic consultation.

Merkel cell carcinomas (MCCs) are rare but highly malignant skin cancers associated with a recently described polyomavirus. MCC tumors were infiltrated by T cells, including effector, central memory, and regulatory T cells. Infiltrating T cells showed markedly reduced activation as evidenced by reduced expression of CD69 and CD25. Treatment of MCC tumors in vitro with IL-2 and IL-15 led to T-cell activation, proliferation, enhanced cytokine production, and loss of viable tumor cells from cultures. Expanded tumor-infiltrating lymphocytes showed TCR repertoire skewing and upregulation of CD137. MCC tumors implanted into immunodeficient mice failed to grow unless human T cells in the tumor grafts were depleted with denileukin diftitox, suggesting that tumor-specific T cells capable of controlling tumor growth were present in MCC. Both CD4(+) and CD8(+) FOXP3(+) regulatory T cells were frequent in MCC. Fifty percent of nonactivated T cells in MCC-expressed PD-1, a marker of T-cell exhaustion, and PD-L1 and PD-L2 were expressed by a subset of tumor dendritic cells and macrophages. In summary, we observed tumor-specific T cells with suppressed activity in MCC tumors. Agents that stimulate T-cell activity, block regulatory T cell function, or inhibit PD-1 signaling may be effective in the treatment of this highly malignant skin cancer.

Squamous cell carcinomas (SCCs) are sun-induced skin cancers that are particularly numerous and aggressive in patients taking T-cell immunosuppressant medications. Imiquimod is a topical immune response modifier and Toll-like receptor 7 (TLR7) agonist that induces the immunological destruction of SCC and other skin cancers. TLR7 activation by imiquimod has pleiotropic effects on innate immune cells, but its effects on T cells remain largely uncharacterized. Because tumor destruction and formation of immunological memory are ultimately T-cell-mediated effects, we studied the effects of imiquimod therapy on effector T cells infiltrating human SCC. SCC treated with imiquimod before excision contained dense T-cell infiltrates associated with tumor cell apoptosis and histological evidence of tumor regression. Effector T cells from treated SCC produced more IFN-gamma, granzyme, and perforin and less IL-10 and transforming growth factor-beta (TGF-beta) than T cells from untreated tumors. Treatment of normal human skin with imiquimod induced activation of resident T cells and reduced IL-10 production but had no effect on IFN-gamma, perforin, or granzyme, suggesting that these latter effects arise from the recruitment of distinct populations of T cells into tumors. Thus, imiquimod stimulates tumor destruction by recruiting cutaneous effector T cells from blood and by inhibiting tonic anti-inflammatory signals within the tumor. PMID: 19516264 [PubMed - indexed for MEDLINE]