Primary cutaneous follicle center lymphoma with aberrant CD8 expression.

We report an unusual case of primary cutaneous follicle center lymphoma (PCFCL) with aberrant expression of the T-cell marker CD8. The patient is a 48-year-old male with no significant past medical history who presented with red indurated plaques on the abdomen. A punch biopsy showed abnormal lymphoid follicles in the dermis with reduced mantle zones and decreased tingible body macrophages. The epidermis was uninvolved. The follicles expressed CD20, PAX-5, and bcl-6 by immunohistochemistry. CD8, however, was strongly positive, highlighting neoplastic cells, which were negative for any additional T-cell markers. TIA and granzyme B were also negative. The patient underwent further staging workup, without evidence of nodal involvement. His course has been indolent thus far. In summary, we present a case of PCFCL with aberrant expression of the T-cell marker CD8, a finding not previously reported in the literature and a potential diagnostic pitfall.

Aesthetic and functional efficacy of subcuticular running epidermal closures of the trunk and extremity: a rater-blinded randomized control trial.

OBJECTIVE: To ascertain whether subcuticular epidermal closures of elliptical excisions of the trunk and extremities result in better functional and cosmetic outcomes than simple running epidermal closures of the same sites. DESIGN: Randomized controlled trial, with allocation of epidermal closure of elliptical excisions to 4 arms, including 1 control arm (simple running polypropylene sutures removed after 14 days) and 3 experimental arms (subcuticular running polypropylene sutures removed after 14 days, subcuticular running polypropylene sutures left in place, and subcuticular running polyglactin 910 sutures left in place). All experimental interventions were preceded by deep dermal closure with simple interrupted polyglactin 910 sutures. Interventions were delivered by 3 surgeons, who underwent 2 training sessions to minimize intersurgeon technique variability. SETTING: Institutional referral practice providing ambulatory care in an urban environment. PATIENTS: A consecutive sample of 36 adult patients (ages 18-65 years), each referred for concurrent elliptical excision of at least 2 clinically atypical nevi of the trunk and/or extremity, were included in the study. MAIN OUTCOME MEASURES: Primary outcome measures obtained at 3 and 9 months included scar width in millimeters and blinded observer ordinal scale assessment of overall scar appearance. Secondary outcome measures included ratings on the standardized Vancouver Scar Scale and the Hollander Scar Scale; an additional nonstandard item was added to assess pruritus. RESULTS: No difference among groups was found in scar width at 3 or 9 months. Differences among groups were detected in overall scar appearance (3 months, P<.001; 9 months, P<.001), vascularity (3 months, P = .001; 9 months, P<.001), excessive distortion (3 months, P = .04; 9 months, P = .02), contour irregularity (3 months, P<.001), and edge inversion (3 months, P = .01). The best overall appearance was with a subcuticular running polyglactin 910 suture left in place, and the next best was with a subcuticular running polypropylene suture left in place; differences across groups persisted but decreased in intensity at 9 months. A secondary analysis that matched high-tension anatomic sites (back and lower leg), and high and moderate tension sites (also chest and shoulder) yielded the same main effects and mostly the same results in pairwise comparisons. CONCLUSION: While scar width does not appear to vary significantly based on choice of epidermal closure, bilayered closures of the trunk and extremity have better overall appearance and less associated erythema at 3 and 9 months after surgery with the use of a subcuticular running polyglactin 910 suture left in place.

Sterility assessment of multiple use botulinum A exotoxin vials: a prospective simulation.

BACKGROUND: A preponderance of evidence now indicates that storage of reconstituted botulinum toxin solution for longer than the 4 hours recommended by the manufacturer does not result in loss of effectiveness. OBJECTIVE: Then purpose of this study was to assess whether serial re-extraction of reconstituted botulinum toxin solution from vials undergoing prolonged storage is associated with increased risk of microbial contamination. METHODS: Consecutive 100-U vials of botulinun A exotoxin were reconstituted with 2.5 mL each of normal saline with preservative (benzyl alcohol). Within 1 week after reconstitution, each vial was used to treat 1 to 3 patients, for a total of 60 to 80 U used. Thereafter, each vial was stored in a plastic kidney basin in an unlocked, multiuse medication refrigerator. Two weeks later, a randomly assigned nurse removed the vial from the refrigerator and withdrew and discarded 0.1 mL (5 U) using the same technique used for therapeutic extractions. Iterations of this withdrawal and discarding procedure were continued until a 0.1-mL aliquot could not be withdrawn without prying off the metal cover. Once this threshold was reached, the vial was sent to the microbiology laboratory for sterility testing using a thioglycolate broth. RESULTS: In all, 127 vials were handled per protocol. On average (mean), vials underwent 4.5 access procedures, including 1.6 therapeutic extractions for a total of 76 U removed during a period of 7 weeks. Sterility analysis with thioglycolate broth indicated no evidence of contamination. LIMITATIONS: Preservative-containing saline was used for reconstitution. CONCLUSION: Routine refrigerator storage of medication vials containing reconstituted botulinum toxin does not result in microbial contamination of the contents even after serial re-extraction of solution from these vials, and after handling of such vials by multiple personnel. Storage and subsequent reuse of botulinum toxin appears safe for at least 7 weeks after reconstitution.

Confidence intervals in procedural dermatology: an intuitive approach to interpreting data.

BACKGROUND: Significant differences observed in therapeutic trials in procedural dermatology are typically denoted by p values of less than .05. Alternatively, significance can be conveyed by use of confidence intervals. OBJECTIVES: The purpose of this article is to clarify how confidence intervals convey the same information about outcomes as p values, albeit in a slightly different manner. METHODS: (1) Selective review of textbooks and other relevant literature and (2) presentation of a brief tutorial describing confidence interval determination for therapeutic clinical trials comparing differences between means of two groups. RESULTS: Routine use of confidence intervals is an intuitively satisfying means for conveying the statistical significance of results and can be used in combination with p values for understanding these results. Specifically, confidence intervals are a useful tool for indicating the size, spread, and direction of the observed differences. Unfortunately, dermatologic surgery trials tend to have low sample sizes, which frequently result in outcomes below the threshold of statistical significance (p > .05, or confidence intervals including 1.00). In the absence of statistical significance, neither p values nor confidence intervals yield definitive results. CONCLUSION: Confidence intervals can complement p values as a means for explaining statistical significant differences. When differences are not statistically significant but are clinically significant and approach statistical significance, neither p values nor confidence intervals can definitively establish whether the observed trends are indicative of an underlying difference. In these cases, common in procedural dermatology, larger, better designed, randomized prospective trials are needed.

Low-level laser therapy for wound healing: mechanism and efficacy.

BACKGROUND: Given the recent interest in light-emitting diode (LED) photomodulation and minimally invasive nonablative laser therapies, it is timely to investigate reports that low-level laser therapy (LLLT) may have utility in wound healing. OBJECTIVES: To critically evaluate reported in vitro models and in vivo animal and human studies and to assess the qualitative and quantitative sufficiency of evidence for the efficacy of LLLT in promoting wound healing. METHOD: Literature review, 1965 to 2003. RESULTS: In examining the effects of LLLT on cell cultures in vitro, some articles report an increase in cell proliferation and collagen production using specific and somewhat arbitrary laser settings with the helium neon (HeNe) and gallium arsenide lasers, but none of the available studies address the mechanism, whether photothermal, photochemical, or photomechanical, whereby LLLT may be exerting its effect. Some studies, especially those using HeNe lasers, report improvements in surgical wound healing in a rodent model; however, these results have not been duplicated in animals such as pigs, which have skin that more closely resembles that of humans. In humans, beneficial effects on superficial wound healing found in small case series have not been replicated in larger studies. CONCLUSION: To better understand the utility of LLLT in cutaneous wound healing, good clinical studies that correlate cellular effects and biologic processes are needed. Future studies should be well-controlled investigations with rational selection of lasers and treatment parameters. In the absence of such studies, the literature does not appear to support widespread use of LLLT in wound healing at this time. Although applications of high-energy (10-100 W) lasers are well established with significant supportive literature and widespread use, conflicting studies in the literature have limited low-level laser therapy (LLLT) use in the United States to investigational use only. Yet LLLT is used clinically in many other areas, including Canada, Europe, and Asia, for the treatment of various neurologic, chiropractic, dental, and dermatologic disorders. To understand this discrepancy, it is useful to review the studies on LLLT that have, to date, precluded Food and Drug Administration approval of many such technologies in the United States. The fundamental question is whether there is sufficient evidence to support the use of LLLT.

Power and sample size of therapeutic trials in procedural dermatology: how many patients are enough?

BACKGROUND: Many new devices and therapeutic interventions are continually introduced in cutaneous surgery. The efficacy of these new techniques must be compared with that of preexisting standards so that patients can be appropriately counseled. OBJECTIVES: The purpose of this article is to (1) review methods for estimating sample size and power, (2) estimate the range of sample sizes sufficient to ensure that true differences are not missed in clinical trials of new procedural dermatologic therapies, and (3) consider the reasons why the sample size may be too small in procedural dermatology trials and how this problem can be addressed. METHODS: (1) Selective review of textbooks and other relevant literature, presentation of a brief tutorial describing sample size and power determination for therapeutic clinical trials comparing two groups with continuous outcomes variables; (2) implementation of standard formulae and assumptions to estimate sample size in cutaneous surgery therapeutic trials. RESULTS: Assuming that one group receives a standard surgical intervention and another group undergoes a new technique, to identify a moderate difference in efficacy between groups, at least 50 to 200 subjects will need to be enrolled if conventional strategies are used to reduce the likelihood of finding a difference that does not really exist (Type I error), as well as the likelihood of missing a true difference (Type II error). CONCLUSION: By face validity, it is apparent that most efficacy comparisons in procedural dermatology have low sample size and a concomitant risk of failing to detect actual differences between therapeutic arms. Owing to the limitations that restrict surgeons from frequently performing large randomized controlled trials in procedural dermatology, meta-analyses may be needed to pool the results of smaller studies. When it is critically important that differences between groups be accurately identified, dermatologic surgeons may consider eschewing smaller trials in favor of collaborating on larger trials with an adequate sample size.

The expression of p63 in actinic keratoses, seborrheic keratosis, and cutaneous squamous cell carcinomas.

BACKGROUND: p63 is a tumor suppressor that likely plays a role in the development of squamous cell carcinomas (SCCs) and possibly premalignant and benign skin tumors. Little data is available on its expression in these tumors. OBJECTIVE: To study the keratinocyte expression profile of p63 in 17 SCCs, 7 actinic keratoses, 2 Bowens tumors, and 7 seborrheic keratoses. METHODS: Skin tumors specimens were stained with an antibody to p63. Quantitative and qualitative data was collected on the staining. RESULTS: There was a statistically significant increase in p63 staining of SCCs when compared with normal. Seborrheic keratoses and actinic keratoses showed a trend towards increased expression in the basal layer compared with normal skin. The pattern of expression showed diffuse staining in SCCs. In actinic keratoses and seborrheic keratoses the pattern was most prominent in the basal layer. CONCLUSIONS: p63 expression is greater and different in SCCs when compared with normal skin, actinic keratoses, and seborrheic keratoses. Interestingly seborrheic keratoses and Bowens lesions showed expression that was mostly restricted to the basal layer, however significant diffuse staining was also noted. Our results support the notion that p63 plays a role in cell differentiation and tumorigenesis of skin tumors.

The development of actinic keratosis into invasive squamous cell carcinoma: evidence and evolving classification schemes.

Actinic keratosis is an incipient form of cutaneous squamous cell carcinoma. Consequently, actinic keratoses must be treated expeditiously to forestall their downward growth. Several classification schemes have been proposed to better categorize actinic keratoses, and to guide their diagnosis and treatment. Among these approaches is the "keratinocyte intraepithelial neoplasia" (KIN) system developed by Cockerell; Goldberg's concept of the "proliferative actinic keratosis" (PAK), and Berhane's emphasis on the "inflamed actinic keratosis" (IAK). In the future, disparate classification schemes may be unified into a single pragmatic approach which accurately reflects the biological process whereby actinic keratoses devolve into invasive squamous cell carcinoma.

Cutaneous surgery in the elderly: ensuring comfort and safety.

Increasingly, cutaneous surgeons are asked to treat cancers and the visible signs of aging in extremely elderly patients. While many elderly patients have functional status similar to that of younger patients, some older patients may have co-morbities and special needs that must be monitored and accommodated by the skin surgeon. A rational approach to surgery can increase the comfort and safety of surgery in such patients. Overall, cutaneous surgery is well-tolerated in even the oldest patients.

Nonablative laser and light treatments: histology and tissue effects--a review.

BACKGROUND AND OBJECTIVES: Nonablative laser and light treatments have largely replaced ablative laser therapy in clinical use for the improvement of the visible signs of cutaneous photoaging, including rhytides, vascular lesions, and pigmentation. However, the mechanisms underlying the reported clinical efficacy of nonablative treatments are not well-understood. The purpose of this analysis is to critically evaluate what is known about histologic and tissue effects of nonablative laser therapy and suggest future directions for research. STUDY DESIGN/MATERIALS AND METHODS: This is a review of the English language literature pertaining to nonablative laser and light treatments available through MEDline (1995-2002), and unpublished reports presented at major national meetings. Only studies that included harvesting and analysis of tissue samples are included. RESULTS AND CONCLUSIONS: (a) Thermal injury to the dermis in association with epidermal cooling most likely affects the dermal vasculature, which initiates a cascade of inflammatory events that includes fibroblastic proliferation and apparent up-regulation of collagen expression; (b) There is no indication that nonablative treatments are harmful or able to induce skin cancer; (c) It is possible that the horizontally distributed collagen reported after nonablative treatments is a "microscar," an enlarged Grenz sone associated with repetitive photo-induced trauma; (d) Further research is needed to elucidate the biophysical mechanisms underlying nonablative treatment, as well as to distinguish the utility of different wavelengths on epidermal and dermal improvement.

Techniques for cutaneous sutured closures: variants and indications.

Many different suture techniques are routinely used by cutaneous surgeons for the closure of surgical wounds. This paper reviews several common suture techniques and their associated subtypes. In particular, for each technique, we discuss the method for placement, generally accepted indications, controversies regarding utility, and objective evidence of efficacy.

Heparan sulphate proteoglycan in scleromyxedema promotes FGF-2 activity.

The cause of progressive dermal sclerosis, proliferation of fibroblasts, and collagen deposition in scleromyxedema is unknown. We analyzed the heparan sulphate proteoglycans (HSPG) in cutaneous nodules from a patient with scleromyxedema in order to ascertain their role in the binding of fibroblast growth factor (FGF) and promoting signaling complex assembly. Total heparan sulphate (HS) was detected with a monoclonal antibody to HSPG on paraffin sections. Binding of FGF to HS was assessed using FGF-2 followed by anti-FGF-2 antibody. The formation of HS-mediated signaling complex was studied using soluble FR1-AP, which contains the extracellular domain of FGF receptor-1 linked to alkaline phosphatase (AP) and monoclonal anti-AP-antibody. Anti FGF-2 and anti-AP antibodies were visualized using the DAKO Envision Plus system. The dermal nodule of scleromyxedema contained ample HS and these bound FGF-2 and FR1-AP. Specificity was confirmed by prior incubation with heparitinase (no staining) and omission of FGF-2 (no staining). Increased amounts of HSPG were present in the dermal nodules of scleromyxedema compared to adjacent normal dermis and these bound FGF-2, immobilized the soluble receptor protein FGFR-1 and, therefore, formed a ternary complex composed of HSPG, FGF-2 and FGFR-1 in vitro. Since this complex resembles the signaling complex formed on live cells, HSPG in the nodules of scleromyxedema are in a configuration that promotes FGF activity.