Background and Objective: Fractional photothermolysis (FP) is a new concept using arrays of microscopic thermal damage patterns to stimulate a therapeutic response. We analyzed epidermal and dermal response to FP with the aim of correlating histological and clinical response. Study Design/Materials and Methods: Twelve subjects received a single treatment with a prototype diode laser emitting at a wavelength of 1,500 nm, delivering 5 mJ per microscopic treatment zone (MTZ), and a density of 1,600 MTZs/cm 2 on the forearm. Biopsies were procured over a period of 3 months. The biopsies were analyzed by two blinded dermatopathologists using hematoxylin and eosin (Hematoxylin and Eosin Stain), Elastica von Gieson, nitro-blue-tetrazolium-chloride (NBTC) viability, and immunohistochemistry stains. Furthermore, the treatment sites were evaluated in vivo by confocal microscopy. Results and Discussion: Twenty-four hours after fractional photothermolysis, the continuity of the epidermal basal cell layer is restored. Complete epidermal regeneration is obtained 7 days after the treatment. Microscopic epidermal necrotic debris (MENDs) are seen as early as 1 day after FP. MENDs contain melanin pigment, and are shed from the epidermis within 7 days. Evidence of increased collagen III production is shown with immunohistochemistry (IHC) staining 7 days after FP. IHC for heat shock protein 70 (HSP 70) shows the expression of HSP 1 day after FP, and IHC for alpha smooth muscle actin shows the presence of myofibroblasts 7 days after FP. These findings are concordant with the induction of a wound healing response by FP. There is no evidence of residual dermal fibrosis 3 months after treatment. Conclusion: A single treatment with fractional photothermolysis induces a wound healing response in the dermis. A mechanism for the precise removal of epidermal melanin is described, in which MENDs act as a melanin shuttle.

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Background and Objectives: Fractional ablation offers the potential benefits of full-surface ablative skin resurfacing while minimizing adverse effects. The purpose of this study was to evaluate the safety, damage profile, and efficacy of erbium fractional lasers. Materials and Methods: Histology from animal and human skin as well as clinical evaluations were conducted with erbium YAG (2,940 nm) and erbium YSGG (2,790 nm) fractional lasers varying pulse width, microbeam (mb) energy, number of passes, and stacking of pulses. Results: Single-pulse treatment parameters from 1 to 12 mJ per 50-70 mm diameter microbeam and 0.25-5 milliseconds pulse widths produced microcolumns of ablation with border coagulation of up to 100 mm width and 450 mm depth. Stacking of pulses generated deeper microcolumns. Clinical observations and in vivo histology demonstrate rapid re-epithelization and limited adverse side effects. Facial treatments were performed in the periorbital and perioral areas using 1-8 passes of single and stacked pulses. Treatments were well-tolerated and subjects could resume their normal routine in 4 days. A statistically significant reduction in wrinkle scores at 3 months was observed for both periorbital and perioral wrinkles using blinded grading. For periorbital treatments of four passes or more, over 90% had !1 score wrinkle reduction (0-9 scale) and 42% had !2. For perioral wrinkles, over 50% had substantial improvements (!2). Conclusion: The clinical observations and histology findings demonstrate that micro-fractional ablative treatment with 2,790 and 2,940 nm erbium lasers resulted in safe and effective wrinkle reduction with minimal patient downtime. The depth and width of the ablated microcolumns and varying extent of surrounding coagulation can be controlled and used to design new treatment procedures targeted for specific indications and areas such as moderate to severe rhytides and photodamaged skin.

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Background and Objective: Basal cell carcinomas (BCCs) have supporting vasculature that could serve as a target for 595 nm pulsed dye laser (PDL). The objective of this study was to determine the effect of repeated PDL treatments on BCCs of superficial and nodular subtypes and of varying diameters. Study Design/Materials and Methods: Twenty biopsyproven BCCs received four 595 nm PDL treatments at 2-week intervals. The tumor and 4 mm of peripheral skin were treated using a set of previously optimized laser parameters: one pass, 15 J/cm 2 energy, 3 ms pulse length, no cooling, and 7 mm spot size with 10% overlap. The treated area was excised and evaluated histologically for residual tumor. Histologic response rates of the PDL treated BCCs were compared with that of non-PDL treated, matched control tumors. Results: Nearly all BCCs <1.5 cm in diameter (n ¼ 12) showed complete response to four PDL treatments (91.7%; n ¼ 11/12) versus 16.7% of controls (n ¼ 2/12, P-value ¼ 0.0003). BCCs !1.5 cm in diameter (n ¼ 8) showed a complete response rate of 25% (n ¼ 2/8) versus 0% of controls (n ¼ 0/8, P-value ¼ 0.2). Mean clinical tumor diameter of the complete responders was 1.1 cm (n ¼ 13) versus 2.2 cm (n ¼ 7) for incomplete responders (P-value ¼ 0.005). Tumor histologic types among the complete responders included superficial, nodular, micronodular, and keratinizing. Incompletely responding BCCs showed a significant reduction in tumor burden after PDL treatment, with residual histologic tumor burden ranging from <1% to 29% of the original clinical tumor diameter, compared to 13-68% residual tumor burden for the corresponding controls (P-value ¼ 0.05). Conclusions: PDL is an effective means of reducing tumor burden in patients with large BCCs and may be an alternative therapy in BCCs <1.5 cm in diameter.

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Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is an underrecognized low-grade carcinoma with predilection to the eyelid. Only 4 cases of this entity have been described in the literature. Here, we describe 12 cases of EMPSGC. The lesions were twice as frequent in females than males with an average age of 70 years (range, 48-84 years). Clinically, they presented as a slowly growing cyst or swelling. The most common site of occurrence was the lower eyelid (8 cases). Two lesions occurred on the upper eyelid and 2 on the cheek. Histologically, they were well-circumscribed, typically multinodular tumors with solid or partially cystic nodules, frequently showing areas of papillary architecture. Focal cribriform arrangements were also present. The nodules were formed by uniform small- to medium-sized oval to polygonal epithelial cells with lightly eosinophilic to bluish cytoplasm. The nuclei were bland with diffusely stippled chromatin and inconspicuous nucleoli. Intracytoplasmic and extracellular mucin was usually present. Mitotic activity was present but never brisk. All tumors examined immunohistochemically expressed at least one neuroendocrine marker, synaptophysin or chromogranin. CD57 and neuron specific enolase, secondary markers of neuroendocrine differentiation, were expressed in most cases. All tumors tested expressed estrogen and progesterone receptors, cytokeratin 7, low molecular cytokeratin Cam5.2, and epithelial membrane antigen and were negative for cytokeratin 20 and S-100 protein. Calponin, smooth muscle actin, and p63 immunohistochemical stains did not disclose myoepithelial cells around larger tumor nests in most cases, supporting the notion that EMPSGC is an invasive carcinoma. In 10 cases, cystic areas lined by benign epithelium indistinguishable from eccrine ducts were present. In some foci, the benign ductal epithelium was undermined or replaced by carcinoma in situ with similar cytologic features to the solid or papillary areas of EMPSGC. Myoepithelial cells were preserved in the areas of in situ carcinoma. In 6 cases, EMPSGC was associated with invasive mucinous carcinoma. In situ carcinoma and mucinous carcinoma also expressed neuroendocrine markers. Clinical follow-up showed no recurrences or metastases, consistent with low-grade carcinoma. The series provides histologic evidence for a multistage progression of noninvasive sweat gland neuroendocrine carcinoma to EMPSGC and then to mucinous carcinoma of the eyelid. Although the data from this series support the notion that the prognosis of EMPSGC and mucinous carcinoma is good, longer follow-up is needed for better understanding of their pathogenesis and clinical behavior.