Clinical stage of Merkel cell carcinoma and survival are not associated with Breslow thickness of biopsied tumor.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive malignancy that often presents on the skin with concurrent metastatic disease. OBJECTIVE: To determine whether Breslow thickness of biopsied MCC correlates with clinical disease stage. MATERIALS AND METHODS: We performed a retrospective review of clinical data and histopathology specimens from 34 individuals with MCC treated at the Roswell Park Cancer Institute for whom complete clinical information and histopathology specimens were available. RESULTS: There was no correlation between Breslow thickness of biopsied MCC on the head and neck or body and clinical stage of disease, progression-free survival, or overall survival. Hence, thin MCCs should not be taken to represent lesions with less-aggressive clinical behavior. CONCLUSION: Our findings validate the current practice of staging all newly diagnosed MCC, irrespective of size or Breslow thickness.

All you need is light: antimicrobial photoinactivation as an evolving and emerging discovery strategy against infectious disease.

The story of prevention and control of infectious diseases remains open and a series of highly virulent pathogens are emerging both in and beyond the hospital setting. Antibiotics were an absolute success story for a previous era. The academic and industrial biomedical communities have now come together to formulate consensus beliefs regarding the pursuit of novel and effective alternative anti-infective countermeasures. Photodynamic therapy was established and remains a successful modality for malignancies but photodynamic inactivation has been transformed recently to an antimicrobial discovery and development platform. The concept of photodynamic inactivation is quite straightforward and requires microbial exposure to visible light energy, typically wavelengths in the visible region, that causes the excitation of photosensitizer molecules (either exogenous or endogenous), which results in the production of singlet oxygen and other reactive oxygen species that react with intracellular components, and consequently produce cell inactivation. It is an area of increasing interest, as research is advancing i) to identify the photochemical and photophysical mechanisms involved in inactivation; ii) to develop potent and clinically compatible photosensitizer; iii) to understand how photoinactivation is affected by key microbial phenotypic elements (multidrug resistance and efflux, virulence and pathogenesis determinants, biofilms); iv) to explore novel delivery platforms inspired by current trends in pharmacology and nanotechnology; and v) to identify photoinactivation applications beyond the clinical setting such as environmental disinfectants.

Noninvasive extramammary Paget's disease treated with photodynamic therapy: case series from the Roswell Park Cancer Institute.

BACKGROUND: Extramammary Paget's disease (EMPD) is a rare low-grade cutaneous malignancy that affects apocrine gland-bearing areas and most commonly occurs on the perineal skin. Photodynamic therapy (PDT) may represent a useful treatment option for extensive, noninvasive EMPD, alone or as part of multimodal therapy. OBJECTIVE: To analyze the clinical outcomes of PDT for noninvasive EMPD with topical aminolevulinic acid (ALA) or intravenous porfimer sodium as photosensitizing agents and argon laser as the photoactivator. METHODS: Retrospective case series of patients with noninvasive EMPD treated at Roswell Park Cancer Institute with PDT from April 20, 1995, to December 4, 2008. Identified patients included five men and three women aged 50 to 80 (mean age 67) with a total of 24 distinct lesions of noninvasive EMPD without distant metastases. Four patients received topical ALA only as a photosensitizer, three received intravenous porfimer sodium only, and one received both. All patients were treated using a 632.8-nm argon-pumped dye laser, and some were also treated using a red lamp (590-729 nm). RESULTS: Seven of nine lesions (78%) treated with PDT using intravenous porfimer sodium showed a complete response (CR) and were disease free at 12 to 96 months. Eight of 16 lesions (50%) treated with PDT using topical ALA showed a CR, and 38% were disease free at 9 to 88 months. None of the treated patients developed any serious cosmetic or functional impairments, such as loss of sphincter control or dysesthesias. CONCLUSION: PDT with intravenous porfimer sodium or topical ALA and argon laser may represent a useful, surgery-sparing therapeutic option for management of noninvasive EMPD in selected patients. Prospective, randomized clinical trials are necessary to compare the effectiveness of PDT with that of surgery for noninvasive EMPD.

Safety and effectiveness of black tattoo clearance in a pig model after a single treatment with a novel 758 nm 500 picosecond laser: a pilot study.

BACKGROUND: Optimal selective photothermolysis of a pigment particle requires pulse durations equal to or less than the particle's thermal relaxation time (t(1/2)). Since tattoo particles in skin range in diameter from 40 to 300 nm, picosecond pulses would approximate t(1/2) more closely and, therefore, might be more effective at tattoo particle fragmentation. MATERIALS AND METHODS: India Ink (carbon) or iron oxide tattoos were placed on the back of a Yorkshire pig. Six weeks later, each tattoo was treated with either a 758 nm 500 picosecond laser (Cynosure), a 755 nm 30-50 nanoseconds laser, or left untreated. After 4 weeks, clinical responses were evaluated by three dermatologists based on pre- and post-treatment photographs; histopathologic findings were evaluated by a dermatopathologist; and electron microscopic findings were analyzed for treated and non-treated carbon tattoos. RESULTS: After a single treatment, picosecond-domain pulses at 758 nm produced a significantly greater degree of carbon tattoo clearance compared to nanosecond-domain pulses at 755 nm. For iron oxide tattoos, both modalities produced minimal-to-poor clearance that was generally comparable. Neither modality resulted in scarring, textural changes, or hypopigmentation, and there was no histopathologic evidence of scarring. Electron micrographs revealed the presence of amorphous material (treated pigment) in picosecond and nanosecond laser-treated tattoos, consistent with effective targeting of India Ink pigment. CONCLUSIONS: The 758 nm 500 picosecond laser is more effective at carbon tattoo clearance after one session in a porcine model than the 30-50 nanosecond laser emitting at a similar wavelength. Both lasers cleared carbon tattoos more effectively than iron oxide tattoos. Both lasers have a comparable safety profile, and neither produced clinical or histopathologic scarring. Further studies in humans are necessary to evaluate whether repeated treatments with picosecond versus nanosecond domain modalities might yield superior tattoo pigment clearance with a comparable safety profile.

Non-infectious granulomatous diseases of the skin and their associated systemic diseases: an evidence-based update to important clinical questions.

Non-infectious granulomatous diseases of the skin are a broad group of distinct reactive inflammatory conditions that share important similarities. As a group, they are relatively difficult to diagnose and distinguish both clinically as well as histologically. Many of these disorders have significant associations with systemic diseases that impact the patient's overall prognosis. In this update, we offer a discussion of emerging concepts and controversies in this field, as presented through evidence-based answers to seven important clinical questions regarding palisading and epithelioid granulomata. These questions offer an opportunity to review ten non-infectious granulomatous conditions that have implications for systemic disease: granuloma annulare, annular elastolytic giant cell granuloma, necrobiosis lipoidica, methotrexate-induced accelerated rheumatoid nodulosis, necrobiotic xanthogranuloma, interstitial granulomatous dermatitis, interstitial granulomatous drug reaction, palisaded neutrophilic granulomatous dermatitis, sarcoidosis, and metastatic Crohn disease. Recent clinical, epidemiologic, and laboratory studies have shed some light on these diseases, the association of these conditions with systemic disorders, and their overall prognoses.

Treatment of hypertrophic and resistant port wine stains with a 755 nm laser: a case series of 20 patients.

BACKGROUND AND OBJECTIVE: Port wine stains (PWS) are heterogeneous vascular malformations that can be treated with vascular-selective pulsed dye lasers (PDL). Hypertrophic PWS, especially in adults, are consistently less responsive to PDL. Furthermore, many PWS that respond well initially to PDL treatment may reach a response plateau, becoming unresponsive to further PDL treatments, a phenomenon termed "treatment resistance." Based on the theory of selective photothermolysis, vessels in such lesions may also be specifically targeted with a 755 nm laser that has selectivity for deoxyhemoglobin as well as oxyhemoglobin and increased depth of skin penetration. STUDY DESIGN/PATIENTS AND METHODS: Retrospective case review of 20 patients with either hypertrophic or PDL-resistant PWS treated with a 755 nm laser alone or in combination with other lasers, including PDL. RESULTS: Hypertrophic PWS showed significant lightening after treatment with a 755 nm laser in combination with PDL. Most PDL-resistant PWS showed moderate improvement after treatment with either a 755 nm laser alone or in combination with another laser, including PDL. Some lesions showed only mild improvement or did not respond. Serious side effects were infrequent. Most commonly encountered complications included pain, edema, bullae, crusting, and rare scarring. CONCLUSIONS: Alexandrite 755 nm laser can be useful for the treatment of hypertrophic and treatment-resistant PWS in adult and pediatric patients. Complications are infrequent and predictable. Careful attention to using a fluence at or near the threshold for clinical response with this deeply penetrating laser is essential to prevent serious sequelae.

Treatment endpoints for resistant port wine stains with a 755 nm laser.

Laser therapy of port wine stains (PWS) resistant to pulsed dye laser is challenging and controversial. Based on the theory of selective photothermolysis, vessels in such lesions may be specifically targeted with the laser wavelength of 755 nm. There is much deeper penetration of the near-infrared light and it is difficult to visualize laser-induced changes within the deeper dermis. The recognition of an appropriate immediate endpoint response with this wavelength would be helpful. This is a clinical observations report. We present examples of an appropriate PWS tissue response endpoint based on our clinical observations in resistant PWS treated with a 755 nm laser at high fluences (40-100 J/cm(2)), 1.5-ms pulse duration, with dynamic cooling device (DCD) cooling. Mild-to-moderate PWS lightening was associated with the immediate endpoint of a transient gray color that gradually evolved into persistent deep purpura within several minutes. We also discuss the clinical endpoints that represent undertreatment and overtreatment of PWS. It is important to attain, and maintain, the correct endpoint when treating PWS with this deeply penetrating near-infrared laser at high fluences in order to (a) induce lesional lightening, and (b) avoid deep dermal burns that may produce scarring. Judicious use of the 755 nm laser can be beneficial for resistant PWS.

Treatment of port wine stains with pulsed dye laser in patients with systemic lupus erythematosus: practical considerations and complications.

There is a paucity of clinical information on the treatment of port wine stains (PWS) with pulse dye lasers (PDL) in patients with connective tissue diseases. Systemic lupus (SLE) is characterized by increased skin fragility and the potential for pigmentary alterations. Additionally, medications used to treat SLE may alter patient responses to laser therapy. We describe two complications, tense blisters and hypopigmentation, after PDL treatment of PWS in SLE, and discuss the current knowledge on the use of PDL in patients with lupus.

Laser photorejuvenation of Asian and ethnic skin.

Laser therapy of Asian and ethnic skin has been relatively poorly studied in the literature. Owing to particular physiologic aspects of darker skin, the physical properties of currently available lasers, and the nature of laser-tissue interactions, the use of lasers to treat chronological and photodamage in such patients may be challenging and fraught with complications. Nevertheless, both ablative and non-ablative technologies have been used successfully to address various cosmetic concerns. This article is a review of skin physiology and laser-tissue interactions in Asian and ethnic skin, particular aesthetic concerns and medical pre- and postoperative considerations in such patients, and a summary of the past 20 years of experience with ablative and non-ablative technologies for effective and safe photorejuvenation.

Transient immunoreactivity after laser tattoo removal: report of two cases.

BACKGROUND AND OBJECTIVE: Laser tattoo removal is one of most commonly used indications for medical lasers. Professional tattoos contain a multitude of potentially immunogenic chemicals that are released or modified by laser treatment. We studied potential immunologic reactions following laser tattoo removal. STUDY DESIGN/PATIENTS AND METHODS: Case report of two patients with immunologic reactions after laser tattoo removal. RESULTS: Two patients developed transient immunoreactivity that presented as regional lymphadenopathy after laser tattoo removal of professional black and blue-green tattoos. These reactions resolved without any complications. CONCLUSIONS: Tattoo pigments released or modified by laser therapy may trigger transient immunoreactivity in susceptible individuals.

The flushing patient: differential diagnosis, workup, and treatment.

UNLABELLED: Cutaneous flushing-a common presenting complaint to dermatologists, allergists, internists, and family practitioners-results from changes in cutaneous blood flow triggered by multiple conditions. Most cases are caused by very common, benign diseases, such as rosacea or climacterum, that are readily apparent after a thorough taking of history and physical examination. However, in some cases, accurate diagnosis requires further laboratory, radiologic, or histopathologic studies to differentiate several important clinicopathologic entities. In particular, the serious diagnoses of carcinoid syndrome, pheochromocytoma, mastocytosis, and anaphylaxis need to be excluded by laboratory studies. If this work-up is unrevealing, rare causes, such as medullary carcinoma of the thyroid, pancreatic cell tumor, renal carcinoma, and others, should be considered. LEARNING OBJECTIVE: At the completion of this learning activity, participants should be familiar with the mechanisms of flushing, its clinical differential diagnosis, the approach to establish a definitive diagnosis, and management of various conditions that produce flushing.

The ICOS molecule plays a crucial role in the development of mucosal tolerance.

The ICOS molecule stimulates production of the immunoregulatory cytokine IL-10, suggesting an important role for ICOS in controlling IL-10-producing regulatory T cells and peripheral T cell tolerance. In this study we investigate whether ICOS is required for development of oral, nasal, and high dose i.v. tolerance. Oral administration of encephalitogenic myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide to ICOS-deficient (ICOS-/-) mice did not inhibit experimental autoimmune encephalomyelitis (EAE), T cell proliferation, or IFN-gamma production, in striking contrast to wild-type mice. Similarly, intranasal administration of MOG(35-55) before EAE induction suppressed EAE and T cell responses in wild-type, but not in ICOS-/-, mice. In contrast, ICOS-/- mice were as susceptible as wild-type mice to high dose tolerance. These results indicate that ICOS plays an essential and specific role in mucosal tolerance and that distinct costimulatory pathways differentially regulate different forms of peripheral tolerance. Surprisingly, CD4+ cells from MOG-fed wild-type and ICOS-/- mice could transfer suppression to wild-type recipients, indicating that functional regulatory CD4+ cells can develop in the absence of ICOS. However, CD4+ T cells from MOG-fed wild-type mice could not transfer suppression to ICOS-/- recipients, suggesting that ICOS may have a key role in controlling the effector functions of regulatory T cells. These results suggest that stimulating ICOS may provide an effective therapeutic approach for promoting mucosal tolerance.

Androgen receptor expression helps to differentiate basal cell carcinoma from benign trichoblastic tumors.

Histologic differentiation between basal cell carcinoma and benign trichoblastic neoplasms such as trichoepithelioma and trichoblastoma can be difficult on small biopsies. Therefore, several attempts have been made to identify immunohistochemical differences between these entities. Recent studies have shown androgen receptor expression in a number of mature epithelial structures in the skin and in epithelial neoplasms including basal cell carcinoma. In contrast, androgen receptor expression was absent in mature hair follicles or the few trichogenic neoplasms studied to date. These findings suggested that androgen receptor expression might be a useful adjunct in the histologic differential diagnosis between basal cell carcinoma and benign trichoblastic neoplasms. Therefore, we performed immunohistochemical analysis of androgen receptor expression in 32 basal cell carcinomas and 10 benign trichoblastic tumors (6 trichoepitheliomas and 4 trichoblastomas). In our study, at least focal expression of androgen receptor was detected in 78% of basal cell carcinomas. None of the trichoblastic tumors showed any androgen receptor immunoreactivity. These results confirm the lack of expression of androgen receptor in benign trichoblastic neoplasms and indicate that androgen receptor expression by tumor cells points to basal cell carcinoma as the most likely diagnosis.