Scott M. Dinehart

Acne keloidalis : transverse microscopy, immunohistochemistry, and electron microscopy

The earliest stages of acne keloidalis are not well characterized. In the present study, transverse sections of the early lesions revealed follicular units in several stages of inflammation. These follicles surrounded the central follicular units that gave rise to the clinically evident papule. Despite a spectrum of inflammatory changes, the most marked inflammation consistently occurred in the deep infundibular and isthmian levels of the hair follicles. Two follicles, presumably in the earliest stage, exhibited primarily an acute folliculitis and perifolliculitis, with destruction of the follicular wall and the release of hair. Central follicles showed predominantly acute neutrophilic or chronic lymphocytic inflammation at the upper isthmian levels and granulomatous inflammation at the deeper isthmian levels. Other follicles showed scar at the isthmian levels trapping hair fragments in the inferior portion of the follicle, with granulomatous inflammation and scarring. Sebaceous glands were absent in all stages of folliculitis in seven of eight follicular units.

Q-switched neodymium:yttrium-aluminum-garnet laser treatment of lentigo maligna☆☆☆

Lentigo maligna is a premalignant lesion of atypical melanocytes that typically arises on the head and neck of elderly patients. It is considered a melanoma in situ with a significant risk for transformation to invasive lentigo maligna melanoma. Surgery is the preferred method of treatment; however, because of the advanced age of the typical patient with lentigo maligna, the frequency of complicating medical problems, and the cosmetic or functional aspects of treatment, surgical excision is not always feasible. The purpose of this pilot study was to evaluate the efficacy and safety of Q-switched neodymium:yttrium-aluminum-garnet laser treatment of lentigo maligna. Eight patients were treated with 532 and/or 1064 nm wavelengths from the laser. All patients showed a response to laser therapy, and 2 patients treated with 1 treatment from each wavelength had complete eradication of the LM, with no evidence of recurrence in 42 months. Further study is warranted, but Q-switched neodymium:yttrium-aluminum-garnet laser is a promising alternative treatment for lentigo maligna.

Reporting tumor thickness for cutaneous squamous cell carcinoma.

When a clinician receives a pathology report with a diagnosis of melanoma he/she can usually be assured that it will include a measurement of the melanoma tumor thickness. This is because most dermatopathologists and clinicians view tumor thickness as an important predictor of survival for patients with primary cutaneous melanoma. Clinicians use the tumor thickness to stage patients accurately, therefore facilitating treatment options, determining eligibility for clinical trials, and predicting survival. Current treatment guidelines base the margin of surgical excision for melanoma on tumor thickness. Other histopathologic variables frequently reported for melanoma include ulceration, mitotic rate, lymphoid response, regression, microscopic satellites, and vascular invasion. However, none carry the weight of tumor thickness. In contrast, the measurement and reporting of tumor thickness in cutaneous squamous cell carcinoma is often neglected despite the availability of research that suggests that tumor thickness and depth of invasion are directly related to prognosis in patients with cutaneous squamous cell carcinoma (CSCC). Why is this? The extreme importance given to reporting depth in melanoma may be related to its higher metastatic potential and poorer prognosis. However, there are subgroups of CSCC that have a significant metastatic potential.1 In addition when CSCC metastasizes, the prognosis is poor, with 5-year survival rates of less than 35%.2 Every year in the United States about 7000 people with melanoma are expected to die. Little awareness exists for the fact that about 2500 people with metastatic CSCC also die. A number of studies have examined factors that correlate with an increased risk of metastasis in CSCC. These factors can be divided into tumor factors and patient or host factors. An important patient factor is the status of the immune system, with immunocompromised patients at a much greater risk for metastasis. The tumor factors include the etiology, tumor size, anatomic location, and histopathologic factors including tumor thickness, depth of invasion, tu-

Chronologic aging in black skin.

Histologic studies examining chronologic aging in skin have been confined to white skin. In the present study, we examined the features of sun-protected black skin from individuals 6 weeks to 75 years of age with light and electron microscopy. With age, the dermoepidermal junction became flattened with multiple zones of basal lamina and anchoring fibril reduplication. Microfibrils in the papillary dermis became somewhat more irregularly oriented. Compact elastic fibers showed cystic changes and separation of skeleton fibers with age. The area occupied by the superficial vascular plexus in specimens of equal epidermal surface length decreased from the infant to young adult (21–29 years old) to adult (39–52 years old) age groups, then increased in the aged adult (73–75 years old) age group. With the exception of the vascularity in the aged adult group, the above features are similar to those seen in aging white skin, and suggest that chronologic aging in white and black skin is similar. In addition, there was a decrease in the number of melanocytes with age. Basal keratinocyte melanin granule density increased with age to age 52 and remained dense in the aged adult group, even as the number of melanocytes decreased.

Er:YAG laser-induced changes in skin in vivo and transdermal drug delivery

It has been shown that laser ablation of stratum corneum, in vitro, can result in an increased uptake of topically applied pharmaceuticals. We have performed measurements of drug permeation, using an in vitro model of human skin, that involves a portable Er:YAG laser used to ablate the stratum corneum. For the first time, this method of drug administration was tested in vivo in human volunteers, whereby a hydrocortisone blanching assay was used to assess the efficiency of the procedure. The results show that this is a safe and efficient way to ablate stratum corneum for the purpose of enhanced transcutaneous drug administration.

Photofrin and 5-aminolevulinic acid permeation through oral mucosa in vitro

Photofrin and 5-aminolevulinic acid are photosensitizers that show promise in the photodynamic treatment of cancer, port-wine stains, atherosclerosis and viral lesions. Photofrin is a mixture of porphyrins which, upon the absorption of light, become temporarily cytotoxic. One side-effect associated with the use of Photofrin is long-term cutaneous photosensitivity. It is possible that topical application of this photosensitizing dye will ameliorate such a side-effect. Another way to avoid the cutaneous photosensitivity in photodynamic therapy is to use 5- aminolevulinic acid, which is a porphyrin precursor that causes an increase in the synthesis and concentration of the photosensitizer protoporphyrin IX. 5-aminolevulinic acid is usually applied topically, and so minimizes cutaneous photosensitivity while maximizing the local protoporphyrin concentration. There are a host of disorders in oral mucosa that are potentially treatable by photodynamic therapy. However, since stratum corneum presents an impermeable barrier to many pharmaceuticals, it is not clear that topical application of the photosensitizer will result in a clinically relevant tissue concentration. We have therefore studied the permeation behavior of Photofrin and 5-aminolevulinic acid by applying them to the surface of ex vivo oral mucosa tissue positioned by a Franz diffusion cell. In order to increase the permeability of the photosensitizer across the stratum corneum, we studied the effects of four different drug carriers: phosphate buffered saline, dimethylsulfoxide, ethanol and Azone with isopropyl alcohol.