"Virtual microscopy" and the internet as telepathology consultation tools: diagnostic accuracy in evaluating melanocytic skin lesions.

The Internet offers a widely available, inexpensive tool for telepathology consultations. It allows the transfer of image and text files through electronic mail (e-mail) or file transfer protocols (FTP), using a variety of microcomputer platforms. We studied the use of the Internet and "virtual microscopy" tools for the diagnosis of 35 skin biopsies, including a variety of benign and malignant melanocytic lesions. Digitized images from these lesions were obtained at 40x and 100x optical magnification, using a high resolution digital camera (Microlumina, Leaf Systems, Southborough, MA), a light microscope with a phototube adapter and a microcomputer with a Pentium 166 MHz microprocessor. Two to four images of each case were arranged on a "canvas" to represent the majority or an entire biopsy level, using Photoshop software (Adobe Systems Inc., San Jose, CA). The images were compressed using Joint Photographers Expert Group (JPEG) format. The images were then viewed on a computer video monitor in a manner that closely resembles light microscopy, including scrolling by using the "hand tool" of Photoshop and changing magnification digitally up to 4 times without visible image degradation. The image files, ranging in size from 700 kilobytes to 2.1 megabytes (average 1.6 megabytes) were attached to e-mail messages that contained clinical information, using standard Multipurpose Internet Mail Extension (MIME) protocols and sent through the Internet, for interpretation by a dermatopathologist. The consultant could open the images from the e-mail message, using Microsoft Outlook Express (Microsoft Corp., Redmond, WA) and Photoshop software, scroll them, change magnification and render a diagnosis in a manner that closely simulates light microscopy. One hundred percent concordance was obtained between the telepathology and traditional hematoxylin and eosin slide diagnoses. The Internet and relatively inexpensive "virtual microscopy" tools offer a novel technology for dermatopathology consultations. Potential applications of this technology to pathology and technical problems posed by the use of an open, widely distributed network to share sensitive medical information are discussed.

Virtual microscopy and public-key cryptography for Internet telepathology.

The Internet is a potentially inexpensive, widely available medium for telepathology, but there are concerns about its reliability and security. Using a digital camera, 41 photomicrographs of transbronchial biopsies, at x 100 optical magnification, were captured and digitized at 2700 x 3400 pixel, 24 bit/pixel resolution. The image files were saved in JPEG format at medium compression, attached to text files with patient information, encrypted for security in the S/MIME format using a digital signature and digital envelope, and transmitted by email. Received email files were decrypted automatically and the images viewed with standard software. Telepathology diagnoses were compared with original interpretations. The images averaged 810 kByte in size. The encryption and decryption did not cause significant delays in overall transmission time and, together with transmission, did not produce noticeable image degradation. The received image files could be viewed in a manner that simulated light microscopy. There was agreement between telepathology and original diagnoses in 92% of the cases. All the discrepancies were due to inadequate area selection because the pathological features of interest were present in histological levels other than those photographed. The use of high-resolution digital photomicrography, the Internet and public-key cryptography offers an effective and relatively inexpensive method of telepathology consultation. The method is best suited for the diagnosis of small biopsy specimens that require the transmission of only a few digital images that represent the majority of the biopsy materials.

Congenital neural hamartoma ("fascicular schwannoma"). A light microscopic, immunohistochemical, and ultrastructural study.

A previously undescribed form of a congenital neural hamartoma composed entirely of Schwann cells in a fascicular pattern was found on the leg of a male infant. The lesion was thought to be an unusual variant of plexiform Schwannoma or a newly recognized unencapsulated form of Schwannoma. On light microscopic examination, the lesion, which measured 5 x 4 cm when it was surgically removed when the infant was 7 months old, showed an unencapsulated dermal mass composed of fascicles of spindle cells with frequent Verocay body-like structures. The intervening stroma was collagenous and contained an increased number of mast cells. Special stains did not demonstrate any axons in the tumor. There was a strongly positive immunohistochemical reaction for S-100 protein and collagen type IV in the spindle cells. These cells were weakly or focally positive for Leu-7 and vimentin, and completely negative for neural filaments, neuron-specific enolase, glial fibrillary acidic protein, epithelial membrane antigen, desmin, and muscle-specific actin. On electron microscopic examination, the spindle cells were found to be surrounded by basal lamina and showed frequent cytoplasmic invagination filled with collagen bundles. No unmyelinated nerve fibers were identified.

Isotretinoin revisited.

Isotretinoin (13-cis-retinoic acid) remains the drug of choice for treatment of severe, recalcitrant nodulocystic acne that is unresponsive to conventional therapy, including oral antibiotics. The drug has been shown to produce dramatic clearing of lesions and prolonged remissions. The length of remission may be dependent on both the dosage used and the duration of therapy. Since fetal malformations have been observed in infants born of mothers taking isotretinoin during pregnancy, it is mandatory to prevent women who are pregnant or may become pregnant during treatment from taking isotretinoin. Because the half-life of isotretinoin is ten to twenty hours, and because it is eliminated from the body rapidly enough, women may become pregnant one month after discontinuation of therapy without an increased risk of birth defects. Common side effects of the drug include mucocutaneous reactions, serum lipid alterations, eye irritation, and myalgias. Less commonly observed are hyperostoses and exuberant granulation tissue, and rarely, pseudotumor cerebri. Recommendations for substantially reducing or eliminating these effects are made.

Update on acne.

In summary, the therapy of acne has to be individualized according to the nature of the lesions. Noninflammatory acne requires a different therapeutic approach from that for inflammatory acne, and even among those with inflammatory acne, there can be a difference in the therapeutic approach, depending upon the extent of involvement. Attention to the principles of therapy will be a great aid in the success of the therapeutic program for acne.

Ultrastructural changes in sebaceous glands following treatment of cystic acne with isotretinoin.

Following 20 weeks of treatment with isotretinoin, sebaceous glands in patients with cystic acne shrank in size. The cells remaining in the sebaceous lobules were mainly mature lipid-filled cells, with some undifferentiated cells still present at the periphery. The ultrastructure of the glands 8 weeks after cessation of treatment was directly related to the drug dose given each patient. The larger the dose, the slower the return to pretreatment morphology. In those patients given a lower dose, most of the glands observed 2 months after treatment was stopped were similar in size to those seen prior to treatment.

Ultrastructural changes in open comedones following treatment of cystic acne with isotretinoin.

The primary change found in cellular material expressed from open comedones of patients who had been treated with isotretinoin was disintegration of desmosomes. Consequently, there was lack of cohesion between cornified cells. A marked decrease in the quantity of sebaceous material and bacteria was also evident within the comedones.

Isotretinoin treatment of acne and related disorders: an update.

In the one year since isotretinoin has been available in the United States for the treatment of severe, recalcitrant, nodulocystic acne, there has been extensive clinical verification of the reports of its dramatic efficacy in the treatment of this troublesome disease. Proper selection of patients, as well as treatment with adequate doses of drug for 3 to 5 months, will most often result in significant clinical improvement or total clearing. Although dosages of less than 1 mg/kg/day may produce a nearly equivalent degree of improvement with somewhat fewer or less severe side effects, the recommended daily dose remains 1 mg/kg/day because lower dosages are associated with more frequent relapses. In severe cases, the daily dosage may be increased to 2 mg/kg/day. Teratogenicity, elevation of serum triglycerides, liver function abnormalities, pancreatitis, and pseudotumor cerebri may all be associated with isotretinoin therapy and require close monitoring of the patient.

Skin care and incidence of skin disease in adolescence.

During adolescence there are marked structural and physiological changes in the pilosebaceous unit leading to an increase in sebaceous and apocrine secretion, as well as the development of androgen-dependent hair growth. Because of these changes, there are marked alterations in the pattern of skin care at this age. In addition, during adolescence there is a greater increase in the incidence of skin disease is due to the occurrence of acne vulgaris in 249.9 per thousand youths in the 12 to 17-year old age range. Other skin diseases that are extremely common in this age range include (in decreasing frequency) dermatophytosis, benign tumours, seborrhoeic dermatitis, atopic dermatitis and eczema, ichthyosis and keratosis pilaris, and verruca vulgaris.

The treatment of severe cystic acne with 13-cis-retinoic acid. Evaluation of sebum production and the clinical response in a multiple-dose trial.

Fourteen patients with severe, treatment-resistant, nodulocystic acne have been treated with 13-cis-retinoic acid in a double-blind study. The patients were treated with either 0.1, 0.5, or 1.0 mg/kg/day of 13-cis-retinoic acid for 12 weeks. A marked dose-related decrease in sebum production, which was usually evident within 2 weeks of the onset of therapy, was observed in all patients. At a dose of 1.0 mg/kg/day of 13-cis-retinoic acid, sebum production was decreased to about 10% of the pretreatment value. Clinical improvement, as judged by counting the nodulocystic lesions and measuring their greatest diameters, was noted in all three groups. The most common clinical side effects were cheilitis, desquamation of the skin, and pruritus, but the side effects were not severe enough to require interruption of treatment. Laboratory abnormalities during therapy were minimal and also did not necessitate the cessation of therapy.

The effect of marked inhibition of sebum production with 13cis-retinoic acid on skin surface lipid composition.

Sebum production and skin surface lipid composition have been measured during the oral treatment with 13cis-retinoic acid of a group of patients with severe cystic acne. Two hundred and thirty-eight paired samples have been analyzed and compared. A marked, drug-induced decrease in sebum production was accompanied by a decrease in the concentration of wax esters, a slight decrease in the squalene concentration and in increase in the cholesterol concentration in the skin surface lipids. These changes were consonant with changes in the relative contributions of sebum and epidermal lipid to the surface film, except that at very low levels of sebum production there might be preferential preservation of squalene synthesis.

Age-related changes in sebaceous gland activity.

The sebaceous glands of man show age-related differences in their activity as determined by quantitative and qualitative examination of sebum. Sebaceous secretion is low in children and begins to increase in mid- to late childhood under the influence of androgens. This rise continues until the late teens, after which no further significant change takes place until late in life. In elderly men, sebum levels remain essentially unchanged from those of younger adults until the age of 80. In women, sebaceous secretion decreases gradually after menopause and shows no significant change after the 7th decade. The most likely explanation for the decrease in sebaceous gland secretion with age in both men and women is a concomitant decrease in the endogenous production of androgens. Although surface lipid levels fall with age, paradoxically the sebaceous glands become larger, rather than smaller, as a result of decreased cellular turnover. Nonetheless, as the higher surface lipid levels after administration of fluoxymesterone (a synthetic testosterone derivative) indicate, the glands have the capacity to respond to androgens.

Prolonged remissions of cystic and conglobate acne with 13-cis-retinoic acid.

Fourteen patients with treatment-resistant cystic and conglobate acne were treated for four months with oral 13-cis-retinoic acid, a synthetic isomer of naturally occurring all-trans-retinoic acid. The average dose was 2.0 mg per kilogram per day. Thirteen patients experienced complete clearing of their disease; the other had 75 per cent improvement, as determined by the number of acne nodules and cysts present before and after therapy. Prolonged remissions, currently lasting as long as 20 months after discontinuation of therapy, have been observed in all 14 patients. Clinical toxicity was limited to the skin and mucous membranes in most patients and was dose dependent and rapidly reversible upon discontinuation of therapy. The mechanism of action of 13-cis-retinoic acid in the therapy of acne probably involves a direct inhibitory effect of the drug on the sebaceous gland.

Unusual subepidermal bullous diseases with immunologic features of bullous pemphigoid.

Sixty-seven patients with histologic and immunologic features of bullous pemphigold (BP) were evaluated. Eleven patients had a localized blistering disease that was predominantly confined to one area of the body, most commonly the lower extremities. Two patients displayed a dapsone-responsive blistering disease that was characterized by a flexural distribution of ten to 20 1-cm or less, intensely pruitic, subepidermal bullae and linear IgA basement membrane zone deposition. Two patients had a chronic recalcitrant generalized scarring, hyperkeratotic, subepidermal blistering eruption that demonstrated serologic and direct immunofluorescence (IF) findings of BP. One patient displayed grouped small vesicles surmounted on an erythematous base; the clinical diagnosis was dermatitis herpetiformis, but direct IF examination of the biopsy specimen showed features of BP. One patient with epidermolysis bullosa acquisita had serologic and direct IF features suggestive of BP.

A reexamination of the potential comedogenicity of sulfur.

The present study was designed to reexamine the question of the potential comedogenicity of topical sulfur. Studies were done by two different investigators in two separate institutions with groups of 12 and 40 subjects, respectively. Biopsy specimens were obtained from the occluded test sites before and after a six-week period of treatment. Each subject received a patch test of 5% sulfur in either an octoxynol 9 (Triton X-100) or a carbomer 934P (Carbopol 934P) vehicle and one of two controls consisting of the Triton X-100 vehicle or a dry patch test. We conclude that no trend or correlation was noted between the presence or absence of sulfur in the formulation and the appearance of comedones. The Triton X-100 vehicle itself appeared to be comedogenic under the experimental conditions.

In-vitro metabolism of [3H]testosterone by scalp and back skin: conversion of testosterone into 5alpha-androstane-3beta, 17beta-diol.

The in-vitro metabolism of [3H]testosterone by human scalp and back skin was examined for possible differences in enzyme activity in skin from these two areas, both of which contain large sebaceous glands but only one of which, the back, is prone to develop acne. Punch biopsy specimens of skin, obtained from the scalp and back of adult men, were minced and incubated with [3H]testosterone. The metabolic products were diluted with carrier steroids, then separated and measured by thin-layer chromatography and by gas chromatography on an instrument equipped with a splitter. The results showed that of the 5alpha-reduced metabolites identified, a major one in both the scalp and back skin incubations was 5alpha-androstane-3beta,17beta-diol. Formation of the androstanediol was especially pronounced in scalp skin where it accounted for up to 50% of the 5alpha-reduced metabolites produced. This finding that 5alpha-androstane-3beta,17beta-diol is a major product of testosterone metabolism in vitro by human skin containing sebaceous glands, supports the possibility, previously suggested by studies in the rat, that this steroid can stimulate sebum secretion.