RESUMEN

Despite detailed microscopic descriptions and clinical observation, little is known regarding the pathogenesis of the perforating disorders of skin, which have traditionally been subdivided into numerous microscopic entities associated with various clinical settings. An increasing body of evidence now suggests that the perforating disorders of skin are akin, and may constitute an expanded single pathologic entity. Each of the classic perforating disorders of skin, including elastosis perforans serpiginosa, perforating folliculitis, reactive perforating collagenosis, Kyrle's disease, and perforating disorder of uremia, have been shown to extrude collagen, elastin, and related extracellular matrix components through the epidermis. Considering a shared pathogenic mechanism among these entities, we explored the possible role of the extracellular matrix, in particular fibronectin, in perforating disorders of skin. Using immunohistochemical and serum determinations of extracellular matrix constituents, including fibronectin, collagen type IV, laminin, and tenascin, we showed consistent serum elevation and/or deposition of fibronectin, in each case, without a commensurate increase in laminin, collagen type IV, and tenascin. We propose that elevated serum and tissue concentrations of fibronectin may be responsible for inciting, in a physiologically aberrant manner, increased epithelial migration and proliferation culminating in perforation.

Asunto(s)

RESUMEN

A histologic, immunohistochemical, and DNA ploidy analyses were performed on two cases of angiomatoid malignant fibrous histiocytoma to ascertain the histogenesis and relationship of endothelial, histiocytic, and fibroblastic elements. Both cases were slowly growing, grossly encapsulated. Subcutaneous masses resected from pediatric patients. Microscopically, the tumors were composed of solid masses of epithelioid and spindle cells with abnormal endothelial-lined and blood-filled cystic spaces surrounded by normal vascular structures and aggregates of lymphocytes occasionally forming germinal follicles. The tumor cells stained exclusively with CD34 and vimentin antibodies. Tumor-associated vessels stained for CD31, CD34, vimentin, and Ulex europaeus. Occasional cells within germinal follicles stained for lysozyme, CD68, and HAM56. Ploidy analysis of tumor cells showed intermediate aneuploidy with a DNA index of 1.14. Blood vessels within and surrounding the tumor as well as inflammatory cells were DNA euploid. These studies suggest that the tumor--though comprised of histologically and immunohistochemically benign-appearing euploid endothelial, fibroblastic, and inflammatory elements--contains an aneuploid population of undifferentiated mesenchymal cells.

Asunto(s)

RESUMEN

Dermatofibroma (DF) refers to a spectrum of firm, nodular, nonencapsulated lesions that occur commonly on the extremities. Histologically, DF is composed of spindle cells with variable differentiation toward histiocytic and vascular elements, often associated with epithelial hyperplasia and basilar keratinocyte pigmentation that histologically may simulate basal cell carcinoma (BCC). The characteristic epithelial changes are likely to be mesenchyma-mediated and probably represent a host reparative response otherwise known as the inductive phenomenon. Epidermal-mesenchymal cellular interactions, including induction, occur in various stages of embryonic skin development and in response to injury with tissue repair. Cellular interaction is mediated by direct apposition of cells or by soluble protein hormones produced directly by the cell (autocrine effect) or adjacent cells (paracrine effect). Among the important soluble mediators are epidermal growth factor (EGF), which is known to stimulate the proliferation and differentiation of a variety of transformed and benign tissues. We investigated the possible etiologic association between EGF receptor (EGF-R) expression and epithelial induction in a prospective series of 20 cases of DF compared to entities such as granular cell tumor, scar tissue, and nevus sebaceus similarly showing epithelial hyperplasia. Immunohistochemical staining for EGF-R showed strong dermal staining of dendritic spindle cells and overlying hyperplastic keratinocytes in each of the DF cases. Immunohistochemical staining for EGF-R was absent within all dermal loci of granular cell tumor (n = 3), nevus sebaceus (n = 6), and scar tissue (n = 12).

Asunto(s)

RESUMEN

BACKGROUND AND DESIGN: A consecutive sample of 46 cases was collected for comparative histologic evaluation. Results of incisional biopsies of cutaneous pigmented lesions interpreted as lentigo maligna, melanoma in situ, or invasive melanoma, and those suggestive, but not diagnostic, of melanoma were collected. Those lesions that were on actinically damaged skin and in which biopsy was followed by complete excision within 6 months were included. Incisional biopsies that removed greater than 50% of the surface area of the lesion were excluded. RESULTS: Of the excisional specimens, 40% demonstrated histopathologic features more pronounced than those in the biopsy specimens. Areas of invasive melanoma not detected in the biopsy specimens were observed in 20% of the excisional specimens. Accurate diagnosis based on small biopsy specimens was not always possible because of the absence of a classic lentigo maligna histologic pattern in many cases. The most frequent deviation from the pattern was the presence of lentiginous epidermal hyperplasia within these lesions. CONCLUSIONS: These results suggest that limited sampling may be inadequate for an accurate diagnosis of pigmented melanocytic lesions on actinically damaged skin. Areas chosen for biopsy may not contain the most advanced areas histologically and may fail to detect foci of invasive melanoma elsewhere within the lesion.

Asunto(s)

RESUMEN

Lymphoepithelioma is a lymphocyte-rich, poorly differentiated, nonkeratinizing carcinoma of the nasopharynx with distinctive clinical, epidemiologic, and etiologic features. Histologically and immunophenotypically identical tumors arising outside the nasopharynx are designated lymphoepitheliomalike carcinomas (LELCs), and have been described in the gastrointestinal tract, lung, salivary glands, thymus, and increasingly in the skin. Despite similarities between LELC and nasopharyngeal lymphoepithelioma, there is growing evidence that they are etiologically distinct. Serologic studies and molecular techniques have consistently demonstrated an etiopathologic association between Epstein-Barr virus (EBV) and lymphoepithelioma and LELC of several locations, including stomach, salivary gland, lung, and thymus. Though histologically similar. lymphoepitheliomalike carcinoma of the skin (LELCS) does not contain EBV DNA by RNA in situ hybridization. Recently, techniques for polymerase chain reaction (PCR) using fixed tissue have been described that to our knowledge have not been applied to LELCS. We studied five cases of LELCS, taking advantage of the higher sensitivity of PCR to evaluate the role, if any, of EBV specifically in the pathogenesis of LELCS.

Asunto(s)

RESUMEN

Two unusual acquired polypoid skin lesions exhibited prominent histological atypia, but were biologically benign. Both patients were elderly females. The lesions clinically mimicked fibroepithelial polyp or nevus lipomatosus. Both had been present for about 20 years. One lesion was located on the back, the other on the posterior thigh. Each lesion exhibited dilated, hyalinized vessels in the dermis with focal fibrin deposits, myxoid stroma, and a population of bizarre, pleomorphic spindle to stellate cells, some of which were multinucleated. Occasional atypical mitoses were present. One lesion had abundant admixed fat. Immunohistochemical staining was strongly positive only for vimentin. The lesions share features with degenerating angiofibroma and vaginal pseudosarcomatous polyp. As in these lesions, the atypia is most probably reactive and degenerative.

Asunto(s)

RESUMEN

Recent work on the molecular genetics of familial melanoma has suggested that the p16 kinase inhibitor gene (CDKN2) is one of the genes causing familial melanoma. Evidence for the candidacy of the p16 gene as a familial melanoma gene is summarized and the characteristics of this class of cell cycle control proteins are reviewed.

Asunto(s)

Asunto(s)

RESUMEN

A prospective two-month epidemiologic and histologic study of all melanocytic nevi biopsied (n = 434) at the University of Oklahoma Health Center was undertaken. Melanocytic nevi with papillomatous features (PAP) (n = 50) were found to occur predominantly in females (females = 44, males = 6; p < 0.01 adjusted for sex distribution of all melanocytic nevi). Immunohistochemical analysis of melanocytic nevi revealed concordance between PAP and intracytoplasmic nevocellular staining for estrogen-inducible pS2 protein. Melanocytic nevi without papillomatous features failed to stain for pS2 protein. These results suggest a hormone responsiveness exclusive of patient sex which may influence the pathogenesis of these distinctive melanocytic nevi.

Asunto(s)

RESUMEN

Epithelioid cell histiocytoma is a recently recognized lesion that is considered to be a variant of cutaneous fibrous histiocytoma (dermatofibroma). Ten cases are presented, including their light microscopic, immunohistochemical, and ultrastructural features. Eight of the cases are similar to those previously reported, presenting as elevated nodules arising on the extremities and composed of epithelioid histiocytes with overlying epidermal effacement. Two of the cases were composed of cells with the same morphologic and immunohistochemical characteristics as typical epithelioid cell histiocytoma, including factor XIIIa positivity, but these arose in the reticular dermis and exhibited prominent cellularity.

Asunto(s)

RESUMEN

Variations in human pigmentation among different racial groups are due to differences in the production and deposition of melanin in the skin. Although melanin synthesis is known to be controlled by the rate-limiting enzyme tyrosinase, the role of this enzyme as the principal determinant of skin pigmentation is unclear. Results from studies with human melanocyte cultures derived from different racial skin types reveal an excellent correlation between the melanin content of melanocyte cultures and the in situ activity of tyrosinase. Melanocytes derived from black skin have up to 10 times more tyrosinase activity and produce up to 10 times more melanin than melanocytes derived from white skin. However, the higher level of tyrosinase activity in melanocytes derived from black skin is not due to a greater abundance of tyrosinase. Results from immunotitration experiments and Western immunoblots reveal that the number of tyrosinase molecules present in white-skin melanocytes may equal the number found in highly pigmented black skin types. Moreover, approximately equivalent levels of tyrosinase mRNA are present in white and black skin cell strains. In contrast, melanocytes derived from red-haired neonates with low tyrosinase activity contain low numbers of tyrosinase molecules and low levels of tyrosinase mRNA. These results show that tyrosinase activity and melanin production in most light-skinned people is controlled primarily by a post-translational regulation of pre-existing enzyme and not by regulating tyrosinase gene activity. In contrast, melanocytes from red-haired (type I) people have low levels of tyrosinase protein and mRNA, suggesting that transcriptional activity of the tyrosinase gene is suppressed.

Asunto(s)

RESUMEN

We describe a 43-year-old white man who rapidly developed multiple, extensive angiomatous lesions on the temple and scalp after excision of a solitary lobular capillary hemangioma. This is a well-recognized but rare event. Our case differs from previously reported examples in terms of the age of the patient, the location and extent of the lesions, the histologic features in the form of small foci of angiosarcoma-like infiltration, and possibly with respect to the response to therapeutic intervention. Because of the alarming clinical picture produced by multiple lobular capillary hemangiomas, in addition to the occurrence of disturbing histologic features, the benign and self-limited nature of this disease must be emphasized.

Asunto(s)

Asunto(s)

Asunto(s)

RESUMEN

Congenital nevi (CN) can be recognized at birth or shortly thereafter. In adults, only those nevi over 5 cm in diameter can be assumed to be congenital in the absence of documentation in infancy. CN cannot be identified with certainty by histological examination, nor can melanomas be presumed to originate from CN on the basis of histologic findings. Up to 5% of patients with large CN (as defined by the National Institutes of Health (NIH) consensus information) will develop melanoma, and 80% of these will appear before the age of seven years. Increased risk of melanoma from smaller CN has not been substantiated. Although total excision of large CN immediately following birth would reduce the approximate 5% risk for melanoma from these lesions, because of the complexity of the procedure, large lesion removal is seldom completed prior to the ages of 7 to 10 years, and nevus cells frequently remain at the base of the excision with resultant negligible risk reduction. Melanoma risk from large CN is predominantly risk of melanoma in childhood. CN do not contribute significantly to risk for adult melanoma. Sunburn constitutes the most important reducible risk factor for adult melanoma. Ultimately, the greatest hazard of large CN is not melanoma risk but cosmetic deformity.

Asunto(s)

RESUMEN

Tyrosinase activity was assayed in black and white human foreskin samples by measuring both the hydroxylation of tyrosine to dopa (tyrosine hydroxylase activity) and the conversion of [14C]tyrosine to [14C]melanin (melanin synthesis assay). Enzyme activity was found both in the particulate (75%) and soluble (25%) fractions of the cell. Membrane-bound tyrosinase was readily solubilized by either zwitter-ionic or nonionic detergents. The anionic detergent, sodium cholate, inhibited enzyme activity. Tyrosinase activity in black foreskin homogenates averaged almost three times that in white skin samples (33.8 pmols 3H2O/h/mg skin in black and 12.71 pmoles 3H2O/h/mg skin in white skin), although considerable overlap in activities existed among the two groups. Tyrosinase activities measured with two separate assays, tyrosine hydroxylase and [14C]melanin assays, were similar, suggesting that tyrosine hydroxylase activity is tightly coupled to melanin synthesis. Tyrosinase activity determined by either assay method generally correlated with skin melanin content. Kinetic analysis of tyrosinase from black and white foreskin revealed a Km for tyrosine of 2.5 X 10(-4) M in both skin types. Immunotitration experiments suggested that the difference in tyrosinase activities between white and black skin may be due, not only to different amounts of enzyme present in the melanocytes, but also possibly to differences in the catalytic activities of the enzyme found in melanocytes of black and white skin.

Asunto(s)

RESUMEN

A human foreskin organ culture system has been developed to study the response of human skin to hormonal stimulation. Foreskins are maintained in culture on floating plastic supports which allows the epidermal surface to be exposed to air while the dermis is bathed in nutrient medium. Both black and white human foreskins can be maintained in organ culture for at least 1 wk with no change in the tissue structure or cell viability as determined by histochemical staining and by dopa reaction staining. Tyrosinase activity in both black and white human foreskin cultures decays markedly during the first 2 d of culture to a new steady state level which remains stable throughout the culture period. Both black and white foreskin cultures consistently demonstrate 2- to 10-fold increases in tyrosinase activity when treated with theophylline (1 mM). Approximately 90% of all skin cultures examined showed an increase in enzyme activity when treated with this phosphodiesterase inhibitor. Dibutyryl cAMP (0.1 mM) and [Nle4, D-phe7]-alpha MSH (10(-8) M), were also found to markedly stimulate tyrosinase activity in some skin cultures, whereas alpha-MSH and prostaglandin E1 produced only an inconsistent and small increase in the activity of the enzyme. Histamine (1 microM), vitamin D3 (1 microM), and retinoic acid (1 microM) failed to stimulate tyrosinase activity in either white or black foreskin cultures. This hormone-responsive organ culture system can be utilized to characterize the molecular processes responsible for the regulation of tyrosinase and pigmentation in human skin.

Asunto(s)

RESUMEN

Between 1982 and 1985, a total of 39 congenital pigmented nevi (CN) were removed from patients in the Oklahoma Children's Memorial Hospital. Multiple sections were examined from each of the lesions removed. The histologic patterns were recorded with special note of those features traditionally associated with CN. These include nevus cells in the lower reticular dermis and subcutaneous tissue, association of nevus cells with and in appendageal structures, and infiltration of nevus cells between collagen bundles. These features were primarily observed in larger CN (greater than 3 cm). Most small nevi do not show these features. The histologic patterns were consistent throughout multiple sections of the nevi. It is concluded that the histology traditionally associated with CN relates primarily to the size of the nevus rather than to the time of its appearance.

Asunto(s)

Asunto(s)

RESUMEN

The DERMatology INFOrmation NETwork (DERM/INFONET) of the American Academy of Dermatology has become a reality. DERM/INFONET consists of a number of data bases providing information and educational programs for the dermatologist. Currently the components are: DERM/MLS (Medical Literature Search), DERM/RX (dermatologic therapy), DERM/USP (United States Pharmacopeia data base), DERM/ALLERGENS (Food and Drug Administration and Environmental Protection Agency Listings of allergens); Melanoma Prognosis Model; Electronic Mail; Bulletin Board; Meetings Calendar; ICD/CPT (International Classification of Diseases/Current Procedural Terminology) codes; AAD Membership/Committee Directories; and Dermatology Quiz. Additional data bases are planned. As audiovisual and alphanumeric communication systems evolve, newer opportunities for enhancing the DERM/INFONET Biomedical Communication Network will undoubtedly provide even greater opportunities for aiding the dermatologist in delivering state-of-the art management for their patients.

Asunto(s)