Neutral endopeptidase expression and distribution in human skin and wounds.

Cutaneous sensory nerves mediate inflammation and wound healing by the release of neuropeptides such as substance P. Neutral endopeptidase is a cell surface enzyme that degrades substance P and thereby terminates its biologic actions. The distribution of neutral endopeptidase in normal skin and wounded human skin, however, has not been examined. The objectives of this study were to evaluate neutral endopeptidase expression in wounded and unwounded skin as well as in cells derived from human skin. Neutral endopeptidase was strikingly localized in normal skin by immunohistochemistry to keratinocytes of the epidermal basal layer, to hair follicles, eccrine and sebaceous glands as well as to endothelium of blood vessels and to large nerves. Standard incisional human wounds were studied at several time points between 1 h and 28 d after wounding. Staining for neutral endopeptidase was noted in the wound bed 6 h after wounding. In contrast to normal skin, staining of all the epidermal cell layers was noted in the migrating tongue of epithelium in l d wounds. Similar full-thickness staining was noted in 3 d and 7 d wounds in all layers of the new wound epithelium and in a "transition epithelium" near the wound edge. By 28 d post wounding neutral endopeptidase staining again was detected only in the basal layer of the epidermis. Neutral endopeptidase mRNA was detected in normal skin and wounds as well as cultured keratinocytes, fibroblasts and endothelial cells. Neutral endopeptidase enzymatic bioactivity was demonstrated in cultured keratinocytes. While it is known that several metalloproteinases important to tissue repair are produced by keratinocytes, this is the first evidence that keratinocytes produce neutral endopeptidase. Neutral endopeptidase may terminate the proinflammatory and mitogenic actions of neuropeptides in normal skin and wounds.

Quantitative detection of silicone in skin by means of electron spectroscopy for chemical analysis (ESCA).

BACKGROUND: Evaluation of silicone-induced morbidity in skin has been hampered by the difficulty of detecting silicone in tissue because conventional methods are nonquantitative and insensitive. OBJECTIVE: We attempted to determine whether silicone could be identified and quantitated in skin by means of electron spectroscopy for chemical analysis (ESCA). METHODS: Skin biopsy specimens were obtained from the nose, chin, malar region, and inner arm of a patient who had received injections of silicone gel in his nose and chin. Frozen sections were dried under vacuum and examined by means of ESCA. Contiguous sections were examined by light microscopy. RESULTS: The surface concentrations of silicone were as follows: chin, 20.6% +/- 3.6%; nose, 19.0%; malar region, 2.6% +/- 1.6%; inner arm, 0.0% +/- 0.0%. Light microscopy revealed homogeneous "globules" consistent with silicone in the chin and nose sections only; the malar region and inner arm sections showed no evidence of silicone. CONCLUSION: ESCA can be used to detect silicone in skin in a specific, highly sensitive, and quantitative manner. This is the first report of quantification of silicone in skin by means of ESCA.

Role of human papillomavirus typing in diagnosis and clinical decision making for a giant verrucous genital lesion.

A 60-year-old man presented with a 12.0 x 10.0-cm exophytic, verrucous genital plaque. Multiple biopsy specimens were evaluated by standard histologic analysis and polymerase chain reaction assays for human papillomavirus (HPV) deoxyribonucleic acid. All biopsy specimens showed histopathologic changes consistent with giant condyloma of Buschke-Lowenstein (GCBL), were uniformly positive for HPV 6/11, and showed a weaker signal for HPV 16. Published reports suggest that the presence of HPV may be useful in differentiating GCBL from verrucous carcinoma (VC), but absence of "high-risk" HPV types in GCBL cannot exclude focally invasive squamous cell carcinoma. Screening for HPV may be a helpful adjunct in differentiating GCBL from VC, but histopathologic criteria for malignancy should take precedence over HPV typing when determining management.

Trichodysplasia spinulosa--a newly described folliculocentric viral infection in an immunocompromised host.

This is a case report of an immunocompromised individual who presented with progressive alopecia, friable follicular spinous processes, and erythematous, indurated papules. Examination of skin biopsies using light microscopy and immunohistochemistry revealed pathologic changes of the follicular inner root sheath epithelium with dystrophic trichohyaline granules. Electron microscopy of thin sections of tissue revealed intracellular viral particles with a size and appearance consistent with those in the Papovaviridae family. Electron microscopy of negatively stained extract from a homogenized lesion also demonstrated icosahedral viruses with papovavirus morphology. We believe this is a previously unreported folliculocentric viral infection in an immunosuppressed human host and have termed this entity "trichodysplasia spinulosa".

Subcutaneous T-cell lymphoma treated with systemic chemotherapy, autologous stem cell support, and limb amputation.

Subcutaneous T-cell lymphoma is an unusual variant of peripheral T-cell lymphoma in which the malignant infiltrate preferentially involves the subcutis. The disease is often initially misdiagnosed as a benign inflammatory panniculitis or a granulomatous disease. We describe subcutaneous T-cell lymphoma in a 39-year-old man who was treated with systemic chemotherapy, autologous stem cell support, and amputation of the limb primarily involved with the lymphomatous infiltrate. This is the first report of amputation being included in the treatment regimen of subcutaneous T-cell lymphoma. Because preferential involvement of the extremities often occurs in patients with subcutaneous T-cell lymphoma, surgical debulking of refractory disease by partial or complete limb amputation may be a useful therapeutic adjunct.

Immunohistochemical characterization of dermatofibrosarcoma protuberans with practical applications for diagnosis and treatment.

Dermatofibrosarcoma protuberans (DFSP) is a rare, clinically challenging, soft tissue tumor. The main histologic differential of DFSP is usually a dermatofibroma. In 1990, the first report appeared demonstrating that cells of DFSP express the human progenitor antigen CD34 on their surface. Since then, there have been increasing reports of the usefulness of immunohistochemical staining with CD34 to differentiate DFSP from dermatofibroma and other soft tissue tumors. This literature is reviewed with special emphasis on the insights studies have provided into the histogenesis of DFSP. The literature demonstrating the practical applications of CD34 staining in the diagnosis and treatment of DFSP is also discussed.

Dermatofibrosarcoma protuberans (DFSP): growth characteristics based on tumor modeling and a review of cases treated with Mohs micrographic surgery.

Dermatofibrosarcoma protuberans (DFSP) is a relatively rare cutaneous tumor that is clinically challenging since it is locally highly invasive and aggressive, although it rarely metastasizes. Traditionally, wide and deep local surgical excision has been regarded as the treatment of choice for DFSP. However, even 3-cm-wide local excision margins have resulted in a local recurrence rate of 11%. In recent years, reports of DFSPs successfully treated with Mohs micrographic surgery have been appearing in the literature. The DFSP literature is reviewed here, including worldwide experience reported to date in the use of Mohs surgery to excise DFSPs. Using this margin control technique, the recurrence rate is shown to be 2.4%, much lower than the best previously reported recurrence rate of 11% when wide local excision was used. Three-dimensional reconstructions of DFSPs, based on Mohs micrographic surgical technique, are also presented. These illustrations provide new insight into the growth characteristics of these tumors and why Mohs micrographic surgery is emerging as the treatment of choice for DFSP.

In vitro platelet interactions in whole human blood exposed to biomaterial surfaces: insights on blood compatibility.

A short-term in vitro test to study platelet interactions with biomaterials is described. Using fresh human blood and a modified Chandler loop system, beta-thromboglobulin release was measured. Also, adherent platelets were observed by using scanning electron microscopy (SEM) and a colorimetric stain specific for human platelet GPIIIa. Materials studied in these experiments were polyethylene (PE), Biomer, poly(vinyl alcohol) (PVA), and a polyurethane prepared with octadecyl pendant groups (ODCE). Four blood reactions were observed: (1) Platelets continually adhere and activate on the Biomer; (2) platelets initially adhere and activate but then spread to a thin, passivating film on the PE; (3) platelets do not adhere to the PVA surface but continually react with it upon contact; and (4) platelets neither adhere to nor activate on the ODCE surface. Reactions (2) and (4) are considered characteristic of blood-compatible materials.

Glow discharge plasma deposition of tetraethylene glycol dimethyl ether for fouling-resistant biomaterial surfaces.

The glow discharge plasma deposition (GDPD) of tetraethylene glycol dimethyl ether is introduced as a novel method for obtaining surfaces that are resistant to protein adsorption and cellular attachment. Analysis of films by x-ray photoelectron spectroscopy and several biological assays indicate the formation of a fouling-resistant, PEO-like surface on several substrata (e.g., glass, polytetrafluoroethylene, polyethylene). Adsorption of 125I-radiolabelled proteins (fibrinogen, albumin and IgG) from buffer and plasma was very low (typically less than 20 ng/cm2) when compared to the untreated substrata, which exhibited much higher levels of protein adsorption. Not all coated substrata adsorbed equal amounts of protein (e.g., coated glass samples typically adsorbed more protein than coated polyethylene or coated polytetrafluoroethylene samples), suggesting that the substratum used may affect the amount of protein adsorbed. Measurement of dynamic platelet adhesion, using epifluorescent video microscopy, and endothelial cell attachment further demonstrates the short-term nonadhesiveness of these surfaces.