Effects of moisturization on epidermal homeostasis and differentiation.

Moisturizers are commonly used for routine skin care. This study assessed the effects of a moisturizer on barrier function, epidermal architecture, keratinocyte proliferation, and physiological regulation of the epidermis in photoaged but otherwise normal skin. Fifteen women with moderately photoaged forearms were treated twice a day for 4 weeks with a moisturizer containing dimethicone and glycerine. Baseline and post-treatment transepidermal water loss (TEWL) and ipsilateral forearm biopsies were obtained. Epidermal thickness, melanin levels, keratinocyte proliferation, and expression of keratins were evaluated. Induction of keratins 6 and 16, commonly associated with keratinocyte proliferation and wound healing, was observed. Epidermal thickness increased by 0.019 mm (P = 0.005), barrier function improved (TEWL decreased by 13%) and melanin intensity decreased (P = 0.004). Even nonxerotic, photoaged skin may appear younger, benefiting structurally and functionally from routine use of moisturizers containing dimethicone and glycerine.

Thyroid autoimmunity in children and adolescents with type 1 diabetes: a multicenter survey.

OBJECTIVE: To investigate thyroid autoimmunity in a very large nationwide cohort of children and adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: Data were analyzed from 17,749 patients with type 1 diabetes aged 0.1-20 years who were treated in 118 pediatric diabetes centers in Germany and Austria. Antibodies to thyroglobulin (anti-TG) and thyroperoxidase (anti-TPO) were measured and documented at least once in 7,097 patients. A total of 49.5% of these patients were boys, the mean age was 12.4 years (range 0.3-20.0 years), and the mean duration of diabetes was 4.5 years (range 0.0-19.5 years). A titer exceeding 100 units/ml or 1:100 was considered significantly elevated. RESULTS: In 1,530 patients, thyroid antibody levels were elevated on at least one occasion, whereas 5,567 were antibody-negative during the observation period. Patients with thyroid antibodies were significantly older (P < 0.001), had a longer duration of diabetes (P < 0.001), and developed diabetes later in life (P < 0.001) than those without antibodies. A total of 63% of patients with positive antibodies were girls, compared with 45% of patients without antibodies (P < 0.001). The prevalence of significant thyroid antibody titers increased with increasing age; the highest prevalence was in the 15- to 20-year age group (anti-TPO: 16.9%, P < 0.001; anti-TG: 12.8%, P < 0.001). Thyroid-stimulating hormone (TSH) levels were higher in patients with thyroid autoimmunity (3.34 microU/ml, range 0.0-615.0 microU/ml) than in control subjects (1.84 microU/ml, range 0.0-149.0 microU/ml) (P < 0.001). Even higher TSH levels were observed in patients with both anti-TPO and anti-TG (4.55 microU/ml, range 0.0-197.0 microU/ml). CONCLUSIONS: Thyroid autoimmunity seems to be particularly common in girls with diabetes during the second decade of life and may be associated with elevated TSH levels, indicating subclinical hypothyroidism.

Evaluation of a novel synthetic sealant for inhibition of cardiac adhesions and clinical experience in cardiac surgery procedures.

BACKGROUND: Pericardial adhesions subject patients requiring reoperation to potential injuries to the heart, great vessels, and cardiac grafts during the re-sternotomy. These adhesions can severely complicate re-operations by making re-entry hazardous, impeding orientation and visibility, increasing the amount of blood loss, and prolonging the operation time. The efficacy of an in situ-forming polyethylene glycol (PEG) material, CoSeal surgical sealant (CoSeal), for inhibiting cardiac adhesions in an animal model is reported. It is currently estimated that 10-20% of patients undergoing aortic valve replacement and coronary artery bypass grafting (CABG) will require a second operation later in their lives. Successful clinical experience using CoSeal for sealing suture lines of the aorta and CABGs with the data reported here suggest that CoSeal may have multiple applications in cardiac surgery. METHODS: In rabbits, a sternotomy and pericardiotomy were performed to expose the heart and the epicardium of the left ventricular surface. The epicardium was abraded for five minutes with dry gauze and cotton to develop punctate bleeding. In treated animals, CoSeal(R) or Tissucol(R) was applied directly to the abraded bleeding epicardium while retracting the pericardium. The pericardium was released, and the material over-sprayed to the cut edges of the pericardium. No material was applied in control animals. RESULTS: At necropsy, CoSeal(R) was found to significantly reduce the formation of adhesions, the tenacity of the adhesions, and the percent of the abraded site with adhesions as compared to surgical control and Tissucol. Tissucol showed no significant difference from the surgical control in any adhesion parameter. CoSeal treated hearts showed re-establishment of the mesothelial layer and tissue morphology similar to a normal un-operated heart. During the clinical cardiac procedures, CoSeal was easily mixed and applied to the suture lines of the aorta and coronary artery grafts. No bleeding was found at the suture lines. CONCLUSIONS: In the rabbit cardiac adhesion model, CoSeal significantly reduced the formation of adhesions as compared to surgical control and Tissucol, and demonstrated good biocompatibility. In CoSeal treated patients undergoing cardiopulmonary bypass or vessel repair, sealing was achieved comparable to previous cases using Tissucol fibrin sealant. CoSeal effectively sealed the suture lines of the aorta and coronary artery bypass grafts.

Treatment of suture line bleeding with a novel synthetic surgical sealant in a canine iliac PTFE graft model.

CoSeal mark surgical sealant (CoSeal) was evaluated for inhibiting suture line bleeding using a canine iliac PTFE graft model. Both iliac arteries of 12 heparinized canines were grafted with PTFE. CoSeal was applied to the suture lines of one graft in each animal. The contra-lateral graft served as a control and bleeding was controlled with gauze and pressure (tamponade). The cross-clamps were removed 30 s following application of CoSeal. Times to hemostasis and volume of blood loss at each graft site were determined. Compared to tamponade control, CoSeal significantly reduced the time to hemostasis (average of 5 min vs. greater than 15 min, p < 0.05) and blood loss (19 g vs. 284 g, p < 0.05). Small amounts of CoSeal were visible grossly or histologically at day 7. Histology showed moderate to marked inflammation in CoSeal sites and moderate inflammation in control sites at day 7. At 30 and 60 days, no CoSeal was visible grossly or histologically. Histology showed moderate inflammation in both CoSeal treated sites and in control sites at day 30 and mild to moderate inflammation in both CoSeal and control sites at day 60. CoSeal significantly reduced the time to hemostasis and blood loss in comparison to tamponade.

In vivo model of histologic changes after treatment with the superpulsed CO(2) laser, erbium:YAG laser, and blended lasers: a 4- to 6-month prospective histologic and clinical study.

BACKGROUND AND OBJECTIVE: To compare the in vivo histologic effects of the pulsed carbon dioxide (CO(2)) and erbium:ytrium aluminum garnet (Er:YAG) lasers and to assess the effects of combining CO(2) and Er:YAG laser modalities during a single treatment session. We previously reported 10 patients treated with four laser regimens: CO(2) alone, CO(2)/Er:YAG, Er:YAG alone, Er:YAG/CO(2) with time points at 1 hour and 7 days between laser treatment and histologic analysis. This study found that the optimal treatment consisted of limited CO(2) laser passes followed by Er:YAG. This treatment produced less collagen injury, less thermal necrosis, and more robust epithelial and dermal fibrous tissue regeneration in the acute phase of healing. The present study examines the histologic changes resulting from the host healing response to laser treatment on long-term follow-up of 4-6 months. STUDY DESIGN/MATERIALS AND METHODS: The Stanford University Committee on Human Subjects in Medical Research approved this study. Nine patients with actinic damage and indications for rhytidectomy volunteered for this interventional study in which each patient served as both experimental and control. The right preauricular area was treated at five sites with the following: (1) CO(2), (2) CO(2) followed by Er:YAG, (3) Er:YAG, (4) blended CO(2)/Er:YAG (Derma-Ktrade mark), (5) phenol. Each was subjected to full-face or sub-unit treatment. Each patient was followed up initially daily then weekly for healing of the full-face laser and for differences in healing of the five treatment areas. Five patients were selected for histologic evaluation. At 4-6 months, these patients underwent rhytidectomy with immediate removal of laser-treated skin, which was evaluated histologically by the study dermatopathologist, who was blinded to the treatment at each site. RESULTS: CO(2) laser treatment produced the greatest thickness of neocollagen (0.27 mm; P < 0.05), the highest neocollagen density (P < 0.05), the greatest decrease in elastosis (27%), but took the longest time for healing and resolution of erythema and inflammation (up to 6 months). Er:YAG used alone produced the least collagen density, with the thinnest band of neocollagen (0.08 mm), but the most rapid resolution of erythema and inflammation (within 10 days). Combined CO(2)/Er:YAG treatments, including Derma-Ktrade mark and CO(2) followed by Er:YAG produced histologic changes that were intermediate, as well as recovery that was intermediate (resolution of erythema within 1 month); the development of neocollagen was greater in CO(2)-containing modalities than Er:YAG used alone by a statistically significant margin (P = 0.001). These histologic findings were corroborated by clinical correlation by examination of the five treatment spots in nine patients and in full-face treatments in 100 patients. CONCLUSION: Collagenesis is greatest with CO(2) and least with Er:YAG. Elastosis decreased to the greatest degree with CO(2), least with erbium, and to an intermediate extent with blended CO(2)/Er:YAG regimens (sequential and Derma-K). These changes from control are statistically significant with all regimens (P < 0.05). Blended CO(2)/Er:YAG treatments provide an optimal combination of the benefits of CO(2) but with lesser erythema and healing delay. Clinical and histologic findings change over time for different treatments. Thus, long-term histology is critical for predicting results of treatment.

Reduced hyaluronan in keloid tissue and cultured keloid fibroblasts.

Extracellular matrix hyaluronan is prominent during wound healing, appearing at elevated levels early in the repair process. It is prevalent throughout the course of fetal wound healing, which is scar-free, but decreases late in adult wound repair, that is often marked by scarring. To determine whether aberrant hyaluronan metabolism is associated with the excessive scarring that characterizes keloids, cultured fibroblasts derived from keloids and from the dermis of normal human skin and scar were compared. Levels of hyaluronan in 48 h conditioned media of keloid-derived cultures were significantly lower than in cultures of normal skin and scar fibroblasts. Profiles of hyaluronan polymer size were comparable in these two cell types, suggesting that excessive hyaluronan degradation was not involved. Hydrocortisone decreased hyaluronan levels approximately 70% in the conditioned media of both keloid and normal fibroblasts. Diminished hyaluronan accumulation in keloid-derived cells compared with normal fibroblasts was also observed in an in vitro wound healing model. Histolocalization of hyaluronan in keloids, normal skin, and scar samples confirmed the biochemical observations that the dermis of keloids, which comprises most of the scar tissue, contained markedly diminished levels of hyaluronan. Alterations in hyaluronan in the epidermis overlying keloids, however, were also observed. A modest increase in hyaluronan staining intensity was observed in the epidermis of keloids, as well as changes in the patterns of distribution within the epidermis, compared with that in normal skin and scar. Increased hyaluronan was present in the granular and spinous layers of the keloid epidermis Abnormalities are present apparently in both the overlying epidermis as well as in the dermis of keloids. Aberrations in signaling between keloid stroma and keloid epidermis may underlie abnormalities that contribute to the excessive fibrosis characteristic of these lesions.

Basal cell carcinoma with tumor epithelial and stromal giant cells: a variant of pleomorphic basal cell carcinoma.

A case of basal cell carcinoma with giant cells of the central epithelial and surrounding stromal components is presented. The lesion was an 8-mm dome-shaped papule on the ear of a 66-year-old man. The giant cells of the epithelial component shared the immunophenotype of the more typical cells of the basal cell carcinoma (keratin, smooth muscle actin, and bcl-2 positive), whereas the stromal giant cells were positive only for bcl-2. This case represents a peculiar variant of pleomorphic basal cell carcinoma, the significance of which is unknown.

Hereditary ochronosis: hyperpigmented skin overlying cartilaginous structures.

Hereditary ochronosis, or alkaptonuria, results from deficiency of homogentisic acid oxidase. It is an autosomal recessive condition found in geographically isolated populations. The excess homogentisic acid deposits in collagenous structures, leading to unusual pigmentation of the skin overlying cartilaginous structures, but on occasion pigment is also seen in the sclera, in sweat after oxidation, and classically, in urine when left standing at room temperature. This case report highlights the pathogenesis and expression of this rare disorder.

Histologic analysis of the thermal effect on epidermal and dermal structures following treatment with the superpulsed CO2 laser and the erbium: YAG laser: an in vivo study.

BACKGROUND AND OBJECTIVE: To compare the in vivo histologic effects of the carbon dioxide (CO2) and erbium:yttrium aluminum garnet (Er:YAG) lasers. To ascertain the effects of combining CO2 and Er:YAG laser modalities during a single treatment session. STUDY DESIGN/MATERIALS AND METHODS: Ten patients underwent laser treatment to four left preauricular sites 7 days prior to rhytidectomy as follows: CO2 alone, CO2/Er:YAG, Er:YAG alone, and Er:YAG/CO2. The right preauricular area was identically treated 1 hour prior to rhytidectomy. Laser treated skin was excised during rhytidectomy and was evaluated histopathologically in a blinded manner. RESULTS: After 7 days, all groups were reepithelialized and showed equal neo-collagen formation. After 7 days, CO2/Er:YAG and Er:YAG alone had the least collagen injury and thickest epidermis and papillary dermis of all groups. Specimens lased 1 hour prior to excision showed the least collagen injury and thermal necrosis when treated with CO2/Er:YAG and Er:YAG alone. Four passes with CO2 removed 250 microm of tissue, while eight passes with the Er:YAG removed 160 microm of tissue. CONCLUSIONS: Limiting CO2 laser passes and ending with Er:YAG produces less collagen injury, less thermal necrosis, and more robust epithelial and dermal fibrous tissue regeneration. CO2 followed by Er:YAG has similar thermal necrosis and collagen injury as Er:YAG alone, presumably due to Er:YAG removal of CO2 induced thermal injury.

The validity of ex vivo laser skin treatment for histological analysis. A prospective controlled study.

BACKGROUND: Laser treatment of skin following removal from human subjects has been the staple of laser research. However, no study has been done to assess the efficacy of ex vivo skin for predicting the behavior of laser treatments in living human tissue. OBJECTIVE: To assess the validity of the ex vivo model by comparing histological characteristics of skin treated with laser prior to and following its removal in rhytidectomy. STUDY DESIGN: Nonrandomized controlled intervention study in which each patient served as both experimental subject and control for different skin sites. PATIENTS: Ten patients with actinic skin changes. INTERVENTIONS: Patients underwent laser treatment to 4 left preauricular sites 1 hour prior to rhytidectomy as follows: carbon dioxide laser treatment alone, carbon dioxide laser treatment followed by erbium:YAG laser treatment, erbium:YAG laser treatment alone, and erbium:YAG laser treatment followed by carbon dioxide laser treatment. The skin was examined by a dermatopathologist blinded to the identity of each specimen. Untreated skin was also removed and immediately subjected to laser treatment identical to that employed in the in vivo skin. This skin was examined histologically. MAIN OUTCOME MEASURES: Regularity of ablation, depth of the necrotic zone, amount of skin removed, degree of collagen injury, and degree of inflammation. RESULTS: There were significant differences between the ex vivo and in vivo groups. The ex vivo specimens demonstrated more than 10 times the irregularity of ablation of the in vivo specimens (irregularity index of 3.0 for the ex vivo group vs 0.25 for the in vivo specimens; P < .05). The incidence of collagen injury was slightly lower for the ex vivo group (1.0 vs 1.3), as was the degree of inflammation (1.4 vs 1.5). The greatest differences were the significantly smaller necrotic zone in the ex vivo specimens (51 vs 71 microns) and the smaller amount of skin removed (118 vs 234 microns). These findings were consistent for all 4 laser treatment regimens studied. CONCLUSIONS: Significant differences were found between the in vivo and ex vivo models. Irregularity of ablation in the ex vivo specimens was 10 times that in the living specimens, limiting histological accuracy in the ex vivo model. The ex vivo skin model underestimated the amount of tissue ablation. This suggests that an in vivo model should be adopted as the standard for laser research.

Infiltrative basal cell carcinoma occurring in sites of biopsy-proven nodular basal cell carcinoma.

Over 200 basal cell carcinomas (BCCs) are biopsied and subsequently excised each year at the Veterans Affairs Palo Alto Health Care System (VAPAHCS). A focal infiltrative pattern developed in the region of the biopsy scar in the re-excision specimens of 20 cases out of approximately 400 BCCs (< 5%) examined histopathologically over a 2-year period. The patient population included predominantly male, elderly Caucasians (mean age 71), and all tumors fulfilled clinical and histologic criteria for nodular BCC at the time of initial punch or shave biopsy. No patient showed recurrence of tumor following simple re-excision with 2-3 mm surgical margins, with a mean follow up of 25.4 months after excisional surgery. These neoplasms had a more benign clinical course, possibly related to scar formation in healing sites of previously biopsied nodular BCC, rather than true aggressive-growth BCC. The authors conclude that a focal infiltrative pattern in a re-excision specimen may occur histologically as a scar-induced pattern which mimics an aggressive-growth BCC, but does not appear to have the same prognosis. We believe this is an important histologic observation, as recognition of biopsy scar changes in an excisional specimen of BCC may help to distinguish it from true aggressive-growth BCC.

Evaluation of artecoll polymethylmethacrylate implant for soft-tissue augmentation: biocompatibility and chemical characterization.

Artecoll polymethylmethacrylate implant (Artecoll) is a combination of polymethylmethacrylate beads suspended in 3.5% atelocollagen and has been designed for use in soft-tissue augmentation applications. The biocompatibility and immunogenicity of Artecoll were evaluated to assess the safety of this product for use in the dermis. To characterize the collagen component, chemical analysis was performed including trypsin sensitivity, differential scanning calorimetry, and pepsin content. Particle size analysis was also performed on the polymethylmethacrylate beads. The ability of this material to elicit an immunologic response was measured in a sensitized and nonsensitized guinea pig intradermal model. In these studies, 24 guinea pigs were injected intradermally with either Artecoll or Zyderm, a bovine collagen product for soft-tissue augmentation. Six sites were evaluated for each material at 3, 7, and 28 days after injection. In the sensitized model, 60 guinea pigs were divided into five groups, and each group received a sensitizing dose (in conjunction with Freund's adjuvant) of Zyderm, Artecoll, or a nonsensitizing dose of the same materials. The fifth group served as a nontreatment control. After the animals were sensitized, they were challenged with intradermal injections of various antigens to evaluate delayed type hypersensitivity reactions. Chemical characterization indicated polymethylmethacrylate beads of varying sizes, including many less than 35 microns, and a vehicle of extensively denatured and impure collagen. In vivo evaluations indicated that Artecoll elicited an immune response in guinea pigs, including delayed type hypersensitivity and antibody reactions. Histological assessment demonstrated particle phagocytosis and transepidermal elimination. Following immunization with Artecoll, guinea pigs were also found to be sensitized to pepsin, an impurity found in the collagen carrier. The biocompatibility of this material was compared with that of bovine dermal collagen (Zyderm collagen implant), which is widely used and accepted as biocompatible. The results of this evaluation indicate that Artecoll polymethylmethacrylate implant has the potential to elicit an immune response in humans, and polymethylmethacrylate beads are susceptible to phagocytosis and elimination.

Birt-Hogg-Dubé syndrome: a review and presentation of the first case with oral lesions.

Birt-Hogg-Dubé syndrome manifests as small, skin-colored, dome-shaped, or pedunculated cutaneous lesions. Three histopathologic patterns have been described: fibrofolliculomas, trichodiscomas, and acrochordons. The patient described in this article also had small, elevated, intraoral papules involving the mucosal surfaces of the lips, buccal mucosa, and gingivae, which represents a finding that had not been described in the literature previously.

Desmoplastic and spindle-cell malignant melanoma. An immunohistochemical study.

The clinical, histologic, and immunohistologic features of 22 desmoplastic melanomas (DMM), 10 mixed desmoplastic and spindle-cell melanomas (DMM/SMM), and two cellular spindle-cell melanomas (SMM) were studied. Patients ranged in age from 35 to 91 years (mean, 67) and included 23 men and 11 women. Seventeen cases occurred in sun-damaged skin of the head and neck. 11 were on the extremities, and six on the trunk. Except for two cases, all were Clark's level IV or V. Twenty-two (65%) cases were associated with a recognizable overlying pigmented lesion. Thirty of 32 (94%) DMM and DMM/SMM were clearly positive for S100. S100 staining was limited to < 5% of the spindle cells in two DMM/SMM. All DMM were negative when stained with HMB45. Three DMM/ SMM were immunoreactive with HMB45, as were both SMM. CD68 staining was limited to < 5% of the spindle cells in two of 32 DMM and DMM/SMM and 20% of the cells in one of two SMM. Nine (32%) DMM and DMM/SMM contained significant numbers of spindle cells immunoreactive for SMA but not desmin. In five cases, the number of actin-positive spindle cells. Two color stains for SMA and S100 demonstrated that these smooth-muscle actin positive cells constituted a separate spindle-cell population, consistent with reactive myofibroblasts. This study indicates that the immunohistologic features of desmoplastic melanoma differ from those of conventional melanoma. If a problematic spindle-cell skin lesion is a suspected melanocytic process, HMB45 is unlikely to provide confirmatory (or exclusionary) evidence for the diagnosis of DMM. Similarly, because of the variability in S100 expression in this neoplasm, the absence of S100 staining should not be relied on too heavily to exclude DMM if the clinical and histologic features favor that diagnosis. Caution should be exercised in the interpretation of numerous actin-positive spindle cells in isolation of additional confirmatory or exclusionary data as desmoplastic melanomas may contain significant numbers of these cells.

Increased proportion of aggressive-growth basal cell carcinoma in the Veterans Affairs population of Palo Alto, California.

BACKGROUND: We have noted a high frequency of aggressive-growth basal cell carcinomas (BCCS) in our patient population. Subtypes observed with increased frequency include morpheaform, infiltrative, and micronodular. OBJECTIVE: Our purpose was to examine the frequency of histologic subtypes of all BCCs seen in the dermatology clinics in the Veterans Affairs Palo Alto Health Care System in an 18-month period. METHODS: We reviewed 432 consecutive primary BCC biopsy specimens taken from 252 patients. RESULTS: Aggressive-growth BCC was observed in 20.7% of biopsy specimens, including 13.4% morpheaform, 5.7% infiltrative, and 1.6% micronodular subtypes. The mean age of the patient population was 70 years, with a standard deviation of 9.1 years. CONCLUSION: Our observed percentage of aggressive-growth BCC is substantially higher than in most other large studies. A high frequency of aggressive-growth BCC coupled with the increasing incidence of nonmelanoma skin cancer may have significant implications for future health care resource allocation.

Benign lymphangioendothelioma.

We describe a 40-year-old white man with a red-brown, indurated plaque on the proximal aspect of his right thigh. The lesion had been present since birth, and the patient had a 20-year clinical history of recurrent cellulitis in the same area. The histopathologic features of the lesion included permeation of the dermis by flattened, endothelium-lined channels without cellular atypia, hemorrhage, or inflammation. The endothelial cells were stained intensely with monoclonal antibody anti-CD34 (clone MY10). In addition, antibodies to factor VIII antigen, HLA-DR, smooth muscle actin, ICAM-1, and the lectin Ulex europaeus labeled the luminal cells. The basement membrane of the channels stained with anti-type IV collagen and laminin. Desmin-positive cells were abundant adjacent to the channels. Factor XIIIa stained both mononuclear cells and occasional dendritic cells in the perivascular area. Ki-67 immunolabeling could not be demonstrated on fresh or frozen tissue. Electron microscopy revealed the presence of both tight junctions and a well-formed, continuous basement membrane but the absence of Weibel-Palade bodies.

Elevated c-Src tyrosine kinase activity in premalignant epithelia of ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon with a high incidence of colon cancer. Dysplasia is a precursor to carcinoma and a predictor of malignant potential; epithelia containing high-grade or severe dysplasia is most likely to develop cancer. The cellular oncogene c-src and its viral homologue v-src (the transforming gene of Rous sarcoma virus) encode 60-kD cytoplasmic, membrane-associated protein tyrosine kinases. For the viral protein or transforming mutants of the cellular protein (Src), a close correlation exists between elevated tyrosine kinase activity and malignant transformation of cells. Previously, we and others observed elevated Src activity in sporadic colon carcinomas and benign adenomas at greatest risk for developing cancer (those with large size, villous architecture, and/or severe dysplasia). Here we report that Src activity and protein abundance are also elevated in neoplastic UC epithelia. Activity is highest in malignant and severely dysplastic epithelia, and 6-10-fold higher in mildly dysplastic than in nondysplastic epithelia. Thus, Src activity is elevated in premalignant UC epithelia, which is at greatest risk for developing cancer. The data suggest that activation of the src proto-oncogene is an early event in the genesis of UC colon cancer.

Desmoplastic neurotropic malignant melanoma.

Desmoplastic neurotropic malignant melanoma is a rare spindle cell variant of malignant melanoma. This chapter reviews its clinical presentation; histologic, immunohistochemical, and ultrastructural features; differential diagnosis; and critical therapeutic issues.

Caterpillar bodies: distinctive, basement membrane-containing structures in blisters of porphyria.

In a previous study, we reported on the observation of a relatively specific, linear body in the roofs of bullae from cases of porphyria cutanea tarda. In the present study, we expand on these observations to show the presence of these bodies in lesions of pseudoporphyria cutanea tarda and erythropoietic protoporphyria. Furthermore, we have applied immunoperoxidase techniques using antibodies to type IV collagen and laminin to show that they are composed of basement membrane material. Because the segmented, elongated shapes of these bodies reminded us of the larvae of butterflies, we coined the term "caterpillar bodies" to describe them. These bodies are similar in their composition to the Kamino bodies of Spitz's nevi, cylindrical bodies in adenoid cystic carcinoma, Civatte bodies of lichen planus, and the collagenous spherules seen in a number of conditions, and may provide a unique clue to the diagnosis of the porphyric bullous eruptions.