Penoscrotal extramammary Paget's disease: a review of 33 cases in a 20-year experience

Extramammary Paget's disease in men most frequently involves the penoscrotal area. The uncertainty of the outcome and of the relationship to the underlying adnexal carcinoma and associated internal malignancy still exists. From 1982 to 2001, 33 patients with penoscrotal extramammary Paget's disease were treated and followed up. Therapeutic modalities included carbon dioxide laser ablation (two patients) and local wide excision (31 patients). Split-thickness skin graft (22 patients), local scrotal flap (six patients), and primary closure (three patients) were utilized to reconstruct the penoscrotal defects after local wide excision. An underlying adnexal carcinoma occurred in seven of 33 patients (21.2 percent). The incidence of associated internal malignancy was 9.1 percent (three of 33 patients), including one concurrently and two nonconcurrently associated malignancies. Eight of 33 patients had local recurrence, representing an incidence of 24.2 percent. Three patients (9.1 percent) had distant metastasis and ultimately died of metastatic carcinoma. Of these patients, 31 were grouped according to the degrees of involvement: limited to the epidermis (group 1, n = 14), involvement of the adnexal gland and/or hair follicle (group 2, n = 10), and the presence of an underlying adnexal carcinoma (group 3, n = 7). Local wide excision with subsequent reconstruction by split-thickness skin graft was favored in this series. Patients with an underlying adnexal carcinoma or pathological invasion of the dermis (group 2 or 3) had a worse prognosis than patients without. From this study, it is difficult to address the particular relationship between the outcome and the associated internal malignancy.     

Expression of Hex during feather bud development

We studied proline-rich divergent homeobox gene Hex/Prh expression in the dorsal skin of chick embryo during feather bud development. Hex mRNA expression was first observed in the dorsolateral ectoderm and mesenchyme at 5 days, then in the epithelium and the dermis of the dorsal skin before placode (primordium of feather bud) formation and then was restricted to the placode and the dermis under the placode. Afterward, Hex expression was seen in the epidermis and the dermis of the posterior region of short bud. In accordance with Hex mRNA expression in the placode, Hex protein was observed in the epidermis as well as in the dermis of the placode. Immunoelectron microscopic study indicated that the protein located both in the nuclei and cytoplasm of the epidermis and the dermis at the short bud stage. The Wnt signaling pathway plays an essential role in the early inductive events in hair (Wnt3a and 7a) and feather (Wnt7a) follicles. The pattern of Hex expression in the epidermis was similar to that of Wnt7a, while little, if any, expression of Wnt7a was detected in the dermis under the placode or the dermis of the short bud compared with that of Hex, suggesting that Hex plays an important role in the initiation of feather morphogenesis.     

Enhancement of epigastric skin flap survival by adenovirus-mediated VEGF gene therapy

A novel approach to treat ischemic tissues by using gene therapy has recently been introduced on the basis of the angiogenic potential of certain growth factors. The authors investigated the effect of adenovirus-mediated gene therapy with vascular endothelial growth factor (VEGF) delivered into the subdermal space to treat compromised skin flaps. For this purpose, the epigastric skin flap model in rats, based solely on the right inferior epigastric vessels, was used. Thirty male Sprague-Dawley rats were divided into five groups of six rats each. Viral transfection with 108 plaque-forming units was performed 2 days before the epigastric flap elevation. Rats received subdermal injections of adenovirus encoding VEGF (Ad-VEGF) or green fluorescent protein (Ad-GFP) as treatment control. Another set of animals (n = 6) received no injections and were designated as control. To determine whether site of injection had an impact on flap viability, injections were given into the predicted local ischemic area (Ad-VEGF local, n = 6; Ad-GFP local, n = 6) and into the midline of the flap (Ad-VEGF midline, n = 6; Ad-GFP midline, n = 6). A flap measuring 8 x 8 cm was outlined on the abdominal skin extending from the xiphoid process proximally and the pubic region distally, to the anterior axillary lines bilaterally. Then, the epigastric flap was elevated as an island on the right inferior epigastric vessels and sutured back to its bed. Flap viability was evaluated at 7 and 14 days after the first operation. The epigastric flaps were scanned to the computer and areas of hypoxic and/or necrotic zones relative to total flap surface area were measured and expressed as percentages by using Image Pro Plus software. Specimens were taken for histologic evaluation at day 14 before the animals were killed. Combined area of necrotic and hypoxic zones as well as necrotic zone were decreased to 9.7 +/- 1.4 percent and 1.4 +/- 0.9 percent in Ad-VEGF local, and 11.8 +/- 1.9 percent and 3.5 +/- 1.64 percent in Ad-VEGF midline compared with the control and Ad-GFP treatment groups (control, 23 +/- 3.6 percent and 20.1 +/- 3.3 percent; Ad-GFP local, 24.8 +/- 4.8 percent and 16.2 +/- 5.9 percent; and Ad-GFP midline, 23.4 +/- 6.9 percent and 19.5 +/- 7.7 percent; p < 0.05). Histologic evaluation by light microscopy failed to demonstrate any quantitative difference in vascularity of skin flaps between the treatment groups. In this study, the authors demonstrated that adenovirus-mediated gene therapy using VEGF enhanced epigastric skin flap survival, as confirmed by the significant reduction in combined area of necrotic and hypoxic zones of the flap. Compared with the control, both local and midline subdermal injections of Ad-VEGF showed improvement in overall flap survival by 57.9 and 48.7 percent, respectively. The results of this study raise the possibility of using adenovirus-mediated therapeutic angiogenesis for safer flap surgery in high-risk patients.     

Structural and functional evaluation of modifications in the composite skin graft: cryopreserved dermis and cultured keratinocytes.

Structural and functional aspects of modifications in the composite skin graft consisting of cultured keratinocytes and cryopreserved dermis were determined. Cryopreserved human cadaveric dermis separated from skin by short and mild trypsinization was compared with dermis obtained by prolonged incubation in medium and with fresh dermis obtained by the same methods. All types of dermis were shown to retain normal ultrastructure and topographic organization, as detected by scanning and transmission electron microscope and immunofluorescence analysis. However, in fresh skin, the layers were more firmly attached, mechanical separation was more difficult, and residual epidermis often remained attached to the dermis. Keratinocytes attached better, began replication earlier, and generally reached higher cell numbers when cultured on trypsinized dermis than on medium-treated dermis. The performance of several modifications in the reconstitution and grafting procedures of the composite skin graft after transplantation to athymic mice was examined. Cultured epidermis combined onto trypsinized or medium-treated whole and meshed dermis, dermis pregrafted and allowed to take before transplanting epidermis on top, and keratinocytes grown into multiple epithelia on top of trypsinized meshed or whole dermis prior to grafting. The best grafting results were obtained with an "instant" reconstituted skin model: multiple epithelia grown in vitro combined immediately before grafting onto meshed trypsinized dermis. The transplantation results of this modification were significantly better than those of all the other modifications, including initial growth of keratinocytes into multiple epithelia on top of trypsinized dermis prior to grafting.     

Effect of diethylstilbestrol on skin sterols of the male rat

Diethylstilbestrol (DES) was injected in doses ranging from 600 micro g to 0.4 micrograms/kg body weight into mature male rats over a 3 wk period. Profound effects on skin morphology and on sterol content of skin were noted. The sebaceous glands atrophied and the epidermis lost granularity. The concentrations of all skin sterols, with the exception of cholesterol, were reduced. At a dose level of DES of 4 micrograms/kg there was still a perceptible reduction in the concentration of Delta(7)-cholestenol. Incubation of skin fragments with acetate-2-(14)C for 2 hr demonstrated a reduced uptake of (14)C into the nonsaponifiable fraction of skin lipids at all dose levels studied. Preliminary thin-layer chromatography of the nonsaponifiable fraction revealed that the uptake of (14)C into cholesterol was only slightly decreased; uptake into cholesterol precursors was decreased somewhat more. The epidermis and dermis were separated by incubation of skin with elastase and hyaluronidase. The epidermis contained at least three times as much sterol per mg dry weight as did the dermis. Unesterified cholesterol was the major sterol present in both layers; the other sterols were present mainly as esters. DES injection resulted in no change in the free sterol content but markedly reduced the ester content of the epidermis and dermis.     

Regional specificity of anuran larval skin during metamorphosis: dermal specificity in development and histolysis of recombined skin grafts

Summary Skins from back and tail were dissected from tadpoles of Rana japonica prior to resorption of the tail and separated into epidermis and dermis by treatment with neutral protease. Homotypically and heterotypically recombined skins were constructed from the separated epidermis and dermis and transplanted into the tail of the original tadpole. Skin grafts using dermis from tail region degenerated simultaneously with resorption of the tail. However, skin grafts containing dermis from back region survived on the posterior part of the juvenile frog beyond metamorphosis. Furthermore, all epidermis underlaid with dermis from back region formed secretory glands and became flattened epithelia characteristic of adult back skin, regardless of region from which the epidermis came. Even when epidermis isolated from tail skin was cultured inside a back skin graft, the tail epidermis survived forming an epithelial cyst and developed secretory glands. These results suggest that regional specificities of anuran larval skin, i.e., development of back skin and even histolysis of tail skin, are determined by regionally specific dermis. The results also suggest that some of epidermal cells of tail skin are able to differentiate into epithelial cells similar to back skin of the adult under the influence of back dermis.     

Histopathological and cellular studies of a case of cutaneous radiation syndrome after accidental chronic exposure to a cesium source.

This study was designed for the histopathological, cellular and biochemical characterization of a skin lesion removed surgically from a young male several months after accidental exposure to cesium-137, with an emphasis on expression of transforming growth factor beta1 (TGFB1) and tumor necrosis factor alpha (TNFA) and the occurrence of apoptosis. Under a hypertrophic epidermis, a highly inhomogeneous inflammatory dermis was observed, together with fibroblastic proliferation in necrotic areas. Immunostaining revealed overexpression of TGFB1 and TNFA inside the keratinocytes of the hypertrophic epidermis as well as in the cytoplasm of the fibroblasts and connective tissue of the mixed fibrotic and necrotic dermis. Inside this dermis, the TUNEL assay revealed areas containing numerous apoptotic fibroblasts next to areas of normal viable cells. Overexpression of TGFB1 was found in the conditioned medium and cellular fractions of both hypertrophic keratinocytes and fibrotic fibroblasts. This overexpression lasted for at least three passages in tissue culture. The present observations were consistent with the central role of TGFB1 in the determination of chronic radiation-induced damage to the skin and a significant involvement of TNFA. In addition, programmed cell death appeared to take place during the remodeling of the mixed fibrotic and necrotic tissue.     

Significant decreases in the intensity of staining for proteins and protein thiols in basal-cell epitheliomas (basaliomas) as compared to normal skin

Microphotometric measurements of fast reacting protein thiols (PSHr) and proteins were performed on freshly frozen sections of samples from normal skin (26 cases as controls) and from 45 basal cell epitheliomas (basalioma; BCE). The intensity of the staining (E/micron2) for both proteins and PSHr was significantly higher in normal epidermis than in the adjacent dermis. The values of QE (quotient of values observed in the epidermis divided by those observed in the dermis) were calculated to be 3.48 for proteins (QE, Prot) and 4.62 for PSHr (QE, PSHr). In cases of BCE, significantly lower QE values were found: QE, Prot = 2.16 and QE, PSHr = 1.72. The decrease of QE, PSHr was due to a decrease in the staining intensity observed in the BCEs, whereas practically no changes occurred in the adjacent dermis. The decrease of QE, Prot was mainly caused by a decrease in the staining intensity in the BCE (by 68%) as well as in the adjacent dermis (by 36%). By dividing the mean extinction value (E/micron2) for PSHr by the E/micron2 for proteins, a new quotient, PSHr/Prot, is obtained which can serve as a quantitative measure of the content of the tissue proteins of PSHr. The proteins of normal epidermis contained more PSHr than dermal proteins. The proteins of BCEs also contained more PSHr than those of the adjacent dermis, but the PSHr/Prot values of both tissues were 1.5 to 1.6 times greater than the corresponding values for normal epidermis and dermis, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Monoclonal antibody analysis of skin in chronic murine graft vs host disease produced across minor histocompatibility barriers

Chronic graft vs host disease (GVHD) across minor histocompatibility barriers was produced in BALB/c mice by the injection of spleen cells from B10.D2 mice. Changes in the skin were analyzed in frozen sections using a panel of monoclonal antibodies detected by immunoperoxidase methods. Compared to control animals, a number of changes occurred in the skin of animals with chronic GVHD. In the epidermis, there were increased numbers of Thy-1-positive dendritic cells; keratinocytes expressed Thy-1 and Ia antigens. T lymphocytes appeared in both dermis and epidermis. In the early stages, cells with "helper" and "suppressor" phenotypes were present, while at later times "helper" cells remained in the epidermis and "suppressor" cells remained in the dermis. Cells bearing markers of macrophages were prominent in both dermis and epidermis after the second week. Of great interest was the appearance of spindle-shaped cells in the dermis which expressed Thy-1 and Ia. These cells resembled fibroblasts which may be activated to produce the excess collagen seen in the skin of chronic GVHD.     

Reversing the detrimental effect of adriamycin on skin grafts in rats

We evaluated in a rat model the effects of a homologous fibrin glue in reversing the effects of Adriamycin on adherence and take of skin grafts. A total of 40 male Fisher rats were used in the study. During the first phase of the experiment, the animals were assigned to either group I (N = 10) receiving normal saline or group II (N = 10) receiving 6 mg/kg Adriamycin by tail vein injection 24 hours before surgery. Skin grafts with and without fibrin glue were placed over wounds in the backs of the animals and adherence was measured at 24 and 48 hours. In the second phase (N = 20), the experiment was repeated, this time evaluating the total area of skin graft take at 7 days. Fibrin glue was found to increase adherence and take of skin grafts in all Adriamycin-treated animals.     

Cellular responses in the skin of the trout (Oncorhynchus mykiss) exposed to temperature elevation

The skin of rainbow trout was examined at the ultrastructural and cytochemical level after a 3–h exposure to an elevation of the water temperature, from 15 to 22° C. Within 3 h, the thickness of the epidermis had significantly ( P <0·05) decreased when compared to control fish. After 24 h it was restored, and from day 4 onwards even increased above control levels. The thickening of the epidermis was associated with appearance of many mitotic cells, not observed in control fish. Within 24 h many apoptotic epidermal cells were found, indicating enhanced ageing of the cells. Filament cells from the outer epidermal layers synthesized vesicles with peroxidasc activity within 3 h after temperature elevation. This enzyme was found also in apoptotic as well as in necrotic filament cells. Mucous cells became elongated and their mucosomes displayed peroxidase activity. Occasionally electrondense, probably serous, mucosomes appeared. In the epidermis rodlet cells were found. Both epideimis and dermis, became invaded by many lymphocytes and macrophages. The latter contained vesicles with peroxidase activity. Pigment–containing cytoplasmic extensions of melanocytes penetrated the epidermis while iridocytes disappeared from the dermis. The synthetic activity of dermal fibroblasts was stimulated. These results show that a moderate temperature elevation has pronounced and prolonged effects on the skin of the exposed fish. The effects are to a high extent comparable with those of stressors such as heavy metals, acid water or wounding.     

Embryonic dermal condensation and adult dermal papilla induce hair follicles in adult glabrous epidermis through different mechanisms

Hair induction in the adult glabrous epidermis by the embryonic dermis was compared with that by the adult dermis. Recombinant skin, composed of the adult sole epidermis and the embryonic dermis containing dermal condensations (DC), was transplanted onto the back of nude mice. The epidermis of transplants formed hairs. Histology on the induction process demonstrated the formation of placode-like tissues, indicating that the transplant produces hair follicles through a mechanism similar to that underlying hair follicle development in the embryonic skin. An isolated adult rat sole skin piece, inserted with either an aggregate of cultured dermal papilla (DP) cells or an intact DP between its epidermis and dermis, was similarly transplanted. The transplant produced hair follicles. Histology showed that the epidermis in both cases surrounded the aggregates of DP cells. The epidermis never formed placode-like tissues. Thus, it was concluded that the adult epidermal cells recapitulate the embryonic process of hair follicle development when exposed to DC, whereas they get directly into the anagen of the hair cycle when exposed to DP. The expression pattern of Edar and Shh genes, and P-cadherin protein during the hair follicle development in the two types of transplants supported the above conclusion.     

Innervation and cholinesterase activity in the skin of albino and desert rats

The distribution of nerves and cholinesterase activity in the skin of the desert and albino rats has been studied using both histological and histochemical techniques. In the desert rat, the skin was richly innervated. Specific cholinesterase was concentrated in the nervous network of the dermis and around the hair follicles, in the nerve bundles of the dermis, in perivascular nerves, in fine intra-epithelial nerves and in sensory end organs in the junctional area between the dermis and epidermis. In the albino rat, specific cholinesterase was concentrated in the sebaceous glands. The positive cholinesterase activity that was seen in the desert rat in intra-epithelial nerves, and in dermal and hair follicle networks could not be demonstrated.     

Expression of the WE3 antigen in newt epithelium originating from subcutaneous grafts of skin

mAb WE3 recognizes an antigen that is developmentally regulated in the wound epithelium of regenerating newt limbs. The antigen is precociously expressed when pieces of WE3-negative wound epithelium are grafted subcutaneously (Tassava et al.: Recent Trends in Regeneration Research. New York: Plenum Publishing Co., pp. 37-49, 1989). In the present study, we investigated whether the WE3 antigen is expressed in epidermis of subcutaneous grafts of skin. Small pieces of limb skin were grafted into small tunnels in the lower jaw, limb, and tail, oriented either the same as (epidermis facing out) or opposite to (epidermis facing in) the orientation of the host skin. In most cases, the epithelium migrated from the graft along the wounded surface of the tunnel, closed onto itself, and formed a multilayered "emigrant" epithelium. Infrequently, the migrating epithelium combined with the wound epithelium of the insertion wound. In no case did the epithelium migrate over the cut edge of the grafted dermis. Reactivity to mAb WE3 was first seen at 4 days after grafting, when the migrating epithelium had almost closed over onto itself. By 6 days and thereafter, the entire emigrant epithelium was reactive to mAb WE3. While initially restricted to the emigrant epithelium, at 10 days after grafting and thereafter, reactivity was also seen in the epidermis that remained in contact with the dermis. Expression of the WE3 antigen was not influenced by the orientation of the graft nor by the graft site. The results show that, compared to amputated limbs, the epithelium originating from these grafts precociously expresses the WE3 antigen. Also, epidermis of grafted skin is capable of expressing the WE3 antigen.     

Stimulation of rat cutaneous fibroblasts and their synthetic activity by implants of powdered nacre (mother of pearl)

The components of the cutaneous envelope, the epidermis and the dermis, change in response to aging or environmental stress factors. The fibroblasts involved in maintaining skin tone are the main targets. Nacre, mother of pearl, from Pinctada maxima, which can stimulate and regulate bone forming cells, was implanted in the dermis of rats to test its action on the skin fibroblasts. This report describes the effect of nacre on the skin fibroblast recruitment and physiological activity. It resulted in enhanced extracellular matrix synthesis and the production of components implicated in cell to cell adhesion and communication (such as decorine) and in tissue regeneration (type I and type III collagens). The nacre implant produced a well vascularized tissue. The physiological conditions in the region around the implant are thus those required for the positive interactions between the dermis and epidermis which are fundamental for the physiological function of the skin.     

Expression of angiotensin II AT2 receptors in the rat skin during experimental wound healing.

We localized and characterized angiotensin II AT1 and AT2 receptors in the skin of 2-week-old rats during experimental wound healing. Both AT1 and AT2 were present in the skin. Three days after wounding, the expression of angiotensin II receptors was significantly enhanced in the dermis as well as in a localized band within the superficial dermis of the skin surrounding the wound. The major proportion of this increase was due to angiotensin II AT2 receptors. Our results suggest a physiological role for AT2 receptors in the process of tissue repair.     

Evaluation of CT Perfusion Biomarkers of Tumor Hypoxia

BackgroundTumor hypoxia is associated with treatment resistance to cancer therapies. Hypoxia can be investigated by immunohistopathologic methods but such procedure is invasive. A non-invasive method to interrogate tumor hypoxia is an attractive option as such method can provide information before, during, and after treatment for personalized therapies. Our study evaluated the correlations between computed tomography (CT) perfusion parameters and immunohistopathologic measurement of tumor hypoxia.MethodsWistar rats, 18 controls and 19 treated with stereotactic radiosurgery (SRS), implanted with the C6 glioma tumor were imaged using CT perfusion on average every five days to monitor tumor growth. A final CT perfusion scan and the brain were obtained on average 14 days (8–22 days) after tumor implantation. Tumor hypoxia was detected immunohistopathologically with pimonidazole. The tumor, necrotic, and pimonidazole-positive areas on histology samples were measured. Percent necrotic area and percent hypoxic areas were calculated. Tumor volume (TV), blood flow (BF), blood volume (BV), and permeability-surface area product (PS) were obtained from the CT perfusion studies. Correlations between CT perfusion parameters and histological parameters were assessed by Spearman’s ρ correlation. A Bonferroni-corrected P value < 0.05 was considered significant.ResultsBF and BV showed significant correlations with percent hypoxic area ρ = -0.88, P < 0.001 and ρ = -0.81, P < 0.001, respectively, for control animals and ρ = -0.7, P < 0.001 and ρ = -0.6, P = 0.003, respectively, for all animals, while TV and BV were correlated (ρ = -0.64, P = 0.01 and ρ = -0.43, P = 0.043, respectively) with percent necrotic area. PS was not correlated with either percent necrotic or percent hypoxic areas.ConclusionsPercent hypoxic area provided significant correlations with BF and BV, suggesting that CT perfusion parameters are potential non-invasive imaging biomarkers of tumor hypoxia.     

Biological and physical factors influencing the successful engraftment of a cultured human skin substitute

Skin tissue may be engineered in a variety of ways. Our cultured skin substitute (Graftskin, living skin equivalent or G-LSE), Apligraftrade mark, is an organotypic culture of skin, containing both a "dermis" and "epidermis." The epidermis is an important functional component of skin, responsible for biologic wound closure. The epidermis possesses a stratum corneum which develops with time in culture. The stratum corneum provides barrier function properties and gives the LSE improved strength and handling characteristics. Clinical experience indicated that the stratum corneum might play an important role in improving the clinical utility of the LSE. Handling and physical characteristics improved with time in culture. We examined the LSE at different stages of epidermal maturation for barrier function and ability to persist as a graft. LSE grafted onto athymic mice before significant development of barrier function did not withstand bandage removal at 7 days postgraft. LSE grafted after barrier function had been established in vitro were able to withstand bandage removal at day 7. Corneum lipid composition and structure are critical components for barrier function. Media modifications were used in an attempt to improve the fatty acid composition of the stratum corneum. The barrier developed more rapidly and was improved in a serum-free, lipid-supplemented condition. Lipid lamellar structure was improved with 10% of the stratum corneum exhibiting broad-narrow-broad lipid lamellar arrangements similar to human skin. Fatty acid metabolism was not appreciably altered. Barrier function in vitro was 4- to 10-fold more permeable than human skin. Epidermal differentiation does not compromise engraftment or the wound healing ability of the epidermis. The stratum corneum provides features beneficial for engraftment and clinical use. (c) 1996 John Wiley & Sons, Inc.     

Nacre-driven water-soluble factors promote wound healing of the deep burn porcine skin by recovering angiogenesis and fibroblast function

To assess the recovery effect of water-soluble components of nacre on wound healing of burns, water-soluble nacre (WSN) was obtained from powdered nacre. Alterations to WSN-mediated wound healing characteristics were examined in porcine skin with deep second-degree burns; porcine skin was used as a proxy for human. When WSN was applied to a burned area, the burn-induced granulation sites were rapidly filled with collagen, and the damaged dermis and epidermis were restored to the appearance of normal skin. WSN enhanced wound healing recovery properties for burn-induced apoptotic and necrotic cellular damage and spurred angiogenesis. Additionally, WSN-treated murine fibroblast NIH3T3 cells showed increased proliferation and collagen synthesis. Collectively, the findings indicate that WSN improves the process of wound healing in burns by expeditiously restoring angiogenesis and fibroblast activity. WSN may be useful as a therapeutic agent, with superior biocompatibility to powdered nacre, and evoking less discomfort when applied to a wounded area.     

Dorsal skin responses to subchronic ultraviolet B (UVB)-irradiation in Wistar-derived hypotrichotic WBN/ILA-Ht rats

Dorsal skin responses to a subchronic UVB-irradiation (10kJ/m2/rat /day), were examined in Wistar-derived hypotrichotic WBN/ILA-Ht rats for up to 3 months. Hyperplasia of epidermal cells and hair follicle epithelial cells as well as parakeratosis developed at 1 month and progressed thereafter, resulting in a prominent epidermis thickening and formation of epidermal ingrowths projecting into the dermis. At the same time, the percentage of proliferating cell nuclear antigen (PCNA)-positive epidermal cells significantly increased after I month. In some portions of the hyperplastic epidermis, especially of the epidermal ingrowths, keratinocytes were somewhat pleomorphic and migrated into the dermis. In the upper dermis, edema with capillary congestion, mast cell infiltration and fibroblast proliferation developed at I month, and the intensity of edema and the number of dermal mast cells was most prominent at 3 months. Edema spread to the epidermis, resulting in intercellular edema and subsequent dissociation of epidermal cells. Degeneration of collagen fibers was also detected in the upper dermis, especially beneath the epidermis. In addition, although not significant because of a large individual difference, the serum IgE concentration, showed a tendency to increase after 2 months. The present study clarified the characteristics of the dorsal skin responses to a subchronic UVB-irradiation in rats.