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Previous studies suggest that altered peripheral blood circulation might be associated with erythema or inflammation in atopic dermatitis (AD) patients. However, the overall structure of blood vessels and capillaries in AD skin is poorly understood because most studies have involved light-microscopic observation of thin skin sections. In the present study, we compared the 3-dimensional structures of peripheral blood vessels of healthy subjects and AD patients in detail by means of 2-photon microscopy. In skin from healthy subjects, superficial vascular plexus and capillaries originating from flexous blood vessels were observed. However, skin from AD patients contained thickened, flexuous blood vessels, which might be associated with increased blood flow, in both erythematous and nonlesional areas. However, patients with lichenification did not display these morphological changes. Bifurcation of vessels was not observed in either erythematous or lichenification lesions. These results might be helpful for developing new clinical strategies to treat erythema in AD patients.

Sclerosing perineurioma is a relatively rare tumor that has remained widely unknown since first reported by Fetsch in 1997. To our knowledge, no large or small series of claudin-1 in sclerosing perineurioma has been confirmed to date. We collected 7 new cases of sclerosing perineurioma. Six patients were female, and 1 was male. The patients' age ranged from 15 to 58 years (mean, 36.6 years; median, 42.0 years). The primary reason for consultation at the outpatient clinics was a slowly enlarging mass. The preoperative durations were available for 4 of the 7 cases and ranged from 2 to 7 years. Six tumors were located in the fingers, and the other tumor was found in the palm. The sizes ranged from 4 to 12 mm in diameter (mean, 6.7 mm; median, 6.0 mm). Microscopically, all tumors were nodular lesions, with sclerotic stroma involving reticular dermis primarily consisting of small oval epithelioid cells and plump spindle cells, scattered and arranged in corded, trabecular, reticular, and/or whorled growth patterns. The neoplastic cells were immunoreactive for epithelial membrane antigen (7 of 7) and glucose transporter 1 (7 of 7). The periodic acid-Schiff reaction and positive immunostaining for type IV collagen were observed directly adjacent to the lesional cells in all cases (6 of 6). Claudin-1 immunostaining was positive in all 7 cases, suggesting that claudin-1 may serve as a helpful diagnostic marker for sclerosing perineurioma.

Anti-p200 pemphigoid is an autoimmune subepidermal blistering disease characterized by circulating and tissue-bound antibodies against a 200-kd glycoprotein (p200) of the human dermis. We reviewed 10 lesional biopsies from seven patients with anti-p200 pemphigoid in an attempt to define typical histopathologic features of this disease. All biopsy specimens showed subepidermal blistering and a moderate to dense inflammatory infiltrate in the upper dermis. Immunohistochemical analysis localized type IV collagen to the dermal side of the blister, suggesting that split formation occurred within the lamina lucida of the cutaneous basement membrane. The inflammatory infiltrate was composed almost exclusively of neutrophils in six biopsies and contained a mixture of neutrophils and eosinophils in the remaining four. In three specimens, microabscess formation in the papillary dermis adjacent to the blister cavity was noted. Neutrophilic and eosinophilic spongiosis was found in five and three biopsies, respectively. We conclude that histopathology of anti-p200 pemphigoid is characterized by subepidermal blistering and a superficial inflammatory infiltrate, which is usually dominated by neutrophils but occasionally contains significant numbers of eosinophils. While this microscopic picture mimics that of linear IgA disease, dermatitis herpetiformis, or bullous pemphigoid, it should also alert a histopathologist to the possibility of anti-p200 pemphigoid and prompt immunofluorescence and immunoblotting studies for definite diagnosis or exclusion of this autoimmune subepidermal blistering disease.

A 38-year-old woman had a polypoid nodule on her scalp. The lesion histopathologically demonstrated an extensive myxoid lobular lesion associated with a nonmyxoid and cellular area in the peripheral area of the lesion. The features of the peripheral cellular area resembled those of palisaded encapsulated neuroma (PEN). Most of the lesion was myxoid, with a large lobule in which several thin fibrous septa were present, dividing it into smaller lobules. The myxomatous area was composed of spindle cells or stellate cells with elongated cytoplasmic processes. There was a loose cellular network with a reticular and netlike network pattern or a lamellar pattern. From the immunohistochemical findings, as well as the histopathologic features, the whole lesion was thus considered to be a PEN, whereas the main, myxoid, lobular lesion was thought to have been caused by myxoid changes within a PEN, namely, myxoid PEN. It cannot be completely ruled out, however, that this case could be that of a nerve sheath myxoma with a PEN/PEN-like lesion. Thus, the present case may suggest that PEN can show extensive myxoid change or may demonstrate a relationship between PEN and nerve sheath myxoma.

Background and Aims: The imbalance between synthesis and degradation of extracellular matrix (ECM) proteins is a characteristic feature in chronic pancreatitis. We evaluated the relationship between type IV collagen structure in the basement membrane (BM) and the development of acinar atrophy or the regeneration from acinar injury., Methods: Three different models of pancreatitis were induced in rats by repetitive intraperitoneal injections of 500 mg/100 g body weight of arginine (Arg) or 20 microg/kg body weight of caerulein (Cn) or a single retrograde intraductal infusion of 40 microL/100 g body weight of 3% sodium taurocholate (NaTc). We examined the changes in type IV collagen structure by immunostaining, and the serial changes in the gelatinolytic activity of pro- and active matrix metalloproteinase-2 by zymography in these models of pancreatitis., Results: The pancreas appeared to be histologically normal on day 35 after the first intraperitoneal Cn injection and on day 42 after intraductal infusion of NaTc, whereas 85% to 90% of acinar tissue was replaced by fatty tissue and dilated pancreatic ducts on day 54 after the first intraperitoneal Arg injection. Immunoreactivity for type IV collagen appeared as a discontinuous line along the BM of ducts, vessels, tubular complexes, and acinar cells on day 40 in Arg-induced pancreatitis, whereas it was detected as a continuous line along the BM on day 35 in Cn-induced pancreatitis and on day 42 in NaTc-induced pancreatitits. Gelatinolytic activity of active MMP-2 increased significantly from day 13 to day 40 after the first intraperitoneal Arg injection, whereas it decreased to the baseline level on day 35 after the first intraperitoneal Cn injection and on day 42 after intraductal infusion of NaTc., Conclusions: Our findings indicate that a long-term increase in gelatinolytic activity of active MMP-2 in Arg-induced pancreatitis causes continuous disorganization of type IV collagen in the BM and progressive acinar atrophy, whereas a transient increase in gelatinolytic activity of active MMP-2 is involved in the regeneration of type IV collagen structure in the BM and recovery from acinar injury.

Purpose: Cultivated limbal epithelial transplantation using an amniotic membrane (AM) carrier is now widely used for ocular surface reconstruction. The reasons for the exceptional success of AM as a carrier are not fully understood but are believed to be related to its unique composition. In this project we characterize, at the ultrastructural level, the extracellular matrix (ECM) components present in AM. We also compare the distribution of ECM components of cellular AM with that of denuded AM., Methods: Scanning, transmission, and atomic force microscopy was used to examine the structure of cellular and denuded amniotic membranes. Immunogold labeling with a panel of antibodies against ECM molecules was carried out on cellular and denuded AM., Results: Heparan sulfate, fibronectin, and laminin were present at high concentration in the lamina densa, Collagen IV was the major component of the basal lamina. Type I collagen was confined to the stroma along with significant amounts of keratan and chondroitin sulfate. Both cellular and denuded AMs had similar distributions of the ECM components., Conclusions: We were able to determine the distribution of ECM molecules in the lamina densa, basal lamina, and stroma of AM at the ultrastructural level. The removal of amniotic epithelial cells using our protocol does not appear to have any significant effects on the structure of the basal lamina or the distribution of ECM components.

Background: Cells of melanocytic naevi and cutaneous malignant melanomas (MM) are surrounded by a basement membrane (BM)., Aim: To scrutinize any difference between the deposits of alpha1 (IV) and alpha5 (IV) collagen chains in melanocytic naevi and MM., Methods: A total of 27 common melanocytic naevi, 11 dysplastic naevi, 21 atypical naevi (melanocytomas) including Spitz and non-Spitz types, as well as 24 MM were studied. Their phenotypic and functional characteristics defined by immunohistochemistry using a panel of antibodies, including those directed to the alpha1 (IV), alpha3 (IV) and alpha5 (IV) collagen chains., Results: Almost all naevi and half the melanocytomas exhibited a strong positivity for the alpha1 (IV) collagen chain. By contrast, the remaining melanocytomas and MM presented a heterogeneous staining pattern for the alpha1 (IV) collagen chain. One third of the naevi, 23% of the MM without cutaneous micrometastasis and 83% of MM with cutaneous micrometastasis showed discrete cytoplasmic positivity for the alpha5 (IV) collagen chain. All other melanocytic tumours were negative for this antibody. Rare MM cells in transepidermal migration were stained with the anti-alpha1 (IV) or alpha5 (IV) collagen chain antibodies. No immunoreactivity for the alpha3 (IV) collagen chain was disclosed in any of the samples., Conclusion: We report the expression of alpha1 (IV) and alpha5 (IV) collagen chains in naevi and MM. The inconsistent staining pattern for alpha1 (IV) collagen chain in phenotypically atypical melanocytomas and in MM highlight the heterogeneity in both cell differentiation and stroma-tumour interactions. This biological aspect may be related to neoplastic progression and influence metastatic potential.

The type IV collagen (Col-IV) consists of 3 alpha chains. Six different alpha chains [alpha1(IV), alpha2(IV), alpha3(IV), alpha4(IV), alpha5(IV), and alpha6(IV)] have been identified, and their combination is considered to be organ specific. We investigated the immunohistochemical localization of alpha (IV) chains in the basement membrane (BM) of the pancreatic duct in human normal pancreas (NP) and pancreatic diseases. Fifty specimens [10 NP, 10 chronic pancreatitis (CP), 10 intraductal papillary mucinous tumor (IPMT), and 20 pancreatic adenocarcinoma (PAC)] were examined. Alpha 1(IV), alpha2(IV), alpha5(IV), and alpha6(IV) were linearly immunostained in NP, CP, and IPMT. In PAC, alpha(IV) and alpha2(IV) were immunostained, but alpha5(IV) and alpha6(IV) were not stained in 30% and 40% of the cases, respectively. In conclusion, immunohistochemically, the Col-IV of human normal pancreatic duct consisted of alpha1(IV), alpha2(IV), alpha5(IV), and alpha6(IV). alpha5(IV) and alpha6(IV) were frequently absent in PAC, and their absence might be related to the invasion of cancer cells.

Introduction: Pancreatic tissues are almost completely restored to normal after an attack of acute pancreatitis, once the cause of the disease is removed. Transforming growth factor (TGF)-beta and extracellular matrix (ECM) are known to play an important role in the process of wound healing in pathologic diseases. Tissue repair is a process regulated by a balance between synthesis and degradation of ECM., Aims: To elucidate the role of TGF-beta, ECM, and matrix metalloproteinase (MMP) in the process of regeneration occurring after acute necrotizing pancreatitis., Methodology: Acute necrotizing pancreatitis was induced by intraperitoneal injection of 500 mg/100 g body weight of L-arginine in male Wistar rats. Expression of TGF-beta1 and ECM messenger RNA (mRNA) was determined by Northern blot analysis, and that of MMP-1 and MMP-2 mRNA was examined by the reverse transcription polymerase chain reaction (RT-PCR). Immunoreactivity for ECM components, TGF-beta1, and MMP-2 in the pancreas was assessed by using a monoclonal antibody., Results: TGF-beta1 mRNA expression reached a peak value on day 2.5, with a decrease on day 3, and reached the control level on day 7. Procollagen types III and IV and fibronectin mRNA reached a peak value on day 2.5, whereas the expression level of procollagen type I mRNA was maximal on day 3, and gradually decreased to control levels by day 7. MMP-2 mRNA was significantly elevated on day 3, and peaked on day 5, whereas MMP-1 mRNA levels did not change throughout the observation period. Immunoreactivity for MMP-2 was observed around disrupted acinar cells and interstitial spaces on day 3, and maximally on day 7. Immunoreactivity for fibronectin was detected around disrupted acinar cells and interstitial spaces. On day 7, it was less than on day 5 around disrupted acinar cells and interstitial spaces, whereas in the regenerated acinar cells, it was undetected., Conclusion: Our results show that TGF-beta1 mRNA expression peaked earlier than that of ECM mRNA. Furthermore, increased level of the MMP-2 transcript was followed by disappearance of fibronectin. Our findings suggest that TGF-beta1 plays an important role in ECM production in the early phase of acute pancreatitis, and that MMP-2 is involved in the subsequent healing process.