Effect of RU 486 on the atrophogenic and antiinflammatory effects of glucocorticoids in skin.

Clobetasol-17-propionate (CP), a synthetic glucocorticoid (GC), reduced skin thickness in rats. Both the subcutaneous injection and topical applications of RU 486 counteracted CP-induced reduction in skin thickness. Topical application of the CP cream completely inhibited the ear edema produced by croton oil. A less potent GC, hydrocortisone-17-butyrate, also inhibited ear edema. This antiinflammatory effect was not abolished by the subcutaneous injection or topical application of RU 486. These observations suggest that GC-induced skin atrophy is mediated by glucocorticoid receptors (GRs), while the inhibition of croton oil-induced inflammation by GC is primarily related to the direct effects of GC, which are not mediated by GRs. Our findings suggest that RU 486 inhibits the atrophogenic effect of GCs without interfering with their antiinflammatory effect. Dissociation of antiinflammatory and atrophogenic activity of GC seems favorable in treating inflammatory skin diseases lacking epidermal proliferation.

Primary cutaneous meningioma on the scalp: report of two siblings.

Primary cutaneous meningioma (PCM) is a rare tumor whose pathogenesis is quite obscure. We reported PCMs occurring on almost the same occipital region of two siblings studied by histology, immunohistochemistry, and electron microscopy. Both lesions were attached to duras, but extracranial. One lesion was histologically diagnosed as meningothelial meningioma; its tumor cells showed electron microscopically interdigitating cytoplasmic processes with junctional complexes. The other was interpreted as fibroblastic meningioma; its tumor cells were arranged linearly in a stepping-stone arrangement and had small dense bodies in the cytoplasm. The tumor cells stained positively with anti-vimentin antibody. Both lesions had adenomatous hyperplasia of the eccrine glands. Although the histologic and electron microscopic features of these two lesions slightly differed from each other, their pathogenesis was essentially considered to be acoelic or rudimentary meningocele.

A case of Bowen's disease with tissue eosinophilia.

An 85-year-old Japanese man with Bowen's disease on the left inguinal area is reported. Most of the inflammatory cells adjacent to the tumor were eosinophils. Tissue eosinophilia spontaneously improved after biopsy.

A case of chronic GVHD following bone marrow transplantation from a phenotypically HLA-matched unrelated donor.

A 45-year-old male with chronic myelocytic leukemia who received a bone marrow transplantation from a phenotypically HLA-matched unrelated donor developed chronic GVHD on day 100 post transplantation. He developed a slight fever, malaise, hepatic dysfunction and extensive itchy erythema with scaling over his entire body. The inflammatory skin lesion developed into erythroderma in about two weeks. H&E staining of a skin biopsy revealed eosinophilic bodies and a lymphocytic infiltration in the dermis and epidermis, which were compatible with the early phases of chronic GVHD. Immunohistochemistry revealed that keratinocytes expressed dense HLA-DR and ICAM-1 epitopes. Langerhans cells (CD1a+ cells) had disappeared from the epidermis. Many T cells (CD3+ cells) had migrated into the epidermis as well as into the reticular dermis. The majority of the T cells in the epidermis were CD8+ cells, while almost all the T cells in the dermis were CD4+ cells. These immunohistochemical features were similar to those previously reported for acute cutaneous GVHD. Despite the corticosteroid therapy, the eruptions did not disappear. The patient was then treated with whole body bath-methoxsalen (Oxsoralen) plus ultraviolet A (UVA). The bath-psoralen plus UVA therapy was effective in this patient.

Psoriasis verrucosa showing peculiar histologic features.

A 60-year-old man had a 10-year history of linearly arranged verrucous papules on his left fingers in addition to psoriatic erythematosquamous papules and plaques on his trunk and extremities. The verrucous papules were clinically classified into two types: dome-shaped papules with a keratotic plug and crater-shaped papules with a central depression. Histopathologically, the former showed cup-shaped acanthosis with a parakeratotic column containing Munro's microabscesses, while the latter showed a cup-shaped epidermal invagination with Kogoj's spongiform pustule-like changes. Both types of papules were clinically diagnosed as psoriasis verrucosa, but their histologic features differed from those reported previously.

Lichen sclerosus et atrophicus. A histological, immunohistochemical and electron microscopic study.

We studied three cases of genital lichen sclerosus et atrophicus (LSA) using histological, immunohistochemical and ultrastructural techniques to elucidate the characteristics of the collagen fibres, the elastic fibres and the interfilamentous matrix in the upper dermal homogeneous zone. In the early stages of LSA, the homogeneous zone caused elaunin fibres to push downwards and partially disappear, the collagen fibres were presumably phagocytosed by fibroblasts, and there were peculiar cells containing numerous vacuoles in the cytoplasm. In the advanced stages of LSA, the homogeneous zones showed newly formed collagen fibres and amorphous, dispersed, medium electron-dense substances that were probably composed of elastin or elastin-like substances and microfilaments originating from the collagen fibres. Immunohistochemically, there were numerous anti-aortic alpha-elastin-positive substances, but there was no positivity for anti-amyloid P component. These findings suggest that in advanced LSA a hybrid substance (elastocollagenous mass) between collagen fibres and elastic fibres may be formed in the homogeneous zone.

Neutrophilic dermatosis of the face associated with aortitis syndrome and Hashimoto's thyroiditis.

This is the first reported case of neutrophilic dermatosis of the face (Sweet's syndrome) associated with aortitis syndrome (Takayasu arteritis) and Hashimoto's thyroiditis. The patient was a 39-year-old Japanese female for whom corticosteroid therapy was effective.

Evaluation of the antigen specificity of the cellular infiltrate at the delayed type hypersensitivity reaction site with the use of an antigen-specific T cell clone.

Antigen specific T lymphocytes in delayed type hypersensitivity (DTH) test sites were analyzed in cell-transfer experiments. T lymphocytes from B6 mice were transferred into B6PL mice which differ from B6 at the Thy1 allele. When peritoneal exudate cells (PEC) from ovalbumin (OA)-immunized B6 mice were transferred into B6PL mice intravenously, DTH reaction was observed on footpads. A greater number of B6 T cells was identified at the DTH site. OA-reacting B6 T clones were then transferred with antigens into the footpads of B6PL mice. DTH reaction was induced at the footpads. More T cell clones were identified at the DTH test sites than in the control.

Detection of human papillomavirus type 2a DNA in verrucae vulgares by electron microscopic in situ hybridization.

Electron microscopic in situ hybridization (EMISH) of common warts (verrucae vulgares) of the hands was performed using a biotinylated human papillomavirus type 2a (HPV-2a) DNA probe and immunogold labelling of ultrathin sections of 2% glutaraldehyde-fixed, Lowicryl K4M-embedded tissues. It was first established that the warts contained HPV-2a DNA by light microscopic in situ hybridization. The HPV-2a probe chiefly labelled cells in the horny, granular and upper spinous layers of the epidermis, and labelling decreased towards the basal cell layer. The gold particles were located precisely on the viral particles in the nuclei of granular cells. The lower limit of detection by EMISH was found to be the keratinocytes of the third cellular layer above the basal cells. These keratinocytes showed evidence of a viral cytopathic effect, suggesting that vegetative DNA replication in infected keratinocytes occurs at least as early as this level of the epidermis.

Acquired tufted angioma showing spontaneous regression.

We report a 62-year-old woman with acquired tufted angioma. Several scattered reddish nodules were present on the neck and upper chest. During a follow-up period of 6 months, some of the lesions showed transient spontaneous regression and one disappeared completely. Electron microscopy revealed that a few tumour cells contained Weibel-Palade bodies in their cytoplasm.

Scanning electron microscopy of the epidermal lamina densa in normal human skin.

The lamina densa of normal human epidermis was exposed by treatment with 1 M sodium chloride and was examined by high-power scanning electron microscopy before and after trypsinization. Localization of type IV collagen in the lamina densa was also studied by transmission and scanning immunoelectron microscopy. Before trypsinization, the surface of the lamina densa consisted of microridges and microvalleys. The microridges varied in height and were connected with each other. They were arranged in a concentric fashion around the tips of the dermal microprojections. At a higher magnification, the surface of the lamina densa was composed of densely packed cobblestone-like structures approximately 7-15 nm in size, between which were interspaces 4-11 nm wide. These structures expressed type IV collagen. After trypsinization, the lamina densa was found to be composed of microfilaments approximately 10 nm thick showing beaded appearances. These microfilaments exhibited the same cobblestone-like structures as the lamina densa surface. Observation of the torn lamina densa demonstrated anchoring fibrils and oxytalan fibers that were attached to the lamina densa itself. Another kind of filament about 7 nm thick linked the anchoring fibrils and the oxytalan fibers. Beneath the lamina densa was a network of fibers about 40-50 nm thick, which was composed of collagen fibers and possibly also elaunin fibers. In conclusion, this study revealed the detailed surface ultrastructure of the epidermal lamina densa and its underlying filamentous elements.

Centrifugal lipodystrophy of the face mimicking progressive lipodystrophy.

We report a Japanese boy with centrifugal lipodystrophy. The initial lesion developed on the forehead as an area of erythema which showed centrifugal spread and central fading to leave a residual depression. Three years later, similar erythematous lesions appeared on the cheeks, and he developed a cadaverous appearance. A central depression on the upper trunk was surrounded by an erythematous border and there was right cervical lymphadenopathy. Histological examination revealed inflammatory changes in the subcutaneous fat. Although this patient showed the characteristics of both centrifugal and progressive lipodystrophy (partial lipodystrophy), we consider that he has centrifugal lipodystrophy of the face because of the overall features of the lesions.

Neuroradiological findings in glutaric aciduria type I: report of four Japanese patients.

We examined neuroradiological computerized tomography (CT) findings and the clinical course of four Japanese children with glutaric aciduria type I (GA1) whose enzyme activity of glutaryl-CoA dehydrogenase was undetectable. Brain CT in all cases examined showed low density white matter, fluid collection in bilateral frontotemporal regions (particularly surrounding the Sylvian fissures), enlargement of the lateral ventricles and slight atrophy of the basal ganglia. Although these findings seemed to be characteristic for GA1, they were unlikely to be more extended, at least over 2 years after infancy. The low density white matter was observed more evidently in the neonatal or early infantile periods than in later periods. The degree of enlargement of fissures in bilateral frontotemporal regions about the Sylvian fissures appeared to correlate with the severity of symptoms such as dystonia or choreoathetosis. Magnetic resonance images (MRI) in one case showed bilateral linear-shaped low intensity in areas of the external capsules and putamen on a T1-weighted image. These CT and MRI findings, as well as clinical symptoms such as choreoathetosis or dystonia, may suggest that metabolic abnormalities in GA1, such as glutaconate, are toxic to the extrapyramidal tract system in the central nervous system, and that the clinical symptoms of the patients are attributable to atrophy of basal ganglia. Brain CT may be useful in diagnosis and evaluation of the clinical course of GA1 patients.

Proteus syndrome: report of the first Japanese case with special reference to differentiation from Klippel-Trenaunay-Weber syndrome.

This is the first report of a Japanese girl with Proteus syndrome. She presented with growth acceleration and precocious development of the left breast as well as macrodactyly, hemihypertrophy, a subcutaneous preaxillary mass, portwine stains, connective tissue nevi, and a depigmented macule. All these abnormalities were confined to the left side of her body. Although most of the manifestations fit those of Proteus syndrome, the presence of the portwine stains and hemihypertrophy also suggested Klippel-Trenaunay-Weber syndrome. The findings in our patient suggest that the most important characteristic distinguishing Proteus syndrome from Klippel-Trenaunay-Weber syndrome is the presence of functional abnormalities such as a growth spurt and precocious breast development. Proteus syndrome may be genetically different from the Klippel-Trenaunay-Weber syndrome.

Cutaneous nerves in cafe au lait spots with white halos in infants with neurofibromatosis. An electron microscopic study.

BACKGROUND AND DESIGN: Although two cardinal skin manifestations of neurofibromatosis are cutaneous neurofibromas and cafe au lait spots, the pathogenesis of cafe au lait spots are very poorly known compared with that of cutaneous neurofibromas. Thus, the cafe au lait spots in two Japanese infants were clinically, histologically, and electron-microscopically investigated. OBSERVATIONS: Some of the cafe au lait spots in the mongolian spots were surrounded by white halos. Histologically, in the cafe au lait spots, the epidermal basal cells had abundant melanin pigment, but macromelanosomes were not seen throughout the epidermis. In the white halo, the epidermal basal cells had a small amount of melanin pigment. Electron microscopically, the cafe au lait spots and their white halos had many subepidermal and intraepidermal nerves that belonged to free nerve endings. All the cutaneous nerves were mature. Some of the intraepidermal nerves had partially or completely naked axons that contacted tightly with the cytomembranes of the basal keratinocytes. Some of the axons in the subepidermal nerves showed degenerative changes only in the white halos. No ultrastructural pathologic changes were observed in the melanocytes, the epidermal keratinocytes, or melanosomes in those cells in the cafe au lait spots and their white halos; also, dermal melanocytes were absent in the both areas. CONCLUSIONS: The increase of the cutaneous nerves and the absence of dermal melanocytes in the cafe au lait spots and their white halos may be considered as characteristic histologic cutaneous findings in infants with neurofibromatosis. However, no evidence indicates that the cutaneous nerves may participate closely in the pathogenesis of the white halos.

Angiosarcoma of the thigh with thrombosis in the femoral artery.

We report a case of angiosarcoma with some peculiar clinical features developing on the left thigh of a 63-year-old man. The early primary lesion was erythematous with necrotic areas. The initial biopsy specimen of the lesion indicated a benign angioproliferative process. However, the necrotic area enlarged rapidly, ulcerated with severe pain, and thus was widely excised. The excised specimen had a malignant histologic appearance, particularly in the fascia, and was diagnosed as angiosarcoma. Following local recurrence, the lesion was complicated by thrombosis of the femoral artery at the affected site. A similar cutaneous lesion subsequently arose on the right lower leg, and thrombosis developed in the right femoral artery. Both legs had to be amputated. There were no distant metastases.

Linear focal elastosis. An ultrastructural study.

We studied an 86-year-old Japanese man with linear focal elastosis. The lesions were asymptomatic yellow striae in the lumbar region, histologically composed of massive, well-demarcated basophilic fibers that stained positively with elastic tissue stains. Electron microscopy revealed fine, reticular or granular electron-dense materials, and elastic fiber microfibril-like materials in the matrix, in addition to numerous mature and immature elastic fibers. These findings suggest that active elastogenesis was occurring in the lesions. The four cases reported so far have the three common features of age, sex, and lesion location.