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.

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.

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.

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.

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.

Posttraumatic occurrence of infantile digital fibromatosis. A histologic and electron microscopic study.

We encountered a patient with infantile digital fibromatosis. The representative lesion was a firm, indurated nodule, which developed in the scar of a previous injury on the skin of the left thigh of an 11-year-old girl. Electron microscopy revealed tumor cells that were strongly reminiscent of myofibroblasts. Histopathologically, the cytoplasmic inclusion bodies in the tumor cells stained positively or negatively with hematoxylin-eosin. Electron microscopically, they were either well-defined dense bodies that often showed a doughnutlike appearance or ill-demarcated dense bodies. Spotty calcified foci were seen in the central area of the tumor mass.

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.

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.

A case of primary biliary cirrhosis associated with generalized morphea.

A 50-year-old female with primary biliary cirrhosis associated with generalized morphea is reported. She had suffered from multiple painful indurated plaques on the trunk which was diagnosed as generalized morphea; subsequently, primary biliary cirrhosis was diagnosed on the basis of her hepatic dysfunction. Although progressive systemic sclerosis has been reported to occur in patients with primary biliary cirrhosis, this localized form of cutaneous sclerosis has not previously been reported. Since generalized morphea is one of the most common manifestations of chronic graft-versus-host disease, and primary biliary cirrhosis is known to have a hepatic histology resembling chronic graft-versus-host disease, this case report may represent evidence in support of a common pathogenesis for the two entities.

A case of minocycline-induced fixed drug eruption.

A case of fixed drug eruption induced by minocycline on the glans penis of a 26-year-old man is reported. Later oral administration of minocycline reproduced the same type of eruption, but tetracycline, possessing the same starting structure as minocycline, did not induce the eruption. Laboratory findings were normal. This seems to be the first case of fixed drug eruption induced by minocycline to appear in the literature.

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.

Lichen nitidus: a histologic and electron microscopic study.

A lesion of lichen nitidus in a 53-year-old man was examined by histology and electron microscopy. The histology showed typical features. The electron microscopy revealed primary changes in hydropic degeneration of basal cells which possibly indicated severe edema between the basal keratinocytes and in the subepidermal area. The basal keratinocytes themselves were not particularly altered, except for clustered micro-vacuolar structures in a small portion of the peripheral cytoplasm. In one of the eight blocks observed, the cytoplasmic process of a mast cell was found between the basal keratinocytes, indicating that mast cells may possibly infiltrate the epidermis in lichen nitidus. Scattered mast cells in the dermis were also noted. Thus primary pathologic changes of lichen nitidus may be induced by severe edema, which was accompanied by inflammatory cells including mast cells, in the region of the dermal-epidermal junction.

Biphasic amyloidosis arising from friction melanosis.

A 40-year-old woman who had used nylon towels in the bath for about 10 years noticed hyperpigmentation on the prominent regions over the bones of the trunk and extremities. She also developed lichenoid papules with itching on her back. Histologically, both the pigmented and the papular lesions had amyloid deposits beneath the epidermis. In this case it is presumed that the papular lesions with amyloid (lichen amyloidosus) developed initially from friction melanosis which became macular pigmented lesion (macular amyloidosis). The etiologic factor of these sequential pathologic changes is considered to be repeated scrubbing with nylon towels.

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.

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.

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.

The local recurrence of pigmented Spitz nevus after removal.

A seventeen-month-old female had a pigmented nodule on her left lower leg. The excised lesion was histologically diagnosed as a Spitz nevus, composed mainly of spindle-shaped melanocytes containing large amounts of melanin pigment. When nodular regrowth was seen at the operative site, the recurrent lesion was radically excised as nodular melanoma. However the histological characteristics of the second excised specimen were essentially the same as those in the initially excised one except for the existence of the newly formed collagen fibers, which may suggest an involuting stage in the central portion of the lesion.

Persistent facial ulcerations with a unique clinical appearance: possible trigeminal trophic syndrome.

We reported a 53-year-old woman with a persistent facial ulcer which moved gradually from the right marginal portion of the nasal root to the right lateral canthus along the margin of the right lower eyelid. The ulcer healed spontaneously. A similar ulcer developed at the entrance of the right anterior naris. The clinical findings were suggestive of squamous cell carcinoma, deep mycosis, mycobacterial infection, or a related condition. However, no definitive diagnosis could be made from the clinicopathological findings or the laboratory examinations, including bacterial, mycobacterial, and fungal cultures. The characteristic location of the lesion, and course of the disease, however, suggested the diagnosis of trigeminal trophic syndrome.

Cutaneous sarcoidosis showing multiple papular eruptions with keratotic plugs.

A 26-year-old woman developed 249 discrete papules on her lower extremities. Twenty-three of them had keratotic plugs. Histologic examination demonstrated granulomatous foci consisting of epithelioid cells and a epidermal invagination which was disrupted at the base and lateral sites. This invagination was considered to represent transepithelial elimination.

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.