A Histopathologic Study of the Human Skin in the Early Stage After a Tick Bite: A Special Reference to Cutaneous Tissue Reaction to the Cement Substance of Tick Saliva.

The Ixodidae family of hard ticks has cement-producing and non-cement-producing species. Involved skins of four patients bitten by cement-producing ticks and two by non-cement-producing ticks were histopathologically examined. Those of the latter two patients were also studied immunohistochemically to characterize the infiltrating inflammatory cells. In patients with cement-producing ticks, the cement substance was observed as external cement or outer zone of internal cement, respectively. Coagulative necrosis was present in the epidermis in one patient and from the epidermis to the dermis in another patient. Epidermal cells were damaged in the remaining two patients. Despite these severe tissue damages, the cutaneous inflammatory reaction in all four patients was very mild. In contrast, the patients bitten by non-cement-producing ticks had severe cutaneous inflammatory reaction. In addition to caseous necrosis-like change in the entrance site of the inserted mouthparts, extensive interstitial lymphohistiocytic infiltrate was present diffusely from the dermis to the subcutaneous tissue. In one of the patients coagulative necrosis was present from the dermis to the subcutaneous tissue. Immunohistochemically, the infiltrating lymphocytes were T-cell dominant and mixed moderately with B-cells. Pathogenetically, the cutaneous inflammatory reaction is only mild in the skins involved by the cement-producing ticks, perhaps because inflammatory reaction in the host skin is suppressed by antiinflammatory and immunosuppressive substances contained in tick's saliva in order to prevent position of their mouthparts fixed to the host skin from rejection of the host until finishing their engorgement. In contrast, the cutaneous inflammatory reaction induced by the non-cement-producing ticks is severe, possibly because these ticks have no antiinflammatory and immunosuppressive substances in their saliva, and because their saliva is much more injurious than that of the cement-producing ticks.

Epithelial Stem Cells of the Skin Contribute to the Histopathologic Umbrella-like Appearance in Actinic Keratosis.

Although the histopathologic umbrella-like appearance of the epidermis in actinic keratosis (AK) is well known, its histopathogenesis has remained unknown. The author suggests that the penetration depth of ultraviolet B (UVB) radiation can account for such a histopathologic feature by affecting specific epidermal stem cell pools, as the stem cells in the epidermis and the bulge stem cells and sebocyte stem cells in the mid-dermis reside at different depths.

Eczematous Dermatitis Occurring on a Café-au-Lait Spot Long after Laser Radiation.

A 40-year-old woman presented with an itchy erythematosquamous change of a café-au-lait spot in her face. The onset of this change occurred just after her relocation. The café-au-lait spot had been irradiated by laser approximately 20 years ago. Clinically, there was a coin-sized erythema with a slight scale on the pigmented lesion in the left lateral orbital region. Histopathologically, the lesion demonstrated both spongiotic dermatitis and interface dermatitis together with lymphohistiocytic cell infiltration, in addition to moderate acanthosis and elongation of rete ridges with slight basal hyperpigmentation. From these clinical and histopathological findings, the lesion was diagnosed as eczematous dermatitis occurring on the café-au-lait spot after laser radiation. Another interesting histopathological finding was that some parts of a lobule of the sebaceous gland were occupied exclusively by degenerative atrophic sebocytes. From the viewpoint of pathogenesis, the eczematous dermatitis of this patient could have been an accompanying feature of a neurogenic inflammation occurring on the café-au-lait spot after laser radiation, and the atrophic change of a part of the sebaceous lobule might have been induced by a morphogenetic alteration of certain germinative cells of the sebaceous lobule due to laser radiation.

Sequential observation of morphogenesis of cutaneous nerve fibers in fetal rat skin: an immunohistochemical and electron microscopic study.

Skin of DA/Slc rat fetuses removed on the fetal days 11 to 20 and on delivery day (21 days post-fertilization) was used. In the immunohistochemistry, the anti-neurofilament 69 kDa (NF68)-positive fibers appeared in the subepidermal dermis on the fetal day 12. The subepidermal and intraepidermal NF68-positive fibers reached to a maximum number on the fetal day 14. They disappeared completely on the fetal day 16. After the fetal day 19, a small number of the subepidermal and intraepidermal NF68-positive fibers were seen again. As for anti-nerve growth factor (NGF), intermediate cells, spinous cells and granular cells of the epidermis showed strongly positive stain. In the electron microscopy, there were bundles of immature axons which were packed by abundant microtubules and neurofilaments during the entire fetal period. On the fetal days 16 and 17, a considerable number of axons showed severe degenerative changes. From these findings, the subepidermal and intraepidermal nerve fibers in the fetal rat skin increased temporarily to a maximum number, and soon after they disappeared completely, followed by another period of re-appearance until delivery day. Such a dynamic change of the number of the cutaneous nerve fibers was not synchronous with expression of NGF of the epidermal cells.

Epstein-Barr virus-infected malignant T/NK-cell lymphoma in a patient with hypersensitivity to mosquito bites.

We report an autopsy case of Epstein-Barr virus (EBV)-infected malignant lymphoma in a young male who had hypersensitivity to mosquito bites. The autopsy revealed multiple confluent lymphoma lesions in the lungs, and on the right leg irregular-shaped skin ulcers were seen. The left pleural effusion also contained a large number of lymphoma cells. The lymphoma cells were determined as T/NK-cell type cells by immunohistochemistry. EBV DNA was detected most intensively in the lungs and EBV-encoded small RNAs-positive lymphoma cells were also observed in the lungs at a high frequency. EBV latent membrane protein-1 expression and a high Ki-67 labeling indices were noted in the lymphoma cells of the lung lesions. These findings indicate that the development of the malignant lymphoma was associated with the proliferation of EBV-infected lymphoma cells, and the cells that infiltrated the whole the body, especially the lungs, caused the patient's death.

Time course effect and sequential morphological changes of subepidermal nerve fibers in guinea pig skin after application of histamine ointment: a laser scanning confocal fluorescence microscopic and electron microscopic study.

This study was undertaken to elucidate the morphological effects of histamine on subepidermal nerve fibers. A 10% histamine ointment was topically applied to the back skin of 17 adult male Hartley guinea pigs. Biopsy specimens were obtained at times from 5 min to 24 h, and were examined by conventional immunofluorescence (IF), laser scanning confocal fluorescence microscopy (LSCM) and transmission electron microscopy. On IF and LSCM, marked diminutions in the immunoreactivity of protein gene product 9.5-immunoreactive (PGP 9.5-IR) fibers as well as of substance P-immunoreactive (SP-IR) and calcitonin gene-related peptide-immunoreactive (CGRP-IR) substances were observed 5 min after histamine application. By 30 min, immunoreactivity of PGP 9.5, SP and CGRP was completely lost. By 2 h, however, immunoreactivity of PGP 9.5-IR fibers and CGRP-IR substances started to show recovery. By 4 h, immunoreactivity of PGP 9.5, SP and CGRP had almost recovered, but the recovery time for each substance was slightly different (PGP 9.5 first, CGRP next, and SP last). By 6 h after histamine application, immunoreactivity of all these substances had fully recovered. Ultrastructurally, 5 min after histamine application, axonal and mitochondrial swelling and glycogen deposition were seen in the axons of subepidermal nerve fibers. By 30 min, severe axonal degeneration had occurred in some of the axons. It was only by 4 to 6 h that almost normal ultrastructural features were observed. Schwann cells and perineurial cells did not show any pathological changes. These findings demonstrate that 10% histamine ointment produced organic changes in the axons in the subepidermal nerve fibers of guinea pig skin, but these morphological changes were short-lived, reversible and transitory.

Lack of marital support and poor psychological responses in male cancer patients.

A total of 272 men and 252 women with cancer participated in a study of the impact of being married and the presence of spousal support on psychological distress and coping with cancer. All participants underwent a structured interview and completed the Profile of Mood States and the Mental Adjustment to Cancer scale. Multivariate analysis controlling for potentially confounding biomedical and psychosocial variables revealed that unmarried men had significantly higher levels of psychological distress and lower levels of fighting spirit than married men, and that men with spousal support showed higher levels of fighting spirit than men without spousal support. However, no such difference was observed between unmarried and married women or between women with and without spousal support. These findings suggest that being married may play an important role in reducing psychological distress and enhancing fighting spirit of men with cancer, and that being unmarried may be a risk factor for psychological distress and lower fighting spirit for men with cancer.

Performance status 1 predicts psychological response in female, but not male, ambulatory cancer patients.

This study aimed to identify gender differences in the impact of performance status (PS) 1, that is, of physically mild impairment, on psychological distress and coping in ambulatory cancer patients. The subjects were 260 male and 242 female cancer outpatients who participated in a structured interview and completed the Profile of Mood States and the Mental Adjustment to Cancer scale. Multivariate analyses controlling for confounding biomedical and psychosocial variables revealed a significant impact of PS 1 on helplessness/hopelessness and a trend toward an impact on fighting spirit in women alone, whereas a trend was observed in regard to psychological distress in both genders. The results of this study suggest that PS 1 may be a risk factor for negative ways of coping in female, but not male, cancer outpatients.

A case of non-selective phagocytosis of hemosiderin and melanin of dermal histiocytes in stasis dermatitis.

A case study was undertaken to determine whether or not the same dermal histiocytes could phagocytose both melanin and hemosiderin simultaneously. A biopsy specimen was taken from a pigmented lesion of the lower leg of a 57-year-old woman with stasis dermatitis. The specimen was processed for histology, conventional transmission electron microscopy and electron-probe X-ray microanalysis. Histologically, numerous histiocytes with their cytoplasm packed with either Prussian blue-positive granules or Fontana-Masson-positive granules were distributed almost equally in the dermis. Electron microscopically, the dermis had many histiocytes with their cytoplasm containing solitary or compound electron-dense substances. The electron-dense substances were classified into three types according to their degree of electron density. By electron-probe X-ray microanalysis, these electron-dense substances were classified into iron-containing and non-iron-containing substances. Both substances were seen in the cytoplasm of the same histiocytes and even in the same compound electron-dense substance. The former were siderosomes and the latter were probably melanosomes. These results show that the same dermal histiocytes probably phagocytose non-selectively both hemosiderin and melanin granules.

Bird's eye view observations of the subepidermal nerve network of normal guinea pig skin.

This study was undertaken to visualize the subepidermal nerve networks immunohistochemically. Specimens were obtained from the normal skin of the back, abdomen and nose of seven adult male Hartley guinea pigs, and immersed in 1 M NaCl solution. Dermal sheets were obtained by separating the dermis and epidermis, followed by fixation in Zamboni's fixative. The dermal sheets were sectioned parallel to the separated surface. Using the immunoperoxidase technique and immunofluorescence, the sections were immunostained with primary antibodies to S 100 protein (S100), protein gene product 9.5 (PGP 9.5), neuron-specific enolase (NSE), substance P (SP) and calcitonin gene-related peptide (CGRP). In double-labeled immunofluorescence of PGP 9.5 and SP or CGRP, the sections were viewed under a confocal laser scanning microscope. In skin of the back and abdomen, networks of S100-, PGP 9.5- and NSE-positive fibers were observed, some of which showed a multicentric arrangement. The outermost structures were formed by the thickest fibers which were 5-10 micro m thick, the outer networks consisted of fibers 3-6 micro m thick, and the inner networks consisted of fibers 1-3 micro m thick. From these networks, single fibers approximately 0.5 micro m thick branched out and terminated in free endings. The SP- and the CGRP-positive substances appeared as granules on the PGP 9.5-positive fibers. These results confirm that the dermis has a three-layered sensory nerve plexus, i.e. deep, superficial and subepidermal. In the skin of the nose, however, nerve networks were made up of only thick fibers which were probably situated in the subpapillary dermis.

Acral pseudolymphomatous angiokeratoma of children: immunohistochemical and clonal analyses of the infiltrating cells.

BACKGROUND: Acral pseudolymphomatous angiokeratoma of children (APACHE) is a disorder characterized clinically by red nodules and histopathologically by a massive subepidermal lymphohistiocytic infiltrate. Although it was initially thought to be a vascular nevus, it has never been regarded as a pseudolymphoma. CASE REPORT: We report a 7-year-old-girl with small red nodules on the dorsum of the right foot and a 73-year-old man with asymptomatic brown-red nodules on the lower extremities. RESULTS: Histopathologic examination revealed a massive lymphohistiocytic infiltrate with plasma cells, some eosinophils, or a multinucleated giant cell immediately beneath the epidermis. Thick-walled vessels were observed in the infiltrate. These characteristics are identical to those of acral pseudolymphomatous angiokeratoma of children. The infiltrate was composed mainly of equal numbers of CD4+ or CD8+ T cells and equal numbers of B cells stained for kappa or lambda light chains. PCR amplification of rearranged immunoglobulin heavy chain genes or T-cell receptor gamma genes showed no evidence of clonality, suggesting that these infiltrates were polyclonal both for B and T cells. CONCLUSIONS: Our data support the idea that this disorder represents a reactive process. The modified term 'papular angiolymphoid hyperplasia' would define this disorder more appropriately.

Centrifugal lipodystrophy presenting with serpiginous erythema and alopecia.

We describe serpiginous erythema with alopecia developing on the scalp of a 10-year-old boy during follow-up of centrifugal lipodystrophy. Because the clinical and histopathologic features of these lesions were identical to those of centrifugal lipodystrophy, we conclude that involvement of a hairy region by this disorder could cause alopecia and that the hair loss might be an indirect effect of interstitial inflammatory infiltrates around the hair follicles and in the subcutaneous fat.