Increased anti-oxidative action compensates for collagen tissue degeneration in vitiligo dermis.

Vitiligo is a common depigmentation disorder characterized by the selective loss of melanocytes. In our daily clinic experience, we noticed that the skin tightness of hypopigmented lesions would be more evident in comparison to that of uninvolved perilesional skin in vitiligo patients. Therefore, we hypothesized that collagen homeostasis might be maintained in vitiligo lesions, irrespective of the substantial excessive oxidative stress that occurs in association with the disease. We found that the expression levels of collagen-related genes and anti-oxidative enzymes were upregulated in vitiligo-derived fibroblasts. Abundant collagenous fibers were observed in the papillary dermis of vitiligo lesions in comparison to uninvolved perilesional skin by electron microscopy. The production of matrix metalloproteinases that degraded collagen fibers was suppressed. The deposition of acrolein adduct protein, which is a product of oxidative stress, was significantly reduced in vitiligo dermis and fibroblasts. As part of the mechanism, we found upregulation of the NRF2 signaling pathway activity, which is an important defense system against oxidative stress. Taken together, we demonstrated that the anti-oxidative action and collagen production were upregulated and that the collagen degeneration was attenuated in vitiligo dermis. These new findings may provide important clues for the maintenance of antioxidant ability in vitiligo lesions.

Leukoderma induced by rhododendrol is different from leukoderma of vitiligo in pathogenesis: A novel comparative morphological study.

BACKGROUND: Rhododendrol (rhododenol), an inhibitor of tyrosinase activity, is used as a skin-whitening component. Many cases of leukoderma after the application have been reported, termed rhododenol-induced leukoderma (RIL). The aim of this study was to clarify the pathogenesis of RIL morphologically through comparison with vitiligo. METHODS: We examined 14 cases of RIL and 15 cases of vitiligo using routine histopathology and immunohistochemistry. Thirteen cases of RIL, six cases of vitiligo and specimens of the RIL mouse model were evaluated by electron microscopy. RESULTS: There were common findings in RIL and vitiligo at the light-microscopic level: (a) vacuolar changes in the dermo-epidermal junction, (b) melanophages in the papillary dermis, (c) perifollicular lymphocyte infiltration, (d) loss or decrease of basal melanin pigment and (e) decrease of melanocytes in the lesions. The ultrastructural observations showed specific findings of RIL: (a) remaining melanocytes in depigmented lesions, (b) inhomogeneous melanization in melanocytes and (c) degenerated melanosomes in melanocytes. Some of the findings were observed in a RIL mouse model. Furthermore, it is notable that cell organelles of melanocytes were intact in our RIL cases. CONCLUSION: Morphological changes of RIL targeting melanosomes in melanocytes without degeneration of organelles reflect the reversible clinical course of most cases.

Pseudocheckerboard pattern: an interesting histopathological finding in mechanic's hands.

BACKGROUND: Mechanic's hands are a well-known symptom often associated with dermatomyositis and are similar to hand eczema clinically. Histopathology of them usually shows hyperkeratosis, focal parakeratosis, psoriasiform acanthosis, basal vacuolar changes and necrotic keratinocytes in the epidermis and upper dermal mucin deposition. However, there have been few comparative histopathologic evaluations of mechanic's hands and palmoplantar eczema. METHODS: We evaluated the histopathology of mechanic's hands in 6 patients with dermatomyositis who visited our hospital between 2006 and 2014 comparing with histopathology of 27 patients with palmoplantar eczema, retrospectively. RESULTS: As previously reported, hyperkeratosis, basal vacuolar change and necrotic keratinocytes were seen in all cases of mechanic's hands. Basal vacuolar change was not observed in any cases of palmoplantar eczema. Three cases of mechanic's hands demonstrated a characteristic finding, a pseudocheckerboard pattern, in the hyperkeratotic horny layer; there were areas of alternating parakeratosis and orthokeratosis in a vertical arrangement and these areas alternated with the completely orthokeratotic areas in a horizontal arrangement. This pattern has not been focused in mechanic's hands so far. Same pattern was also observed in four patients with palmoplantar eczema. CONCLUSION: 'Pseudocheckerboard pattern' was not specific but may be a possible diagnostic clue for mechanic's hands.

Three-dimensional structure of a parameatal urethral cyst by scanning electron microscopy.

We report scanning electron microscopy (SEM) for a case of parameatal urethral cyst. A 6-year-old Japanese boy presented with a cyst on the right lateral side of the urethral meatus. Histological examination revealed a cyst lined with columnar epithelium. An immunohistochemical study showed positive staining for CK7, CK13, and CEA, and negative for CK20 in luminal cells. On SEM examination, the inner surface of the cyst showed ridges arranged in a gyrus-like manner at lower magnification. Higher magnification revealed luminal cells with short microvillus projections. Some cells showed apocrine, merocrine, and possibly holocrine-type secretions.

Syringocystadenoma papilliferum on the male nipple.

Syringocystadenoma papilliferum is a rare benign adnexal tumor that most frequently arises from an organoid nevus on the head and neck. Occurrence of this tumor on the male breast is extremely rare. A 74-year-old Japanese man presented with a nodule on his left nipple. Histopathological findings were typical for syringocystadenoma papilliferum. Ultrastructurally, constituent epithelial cells of the tumor were divided into three types. We focused on one cell type, undifferentiated clear cells, which have been suggested to be pluripotent cells bearing stem cell nature in syringocystadenoma papilliferum. Immunohistochemically, the tumor cells were negative for cytokeratin 15, which is known as a relatively specific marker for multipotent stem cells in the follicular bulge. We speculated that the clear cells are slightly differentiated toward apocrine rather than stem cells. We also ruled out the possibility of a relationship between the clear cells and Toker cells, which have a clear cytoplasm and are present in the areola region. Dermoscopic examination revealed amorphous milky white areas that corresponded to the pathological findings of luminal deposition of the tumor.

Myofibroblastic differentiation in atypical fibroxanthomas occurring on sun-exposed skin and in a burn scar: an ultrastructural and immunohistochemical study.

Herein, we report the investigation of two cases of atypical fibroxanthoma (AFX). One AFX developed within actinically damaged skin, as is typical, while the other developed within a burn scar within non-sun-exposed skin. The two tumors showed almost identical histopathological, immunohistochemical and ultrastructural features. The tumors were composed of pleomorphic spindled, epithelioid, multinucleated and bizarre cells with enlarged atypical nuclei. Most tumor cells expressed vimentin and about 50% expressed CD10. Some tumor cells also expressed α-smooth muscle actin and CD68. However, there was no expression of cytokeratins, p63, S-100 protein, melan-A, HMB 45, desmin, epithelial membrane antigen or CD34. Ultrastructurally, the tumor cells contained myofilaments with dense patches but lacked plasmalemmal caveolae and basal lamina. The most prominent finding was the identification of fibronexus junctions. In addition, there were tumor cells containing numerous lysosomal granules. In conclusion, we clearly showed myofibroblastic differentiation in AFX by electron microscopy. We report also a case of AFX directly developing within a burn scar in the absence of actinic damage.