Nobuyuki Mizuno

Microcystic adnexal carcinoma: a light microscopic, immunohistochemical and ultrastructural study

We report a case of microcystic adnexal carcinoma (MAC) occurring on the upper lip of an 82‐year‐old woman. Microscopically the tumor showed both pilar and sweat gland differentiation, involved the entire dermis and subcutaneous tissue, and invaded perineural spaces. Immunoperoxidase studies revealed carcinoembrionic antigen to be present in the ductal lining cells and in the amorphous content in the lumen, confirming sweat gland differentiation. The S‐100 protein was positive in dendritic cells within the solid cell nests, but negative in cells lining cystic spaces. Ultrastructural study confirmed that the neoplasm was composed of two components, with pilar and eccrine differentiation. The former showed concentric layers of squamous epithelial cells with well‐developed desmosomes and cytofilaments. The latter had ductal and alveolar structures; the ultrastructural features included i) numerous villous folds of plasma membrane to interdigitate each other by focal desmosomes, ii) aggregates of cytofilaments, and iii) basally located myoepithelial cells which were separated from the surrounding stroma by rather thick basement membrane. In addition, distinct amyloid deposition was also observed on ultrastructural examination. To our knowledge, amyloid deposition has not been previously reported in MAC.

Cell cycle analysis of human dermal fibroblasts cultured on or in hydrated type I collagen lattices

SummaryThe proliferation and cell cycle phase composition of human dermal fibroblasts cultured on or in type I collagen lattices (reconstituted dermis model) were examined. On collagen lattices, as compared with conventional cultures on plastic dishes, the proliferation of human dermal fibroblasts was suppressed, being arrested at about one-half the saturation density after 10 days of culture. In collagen lattices, proliferation was further suppressed, being nearly arrested within 4–7 days of culture. Cells were analyzed for cell cycle phases by two-color flow cytometry using DNA staining and S phase cell staining with FITC-conjugated antibromodeoxyuridine antibody. After 5 days of culture, the number of S phase cells on collagen lattices was 49.3% of that on plastic dishes, with an increase in G0G1 phase cells of 79.8%. In collagen lattices, the number of S phase cells was very small (4.3% of all cells), and most of the cells accumulated in G0G1 phase. These findings suggest that the cell cycle of fibroblasts is arrested at G0G1 phase by their interaction with collagen. On the basis of these results, the reconstituted dermis model using collagen lattice is considered to be analogous to the dermis in vivo with respect to cell growth and cell cycle phase composition.

An Alternative Approach to Atopic Dermatitis: Part I—Case-Series Presentation

Atopic dermatitis (AD) is a complex disease of obscure pathogenesis. A substantial portion of AD patients treated with conventional therapy become intractable after several cycles of recurrence. Over the last 20 years we have developed an alternative approach to treat many of these patients by diet and Kampo herbal medicine. However, as our approach is highly individualized and the Kampo formulae sometimes complicated, it is not easy to provide evidence to establish usefulness of this approach. In this Review, to demonstrate the effectiveness of the method of individualized Kampo therapy, results are presented for a series of patients who had failed with conventional therapy but were treated afterwards in our institution. Based on these data, we contend that there exist a definite subgroup of AD patients in whom conventional therapy fails, but the ‘Diet and Kampo’ approach succeeds, to heal. Therefore, this approach should be considered seriously as a second-line treatment for AD patients. In the Discussion, we review the evidential status of the current conventional strategies for AD treatment in general, and then specifically discuss the possibility of integrating Kampo regimens into it, taking our case-series presented here as evidential basis. We emphasize that Kampo therapy for AD is more ‘art’ than technology, for which expertise is an essential pre-requisite.

Parallel Arrangement, Growth Inhibition and Cell Cycle Phase Analysis of Human Dermal Fibroblasts Cultured in Collagen Lattice

Human dermal fibroblasts were cultured in a hydrated type I collagen lattice. When collagen fibers were arranged in one direction, fibroblasts were arranged in the same direction. Cell proliferation was markedly suppressed in the collagen lattice as compared with that on plastic, with growth being arrested after day 5. No differences in proliferation were observed between aligned cells and randomly oriented cells.

An Alternative Approach to Atopic Dermatitis: Part II—Summary of Cases and Discussion

In the first part of this Review, we presented case-series where Kampo treatment was introduced for those atopic dermatitis (AD) patients who had failed with conventional therapy, in an attempt to prove that there exists a definite subgroup of AD patients for whom Kampo treatment is effective. In this second part, we will first provide the summary of the results for 140 AD patients we treated in 2000. The results suggest that Kampo treatment is effective for more than half of AD patients who fail with conventional therapy. In the Discussion, we will examine the evidential basis for conventional AD therapy and discuss how Kampo treatment should be integrated into the guidelines for AD therapy. We contend that Kampo treatment should be tried before systematic immunosuppressive agents are considered. As each Kampo treatment is highly individualized, it should be regarded more as ‘art’ than technology, and special care should be taken to assess its efficacy in clinical trial.

Mild phenotype of familial cylindromatosis associated with an R758X nonsense mutation in the CYLD tumour suppressor gene.

Familial cylindromatosis is a rare dominantly inherited disease characterized by the development of multiple benign tumours of the skin appendages, including cylindromas, trichoepitheliomas and spiradenomas. The gene responsible was positionally cloned recently, and was designated CYLD. We describe a family with cylindromatosis, in which affected individuals have an inherited R758X nonsense mutation of CYLD. Affected members of this family manifest a relatively mild tumour phenotype; the largest tumour was only 30 mm in diameter. Thus far, there is no evident genotype–phenotype relationship in cylindromatosis, although the number of families reported with both phenotypic and genotypic data remains small.

Effects of Human Recombinant Tumor Necrosis Factor‐α (TNF‐α) on the Proliferative Potential of Human Keratinocytes Cultured in Serum‐free Medium

The effects of human recombinant tumor necrosis factor‐α (TNF‐α) on human keratinocytes cultured in a serum‐free medium were investigated. TNF‐α markedly suppressed cell growth. The growth‐inhibitory effect was reversible and cytostatic at a concentration of 1–5 U/ml, but appeared to be irreversible and cytocidal at 10 U/ml. The growth suppressive effect was more marked when TNF‐α was added in the late growth phase or preconfluent phase than when it was added in early or mid‐growth phases. No effects of TNF‐α on cell adhesion to the substrate were observed. These results indicate that TNF‐α is a very potent anti‐proliferative agent for human keratinocytes.

Cutaneous polyarteritis nodosa induced by Mycobacterium tuberculosis

condition. In addition to the skin, the lungs and kidneys are often involved in patients with microscopic polyangiitis. Renal involvement, such as necrotizing crescentic glomerulonephritis or hemorrhagic pulmonary capillaritis, is present in 90% of the cases. In our case, hematuria and non-nephritic range proteinuria were observed, but severe renal symptoms and pulmonary alveolar hemorrhage were absent. Discontinuation of PTU at a relatively early stage and systemic, high-dose prednisolone therapy might account for the prevention of damage to the internal organs. Microscopic polyangiitis should be considered in the differential diagnosis of deep skin ulcers resembling PG during the antithyroid therapy using PTU.

Apoptosis of neutrophils resulting after emperipolesis in cutaneous Rosai-Dorfman disease: a new ultrastructural finding.

Fig. 1. A) Multiple erythematous papules extensively involve the face. B and C) Large pale-staining histiocytes show cytophagocytosis (emperipolesis) of neutrophils and lymphocytes. There is an accompanying infiltrate spanning the full thickness of the dermis (hematoxylin and eosin staining; original magnification B: ×100; C: ×400). D) Terminal deoxy-UTP nick-end labeling (TUNEL) staining of the section showed phagocytized cells exhibiting apoptosis (original magnification, ×400).

Three-base deletion mutation c.120_122delGTT in ATP2A2 leads to the unique phenotype of comedonal Darier disease

Darier disease (DD; Darier―White disease; OMIM 124200) is an autosomal dominant inherited disorder. 1 Clinically, it is characterized by recurrent and multiple hyperkeratotic papules or nodules affecting the trunk and flexural aspects of the extremities. 1 Characteristic histopathological features are dyskeratotic cells in the form of corps ronds and grains, suprabasal acantholysis forming suprabasal lacunae and irregular upward proliferation into the lacunae of papillae lined with a single layer of basal cells, the so-called villi. 2 The causative gene is ATP2A2 (OMIM 108740) on chromosome 12, which encodes the sarco/endoplasmic reticulum calcium pump ATPase (SERCA2). 2 Clinical variants include the hypertrophic, vesiculobullous, hypopigmented, cornifying, zosteriform and linear subtypes, and the rare subtype comedonal Darier disease (CDD). 1,3―6 CDD tends to appear in seborrhoeic areas. The characteristic morphological features are prominent follicular involvement, sometimes associated with keratotic plugs, and the presence of greatly elongated dermal villi and papillary projections. 4 There have been no conclusive reports on the aetiology of CDD and it is still controversial as to whether or not CDD is a variant of DD, and if it is caused by ATP2A2 gene mutations, although a combination of CDD and classic DD was reported in one patient. 7 The present study identifies a previously unreported three-base deletion mutation in ATP2A2 in a patient with CDD.