Atsumichi Urabe

Extramammary Paget's disease: comparative histopathologic studies of intraductal carcinoma of the breast and apocrine adenocarcinoma.

We examined 32 cases (38 lesions) of extramammary Pagets disease (EMPD) in relation to comparative studies on intraductal carcinoma of the breast (ductal carcinoma in situ, DCIS) and apocrine adenocarcinoma (AAC). Lesions included scrotum (18 lesions), vulva (8), axilla (6), groin (3), penis (2) and chest wall (1), and the distribution was compatible with that of apocrine or supernumerary mammary glands. Histologically, extra‐mammary Pagets and DCIS cells exhibited a large amount of a pale‐stained cytoplasm. The cytoplasm of AAC cells frequently contained granules, was eosinophilic and differed from that of Pagets or DCIS cells. Immunohistochemical studies revealed positive reactions for polyclonal and monoclonal antibodies to carcinoembryonic antigen in all EMPD and most DCIS, but not in AAC. Recent studies have shown that extramammary Pagets cells exhibit characteristics of glandular epithelial cells and that most cases of EMPD are not accompanied by an underlying carcinoma. The results obtained in this study, coupled with data on the frequency of the supernumerary breasts, lead to the speculation that extramammary Pagets cells originate from ectopic mammary glands or from pluripotential germinative cells in the epidermis, capable of differentiating toward the mammary glands.

ALOPECIA UNIVERSALIS TREATED WITH ORAL CYCLOSPORINE A AND PREDNISOLONE: IMMUNOLOGIC STUDIES

Alopecia universalis is a refractory condition. Although the cause of this disease is unknown, immunologic abnormalities have recently been suspected. Thus, we treated six cases of refractory alopecia universalis with immunotherapy. Oral administration of cyclosporine A (2.5 mg/kg) and prednisolone (5 mg/day) resulted in marked symptomatic improvement. Cyclosporine A did not produce any side effects because the administered dosage was relatively low. At present, more than 6 months after the cessation of treatment, recurrence of alopecia has not been seen. Oral administration of low‐dose cyclosporine A and prednisolone is considered to be an effective treatment for this disease. Immunologic examination of peripheral blood demonstrated improvement of immunologic function. In particular, cos‐positive T cells, NK cells, and C3, which had been reduced, were increased. A reduction in active CD4 cells, eosinophils, and circulating immune complexes was observed. Histology with fluorescent antibodies showed T‐cell infiltration around the hair matrixes. This phenomenon was no longer observed after treatment. These improvements in immunologic function were seen in parallel with the resolution of the clinical symptoms, indicating that immunologic abnormalities are related to this disease.

Malignant Granular Cell Tumor

A malignant granular cell tumor (MGCT) appeared on the subungual tissue of the right index finger of a 51‐year‐old woman. Two years after resection of the tumor, it recurred, and the finger finally had to be amputated. Six months later, she noticed multiple cutaneous nodules on her trunk. Despite chemotherapy and X‐ray irradiation, the patient died 18 months after the second operation. Histology of the specimen revealed a proliferation of both polygonal and spindle‐shaped cells with large hyperchromatic nuclei and an eosinophilic granular cytoplasm. Peripheral nerves were encompassed by the tumor cells. Immunohistochemically, the tumor cells were positive for S‐100 protein and Leu 7 (myelin‐associated glycoprotein). These findings support the hypothesis that MGCT cells are of Schwann cell origin.

Distribution of Epithelial Membrane Antigen in Eccrine Poroma

Using immunohistochemical methods, we investigated the distribution of epithelial membrane antigen (EMA) on the normal eccrine gland, eccrine poroma and hidroacanthoma simplex. Granular membrane-associated reaction of EMA was detected on the outer cells of both the intraepidermal and the upper portion of intradermal eccrine ducts, as well as on the luminal surfaces and intercellular canaliculi of eccrine glands. Clear immunolabeling was also present in the tumor cells of eccrine poroma and hidroacanthoma simplex. Thus, it is suggested that the constituent cells of these tumors originate from the outer cells of the intraepidermal and/or the upper portion of the intradermal eccrine ducts. There was no immunolabeling for EMA on the tumor cells of seborrheic keratosis and basal cell carcinoma. Immunohistochemical staining for EMA is a useful tool for the diagnosis of skin appendage tumors.

Immunohistochemical Characterization of Cellular Infiltrates in Epidermal Tumors Induced by Two-stage and Complete Chemical Carcinogenesis in Mouse Skin

We investigated the population and pattern of the infiltrated cells in both benign and malignant epidermal tumors which were induced chemically with benzo(a)pyrene (B(a)P) in murine skin. In benign papillomas, which were evolved by a two stage carcinogenesis regimen, a slight to mild inflammatory infiltration around the tumors was observed, and cells infiltrating into the tumor nests were rarely seen. In carcinomas, which were produced by a complete carcinogenesis regimen, a dense inflammatory infiltration was observed around the tumor nests. The infiltrated cells were characterized as T‐lymphocytes, macrophages, and neutrophils. Natural killer (NK) cells were found around and in the tumor nests, but their number was small. Both T‐lymphocytes and macrophages were found to invade the tumor nests in squamous cell carcinoma whose duration was more than four weeks. This experimental carcinogenesis animal model allows the detailed quantitative and functional analysis of the infiltration of immunocompetent cells into epidermal tumors.

A combined therapeutic modality with hyperthermia and locally administered rIFN-β inhibited the growth of B16 melanoma in association with the modulation of cellular infiltrates

Murine B16-F10 melanoma was treated with local microwave hyperthermia, local injection of murine recombinant interferon-beta (rIFN-beta) or a combination of both in order to investigate the augmentation of anti-proliferative effects with this combination treatment. Concerning the local modulation of immunological reactions of the host, local hyperthermia at 43 degrees C for 15 min on murine melanoma caused remarkable infiltration of natural killer cells and local injection of rIFN-beta led to considerable infiltration of T cells. When these two modalities were combined, the infiltration of NK cells completely disappeared and, instead, remarkable augmentation of T cell infiltration occurred. Synergistic suppressive effects on melanoma growth with occasional scar formation were seen with this combined modality. These results indicate that local hyperthermia with a combination of rIFN-beta modulates local immune reactions of the host, and probably this immune reaction is partly involved in the course of the suppression of tumor growth.

Suppression of murine melanoma growth with a combination of microwave hyperthermia and local injection of interleukin 2

Local microwave hyperthermia in combination with local injections of interleukin 2 (IL‐2) was found to exert a remarkable suppressive effect on murine melanoma growth. Both of these therapeutic modalities caused marked tumour infiltration with natural killer cells. After microwave hyperthermia or IL‐2 injection alone there was minimal T‐cell infiltration, but T cells were more in evidence following combination therapy.

Identification of a cell layer containing α-smooth muscle actin in the connective tissue sheath of human anagen hair

SummaryImmunohistochemical and immunoelectron microscopy studies revealed the presence of α-smooth muscle (α-SM) actin in fibroblasts located in the connective tissue sheath (CTS) of human anagen hair follicles. Immunostaining was positive from the base of the bulb to the upper part of the lower portion of the mature anagen hair follicles. The late catagen hair follicles did not stain. Ultrastructurally, α-SM actin was detected only in the fibroblasts located in the innermost layer of the transverse collagenous fibres. Since α-SM actin is located in cells with contractile potential, this newly identified layer may play an important role in the morphological changes of the lower portion of the hair follicle during the hair growth cycle.

Expression of the fos oncogene in basal cell carcinoma

Using immunohistochemical technique and Western blot analysis, we demonstrated the increased expression of the c-fos oncogene in the infiltrative type of solid basal cell carcinoma (BCC), but low or no expression in the circumscribed type of solid BCC. The infiltrative type is called aggressive BCC and had been shown to exhibit a higher rate of recurrence than the circumscribed type. Our results indicate that increased expression of the fos oncogene is closely related to the invasive ability of the tumor cells.

Expression of the fos oncogene in B16 melanoma cells exhibiting different metastatic abilities

Expression of the c-fos oncogene in B16 melanoma with high and low metastatic abilities was investigated. In Northern blot analysis, a highly metastatic B16-F10 melanoma cell line showed a higher extent of transcription of the fos gene than did a low metastatic B16-F1 cell line. Immunohistochemical studies revealed that B16-F10 cells stained more strongly than B16-F1 cells, both in vitro and in vivo, using the antibody against fos proteins. These results suggest that fos product may be involved in the regulation of gene expressions related to metastasis of B16 melanoma.