Hiromaro Kiryu

Macrophage infiltration correlates with tumor stage and angiogenesis in human malignant melanoma: Possible involvement of TNFα and IL‐1α

We examined whether macrophage infiltration is associated with angiogenesis in cutaneous melanoma. The numbers of macrophages and microvessels increased significantly with increasing depth of tumor and with tumor angiogenesis. Macrophage infiltration thus appeared to provide a useful diagnostic marker for the progression of cutaneous melanoma. We further examined whether human melanoma cells produce angiogenic factors in response to macrophage‐derived cytokines, tumor necrosis factor alpha (TNFα) and interleukin‐1 alpha (IL‐1α). Treatment of melanoma cells with TNFα and IL‐1α in vitro enhanced the production of interleukin‐8 (IL‐8) and vascular endothelial growth factor (VEGF), and of basic fibroblast growth factor (bFGF) to a lesser degree, in human melanoma cells. Lipopolysaccharide (LPS)‐activated human monocytes enhanced production of IL‐8, VEGF, TNF α, as well as IL‐1α, but not bFGF. Co‐culture of human monocytes and human melanoma cells was also found to significantly enhance production of IL‐8 and VEGF in the absence and presence of LPS, compared with either monocytes or melanoma cells alone. The production of IL‐8 and VEGF from co‐cultured melanoma cells and LPS‐activated monocytes was blocked when anti‐TNF‐α antibody or anti‐IL‐1α antibody was co‐administrated. This is direct evidence that production of the potent angiogenic factors IL‐8 and VEGF from melanoma cells is up‐regulated through TNFα and/or IL‐1α secreted by activated monocytes/macrophages, influencing both tumor growth and angiogenesis in melanomas. Int. J. Cancer 85:182–188, 2000. ©2000 Wiley‐Liss, Inc.

Prurigo pigmentosa: a distinctive inflammatory disease of the skin.

More than 200 patients with prurigo pigmentosa, a disease described first by Nagashima in 1971, have been reported on in Japan, but only 28 non-Japanese patients have come to notice as of today. In order to establish reliable, repeatable criteria for diagnosis of the disease, we studied 25 patients with prurigo pigmentosa and reviewed the literature pertaining to it as recorded in another 182 patients.Clinically, prurigo pigmentosa presents itself as pruritic urticarial papules, papulovesicles, and vesicles arranged in reticular pattern and distributed symmetrically on the back, neck, and chest. Lesions involute in a matter of days, leaving behind netlike pigmentation. Exacerbations and recurrences are the rule. Histopathologically, prurigo pigmentosa begins with a superficial perivascular infiltrate of neutrophils. Shortly thereafter, neutrophils are scattered in dermal papillae and then sweep rapidly through an epidermis in which spongiosis, ballooning, and necrotic keratocytes are accompaniments. En route, abscesses may form in the surface epithelium. Very soon, eosinophils and lymphocytes come to predominate over neutrophils in a dermal infiltrate that assumes a patchy lichenoid pattern. Intraepidermal vesiculation follows on spongiosis and ballooning and, sometimes, subepidermal vesiculation on vacuolar alteration at the dermo-epidermal junction. As the epidermis becomes hyperplastic, parakeratotic, and slightly hyperpigmented, melanophages begin to appear in the dermis. Studies by immunofluorescence are negative invariably. Dapsone or minocyclin are effective treatments; both of those agents inhibit migration and/or function of neutrophils. The cause and pathogenesis have yet to be determined. Prurigo pigmentosa is unique among inflammatory diseases of the skin and the singularity of it is manifest both clinically and histopathologically.

Encapsulated fat necrosis – A clinicopathological study of 8 cases and a literature review

Eight cases of encapsulated fat necrosis are described. The patients were two males and six females from 10 to 77 years of age. The majority of the lesions clinically presented as asymptomatic, multiple, mobile, small nodules. All patients were treated by simple excisions of the nodules. Grossly, the lesions were whitish‐yellow in color, smoothly‐surfaced, round nodules measuring 3 to 20 mm in the greatest diameter. Histopathologically, the nodules were basically composed of variably degenerated and necrotic fatty tissue covered by fibrous connective tissue capsule associated with occasional calcification and inflammatory cell infiltrates. Among several terms proposed for this disease, encapsulated fat necrosis is considered most preferable term based on the clinical and histological findings of the present and reported cases.

Naevoid hyperkeratosis of the nipple and areola in a man

Sir, We read with interest the recent report by Cox et al. on the association of atopic dermatitis with the beta subunit of the high-affinity IgE receptor (Fc1RI-b). The gene was originally identified as a candidate for atopy on human chromosome 11q. Fc1RI-b has been shown to be involved in the amplification of Fc1RI-mediated signalling that might be related to the pathogenesis of atopic disease. Because of the predominantly maternal transmission of atopy, it has been strongly suggested that the gene for Fc1RI-b may show a parent-of-origin effect such as genomic imprinting. One previous report consistent with this notion showed maternal transmission of the I181L allele in a British population, while another showed no parent-of-origin effect of the transmission of the E237G allele in an Australian population. The report by Cox et al. again raises this issue by demonstrating exclusive maternal transmission of Fc1RI-b alleles to offspring with atopic dermatitis. None the less, as far as we know, there has been no direct test of possible allele-specific expression of this gene. To study the possible involvement of a genomic imprinting mechanism, we have used the widely applicable mouse model system. We find, as detailed below, that the Fc1RI-b gene shows no parent-of-origin-specific expression, using F1 hybrids between a laboratory mouse strain (C57BL/6J) and wild mouse strains [either Mus musculus molossinus (MOLF/Ei) or M. spretus (SPRET/Ei)]. The parental mouse strains (C57BL/6J, MOLF/Ei, SPRET/ Ei) were purchased from Jackson Laboratory (Bar Harbor, ME, U.S.A.). Cloning, sequencing, total RNA extraction and reverse transcription±polymerase chain reaction (PCR) analysis of Fc1RI-b were done as described previously. Based on a human genomic DNA sequence (GenBank M89796) and a mouse cDNA sequence (GenBank J05019), we designed a PCR primer pair spanning exon 6, intron 6 and exon 7 of the Fc1RI-b gene, so that an intron could be included in the PCR target. This allowed us to measure the gene expression directly, without interference by possible contamination of genomic DNAs in RNA samples. Sequence polymorphisms among C57BL/6J, MOLF/Ei and SPRET/Ei were identified by sequencing PCR products from each strain (deposited in GenBank; accession numbers U90217±U90219). A 395-base pair (bp) fragment of the gene for Fc1RI-b was amplified from cDNAs with primers up6: 5 0-ATCCTGGCCTTTTGCAGTGC-3 0 and dn10: 5 0-TGTATGTGAAATTGTGACAC-3 0. To obtain enough DNA for analyses, a shorter fragment (361 bp) was reamplified from the PCR products with primers up6 and dn4: 5 0-GGAGTGAATGATATCCGCAA-3 0. Allele-specific expression in reciprocal crosses between C57BL/6J and MOLF/Ei was examined by using a Sau3AI restriction fragment length polymorphism (RFLP) in a 361-bp PCR product (Fig. 1A). For RFLP analysis, 3 mL of unpurified PCR products were digested with 5 U of Sau3AI in a 15-mL reaction mixture at 37 8C for 3 h, then electrophoresed in a 12% polyacrylamide gel. The gel was stained by ethidium bromide and photographed under ultraviolet radiation. Both paternally and maternally derived alleles were expressed in all examined tissues, i.e. embryo, placenta and yolk sac at 14 ́5 days postconception, whole body and skin at the newborn stage (Fig. 1B), and spleen, lung and colon in adults (not shown). The data clearly demonstrate the biallelic expression of the gene for Fc1RI-b. To confirm these data, interspecific hybrids between a laboratory mouse strain and M. spretus were used. In these crosses, the C57BL/6J-specific allele (296 bp) can be distinguished from the SPRET/Ei-specific allele (279 bp) by length

Malignant Melanoma In situ Arising in the Nail Unit of a Child

A very rare case of malignant melanoma in situ of the nail unit of a child is presented. Clinically, a pigmented streak was present on the finger nail of a 3‐year‐old girl, and the lesion increased in size and in darkness of the color associated with periungual pigmentation in the following two years. Histopathologically, sections showed proliferation of atypical melanocytes, arranged mostly in single units but some in nests, in and above the basal layer of the epithelium and admixed with long dendrites and a few mitotic figures. Pigmented lesions of nail units of children often show fading or loss of pigmentation clinically; however, a biopsy should be done when they show augmentative changes which clinically suggest malignancy, because subungual malignant melanoma can exist even in children, and proper biopsy can detect it in its early stages.

A case of genital folliculosebaceous cystic hamartoma with an unique aggregated manifestation

Folliculosebaceous cystic hamartoma (FCH) is a recently recognized cutaneous hamartoma composed of follicular, sebaceous and mesenchymal components, and usually occurring on the head and neck. We describe herein a case of FCH with an unique aggregated manifestation in a genital lesion. The patient was a 40‐year‐old woman with a genital lesion composed of a pedunculated nodule, a dome‐shaped nodule and a subcutaneous nodule, measuring 5 cm in the greatest dimension. The largest, pedunculated nodule was histologically composed of an infundibulo‐cystic structure with follicular, sebaceous and mesenchymal elements accompanied by cystic structures of various sizes lined by stratified squamous epithelium and follicular germinative cells suggesting follicular cysts. The dome‐shaped nodule consisted of anastomosing strands of epithelial cells with follicular components. The subcutaneous nodule had two components, an infundibulo‐cystic structure and a cyst lined by squamous epithelium. In our case, the unusual clinical feature of large and multiple nodules was due to the presence of several prominent hamartomatous cystic structures with FCH. This is the third case of giant FCH. The clinical presentation and location of giant FCH is unusual.

Ossifying epithelioid hemangioendothelioma

A case of small epithelioid hemangioendothelioma encapsulated by an egg‐shaped bony shell composed of newly formed mature lamellar bone is presented. A nodule measuring 10 × 5 × 5 mm was excised from inside of the right cheek muscle of a 46‐year‐old man. Histopathologically, the nodule consisted mainly of round‐to‐short spindled epithelioid cells with round nuclei and occasional cytoplasmic vacuoles associated will some foci of osseous metaplasia. Characteristically, egg shell‐like lamellar bone enclosed this lesion showing well‐circumscribed appearance. The main component cells were immunohistochemically stained positive for factor VIII‐related antigen, CD 34, UEA‐1, and vimentin, and proved to be vascular endothelial cells. The term ossifying epilhelioid hemangioendolhelioma is proposed for this unique lesion. This type of epithelioid hemangioendothelioma has not been previously reported to our knowledge, and differentiation from ossifying fibromyxoid tumor of soft parts is considered to be important.

Cutaneous metastasis of CNS chordoma.

A rare case of cutaneous skin metastasis from an intracranial chordoma is presented. A large nodule developed in the left thigh of a 22-year-old woman who had been previously diagnosed to have a chordoma at the base of her skull. Sections from the biopsied specimens of the nodule showed proliferations of physaliphorous cells and stellate cells in cords and in nests in a myxoid stroma. Immunohistochemically, neoplastic cells were stained positively with antibodies to S-100 protein and cytokeratin. The results of the histopathological and immunohistochemical studies of the nodule were interpreted as pointing to a diagnosis of metastatic chordoma based on their similarity to the results of studies of the primary neoplasm in the cranial region. Based on the number of cases of skin metastasis from chordoma reported in the literature, skin should be kept in mind as one of the target organs, although such metastases are still rare.

Proliferative fasciitis: Report of a case with histopathologic and immunohistochemical studies

We present a case of proliferative fasciitis arising adjacent to an operative scar of the right lower leg of a patient with chronic lymphatic leukemia, diabetes mellitus, and multiple subcutaneous angiolipomas. A 61-year old man had a hard mass in his right lower leg that had rapidly increased in size in the past 10 days. The mass was microscopically composed of a dense proliferation of spindle cells forming interlacing fascicles admixed with an inflammatory infiltrate of lymphocytes and eosionphils, focal hemorrhage, and myxomatous change as typically seen in nodular fasciitis as well as many characteristic ganglion cell-like giant cells. Immunohistochemically, most of the spindle-shaped cells were positive for vimentin and alpha-actin, whereas the ganglion cell-like giant cells were positive for vimentin and negative for alpha-actin and lysozyme. We suggest that the main component cells of proliferative fasciitis are fibroblastic in nature, many of which are myofibroblasts in large part, whereas the ganglion cell-like giant cells are related more closely to fibroblasts rather than histiocytes or pericytes. Additionally, proliferating cell nuclear antigen (PCNA) stain revealed that many of the fibroblastic cells showed high proliferative activity, especially in the hypercellular areas, although there was no significant difference in PCNA staining between the focus traumatized by the needle biopsy and the nontraumatized areas.

Clinical and Immunohistochemical Studies of Skin Eruptions: Relationship to Administration of Interferon‐α

We observed transient, erythematous skin eruptions in 6 patients during the intravenous administration of interferon (INF)‐α for chronic active hepatitis C. The eruptions appeared 5 to 14 days (mean: 6.8 days) after initiating its administration. They were localized or disseminated and consisted of edematous, erythematous, and/or papular changes. Vesicles and petechiae also appeared in some cases. The eruptions disappeared in 10 to 14 days, despite the continuance of INF‐α and without specific treatment.