Shinichi Shibata

Human papillomaviruses of the mucosal type are present in some cases of extragenital Bowen's disease

Background  Bowens disease in the genital area is generally considered to be caused by mucosal high‐risk human papillomaviruses (HPVs). However, the detection rate and spectrum of HPVs in extragenital Bowens disease are various and it is not clear to what extent HPV is involved in its pathogenesis.

Dermoscopic evaluation of vascular structures of various skin tumors in Japanese patients.

Dermoscopic analysis of skin tumor has been mainly focused on pigmented structures. Recently, several different morphological types of vessels were found to be well associated with pigmented or non‐pigmented skin tumors in white subjects. Therefore, the recognition of such vascular structures has been applied for diagnostic purposes. As little statistical information on the various pigmented skin tumor vessels of Japanese patients has been reported, we therefore tried to evaluate the association between various vascular structures and 741 tumor lesions of Japanese patients. Vascular structures were dermoscopically recognized in 41 of 102 cases of melanoma, 104 of 119 basal cell carcinoma (BCC), 86 of 257 seborrheic keratosis (SK), 35 of 210 dermal and compound nevus (DN/CN), six of 12 squamous cell carcinoma (SCC) and 16 of 41 Bowen disease (BD). The structures of arborizing and glomerular vessels statistically revealed diagnostic specificity for BCC and BD, respectively, and hairpin vessels were helpful for differentiating SK from other pigmented tumors, as already reported in white patients. The most common vascular pattern observed in melanoma was the linear–irregular structure, but this pattern in Japanese patients had less diagnostic value than in white patients, because its sensitivity was not significantly higher than in SCC. The most remarkable differences between our study and previous reports with white patients were low frequency and sensitivity of dotted, comma and polymorphous vessels in lesions of melanoma, BCC and DN/CN; these vessels had less diagnostic value for Japanese patients. Finally, the frequency of vascular structures observed in melanoma rose along with the increase of the Breslow’s tumor thickness, and 88% of melanomas with vascular vessels revealed tumor thicknesses of more than 2 mm.

A Pilot Study of Human Interferon β Gene Therapy for Patients with Advanced Melanoma by in vivo Transduction Using Cationic Liposomes

BACKGROUND Cationic liposomes containing the human interferon beta (HuIFNbeta) gene (IAB-1) was used for the clinical trial for glioma patients. HuIFNbeta gene therapy showed much higher anti-tumor activity compared with the administration of HuIFNbeta protein for melanoma. These results suggest that HuIFNbeta gene therapy is an attractive strategy for the treatment of melanoma. METHODS Stage IV or III melanoma patients with cutaneous or subcutaneous metastatic lesions were enrolled in this pilot study. IAB-1 was dissolved by sterile PBS at a concentration of 30 microg DNA/ml and was injected into cutaneous or subcutaneous metastatic nodules three times a week for 2 weeks and the effect on the injected and non-injected metastatic lesions was evaluated. RESULTS Clinical responses were as follows (five patients): mixed response (MR) and no change in each one patient, and progressive disease in three patients. In the MR patient, the IAB-1 injected lesion disappeared clinically and histopathologically and one-half of IAB-1 non-injected skin metastases were transiently inflamed and mostly regressed. In the responded non-injected lesions of this patient, histopathologically, infiltration of CD4 positive T cells was observed around the melanoma cells in the dermis, which expressed the HLA-Class II antigen. Adverse events due to this gene therapy were not recognized in any of the patients. CONCLUSIONS The efficacy of this gene therapy was generally insufficient; however, some immunological responses were recognized in one patient. No adverse events were observed. HuIFNbeta gene therapy could be an attractive strategy for treatment of a variety of malignancies, including melanoma, though some modifications should be required.

Interval sentinel lymph nodes in patients with cutaneous melanoma: A single-institution study in Japan

Interval sentinel lymph nodes (ISLN) are defined as the lymph nodes located between the primary melanoma and anatomically well‐defined lymph nodal basins. It was reported that the ISLN appeared to be at the same metastatic risk as sentinel lymph nodes (SLN) in the traditional nodal basins. This study aimed to examine the incidence and metastatic risk of the ISLN in melanoma patients. Between June of 1999 and December of 2008, 117 patients enrolled at Nagoya University Hospital underwent SLN biopsy for primary cutaneous melanoma with a Breslow thickness of at least 1.0 mm. Triple techniques with lymphoscintigraphy, blue dye injection and gamma probe were used for the biopsy except for 13 cases that underwent lymphoscintigraphy, ultrasonography and blue dye injection, but without gamma probe. Patients who had melanoma of the head and neck were excluded from this analysis. The SLN were identified in 253 nodal basins from 117 patients, and ISLN were found in six patients (5%). We recognized 41 (17%) SLN metastases in 246 conventional nodal basins and one (14%) in seven ISLN. Although ISLN were identified infrequently, the incidence of metastasis into the ISLN was similar to that into SLN in conventional nodal basins. It is therefore recommended that preoperative lymphoscintigraphy and intraoperative recognition of ISLN should be performed.

Proposed classification of longitudinal melanonychia based on clinical and dermoscopic criteria.

For longitudinal melanonychia, clinical and dermoscopic criteria for differentiating malignant melanoma in situ from benign nevus/lentigo/functional melanonychia have not been fully established.

Postoperative DAV-IFN-β therapy does not improve survival rates of stage II and stage III melanoma patients significantly.

Background  DAV‐interferon (IFN)‐β therapy is a combination chemotherapy of dacarbazine (DTIC), nimustine (ACNU) and vincristine (VCR) with local subcutaneous injection of IFN‐β that is widely employed as postoperative adjuvant chemotherapy to treat malignant melanoma in Japan. However, the efficacy of DAV‐IFN‐β therapy has not been confirmed by randomized controlled trials and the benefit of DAV‐IFN‐β therapy has not been established yet. This study evaluated the contribution of DAV‐IFN‐β therapy to improve survival of postoperative patients with cutaneous melanoma.

Clinicopathologic analysis of 66 Japanese thin melanomas with metastasis of sentinel or regional lymph node.

Assessment of sentinel lymph node status is commonly performed in the treatment of cutaneous melanoma. However, there are no definite guidelines for thin melanomas with Breslow tumor thickness <1.0 mm, in part because thin melanomas are relatively infrequently positive for lymph node metastasis.

Eight cases of malignant melanoma treated with inguinal and iliac lymph node dissection

センチネルリンパ節生検の概念が普及した現在では, 悪性黒色腫の鼠径リンパ節郭清は, センチネルリンパ節で転移を認める場合や臨床的に明らかにリンパ節が腫脹している場合が適応とされるようになってきた。しかし鼠径リンパ節転移を認めた場合の骨盤内リンパ節郭清の適否は施設間によってさまざまなのが現状である。我々は1999年4月～2003年10月までに悪性黒色腫の鼠径リンパ節郭清を23例行った。そのうち, 鼠径リンパ節が明らかに腫大している症例, 鼠径部のセンチネルリンパ節転移陽性で原発腫瘍の厚さが4mm以上, もしくは潰瘍を伴う症例の計8例に対して骨盤内リンパ節郭清も行った。その8例中2例に骨盤内リンパ節に転移を認め, さらに術後1年半以内に多臓器転移を認めた。これらの経験をもとに骨盤内リンパ節郭清の適応と意義について考察した。