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

BACKGROUND: For longitudinal melanonychia, clinical and dermoscopic criteria for differentiating malignant melanoma in situ from benign nevus/lentigo/functional melanonychia have not been fully established. OBJECTIVE: To propose a clinical classification of longitudinal melanonychia that is useful in judging the need for follow-up. METHODS: A total of 137 patients with longitudinal melanonychia referred to our outpatient clinic in the most recent eight years were included. The mean and median lengths of follow-up for patients were 5.0 and 5.5 years, respectively. We classified the 137 lesions into three types by clinical and dermoscopic features of the nail and periungual skin, including Hutchinson sign, variation of color, and borders in the pigmentation band. We observed type I and II lesions with dermoscopy every six months and three months, respectively. RESULTS: After follow-up, all 72 lesions classified as type I were thought to be benign nevus/lentigo/functional melanonychia. Five of the 52 lesions classified as type II showed enlargement during follow-up, and biopsy was performed. Of these five lesions, three were diagnosed as nevus/lentigo, and the other two were diagnosed as malignant melanoma in situ. All 13 lesions classified as type III were diagnosed as malignant melanoma in situ. CONCLUSION: We can expect a type I lesion to be a benign nevus/lentigo/functional melanonychia and a type III lesion to be a malignant melanoma in situ; however, type II lesions fall in a gray zone. We believe this classification is useful in deciding treatment and follow-up.

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

BACKGROUND: 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. METHODS: We analyzed the clinicopathologic relationship among tumor thickness, mitotic index, tumor infiltrating lymphocytes (TIL), tumor size, regional lymph node metastasis and prognosis in 66 Japanese patients with thin melanomas. Immunohistochemical evaluations for TIL were also performed. RESULTS: Thirty-one of the 66 melanomas were Clark level I without lymph node metastasis (0/31, 0%). In tumors of Clark level II or higher (35/66), there were five (14%) regional lymph node metastasis. Melanomas with two or more mitoses in 1 mm(2) per high-power fields showed higher frequencies of lymph node metastasis (2/3, 67%), compared to those with fewer than two mitoses (3/32, 9%). Tumors with intensive TIL that partially or completely surrounded the tumor revealed higher frequencies of lymph node metastasis (5/28, 18%), compared to those with none or slight TIL (0/7, 0%). The main components of TIL were CD8-positive T lymphocytes. No metastasized tumors were under 2.0 cm(2) . CONCLUSIONS: The presence of mitotic activity, large tumor size and an intense lymphocytic infiltrate should prompt sentinel lymph node biopsy in thin melanomas.

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.

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 beta 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.

Establishment of tyrosinase sequence database in normally pigmented Indians and Japanese for rapid determination of novel mutations.

BACKGROUND: Many mutations of the tyrosinase gene have been reported in oculocutaneous albinism type I (OCA1) patient. In the future, a greater number of novel mutations will be found as the search for pathological mutations in the tyrosinase genes of OCA patients from various ethnic origins. For rapid determination in future whether an observed mutation is a polymorphism or a novel pathological one, sequence databases of the gene of various ethnic people are needed. OBJECTIVE: We established a sequence database of the tyrosinase gene of Japanese as well as Indian people. METHOD: We collected DNA from 109 Japanese and 103 Indians with normal pigmentation and analyzed their tyrosinase gene using a direct sequencing method. RESULT: The database shows an apparent difference between the two ethnic groups in polymorphisms of the tyrosinase gene namely, Q402 allele, Y192 allele and IV2+24 insT were found in the Indian population, but not in the Japanese. On the other hand, some Japanese had IV2-21 insT but none of the Indians did. The database supports the notion that the tyrosinase gene evolved and extended separately in the two ethnic groups. And the developing database confirmed that the reported mutations causing Indian and Japanese OCA were not among the polymorphisms in the database, which conversely gives genetical proof of the "genuine" pathological mutations. CONCLUSION: Eventually, the sequence database we established will contribute to demonstrating novel mutations of albinism in Indians and Japanese.