Key point in dermoscopic differentiation between early nail apparatus melanoma and benign longitudinal melanonychia

Longitudinal melanonychia presents in various conditions including neoplastic and reactive disorders. It is much more frequently seen in non-Caucasians than Caucasians. While most cases of nail apparatus melanoma start as longitudinal melanonychia, melanocytic nevi of the nail apparatus also typically accompany longitudinal melanonychia. Identifying the suspicious longitudinal melanonychia is therefore an important task for dermatologists. Dermoscopy provides useful information for making this decision. The most suspicious dermoscopic feature of early nail apparatus melanoma is irregular lines on a brown background. Evaluation of the irregularity may be rather subjective, but through experience, dermatologists can improve their diagnostic skills of longitudinal melanonychia, including benign conditions showing regular lines. Other important dermoscopic features of early nail apparatus melanoma are micro-Hutchinson's sign, a wide pigmented band, and triangular pigmentation on the nail plate. Although there is as yet no solid evidence concerning the frequency of dermoscopic follow up, we recommend checking the suspicious longitudinal melanonychia every 6 months. Moreover, patients with longitudinal melanonychia should be asked to return to the clinic quickly if the lesion shows obvious changes. Diagnosis of amelanotic or hypomelanotic melanoma affecting the nail apparatus is also challenging, but melanoma should be highly suspected if remnants of melanin granules are detected dermoscopically.ArticleJOURNAL OF DERMATOLOGY. 38(1):45-52 (2011)journal articl

Sentinel lymph node biopsy in Japan

Similar to the practice in Western countries, intra-operative lymphatic mapping and selected lymphadenectomy (SLNB) have been validated and are widely performed for the staging of melanoma in Japan. Recent studies have shown that approximately 90% (73/81) of university hospitals and several cancer hospitals routinely perform SLNB, and half of all melanoma patients receive this examination. SLNB is performed according to a variation of the standard procedure described by Morton and Cochran. The most frequently used tracers are Tc-99m-tin colloid or Tc-99m-phytate for scintigraphy and patent blue violet or indigo carmine as a blue dye. Some institutions use indocyanine green, which is fluorescent and can be used to visualize sentinel lymph node(s) (SLNs) under an infrared camera. The recent detection rate of SLNs has increased to more than 95% with the method using blue dye, lymphoscintigraphy, and a handheld gamma probe. In a multicenter study, the rates of metastasis in SLN were as follows: pTis, 0% (0/36); pT1, 10.7% (6/56); pT2, 21.0% (13/63); pT3, 34.0% (35/103); and pT4, 62.4% (63/101). The metastasis rate was also significantly related to ulceration of the primary tumor. Here, we discuss data from Japanese patients and the present status of SLNB in Japan.ArticleINTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY. 14(6):490-496 (2009)journal articl

High-frequency 30-MHz sonography in preoperative assessment of tumor thickness of primary melanoma: usefulness in determination of surgical margin and indication for sentinel lymph node biopsy

The original publication is available at www.springerlink.comHigh-frequency sonographic imaging has been used for the preoperative evaluation of primary malignant melanoma. In the present study, to identify the usefulness of 30-MHz sonography for determination of the surgical margin and indication for sentinel lymph node biopsy, the correlation between sonometric and histometric tumor thickness was investigated. A total of 74 primary melanomas, in patients seen at the dermatology clinic, Shinshu University Hospital, from 1998 to 2006, were evaluated using high-frequency sonographic equipment with two probes (15 MHz and 30 MHz), and tumor thickness was measured using electronic calipers before surgical treatment. All the primary lesions were surgically excised and Breslow's tumor thickness was measured histologically. In 68 melanomas, excluding 2 lesions of melanoma in situ and 4 lesions with poor sonographic images, sonographic and histologic thickness showed good correlation (r = 0.887). Particularly, in 26 melanomas affecting the soles of the feet, sonographic and histologic thickness showed excellent correlation (r = 0.945). Regarding the T categorization, in which T1-T4 are divided at 1, 2, and 4 mm in thickness, the categories determined with sonometry corresponded very well to those determined with histometry. The correspondence was particularly excellent in thinner primary lesions with thickness around 1 mm. We excised almost all these primary melanomas with surgical margins based on the sonometric thickness. In 22 patients with sonometric thickness more than 1 mm, sentinel lymph node biopsy and/or radical lymphadenectomy was performed. High-frequency sonography (30-MHz) is very useful in the preoperative prediction of tumor thickness, particularly in thinner primary lesions, which allows us to determine surgical margins and indication for sentinel lymph node biopsy.ArticleINTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY. 14(5):426-430 (2009)journal articl

Platinum and anthracycline therapy for advanced cutaneous squamous cell carcinoma

Because metastatic cutaneous squamous cell carcinoma (CSCC) is rare, standard chemotherapy has not been fully established. In Japan, combination platinum and anthracycline chemotherapy has been used for elderly patients with advanced CSCC because of its low toxicity. However, the clinical benefit of this therapy has not been fully examined. We retrospectively examined the response rate of combination platinum and anthracycline chemotherapy for metastatic CSCC. Eight patients received combination chemotherapy for metastatic lesions; there were lymph node lesions in 6 patients and skin and lung lesions in one patient each. The combination regimens were as follows: cisplatin (CDDP) (60-90 mg/m(2)/day, day 1) and adriamycin (ADM) (20-40 mg/m(2)/day, day 1 or 2) was administered in 5 patients; CDDP (10-15 mg/m(2)/day, days 1-5) and epirubicin (epi-ADM) (10-15 mg/m(2)/day, days 1-5) was administered in 2 patients; and carboplatin (CBDCA) (200-400 mg/m(2)/day, day 1) and ADM (20-40 mg/m(2)/day, day 1 or 2) was administered in one patient. The responses were as follows: complete response in 2 patients (CDDP + ADM for lung metastasis, CDDP + epi-ADM for lymph node metastasis), partial response in 1 (CDDP + ADM for lymph node metastasis), stable disease in 2, and progressive disease in 3. A durable response was observed in 2 patients showing complete responses (58 and 112 months). The clinical effect of the combination of platinum and anthracycline for metastatic CSCC was limited despite the findings of two patients showing durable complete responses.ArticleINTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY. 18(3):506-509 (2013)journal articl

Polyclonality of BRAF Mutations in Acquired Melanocytic Nevi

Melanocytic nevi are thought to be senescent clones of melanocytes that have acquired an oncogenic BRAF mutation. BRAF mutation is considered to be a crucial step in the initiation of melanocyte transformation. However, using immunomagnetic separation or laser-capture microdissection, we examined BRAF mutations in sets of approximately 50 single cells isolated from acquired melanocytic nevi from 13 patients and found a substantial number of nevus cells that contained wild-type BRAF mixed with nevus cells that contained BRAF(V600E). Furthermore, we simultaneously amplified BRAF exon 15 and a neighboring single nucleotide polymorphism (SNP), rs7801086, from nevus cell samples obtained from four patients who were heterozygous for this SNP. Subcloning and sequencing of the polymerase chain reaction products showed that both SNP alleles harbored the BRAF(V600E) mutation, indicating that the same BRAF(V600E) mutation originated from different cells. The polyclonality of BRAF mutations in acquired melanocytic nevi suggests that mutation of BRAF may not be an initial event in melanocyte transformation.ArticleJOURNAL OF THE NATIONAL CANCER INSTITUTE. 101(20):1423-1427 (2009)journal articl

Applicability of radiocolloids, blue dyes and fluorescent indocyanine green to sentinel node biopsy in melanoma

Patients with primary cutaneous melanoma underwent sentinel node (SN) mapping and biopsy at 25 facilities in Japan by the combination of radiocolloid with gamma probe and dye. Technetium-99m (99mTc)-tin colloid, 99mTc-phytate, 2% patent blue violet (PBV) and 0.4% indigo carmine were used as tracers. In some hospitals, 0.5% fluorescent indocyanine green, which allows visualization of the SN with an infrared camera, was concomitantly used and examined. A total of 673 patients were enrolled, and 562 cases were eligible. The detection rates of SN were 95.5% (147/154) with the combination of tin colloid and PBV, 98.9% (368/372) with the combination of phytate and PBV, and 97.2% (35/36) with the combination of tin colloid or phytate and indigo carmine. SN was not detected in 12 cases by the combination method, and the primary tumor was in the head and neck in six of those 12 cases. In eight of 526 cases (1.5%), SN was detected by PBV but not by radiocolloid. There were 13 cases (2.5%) in which SN was detected by radiocolloid but not by PBV. In 18 of 36 cases (50%), SN was detected by radiocolloid but not by indigo carmine. Concomitantly used fluorescent indocyanine green detected SN in all of 67 cases. Interference with transcutaneous oximetry by PVB was observed in some cases, although it caused no clinical trouble. Allergic reactions were not reported with any of the tracers. 99mTc-tin colloid, 99mTc-phytate, PBV and indocyanine green are useful tracers for SN mapping.ArticleJOURNAL OF DERMATOLOGY. 39(4):336-338 (2012)journal articl