Kuniaki Ohara

Computer-Based Classification of Dermoscopy Images of Melanocytic Lesions on Acral Volar Skin

We describe a fully automated system for the classification of acral volar melanomas. We used a total of 213 acral dermoscopy images (176 nevi and 37 melanomas). Our automatic tumor area extraction algorithm successfully extracted the tumor in 199 cases (169 nevi and 30 melanomas), and we developed a diagnostic classifier using these images. Our linear classifier achieved a sensitivity (SE) of 100%, a specificity (SP) of 95.9%, and an area under the receiver operating characteristic curve (AUC) of 0.993 using a leave-one-out cross-validation strategy (81.1% SE, 92.1% SP; considering 14 unsuccessful extraction cases as false classification). In addition, we developed three pattern detectors for typical dermoscopic structures such as parallel ridge, parallel furrow, and fibrillar patterns. These also achieved good detection accuracy as indicated by their AUC values: 0.985, 0.931, and 0.890, respectively. The features used in the melanoma-nevus classifier and the parallel ridge detector have significant overlap.

Loricrin gene mutation in a Japanese patient of Vohwinkel's syndrome

Vohwinkels syndrome (VS) is a rare, dominantly inherited keratoderma with pseudoainhum. Recently, a mutation in loricrin gene has been reported in two VS families of British extraction. In the present study, we examined the loricrin gene mutation in a Japanese VS patient. The patient was a 20-year-old woman. She had palmoplantar keratoderma, constricting bands encircling all the fingers, fifth toes, wrist, and neck. She also had generalized mild ichthyosis and suffered from acoustic impairment. Her parents and a brother showed no skin abnormality. Histopathology of the patient revealed hyperkeratosis with parakeratosis, together with hypergranulosis. The clinical and histopathological findings were consistent with an ichthyotic (or Camisa) variant of VS. The sequence analysis of the loricrin gene revealed that the patient had a heterozygous mutation identical to that described in previous reports, i.e. a G insertion producing a frameshift at codon 231 with an abnormal C-terminus. These results clearly demonstrate that a common loricrin gene mutation underlies VS in different ethnic groups.

Acquired digital arteriovenous malformation: a report of six cases

Arteriovenous malformation (AVM) is usually congenital, but an acquired type is also known, of which most are due to a previous injury. We report six patients with acquired digital AVM, all having a small patch of AVM localized to the tip of one finger, and therefore quite different from ordinary AVM which consists of a large pulsatile mass. Histologically, dilated venous and arterial vessels were present in the dermis. Tumour‐like growth was absent; thus, these six cases could be differentiated from arteriovenous haemangioma. Because of the characteristic anatomical site, unique clinical manifestations and histology, this appears to be a new and distinctive entity.

Basal cell carcinoma of the vulva with lymph node and skin metastasis--report of a case and review of 20 Japanese cases.

A 79‐year‐old Japanese woman who had basal cell carcinoma presenting as a large ulcer on her vulva with lymph node and skin metastasis is described. Histological examination revealed that tumor nests with peripheral palisading invaded deeply into the subcutaneous tissue and were accompanied by marked mucinous changes and fibrous reaction. Vascular invasion was also observed. There were inguinal lymph node metastases and two papular skin metastases on her right thigh. The primary tumor and the metastases were excised. The defect was repaired by bilateral gracilis musculo cutaneous flaps and a skin graft.

Subungual melanoma: Histological examination of 50 cases from early stage to bone invasion

Subungual melanoma is a rare form of malignant melanoma. It is extremely difficult to differentiate it histologically from benign melanonychia striata or melanocytic nevus, especially in the early stage. We divided 50 cases of subungual melanoma into four groups according to clinical progress, and examined their histological findings in each respective stage. In the early stage (19 cases), atypical melanocytes were polygonal showing slight nuclear atypia with no mitoses at all. In six out of 19 cases (31.6%), the atypical melanocytes proliferated more in the hyponychium than in the nail matrix, and only very few in the nail bed. Periungual pigmentation (Hutchinsons sign) appeared from the early stage in almost all cases. With stage progression (middle stage, 13 cases; progressive stage, 13 cases; and bone invasive stage, five cases) the number of atypical melanocytes and their degree of nuclear atypia increased, and the ascent of atypical melanocytes and pagetoid spread became conspicuous. Mitoses became apparent only from the progressive stage. From these observations, we would like to propose three new pathological clues of early stage subungual melanoma: (i) “skip lesion”, proliferation of the tumor cells are more prominent in the hyponychium than in the nail bed or nail matrix; (ii) histological confirmation of Hutchinsons sign; and (iii) epithelial thickening and/or compact arrangement of the elongated basal cells.

Lectin-binding sites in Paget's disease.

The presence and distribution of lectin‐binding sites on neoplastic cells of Pagets disease was studied using fluorescein isothiocyanate (FITC)‐conjugated peanut agglutinin (PNA), and FITC‐conjugated wheatgerm agglutinin (WGA), and compared with such lectin‐binding sites on keratinocytes, and cells of eccrine glands, apocrine glands, and mammary glands. Neoplastic cells of both mammary and extramammary Pagets disease showed cytoplasmic staining with both lectins. There were however fewer stained cells in mammary Pagets disease than in extramammary Pagets disease. The cytoplasmic staining of lectin‐binding sites in cells of apocrine glands was in sharp contrast to the cell‐surface staining seen on keratinocytes, or cells of eccrine glands or mammary glands. These results indicate that the lectin‐binding sites of neoplastic cells of Pagets disease more closely resemble those of cells of apocrine glands than of keratinocytes, cells of eccrine glands or cells of mammary glands.

The role of sentinel lymph node biopsy in the management of invasive extramammary Paget's disease: Multi-center, retrospective study of 151 patients

BACKGROUND Although extramammary Pagets disease (EMPD) mostly presents as intraepithelial carcinoma, we sometimes encounter patients with invasive EMPD (iEMPD) who have lymph node metastasis and may develop distant metastasis. Although sentinel lymph node biopsy (SLNB) is widely accepted for various cancers, there is no large study that has assessed its role in iEMPD. OBJECTIVE The main objective of this study is to assess the role of SLNB in patients with iEMPD. MATERIALS AND METHODS We retrospectively collected data on 151 iEMPD patients treated from 1998 to 2012 in 11 institutes in Japan. All 151 patients received curative surgery for their primary tumor and none of them had distant metastasis. SLNB was performed on the 107 patients without lymphadenopathy to determine their LN status. The 44 other patients with lymphadenopathy underwent one of the following procedures to determine their LN status: SLNB in 22 cases, immediate LN dissection in 21, and LN biopsy in 1. RESULTS Compared to those without lymphadenopathy, patients with lymphadenopathy had advanced primary tumors (nodule in the primary tumor, thicker tumor, deeper invasion level, and lymphovascular invasion). The rate of LN metastasis in patients with lymphadenopathy was 80%, compared to 15% in patients without lymphadenopathy who underwent SLNB. Compared to those with negative SLN, patients with positive SLN had advanced primary tumors (nodule in the primary tumor, deeper invasion level, and lymphovascular invasion). Multivariate analysis revealed that dermal invasion (odds ratio 5.8, p=0.04) and lymphovascular invasion (odds ratio 18.0, p=0.0023) were independent factors associated with SLN positivity. Notably, there was no difference in survival between patients with or without SLN metastasis (p=0.71). On the other hand, patients with lymphadenopathy showed worse survival than those with positive SLN (p=0.045). CONCLUSION Clinical lymphadenopathy was strongly correlated with pathological LN metastasis and also associated with worse survival than absence of lymphadenopathy. The rate of occult LN metastasis detected by SLNB was 15%. Survival was not affected by SLN status even when an advanced primary tumor was present in patients with positive SLN. Our results raise the possibility that SLNB and subsequent LN dissection improved the survival of patients with early stage lymphatic spread. Our study indicates that SLNB should be considered for iEMPD if lymphadenopathy is not apparent.

Usefulness of docetaxel as first-line chemotherapy for metastatic extramammary Paget's disease

In invasive extramammary Pagets disease (EMPD), distant metastases may develop and the condition may become fatal; however, no standardized treatment has been established. Although based on only a few cases, several chemotherapy regimens were reported to be promising. We conducted a multicenter, retrospective study to evaluate the efficacy of docetaxel for metastatic EMPD. We retrospectively collected data on 18 metastatic EMPD patients treated using docetaxel from 1998 to 2012 in 12 institutes in Japan. The following clinical data were collected: tumor response, time to progression, overall survival and adverse effects. Of those, three patients treated combined with S‐1, one patient treated with weekly schedule and one patient treated combined with radiotherapy were excluded from the further analysis. All 13 patients received monthly docetaxel as the first‐line treatment. The average number of treatment cycles was 9.1. Among the 12 patients with a confirmed response, seven (58%) showed a partial response, three (25%) stable disease and two (17%) progressive disease. The disease control rate (partial response + stable disease) was as high as 83%. The time to progression and median overall survival were 7.1 and 16.6 months, respectively. The 1‐year overall survival rate determined by the Kaplan–Meier method was 75.0%. All adverse effects were manageable and no treatment‐related deaths were observed. The high disease control rate and overall survival shown by this study suggest that first‐line use of docetaxel may be a promising treatment for metastatic EMPD. A prospective clinical trial is required to confirm our results.

A proposal for a TNM staging system for extramammary Paget disease: Retrospective analysis of 301 patients with invasive primary tumors

BACKGROUND Although extramammary Paget disease (EMPD) usually appears as carcinoma in situ, it sometimes becomes invasive (iEMPD) and fatal. However, a TNM staging system for iEMPD has yet to be established. OBJECTIVE The aim of this study was to establish a TNM staging system for iEMPD. METHODS We retrospectively collected iEMPD patients treated at 12 institutes in Japan. Factors reported to be associated with survival such as distant metastasis, lymph node (LN) metastasis, and primary tumor status were evaluated using the log-rank test. RESULTS We enrolled 301 iEMPD patients, of whom 114 had remote metastases (49 had both distant and LN metastasis; 2, distant metastasis only; and 63, LN metastasis only) and the remaining 187 patients had no remote metastasis. Distant metastasis (M1) showed worse survival (P<0.00001). In the analysis of the 250 patients without distant metastasis, LN metastasis also showed worse survival (P<0.00001). Among the patients with LN metastasis, 2 or more LN metastases (N2) showed worse survival than did single LN metastasis (N1, P=0.02). Lastly, in the analysis of the 187 patients without metastasis, tumor thickness of over 4mm or lymphovascular invasion showed worse survival (T2, P<0.05 and P<0.001, respectively). Patients with neither of these features were defined as T1. From these results, we propose this TNM staging system: stage I, T1N0M0; stage II, T2N0M0; stage IIIa, anyTN1M0; stage IIIb, anyTN2M0; stage IV, anyTanyNM1. Other than stages II and IIIa, each stage had a statistically distinct survival curve. CONCLUSION We propose a TNM staging system for EMPD using simple factors for classification that could provide important prognostic information in managing EMPD. However, accumulation of more patient data and further revision of the system are required.

Surgical Treatment of a Deep Fungal Infection of the Skin by Trichosporon cutaneum

We treated a patient with facial granuloma caused by Trichosporon cutaneum, in whom various therapeutic modalities had been ineffective. A surgical procedure combining excision, topical chemotherapy of the open wound, and covering the defect with a cervicofacial flap was finally successful.