Rosamaria Corona

Interobserver variability on the histopathologic diagnosis of cutaneous melanoma and other pigmented skin lesions.

PURPOSE To assess the interobserver agreement on the diagnosis and classification of cutaneous melanoma. MATERIALS AND METHODS A set of 140 slides of cutaneous melanoma, including a small subset of benign pigmented skin lesions, were circulated to four experienced histopathologists. The kappa statistic for multiple ratings per subject was calculated using the method described by Fleiss. RESULTS The kappa value on the diagnosis of cutaneous melanoma versus benign lesions was 0.61. There was some discordance on the diagnosis in 37 of 140 cases (26%). For the histopathologic classification of cutaneous melanoma, the highest kappa values were attained for Breslow thickness (kappa = 0.76) and presence of ulceration (kappa = 0.87). The agreement was generally poor for other histologic features, such as level of dermal invasion (kappa = 0.38), presence of regression (kappa = 0.27), and lymphocytic infiltration (kappa = 0.27). CONCLUSION Our study suggests considerable disagreement among pathologists on the diagnosis of melanoma versus other pigmented lesions. Tumor thickness and presence of ulceration are the most reproducible histologic features of cutaneous melanoma.

Dermoscopy Improves Accuracy of Primary Care Physicians to Triage Lesions Suggestive of Skin Cancer

PURPOSE Primary care physicians (PCPs) constitute an appropriate target for new interventions and educational campaigns designed to increase skin cancer screening and prevention. The aim of this randomized study was to determine whether the adjunct of dermoscopy to the standard clinical examination improves the accuracy of PCPs to triage lesions suggestive of skin cancer. PATIENTS AND METHODS PCPs in Barcelona, Spain, and Naples, Italy, were given a 1-day training course in skin cancer detection and dermoscopic evaluation, and were randomly assigned to the dermoscopy evaluation arm or naked-eye evaluation arm. During a 16-month period, 73 physicians evaluated 2,522 patients with skin lesions who attended their clinics and scored individual lesions as benign or suggestive of skin cancer. All patients were re-evaluated by expert dermatologists at clinics for pigmented lesions. Referral accuracy of both PCP groups was calculated by their scores, which were compared to those tabulated for dermatologists. RESULTS Referral sensitivity, specificity, and positive and negative predictive values were 54.1%, 71.3%, 11.3%, and 95.8%, respectively, in the naked-eye arm, and 79.2%, 71.8%, 16.1%, and 98.1%, respectively, in the dermoscopy arm. Significant differences were found in terms of sensitivity and negative predictive value (P = .002 and P = .004, respectively). Histopathologic examination of equivocal lesions revealed 23 malignant skin tumors missed by PCPs performing naked-eye observation and only six by PCPs using dermoscopy (P = .002). CONCLUSION The use of dermoscopy improves the ability of PCPs to triage lesions suggestive of skin cancer without increasing the number of unnecessary expert consultations.

Three-point checklist of dermoscopy

Background: Dermoscopy used by experts has been demonstrated to improve the diagnostic accuracy for melanoma. However, little is known about the diagnostic validity of dermoscopy when used by nonexperts. Objective: To evaluate the diagnostic performance of nonexperts using a new 3-point checklist based on a simplified dermoscopic pattern analysis. Methods: Clinical and dermoscopic images of 231 clinically equivocal and histopathologically proven pigmented skin lesions were examined by 6 nonexperts and 1 expert in dermoscopy. For each lesion the nonexperts assessed 3 dermoscopic criteria (asymmetry, atypical network and blue-white structures) constituting the 3-point method. In addition, all examiners made an overall diagnosis by using standard pattern analysis of dermoscopy. Results: Asymmetry, atypical network and blue-white structures were shown to be reproducible dermoscopic criteria, with a kappa value ranging from 0.52 to 0.55. When making the overall diagnosis, the expert had 89.6% sensitivity for malignant lesions (tested on 68 melanomas and 9 pigmented basal cell carcinomas), compared to 69.7% sensitivity achieved by the nonexperts. Remarkably, the sensitivity of the nonexperts using the 3-point checklist reached 96.3%. The specificity of the expert using overall diagnosis was 94.2% compared to 82.8 and 32.8% achieved by the nonexperts using overall diagnosis and 3-point checklist, respectively. Conclusion: The 3-point checklist is a valid and reproducible dermoscopic algorithm with high sensitivity for the diagnosis of melanoma in the hands of non-experts. Thus it may be applied as a screening procedure for the early detection of melanoma.

Clinically equivocal melanocytic skin lesions with features of regression: a dermoscopic-pathological study.

Background  Benign melanocytic skin lesions may be difficult to differentiate from melanoma both clinically and dermoscopically. One of the most confounding dermoscopic features, commonly seen in melanoma but in our experience also in melanocytic naevi, is represented by the so‐called blue–white structures (BWS).

Beauty treatments and risk of parenterally transmitted hepatitis : results from the hepatitis surveillance system in Italy

The role of ear-piercing, tattooing, attendance at chiropodist or manicurist and barber shop shaving in transmitting hepatitis B and hepatitis non-A, non-B was evaluated. Data reported here were collected from 1985 to 1993 by the National Viral Hepatitis Surveillance System. The association between parenterally transmitted hepatitis and the considered risk factors was estimated, comparing 6,395 hepatitis B and 2,558 hepatitis non-A, non-B cases with 4,789 hepatitis A cases, using the case-control method. Of the non-A, non-B cases tested from 1991 to 1993, 56.6% were anti-HCV positive. The incidence of parenterally transmitted hepatitis cases reporting specific beauty treatments was also evaluated. Tattooing, ear-piercing and barber shop shaving were associated with both parenterally transmitted hepatitides, while attendance at a chiropodist or manicurist was associated only with hepatitis B. During the study period the incidence of acute hepatitis B and non-A, non-B cases reporting beauty treatments declined by 49%. In spite of this decline, considering that a large part of the general population is exposed to the considered risk factors, the role of beauty treatments in transmitting hepatitis B and hepatitis non-A, non-B should not be underestimated.

Melanoma Computer-Aided Diagnosis Reliability and Feasibility Study

Background: Differential diagnosis of melanoma from melanocytic nevi is often not straightforward. Thus, a growing interest has developed in the last decade in the automated analysis of digitized images obtained by epiluminescence microscopy techniques to assist clinicians in differentiating early melanoma from benign skin lesions. Purpose: The aim of this study was to evaluate diagnostic accuracy provided by different statistical classifiers on a large set of pigmented skin lesions grabbed by four digital analyzers located in two different dermatological units. Experimental Design: Images of 391melanomas and 449 melanocytic nevi were included in the study. A linear classifier was built by using the method of receiver operating characteristic curves to identify a threshold value for a fixed sensitivity of 95%. A K-nearest-neighbor classifier, a nonparametric method of pattern recognition, was constructed using all available image features and trained for a sensitivity of 98% on a large exemplar set of lesions. Results: On independent test sets of lesions, the linear classifier and the K-nearest-neighbor classifier produced a mean sensitivity of 95% and 98% and a mean specificity of 78% and of 79%, respectively. Conclusions: In conclusion, our study suggests that computer-aided differentiation of melanoma from benign pigmented lesions obtained with DB-Mips is feasible and, above all, reliable. In fact, the same instrumentations used in different units provided similar diagnostic accuracy. Whether this would improve early diagnosis of melanoma and/or reducing unnecessary surgery needs to be demonstrated by a randomized clinical trial.

Three-point checklist of dermoscopy: an open internet study

Background  In a pilot study, the three‐point checklist of dermoscopy has been shown to represent a valid and reproducible tool with high sensitivity for the diagnosis of skin cancer in the hands of a small group of nonexperts.

Therapy with rituximab for autoimmune pemphigus: Results from a single-center observational study on 42 cases with long-term follow-up

BACKGROUND Rituximab induces depletion of B cells and has shown efficacy in antibody-mediated autoimmune disorders. In studies on small series of patients with pemphigus, rituximab administration results in significant improvement. However, differences in inclusion criteria, treatment protocols, and follow-up make it difficult to derive uniform conclusions. OBJECTIVES We sought to test the efficacy and tolerability of rituximab as adjuvant therapy to corticosteroids in the treatment of pemphigus. METHODS In all, 42 patients with pemphigus were treated with rituximab and followed up for up to 5 years. No additional immunosuppressive agents were used. Steroids were rapidly tapered. Outcomes were the proportion of patients who achieved a complete response on or off therapy, the rate of discontinuation of corticosteroid within 6 months, length of remission, time to relapses, and occurrence of adverse events. RESULTS In all, 36 of 42 patients (86%; 95% confidence interval 75%-96%) achieved a complete response on or off therapy and discontinued steroids within 6 months from induction therapy. Six patients had a complete response off therapy with an additional infusion of rituximab 6 months after initial treatment. Twenty patients experienced a total of 34 relapses; the time to relapse was 8 to 64 months. Every relapse was treated with rituximab (500 mg) without corticosteroids, which induced a new complete response. No serious adverse events were observed. LIMITATIONS Lack of a control group is a limitation. CONCLUSIONS Rituximab therapy induces prolonged clinical remission in patients with pemphigus. Coadministration of other immunosuppressive agents is not necessary. Relapses can be managed with additional infusions administered on demand.

UV mutation signature in tumor suppressor genes involved in skin carcinogenesis in xeroderma pigmentosum patients

Molecular analysis of p53 and patched (PTCH), two candidate tumor suppressor genes for non-melanocytic skin cancer, was performed in skin tumors from six patients affected by the cancer-prone disease xeroderma pigmentosum (XP). UV-specific p53 mutations were detected at a frequency of 38–50% in all the tumor types analysed, including melanomas. Additional analysis of PTCH mutations in the subset of eight basal call carcinomas (BCC) revealed a very high mutation frequency of this gene (90%) which exceeded that detected in the p53 gene in the same tumors (38%). PTCH mutations were predominantly UV-specific C>T transitions. This mutation pattern is different from that reported in BCC from normal donors where PTCH mutation frequency is 27% and mutations are frequently deletions and insertions. These findings suggest that PTCH mutations represent an earlier event in BCC development than p53 alterations and that the inability of XP patients to repair UV-induced PTCH mutations might significantly contribute to the early and frequent appearance of BCC observed in these patients.

Heterosexual and homosexual transmission of hepatitis C virus: relation with hepatitis B virus and human immunodeficiency virus type 1

A seroprevalence study was carried out on 1757 outpatients consecutively seen in a sexually transmitted disease (STD) clinic in order to evaluate the sexual transmission of hepatitis C virus (HCV). A total of 1442 consenting patients were tested for hepatitis C, hepatitis B and human immunodeficiency virus type 1 (HCV, HBV, HIV-1) antibodies. The relations between anti-HCV, anti-HBc and anti-HIV-1 were studied. Of 73 anti-HCV positive reactions, 45 (61.6%) were confirmed by the recombinant immunoblot assay (RIBA). The proportion of individuals with anti-HCV was higher in outpatients with a history of sexually transmitted disease than without. It was 2.8% in non drug user heterosexuals and 2.9% in non drug user homosexuals. Intravenous drug users (IDU) had higher anti-HCV prevalence when a history of STD was taken into account (42.3% in subjects with STD versus 36.7% in subjects without STD). Among non drug user heterosexuals an association was found between anti-HCV and anti-HBc. These data suggest that sexual transmission of HCV occurs, although it seems to be less efficient than other parenteral modes of transmission. When a more sensitive and specific marker of HCV infection become available, a more accurate estimate of the frequency and efficiency of the sexual transmission will be possible.