Sebastiana Boi

Dermatoscopy: usefulness in the differential diagnosis of cutaneous pigmentary lesions.

Dermatoscopy has been reported to give valid Information in the differential diagnosis of cutaneous pigmentary lesions. Using a dermatoscopy Delta 10 Heine optotechnique, we evaluated 220 pigmented lesions during a health campaign for the early diagnosis of cutaneous melanoma and compared clinical and dermatoscopic diagnosis. Histologic diagnosis was carried out after removal of the lesions. Sensitivity, specificity, positive predictive value, negative predictive value and overall agreement were evaluated. In our experience clinical and dermatoscopic diagnosis gave similar results; sensitivity and specificity were slightly better for dermatoscopy than for clinical diagnosis. The agreement between clinical and dermatoscopic diagnosis was better in histologically negative lesions. Dermatoscopy Is useful in the diagnosis of pigmentary lesions, but clinical diagnosis by experienced dermatological staff, is unreplaceable, especially during a health campaign for the early diagnosis of cutaneous melanoma.

A gigantic, metastasizing keratoacanthoma: report of a case and discussion on classification

A case of a gigantic metastasizing keratoacanthoma in a woman who had impaired cellular immunity and autoimmune hemolytic anemia is described. The case suggests that disorders of humoral and cellular immunity may be responsible for development of recurrent and metastasizing keratoacanthomas.

Digital epiluminescence microscopy: usefulness in the differential diagnosis of cutaneous pigmentary lesions. A statistical comparison between visual and computer inspection.

Epiluminescence light microscopy (ELM) has been confirmed to be a useful tool for the diagnosis of pigmented skin lesions. The application of digital systems to epiluminescence represents the latest attempt to improve the diagnosis of cutaneous melanoma. The aim of this study was to compare the diagnostic accuracy of one of these systems, the DB-Dermo MIPS, with the accuracy of well-trained dermatologists using the ELM technique in order to establish the real usefulness of this instrument and to verify how much it can help the clinician make a diagnosis in a clinical setting. During a campaign for the early diagnosis of cutaneous melanoma, 311 patients with non-melanocytic lesions, common naevi, dysplastic naevi and melanomas underwent clinical diagnosis using ELM, computerized evaluation with DB-Dermo MIPS and skin biopsy. Sensitivity, specificity, true and negative predictive value were evaluated for epiluminescence and digital epiluminescence. Our study revealed that the inspection of pigmented skin lesions by digital epiluminescence has a better diagnostic accuracy than that of a trained dermatologist using the epiluminescence technique only. In our experience, this computerized system can play an essential role in the detection of early melanomas.

Expert pathology consultation through the Internet: melanoma versus benign melanocytic tumours

Twenty consecutive cases of melanocytic lesions were chosen from the archives of the Institute of Anatomic Pathology at Santa Chiara Hospital, Trento. Representative images were acquired at a spatial resolution of 512×512 pixels, saved in JPEG format and delivered to the remote pathologist by multimedia Internet electronic mail. Six cases were diagnosed as benign melanocytic lesions by the local pathologist. Of the 20 cases transmitted, each with an average of 5.3 images, the remote pathologist suggested a diagnosis of malignancy in nine cases while 10 cases were thought to be benign. In one case the images were not considered sufficient for diagnosis. Overall, the diagnostic agreement between local and remote pathologist was 79%(κ=0.58, P=0.002). This preliminary study suggest that telepathology by Internet electronic mail can be a valuable tool for remote consultation in dermatopathology, as well as for other diagnostic fields where expert consultation is necessary.

Robotic Telepathology for Intraoperative Remote Diagnosis Using a Still-Imaging-Based System

The aim of the present study was to assess whether a telemicroscopy system based on static imaging could provide a remote intraoperative frozen section service. Three pathologists evaluated 70 consecutive frozen section cases (for a total of 210 diagnoses) using a static telemicroscopy system (STeMiSy) and light microscopy (LM). STeMiSy uses a robotic microscope, enabling full remote control by consultant pathologists in a near real-time manner. Clinically important concordance between STeMiSy and LM was 98.6% (95.2% overall concordance), indicating very good agreement. The rates of deferred diagnoses given by STeMiSy and LM were comparable (11.0% and 9.5%, respectively). Compared with the consensus diagnosis, the diagnostic accuracy of STeMiSy and LM was 95.2% and 96.2%. The mean viewing time per slide was 3.6 minutes, and the overall time to make a diagnosis by STeMiSy was 6.2 minutes, conforming to intraoperative practice requirements. Our study demonstrates that a static imaging active telepathology system is comparable to dynamic telepathology systems and can provide a routine frozen section service.

Syringotropic mycosis fungoides: a rare variant of the disease with peculiar clinicopathologic features.

A rare variant of mycosis fungoides (MF) characterized by prominent involvement of the eccrine glands with syringometaplasia has been reported in the past as “syringolymphoid hyperplasia with alopecia,” “syringotropic cutaneous T-cell lymphoma,” “adnexotropic T-cell lymphoma,” or “syringotropic MF.” The clinicopathologic features of this variant are not well understood, and only a few case reports or small series have been published to date. We reviewed the clinicopathologic features of 14 patients with syringotropic MF (male:female=10:4; median age, 59 years; mean age, 57.8; age range, 33 to 83 y). Six patients had variably large, solitary patches or plaques, located on the thigh (n=3), arm, trunk, or eyebrow (1 each). The other 8 patients had multiple, mostly generalized lesions. A history of MF was known in 4 of these 8 patients. With the exception of 1 biopsy specimen that was too superficial and did include the eccrine secretory coils but not the eccrine glands, all cases showed prominent involvement of the eccrine glands. Variable degrees of syringometaplasia ranging from small to large epithelial complexes were present in all specimens. The eccrine glands and syringometaplastic structures were surrounded by dense lymphoid infiltrates with prominent epitheliotropism. Concomitant involvement of the epidermis and of the hair follicles was observed in 13 and 8 biopsies, respectively. This is the largest series of syringotropic MF, showing that this is a rare variant of the disease with peculiar clinicopathologic features. Dermatologists and dermatopathologists should be aware of this rare variant of MF to avoid delayed diagnosis and treatment.

Epidemiology of skin tumors: data from the cutaneous cancer registry in Trentino, Italy.

Background: A Skin Cancer Registry was established in the province of Trento in northeast Italy in 1992 with the aim of collecting data on all cutaneous tumors affecting residents. These neoplasms are responsible for considerable morbidity and utilization of the Health Service because of their high frequency and, therefore, knowledge of the exact incidence is very important in planning health policies. Registry data are also very helpful in performing studies of analytical and descriptive epidemiology. Methods: For each patient, we collected personal data, phenotypical characteristics, professional history, concurrent diseases, previous therapy or trauma, and all data regarding the tumors. Patients were interviewed in person or, less frequently, by phone. All data were verified and put in a computerized file, in a protected room. The Statistics Institute of Trento University analyzed the data. Comparison among means was performed using the analysis of variance and differences among proportions were tested by chi-squared analysis. Poisson regression and the likelihood ratio test were used to compare incidence rates. We analyze here the data regarding epiteliomas and melanoma. Results: During the study period we registered 3435 primary skin tumors in 2868 individuals. Crude incidence rates, calculated using the number of subjects (not the number of tumors), were 87.9 for basal cell carcinoma (BCC), 28.9 for squamous cell carcinoma (SCC), and 14.2 for cutaneous melanoma (CM), per 100,000 per annum. We also calculated the same figures in females and males and specific incidence rates in both sexes and evaluated the distribution of skin cancer according to sex and anatomical site. Conclusion: We report the analysis of the data collected by the Skin Cancer registry in a 6 year period and compare the data with published data in literature and with data of a previously registered melanoma file. Our results confirm the high incidence of nonmelanoma skin cancers and the variation in the histological patterns of CM.SommaireAntécédents: En 1992, un registre de cancer de la peau a été établi dans la province de Trento, nord-est de l’Italie, dans l’objectif de collecter toutes les tumeurs malignes affectant les résidents. Vu leur fréquence élevée, ces néoplasmes sont la cause d’une forte morbidité et d’une grande utilisation du système de santé. Donc, connaÑtre leur incidence exacte contribue à une meilleure planification des politiques en matière de santé. Les données du registre sont également très utiles dans les études d’pidémiologie analytique et descriptive. Méthodes: Nous avons recueilli, pour chaque patient, des données personnelles, les caractéristiques phénotypiques, les antécédents professionels, les maladies actuelles, les thérapies ou les traumatismes précédents ainsi que toutes les données relatives aux tumeurs. Une entrevue a été effectuée auprès de chaque patient en personne, plus rarement par téléphone. Toutes les données ont été vérifiées, consignées dans un fichier informatique et gardées dans une chambre protégée. L’institut des statistiques de l’université de Trento a analysé les données. Une comparaison des moyens a été effectuée par analyse de la variance et les différences entre les proportions ont été évaluées par Khi carré. La régression Poisson et le taux de probabilité ont servi à comparer les taux d’incidence. Nous analysons dans le présent article les données relatives aux tumeurs épithéliales et aux mélanomes. Résultats: Durant l’étude, nous avons enregistré 3 435 tumeurs cutanées primaires chez 2 868 personnes. Les taux d’incidence bruts, calculés en utilisant le nombre de sujets (et non le nombre de tumeurs), étaient de 87,9 dans les cas de carcinomes basocellulaires, de 28,9 dans les cas de carcinomes spinocellulaires et de 14,2 dans les cas de mélanomes, par 100 000 sujets par an. Nous avons également effectué les mémes calculs pour les femmes et pour les hommes séparément, avec les taux d’incidence selon le sexe et une évaluation de la distribution du cancer de la peau selon le sexe. Conclusion: Nous présentons les données recueillies par le registre de cancer de la peau durant une période de six ans et les comparons aux données publiées dans les revues spécialisées et aux données tirées d’un registre précédent. Nos résultats confirment une incidence élevée de cancers non mélaniques et une variation des tendances histologiques des mélanomes.

Image sampling in static telepathology for frozen section diagnosis

BACKGROUND: A frozen section diagnostic service is often not directly available in small rural or mountain hospitals. In these cases, it could be possible to provide frozen section diagnosis through telepathology systems. Telepathology is based on two main methods: static and dynamic. The former is less expensive, but involves the crucial problem of image sampling. AIMS: To characterise the differences in image sampling for static telepathology when undertaken by pathologists with different experience. METHODS: As a test field, a previously studied telepathology method based on multimedia email was adopted. Using this method, three pathologists with different levels of experience sampled images from 155 routine frozen sections and sent them to a distant pathology institute, where diagnoses were made on digital images. After the telepathology diagnoses, the glass slides of both the frozen sections and the definitive sections were sent to the remote pathologists for review. RESULTS: Four of 155 transmissions were considered inadequate by the remote pathologist. In the remaining 151 cases, the telepathology diagnosis agreed with the gold standard in 146 (96.7%). There was no significant divergence between the three pathologists in their sampling of the images. Each case comprised five images on average, acquired in four minutes. The overall time for transmission was about 19 minutes. CONCLUSIONS: The results suggest that in routine frozen section diagnosis an inexperienced pathologist can sample images sufficiently well to permit remote diagnosis. However, as expected, the internet is too unreliable for such a time dependent task. An improvement in the system would involve integrated real time features, so that there could be interaction between the two pathologists.

Increased frequency of minimal homozygous deletions is associated with poor prognosis in primary malignant melanoma patients.

Identification of prognostic melanoma‐associated copy number alterations (CNAs) is still an area of active research. Here, we investigated by high‐resolution array comparative genomic hybridization (aCGH) a cohort of 31 paraffin‐preserved primary malignant melanomas (MMs), whose prognosis was not predictable on the basis of conventional histopathological parameters. Although we identified a variety of highly recurrent sites of genomic lesions, the total number of CNAs per patient was not a discriminator of MM outcome. Furthermore, validation of aCGH by quantitative PCR on an extended population of 65 MM samples confirmed the absence of predictive value for the most recurrent CNA loci. Instead, our analysis revealed specific prognostic potential of the frequency of homozygous deletions (representing less than 3% of the total CNAs on average per sample), which was strongly associated with sentinel lymph node (SLN) invasion (P = 0.003), and distant metastasis (P = 0.003). Increased number of homozygous deletions was also indicative of poor patient survival (P = 0.01), both in our samples and in an independent validation of public dataset of primary and metastatic MMs. Moreover, we identified 77 hotspots of minimal common homozygous deletions, enriched in genes involved in cell adhesion processes and cell‐communication functions, which preferentially accumulated in primary MMs showing the most severe outcome. Therefore, specific loss of gene loci in regions of minimal homozygous deletion may represent a pivotal type of genomic alteration accumulating during MM progression with potential prognostic implication.

TrkA is amplified in malignant melanoma patients and induces an anti-proliferative response in cell lines.

BackgroundThe nerve growth factor (NGF) receptor tyrosine-kinase TrkA is a well-known determinant of the melanocytic lineage, through modulation of the MAPK and AKT cascades. While TrkA gene is frequently rearranged in cancers, its involvement in malignant melanoma (MM) development is still unclear.MethodsWe analyzed a dataset of primary cutaneous MM (n = 31) by array comparative genomic hybridization (aCGH), to identify genomic amplifications associated with tumor progression. The analysis was validated by genomic quantitative PCR (qPCR) on an extended set of cases (n = 64) and the results were correlated with the clinical outcome. To investigate TrkA molecular pathways and cellular function, we generated inducible activation of the NGF-TrkA signaling in human MM cell lines.ResultsWe identified amplification of 1q23.1, where the TrkA locus resides, as a candidate hotspot implicated in the progression of MM. Across 40 amplicons detected, segmental amplification of 1q23.1 showed the strongest association with tumor thickness. By validation of the analysis, TrkA gene amplification emerged as a frequent event in primary melanomas (50 % of patients), and correlated with worse clinical outcome. However, experiments in cell lines revealed that induction of the NGF-TrkA signaling produced a phenotype of dramatic suppression of cell proliferation through inhibition of cell division and pronounced intracellular vacuolization, in a way straightly dependent on NGF activation of TrkA. These events were triggered via MAPK activity but not via AKT, and involved p21cip1 protein increase, compatibly with a mechanism of oncogene-induced growth arrest.ConclusionsTaken together, our findings point to TrkA as a candidate oncogene in MM and support a model in which the NGF-TrkA-MAPK pathway may mediate a trade-off between neoplastic transformation and adaptive anti-proliferative response.