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      A juvenile case of conjunctival atypical nevus

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          Abstract

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          The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2973228795724608

          Melanocytic nevi are the most common tumors of the conjunctiva, accounting for 28% of all neoplastic lesions. These tumors, despite their benign behavior, share some atypical histological features with nevi found in other anatomic sites like the genital and acral regions, globally designated as nevi with site-related atypia. Moreover, in children and adolescents, rapidly growing conjunctival nevi show sometimes worrisome histological patterns in association with a prominent inflammatory infiltrate that may lead to diagnostic problems. In this paper we describe a juvenile compound nevus characterized by marked melanocytic atypia and severe inflammation, which can be considered a rare case of juvenile conjunctival atypical nevus. The final diagnosis relied on morphological and immunohistochemical characterization of the large epithelioid melanocytic cells, and on the results of FISH analysis.

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          Most cited references 12

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          Fluorescence in situ hybridization (FISH) as an ancillary diagnostic tool in the diagnosis of melanoma.

          Although the clinical and pathologic diagnosis of some melanomas is clear-cut, there are many histopathologic simulators of melanoma that pose problems. Over-diagnosis of melanoma can lead to inappropriate therapy and psychologic burdens, whereas under-diagnosis can lead to inadequate treatment of a deadly cancer. We used existing data on DNA copy number alterations in melanoma to assemble panels of fluorescence in situ hybridization (FISH) probes suitable for the analysis of paraffin-embedded tissue. Using FISH data from a training set of 301 tumors, we established a discriminatory algorithm and validated it on an independent set of 169 unequivocal nevi and melanomas as well as 27 cases with ambiguous pathology, for which we had long-term follow-up data. An algorithm-using signal counts from a combination of 4 probes targeting chromosome 6p25, 6 centromere, 6q23, and 11q13 provided the highest diagnostic discrimination. This algorithm correctly classified melanoma with 86.7% sensitivity and 95.4% specificity in the validation cohort. The test also correctly identified as melanoma all 6 of 6 cases with ambiguous pathology that later metastasized. There was a significant difference in the metastasis free survival between test-positive and negative cases with ambiguous pathology (P=0.003). Sufficient chromosomal alterations are present in melanoma that a limited panel of FISH probes can distinguish most melanomas from most nevi, providing useful diagnostic information in cases that cannot be classified reliably by current methods. As a diagnostic aid to traditional histologic evaluation, this assay can have significant clinical impact and improve classification of melanocytic neoplasms with conflicting morphologic criteria.
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            p16 and p21WAF1 protein expression in melanocytic tumors by immunohistochemistry.

            To determine whether variation in the level of expression of p16 and p21WAF1 (p21) is associated with critical stages in cutaneous melanoma development or progression, the expression of these antigens was analyzed by immunohistochemistry in 110 benign and malignant melanocytic lesions. Differential expression of p16 protein has been reported in cutaneous melanocytic lesions, with loss of expression associated with the invasive stage of tumor development. Expression of p16 was seen in 31 of 35 benign melanocytic tumors (89%), 11 of 12 in situ melanomas (92%), 19 of 38 invasive primary melanomas (50%), and 16 of 25 metastatic melanomas (64%). There was a significant difference in the expression level of p16 observed in in situ versus invasive primary melanomas (p = 0.006), which is consistent with loss of normal p16 activity occurring in association with malignant tumor invasion. Overall, p21 levels were found to be low or undetectable in the majority of benign lesions, with greater p21 expression seen in malignant tumors. p21 was expressed in 28% of nevi, 60% of in situ melanomas, 61% of invasive melanomas, and 48% of metastatic melanomas. Among primary invasive tumors, the frequency of p21 expression increased with level of invasion (p < 0.01) and with increasing thickness (p < 0.01). However, differences in p21 expression were not clearly related to a particular stage of melanoma development.
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              Melanocytic lesions of the conjunctiva.

              Melanocytic proliferations are among the most common neoplasms of the conjunctiva. They often represent challenging lesions for pathologists unfamiliar with unique histologic features of melanocytic proliferations in this location and with nomenclature used by ophthalmologists. To comprehensively review clinical aspects, pathologic features, and management of melanocytic proliferations of the conjunctiva. Review of the literature and personal experience of the authors. Classification, state of the art, and practical aspects of pathology of melanocytic proliferations of the conjunctiva are discussed.
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                Author and article information

                Journal
                Diagn Pathol
                Diagn Pathol
                Diagnostic Pathology
                BioMed Central
                1746-1596
                2013
                22 April 2013
                : 8
                : 64
                Affiliations
                [1 ]Pathology Unit, Department of Experimental Oncology, Mediterranean Institute of Oncology, Via Penninazzo 7, Viagrande, CT, Italy
                [2 ]Gecas srl, Via San Paolo 68, Gravina di Catania, CT, Italy
                [3 ]Division of Pathological Anatomy, Department of Critical Care Medicine and Surgery, University of Florence, Viale GB Morgagni 85, Florence, Italy
                [4 ]Division of Pathology, CRO - Centro di Riferimento Oncologico, Istituto Nazionale Tumori, Via Franco Gallini 2, Aviano, PN, Italy
                Article
                1746-1596-8-64
                10.1186/1746-1596-8-64
                3662158
                23607499
                Copyright ©2013 Colarossi et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Categories
                Case Report

                Pathology

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