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      EBV-negative lymphoepithelial-like carcinoma of the lower lip

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          Abstract

          Lymphoepithelial-like carcinoma (LEC) is a rare malignant neoplasm, which can be associated with Epstein-Barr virus (EBV) infection. Histologically, LEC is an undifferentiated carcinoma with an intermixed reactive lymphoplasmacytic infiltrate. LEC appears to be an uncommon tumor type of lip carcinoma. An 82-year-old white woman presented a lesion on her lower lip that developed over the last year. The lesion was characterized by ulceration with flat edges, hardened base, painful, and absence of regional lymphadenopathy. Microscopical analysis evidenced an intense inflammatory infiltrate, composed of lymphoplasmacytic cells, associated with scarce pleomorphic epithelial cells. Immunohistochemistry highlighted the LEC cells with strong expression of pan-CK AE1/AE3, EMA, p63, and p53. CD138 was also faintly positive. Ki-67 was >85%. In situ hybridization analysis did not show evidence of EBV. A diagnostic of EBV-negative LEC was made. We present an uncommon type of lip carcinoma, which can represent a diagnostic challenge for clinicians and pathologists.

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          Most cited references 8

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          The role of Epstein-Barr virus in lymphoepithelioma-like carcinomas.

          Epstein-Barr virus (EBV) has been implicated in the pathogenesis of a variety of lymphoproliferative disorders and several epithelial neoplasms, including undifferentiated nasopharyngeal carcinoma (UNPC; lymphoepithelioma). Lymphoepithelioma-like carcinomas (LEC) are tumors with morphologic features identical to UNPC that occur outside the nasopharynx. To determine whether EBV is associated with LEC, the authors conducted a comprehensive literature review of all pathologically documented LEC reported to date in the English literature. In summary, EBV is associated consistently with LEC from only four anatomic sites: stomach, salivary gland, lung, and thymus. Racial and/or geographic factors influence the association of EBV with LEC in some of these organs. Specifically, the association of EBV with LEC of the salivary gland and lung is restricted to Asian patients, whereas the association of EBV with gastric and thymic LEC is independent of race. The presence or absence of EBV in LEC does not appear to be prognotically important in those cases studies to date.
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            Reduced syndecan-1 expression is correlated with the histological grade of malignancy at the deep invasive front in oral squamous cell carcinoma.

            Although many histopathological characteristics of oral squamous cell carcinoma (O-SCC) have been identified as prognostic factors, no factor is completely accurate and unequivocal. This study evaluated the association between the loss of syndecan-1 expression and the histological grade of malignancy at the deep invasive front in O-SCC. The expression of syndecan-1 at the invasive tumor front of O-SCC was examined immunohistochemically using archived tissue from 72 cases. The mean age of the patients was 62.5 years (range: 23-90 years) and the male-female ratio was 1.3:1 (41 men, 31 women). There were 26, 24, 11, and 11 cases classified as stages I-IV respectively. The correlation between the intensity of syndecan-1 immunostaining and the clinicopathological factors, especially the histological grade of malignancy at the deep invasive front (invasive front grade) was analyzed. Of the 72 cases, seven (9.7%), 29 (40.3%), 36 (50.0%) showed strong, intermediate, and weak or negative syndecan-1 staining respectively. There were significant differences between syndecan-1 expression and prognosis, differentiation, and pattern of invasion at the deep invasive front. Moreover, the invasive front grade scores, based on the intensity of syndecan-1 staining, were 5.6 +/- 1.0, 8.0 +/- 2.1, and 10.2 +/- 2.3 points with strong, intermediate, and weak or negative intensity respectively; and the difference was significant (P < 0.0001). Patients with intermediate or strong intensity for syndecan-1 had significantly better prognoses than did those with negative or weak intensity (P = 0.0138). This study demonstrated that the reduced expression of syndecan-1 seems to be a useful marker of histological malignancy at the deep tumor invasive front and may be a useful prognostic factor in O-SCC.
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              Lymphoepithelial carcinoma: two case reports and a systematic review of oral and sinonasal cases.

              Lymphoepithelial carcinoma (LEC) is a rare malignancy. Histologically, it is an undifferentiated carcinoma with an intermixed reactive lymphoplasmacytic infiltrate. Herein, we report two cases of LEC in the head and neck region that presented to Oulu University Hospital. Our first case is a 30-year-old man with LEC in the left maxillary sinus. The second case is a 49-year-old man with LEC in the soft palate and uvula with regional lymph node metastases at diagnosis. In addition, a systematic review of the literature from 1980 to 2010 was performed with MEDLINE and cross-references were searched manually. Case reports and clinical series of oral, oropharyngeal, nasal, and paranasal sinus LECs were reviewed revealing a total of 110 cases. Most of the oral cases were found in the tonsils (n = 29), oropharynx (n = 19), and in oral mucosa (n = 18), while sinonasal cases (n = 40) were mainly in the paranasal sinuses and nasal cavity. From 37 case reports, including ours, the median age was 58 and 62 years for sinonasal and oral/oropharyngeal LECs, respectively. Oral and oropharyngeal LECs have a 70.0% tendency to metastasize and 16.6% spread locally. In contrast, none of the nasal and paranasal LECs metastasized, but 60% spread locally. Epstein-Barr virus (EBV) had been detected in 87.5% of all tested LEC cases. Treatment of LECs, during the last decade, has largely consisted of surgery, combined with radiotherapy or chemoradiation. Although local spread or nodal metastases are fairly common at the time of diagnosis, the mortality rate of adequately treated LEC patients is low.
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                Author and article information

                Journal
                Autops Case Rep
                Autops Case Rep
                Autopsy & Case Reports
                São Paulo, SP: Universidade de São Paulo, Hospital Universitário
                2236-1960
                13 December 2019
                Jan-Mar 2020
                : 10
                : 1
                Affiliations
                [a ]Universidade Estadual de São Paulo (Unesp), Faculdade de Odontologia de Araraquara, Medicina Oral, Departamento de Diagnóstico e Cirurgia . Araraquara, SP, Brasil.
                [b ]Universidade de São Paulo (USP), Faculdade de Odontologia de Ribeirão Preto, Patologia Oral, Departamento de Estomatologia, Saúde Coletiva e Odontologia Legal. Ribeirão Pareto, SP, Brasil.
                [c ]Dentista, Estratégia Saúde da Família, Ministério da Saúde do Brasil. Ribeirão Pareto, SP, Brasil.
                [d ]Universidade de São Paulo (USP), Faculdade de Medicina de Ribeirão Preto, Departamento de Patologia e Medicina Legal . Ribeirão Preto, SP, Brasil.
                Author notes

                Author contributions: Almeida LY, Bufalino A and de Paula JA contributed to the clinical and microscopic analyses and the review of the literature. Silveira HA, Silva EV and Barbeiro CO contributed with the immunohistochemical and in-situ hybridization reactions and manuscript writing. Ribeiro-Silva A and León JE, contributed to the manuscript design, final data analyses and critical review. All authors collectively proofread the final version and approved it for publication.

                Conflict of interest: None

                Correspondence
Jorge Esquiche León
Patologia Oral - Departamento de Estomatologia - Saúde Coletiva e Odontologia Legal - Faculdade de Odontologia de Ribeirão Preto - Universidade de São Paulo (FORP/USP)
Avenida do Café, s/n – Ribeirão Preto/SP – Brasil
CEP: 14040-904
Phone: +55 (16) 3315-4063/ +55 (16) 3315-4102.
 jleon@ 123456forp.usp.br
                Article
                autopsy-10-01e2020138
                10.4322/acr.2020.138
                6945326
                Autopsy and Case Reports. ISSN 2236-1960. Copyright © 2020.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium provided the article is properly cited.

                Funding
                Funded by: FAPESP
                Award ID: 2016/02713-2
                Funded by: FAPESP
                Award ID: 2018/12734-2
                Funded by: FAPESP
                Award ID: 2016/11419-0
                Categories
                Article / Clinical Case Report

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