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3. Ellis GL. Lymphoid Lesions of Salivary Glands: Malignant And

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3. Ellis GL. Lymphoid Lesions of Salivary Glands: Malignant And Med Oral Patol Oral Cir Bucal. 2007 Nov 1;12(7):E479-85. Lymphoid lesions of salivary glands Lymphoid lesions of salivary glands: Malignant and Benign Gary L. Ellis D.D.S. Adjunct Professor, University of Utah School of Medicine. Director, Oral & Maxillofacial Pathology. ARUP Laboratories. Salt Lake City, Utah, USA Correspondence: Gary L. Ellis, D.D.S. 500 Chipeta Way Salt Lake City, UT, USA E-mail: [email protected] Received: 20-05-2007 Ellis GL. Lymphoid lesions of salivary glands: Malignant and Benign. Accepted: 10-06-2007 Med Oral Patol Oral Cir Bucal. 2007 Nov 1;12(7):E479-85. © Medicina Oral S. L. C.I.F. B 96689336 - ISSN 1698-6946 Indexed in: -Index Medicus / MEDLINE / PubMed -EMBASE, Excerpta Medica -SCOPUS -Indice Médico Español -IBECS ABSTRACT Lesions of salivary glands with a prominent lymphoid component are a heterogeneous group of diseases that include benign reactive lesions and malignant neoplasms. Occasionally, these pathologic entities present difficulties in the clinical and pathological diagnosis and prognosis. Lymphoepithelial sialadenitis, HIV-associated salivary gland disease, chronic sclerosing sialadenitis, Warthin tumor, and extranodal marginal zone B-cell lymphoma are examples of this pathology that are sometimes problematic to differentiate from one another. In this paper the author reviewed the main clinical, pathological and prognostic features of these lesions. Key words: Lymphoepithelial sialadenitis, HIV-associated salivary gland disease, chronic sclerosing sialadenitis, Warthin tumor, extranodal marginal zone B-cell lymphoma. INTRODUCTION tion of disease, and disease is often confined to the salivary Lymphocytic infiltrates of the major salivary glands are glands. Because normal parotid glands contain intra-paren- involved in a spectrum of diseases that range from reactive chymal nodal tissue, some parotid lymphomas have a nodal to benign and malignant neoplasms. In many cases, the origin, but most do not. Salivary gland involvement by lymphocytic infiltrate is a minor inflammatory component Hodgkin lymphoma is rare and probably always secondary that is easily distinguished from the primary disease pro- to nodal disease outside of the salivary glands.(1) cesses. In some cases, however, the lymphocytic infiltrate Lymphomas are a significant proportion of malignancies of is a major component of the disease, and histopathologic the major salivary glands, accounting for 1.7 to 7.7 percent features that distinguish reactive and benign lesions from of tumors.(1) Use of flow cytometry, immunohistochemis- malignant lesions are often subtle. Lymphoepithelial sia- try, and other molecular studies has most likely increased ladenitis (as occurs in Sjögren syndrome), HIV-associated the frequency of diagnosis of lymphoma. sialadenitis, and extranodal marginal zone B-cell lymphoma Patients with autoimmune disease, particularly Sjögren are good examples of diagnoses that are often problematic syndrome, have a markedly increased risk of developing to differentiate from one another. In this paper, benign lymphoma, which may be 44 times greater than in the ge- and malignant diseases of salivary gland with a prominent neral population.(1) However, most patients with salivary lymphocytic component will be discussed with an emphasis lymphomas do not have Sjögren syndrome.(2) Viral DNA on their distinguishing histopathologic featurers and diffe- in lymphomatous tissue or increased antibody titers against rential diagnoses. virus have been detected in some patients.(3) Females are affected more than males, especially when there MARGINAL ZONE B-CELL LYMPHOMA is preceding autoimmune disease, as is the case with margi- Clinical features. Lymphomas are malignant neoplastic nal zone B-cell lymphomas. Disease in children is rare, and proliferations of lymphocytes. When major salivary glands patients average 63 years of age. Patients often have diffuse are involved, they are commonly the first clinical manifesta- glandular enlargement, which is sometimes bilateral.(1) E479 Article Number: 9996143853 © Medicina Oral S. L. C.I.F. B 96689336 - ISSN 1698-6946 eMail: [email protected] Med Oral Patol Oral Cir Bucal. 2007 Nov 1;12(7):E479-85. Lymphoid lesions of salivary glands Pathologic features. Most salivary lymphomas are non- tissue. Immunostaining for MT-2, bcl-2, and CD10 helps Hodgkin, B-cell lymphomas, and T-cell lymphomas are distinguish follicular lymphoma. rare.(4) Many different types of lymphoma occur, but the majority is extranodal marginal zone B-cell lymphoma. LYMPHOEPITHELIAL SIALADENITIS Follicular and diffuse large B-cell lymphomas comprise Clinical features. Lymphoepithelial sialadenitis is a benign most of the others.(1) lymphocytic infiltrate of salivary gland with parenchymal Proliferating lymphocytes alter the normal lobular salivary atrophy and foci of ductal hyperplasia with lymphocytic gland architecture, replace acini and ducts, surround nerves, epitheliotropism. The lymphocytic infiltrate is the saliva- and infiltrate into fat and interlobular and periglandular ry manifestation of mucosa-associated lymphoid tissue connective tissues. Marginal zone B-cell lymphomas are (MALT), which in the salivary glands is acquired MALT. It composed of small lymphocytes that proliferate as multiple is an autoimmune lesion and a component of Sjögren syn- foci or large confluent sheets. The neoplastic cells are post- drome. Sjögren syndrome is an autoimmune disease complex germinal center B-cell lymphocytes, which in their normal, that includes lacrimal and salivary gland disease, keratocon- non-neoplastic state are destined to differentiate to plasma junctivitis sicca, xerostomia, and serum autoantibodies like cells. These neoplastic lymphocytes are slightly larger than anti-SSA, anti-SSB, rheumatoid factor, and salivary duct normal small lymphocytes and have a centrocyte-like or antibodies. Sjögren syndrome is sometimes associated with monocytoid appearance. The latter have pale-stained cyto- other autoimmune diseases and called secondary Sjögren plasm, which makes them conspicuous in histologic sections. syndrome. It affects women 3:1 over men. It occurs most Most, if not all, marginal zone B-cell lymphomas arise frequently in the fourth to seventh decades of life and affects within pre-existing lymphoepithelial sialadenitis, which is parotid glands in about 90% of cases.(1) the histopathologic presentation of autoimmune sialadenitis Bilateral disease is typical, although one gland may be more seve- and acquired mucosal associated lymphoid tissue (MALT). rely affected. Patients experience recurring and often progressive Most of the salivary parenchyma is destroyed, but some swelling and sometimes experience discomfort or pain. hyperplastic ductal epithelium persists and is permeated by Pathologic features. Lymphocytic infiltration, parenchymal neoplastic lymphocytes, so called lymphoepithelial lesions. atrophy, and foci of epithelial proliferation characterize An emerging MZBCL is recognized by foci of expansion lymphoepithelial sialadenitis. The lobular architecture of the of marginal zone B-cells around lymphoepithelial lesions. gland is usually preserved. In the early stages, the extent of Typically associated with the neoplastic lymphocytic pro- lymphocytic infiltrate varies among lobules of gland, but in liferation is a non-neoplastic lymphoid infiltrate of T-cells, late stage disease, nearly all of the parenchyma is infiltrated. B-cells, plasma cells, reactive germinal centers, and scattered The number of lymphoid germinal centers varies from few centroblasts or immunoblasts. to numerous. Multiple foci of ductal epithelial hyperplasia The neoplastic marginal zone lymphocytes are immuno- are permeated by lymphocytes, lymphoepithelial lesions. reactive for CD20 and CD79a and non-reactive for CD3, Within the lymphoepithelial lesions, lumens are sometimes UCHL-1, and cyclin D1. They are usually negative for CD5, evident, but most are irregularly shaped islands of polygo- CD10, and CD23, but frequently express CD43. Most cases nal and spindled cells, often with deposits of intercellular express monotypic surface immunoglobulin.(5) The epithe- eosinophilic hyalin material. The hyperplastic epithelium lial component of the lymphoepithelial lesions is reactive is predominantly ductal basal cells that lack immunohisto- for cytokeratin. chemical markers specific to myoepithelium. Gene translocations t(11;18)(q21;q21) and t(1;14)(p22;q32) The lymphoid infiltrate has a predominance of T-cells, but are frequent in gastric and pulmonary marginal zone lym- within the foci of epithelial proliferation, lymphocytes have phomas but rare in those of salivary glands. Translocation features of monocytoid B-cells or centrocyte-like cells, i.e. t(14;18)(q21;q32) of the MLT/MALT1 gene and immuno- marginal zone B-cells. In some cases, some foci of intra-epi- globulin heavy chain locus is relatively frequent in tumors thelial B-cell infiltration are clonal;(8) however, in the absence of the parotid.(2,6) of expansion of these B-cell clones, it is controversial whether Prognosis. Salivary MZBCL lymphoma is rather indolent they represent the very earliest manifestation of lymphoma. and usually remains localized. Some patients are cured In Sjögren syndrome, minor salivary glands manifest chro- with local therapy, and spontaneous regression has been nic sialadenitis but typically lack lymphoepithelial lesions. reported.(1,7) Transformation of low-grade marginal zone Labial minor salivary gland biopsy is commonly used, in lymphomas
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