Section 5 -

Lymphoid Lesions (Dr. Faquin) William C. Faquin, M.D., Ph.D. Celeste N. Powers, M.D., Ph.D.

Clinical History: A 49 year-old woman with a several year history of rheumatoid arthritis presents with a markedly enlarged left parotid gland. By clinical exam, the parotid gland was diffusely enlarged and firm; however, a discrete mass was not identified. An FNAB was performed. Cytologic Findings: The smears in this case were cellular and showed an abundance of lymphocytes in a mixed pattern with a predominance of small mature-appearing cells as well as scattered intermediate-sized and larger lymphocytes. The initial working diagnosis in this case included a reactive lymph node, chronic sialadenitis, lymphoepithelial sialadenitis (LESA), and lymphoma - therefore, material was sent for flow cytometry. Scattered loosely cohesive lymphohistiocytic aggregates with occasional tingible body macrophages, representing aspirated fragments of germinal centers were present, and a key finding in this case were the many cohesive clusters of cytologically bland epithelial cells (some with squamoid features) with lymphocytes surrounding and percolating within the epithelial groups. These are lymphoepithelial lesions, and based upon their presence, the differential diagnosis was essentially narrowed to include lymphoepithelial sialadenitis and low-grade lymphoma. Flow cytometric studies that had been submitted the day before showed polyclonal B and T cells - a population of B cells with monotypic light chain expression was not present. Based upon the cytomorphologic features and flow cytometric profile in this case, a diagnosis of LESA was made. Section 5 - Figure 1 LESA showing mixed lymphocytes and lymphoepithelial lesion. Discussion: Lymphoepithelial Sialadenitis (LESA) LESA has been known by a variety of names, including Mikulicz's disease, benign lymphoepithelial lesion, and myoepithelial sialadenitis (MESA). Due in part to the recent discovery that the cells comprising the lymphoepithelial islands of this disorder are almost entirely epithelial, the term lymphoepithelial sialadenitis (LESA) has emerged as the preferred terminology. LESA is believed to be an autoimmune disorder seen in the majority of patients with Sjogren's syndrome; however, approximately 50% of patients with LESA do not have Sjogren's syndrome but rather some other connective tissue disorder (especially rheumatoid arthritis as in the case presented here), or no disease whatever. LESA can be unilateral or bilateral, cystic or solid. The diagnosis of LESA carries with it an increased for the development of B-cell lymphoma, especially extranodal marginal zone lymphoma of MALT type. As illustrated by this case, aspirates of LESA are typically cellular and show a mixed population of abundant mature lymphocytes, plasma cells, tingible body macrophages, germinal center fragments, and characteristic lymphoepithelial lesions. The latter are cohesive clusters of pale overlapping ductal-type or squamoid epithelial cells with reactive changes and epithelial-associated lymphocytes. Acinar cells are rarely present. Cytologic features of LESA: Cellular aspirate Mixed population of lymphocytes, plasma cells, tingible body macrophages Germinal center fragments Lymphoepithelial lesions Histologic Features of LESA: Microscopically, the salivary gland parenchyma in LESA shows a dense lymphoid infiltrate with loss of the normal acinar cells in lobules, and the presence of lymphoepithelial lesions. The lymphoid tissue is comprised of a mixture of B and T lymphocytes, and germinal centers are present. Section 5 - Figure 2 The lymphoepithelial lesion is a key feature of LESA. Differential Diagnosis: The differential diagnosis of LESA includes a variety of lymphocyte-containing entities - reactive, benign, and malignant. The most important and difficult lesion to exclude from the differential diagnosis is lymphoma, particularly MALT-type lymphoma. Therefore, ancillary studies for clonality such as flow cytometry or immunocytochemistry should be employed liberally to avoid this pitfall! Differential Diagnosis of LESA: Chronic sialadenitis Reactive lymph node B-cell lymphoma MALT Follicular Diffuse large B-cell Epithelial neoplasms with lymphocytes Warthin's tumor Mucoepidermoid carcinoma Acinic cell carcinoma Lymphoepithelial carcinoma Metastatic squamous cell carcinoma In some cases, LESA can be cystic, and when this occurs, a variety of other benign and malignant cystic entities should be considered in the differential diagnosis. Differential Diagnosis of Cystic LESA: HIV-associated cystic lymphoepithelial lesions Simple lymphoepithelial cyst Warthin's tumor Mucoepidermoid carcinoma Metastatic cystic squamous cell carcinoma Lymphoma involving the salivary gland: Primary and secondary malignant lymphomas occur in the salivary glands and intraparotid lymph nodes, and constitute 2-5% of salivary gland neoplasms. The parotid gland is the most frequently involved. Most lymphomas are B-cell non-Hodgkin lymphomas; the most common are extranodal marginal zone B-cell lymphoma of the MALT type, and diffuse large B-cell lymphoma (DLBCL). Section 5 - Figure 3 MALT DLBCL Section 5 - Figure 4 Lymphoma Cytologic features of Selected Malignant Lymphomas: Extranodal marginal zone B-cell lymphoma of MALT type Small to intermediate size lymphocytes Round to slightly irregular nuclei Occasional immunoblasts CD45+, CD20+, CD23-, CD10-, CD5-, cyclin D1 - Follicular lymphoma Mixed population of small and large cleaved and large noncleaved cells CD45+, CD20+, CD10+, CD5- Diffuse large B-cell lymphoma Large markedly atypical lymphocytes CD45+, CD20+, keratin-, S-100 -