Pathology of the Head and Neck

Major and Minor Salivary Glands Chapter 5 163Table 5.5. Overview of autoimmune and neoplastic salivary lymphoid proliferations, adapted from Quintana et al. [165]BenignBorderlineLow-grade lymphomaLESA (lymphoepithelial sialadenitis), non-clonal(Histological or clonal evidence of neoplasia, but unlikely to disseminate): LESA,clonal; LESA with halos of marginal zone B-cellsPotential for spread to nodes and less often, systemically: low-grade marginal zoneB-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma)– confluent proliferation of marginal zone B-cellsLow-grade marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue(MALT lymphoma) with plasmacytic differentiation5.14.2 Benign AutoimmuneLymphoid InfiltratesThe most frequent form of autoimmune sialadenitis goesunder several synonyms, such as Mikulicz sialadenitis/disease, myoepithelial sialadenitis (MESA) and benignlymphoepithelial lesion, none of which is satisfactory[194]. In 1999, Harris introduced the much more accurateterm, lymphoepithelial sialadenitis (LESA) [91], andthis has begun to gain general acceptance, and will beused here. Sjögren’s syndrome is not a pathological term,but a clinical combination of dry eyes and mouth dueto autoimmune infiltrates of the lacrimal and salivaryglands. It is often associated with other autoimmune orconnective tissue diseases, particularly rheumatoid arthritis,but also for example scleroderma, systemic lupuserythematosus, Hashimoto’s thyroiditis and chronicactive hepatitis. Most patients with Sjögren’s syndromedevelop LESA, but not so the reverse, as up to 50% ofpatients with LESA do not develop the clinical featuresof Sjögren’s syndrome [81].Lymphoepithelial sialadenitis is considered to be anautoimmune disease [40, 77] of unknown aetiology. Severalviruses have been implicated [76, 88], but they actprobably only as cofactors.About 80% of patients with LESA are female, with amean age at presentation of 55 years (range 1 to 86). Theparotids are involved in over 80% of cases (20% bilaterally),the submandibular glands in 11%, usually in combinationwith the parotids [40], and other sites in thehead and neck in 6% [40, 81]. Tumour-like lesions of theminor glands are rare, but in contrast, subclinical focalperiductal and periacinar lymphoplasmacytic infiltratesare frequently seen in the labial salivary glands inSjögren’s syndrome, and a semi-quantitative assessmentof the amount of inflammation in a lip biopsy may beuseful as part of the investigation of patients with a drymouth [41].In the earliest stages of LESA salivary ducts are dilatedand surrounded by a lymphoid infiltrate withgerminal centres. B-cells appear to concentrate aroundthe ducts and focally infiltrate the epithelium, unlikein many non-autoimmune chronic inflammatory infiltrates,where lymphocytic invasion of the ducts isless marked. In LESA many B-cells are of monocytoidor marginal zone type [91]. They are slightly largerthan small lymphocytes of the mantle zone, and arecharacterised by nuclei with irregular outlines somewhatresembling centrocytes [105]. Plasma cells and T-lymphocytes are also present. In time, the ducts condense,with partial or complete loss of their lumina, toform lymphoepithelial lesions (LELs) [105, 172, 194];these were previously inaccurately called epimyoepithelialislands and similarly, the old usage of LEL torefer to the whole lesion should be discontinued [91].LELs consist of cohesive aggregates of epithelium withhyalinised basal lamina material containing variablenumbers of B-cells (Fig. 5.55). Myoepithelial cells arepresent as well, but are often relatively inconspicuous[42]. As the disease progresses the acini become atrophiedand are then totally replaced by lymphoid tissueleading to clinical enlargement of the salivary glands.Monoclonality by PCR can be demonstrated in over40% of patients with LESA [165], but this alone is probablyinsufficient for a diagnosis of lymphoma, andstronger evidence is required from the demonstrationof monoclonality by immunohistochemistry or flowcytometry [107].5.14.3 MalignantLymphomaICD-O:9590/3Overall, extranodal and nodal lymphomas represented16.3% of all malignant tumours of the major salivaryglands at the AFIP from 1985 to 1995 [62]. Almost allextranodal lymphomas are marginal zone B-cell lymphoma(MALT lymphomas), which is the preferred terminologyof the current WHO classification of lymphomas[108].