System: Head and Neck: Salivary Gland: Neoplastic: MALT Lymphoma
The salivary parenchyma is effaced by a monotonous small lymphoid infiltrate with some nodular or follicular hint.
A vague nodularity is seen. These nodules can be either lymphoepithelial lesions, reactive germinal centers or follicles colonized by the neoplastic infiltrate.
Lymphoepithelial lesions are one of the key features, consisting of ductal structures being invaded by lymphocytes.
The rounded structure in the center is most an expanded ductal structure with lymphoid infiltration (lymphoepithelial lesion).
Similar to other MALT lymphomas, centrocyte-like B-cells with small dark angulated nuclei, inconspicuous nucleoli and a small rim of clear cytoplasm comprise the dominant neoplastic infiltrate. The cells can have also have more rounded nuclei and more abundant clear cytoplasm, appearing monocytoid.
MALT lymphomas are positive for multiple B-cell markers such as CD19 and CD20. CD20 positivity is shown here.
Additionally, bcl-2 is positive.
Aberrant co-expression of CD43 (normally a T-cell marker) by the neoplastic B-cells expression is seen in ~50% of MALT lymphomas.
Extranodal marginal zone B-cell lymphomas of MALT (mucosa-associated lymphoid tissue) can arise in a variety of extranodal sites. The most common sites include the GI tract, thyroid, salivary gland and lung (Fletcher). Among the salivary glands, the parotid gland is the most common site of involvement (>75%), with greater than one salivary gland involved in about 15% of cases. Cervical lymph node involvement is seen in about one quarter of patients (Isaacson, Fletcher).
Mucosa-associated lymphoid tissue (MALT) is recognized as nonencapsulated clusters of lymphocytes found throughout the mucosal tissue of the aerodigestive tract. Typically, MALT is composed of lymphocytes, however, plasma cells and macrophages may also be present. MALT is positioned to process antigens passing traversing the mucosa, and thus plays an important role in modulating mucosal immunity. Isaacson and Wright first published on lymphoma arising from MALT in 1983 (Isaacson).
As previously mentioned, almost any mucosal site may be involved, the most common being the GI tract, respiratory tract, and the skin. MALT lymphomas occur develop associated with local inflammation(H. pylori infection), immunostimulation (Sjögren’s & Hashimoto thyroiditis) or immunodeficiency. MALT lymphomas tend to have an relatively indolent behavior and often remain localized for long periods. Salivary glands do not usually harbor MALT, however, lymphocytes may infiltrate the glands as a result of a chronic inflammation or autoimmune disorders, leading to MALT lymphoma.
Histologically, MALT lymphomas in the salivary gland have a similar appearance to those seen in other mucosal sites. There is a mixture of cells types, the most predominant being centrocytes and monocytoid B-cells. The neoplastic lymphoid infiltrate is interfollicular (between the reactive follicles) but may invade and replace follicles - "follicular colonization". Lymphoepithelial lesions where lymphoid cells invade epithelial structures such as gastric glands or in ducts in the case of salivary gland MALT lymphoma.
The tumor itself is a low-grade B-cell lymphoma and has the following immunoprofile: positive for CD19/CD20 (B-cell markers) as well as bcl-2. It is negative for CD5/CD10/CD23/cyclin D1/bcl-6. Co-expression of CD43 is seen in approximately 50% of cases. The t(14;18) translocation resulting in the fusion gene IgH/MALT1 along with trisomies 3 and 18 are seen in a subset of salivary gland and lung MALT lymphomas. The t(11;18) and t(1;14) seen in a subset of gastric MALT lymphomas (which predict a lack of response to anti-H. pylori therapy)(Fletcher).
The median age at diagnosis is in the sixth decade with a F/M ratio of ~ 3/1. Risk factors include lymphepithelial sialadenitis, Sjogren syndrome and hepatitis C. In a study of 33 cases, 46% of patients had Sjogren syndrome and 29% had hepatitis C (Ambrosetti).
Therapy for salivary MALT lymphoma is not standardized. The diagnosis may be made after salivary gland surgery. In these cases, radiotherapy and or chemotherapy may be used after surgery. Alternatively, reports exist of treatment with radiation an/or chemotherapy without surgery for cases diagnosed without gland removal. Radiotherapy does appear to positively effect disease free survival and has been touted as a mainstay of treatment (Toso, Goda). With a preoperative diagnosis of MALT lymphoma, surgical removal of the salivary gland is rarely indicated.
5-year disease specific survival(DSS) has been seen to be in the mid 90 range% (Isaacson, Toso). Prognostic factors effecting DSS are presence of residual tumor after primary therapy and disease relapse.
• Salivary Gland : Warthin's Tumor
• Salivary Gland : Lymphoepithelial Cyst
Ambrosetti A, Zanotti R, Pattaro C, et al. Most cases of primary salivary mucosa-associated lymphoid tissue lymphoma are associated either with Sjoegren syndrome or hepatitis C virus infection. Br J Haematol. 2004 Jul;126(1):43-9.
Anacak Y, Miller RC, Constantinou N et al. Primary Mucosa-Associated Lymphoid Tissue Lymphoma of the Salivary Glands: A Multicenter Rare Cancer Network Study. Int J Radiat Oncol Biol Phys. 2010 Nov 12.
Fletcher CDM, ed. Diagnostic Histopathology of Tumors. 3rd Ed. Philadelphia, PA: Elsevier; 2007: 307-8.
Goda JS, Gospodarowicz M, Pintilie M et al., Long-term outcome in localized extranodal mucosa-associated lymphoid tissue lymphomas treated with radiotherapy, Cancer 116 (2010), pp. 3815–3824.
Isaacson P, Wright DH. Malignant lymphoma of mucosa-associated lymphoid tissue: A distinctive type of B-cell lymphoma, Cancer 52 (1983), pp. 1410–1416.
Toso A, Aluffi P, Capello D et al., Clinical and molecular features of mucosa-associated lymphoid tissue (MALT) lymphomas of salivary glands, Head Neck 31 (2009), pp. 1181–1187