Immunohistochemistry

The Natural Thyroid Diet

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The use of immunohistochemistry in thyroid lymphomas is somewhat limited in that there isn't a characteristic or diagnostic immunoprofile. The application of LCA and cytokeratins as a first line investigation usually accomplishes the separation of lymphoma from carcinoma. MZBL of MALT-type, MZBL with blasts and DLBCL are all B-cell lymphomas and will stain positively with traditional B-cell markers (CD20, CD79a). The reactive T-cells decorate with CD3, while light chain restriction in plasma cells, which is seen in about 20% of cases, can be demonstrated with kappa and lambda stains. In some instances light chain restriction (cytoplasmic and membrane staining) can be demonstrated in the neoplastic lymphoid cells too. The neoplastic centrocyte-like cells of MALT origin are usually: CD5, CD10, CD23, cyclin D1 and IgD negative and positive for IgM. This immunophenotype reflects their origin from marginal zone B-cells in sites of chronic organ-specific inflammation caused by autoimmune disease or a specific inflammatory lesion (43-45). The use of bcl-2 immunostaining will also assist in excluding follicular lymphoma from reactive lymphoid follicles. In must be borne in

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Figure 12. A MZBL of MALT-type with high-grade transformation. Here large cells have formed a lymphoepithelial lesion and occupy a thyroid follicle lumen (MALT-ball).

mind that the centrocyte-like cells in lymphoepithelial lesions and colonized follicles may also express bcl-2 protein (46, 47). Bcl-2 immunoexpression does not separate MZBL of MALT-type from Hashimoto's thyroiditis, as the centrocyte-like cells can be positive in both conditions. However, high-grade lesions lose bcl-2 immunoexpression with an accompanying increase in p53 protein expression (47).

Cytokeratin stains obviously also highlight the thyroid follicle epithelium and the degree of destruction caused by lymphoepithelial lesions. Cytokeratin staining is useful in the DLBCL cases in showing the remnants of epithelium and hence a morphological features of a MALT-lymphoma. Obviously, more directed lymphoid markers could be employed if wanting to exclude or confirm the various other types of lymphoma that may occur primarily in the thyroid gland.

CYTOGENETICS/MOLECULAR BIOLOGY

As with immunohistochemistry, there is no single cytogenetic or molecular aberration that typifies MALT-lymphomas. Within the remit of MALT-lymphomas some similar genetic findings have been noted irrespective of site, however, gastric MALT-lymphomas have been more intensively examined and have chromosomal abnormalities that tend to be commoner at this site than other MALT sites. There are some repetitive abnormalities, however. Trisomy 3 has been identified in approximately 60% of

MALT-lymphomas (48). The t (1;14) translocation involving the bcl-10 gene, which then undergoes further mutations has been identified in 6-8% of MALT-lymphomas, especially those showing large cell transformation (49). The t (11;18) (q21;q21) translocation, leading to fusion ofthe apoptosis inhibitor-2 gene and the MALT lymphoma associated translocation (MALT1) gene, has been found in 18-35% of MALT-lymphomas but mainly those occurring in the gastrointestinal tract and are rarely encountered in thyroid MALT-lymphomas (50). Similarly, the t( 14; 18)(q32;q21) translocation tends not to be present in thyroid MALT-lymphomas (50). It is clear that no single chromosomal abnormality occurs in thyroid MALT-lymphomas and that some translocations within the MALT-lymphoma group are site-specific. It is thought that the various translocations and other cytogenetic abnormalities render the lymphoid tissue unstable and permissive for the process of lymphomagenesis.

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