The coexistence of low- and high-grade MALT-lymphoma suggests either a patho-genetic link between the two components, or that they represent two independent de novo clones. The weight of evidence points to a close relationship between the low-and high-grade foci: often there is a transition noted microscopically, both immuno-histochemical and molecular studies substantiate commonality and transformation of low-grade to high-grade lymphoma, and the clinical presentation of a sudden and/or rapid increase in size of an already enlarged thyroid gland (51-55). Peng and colleagues performed PCR and mutational analyses to identify clone-specific rearranged immunoglobulin heavy chain gene sequences (55). The PCR products from both the low- and high-grade foci were identical in size and direct sequencing revealed common clone-specific immunoglobulin heavy chain gene rearrangements (55).
DIFFERENTIAL DIAGNOSIS Anaplastic (small cell) carcinoma
This type of carcinoma is likely to simulate high-grade lymphoma. Attention to the cohesive growth pattern, stromal sclerosis/desmoplasia, absence of MALT-lymphoma morphological features, especially the admixture of plasma cells, should alert one to the possibility of carcinoma. Confirmation is readily achieved by the use of epithelial immunohistochemical markers.
It is important to note that similar cellular constituents (centrocyte-like and plasma cells) together with lymphoepithelial lesions are encountered in Hashimoto's thyroiditis. Hence, florid cases can be exceptionally difficult to separate from MZBL of MALT-type. It has been suggested that a dense lymphoid infiltrate with fewer intervening reactive lymphoid follicles, broad bands of centrocyte-like or clear cells and large number of lymphoepithelial lesions that diffusely efface the thyroid parenchyma, favour a diagnosis of lymphoma. In the histologically suspicious cases, the demonstration of sheets of B-cells, light chain restriction and heavy chain gene rearrangement are ancillary features that will help in confirming the diagnosis of lymphoma. The clinical picture of sudden or rapid enlargement of the thyroid in a patient previously diagnosed as having Hashimoto's thyroiditis will also be useful. At the end of the day, there are going to be some cases (hopefully a very small number!) that clinical information, light microscopy, immunohistochemistry and molecular techniques will not be able to separate. When unsure, the possibility of lymphoma should be raised and careful follow-up of the patient should be recommended.
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