Answer: Low grade lymphoma of mucosa-associated lymphoid tissue

Histology: The thyroid gland is diffusely enlarged. In areas, a dense lymphoplasmacytic infiltrate with occasional well-developed lymphoid follicles involves the interfollicular stroma. This infiltrate is associated with varying degrees of follicular atrophy, but the lymphoid infiltrate respects the boundaries of the epithelial/stromal interface. The follicular epithelium demonstrates prominent Hurthle cell change. In other areas, the dense plasmacytic infiltrate seems to target the follicular epithelium. Here, the small plasmacytic cells actually infiltrate the epithelium and pack the follicle spaces, forming “lymphoepithelial lesions”.

Discussion: Most cases of primary thyroid lymphomas are of the large B-cell category. These large cell lymphomas are clinically aggressive and usually do not pose a significant diagnostic challenge from the pathological point of view. Those cases of the thyroid lymphomas comprised of small lymphoplasmacytic cells fall within the family of neoplasms derived from the mucosal associated lymphoid tissues (MALT). These indolent B-cell lymphomas are CD20-positive and CD5- and CD10-negative. The molecular changes observed include trisomy 3, t(11;18), and t(1;14) translocations. In addition to the thyroid gland, they commonly occur in the stomach, orbit, and salivary glands.

MALT is not native to the thyroid gland. Instead, a background of chronic lymphocytic thyroiditis (Hashimoto’s thyroiditis) consistently serves as a background from which thyroid MALT lymphomas arise. The distinction of MALT lymphoma from its chronic inflammatory background is not always straightforward. One of the more helpful morphologic features is the presence of lymphoepithelial lesions – a term that refers to the permeation of epithelium by lymphoma cells. In the thyroid, the permeation of the follicular epithelium results in “follicular packing” where the centers of the follicles become filled or packed with tumor cells. In contrast, the reactive lymphocytes of chronic lymphocytic throiditis remain confined to the stroma and are much more respectful of the stromal/epithelial interface.

MALT lymphomas of the thyroid, like MALT lymphomas elsewhere, are indolent tumors. Localized disease is present in 60% to 70% of patients. Involvement of multiple extranodal sites has been observed at presentation or during the course of disease. Local therapy, either through surgery or radiotherapy, is curative in a high proportion of patients. MALT lymphomas respond to chemotherapy, but there is no evidence that cure can be achieved, although prolonged survival is common.