Keywords

The thyroid may be involved secondarily by lymphoma from other sites in the body or by leukemic infiltrates [1–3]. Most primary thyroidal lymphomas are B-cell types, but both Hodgkin’s lymphoma [1, 3] and T-cell lymphoma [4] may occur.

From an epidemiologic viewpoint, almost all primary thyroid lymphomas arise on a background of severe chronic lymphocytic thyroiditis [1–3]. Clinically, women are more commonly affected. These patients often have a history of a goiter with hypothyroidism. Rapid growth of a mass lesion is noted.

Gross examination reveals homogeneous, pale, and firm tissue that has replaced the thyroid irregularly. If advanced autoimmune thyroiditis is also present, the lymphoma probably cannot be distinguished from the inflammatory infiltrate without histologic examination. Microscopically, the regions of autoimmune thyroiditis reveal either the usual benign lymphoplasmacytic infiltrates or the common alterations of the follicular epithelial cells (e.g., oxyphilic cell metaplasia) [1, 5].

The lymphoma usually consists of a monotonous infiltrate of abnormal lymphoid cells which replace the thyroid parenchyma, fill and distend some thyroid follicles (Figs. 92.1 and 92.2), and permeate the walls of some of the larger vessels [1]. Extra-glandular extension into perithyroidal fat and skeletal muscle is very often present [1, 6]. Cytokeratin antibodies can demonstrate displaced and distorted follicular epithelium; lymphoepithelial lesions characteristic of so-called mucosa-associated lymphoid tissue (MALT) lymphoma are seen [6–8]. Cervical lymph nodes may be involved.

Fig. 92.1
figure 1

Malignant lymphoma. A number of thyroid follicles are formed by metaplastic epithelial cells, presumably because of previous Hashimoto’s thyroiditis. Both the interstitial tissue and the altered follicles are extensively infiltrated by the lymphoma (H&E stain)

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Fig. 92.2
figure 2

Malignant lymphoma. Many abnormal lymphoid cells are visible. The smallest cells are likely normal lymphocytes that accompany the malignant infiltrate (H&E stain)

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Smears from the aspirates may show predominantly chronic lymphocytic thyroiditis , and it is necessary to perform multiple aspirates until the lymphomatous regions are sampled [9, 10]. The latter show a monotonous lymphoid population, readily observed mitotic figures, and a conspicuous absence of follicular epithelial cells. There is controversy about the wisdom of making a primary cytological diagnosis of malignant lymphoma without addition of ancillary techniques such as flow cytometry or gene rearrangement studies [11, 12].

Sometimes in order to make a diagnosis of a specific subtype of lymphoma, an open surgical wedge biopsy of the mass may be needed.

The lymphoma may be diffuse or follicular (nodular). Separating the lymphoma from an adjacent infiltrate of autoimmune thyroiditis requires careful appraisal of the abnormal cells in the routine histologic sections and the use of immunohistochemical stains. In large cell malignant lymphoma, this is usually confirmatory and the histologic diagnosis is obvious; in cases of small cell lymphoma, special studies are warranted and needed to make the diagnosis [13].

Some thyroid lymphomas present as aggressive neoplasms, often in the elderly. A considerable number of thyroid lymphomas are of intermediate or low grade. Cases of this type have led to the concept that a thyroid involved with autoimmune disease is comparable to mucosa-associated lymphoid tissue (MALT) , such as the Peyer’s patches of the intestine [13, 14]. Thus, it has been suggested that the majority of thyroidal lymphomas are MALT lymphomas [14]. These lymphomas may tend to be localized for extended periods of time, possibly explaining why some thyroid lymphomas have been cured by surgery alone. Thyroid lymphomas may spread to other sites of MALT (e.g., small bowel); in some patients, extranodal MALT lymphoma of the lung or bowel may precede the development of thyroid lymphoma. Some of these tumors may show plasmacytic differentiation [1, 3]. Such cells are usually monotypic with immunoglobulin light-chain restriction. The lymphoma cells may extend into the reactive lymphoid follicles of the autoimmune thyroiditis, thereby explaining the follicular (nodular) pattern of some lymphomas [15]. Also, persisting lymphoid follicles have been reported in the rare plasmacytomas of the thyroid [16], possibly supporting the theory that plasmacytomas of the thyroid are mature MALT lymphomas. When a high-grade lymphoma is present, there is often evidence that it has arisen from a low-grade MALT lymphoma [17].