Lymph node metastases of papillary thyroid carcinoma.

Thyroid carcinoma is a relatively uncommon tumor that only rarely causes death. In the United States, the estimates for 2007 were 33,550 new cases and approximately 1,500 deaths from thyroid carcinoma (1). There are a number of histologic types of thyroid carcinoma, of which papillary thyroid carcinoma (PTC) is, by far, the most common. PTC accounts for up to 80% of all thyroid cancers. Many histologic variants of PTC also exist (2,3). Other, less common types of thyroid carcinoma include follicular, Hürthle cell (oncocytic), poorly differentiated (insular), anaplastic (undifferentiated), and medullary. In lymph nodes, metastatic PTC is of the greatest clinical importance for two reasons: PTC is most common, and it has a great propensity to metastasize to the cervical lymph nodes (4). For these reasons, the remainder of this chapter focuses on PTC.

The propensity of PTC to spread via lymphatic vessels results in the formation of multiple tumor foci formed within the thyroid gland, as well as frequent lymph node metastases that often occur early in disease evolution. In a large retrospective study of 859 patients with PTC conducted at the Mayo Clinic, 319 (37%) had metastases in cervical lymph nodes (5). In a study of 241 cases of PTC at the University of Florence, the prevalence of lymph node metastases was even greater—53.7% to cervical and 4.5% to mediastinal lymph nodes (6). By contrast, in patients with follicular thyroid carcinoma, metastases restricted to lymph nodes are rare (4,7). Hematogenous metastasis occurs much more frequently in patients with follicular thyroid carcinoma and is uncommon (approximately 5%) in patients with PTC (7).

In PTC, invasiveness and prognosis are related to the size and stage of the primary tumor, and these tumors can be divided into three stages: occult, intrathyroidal, and extrathyroidal (8). Occult (microscopic) thyroid carcinomas are up to 1 cm in diameter (average, 5 to 7 mm) and are often multifocal. Occult PTC is relatively common and may be an incidental finding in thyroid glands removed for other reasons (9,10). In autopsy studies, the prevalence of occult PTC was as high as 11.3% in Japan (9) and 35.6% in Finland (10). Fortunately, occult PTCs in most cases remain small and circumscribed without ever becoming a clinical carcinoma.

Small nests of thyroid colloid-containing follicles can be found in cervical lymph nodes and have been interpreted by some authors as benign ectopic inclusions of thyroid tissue. However, this concept is controversial. Others deny the existence of benign thyroid tissue inclusions in lymph nodes, and consider all such foci as metastatic tumors (11). In support of the latter opinion, in many patients with thyroid tissue inclusions in cervical lymph nodes, a primary focus of occult thyroid carcinoma is eventually found after extensive thyroid gland sampling (12). Therefore, the criteria for diagnosing benign thyroid inclusions in lymph nodes must be very stringent. Only a few, small, subcapsular thyroid follicles should be considered as possible benign thyroid inclusions. If thyroid tissue has replaced more than a third of a lymph node, the diagnosis of metastatic thyroid carcinoma should be established (4). The presence of psammoma bodies, papillae, or the typical nuclei (described below) supports metastatic PTC.

The mean age of patients with PTC is approximately 45 years in males and 43 years in females (range, 5 to 90 years) (5,6). The male-to-female ratio ranges from 1:2 to 1:3 (1,5,6,13). Most patients have a palpable mass or nodule(s). In one study, 98.7% of patients presented with clinically evident disease in the neck (6), located in the thyroid gland in 67.2%, thyroid gland and lymph nodes in 13%, and only in cervical lymph nodes in 19.7%. Thus, cervical lymphadenopathy without a thyroid mass occurs in approximately one-third of patients. Lymph node involvement is usually on the same side as the thyroid tumor, but in 10% of cases metastases to cervical lymph nodes are bilateral (4). Mediastinal lymph nodes become involved after cervical lymph nodes (4).

The prognostic significance of lymph node metastases in patients with PTC is not straightforward. In many studies, the presence of lymph node metastases at time of presentation was reported to not affect prognosis (8,13,14,15). However, a study published in 2005 using the large Surveillance, Epidemiology, and End Results (SEER) database found that lymph node involvement predicted poorer outcome in patients with well-differentiated thyroid carcinomas (16).

Risk factors for thyroid carcinoma are reported. Of these, radiation to the neck is perhaps the best established, and is most pronounced in children. In one large study of PTC, a history of radiation to the neck for various thymic or skin conditions was recorded in 6.6% of patients (6). The mean interval between irradiation and the appearance of PTC can vary from approximately 10 to 20 years (3,5). Children who were victims of the Chernobyl nuclear reactor accident in Belarus also have a markedly increased frequency of thyroid carcinoma (17,18,19). The latency interval in this group correlates with histologic type, being shorter in patients with more poorly differentiated tumors (19).

Papillary carcinoma of the thyroid gland is currently defined primarily by its nuclear features, although it was named for its common histologic pattern (Figs. 90.1,90.2,90.3,90.4,90.5) (4,5,6,20). The papillary pattern is usually predominant, but it can be focal and is almost never exclusive. Microfollicular and macrofollicular, solid, trabecular, and cystic patterns can be admixed with the papillary pattern (Figs. 90.1,90.2,90.3,90.4,90.5). The size and shape of the papillae vary from short and stubby to long and arborizing; they project within a cystic cavity. The papillae consist of
fibrovascular stalks containing thin-walled vessels and loose connective tissue lined by neoplastic epithelial cells (Fig. 90.2). The presence of a fibrovascular stalk distinguishes true papillae from pseudopapillae, which result from occasional infoldings of follicular epithelium or more commonly when spared pieces of epithelium hang in a cystic area of tissue degeneration. The papillary stalks may be swollen by edematous fluid, infiltrates of lymphocytes, or clusters of foamy macrophages. Psammoma bodies—round, calcified concretions with a concentric laminar structure—are present in approximately half of PTC and in lymph node metastases of such carcinomas (Fig. 90.3); therefore, they represent a helpful histologic finding when present. Psammoma bodies are usually located at the tips of the papillae or in the stroma. Colloid, often with scalloped edges, can be abundant in PTC (Fig. 90.4).