Surgical Pathology of the Thyroid Gland

Introduction

Most surgical thyroid disease involves lesions that produce thyroid enlargement—sometimes diffuse but usually nodular. This chapter will discuss lesions of the thyroid that produce nodules. We will describe and discuss the pathologic features of these lesions as well as their differential diagnosis and prognostic features.

All neoplasms that arise from thyroid epithelial cells can have some functional capacities. They may respond to thyroid-stimulating hormone (TSH) and even produce excessive amounts of thyroid hormones, or if medullary carcinoma, they may release abnormal quantities of calcitonin or other peptide hormones. Immunohistochemical localization of thyroid transcription factor-1 (TTF-1), thyroglobulin, or calcitonin aids in classifying unusual thyroidal tumors and in providing definite identification of metastatic thyroid carcinomas.

Benign Neoplasms: Adenomas and Adenomatous Nodules

The definition of a follicular adenoma is controversial. Many pathologists believe that a follicular adenoma is a solitary, encapsulated lesion having a uniform internal architecture that is substantially different from the surrounding thyroidal parenchyma by both growth pattern and cytologic features.

However, this definition of adenoma is too restrictive, especially the requirement that the lesion be completely encapsulated. In some instances, it is difficult to separate clearly hyperplastic/adenomatous nodules arising in the background of goiter or thyroiditis from adenomas; up to 70% of the hyperplastic nodules in goiter are clonal, thus representing neoplastic proliferations. Therefore we propose that an adenoma should be defined as a follicular-derived and encapsulated (partially or completely) or circumscribed nodule with a distinct growth pattern limited to the confines of its capsule that is different from the surrounding thyroid parenchyma. These follicular lesions are rarely multiple; they arise in a background of a normal thyroid or in the setting of nodular goiter, toxic goiter, or thyroiditis.

Grossly, adenomas and nodules are well circumscribed and often demarcated from adjacent tissue. Their size varies from about 1 mm in diameter to several centimeters. A classic adenoma is fleshy and pale; hemorrhage, fibrosis, and cystic change may be evident. Long-standing lesions, especially in elderly patients, and calcifications (often multiple and centrally located in the lesion) may be seen.

Microscopically, an adenomatous nodule shows a varied pattern of large and small follicles, usually with abundant colloid. The cells range from flat to cuboidal or columnar with small, round nuclei with even chromatin pattern. The stroma of the nodule often appears edematous. Macrophages, lymphocytes, hemosiderin, fibrosis, and even calcification can be found. Cystic change is common, especially in adenomatous nodules, and it may frequently be accompanied by the formation of papillae. Occasionally benign lesions are hyperfunctional, or “hot”; usually this occurs in nodules arising in a multinodular goiter rather than with a classic adenoma. In adolescents, especially females, many of the hot, or toxic, nodules contain numerous papillae, often sufficient in number to cause a pathologist to suggest a diagnosis of papillary carcinoma.

In the era of fine-needle aspiration (FNA), some cases of adenomatous nodules and adenomas, especially of oncocytic follicular (Hürthle) cell type, may exhibit prominent post-FNA changes, which include focal hemorrhage, fibrosis, endothelial proliferation, pseudovascular and capsular invasion, and even partial or total infarction.

By immunohistochemistry, all adenomatous nodules and adenomas express TTF-1, thyroglobulin, and show cytokeratin expression similar to normal thyroid parenchyma.

Several studies have suggested different biologic markers to differentiate between follicular adenoma and carcinoma. Via immunohistochemistry or molecular analysis, these studies have identified differences in expression of p53, PAX8 PPAR-gamma translocation, and RAS mutation in adenomas and carcinomas. However, these differences are not sufficient or specific enough to allow definitive diagnosis, and hence one should rely on morphologic criteria alone to differentiate between follicular adenoma and carcinoma.

Variants of Follicular Adenoma

Malignant Neoplasms

The most common malignant neoplasms that originate in the thyroid are well-differentiated carcinomas of follicular cell origin; most are papillary carcinomas.

Most nonneoplastic diseases of the thyroid are not precursors of malignant diseases; autoimmune thyroiditis is an important exception, and it may predispose a patient to malignant lymphoma. Rarely may an adenoma or adenomatous nodule contain a focus of papillary carcinoma.

Anaplastic carcinomas can arise in goitrous thyroids, and careful examination of resected tissues may demonstrate benign tumors or well-differentiated carcinomas in close association with the carcinoma. Such findings suggest that the benign tumor or low-grade carcinoma has “transformed” into the anaplastic carcinoma.

In modern endocrine practice, the initial approach to thyroid nodules is FNA; this technique can triage lesions, which must be removed surgically. However, about 30% of cases will yield an indeterminate diagnosis (see Chapter 10 , The Evaluation and Management of Thyroid Nodules, and Chapter 11 , Fine-Needle Aspiration of the Thyroid Gland–The 2017 Bethesda System).

Frozen sections can be helpful in papillary cancer, but follicular and Hürthle cell tumors cannot be definitively diagnosed by frozen section.