Thyroid

The thyroid gland is a butterfly-shaped organ located in the neck that plays a central role in metabolism, growth, and development through the production of thyroid hormones. This chapter reviews normal thyroid histology and common pathological conditions affecting the thyroid gland, including both benign and malignant neoplasms.

NORMAL HISTOLOGY OF THE THYROID:

The thyroid gland is made up of numerous spherical structures called follicles. Each follicle is lined with follicular cells that secrete thyroglobulin, the precursor to thyroid hormones. The follicular cells surround a central cavity filled with colloid, a substance containing stored thyroid hormones. (NOTE: Thyroid hormone synthesis is beyond the scope of this histopathology text; please refer to the thyroid endocrinology lecture for detailed information).

• Follicular Cells: Cuboidal cells that become flattened when the gland is inactive and more columnar when the gland is active in hormone production.
• Colloid: The storage form of thyroid hormones within the follicles.
• Parafollicular Cells (C cells): Found between the follicles, these cells produce calcitonin, a hormone involved in calcium homeostasis.

NON-NEOPLASTIC THYROID PATHOLOGY:

• Thyroglossal Duct Cyst: A congenital anomaly resulting from the persistence of the thyroglossal duct, a structure involved in the development of the thyroid gland. It often presents as a midline neck mass and can become infected or require surgical removal.

• Hashimoto’s Thyroiditis: An autoimmune disorder where the body’s immune system attacks the thyroid gland. Patients typically develop hypothyroidism due to the destruction of thyroid tissue. Histologically, the thyroid is infiltrated with lymphocytes and plasma cells, with the formation of germinal centers and Hürthle cell changes in the thyroid epithelium.

• Graves’ Disease: An autoimmune disorder characterized by hyperthyroidism due to antibodies stimulating the TSH receptor on follicular cells, leading to overproduction of thyroid hormones. Histologically, the thyroid gland is enlarged, with hyperplasia of the follicular cells and scalloped colloid due to increased hormone release.

NEOPLASTIC PATHOLOGY OF THE THYROID:

• Follicular Adenoma: A benign tumor of the thyroid that presents as a single “cold” nodule on a radioactive iodine scan. The lesion is encapsulated, with no invasion into surrounding tissue. Histologically, the tumor resembles normal thyroid tissue but is confined within a fibrous capsule.

• Papillary Thyroid Carcinoma: The most common type of thyroid cancer, often associated with exposure to ionizing radiation. It tends to spread via the lymphatics, and histologically shows characteristic  Orphan Annie eye nuclei and psammoma bodies. It has an excellent prognosis.

• Follicular Thyroid Carcinoma: This cancer often resembles a follicular adenoma but invades the capsule and blood vessels. It tends to spread hematogenously rather than through the lymphatics, which distinguishes it from papillary carcinoma.

• Medullary Thyroid Carcinoma: A malignancy of the C cells that secrete calcitonin. Medullary carcinoma may be sporadic or associated with Multiple Endocrine Neoplasia (MEN) syndromes, particularly MEN 2A and 2B. Histologically, these tumors are often associated with amyloid deposits derived from misfolded calcitonin.

• Anaplastic Thyroid Carcinoma: One of the most aggressive cancers, often seen in elderly patients. Histologically, these tumors are undifferentiated and exhibit marked anaplasia with numerous mitoses. Patients often present with rapidly enlarging neck masses and die within months.

Mutations in Thyroid Cancer: