Pathophysiology
Summary
Thyroid nodularity ranges from benign conditions like multinodular goiter and follicular adenomas to malignant forms like papillary and follicular thyroid carcinomas. Multinodular goiter is commonly due to iodine deficiency and may contain hot nodules, which are typically benign. Solitary thyroid nodules are usually benign cysts or arise from inflammatory conditions like Hashimoto's thyroiditis.
Thyroid malignancies are more common in children and males, and often associated with neck radiation. Papillary thyroid carcinoma is the most prevalent, especially in adult women, and is linked to mutations in the MAPK signaling pathway. Histologically, these show psammoma bodies and "Orphan Annie eye" cell nuclei. Follicular thyroid carcinoma, the second most common type, is marked by capsular invasion and spreads hematogenously to distant organs. It is more common in older women and iodine-deficient regions and is often caused by RAS oncogene activation. Cold nodules should be biopsied to rule out malignancy.
Specialized thyroid carcinomas include anaplastic and medullary thyroid carcinomas, which are generally more aggressive than papillary and follicular types. Anaplastic thyroid carcinoma most frequently occurs in those over 65 and is marked by a nearly 100% mortality rate. It may arise sporadically or from existing thyroid cancers and is characterized by the loss of p53 regulation. Histologically, it shows large, pleomorphic nuclei, prominent mitotic figures, & capsular invasion. Anaplastic thyroid carcinomas grows aggressively into surround tissue, often resulting in tracheal compression.
Medullary thyroid carcinomas originate from parafollicular C cells, which are neuroendocrine cells lining the periphery of thyroid follicles. While most cases are sporadic, up to 20% are associated with MEN2A & MEN2B syndromes, especially in patients with RET protooncogene mutations. They may be localized or metastasize to cervical lymph nodes. Because of their C cell origin, these tumors often produce calcitonin, which serves as a useful tumor marker. Elevated calcitonin levels can also lead to GI symptoms like diarrhea. Other hormones, such as VIP and serotonin, may also be produced, leading to symptoms like flushing and Cushing's syndrome. Histologically, these tumors are solid masses with areas of necrosis and hemorrhage, composed of nests of polygonal or spindle-shaped neuroendocrine cells containing dense secretory granules. Amyloid deposits, which are precipitated calcitonin, may be present and appear red or green when stained with Congo red.
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FAQs
Multinodular goiter is most commonly caused by iodine deficiency hypothyroidism. When iodine levels are insufficient, the thyroid gland struggles to produce enough thyroid hormone. To compensate, the gland enlarges, leading to the formation of multiple nodules.
'Hot' nodules absorb radioactive iodine during scans, indicating they are functional and rarely malignant. In contrast, 'cold' nodules do not absorb radioactive iodine, suggesting they may be non-functional and potentially cancerous. Therefore, 'cold' nodules are often biopsied to rule out malignancy.
Follicular adenomas are benign nodules with a well-defined, intact capsule made up of follicular cells surrounding colloid. Follicular carcinomas, on the other hand, show invasion of this capsule, indicating malignancy. The presence or absence of capsular invasion is a crucial diagnostic factor in distinguishing between these two conditions.
Papillary thyroid carcinoma is the most common type of thyroid cancer and has a strong association with radiation exposure. It accounts for up to 85% of thyroid malignancies, predominantly affecting adult women. Key microscopic features include 'Orphan Annie eye' nuclei and the presence of psammoma bodies, which are dystrophic calcifications.
Medullary thyroid carcinoma arises from parafollicular C cells, which are neuroendocrine cells lining the thyroid follicles. While most cases are sporadic, up to 20% are associated with genetic syndromes like MEN2A and MEN2B. These carcinomas can produce calcitonin, which serves as a tumor marker, and may also form amyloid deposits from precipitated calcitonin.
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