A 61-year-old woman comes to the office due to a neck lump. She is otherwise in good health and has no other symptoms. Temperature is 36.7 C (98.1 F), blood pressure is 115/70 mm Hg, and pulse is 78/min. On physical examination, there is a nontender, firm nodule in the left lobe of the thyroid. Laboratory results show a normal serum TSH level. Thyroid ultrasonography reveals a 2-cm, hypoechoic thyroid nodule with increased central blood flow. Fine-needle aspiration biopsy shows clusters of cells with large, overlapping nuclei containing finely dispersed chromatin. Numerous intranuclear inclusion bodies and grooves are also seen. Which of the following is the most likely diagnosis?
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The 4 main types of primary thyroid carcinoma include papillary, follicular, medullary (derived from the parafollicular, calcitonin-secreting C cells), and anaplastic. The papillary type is most common, accounting for >70% of cases. Risk factors include a positive family history of thyroid cancer and radiation exposure, especially in childhood.
Papillary carcinoma cells are characteristically large with overlapping nuclei containing finely dispersed chromatin, giving them an empty or ground-glass appearance (sometimes termed Orphan Annie eye nuclei after a cartoon character whose eyes were drawn without pupils or irises). Numerous nuclear grooves as well as intranuclear inclusions composed of cytoplasm (ie, pseudoinclusions) can be seen due to invagination of the nuclear membrane. Psammoma bodies (laminated calcium deposits) may also be found within the tumor.
(Choice A) Anaplastic thyroid carcinoma is an aggressive tumor with a very poor prognosis. It is most common in patients age >60. Cytologic features include markedly pleomorphic cells, including irregular giant and spindle cells.
(Choice B) Most benign thyroid nodules are colloid nodules formed from focal hyperplasia of normal thyroid follicular cells. On cytopathology, a colloid nodule consists of variable-sized thyroid follicles, colloid, and macrophages.
(Choices C and D) Follicular neoplasms lack the characteristic nuclear features and psammoma bodies found in papillary carcinoma. Distinguishing a benign follicular adenoma from a well-differentiated follicular carcinoma depends on the presence of vascular or capsular invasion, which cannot be determined on a fine-needle aspiration specimen.
(Choice E) Medullary thyroid carcinoma appears histologically as polygonal or spindle-shaped cells with a slightly granular cytoplasm that stains for calcitonin. Extracellular amyloid deposits consisting of calcitonin polypeptide may also be seen. Medullary thyroid cancer is a component of multiple endocrine neoplasia types 2A and 2B.
Educational objective:
Papillary thyroid carcinoma is the most common type of thyroid cancer. Characteristic microscopic features include large cells with nuclei containing finely dispersed chromatin, giving them an empty or ground-glass appearance (ie, Orphan Annie eye), as well as intranuclear inclusions and nuclear grooves.