A 30-year-old man comes to the office with a neck lump. The patient is otherwise asymptomatic and discovered the nodule incidentally while showering. His medical history is significant for a recently diagnosed pheochromocytoma, which was successfully removed. The patient's father died of thyroid cancer in his 30s. An ultrasound reveals a hypoechoic 3-cm nodule in the right lobe of the thyroid gland. Fine-needle biopsy of the nodule is consistent with a subtype of thyroid cancer. The patient undergoes total thyroidectomy with central neck dissection. Which of the following is the most likely histological finding?
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This patient has a personal history of pheochromocytoma and a family history of thyroid cancer. His new thyroid malignancy therefore raises suspicion for multiple endocrine neoplasia type 2 (MEN2), which is characterized by:
Approximately 20% of medullary thyroid cancers are familial, occurring as part of MEN2 or familial medullary thyroid cancer syndrome due to germ-line mutations of the RET proto-oncogene. Medullary thyroid cancer is a neuroendocrine tumor that arises from parafollicular calcitonin-secreting C cells. Nests or sheets of polygonal or spindle-shaped cells with extracellular amyloid deposits are seen microscopically. These amyloid deposits are derived from calcitonin secreted by the neoplastic C cells and stain with Congo red. Despite overproduction of calcitonin, hypocalcemia is not a prominent feature.
(Choice A) Gross inspection of papillary thyroid cancer may reveal formation of visible papillae; microscopic inspection of papillae shows a fibrovascular core, often with laminar calcifications (psammoma bodies). The cells contain pale nuclei with finely dispersed chromatin, giving them an empty or ground-glass appearance (Orphan Annie eye nuclei). Intranuclear inclusions and grooves can be seen due to invagination of the nuclear membrane.
(Choice B) Hyperplastic follicles with tall, crowded cells forming intrafollicular projections can be seen in Graves disease, often with hyperactive resorption of colloid leading to scalloping of the colloid edges.
(Choice D) Anaplastic thyroid cancer is an aggressive tumor with a very poor prognosis. It is most common in older patients (age >60). Cytologic features include markedly pleomorphic cells, including irregular giant cells and biphasic spindle cells.
(Choice E) The presence of colloid-containing microfollicles suggests a benign follicular adenoma. Follicular carcinoma can also contain small follicles but will show vascular or capsular invasion.
Educational objective:
Medullary thyroid cancer is a neuroendocrine tumor that arises from parafollicular calcitonin-secreting C cells. It is characterized by nests or sheets of polygonal or spindle-shaped cells with extracellular amyloid deposits derived from calcitonin.