Thyroid Pathology

Question 1

Embryology of the thyroid

Answer 1

• Begins as invagination of foramen cecum and descends down to form thyroglossal duct (later disappears)
• Eventually pharyngeal epithelial cells proliferate to form thyroid, and neuroendocrine cells (neural crest) migrate into thyroid gland to become parafollicular (C) cells

Question 2

Congenital anomalies of the thyroid

Answer 2

• Athyreosis: complete absence of thyroid gland, common cause of cretinism
• Thyroglossal duct cyst: midline mass near the hyoid bone (midline)
• Aberrant thyroid: one that fails to descend (lingual thyroid) or goes to other areas

Question 3

Diffuse goiter

Answer 3

• Symmetrically enlarged thyroid w/o nodules

- Usually progresses to multi nodular goiter w/ heterogeneous thyroid activity

Question 4

Multinodular goiter

Answer 4

• Pt is usually euthyroid, may have pressure Sxs
• Variable gross presentation: nodules may be firm, gelatinous, hemorrhagic, calcified
• Micro is also variable: lakes of colloid, hemorrhage, fibrosis/calcification, cholesterol crystals and macro/microfollicles are all possible
• Plummer syndrome is hyperthyroidism secondary to toxic multinodular goiter

Question 5

Grave’s disease

Answer 5

• Hyperthyroidism, diffuse goiter and may show exopthalmos and/or peritibial myxedema
• Due to autoimmune Abs (Th2 reaction) stimulating TSH receptors, mostly in women
• There is marked hyperplasia and hypertrophy on micro w/ tall, columnar follicular cells w/ scant “scalloped” colloid

Question 6

Hashimoto thyroiditis

Answer 6

• Most common form of hypothyroidism in US, is autoimmune T cell (Th1) destruction of thyroid gland (mostly in women)
• Gross: gland is pale, firm, rubbery, tan or white
• Micro: small follicles w/ scant colloid and pink plump granular oxyphil cells (hurtle cells)
• May see germinal centers

Question 7

Granulomatous (subacute) and reidel thyroiditis

Answer 7

Granulomatous: a viral origin, usually Hx of URI leads to tender, enlarged thyroid gland and fever

• Micro: focal involvement w/ a destructive granulomatous inflammatory process w/ giant cells engulfing colloid and variable fibrosis
• Reidel thyroditis: invasive fibrous thyroiditis (rare) where collagen replaces parenchyma

Question 8

Atrophy of the thyroid gland

Answer 8

• Idiopathic: scattered lymphocytes and small clusters of follicular cells are found within collagen (thyroid gland is shrunken and fibrotic)
• Can also be post-radiation (I131)

Question 9

Thyroid adenoma

Answer 9

• Benign nodule, commenest thyroid neoplasm
• Gross: usually solitary, encapsulated
• Micro: distinct fibrous encapsulation, no invasion, uniform cells within nodule
• Usually follicular adenoma, may be function or non-functional (usually non)

Question 10

Papillary CA

Answer 10

• 5% of all thyroid nodules are malignant, papillary is most common and best prognosis
• Associated w/ RET/PTC gene mutations, history of irradiation
• May be multi centric and may have lymph node mets
• Micro: papillary fronds/fingers of epithelial cells w/ large nuclei that appear empty (orphan annie eyes), and some have longitudinal grooves (coffee been appearance)
• May have psamomma body (large dark inclusions)
• Tumors are thyroglobulin and TTF positive
• Follicular variant shows well-formed follicles w/ similar nuclei appearance (worse prognosis)

Question 11

Follicular CA

Answer 11

• RAS oncogene mutations, PAX8-PPARg mutations associated
• Hematogenous spread usually to lung and bone
• Micro: encapsulated shows well differentiated cells w/ capsular and/or vascular invasion
• Looks like adenoma
• Nonencapsulated: variable follicular differentiation, more aggressive invasion usually
• Also thyroglobulin and TTF1 positive

Question 12

Medullary CA

Answer 12

• Tumor of the parafollicular (C) cells, large familial portion (20%), seen in MEN IIA/B syndromes
• MEN 2A: pheo, medullary CA, hyperparathyroidism (TAP)
• MEN 2B: pheo, medullary CA, mucocutaneous (MAT)
• RET mutations involved
• Medullary CA + pheochromocytoma is sipple’s syndrome
• Usually in 5th and 6th decades, if younger think MEN
• Micro: solid cellular tumor w/o papillae/follicles
• Small round spindle cells arranged in trabeculae, nests, or sheets
• Often contains amyloid, hyper secretes calcitonin (no clinical effect)

Question 13

Anaplastic (undifferentiated) CA

Answer 13

• Rare, very aggressive, associated w/ P53 mutation
• Gross: huge tumor (bulk neck)
• Micro: large multinucleate, small or spindle cells
• No significant follicular or papillary growth patterns