Pathology of thyroid gland Hyperthyroidism Diseases Graves Disease -most common cause of endogenous hyperthyroidism -autoimmune disorder produced by autoantibodies to the TSH receptor, thyroid growth stimulating immunoglobulins, TSH binding inhibitor immunoglobulins -triad of clinical findings: 1. Hyperthyroidism owing to hyperfunctional and diffuse enlargement of the thyroid 2. Infiltrative opthalmopathy with exopthalmos 3. Localized infiltrative dermopathy (pretibial myxedema) Multinodular goitre -reflects impaired synthesis of thyroid hormone due to dietary iodine deficiency. -compensatory rise in serum TSH levels causes hypertrophy and hyperplasia of the thyroid follicular cells and enlargement of the gland. -With time, recurrent episodes of hyperplasia and involution (after the stressor is over) causes irregular enlargement of the thyroid resulting in a multinodular goiter. -may be non-toxic or may induce thyrotoxicosis (toxic). Morphology –diffuse hypertrophy and hyperplasia of the thyroid follicular epithelial cells. - lots of interstitial lymphocytes -tall crowding of cells forming papillae that lack fibrovascular cores. -colloid within follicles are pale and scalloped. -large aggregates of lymphoid aggregates. Lab findings –elevated free T4 and T3 and depressed TSH. -multilobulated, asymmetrically enlarged gland which may achieve a weight more than 2000 gm. -irregular nodules with hemorrhage, fibrosis, calcification and cystic change, follicles lined by flattened inactive epithelium. Hashimoto Thyroiditis -most common cause where iodine levels are sufficient -autoimmune destruction of the thyroid gland -primarily disease of older women -some cases assoc with HLA-DR5, minority linked to HLA-DR3 -hypothyroidism followed by thyrotoxicosis due to destruction of the thyroid follicles with release of thyroid hormones -increased risk for the development of B cell lymphoma. Subacute granulomatous thyroiditis (painful) -DeQuervain thyroiditis -less frequent than Hashimoto disease -women more than men. -assoc. with HLA-B35 -Sudden or gradual presentation -thyroid inflammation transient with hyperthyroidism, followed by hypothyroidism -thyroid diffusely enlarged -infiltration of the parenchyma by mononuclear inflammatory infiltrate containing small lymphocytes, plasma cells and with germinal centers -Hurthle cells -unilaterally or bilaterally enlarged gland -early –neutrophils forming microabscess -late –aggregations of lymphocytes, histiocytes, plasma cells, multinucleated giant cells Treatment of acute phase is with aspirin, using short term prednisolone in severely symptomatic cases. VHypothyroidism Subacute lymphocytic thyroiditis (painless) -uncommon cause of thyroiditis -mild hyperthyroidism or goitrous enlargement of the gland -middle age adults, more common in women esp. the postpartum period. -assoc with HLA-DR3 and DR5, considered as a variant of Hashimoto thyroiditis -Both Hashimoto and lymphocytic thyroiditis have elevated levels of antibodies to thyroglobulin and thyroid peroxidase. Ridel thyroiditis -less common form of thyoriditis -extensive fibrosis of the thyroid gland and contiguous neck structures -may be assoc. with idiopathic fibrosis in other sites in the body e.g. retroperitoneum. -mild symmetric enlargement -multifocal inflammatory infiltrate predominantly of small lymphocytes, plasma cells and germinal centers not conspicuous -uniform appearing follicles that contain colloid. -macrofollicular, microfollicular, embryonal (trabecular), Hurthle cell (oxyphil, oncocytic) cells Adenoma Adenoma (benign solitary nodule) -discrete, solitary, encapsulated lesion that is well demarcated from the surrounding thyroid parenchyma. -areas of hemorrhage, fibrosis, calcification and cystic change similar in multinodular goiters are common. -careful integrity of the capsule is important in the distinction of and adenoma from a well differentiated follicular carcinoma. Carcinoma Papillary carcinoma -most common form of thyroid cancer -in 20 to 40 age group -assoc. with ionizing radiation, Gardner syndrome, Cowden disease - less than 1.5 cm: good prognosis -solitary or multifocal lesions -papillary structures with fibrovascular stalks -nucleus with optically clear center (ground-glass or Orphan Annie nuclei) -eosinophilic intranuclear inclusions or grooves -psammoma bodies -encapsulated, follicular and tall-cell variant. Follicular carcinoma -second most common form of thryoid cancer -women at an older age -peak in 40s and 50s -increased in areas with dietary iodine deficiency -nodular goiter may predispose to the neoplasm -single nodules that may be circumscribed or infiltrative -difficult to distinguish from follicular adenoma (benign, derived from follicular epi, solitary usually ) -microscopically composed of fairly uniform cells forming small follicles containing colloid, extensive invasion into the surrounding thyroid parenchyma, -presence of capsular or vascular permeation. - Medullary carcinoma -neuroendocrine neoplasm derived from parafollicular cells or C cells of the thyroid -germline mutation of the RET proto-oncogene plays an important role. Anaplastic carcinoma -undifferentiated tumours of the thyroid follicular epithelium -mortality approaching 100% -less than 5% of all thyroid cancers -older patients, age 60-70 -history of multinodular goiter or concurrent differentiated carcinoma e.g. papillary carcinoma -possibly due to loss of p53 tumour suppressor gene - rapid growth, hoarseness and dyspnea - large amd invasive, most pr die within 1 yr despite all treatment efforts -solitary nodule or multiple lesions -bilaterality and multicentricity common in familial cases -microscopically composed of polygonal to spindle cells in nests, trabeculae and follicles -Acellular amyloid deposits derived from altered calcitonin molecules are present in the adjacent stroma A-Multiple C cell hyperplasia present in the surrounding thyroid parenchyma. -highly anaplastic cells 1. Large, pleomorphic giant cells 2. Spindle cells with sarcomatous appearance 3. Small cells Congenital - Glandular agenesis/ aplasia/ hypoplasia Accessory/ aberrant gland – on the tongue, behind – careful, removal may cause thyroid storm, Thyroglossal (midline) and branchial (lateral, move when sticking out tongue) cyst vs thyroid(moves with swallowing) Lymphoepithelial cysts (benign, slowly growing unilocular or multilocular lesions that appear in the head and neck. They are also called Branchial cyst) Benign thyroid inclusions (Benign thyroid inclusions involve medial inferior neck lymph nodes, whereas any thyroid tissue found lateral to large neck vessels (carotid artery or jugular vein) should be considered metastatic tumor rather than a developmental anomaly)
