Thyroid pathology – Flashcards
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Hyperthyroidism
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- hypermetabolic state (elevated levels of free T3 and T4), sympathetic NS overstimulation the most common causes: - diffuse toxic hyperplasia (Graves d.) - - 80%toxic multinodular goiter (Plumer d.) - toxic (hyperfunctional) adenoma
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Hyperthyroidism clinical symptoms
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- heat intolerance, sweating - tachycardia, palpitations, cardiomegaly, arrhythmias - thyrotoxic cardiomyopathy - ocular changes (exophthalmos: wide-eyed, staring gaze) - neuromuscular system myopathy (proximal muscle weakness, atrophy of skeletal muscle) - tremor, hyperactivity - emotional lability - inability to concentrate - insomnia - GI system (hypermotility, diarrhea) - skin (soft, warm) - weight loss (increased appetite) - osteoporosis (bone resorption)
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Graves disease
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- 2- 4 decade - F>M 10:1 - 1.5-2% of women - the most common endogenous hyperthyroidism - thyroid symetric enlargement > 60g, (toxic) + ophthalmopathy + pretibial myxedema (dermopathy)
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Graves disease histology
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- tall cells, crowded, small papillae, scalloped margins
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Graves disease symptoms triad
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- diffusely enlarged gland, - infiltrative ophthalmopathy with exopthalmos - and infiltrative dermopathy / pretibial myxedema (thickening and induration of shin, seen late in disease in 5-10%) (also cardiac hypertrophy with ischemic changes)
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Opthalmopathy causes
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- displacement of the eyeball - the volume of retroorbital connective tissue is increased: - fatty tissue hyperplasia - infiltration by mononuclear cells (limf. T) - oedema of muscles - accumulation of ECM components : glycosaminoglycans - associated with high titer of anti-TSH antibodies
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Graves disease lab findings
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- increased T3/T4 - increased uptake of radioactive iodine - decreased TSH
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Graves disease antibodies
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autoantibodies: - long-acting thyroid stimulator (LATS): IgG that stimulates thyroid function (similar to but slower than TSH) (i.e. long-acting); specific for Graves' disease - thyroid stimulating immunoglobulins other than LATS also stimulate TSH rec. - TSH binding inhibitor immunoglobulins (have either a stimulatory or inhibitory effect) - antibody production probably due to primary T cell autoimmunity
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Graves disease increased risk
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increased risk for other autoimmune diseases: - lupus erythematosus - pernicious anemia - type I diabetes - Addison disease
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Hypothyroidism
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- decreased T3, T4 production - prevalence icreases with age (subclinical) - F>M 10:1
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Hypothyroidism causes
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- iodine deficiency - radiation (to the neck), surgical ablation - Hashimoto thyroiditis (autoimmune) - drugs (lithium) - inborn errors - rare - suprathyroid (hypothalamic, deficient TSH)
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Dietary iodine deficiency
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- iodine deficiency - low level of T3, T4 - TSH level rises - hypertrophy and hyperplasia of thyroid follicular cells - enlargement of thyroid gland (goiter) - T3, T4 production rises - euthyroid state - if the compensatory respose is not adequate (iodine deficiency is to high) - goiter + hypothyroidism (congenital)
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Cretinism
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- when hypothyroidism begins in infancy or early childhood - endemic dietary iodine deficiency (mountainous areas) - Himalayas, China today: supplementation of food with iodine
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Cretinism symptoms
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- severe mental retardation - impaired development of skeletal system (short stature), coarse facial features - protruding tongue - umbilical hernia
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Myxedema
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- when hypothyroidism begins in adult - slowing of mental and physical activity - fatigue, apathy, listlessness - depression-like state - cold-intolerance, pale, dry skin - overweight, high cholesterol level - constipation (decreased sympathetic activity) - accumulation of glycosaminglycans in subcutaneous tissue: oedema, enlargment of the tongue, deep voice
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Myxedema lab
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- serum TSH - high - T3, T4 - low
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Thyroiditis types
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- Hashimoto thyroiditis (autoimmune) - Riedel thyroiditis - de Quervain thyroiditis (subacute)
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Hashimoto's thyroiditis
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- def: autoimmune disease: goiter + circulating antibodies: anti-thyroid peroxidase and anti-thyroglobulin - also called Hashimoto's disease, struma lymphomatosa, lymphocytic thyroiditis - 90-95% in women (4-6 decade) - can occur in children - most common cause of hypothyroidism in iodine-sufficient areas of the world - most common cause of nonendemic goiter in children
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Hashimoto incidence
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- clusters in families - more common in Whites than Blacks or Japanese cause: breakdown in self-tolerance to thyroid auto-antigens
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Hashimoto clinical presentation
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- goiter - painless - gradual thyroid failure due to autoimmune destruction - initially: transient hyperthyroidism - diffuse enlargment, pale, firm - intact capsule - associated with HLA-DR5 (goitrous form), HLA-DR3 (atrophic form)
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Hashimoto risks
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- may coexist with SLE, rheumatoid arthritis, Sjogren's syndrome, pernicious anemia, type 1 diabetes, Graves' disease, chronic active hepatitis, adrenal insufficiency - MALT lymphomas of GI tract (80:1 relative risk), other B cell lymphomas - associated with well differentiated thyroid cancer may evolve into thyroid lymphoma
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Hashimoto antibodies
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- anti-TSH (specific for Hashimoto's and Graves' disease) - anti-TG (less sensitive but similar specificity as anti-thryoid peroxidase) - anti-thyroid peroxidase (sensitive but not specific: 20% of adult women without disease have these antibodies) - anti-iodine transporter (rare) -note: anti-TSH antibodies block the TSH receptor in Hashimoto's disease but stimulate the TSH receptor in Graves' disease
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Hashimoto treatment
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- at the beginning: no treatment needed - thyroid hormone for hypothyroidism - subtotal thyroidectomy to relieve mass effect - rarely progresses to lymphoma
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Hashimoto histology
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- extensive lymphocytic infiltrate with germinal center formation - lymphocytes: predominantly T cells and plasma cells (polyclonal) - atrophic follicles with abundant Hürthle cells/oncocytes - reduced colloid - fibrosis may be increased but does not extend beyond capsule - single giant cells may be seen - later little thyroid parenchyma is present
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Hürthle cells/oncocytes
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An epithelial cell characterized by an excessive amount of mitochondria, resulting in an abundant acidophilic, granular cytoplasm
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Riedel thyroiditis
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- etiology unknown - extensive fibrosis of thyroid and surrounding tissues
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Subacute (de Quervain) thyroiditis
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- def: inflammation of thyroid gland with granulomas formation - also called granulomatous thyroiditis - rare (less common than Hashimoto's thyroiditis) - most common cause of thyroid pain - F>M 4:1 - 3-5 decade
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de Quervain thyroiditis etiology
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- may be trigered by systemic viral infection - seasonal incidence - associated with epidemics of measles, mumps, - Coxsackie, adenovirus, upper respiratory infection, influenza - virus-induced tissue damage - lymphocytes T - process is self-limited - after 8 weeks: normal thyroid function
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de Quervain thyroiditis clinical presentation
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- enlarged thyroid (variable), intact capsule - painful swallowing (odynophagia), sore throat, thyroid region tenderness - fever, fatigue, malaise - transient hyperthyroidism at 2-6 weeks
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de Quervain laboratory findings
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- high T3/T4 (initially), elevated sedimentation rate (ESR) and CRP suppression of radioactive iodine uptake
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de Quervain thyroiditis histology
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- the foreign body giant cells with destruction of thyroid follicles
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Solitary nodule in thyroid
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- one dominant nodule in multinodular goiter cyst possibilities: - focus of thyroiditis - adenoma (benign neoplasm) - carcinoma (less than 1% of solitary nodules) adenoma>ca 10:1
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Adenoma (follicular adenoma)
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- clinically: nodule difficult to distinguish from dominant nodule of nodular hyperplasia - usually: they are NOT forerunners to carcinoma - majority are nonfunctional (cold) - if functional (toxic adenoma): independent of TSH stimulation - solitary, round encapsulated lesion - well demarcated from the surrounding thyroid - a few cm
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Adenoma clinical features
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- small: asymptomatic (unilateral painless mass) - bigger: difficulty in swallowing - on radionuclide scanning: cold nodule - do not recur, benign
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Adenoma diagnosis
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- only by histological examination, not needle aspiration
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Thyroid carcinomas incidence
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- rare: 1% of all cancer is US - 0.2% of all cancer deaths - estimated 34,000 new cases and 1500 deaths in US in 2007 - increasing incidence (due to new diagnostic practices which detect smaller tumors) - 20 year survival is 90%, because most are indolent papillary carcinomas - F>>M in reproductive age (often estrogen receptor positive, which may explain female predominance) - for other ages (children, >6decade: F=M) - more common in US whites than blacks, for unknown reasons
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Thyroid carcinomas
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- Papillary ca - 80% - Follicular ca - 15% - Medullary ca - 5% - Anaplastic (undifferent.) - less than 5%
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Thyroid carcinoma treatment
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- surgery: lobectomy, subtotal thyroidectomy or total thyroidectomy - post-operative radio-iodine therapy - can assess for recurrence with serum thyroglobulin levels, calcitonin (medullary carcinoma)
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Papillary carcinoma of thyroid
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80% of thyroid carcinomas 70% women of reproductive age (2-5decade) occult tumors in 6% at autopsy (1-10 mm) 46% multicentric 14% with nodal metastases occult tumors in up to 24% with other thyroid disease
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Papillary carcinoma of thyroid risk factors
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Risk factors: - ionizing radiation before age 20 (for acne-tonsillitis, tinea capitis, enlarged thymus) - post-Chernobyl - particularly children, or after exposure to nuclear explosions at Marshall Islands - Hashimoto's thyroiditis (possibly) - (FAP) Familial adenomatous polyposis
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Papillary carcinoma of thyroid clinical presentation
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- painless nodule or mass on the neck - cervical node (usually cold on scan) - can be diagnosed by FNA - at presentation: 67% in thyroid only, in 13% thyroid and cervical nodes - nodal involvement is often not clinically apparent due to small size and similar consistency - nodal metastases may undergo cystic change and resemble branchial cleft cyst
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Papillary carcinoma of thyroid gross features
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- solid, white, firm - solitary / multifocal often - encapsulated (10%) or infiltrative - variable cysts, fibrosis, calcification
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Papillary carcinoma of thyroid histology
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- papillae with fibrovascular cores associated with follicles - papillae lined by cuboidal cells - overlapping nuclei, with finely dispersed optically clear chromatin (also called ground-glass, Orphan-Annie nuclei) - eosinophilic intranuclear inclusions (cytoplasmic invaginations) - nuclear longitudinal grooves (represent folding of redundant nuclear membrane, present in almost every high power field)
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Orphan-Annie cells
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- characteristic for papillary carcinoma of thyroid - nuclei with uniform staining, which appear empty
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Characteristics in cells in papillary carcinoma of thyroid
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- Orphan Annie cells - Eosinophilic intranuclear inclusions - Nuclear longitudinal grooves
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Psammoma bodies
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- round collection of calcium, seen microscopically - in papillary stalk - due to tumor cells necrosis (calcification) - fairly specific for papillary carcinoma (although may be present in metastatic carcinoma to thyroid) Note: presence of psammoma body in neck or cervical lymph node means papillary thyroid carcinoma must be ruled out
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Papillary thyroid carcinoma clinical features
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- asymptomatic thyroid nodule - „cold" nodule on radionuclide scanning - enlarged cervical lymph node - advanced disease: hoarseness, dysphagia, cough lung meta - rare (10%) - good prognosis (even with lymph node meta) - 10 years - 95%
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Follicular carcinoma
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- ca. with follicular differentiation - no papillary nuclear features - 15% of thyroid ca. and 25-40% in iodide-deficient areas - usually solitary - usually "cold" on radionuclide scan - F>M 3:1, (older than PC): 40-50's
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Follicular carcinoma of thyroid risk factors
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- radiation exposure - iodine deficiency - older age * does not arise from preexisting adenomas!
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Follicular carcinoma of thyroid metastases
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- rare lymphatic spread - spread to lungs, liver, bone, brain via veins (hematogenously)
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Follicular carcinoma gross features
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- gray-tan-pink - usually single encapsulated nodule - focally hemorrhagic - variable fibrosis - calcification rare - larger lesions are often - infiltrative
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Follicular carcinoma of thyroid histology
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- need convincing evidence of invasion of adjacent thyroid parenchyma - complete penetration of the capsule blood vessels invasion (medium sized veins / vessels in or beyond the capsule) - capsule is typically thick with calcification - architectural patterns: follicular or solid - may have nuclear atypia, Hürthle cells, focal spindled areas, mitotic figures - no nuclear features of papillary carcinoma; - no psammoma bodies; no/rare lymphatic invasion
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Follicular carcinoma of thyroid FNA
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- nuclear enlargement, overlapping and crowding - cannot distinguish between follicular adenoma and carcinoma by fine needle aspiration since need evidence of capsular or vascular invasion or invasion of adjacent parenchyma - molecular: Ras mutations in 49%
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Main difference between follicular adenoma and follicular carcinoma
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- in papillary carcinoma the capsule is invaded
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Follicular carcinoma of thyroid treatment
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- total thyroidectomy - radioactive iodine metastasis take up the radioactive iodine - (identification of meta)
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Medullary carcinoma of thyroid
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- neuroendocrine tumor derived from C cells (parafollicular cells) of neural crest - secretes calcitonin
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Medullary carcinoma of thyroid incidence
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- 5-10% of thyroid carcinomas - either sporadic (nonhereditary) or hereditary (familial) serum calcitonin - postoperative follow-up
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Sporadic medullary carcinoma
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- 80% - age 40-60 years, solitary - paraneoplastic syndromes (diarrhea from VIP, Cushing's syndrome) - dysphagia and hoarseness (tumor mass)
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Familial medullary carcinoma
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- younger patients (mean: 35 years) - MEN 2A or 2B syndromes, familial medullary - thyroid carcinoma syndrome, von Hippel-Lindau disease or neurofibromatosis (NF) - usually bilateral, multicentric with C cell hyperplasia - usually discovered by screening serum calcitonin - RET oncogene mutational analysis - MEN 2: germ line mutations in RET proto-oncogene
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Medullary carcinoma histology
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- round cell nests - granular cytoplasm - uniform round nuclei with punctate chromatin - amyloid deposits in the stroma (from calcitonin) - prominent vascularity - calcifications - often angiolymphatic invasion - C cell hyperplasia present in familial but not sporadic cases
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Anaplastic carcinoma of thyroid
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- high grade (G3) carcinoma - called: undifferentiated carcinoma, sarcomatoid carcinoma - 2% of thyroid cancers but 40% of thyroid cancer deaths - mean age 65 years - F>M 3:1 - 50% have prior multinodular goiter, 20% have prior differentiated carcinoma - arises as transformation of ca (papillary, follicular or Hürthle cell)
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Anaplastic carcinoma of thyroid clinical features
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- rapidly enlarging, bulky neck mass - invades adjacent structures (hoarseness, dysphagia, dyspnea) - most thyroid sarcoma-like tumors are probably anaplastic carcinomas
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Anaplastic carcinoma of thyroid gross characteristics
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- solid tumor - large - areas of necrosis and hemorrhage - invades adjacent structures
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Anaplastic carcinoma of thyroid treatment
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- resistant to all treatments - death usually within 1 year - mean survival 6 months - <10% survive at least 2 years
