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Thyroid Pathology (Thyroiditis
Inflammatory conditions of the thyroid…
Thyroid Pathology
Thyroiditis
- Inflammatory conditions of the thyroid gland
Subacute (Granulomatous) Thyroiditis
- Aka DeQuervain thyroiditis
- Epidemiology and Associations:
- Female > male
- Most common between ages 40 and 50
- Viral infection (mumps, coxsackievirus, adenovirus)
- Pathogenesis:
- Inciting agent is probably a viral infection or post-viral inflammatory process which damages thyroid follicular cells, releasing a normally sequestered antigen
- This incites cytotoxic T cell mediated injury
- Clinical Features:
- Sudden/gradual presentation of symptoms:
- Painful goitre (jaw, throat, ears, occasional nodule)
- Systemic: fever, malaise, anorexia, myalgia
- Period of disease and recovery lasts 14 weeks
- Usually self-limiting (not self-perpetuating)
- Laboratory test:
- Initial 2-6 weeks: transient mild hyperthyroidism (high T3 and T4, low TSH) due to release of preformed colloid following follicular damage
- Later 2-8 weeks: transient asymptomatic hypothyroidism
- Radioiodine uptake diminished
- Gross:
- Enlarged firm thyroid gland which may be uni- or bilateral
- Patchy appearance (pale yellowish areas intervening with normal brown parenchyma)
- Histology:
- Initially, neutrophilic infiltrate, microabscesses
- Later on, mononuclear infiltrate around damaged follicles
- Multinucleated giant cells engulfing pools of colloid
Subacute Lymphocytic (Painless) Thyroditis
- Epidemiology and Associations:
- Female > male
- Most common in middle age women, postpartum
- Pathogenesis:
- Clinical Features:
- Mild diffuse goitre (condition lasts 2-8 weeks in total)
- Hyperthyroidism lasting 1-2 weeks
- Gross:
- Normal/minimal diffuse enlargement
- Histology:
- Hyperplastic reactive lymphoid nodules
- No Hurthle cell change or fibrosis (distinguishing factor from Hashimoto thyroiditis)
Reidel Thyroiditis
- Unknown eitology - possibly autoimmune
- Clinical Features:
- Extensive fibrosis of thyroid and surrounding structures in the neck
- Presenting as a hard fixed mass in the neck
- Can mimic thyroid carcinoma
Hashimoto Thyroiditis
- Autoimmune destruction of thyroid leading to a gradual thyroid failure
- Epidemiology and Associations:
- Female > Male (10-20x more)
- Most common between ages 45-65
- HLA-DR3, HLA-DR5 (weak association)
- Pathogenesis:
- Cell-mediated cell death by CD8+ cytotoxic T cells
- Cytokine-Mediated cell death by CD4+ Th1 cells
- Antibody-mediated cytotoxicity by anti-thyroid autoantibodies
- Anti-thyroglobulin
- Anti-thyroperoxidase (anti-TPO)
- Anti-TSh receptor
- Clinical Features:
- Painless goitre (often diffused, may be localised)
- Laboratory tests:
- Initial transient hyperthyroidism/Hashitoxicosis (high T3 and T4, low TSH)
- Progressive hypothyroidism (low T3 and T4, high TSH)
- Detection of autoantibodies
- Complications:
- Associated autoimmune disorders (Sjogren syndrome, SLE, Type I DM)
- Extranodal marginal zone B cell lymphoma
- Gross:
- Pale, enlarged thyroid
- Pale yellow firm cut surface +/- nodules
- Histology:
- Lymphocytic infiltrate comprising lymphocytes & plasma cells
- Reactive lymphoid follicles
- Atrophic thyroid follicles
- Follicular cells may display Hurthle cell change
- Cells with abundant eosinophilic cytoplasm; a metaplastic change in response to ongoing injury
- Fibrosis confined within thyroid capsule (unlike Reidel thyroiditis)
Graves Disease
- Can be considered both a hyperplastic thyroid condition as well as a form of thyroiditis; leads to hyperthyroidism
- Epidemiology and Associations:
- Female > Male (7x more)
- Most common between ages 20-40
- HLA-B8, HLA-DR3
- Pathogenesis:
- Breakdown in self-tolerance to thyroid auto-antigens, resulting in the production of multiple autoantibodies:
- Thyroid-stimulating immunoglobulin (TSI)
- Binds to TSH receptor and mimics TSH action
- Induces release of thyroid hormones
- Thyroid growth-stimulating immunoglobulins (TGI)
- Binds to TSH receptor
- Induces proliferation of follicular cells
- TSH-binding inhibitor immunoglobulin (TBH)
- Binds to TSH receptor - blocks normal TSH from binding
- May be agonistic or antagonistic - Graves patients may have episodes of hypothyroidism
- Clinical Features:
- Clinical Triad:
- 1. Hyperthyroidism
- 2. Infiltrative ophthalmopathy
- Exophthalmos (anterior bulging of eyes)
- Due to marked infiltration of retro-orbital space by lymphocytes (predominantly T cells) as orbital periadipocytes express TSH receptors
- Causes inflammatory oedema and swelling of extra ocular muscles (order of involvement: IMSL recti, Obliques)
- Fatty and ECM accumulation
- 3. Infiltrative dermopathy (pretibial myxoedema)
- Scaly thickening and induration of skin over shins
- Due to lymphocytic infiltration and deposition of ECM
- Physical examination:
- Diffuse enlarged thyroid gland
- May have bruit on auscultation of thyroid gland (due to increased blood flow through gland)
- Laboratory Tests:
- Hyperthyroidism (high T3 and T4, low TSH)
- Detection of serum TSI
- Radioiodine uptake is diffusively increased
- Treatment:
- PTU + beta blockers
- Radioiodine ablation, surgical intervention
- Gross:
- Symmetrical diffuse goitre
- Cut surface is soft and meat-like appearance (deep red)
- Histology:
- Follicular cells are tall and overcrowded, giving rise to pseudo papillae (also seen in simple and multi nodular goitre)
- Pale scalloped colloid (due to active colloid reabsorption)
- Lymphocytic infiltration, reactive lymphoid follicles
Congenital Abnormalities
Thyroglossal Duct Cyst
- Vestige of embryonic thyroid gland
- Midline neck cyst anterior to the trachea that rises when sticking out the tongue
- Histology:
- Squamous of cuboidal lining surrounding follicles
- Complications
- Infection
- Malignant change (rarely)
Ectopic Thyroid
- Upper GIT (tongue, larynx, oesophagus)
- Upper Resp Tract (trachea, jugular carotid nodes)
- Soft tissues of the neck and CVS (heart, great vessels)
Abnormal Development of the Thyroid
- Agenesis, hypoplasia, dysplasia
Neoplasms
Benign Thyroid Neoplasms
- Follicular Adenoma
- Hurthle cell adenoma
- Clinical Features:
- Solitary painless nodule
- Rarely hyperfunctioning
- Laboratory tests
- Typically euthyroid
- Typically no increased radio iodine uptake (cold nodules)
- Gross:
- Rounded, encapsulated, well demarcated
- Bulging from the cut surface
- Cut surface: regions of haemorrhage, cystic change and variable color
- Hurthle cell adenoma - orange brown colour
- Histology:
- Completely surrounded by an intact capsule
- Differential diagnosis for FA:
- Dominant nodule in multi nodular goitre
- MNG has no capsule, will have multiple nodules in the background
- Follicular carcinoma
- FC will have capsular or vascular invasion
- Need to assess entire capsule via extensive histologic sampling of tumour-capsule-thyroid interface to make definite diagnosis (hence highlighting limitations of fine needle aspiration and frozen section assessment)
- Papillary carcinoma
- Will have diagnosic nuclear features
Thyroid Carcinoma
Follicular Carcinoma (75-80%)
- Pathogenesis:
- RAS family mutations, t(2;3)
- Ionising radiation (esp for PC), longstanding MNG
- Clinical Features:
- More in women
- Slow growing painless nodule (typically solitary)
- Little propensity for lymphatic spread, vascular spread common (to bone)
- Prognosis: depends on degree of invasion
- Minimally invasive: 10-year survival > 90%
- Widely invasive: 10-year survival = 50-70%
- Gross:
- Minimally invasive:
- Well-defined, hard to find capsular invasion
- Widely invasive:
- Uncommon
- Obvious, extensive capsular or extra thyroidal extension
- Typically solitary
- Histology:
- Similar to follicular adenoma without capsular/vascular invasion
- May have Hurthle cell change (Hurthle cell carcinoma)
Papillary Carcinoma (10-20%)
- Pathogenesis:
- RET, BRAF
- Ionizing radiation (especially for papillary carcinoma); longstanding multinodular goitre
- Clinical Features:
- 20-40s, can occur in children
- Diagnosed based on nuclear features
- Slow growing painless nodule (cold) (may be multifocal)
- Enlarged cervical LN
- Little propensity for vascular spread, lymphatic spread common (to local nodes)
- Prognosis: (depends on age, extra thyroidal extension and distant metastases)
- Generally good prognosis
- Worse prognosis when asc with hoarseness, cough and dysphagia
- Histological type
- Encapsulated variant - excellent prognosis
- Tall cell variant - more aggressive
- Morphology:
- May be solitary or multifocal
- Ranges from being encapsulated to infiltrative
- Whitish nodules, cystic changes, calcifications and fibrosis
- Cut surface may reveal macroscopic papillary foci
- Histology:
- Diagnostic nuclear features (present in all types of PTC):
- Orphan Annie Eye nuclei (optically clear/empty looking due to finely dispersed chromatin)
- Nuclear grooves and pseudoinclusions (due to cytoplasmic invaginations)
- Classical PTC
- Well-formed papillae with fibrovascular cores
- Cuboidal uniform cells
- Psammoma bodies (concentrically calcified bodies within papillae cores)
- Fibrosis, calcifications
- Lymphatic invasion
- Follicular variant
- Need to distinguish from FA and FC (by using diagnostic PC nuclear features)
- Encapsulated variant
- Tall cell variant
- Tall columnar cells with intensely eosinophilic cytoplasm lining papillae
- Papillary microcarcinoma
- Otherwise classical PTC < 1cm
Anaplastic Carcinoma (< 5%)
- Pathogenesis:
- p53 gene mutations
- Ionizing radiation (especially for papillary carcinoma); longstanding multinodular goitre
- Clinical Features:
- Rapidly enlarging bulky mass in the neck
- Compressive symptoms (hoarseness, dyspnea, dysphagia)
- Often spreads beyond thyroid gland with metastases to lung
- Prognosis: Dismal, survival in months
- Morphology:
- Giant tumour cells (osteoclast-like)
- Spindle cells (sarcomatoid features)
- Small anaplastic cells
Medullary Carcinoma (5%)
- Pathogenesis:
- RET (asc with MEN II)
- Ionizing radiation (especially for papillary carcinoma); longstanding multinodular goitre
- Features:
- Neuroendocrine tumour (derived from parafollicular cells of thyroid)
- 80% sporadic, 20% familial (either part of MEN II syndromes or familial medullary thyroid carcinoma)
- Sporadic:
- Localized to one lobe
- No background of parafollicular cell hyperplasia
- Occurs in 5th to 6th decade of life
- Familial:
- Multinodular & affects both lobes
- Background of parafollicular cell hyperplasia
- Occurs in 2nd decade of life
- Gross:
- Firm, pale-grey to tan mass
- Infiltrative edges (beyond thyroid)
- Necrosis and hemorrhage
- Extrathyroidal extension
- Histology:
- Salt and pepper chromatin
- Cells with variable architecture (nests, trabeculae, follicles)
- Back ground of amyloid (deposits of altered calcitonin, shown with Congo Red stain)
- Parafollicular cell hyperplasia in normal surrounding parenchyma (seen mainly in familial tumours)
- Clinical Features:
- Compressive symptoms (dysphagia, hoarseness)
- Paraneoplastic symptoms (VIP causing diarrhoea, ACTH causing Cushing syndrome)
- Raised serum calcitonin (but with no significant hypocalcemia)
- Look out for other related tumours to determine if it is part of a MEN II syndrome (adrenals, parathyroid)
- Prognosis: (depends on degree of invasion)
- Sporadic worse than familial
Thyroid Lymphoma
- Extranodal marginal zone B-cell lymphoma
- Typically occurring in the setting of Hashimoto thyroiditis
- May transform into diffuse large B-cell lymphoma
-
Thyroid Hyperplasia
- Non-neoplastic proliferative growth of the thyroid gland
Simple Goitre
- Diffuse non-toxic enlargement of the thyroid gland
Causes of Simple Goitre:
- Endemic goitre
- Low iodine levels in soil, water and food supply (endemic goitre)
- Ingestion of goitrogens (substances that interfere with thyroid hormone synthesis)
- Vegetables belonging to the Cruciferae family (cabbage, cauliflower, Brussels sprouts, turnips)
- Sporadic goitre
- Dyshormonogenetic goitre (due to AR inherited defects in enzymes for thyroid hormone synthesis)
- Idiopathic
Pathogenesis
- Impaired thyroid hormone synthesis results in lowered
circulating thyroid hormone levels, which increased thyroid stimulation hormone (TSH) production by the anterior pituitary
- Increased TSH levels act on the thyroid gland to cause hypertrophy & hyperplasia of follicular cells
- Results in compensatory diffuse increase in functional thyroid mass
- Allows overcoming of original thyroid hormone deficiency, hence simple goitres are euthyroid
Morphology (2 stages)
- Hyperplastic stage
- Diffuse mild enlargement
- Crowded columnar cells forming pseudo papillae (also seen in multi nodular goitre and Graves)
- Colloid involution stage
- Flattened cuboidal epithelium
- Abundant colloid (brown glass cut surface - normal appearance of thyroid colloid)
Clinical Features
- Diffuse enlargement of thyroid gland without modularity
- Laboratory test:
- Normal free T3 and T4
- Slightly elevated/normal TSH
- Mass effects:
- Airway obstruction
- Dysphagia
- SVC syndrome
- May induce cretinism in infants and young children
Multinodular Goitre
- Irregular enlargement of thyroid as a progression from simple goitre
Pathogenesis
- Recurrent episodes of hyperplasia (simple goitre) and involution produces a more irregular enlargement of the thyroid gland
Clinical Features
- Asymmetrical nodular enlargement of thyroid gland, often with a dominant palpable nodule present
- Laboratory test:
- Normal free T3 and T4
- Slightly elevated/normal TSH
- Mass effects
- Airway obstruction
- Dysphagia
- SVC syndrome
- Toxic multi nodular goiter (Plummer syndrome)
- Development of an autonomous nodule within a longstanding multi nodular goitre which produces hyperthyroidism
Gross:
- Multi-lobulated asymmetrical enlargement
- If it grows behind the sternum and clavicle --> intrathoracic/plunging goitre
- Cut section: brown gelatinous colloid, haemorrhage, cystic change
Histology:
- Colloid-rich follicles lined by crowded columnar cells, giving rise to pseudo papillae appearance (also seen in simple goitre & Graves)
- Lacks fibrous capsule
- IMPT! Distinguishes from follicular adenomas and carcinomas which have a capsule demarcating hyper plastic follicles from the residual normal parenchyma