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Pathology of the Thyroid Gland. Prof. Dipak Shah Department of Pathology UWI, Mona. Diseases of the Thyroid Gland. Congenital diseases Inflammation Functional abnormality Diffuse and Multinodular goiters Neoplasia. Inflammation. Thyroiditis Acute illness with pain Infectious Acute

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Pathology of the Thyroid Gland

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pathology of the thyroid gland

Pathology of the Thyroid Gland

Prof. Dipak Shah

Department of Pathology

UWI, Mona

diseases of the thyroid gland
Diseases of the Thyroid Gland
  • Congenital diseases
  • Inflammation
  • Functional abnormality
  • Diffuse and Multinodular goiters
  • Neoplasia


  • Acute illness with pain
    • Infectious
      • Acute
      • Chronic
    • Subacute or granulomatous (De Quervain’s)
  • Little inflammation with dysfunction
    • Subacute lymphocytic thyroiditis
    • Fibrous (Riedel) thyroiditis
  • Autoimmune
    • Hashimoto thyroiditis
hashimoto thyroiditis
  • Most common cause of hypothyroidism
  • Autoimmune, non-Mendelian inheritance
  • 45-65 years, F:M = 10-20:1
  • Painless symmetrical enlargement
  • Risk of developing
    • B-cell non-Hodgkin’s lymphoma
    • Other concomitant autoimmune diseases
      • Endocrine and non-endocrine
hashimoto thyroiditis pathogenesis
Hashimoto ThyroiditisPathogenesis
  • Immune systems reacts against a variety of thyroid antigens
  • Progressive depletion of thyroid epithelial cells which are gradually replaced by mononuclear cells → fibrosis
  • Immune mechanisms may includes:
    • CD8+ cytotoxic T cell-mediated cell death
    • Cytokine-mediated cell death
    • Binding of antithyroid antibodies → antibody dependent cell-mediated cytotoxicity
hashimoto thyroiditis6
Hashimoto Thyroiditis
  • Diffuse enlargement
  • Firm or rubbery
  • Pale, yellow-tan, firm & somewhat nodular cut surface
hashimoto thyroiditis7
Hashimoto Thyroiditis
  • Massive lymphoplasmcytic infiltration with lymphoid follicles formation
  • Destruction of thyroid follicles
  • Remaining follicles are small and many are lined by Hurthle cells
  • Increased interstitial connective tissue
functional abnormality
Functional Abnormality
  • Hyperfunction
    •  in level of hormone → toxic effects
      • Due to:
        • Diffuse hyperplasia
        • Hyperfunctioning multinodular goiter
        • Hyperfunctioning adenoma
        • Subacute lymphocytic (painless) thyroiditis
functional abnormality9
Functional Abnormality
  • Hypofunction
    •  in level of hormone → impair development in infants and slowing of physical and mental ability in adults
      • Due to:
        • Postablation
          • Surgery
          • Radiation
        • Autoimmune thyroiditis
        • Drugs
        • Dyshormonogenetic
graves disease
Graves Disease
  • Most common cause of endogenous hyperthyroidism
  • Characterized by hyperthyroidism, ophthalmopathy with exophthalmos and dermopathy (pretibial myxedema)
  • Autoimmune disease with genetic susceptibility associated with HLA-B8 and DR3
  • Female:Male = 7:1
  • 3rd to 4th decades
  • Diffuse enlargement with audible bruit
  • Wide,staring gaze,lid lag,exophthalmos,pretibial myxedema
  • ↑ levels of free T4 & T3 and ↓ levels of TSH in blood
  • ↑ uptake of radioactive iodine
graves disease11
Graves’ Disease

Autoimmune disease with breakdown of helper-T-cell tolerance

Excessive production of TWO thyroid autoantibodies:

  • Thyroid-stimulating antibody (TSAb) &
  • Growth-stimulating antibody (GSAb)

Antibodies bind to the TSH receptor of the follicular cell

Stimulation of the cell resulting in:

Increased levels of thyroid hormones &

Hyperplasia of the thyroid gland

Hyperthyroidism and Thyroid gland enlargement

graves disease12
Graves Disease
  • Symmetrical enlargement of thyroid gland
  • Cut-surface is homogenous, soft and appear meaty
  • Hyperplasia and hypertrophy of follicular cells
diffuse multinodular goiters
Diffuse & Multinodular goiters
  • Reflects impaired synthesis of thyroid hormone most often caused by iodine deficiency
  • Impairment leads to compensatory ↑ in TSH levels → hypertrophy and hyperplasia of follicular cells → gross enlargement of gland
  • Euthyroid metabolic state
  • Degree of enlargement is proportional to level and duration
diffuse nontoxic goiter
Diffuse nontoxic goiter
  • Diffuse non-toxic (simple) goiter
    • colloid goiter
    • Endemic
    • sporadic (dyshormonogenetic)
endemic goiter
Endemic Goiter
  • Low iodine content in drinking water & food (Himalayas, Alps, Andes, areas far from the sea)
  • Prevalence decreasing due to prophylactic iodination of salt
  • Iodine deficiency causes decreased hormone levels & consequent elevation in TSH
sporadic goiter
Sporadic Goiter
  • Commonest type of goiter
  • Euthyroid, but may be hypo- or hyper-
  • Mostly idiopathic, but RARELY, may be caused by:
    • Drugs used in Rx of hyperthyroidism
    • Goitrogens e.g. cauliflower, cabbage, cassava
    • Suboptimal iodine intake
    • Hereditary enzymatic defects
multinodular goiter
Multinodular goiter
  • Recurrent episodes of hyperplasia and involution leads to irregular enlargement
  • All long standing diffuse endemic and sporadic goiter may eventually convert to multinodular goiter
  • Causes most extreme enlargement and may be mistaken for neoplasm
  • May arise due to variable response of follicular cells to external stimuli such as trophic hormones
  • With uneven follicular hyperplasia, generation of new follicles and uneven accumulation of colloid → rupture of follicle and vessels →hemorrhage, scarring & calcification → nodularity
multinodular goiter18
Multinodular Goiter
  • Asymmetric enlargement
  • Multinodular
  • Haemorrhage
  • Calcification
  • Fibrosis
  • Cystic degeneration
multinodular goiter19
Multinodular Goiter
  • Numerous follicles varying in size
  • Recent haemorrhage
  • Haemosiderin
  • Calcification
  • Cystic degeneration
  • +/- dominant nodule
thyroid neoplasms
Thyroid Neoplasms

I. Primary Tumours

  • Epithelial
  • Malignant Lymphomas
  • Mesenchymal tumours

II. Metastatic Tumours

epithelial thyroid neoplasms
Epithelial Thyroid Neoplasms
  • Tumours of follicular cells
    • Benign (adenomas)
      • Follicular adenoma
    • Malignant (carcinomas)
      • Follicular carcinoma (10-20%)
      • Papillary carcinoma (75-85%)
      • Undifferentiated (anaplastic) carcinoma (<5%)
  • Tumours of C-cells
    • Medullary thyroid carcinoma (MTC - 5%)
follicular adenoma
Follicular Adenoma
  • Benign, encapsulated tumor showing evidence of follicular differentiation
  • Common
  • Predominantly young to middle women
  • Presents as solitary thyroid nodule
  • Painless nodular mass, cold on isotopic scan
follicular adenoma23
Follicular Adenoma
  • Solitary, Variably sized, encapsulated, well-circumscribed with homogenous gray-white to red-brown cut-surface
  • +/- degenerative changes
follicular carcinoma
Follicular Carcinoma
  • Second most common form, 10-20%
  • Females > Males, average age ~ 45 - 55 yr
  • Rare in children
  • Solitary nodule, painless, cold on isotopic scan
  • Widely invasive Vs minimaly invasive
  • 50% 10 yr survival Vs 90%10 yr survival
  • Haematogenous route is preferred mode of spread
follicular carcinoma25
Follicular Carcinoma
  • Solitary round or oval nodule
  • Thick capsule
  • Composed of follicles
  • Capsular invasion or vascular invasion within our outside capsular wall
papillary carcinoma
Papillary Carcinoma
  • Commonest thyroid malignancy, 75-85%
  • Female:Male = 2.5:1
  • Mean age at onset = 20 - 40 yr
  • May affect children
  • Prior head & neck radiation exposure
  • Indolent, slow-growing painless mass cold on isotopic scan
  • Cervical lymphadenopathy may be presenting feature
papillary carcinoma27
Papillary Carcinoma
  • Variable size (microscopic to several cm)
  • Solid or cystic
  • Infiltrative or encapsulated
  • Solitary or multicentric (20%)
papillary carcinoma28
Papillary Carcinoma
  • Papillae or follicles
  • Psammoma bodies
papillary carcinoma29
Papillary Carcinoma

Nuclear Features

  • Optically clear (ground glass, Orphan Annie) nuclei
  • Nuclear pseudoinclusions or nuclear grooves
papillary carcinoma prognosis
Papillary CarcinomaPrognosis

Excellent but following factors play important role:

  • Age and sex
  • Size
  • Multicentricity
  • Extra-thyroid extension
  • Distant metastasis
  • Total encapsulation, pushing margin of growth & cystic change
anaplastic carcinoma
Anaplastic Carcinoma
  • Rare; < 5% of thyroid carcinomas
  • Highly malignant and generally fatal < 1yr.
  • Elderly  65 yrs; females slightly > males
  • Rapidly enlarging bulky neck mass
  • Dysphagia, dyspnoea, hoarseness
anaplastic carcinoma32
Anaplastic Carcinoma
  • Large, firm, necrotic mass
  • Frequently replaces entire thyroid gland
  • Extends into adjacent soft tissue, trachea and oesophagus
  • Highly anaplastic cell on histology with:
    • Giant, spindle,small or mix cell population
  • Foci of papillary or follicular differentiation
anaplastic carcinoma33
Anaplastic Carcinoma
  • Cellular pleomorphism
  • +/- multinucleated giant cells
  • High mitotic activity
  • Necrosis
medullary thyroid carcinoma mtc
Medullary Thyroid Carcinoma (MTC)
  • Malignant tumour of thyroid C cells producing cacitonin
  • 5 % of all thyroid malignancies
  • Sporadic (80%)
  • Rest in the setting of MEN IIA or B or as familial without associated MEN syndrome
medullary thyroid carcinoma mtc35
Medullary Thyroid Carcinoma (MTC)

Sporadic MTC

  • Middle-aged adults
  • Female:male = 1.3:1
  • Unilateral involvement of gland
  • +/- cervical lymph node metastases
  • Indolent course with 60-70% 5-yr survival after thyroidectomy
multiple endocrine neoplasia types iia iib
Multiple Endocrine Neoplasia Types IIA & IIB
  • Germ-line mutation in Ret protooncogene on chromosome 10q11.2
  • MEN IIA: MTC, phaeochromocytoma, parathyroid adenoma or hyperplasia
  • MEN IIB: MTC, phaeochromocytoma, mucosal ganglioneuromas, Marfanoid habitus, other skeletal abnormalities
medullary thyroid carcinoma mtc37
Medullary Thyroid Carcinoma (MTC)

Associated with MEN IIA

  • Younger patients in twenties
  • Multicentric and bilateral
  • Slow growing

Associated with MEN IIB

  • Even younger patientsin teens
  • Aggressive with early metastasis
  • Poor prognosis
medullary thyroid carcinoma mtc38
Medullary Thyroid Carcinoma (MTC)
  • Histology same for sporadic & familial
  • Solid, lobular or insular growth patterns
  • Tumour cells round, polygonal or spindle-shaped
  • Amyloid deposits in many cases
medullary thyroid carcinoma mtc39
Medullary Thyroid Carcinoma (MTC)
  • Amyloid deposits stain orange-red with Congo Red stain
prognosis of thyroid carcinomas
Prognosis of Thyroid Carcinomas

Papillary Best prognosis



Anaplastic Worst prognosis

secondary tumours
Secondary Tumours
  • Direct extensions from: larynx, pharynx, oesophagus etc.
  • Metastasis from: renal cell carcinoma, large intestinal carcinoma, malignant melanoma, lung carcinoma, breast carcinoma etc.
solitary thyroid nodule
Solitary thyroid nodule
  • Papillary carcinoma
  • Follicular carcinoma
  • Medullary carcinoma
  • Follicular adenoma
  • Hyperplastic (dominant) nodule
  • Metastatic neoplasms
congenital thyroid diseases
Congenital Thyroid Diseases
  • Agenesis /Aplasia
  • Hypoplasia
  • Accessory or aberrant thyroid glands
  • Thyroglossal duct cyst
thyroglossal duct cyst
Thyroglossal Duct Cyst
  • Children
  • Failure of regression
  • Neck, medial
  • Squamous or columnar lining
  • Complications: inflammation, sinus tracts