Pathology of The Pathology of The Thyroid GlandThyroid Gland

Dr Wale TITILOYEDr Wale TITILOYE

Normal Thyroid GlandNormal Thyroid Gland

Thyroid - NormalThyroid - Normal

Normal resting ThyroidNormal resting Thyroid

Thyroid Physiology:Thyroid Physiology:

HypothalamusHypothalamus

TRHTRH

T3, T4T3, T4 PituitaryPituitary

TSHTSH

ThyroidThyroid

Role of ThyroglobulinRole of Thyroglobulin Role of IodineRole of Iodine Release of thyroid hormonesRelease of thyroid hormones Role of T3,T4 (transport via Role of T3,T4 (transport via

transthyretin and thyroxine binding transthyretin and thyroxine binding globulin,binding to thyroid hormone globulin,binding to thyroid hormone nuclear receptor, formation of nuclear receptor, formation of thyroid hormone receptor complex thyroid hormone receptor complex and binding with thyroid hormone and binding with thyroid hormone response elements in target genes response elements in target genes and transcription.and transcription.

Role of GoitrogensRole of Goitrogens Note the role of certain drugsNote the role of certain drugs

1. Propythiouracil- inhibit the oxidation 1. Propythiouracil- inhibit the oxidation of iodide and block production of of iodide and block production of thyroid hormones, inhibits the thyroid hormones, inhibits the peripheral deiodination of T4 to T3peripheral deiodination of T4 to T3

2. Iodide administration(in large 2. Iodide administration(in large quantity) to patients with thyroid quantity) to patients with thyroid hyperfunction inhibit proteolysis of hyperfunction inhibit proteolysis of thyroglobulin thus block release of thyroglobulin thus block release of thyroid hormonesthyroid hormones

Parafollicular cells or Ccells Parafollicular cells or Ccells of thyroid follicleof thyroid follicle

Secretes hormone calcitoninSecretes hormone calcitonin Calcitonin promotes absorbtion of Calcitonin promotes absorbtion of

calcium by skeletal system and calcium by skeletal system and inhibits the resorbtion of bone by inhibits the resorbtion of bone by osteoclastsosteoclasts

Disorders of Thyroid:Disorders of Thyroid: Hyperthyroidism Hyperthyroidism Hypothyroidism Hypothyroidism ThyroiditisThyroiditis Diffuse multinodular Goiter.Diffuse multinodular Goiter. Neoplasms – adenoma/carcinoma.Neoplasms – adenoma/carcinoma. Congenital – Thyroglossal cyst/duct.Congenital – Thyroglossal cyst/duct.

HyperthyroidismHyperthyroidism Thyrotoxicosis Thyrotoxicosis – High T3/T4, low TSH– High T3/T4, low TSH

Hyperthyroidism is a cause of thyrotoxicosis. The term Hyperthyroidism is a cause of thyrotoxicosis. The term primary and secondary hyperthyroididm are primary and secondary hyperthyroididm are applicableapplicable

Different entities in hyperthyroidismDifferent entities in hyperthyroidism

1. Diffuse toxic hyperplasia (Graves)1. Diffuse toxic hyperplasia (Graves)

2. Toxic multinodular goitre2. Toxic multinodular goitre

3. Toxic adenoma3. Toxic adenoma

4. Thyroiditis (subacute granulomatous 4. Thyroiditis (subacute granulomatous thyroiditis, subacute lymphocytic thyroiditis)thyroiditis, subacute lymphocytic thyroiditis)

5. Functioning thyroid carcinoma5. Functioning thyroid carcinoma

6. TSH secreting pituitary adenoma6. TSH secreting pituitary adenoma

Hyper- Hyper- thyroidism thyroidism Features:Features:

Graves Disease:Graves Disease: Commonest cause of endogenous Commonest cause of endogenous

hyperthyroidismhyperthyroidism Commoner in Females(10x), 2% of Commoner in Females(10x), 2% of

Female in USA affectedFemale in USA affected 20-40y, Autoimmune.20-40y, Autoimmune. Triad of clinical features,Triad of clinical features,

• HyperthyroidismHyperthyroidism• exophthalmosexophthalmos• Pretibial myxedema.Pretibial myxedema.

Genetic susceptibility is linked to Genetic susceptibility is linked to polymorphism in immune function polymorphism in immune function genes like CTLA4,PTPN22 and and genes like CTLA4,PTPN22 and and HLADR3 AlleleHLADR3 Allele

Pathogenesis is breakdown of self Pathogenesis is breakdown of self tolerance to thyroid autoantigens most tolerance to thyroid autoantigens most importantly TSH receptor and importantly TSH receptor and production of multiple autoantibodiesproduction of multiple autoantibodies

1.1. Thyroid stimulating immunoglobulins Thyroid stimulating immunoglobulins (LATS)(LATS)

2.2. Thyroid growth-stimulating Thyroid growth-stimulating immunoglobulinsimmunoglobulins

3.3. TSH-binding inhibitor immunoglobulinsTSH-binding inhibitor immunoglobulins

MorphologyMorphology Symetrically enlarged thyroid gland Symetrically enlarged thyroid gland

because of diffuse hypertrophy and because of diffuse hypertrophy and hyperplasiahyperplasia

Tall columnar follicular cells, papillary Tall columnar follicular cells, papillary folds.folds.

Scalloped, pale, scanty colloid.Scalloped, pale, scanty colloid.

Graves’ Thyroiditis:Graves’ Thyroiditis:

Graves DiseaseGraves Disease

HypothyroidismHypothyroidism Cretinism / Myxedema Cretinism / Myxedema – Low T3/T4, High TSH– Low T3/T4, High TSH

Causes:Causes:

1.1. Hashimoto’s thyroiditisHashimoto’s thyroiditis - autoimmune - autoimmune

2.2. Iodine deficiencyIodine deficiency

3.3. Drugs – iodides, lithiumDrugs – iodides, lithium

4.4. Developmental – Atrophy, hypoplasia Developmental – Atrophy, hypoplasia Pituitary disordersPituitary disorders

5.5. Radiation/SurgeryRadiation/Surgery

HypothyroidismHypothyroidism ‘‘Cretin’ism (child)Cretin’ism (child) Impaired cns & Impaired cns &

bone growthbone growth Mental retardationMental retardation Short statureShort stature Coarse facial Coarse facial

featuresfeatures Protruding tongueProtruding tongue Umbilical herniaUmbilical hernia

Myxedema (adult)Myxedema (adult) Slow physical and Slow physical and

mental activitymental activity Cold intoleranceCold intolerance Over weightOver weight Low cardiac outputLow cardiac output Constipation and Constipation and

decreased sweatingdecreased sweating Cool pale thick skinCool pale thick skin

Hypo- Hypo- thyroidismthyroidism

Myxedema Myxedema

Features:Features:

Thyroid AtrophyThyroid Atrophy

Hashimoto ThyroiditisHashimoto Thyroiditis Common non endemic goitre.Common non endemic goitre. more common in females (45-65yr).more common in females (45-65yr). Autoimmune Autoimmune Increase susceptibility is associated with Increase susceptibility is associated with

polymorphism in multiple immune polymorphism in multiple immune regulation associated generegulation associated gene

1.1. Cytotoxic T lymphocyte associated antigen Cytotoxic T lymphocyte associated antigen 4(negative regulator of T cell response)4(negative regulator of T cell response)

2.2. Protein Tyrosine Phosphate-22 gene that Protein Tyrosine Phosphate-22 gene that encode lymphoid tyrosine phosphatase encode lymphoid tyrosine phosphatase which also inhibit T cell function.which also inhibit T cell function.

Antithyroglobulin antibodyAntithyroglobulin antibody Antithyroid peroxidase antibodyAntithyroid peroxidase antibody

Immunological mechanismImmunological mechanism1.1. CD8+ cytotoxic T-Cell-Mediated cell CD8+ cytotoxic T-Cell-Mediated cell

deathdeath2.2. Cytokine mediated cell deathCytokine mediated cell death3.3. Binding of antibodies followed by Binding of antibodies followed by

antibody mediated cytotoxicityantibody mediated cytotoxicity

MorphologyMorphology Firm diffuse enlarged thyroid.Firm diffuse enlarged thyroid. Follicle atrophy with lymphocytic Follicle atrophy with lymphocytic

infilterate with well developed germinal infilterate with well developed germinal centers.centers.

HHüürthle cells – eosinophilic epithelial rthle cells – eosinophilic epithelial cells.cells.

Initial hyperthyroidism.Initial hyperthyroidism. Patient are at risk for other autoimmune Patient are at risk for other autoimmune

diseases e.g Mysthaenia gravis , SLEdiseases e.g Mysthaenia gravis , SLE High risk of B cell Non Hodgkins High risk of B cell Non Hodgkins

lymphoma (MALT Lymphomas)lymphoma (MALT Lymphomas)

Hashimoto’s Thyroiditis:Hashimoto’s Thyroiditis:

Hashimoto’s DiseaseHashimoto’s Disease

Hashimoto’s DiseaseHashimoto’s Disease

Antithyroglobulin AntibodyAntithyroglobulin Antibody

Antimicrosomal AutoantibodyAntimicrosomal Autoantibody

Granulomatous Thyroiditis:Granulomatous Thyroiditis: Subacute or DeQuervain thyroiditis.Subacute or DeQuervain thyroiditis. Less common, Females, 30-60 yearsLess common, Females, 30-60 years Pain, fever, fatigue, myalgia.Pain, fever, fatigue, myalgia. Post viral syndrome.Post viral syndrome. Genetic association - HLA B35Genetic association - HLA B35 Patchy microabscess, granulomas Patchy microabscess, granulomas

with giant cells.with giant cells. Hyperthyroidism.Hyperthyroidism. Heals with normal thyroid function.Heals with normal thyroid function.

DeQuervain's Disease - DeQuervain's Disease - SAGTSAGT

Diffuse Non Toxic (simple) and Diffuse Non Toxic (simple) and Multinodular goitreMultinodular goitre

Endemic (affect more than 10% of a Endemic (affect more than 10% of a population or sporadic typespopulation or sporadic types

Dietary Cassava – thiocyanate – iodide Dietary Cassava – thiocyanate – iodide transport.transport.

Other Goitrogens- Cabbage, Other Goitrogens- Cabbage, cauliflower, Brussels sprouts, turnipscauliflower, Brussels sprouts, turnips

Like cassava, they are vegetables Like cassava, they are vegetables belonging to Barcicacea (cruciferae) belonging to Barcicacea (cruciferae) familyfamily

Sporadic – rare, females, young.Sporadic – rare, females, young. Hyperplastic stage & Colloid stage.Hyperplastic stage & Colloid stage. Repeated attacks Repeated attacks multinodular. multinodular. Hyperplasia, fibrosis, cystic, necrosisHyperplasia, fibrosis, cystic, necrosis Mass effect, dysphagia, airway Mass effect, dysphagia, airway

obstructionobstruction Most cases are euthytoidMost cases are euthytoid Rarely toxic Rarely toxic hyperthyroidism hyperthyroidism

plummer syndromeplummer syndrome

Goitre – Iodine DeficiencyGoitre – Iodine Deficiency

Multinodular Goitre with Multinodular Goitre with Papillary CarcinomaPapillary Carcinoma

Colloid Cysts in MNGColloid Cysts in MNG

Multinodular GoitreMultinodular Goitre

Neoplasms of ThyroidNeoplasms of Thyroid Usually solitary, benign.Usually solitary, benign. Good prognosis - <1% cancer mort.Good prognosis - <1% cancer mort. May be functional – hot nodule.May be functional – hot nodule. Malignancy - Infiltration – fixation, Malignancy - Infiltration – fixation,

hoarseness, recurrent laryngeal hoarseness, recurrent laryngeal nerve damage.nerve damage.

Neoplasms of ThyroidNeoplasms of Thyroid Adenoma – Follicular adenoma – Adenoma – Follicular adenoma –

usually hotusually hot Papillary Carcinoma – 75-80%Papillary Carcinoma – 75-80% Follicular carcinoma - 10-20%Follicular carcinoma - 10-20% Medullary carcinoma – 5%Medullary carcinoma – 5% Anaplastic carcinoma - <5%Anaplastic carcinoma - <5%

AdenomaAdenoma Follicular common, rarely PapillaryFollicular common, rarely Papillary Compact follicles (large in MNG)Compact follicles (large in MNG) Solitary, rarely Functional or hot.Solitary, rarely Functional or hot. Centre may show necrosis/hem.Centre may show necrosis/hem. Well capsulated.Well capsulated. Compressed normal gland.Compressed normal gland.

Follicular AdenomaFollicular Adenoma

Follicular AdenomaFollicular Adenoma

Solitary AdenomaSolitary Adenoma

Follicular AdenomaFollicular Adenoma

Thyroid CarcinomaThyroid Carcinoma Uncommon – child – elderly.Uncommon – child – elderly. Common - Papillary adenocarcinoma.Common - Papillary adenocarcinoma. Associated with radiation exposure.Associated with radiation exposure.

Thyroid CarcinomaThyroid Carcinoma

TypeType %% AgeAge SpreadSpread PrognosisPrognosis

PapillaryPapillary 6565 Young <45yYoung <45y LymphLymph ExcellentExcellent

FollicularFollicular 2020 Middle ageMiddle age B.V.B.V. GoodGood

AnaplasticAnaplastic 1010 elderlyelderly LocalLocal PoorPoor

MedullaryMedullary 55 Elderly Elderly

familialfamilialAllAll variablevariable

Papillary CarcinomaPapillary Carcinoma Most common cancer – 75-80%Most common cancer – 75-80%

• Idiopathic, Radiation, Gardner & Idiopathic, Radiation, Gardner & Cowden syndromes.Cowden syndromes.

• Papillary folds, Psammoma bodies, Papillary folds, Psammoma bodies, Orphan-anne nucleus.Orphan-anne nucleus.

• 98% 10year survival when localized.98% 10year survival when localized.

Papillary CarcinomaPapillary Carcinoma

Papillary CarcinomaPapillary Carcinoma

Medullary CarcinomaMedullary Carcinoma

Amyloid in Medullary Carcinoma – Amyloid in Medullary Carcinoma – Polarised microscopyPolarised microscopy

Papillary CarcinomaPapillary Carcinoma

Anaplastic CarcinomaAnaplastic Carcinoma

Technetium Technetium ScanScan

NormalNormal

Hot nodulesHot nodules

Cold noduleCold nodule

Ultrasound Ultrasound ScanScan

Solid nodule:Solid nodule:

Conclusions:Conclusions: HyperthyroidismHyperthyroidism

• Graves, thyrotoxicosis, LATS.Graves, thyrotoxicosis, LATS.• Hypermetabolism, high T3/T4, low TSHHypermetabolism, high T3/T4, low TSH

hypothyroidismhypothyroidism::• Antithyroglobulin, anti microsomalAntithyroglobulin, anti microsomal• Hypometabolism, Low T3/T4, high TSH.Hypometabolism, Low T3/T4, high TSH.

MultinodularMultinodular goitregoitre – low iodine. – low iodine. NeoplasmsNeoplasms

• Follicular adenoma – capsulated, single.Follicular adenoma – capsulated, single.• Carcinoma: Papillary follicular, medullary, Carcinoma: Papillary follicular, medullary,

anaplastic.anaplastic.

CC A 25 year old presented with anterior neck swelling, exophthalmia and A 25 year old presented with anterior neck swelling, exophthalmia and

pre-tibial myxoedema. Histology shows a diffuse hyperplasia of the pre-tibial myxoedema. Histology shows a diffuse hyperplasia of the thyroid follicular cells with most of them having papillary folds and thyroid follicular cells with most of them having papillary folds and

contained scalloped pale scanty colloid. No capsular invasion was seen.contained scalloped pale scanty colloid. No capsular invasion was seen.   1. The pathology of this disease is the presence 1. The pathology of this disease is the presence

of antibodies to thyroid stimulating hormone of antibodies to thyroid stimulating hormone receptors.Treceptors.T

2. Long acting thyroid stimulants LATS stimulates 2. Long acting thyroid stimulants LATS stimulates the production of thyroid hormone from the the production of thyroid hormone from the follicular cells.Tfollicular cells.T

3. This disease is more common in male.F3. This disease is more common in male.F 4. This disease usually presents with 4. This disease usually presents with

hypothyroidism.Fhypothyroidism.F 5. Weight loss, menorrhagia and osteoporosis are 5. Weight loss, menorrhagia and osteoporosis are

possibilities in this disease.Tpossibilities in this disease.T

A child presents with umbilical hernia, protruding A child presents with umbilical hernia, protruding tongue, short stature and mental retardation. He was tongue, short stature and mental retardation. He was described to be gentle. Hormonal assay shows low described to be gentle. Hormonal assay shows low

T3/ T4 and high TSH.T3/ T4 and high TSH.    6. The adult form of this condition is myxoedema 6. The adult form of this condition is myxoedema

TT 7. This condition may be associated with 7. This condition may be associated with

Hashimoto thyroiditis in the adult THashimoto thyroiditis in the adult T 8. Drugs like iodine and Lithium may cause this 8. Drugs like iodine and Lithium may cause this

condition in the adult Fcondition in the adult F 9. Sub acute thyroiditis in the adult will present in 9. Sub acute thyroiditis in the adult will present in

this form Fthis form F 10. Presence of antimicrosomal and antimicrobial 10. Presence of antimicrosomal and antimicrobial

antibodies in the adult form is diagnostic of Riedel antibodies in the adult form is diagnostic of Riedel thyroiditis Fthyroiditis F

A 35 year old woman presents with anterior neck A 35 year old woman presents with anterior neck swelling. On histology, malignant cells growing in swelling. On histology, malignant cells growing in

papillary folds with presence of orphan annie papillary folds with presence of orphan annie nucleus and psammoma bodies were seennucleus and psammoma bodies were seen   

11. The diagnosis in this case is medullary 11. The diagnosis in this case is medullary carcinoma Fcarcinoma F

12. Amyloids demonstrated by polarized 12. Amyloids demonstrated by polarized microscopy is a diagnostic feature of this cancer Fmicroscopy is a diagnostic feature of this cancer F

13. The morphology described above is the most 13. The morphology described above is the most common type of thyroid cancer Tcommon type of thyroid cancer T

14. The morphology described above carries the 14. The morphology described above carries the worst prognosis among the thyroid cancers Tworst prognosis among the thyroid cancers T

15. This morphology is associated with lymphatic 15. This morphology is associated with lymphatic spread Tspread T