Pathology of Thyroid Gland

8/11/2019 Pathology of Thyroid Gland

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THE THYROID

Dr Ahsan Kazmi

Assoc ProfessorPathology DepartmentAlNafees Medical College


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t1/2= 5-7d

t1/2= < 24 hrs


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HypothalamusPituitaryThyroid Axis


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The interactionof thyroid hormones with their

nuclear thyroid hormonereceptor (TR) results inthe formation of a hormonereceptor complexthat binds to thyroid hormone response elements(TREs) in target genes, regulating their

transcription

Thyroid hormones


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Thyroid hormones have diverse cellulareffects:

(i) Upregulation of carbohydrate catabolism

(ii) Upregulation of Lipidcatabolism

(iii) Stimulation of Protein synthesis

The net result of these processes is

an increase in the basal metabolic rate

Thyroid hormones


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Serum levels of T3 and T4 are increased by TSH

in addition, the conversion of T4 to T3( the moreactive hormone) in peripheral tissues is stimulatedby TSH.

T3 and T4 then enter cells where they bind to

nuclear receptors and promote increasedmetabolic and cellular activity

Thyroid hormones


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Thyroid Function: blood tests

TSH 0.4 4.0 mU/L

Free T4 (thyroxine) 9.1 23.8 pMFree T3 (triiodothyronine) 2.23-5.3 pM


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Thyroid Disease

The main types of clinical thyroid diseases are:

Hypothyroidism

Hyperthyroidism

Thyroiditis

Graves disease

Diffuse and Multinodular Goiter Thyroid Neoplasms


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HYPOTHYROIDISM

Hypothyroidism is caused by any structural or

functional derangement that interferes with theproduction of adequate levels of thyroid

hormone

It can result from a defect anywhere in the

HypothalamusPituitaryThyroid Axis


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Clinical picture of Hypothyroidism

The classic picture of the

Slow,

Dry- haired,

Thickskinned,

Deep voiced patient, with weight gain,

cold intolerance, bradycardia and

constipationmakes the diagnosis easy


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Causes of Hypothyroidism

Primary HypothyroidismPost ablative surgery

Radioactive Iodine

External Radiation

Iodine Deficiency*

Hashimoto,s Thyroiditis*

*Associated with enlargement of thyroid(Goitrous Hypothyroidism)

Hashimotos Thyroiditis and post ablative hypothyroidism account for

the vast majority of cases , particularly in regions with adequate dietary iodine


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Congenital Biosynthetic defects

(dyshormonogenetic defects)*

Drugs( Lithium, Iodides, paminosalicylic acid)*

Rare developmental abnormalities of thyroid

(thyroid dysgenesis)

Secondary causes

Pituitary or Hypothalamic failure ( uncommon)


*Associated with enlargement of thyroid(Goitrous Hypothyroidism)

Hashimotos Thyroiditis and post ablative hypothyroidism account for

the vast majority of cases , particularly in regions with adequate dietary iodine


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Iodine Deficiency:

fairly common in areas of the world where dietary iodine

deficiency is endemic, including the Himalayas, inlandChina, Africa, and other mountainous areas

In Pakistan: It is endemic in Northern mountainous areas



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Causes of Hypothyroidism Hashimoto Thyroiditis: The most common cause of hypothyroidism

in iodine-sufficient areasof the world is ChronicAutoimmune Thyroiditis, or HashimotoThyroiditis.

It accounts for 50 % to 60% cases of

hypothyroidism. Both cellular and humoralfactors contribute to the thyroid injury andhypothyroidism in chronic autoimmunethyroiditis.


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Post Thyroidectomy:

Total thyroidectomy or excision of a primary neoplasm isa common cause of hypothyroidism.

Radiation:Ablation of the thyroid gland by Radioiodineadministered for the treatment of hyperthyroidism

exogenous irradiation, such as external radiationtherapy to the neck

Drugs:

Drugs given intentionally to treat thyroid secretions orother drugs can cause hypothyroidism



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II.SECONDARY HYPOTHYROIDISM

thyroid hormone production due to failure ofpituitary TSH secretion in conditions such ashypopituitirism

Examples(i) Pituitary Tumor

(ii) Postpartum Pituitary necrosis


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CLINICAL FEATURES OF HYPOTHYROIDISM

Classic clinical manifestations of Hypothyroidisminclude:

(i) Myxedemaclinical picture of acquiredhypothyroidism

(ii) Creatinismclinical picture of

hypothyroidism occurring in infancy or childhood


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MYXEDEMA

The term is applied to hypothyroidism developingin the older child or adult

The clinical manifestations vary with the age ofonset of the deficiency

The older child shows signs and symptoms intermediate

between those of the cretin and those of the adults with

hypothyroidism.In adults the condition appears insidiously andmay take years to reach the level of clinical suspicion


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SYMPTOMS OF MYXEDEMA

1. Slowing of physical and mental activity

2. weakness, tiredness, increased sensitivity to cold ,weight gain, constipation,muscle stiffness and cramps

3. Other symptoms

Dryness of skin, hair loss,

hoarseness of voice,and forgetfulness

4. Deafness may occur5. Menstrual disturbances may occur

6. Patients may haveAngina and symptoms of heart failure


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SIGNS OF MYXEDEMA1. Skin is dry and coarse

2. Sweating is absent

3. Face looks puffy and expressionless

4. There is non- pitting edema and diffuse alopecia

5. Speech is slow and husky

6. Voice is hoarse

7. Pulse rate is slow

8.Delayed relaxation of tendon jerks (particularly anklejerk) is an important feature

9. Signs of pericardial/ pleural effusion may be present


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Deposition of Mucopolysaccharides

Deposition of increased amounts of Mucopolysaccharidesin connective tissues, produces:

In skin:producing peculiar diffuse nonpiting edema

In Larynx:causing hoarseness

In Heart:

Cardiac enlargement , pericardial effusionIn tongue:

producing enlargement of tongue


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Systemic Features of Hypothyroidism (Myedema)


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Hyperthyroidism Vs Hypothyroidism


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INVESTIGATIONS OF HYPOTHYROIDISM

1. Serum T3 and T4: Decreased

2. Serum TSH: Raised

Serum TSH is not increased in patients withpituitary diseases (Secondary Hypothyroidism)or because of primary hypothalamic disease(Tertiary Hypothyroidism).

3. Chest X- ray show enlarged cardiac shadow. Itmay be due to pericardial effusion or heartfailure


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COMPLICATIONS OF HYPOTHYROIDISM

Pericardial Effusion

Ischemic heart disease

Myxedema Madness ( frank psychosis withhallucinations and delusions)

Myxedema coma

Hypothermia


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CRETINISM

Creatinism refers to hypothyroidism developing in infancy

or early childhood.

In the past this disorder occurred more frequently inareas where dietary iodine deficiency is endemic. It hasbecome less frequent due to widespreadsupplementation of foods with iodine


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Clinical features include:(i) Impaired development of central

nervous system(mental retardation).

(ii) Impaired development of skeletalsystem

(iii) Short stature(iv) Coarse facial features(v) Protruding tongue(vi) Umbilical hernia


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CRETINISM


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CRETINISM


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T3 T4 TSH

I. ACQUIRED HYPOTHYROIDISM

Primary

Hypothyroidism

Decreased Decreased Increased

SecondaryHypothyroidism

Decreased Decreased Decreased

TertiaryHypothyroidism

Decreased Decreased Decreased

II. CONGENITAL HYPOTHYROIDISM

CretinismDecreased Decreased Increased

Thyroid hormones


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THYROIDITIS

Inflammation ofthe thyroid gland

A diverse group ofdisorders characterized

by some form ofthyroid inflammation

The thyroid glandshows leukocytic

infiltration, fibrosis orboth

(i) Hashimotos thyroiditis (ii) Subacute granulomatous thyroiditis (iii) Subacute lymphocytic thyroiditis

Types:


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Hashimoto

Thyroiditis


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Pathogenesis Of Hashimoto

Thyroditis

Cellular as well as

Humoraltype of immune reactions are involved

Role Of T Lymphocytes

Two roles in this disease:


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Thyroditis(1) CD4+ Helper T cells reacts with thyroid

antigens.

Releases of Cytokines notably IFN Promotes inflammation Activates macrophages,

as in delayed type of hypersensitivity

Injury to thyroid results from the toxicproducts of inflammatory cells


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Thyroditis

(2) CD8+ Cytotoxic T Cells

Recognize Antigens on thyroid cellsand Kill These Cells


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Pathogenesis Of Hashimoto Thyroditis Contd

ROLE OF B - LYMPHOCYTES:

Activated and secrete a number of autoantibodies

directed against thyroid antigens:(1)Anti- Thyroglobulin antibodies

(2) AntiThyroid peroxidase antibodies

(4) AntiTSH receptor antibodies

(5) Antibodies against Iodine transporter


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An immunofluorescence test positive for anti-microsomal

antibody

Note the bright green fluorescence in the thyroid epithelial cells,

whereas the colloid in the center of the follicles is dark.

Immunofluorescence Test


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Immunofluorescence positivity for anti-thyroglobulin antibody.

Patients with Hashimoto's thyroiditis may also have other

autoimmune conditionsincluding Grave's disease, SLE, rheumatoid

arthritis, pernicious anemia, and Sjogren's syndrome.


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Pathogenesis of

HashimotosThyroiditis:Sensitization ofCD4 T helpercells seems tobe the initiatingevent

Thyrocytes

(injury)

T cell mediated

Cytotoxicity

Antibody dependent

cell mediatedcytotoxicity


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MORPHOLOGIC FINDINGS IN HASHIMOTO THYOIDITIS

GROSS EXAMINATION:

Thyroid is firm, rubbery and symmetrically enlarged.

Enlargement is moderate.Capsule is intact

Cut surface is pale gray, fleshy with accentuation ofnormal lobulations.


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Hashimoto Thyroiditis: Notethe lymphoid follicle at the

right centre

Hashimoto Thyroiditis: PinkHurthle cells at the centreand right. There is a

lymphoid follicle at the left.


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CLINICAL FEATURES OF HASHIMOTO THYROIDITIS

Symmetrical enlargement of thyroid

( may be asymmetric)

Initial thyrotoxic but finally hypothyroidism

Initial thyrotoxicosis

1.Concurrent Graves disease (Hashitoxicosis) or

2.Excessive release of hormones from injuredfollicular epithelium

Increased risk of developing Malignant Lymphoma


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LABORATORY DIAGNOSIS OF

HASHIMOTO THYROIDITIS

1.Serum total and free T4 and T3 levels: Initially euthyroid(normal), then hyperthyroid and finally hypothyroid

2. Serum TSH levels: Increased (when patient ishypothyroid)

3. TRH levels: Will increase when patient will be euthyroidor hypothyroid.

4. Thyroid Antibodies: Increased titer


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5. Thyroid Scan:

Decreased uptake

6. Radio Active Iodine Uptake test:Decreased uptake

7. Fine Needle Aspiration Cytology (FNAc):

a. Nature of thyroid lesion can be appreciated

b.Further course of management can be decided8. Thyroid Biopsy:

May be performed to confirm the diagnosis

LABORATORY DIAGNOSIS OF

HASHIMOTO THYROIDITIS


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SUBACUTE GRANULOMATOUS THYROIDITIS(Dequervains, Giant cell or PseudogranulomatousThyroiditis)

DEFINITION:

Self-limiting viral infection of the thyroid characterized bygranulomatous inflammation with multinucleate giantcells

ETIOLOGY AND PATHOGENESIS:Frequently preceded by upper respiratory tract infection .Implicated viruses are measles, mumps, influenza,adeno, Coxsackie's or ECHO viruses


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Granulomatous Thyroiditis:

A chronic inflammatory infiltratewith multinucleate giant cellsShows patchy foci of

necrosis of folliclesUltimately the reactivefoci undergo fibrosiswith residuallymphocytes

Microscopic Examination


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Initially fever, malaise and muscle aches Later painful enlargement of thyroid

In the beginning thyrotoxic due to release of storedhormones but euthyroid within weeks

Occurs in middle age with female to male ratio of 2:1

CLINICAL FEATURES OF SUBACUTE

GRANULOMATOUS THYROIDITIS


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Thyroid function tests are abnormal at first but returnto normal within 5 to 6 months

1. Serum total and free T4 and T3 levels:

Initially thyrotoxic but finally euthyroid

2. Radioactive Iodine Uptake:

Decreased uptake3. Blood Counts:

(ESR) is increased

LAB DIAGNOSIS OF SUBACUTEGRANULOMATOUS THYROIDITIS


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Riedels Thyroiditis

A rare chronic disorder occurring in old patients

A systemic disorder involving fibroblasts

Thyroid antibodies are not present

The gland is mildly enlarged

Gland is replaced by stony hard fibrous tissue


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Painless rockhard enlargement of thyroid

The fibroblasts may constrict the trachea

Dyspnea and strider

Compression of esophagus/Recurrent laryngeal

nerve

Dysphagia

Hoarseness

Usually Euthyroid

Riedels Thyroiditis

HYPERTHYROIDISM THYROTOXICOSIS


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HYPERTHYROIDISM -THYROTOXICOSIS

Thyrotoxicosis is a hypermetabolic state causes by elevated

circulating levels of T3 and T4

Groups:

1stGroup:Associated with hyperfunction of thyroid gland,

e.g., GravesDisease

2ndGroup

In certain conditions the hormone oversupply is related to

(i) To excessive release of preformed thyroid

hormone (e.g., in thyroiditis)

(ii)To an extra- thyroidal source


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Thus strictly speaking Hyperthyroidismis only one (albeit the most common)category of Thyrotoxicosis

The common practice is to use either term,Thyrotoxicosis or Hyperthyroidism, interchangeably

Causes of Thyrotoxicosis


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Causes of Thyrotoxicosis

A.Associated with HyperthyroidismPRIMARY

Diffuse toxic hyperplasia ( Graves disease) Hyperfunctioning (toxic) multinodular goitre Hyperfunctioning (toxic) adenoma

SECONDARY TSHsecreting pituitary adenoma (rare)

B. Not Associated with Hyperthyroidism

Sub acute Granulomatous Thyroiditis (painful) Subacute Lymphocytic Thyroiditis ( painless) Stroma ovarii ( ovarian teratoma with thyroid)

Factitious Thyrotoxicosis (exogenous Thyroxine


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PRIMARY VS SECONDARY HYPERTHYROIDISM

PRIMARY HYPERTHYROIDISM:

Intrinsic thyroid abnormality

SECONDAY HYPERTHYRODISM:

A process outside of the thyroid, such as a

TSHsecreting pituitary tumour

Ectopic thyroid arising in ovarian teratoma


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CLINCAL COURSE OF HYPERTHYRODISM

The clinical manifestations of hyperthyroidism includechanges referable to the Hypermetabolic state inducedby excess thyroid hormone as well as those related tooveractivity of the sympathetic nervous system .

Excessive levels of thyroid hormone result in an increasein the basal metabolic rate.

Cardiac manifestations are among the earliest and mostconsistent features of hyperthyroidism.


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SYMPTOMS OF HYPERTHYRODISM

Patients presents with loss of weight,palpitations, and breathlessness.

Patient complains of excessive sweating ,heat intolerance, and prefers cold weather.

Diarrhea may occur

Menstrual disturbances are common


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SIGNS OF HYPERTHYROIDISM

Signs of Hyperthyroidism:

There is tachycardia which persists during sleep

Pulse pressure is wide

Irregular pulsedue to atrial fibrillation

Hands arewarm and wet. Fine tremoris very common.

Thyroidmay be diffusely enlarged or may be

nodular.A bruitmay be audible over the enlargedthyroid

Proximal muscle weaknessmay be present


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INVESTIGATIONS FOR HYPERTHYROIDISM

Serum T3, and T4 are raised.

Serum TSH are low or not detectable even with verysensitive techniques

TSH does not rise in response to TRH (thyrotrophicreleasing hormone ) injection

Thyroid Scan

Radioactive iodine uptake test


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Graves Disease

Most commoncause ofhyperthyroidism

Goitre,Opthalmopathy,Dermopathy

Age 20-40 yrs

Women 10 times TSH-R antibody

(stimulating)


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Systemic features of Hyperthyroidism:. The marked

features are seen only in Graves Disease


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Pathogenesis

Breakdown in self-tolerance to thyroidauto- Ag ,

most imp TSH receptor

Thyroid Stimulating Immunoglobulins:

Also directed against the TSH receptor. Itis implicated in the proliferation of thyroid

follicular epithelium. This antibody is

relatively specific for Graves disease.


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PathogenesisTSH-binding inhibitor immunoglobulins: (anti-TSH

receptor antibodies)

Prevent TSH from binding normally to its

receptor on thyroid epithelial cells

Some mimic the action of TSH- stimulation ofthyroid epithelial cell activity


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TSH-binding inhibitor immunoglobulins (contd)

Other forms may actually inhibit thyroid cell

function Coexistence of stimulating and inhibiting

immunolglobulins in the serum of same patient

This finding may explain why some patientswith Graves disease spontaneously developepisodes of hypothyroidism andhyperthyroidism


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Autoimmune

Thyroid Disease

TSH-R ab

stimulation

GravesDx

(Hyperthyroid)

TSH-R ab block

Thyroglobulin ab

Microsomal ab

Hashimotos

(Hypothyroid)


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Pathogenesis

Opthalmopathy autoimmune process

T-cell infiltration of retro-orbital space Inflam. Edema & swelling of EO muscles

Extracellular matrix components

Fatty infiltration


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Clinical manifestations Thyrotoxicosis

Goitre, Opthalmopathy, Dermopathy

Sympathetic overactivity T4, T3 , TSH

Radioactive iodine uptake

Radioiodine scans show a diffuse uptake


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Hyperthyroidismsymptoms and signs . Bold type

Indicates signs of greater discriminant value


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DIFFUSE AND MULTINODULAR

GOITREIt is the most common manifestation of thyroid disease Diffuse and multinodular goiters reflect impaired

synthesis of thyroid hormone, most often caused by

dietary iodine deficiency. Impairment of thyroid hormone synthesis

compensatory rise in the serum TSH

Hypertrophy and hyperplasia of thyroid follicular cells

Gross enlargement of the thyroid gland.


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IODINE DEFICIENCY Globally, dietary deficiency is a major cause of

thyroid disease , as Iodine is an essential

requirement for thyroid hormone synthesis

The recommended daily intake of iodine at least140 g

dietary supplementation of salt and bread hasreduced the number of areas where EndemicGoitrestill occurs


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Euthyroid Or Hypothyroiddepending on the severity of Iodine deficiency

IODINE DEFICIENCY

borderlinehypothyroidism

TSH stimulation

thyroidenlargement

in the face ofcontinuing iodine

deficiency.

The mechanism


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Iodine deficiency

Decreased synthesis of T3 and T4

Compensatory increase in TSH level

Follicular cell hypertrophy and hyperplasia

Enlarged Thyroid (Goitre)

Adequate synthesis of T4 and T3

Euthyroid


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DIFFUSE NONTOXIC SIMPLE GOITRE

That diffusely involves the entire gland withoutproducing nodularity.

Not associated with either hypothyroidism or

hyperthyroidism

Because the enlarged follicles are filled with colloid ,the term Colloid Goitre has been applied to this

condition.

This disorder occurs in two forms:

(i) Endemic Goitre

(ii) Sporadic Goitre


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ETIOLOGY OF ENDEMIC GOITRE

Endemic goitre:

Present in more than 10% of the population in a

given region.1. Iodine deficient regions:

Particularly common in mountainous areas ofworld, including Alps, Andes, and Himalayas.

In Pakistan endemic in Northern mountainousareas


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1. Goitrogens:

A. Substances that interferes with thyroid hormonesynthesis at some level

i. Calcium and floride in water supply

ii. Lithium and thiocyanates in food.

iii.Vegetables of Brassica and Cruciferae families like

cabbage, cauliflower and turnipsiv.Anti thyroid drugs like Carbimazole

3. Maternal Iodine Deficiency:

Severe iodine deficiency in mother during fetal

development producescretinismin child

ETIOLOGY OF ENDEMIC GOITRE


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ETIOLOGY OF SPORADIC GOITRE

Less common than endemic goitre .

The female to male ratio 10:1

1. Increased demand for thyroid hormones, as in:

i. Puberty

ii. Pregnancy

2. Autoimmune mechanisms like appearance of TGIs inserum


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CLINICAL FEATURES OF DIFFUSE GOITRE

SWELLING IN NECK Cosmetic defect Pressure effects e.g.

1. dyspnea2. venous engorgement3. difficulty in swallowing


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Endemic goitre occurs in childhoodSporadic goitre in young adult life

Both are common in femalesIt is reversible with iodine or Thyroxine therapybut in longstanding cases, may becomemultinodular

CLINICAL FEATURES OF DIFFUSE GOITRE


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MORPHOLOGICAL APPEARNACE OFDIFFUSE GOITRE

GROSS EXAMINATION:

Diffusely and symmetrically enlarged thyroid

Hyperemic with Increased vascularity

MICROSCOPIC EXAMIANTION: Large follicles filled with colloid

Follicular epithelium flattened Small follicles lined by cuboidal to tall columnar cells Small papillary infoldings


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Variations in growth of one locus relative to another

physical stresses and encroachment on thevascularization

Areas of cell death, fibrosis and compensatoryregeneration of new follicles

All these contribute to multinodularity

More frequently mistaken for neoplastic involvementthan any other thyroid disease

MORPHOLOGICAL APPEARNACE OFDIFFUSE GOITRE


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Colloid Goitre: irregularly enlarged follicles with flattenedepithelium, consistent with inactivity; Follicles are filled with

colloid


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Colloid Goitre


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MULTINODULAR GOITRE

Arises from longstanding diffuse goitre

Causes nodular enlargement of thyroid

It may be

Nontoxic (euthyroid)Toxic ( thyrotoxic)

Endemic and Sporadic forms

Varying levels of TSH over time causes

Repeated cycles of hyperplasia and involution


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Nearly all long standing simple goitres become transformed into

Multinodular goiters

They may be

Nontoxic

Toxic- Induce Thyrotoxicosis (PlummersDisease)

MULTINODULAR GOITRE


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Clinical

features

Graves

Disease

Toxic

Multinodular

Goitre

Eye Changes Present Absent

Dermatopathy Present Absent

HypermetabolicState Pronounced Less severe

Difference between Graves disease &

Toxic Multinodular Goitre


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CLINICAL FEATURES OF MULTINODULAR GOITRE

Asymmetrical massive enlargement of thyroid that producespressure effects e.g., dysphagia, dyspnea,

compression of nerves and blood vessels.

Thyrotoxicosis can develop in 50% casesThis condition is referred as Plummer Syndrome.

not associated with infiltrative opthalmopathy

and dermopathy

Occurs in older females


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MORPHOLOGICAL APPEARNACE OFMULTINODULAR GOITRE

GROSS EXAMIANTION:Asymmetrically enlarged

Patten of enlargement variableone lobe more than the other

Cut section shows nodular areas withfibrosis and cyst changes


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Nodular

Goitre


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Gross : The glandis nodular containareas of fibrosisand cystic changes


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MICROSCOPIC EXAMINATION:

1. Colloidrich follicles

2. flattened, inactive epithelium

3. areas of follicular hypertrophy and hyperplasia4. regressive changes

MORPHOLOGICAL APPEARNACE OFMULTINODULAR GOITRE


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Multinodular Goiter illustrating scarring and variation in

size of follicles

Differential Diagnosis of enlarged Thyroid


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Diffuse

Simple

Physiological

Puberty; Pregnancy)

Autoimmune

Graves disease

Hashimotos thyroiditis

Thyroiditis

Acute (de Quervains

thyroiditis)

Iodine Deficiency

(endemic goitre)

Dyshormonogenesis

Goitrogens(e.g Sulphonylureas)

NodularMultinodular goitre

Solitary noduleFibrotic (Reidalsthyroiditis)

Cysts

TumoursAdenomas

Carcinomas

Lymphomas

MiscellaneousSarcoidosis

Tuberculosis


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Solitary Thyroid Nodule

A common clinical problem

Neoplastic nodule must be differentiated

May be produced due to

Early nodular goiter in over 60% of cases

Benign follicular adenoma- 30%

Malignant neoplasm in less than 5%


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Diagnosis is confirmed by:

(i) Fine needle aspiration and cytologic examinationof

aspirate(ii) Radionuclide Scan of Thyroid:

Cold nodule with low Iodine uptake: chances ofmalignancy are high

Hot nodule with high Iodine Uptake: Non malignant(iii) Ultrasound neck:

To differentiate cystic nodule from solid one becausecystic nodules are always benign

Solitary Thyroid Nodule


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Thyroid Neoplasms


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Thyroid Neoplasms Solitary nodule

female,1-10%

Benign to malignant 10:1 Neoplstic

Younger pt

Males

Radiation Cold nodules


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ADENOMAS

Follicular adenoma

Discrete ,solitary mass derived from follicular

epithelium Clinically distinction difficult

Majority non-functional

Toxic adenoma-thyroid autonomy


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ADENOMAS Genetic predisposition < 20% nonfunctioning

Morphology:

A solitary, spherical, encapsulated, welldemarcated

Size average 3cm , >10cm also seen

Cut surface bulges out,

Color gray-white, red brown

Areas of hemorrhage, fibrosis, calification, cysts


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Follicular Adenoma Thyroid: A solitary wellcircumscribed nodule is seen


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Microscopic appearance Uniform follicles containing colloid

Epithelium normal

Hurthle cell adenoma brightly eosinophiliccytoplasm

Intact capsule- hallmark


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Follicular Adenoma Thyroid: Welldifferentiatedfollicles resemble normal thyroid parenchyma


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Clinical features Unilateral painless mass

Larger masses- local pressure effects

Nonfunctioning adenoma take up lessradioactive iodine

Radionuclide scanning : cold nodules

Other investig. Techniques: USG, FNAC

Definitive diag: resection of whole tumor- cap.integrety


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CARCINOMAS Uncommon in USA

1.5% of all cancers

Female predominance Origin: follicular epithelium , well-differentiated

Classification


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Etiology Genetic factors

Two common pathways- follicular cell derived ca

Mitogen activated protin (MAP) kinase pathways

Phospho inositol-3-kinase (PI-3K) pathways

Environmental factors

Ionizing radiations

Dietary deficiency of iodine


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Papillary Carcinoma Most common

Age 25-50 yrs

Exposure to ionizing radiation Incidence last 30 yrs

Morphology:

Solitary/ multifocal

Encapsulated/local invasion

Fibrosis, calcification, cystic


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Papillary Carcinoma Cut surface- papillary foci- help in diagnosis

Microscopic features

Papillae Orphan Annei eye or ground glass nuclei

Intranuclear (pseudo) inclusions

Psammoma bodies

Foci of lymphatic invasion, cervical L node mets.


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Cut surface- papillary foci- help in diagnosis


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Papillary Carcinoma: The cross sections of several papillaecovered by cuboidalepithelium having the characteristic empty , Orphan Annie eyes nuclei.Inset shows a few cells with scant cytoplasm obtained on fine needleaspiration having characteristic intranuclear inclusions


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Orphan Annie:This cartoon strip character first appearedin the New York New ion 1926. Her forlornlooking(desperate or hopeless) eyes inspired the nameOrphan Annie for the nuclei seen in papillaryAdenocarcinoma


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Papillary Carcinoma: Note the small psammoma body in

the center. The cells have clear vesicular nuclei


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Clinical features Asymptomatic thyroid nodule

Mass in cervical L node

Hoarseness, dysphagia, cough, dyspnea Mets in lung --minority

Investigations:

Radionuclide study

FNAC


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Clinical features Excellent prognosis

10 yr survival > 95%

5-20% local recurrence 10-15% distant metastasis

Prognostic factors:

Bad if

Age > 40 yrs

Extra-thyroid extention

Distant mets


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Follicular Carcinoma 5-15% of primary thyroid Ca

Women 3:1

Age 40-60 yrs Dietary deficiency of iodine

Gross Morphology

Single nodules well demarcated/ widelyinfiltrative

Color tan pink, translucent


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Follicular Carcinoma Microscopic Morphology

Uniform cells follicles colloid

Nests / sheets of cells without colloid Hurthle cell or oncocytic variant of follicular Ca

Nuclei lack the feature of papillary ca

No psammoma bodies

No lymphatic spread


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Follicular Carcinoma Thyroid:A few of the glandularlumens contain recognizable colloid

Follicular AdenomaVsFollicular Carcinoma


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A. Follicular Adenoma:A fibrous capsule, usually thin but occasionally more prominent ,surrounds the neoplastic follicles and no capsular invasion is seen (arrows). Compressed normalthyroid parenchyma is usually present external to the capsule (top).

B. Follicular Carcinoma:demonstrate capsular invasion (arrows) that may be minimal , as inthis case, or widespread with extension into local structures of the neck


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Follicular Carcinoma Widely invasive follicular Ca

Infiltrate thyroid parenchyma & extr thyroid soft

tissue Solid or Trebecular growth pattern

Less follicular differenciation

mitotic activity

Follicular Carcinoma


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Clinical features Slowly enlarging painless nodules Cold nodules Hematogenous spread to bone/lung/liver

Prognosis depend on extent of invasion andstage at presentation

Better prognosis in minimally invasive type Total thyroidectomy-radioactive iodine-thyroid

hormone admin. Serum thyroglobin for monitoring

MEDULLARY CARCINOMA


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MEDULLARY CARCINOMA

Neuroendocrine tumour of thyroid

Derived from the Para follicular C cells and secrete

Calcitonin.

Familial Type: About 20% are familial occurring inMultiple Endocrine Neoplasia ( MEN) syndrome

Sporadic Type: No family history is present


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Gross Examination Findings of MedullaryCarcinoma Thyroid

May arise as a solitary nodule or may present as

multiple lesions involving both lobes of the thyroid.

Multicentricity particularly common in familial cases

Microscopic Findings in Medullary Carcinoma Thyroid


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Polygonal to spindleshaped cellsForm nests, trabeculae and even follicles

Distinctive feature:AcellularAmyloid deposits

derived from altered Calcitonin moleculespresent in many cases

A characteristic feature: Multicentric C- Cell Hyperplasia

in the surrounding thyroid parenchymaNot seen in sporadic type of medullarycarcinomas


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Medullary Carcinoma of Thyroid:Theses tumours typically containAmyloid , visible here as homogenous extracellular material , derivedfrom Calcitonin molecules secreted by neoplastic cells


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Clinical Features of Medullary carcinoma Thyroid

In majority mass in the neck

In some diarrhoeadue to secretion of VIP

Calcitoninis elevated.

The metastasize via the blood stream and are usually

aggressive

Anaplastic Carcinoma of Thyroid


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Anaplastic Carcinoma of Thyroid

Amongst the most aggressive human neoplasms Older persons

Dedifferentiationof Differentiated Tumors:

About half of the patients have a history of multinodular

goitre

20% of the patients with these tumors have a history ofdifferentiated carcinomas

another 20% to 30% have a concurrent differentiated

thyroid tumour, frequently papillary carcinoma

These findings have led to the speculation that anaplasticcarcinoma develops bydedifferentiationfrom more

differentiated tumors as a result of genetic changes

Morphologic Findings in Anaplastic Carcinoma Thyroid


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Presentation:

Bulky masses that typically grow rapidly

beyond the thyroid capsule into adjacent neck structures




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p g g p y

Microscopically

Highly anaplastic cells

Several histologic patterns:

(1) Large Pleomorphic Giant Cells

(2) Spindle Cells

(3) Mixed Spindle and Giant Cells

(4) Small Cells, resembling those seen in

small cell carcinomas at other sites


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Anaplastic CA of Thyroid:Pleomorphic hyper chromatic nuclei,some laying in tumor giant cells. Aberrant mitotic figures

are present


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Pathology of Thyroid Gland

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