endocrine

Lect-2

Pathology of Thyroid

TUCOM- department of pathologyyear 3 endocrine gland lectures 3&4

Normal Thyroid Gland

Thyroid - Normal

Normal resting Thyroid

Disorders of Thyroid:

Hyperthyroidism Hypothyroidism Thyroiditis Diffuse multinodular Goiter. Neoplasms – adenoma/carcinoma. Congenital – Thyroglossal cyst/duct.

Goiter

It is a diffuse or focal enlargement of the thyroid gland.

Caused by: 1- Colloid goiter. 2- Grave’s disease. 3- Thyroiditis. 4- Tumors.

Colloid goiter:

most cases start as diffuse enlargement with nodularity development at later stages.

They represent compensatory hyperplasia of follicular epithelium secondary to decreased thyroid hormone production.

Diffuse-Multinodular goitrePathophysiology

Endemic & sporadic types Endemic: Cassava – thiocyanate – iodide

transport. Sporadic: rare, females, young and usually of

unclear cause. (may be associated mild defect, iodine deficiency and physiological needs).

When there is low T3 and T4 there will be an increase of TRH & TSH that induce secretion of thyroid hs associated with enlargement of thyroid gland by hypertrophy and hyperplasia of follicular epithelium at earlier stages diffuse and by time nodular.

Stages

Hyperplastic stage & Colloid stage. Repeated attacks multinodular due to

uneven hyperplasia and accumulation of colloid as a result of tension and stress that lead to rupture of follicles.

CLINICALLY:

1- Huge size result in dysphagia, airway obstruction, chocking sensation and stridor. SITE as retrosternal extension causing superior vena cava syndrome with vein enlargement, tachycardia and heart failure.

2- Rarely toxic hyperthyroidism plummer syndrome.

3- Mass effect and misdiagnosed as tumor need US, isotope scanning, FNAC, CT scan and MRI.

Morphology: Grossly: at early stages symmetric and

diffusely enlarges the thyroid gland and in late stages there is multiple nodules on cut surfaces. Some nodules show cystic degeneration, hemorrhage, fibrosis, and calcification.

Microscopy show randomly sized colloid filled follicles lined by flattened cells due to pressure of colloid with focal areas of hyperplasia, fibrosis, cystic changes, necrosis & hemorrhage present as hemosiderin laden macrophages.

The mass is relatively symmetric and diffusely enlarges the thyroid gland. The patient is from an endemic goiter area (in this case, Cambodia), where more than 10% of the population have goiters due to low-iodine diets (lack of seafood or iodized salt), often combined with diets high in vegetables that block iodine uptake by the thyroid gland ("goitrogens," such as cabbage or cassava).

Goitre – Iodine Deficiency

Thyroid gland, multinodular goiter - Gross, cut surfaces  The thyroid gland shows multiple nodules on cut surfaces. Some nodules show cystic degeneration, hemorrhage, fibrosis, and calcification.

Multinodular Goitre with Papillary Carcinoma

Colloid Cysts in MNG

Multinodular Goitre

Hyperthyroidism

Thyrotoxicosis it is a hypermetabolic state encountered much more often in females caused by High free T3/T4 in the blood.

CAUSES: COMMON: 1- Diffuse toxic hyperplasia (Graves) 2- Toxic multinodular goiter 3- Toxic adenoma. UNCOMMON CAUSES: 1- Thyroiditis 2- Functioning thyroid carcinoma 3- TSH secreting pituitary adenoma 4- Iatrogenic. 5- Struma ovarii. 6- Choriocarcinoma and hydatidiform mole.

Clinical features Nervousness, palpitations, rapid pulse,

fatigability, muscular weakness, weight loss with good appetite, diarrhea, heat intolerance, warm skin, excessive perspiration, emotional liability, menstrual changes, fine tremor of the hand, eye changes and enlargement of the thyroid gland.

Cardiac manifestations: tachycardia, arrhythmias, especially fibrillation or SVT, cause is obscure but more prone to occur in old age group.

Graves Disease: Common (2%F) Females, 20-40y, Autoimmune, associated with other

autoimmune diseases. HLA B8 and DR3. Triad of clinical features,

Hyperthyroidism Exopthalmos and retraction of the upper eyelid. Pretibial myxedema.

Ab to TSH receptor – thyroid stimulating antibody, thyrotropin binding inhibitor immunoglobulin are responsible for hyperfunction.

Thyroid growth immunoglobulin responsible for hyperplasia.

Micro: Diffuse hyperplasia, tall columnar cells, papillary folds & Scalloped, pale, scanty colloid.

Hyperthyroidism Features:

Graves exophthalmos - Clinical presentation  Although the patient in our scenario did not have exophthalmos, it may be found in Graves disease, as pictured here. The eyes protrude from the orbit due to increased glycosaminoglycans deposition in the retro-orbital fibrofatty tissue and extraocular muscles, as well as to a marked lymphocytic infiltrate.

Graves Disease: e.g. Of orbitopathy before and afterDecompression surgery.

Graves’ Thyroiditis:

(Graves disease) - Gross  This thyroid gland is symmetrically moderately enlarged and would show beefy red parenchyma on cut sections.

Graves Disease

The hyperfunctioning follicular epithelium is tall columnar, representing cellular hypertrophy. Papillary infoldings into the follicular lumens result from epithelial proliferation and overcrowding, representing hyperplasia. Peripheral scalloping of the colloid within follicular lumens represents active pinocytosis by the hyperfunctioning epithelium.

Hypothyroidism

Cretinism / Myxedema – Low T3/T4, High TSH

Causes: Hashimoto’s thyroiditis - autoimmune Iodine deficiency Drugs – PAS, iodides, lithium Developmental – Atrophy, hypoplasia Pituitary

disorders Radiation/Surgery

Hypothyroidism Cretinism (child) Impaired CNS & bone

growth Mental retardation Short stature Coarse facial

features Protruding tongue Umbilical hernia

Myxedema (adult) Slow physical and

mental activity Cold intolerance Over weight Low cardiac output Constipation and

decreased sweating Cool pale thick skin

Hypothyroidism

Myxedema

Features:

Myxedema: showing periorbital bags under eyesNote loss of lateral eyebrow; Anne’s sign

Thyroid Atrophy

Thyroiditis

Some are ill defined as interstitial th. Some are rare as palpation th. And

suppurative (always blood borne). Reidel’s fibrous thyroiditis of unknown

etiology manifested as atrophy and hypothyroidism with fibrous adhesions.

Common types are: 1- Hashimoto’s thyroiditis, 2- subacute lymphocytic thyroiditis and 3- subacute granulomatous.

Hashimoto Thyroiditis Common non endemic goitre. females more common 45-65y. Autoimmune disease with genetic basis HLA-DR5, DR3. ( defect in thyroid specific suppressor T cells lead to

emergence of T helper cells against specific thyroid antigens which cooperate with B cells lead to formation of auto-antibodies as Ab to thyroid peroxidases formerly known as antimicrosomal Abs & Anti- thyroglobulin antibody)

Initial hyperthyroidism and in long standing cases hypothyroidism.

High risk of B cell lymphoma. Grossly: Firm diffuse goitre. Microscopy: Follicle atrophy with lymphocytic infiltration. Hürthle cells – eosinophilic cells. Fibrosis & destruction of follicular tissue.

Hashimoto’s Thyroiditis:

Hashimoto’s Disease

Hashimoto’s Disease

Anti-thyroglobulin Antibody

Anti- microsomal Autoantibody

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

cells. Hyperthyroidism. Heals with normal thyroid function.

DeQuervain's Disease - SAGT

Subacute lymphocytic thyroiditis

Foci of lymphocytic infiltration with mild fibrosis.

Obscure origin but may be an autoimmune in origin.

Thyroid CancerClassification

Epithelial cell tumors:

DifferentiatedPapillary (75- 80%)

Follicular (10-20%)

UndifferentiatedAnaplastic (3-5%)

Parafollicular (C- cell) tumors

Medullary ( 5% )

Lymphoma (1-2%) Others

Neoplasms of Thyroid

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

Neoplasms of Thyroid

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

hoarseness, recurrent laryngeal nerve damage.

Clinical Presentation

Thyroid nodule (most common)

Cervical lymph node(s)

Local compressive symptoms

Distant metastasis

Thyroid dysfunction

Thyroid Nodules

Prevalence :

Physical Exam 4-7%

Ultrasound 30%

Autopsy 50%

Incidence increases with age

Thyroid Nodules(Cont’d)

Most thyroid nodules are BENIGN

A thyroid nodule has 5-12% malignancy rate

History of radiation increases the chance of malignancy to 30-50%

Thyroid NodulesEvaluation

History Physical Examination Laboratory Evaluation

- TSH and FNAC Imaging Studies

NOT VERY HELPFUL

Thyroid NodulesEvaluationThyroid NodulesEvaluation

HISTORY Age < 20 or > 50 Head or neck irradiation Family history Male sex Recent growth Pressure symptoms

Thyroid NodulesEvaluationThyroid NodulesEvaluation

PHYSICAL EXAMINATIONHard non tender noduleNodule of different consistency

within MNGFixed noduleCervical lymphadenopathyImmobile vocal cord

Thyroid Nodules Ultrasonography

Generally has a minor role in the

evaluation of thyroid nodules

Palpable nodules do not need ultrasound

Small non-palpable nodules (<1cm) are

generally unimportant even if malignant

Cystic nodules can be malignant

Ultrasound Scan

Solid nodule:

Thyroid Nodules FNA

The most important test in the evaluation of a thyroid nodule

Has an overall sensitivity of 83-98% and specificity of 92-100%

Complications are very rare and usually minor

Thyroid NodulesRadionucleotide Scans

Most thyroid nodules are cold (95%)

Most cold nodules are benign (80-85%) Hot nodules are usually functioning and can

be detected by TSH (suppressed)

Warm nodules can be malignant

Radioactive iodine

is concentrated from the blood by thyroid follicular cells, allowing correlation of anatomic features with thyroid function. Decay of radioactive iodine is detected as dark spots on the scan. A normal thyroid gland shows diffuse moderate iodine uptake in the right and left lobes and isthmus. Graves disease is characterized by diffuse increased uptake. Multinodular goiter most often shows patchy, irregular uptake with some nodules hyperfunctional compared to normal (dark, or "warm," on scan) and other nodules hypofunctional (pale, or "cold"). The focal rounded defect lacking uptake (cold nodule) is characteristic of thyroid neoplasms and cysts. A focal rounded area of increased uptake that suppresses the remaining thyroid gland (hot nodule, not pictured) is most often a hyperfunctional follicular adenoma or goiter nodule.

Technetium Scan

NormalNormal

Hot nodulesHot nodules

Cold noduleCold nodule

Thyroid NodulesEvaluation (Summary)

Most thyroid nodules are benign TSH determines the thyroid functional

status Thyroid scanning and U/S are generally

not helpful FNA is the most useful diagnostic

procedure

Adenoma

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

Follicular Adenoma

Follicular Adenoma

Solitary Adenoma

Follicular Adenoma

Thyroid Carcinoma

Uncommon – child – elderly. Common - Papillary adenocarcinoma. Associated with radiation exposure,

especially during the first 2 decades.

Thyroid Carcinoma

TypeAgeSpreadPrognosis

PapillaryYoung <45yLymphExcellent

FollicularMiddle ageB.V.Good

AnaplasticelderlyLocalPoor

MedullaryElderly

familial

Allvariable

Papillary Carcinoma

Most common cancer – 75-80% Idiopathic, Radiation, Gardner & Cowden

syndromes.Papillary folds, Psammoma bodies,

Orphan-Anne nucleus.98% 10 year survival when localized.

This is a lobectomy specimen of thyroid gland showing normal parenchyma, within which is a 2-cm, white, slightly irregular, expansile tumor. No grossly discernible papillae are present on the cut surface. The neoplasm is not encapsulated, but is well demarcated from adjacent, beefy-red thyroid parenchyma, and it appears to distend and distort the capsule of the thyroid gland without penetrating through it.

Papillary Carcinoma

Papillary Carcinoma

Papillary Carcinoma

The papillae shown here are covered by cuboidal epithelium that has nuclei that are characteristic of papillary thyroid carcinoma: large, crowded, and overlapping nuclei with vesicular chromatin, small nucleoli, infrequent mitotic figures and loss of polarity. Chromatin clearing (ground-glass "Orphan Annie" nuclei) and irregular nuclear contours with grooves and cytoplasmic pseudoinclusions are hallmark features of papillary thyroid carcinoma. Shared features between histopathology and cytology of papillary thyroid carcinoma are nuclear enlargement, intranuclear inclusions, nuclear grooves, small nucleoli, and nuclear overlapping. Unlike tissue sections, cytologic smears of papillary thyroid carcinoma show finely granular chromatin (inset). Normal follicular cells are roughly the same size as a mature lymphocyte nucleus or a red blood cell. Note

that the inset shows nuclear detail, but the cytoplasm of the tumor cells is pale.

Medullary Carcinoma

Amyloid in Medullary Carcinoma – Polarized microscopy

Anaplastic Carcinoma

Conclusions:

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

Thyrotoxicosis: Antithyroglobulin, anti microsomal Hypometabolism, Low T3/T4, high TSH.

Multinodular goitre – low iodine. Neoplasms

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