endocrine Lect-2

TUCOM- department of pathology year 3 endocrine gland lectures 3&4 Pathology of Thyroid TUCOM- department of pathology year 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 goitre Pathophysiology 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 after Decompression 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) Myxedema (adult) 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 eyes Note 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 Cancer Classification Epithelial cell tumors: Differentiated Papillary (75- 80%) Follicular (10-20%) Undifferentiated Anaplastic (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 Nodules Evaluation History Physical Examination Laboratory Evaluation - TSH and FNAC Imaging Studies NOT VERY HELPFUL

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

Thyroid Nodules Evaluation PHYSICAL EXAMINATION Hard non tender nodule Nodule of different consistency within MNG Fixed nodule Cervical lymphadenopathy Immobile 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 Nodules Radionucleotide 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 Normal Hot nodules Cold nodule

Thyroid Nodules Evaluation (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 Type Age Spread Prognosis Papillary Young <45y Lymph Excellent Follicular Middle age B.V. Good Anaplastic elderly Local Poor Medullary Elderly familial All variable

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 Thyrotoxicosis: 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.