Download Pathology of the Thyroid Gland

Pathology of the Thyroid
Gland
Prof. Dipak Shah
Department of Pathology
UWI, Mona
Diseases of the Thyroid
Gland
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Congenital diseases
Inflammation
Functional abnormality
Diffuse and Multinodular goiters
Neoplasia
Inflammation
Thyroiditis
 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
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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
• 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 Thyroiditis
• Diffuse enlargement
• Firm or rubbery
• Pale, yellow-tan, firm
& somewhat nodular
cut surface
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
• Hyperfunction
  in level of hormone → toxic effects
• Due to:
 Diffuse hyperplasia
 Hyperfunctioning multinodular goiter
 Hyperfunctioning adenoma
 Subacute lymphocytic (painless) thyroiditis
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
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Most common cause of endogenous hyperthyroidism
• Characterized by hyperthyroidism, ophthalmopathy with exophthalmos
and dermopathy (pretibial myxedema)
• Autoimmune disease with genetic susceptibility associated with HLAB8 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’ Disease
Autoimmune disease with breakdown of helper-T-cell tolerance
Excessive production of TWO thyroid autoantibodies:
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Thyroid-stimulating antibody (TSAb) &
2)
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 Disease
• Symmetrical
enlargement of thyroid
gland
• Cut-surface is
homogenous, soft and
appear meaty
• Hyperplasia and
hypertrophy of
follicular cells
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 non-toxic (simple) goiter
• colloid goiter
• Endemic
• sporadic (dyshormonogenetic)
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
• Commonest type of goiter
• Euthyroid, but may be hypo- or hyper• Mostly idiopathic, but RARELY, may be
caused by:
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Drugs used in Rx of hyperthyroidism
Goitrogens e.g. cauliflower, cabbage, cassava
Suboptimal iodine intake
Hereditary enzymatic defects
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 Goiter
• Asymmetric
enlargement
• Multinodular
• Haemorrhage
• Calcification
• Fibrosis
• Cystic degeneration
Multinodular Goiter
• Numerous follicles
varying in size
• Recent haemorrhage
• Haemosiderin
• Calcification
• Cystic degeneration
• +/- dominant nodule
Thyroid Neoplasms
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Primary Tumours
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Epithelial
Malignant Lymphomas
Mesenchymal tumours
II. Metastatic Tumours
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
• 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 Adenoma
• Solitary, Variably
sized, encapsulated,
well-circumscribed
with homogenous
gray-white to redbrown cut-surface
• +/- degenerative
changes
Follicular Carcinoma
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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 Carcinoma
• Solitary round or oval
nodule
• Thick capsule
• Composed of follicles
• Capsular invasion or
vascular invasion
within our outside
capsular wall
Papillary Carcinoma
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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 Carcinoma
• Variable size
(microscopic to
several cm)
• Solid or cystic
• Infiltrative or
encapsulated
• Solitary or
multicentric (20%)
Papillary Carcinoma
• Papillae or follicles
• Psammoma bodies
• NUCLEAR
FEATURES***
Papillary Carcinoma
Nuclear Features
 Optically clear (ground
glass, Orphan Annie)
nuclei
 Nuclear
pseudoinclusions or
nuclear grooves
Papillary Carcinoma
Prognosis
Excellent but following factors play important
role:
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Age and sex
Size
Multicentricity
Extra-thyroid extension
Distant metastasis
Total encapsulation, pushing margin of growth
& cystic change
Anaplastic Carcinoma
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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 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 Carcinoma
• Cellular
pleomorphism
• +/- multinucleated
giant cells
• High mitotic activity
• Necrosis
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
(MTC)
Sporadic MTC
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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
• 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
(MTC)
Associated with MEN IIA
 Younger patients in twenties
 Multicentric and bilateral
 Slow growing
Associated with MEN IIB
 Even younger patients in teens
 Aggressive with early metastasis
 Poor prognosis
Medullary Thyroid Carcinoma
(MTC)
• Histology same for
sporadic & familial
• Solid, lobular or
insular growth patterns
• Tumour cells round,
polygonal or spindleshaped
• Amyloid deposits in
many cases
Medullary Thyroid Carcinoma
(MTC)
• Amyloid deposits stain
orange-red with
Congo Red stain
Prognosis of Thyroid
Carcinomas
Papillary
Best prognosis
Follicular
Medullary
Anaplastic
Worst prognosis
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
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Papillary carcinoma
Follicular carcinoma
Medullary carcinoma
Follicular adenoma
Hyperplastic (dominant) nodule
Metastatic neoplasms
• FINE NEEDLE ASPIRATION CYTOLOGY
Congenital Thyroid Diseases
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Agenesis /Aplasia
Hypoplasia
Accessory or aberrant thyroid glands
Thyroglossal duct cyst
Thyroglossal Duct Cyst
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Children
Failure of regression
Neck, medial
Squamous or columnar lining
Complications: inflammation, sinus tracts