Transcript Pathology of the thyroid

Pathology of the
thyroid
 Derived from pharyngeal epithelium
 Descends from foramen cecum to lower neck
 Lingual thyroid or ectopic in neck
 2 lobes and isthmus, 15-25 gr, richly vascular
 Follicular cells : T4
 Parafollicular cells : Calcitonin
 T4,3 mostly bind to TBG, the remaining FT4,3
 T3 10 folds greater affininty than T4

TRH
TSH
T4
T3
Normal thyroid gland
Thyroid diseases
Hyperthyroidism
Hypothyroidism
Mass lesions
Causes of thyrotoxicosis
 With hyperthyroidism
Primary
1. Graves disease
2. Toxic multinodular goiter
3. Toxic adenoma
Secondary
TSH-secreting pituitary adenoma (rare)
 Without Hyperthyroidism
Thyroiditis (Subacute granulomatous/lymphocytic)
Struma ovarii
Factitious thyrotoxicosis
Hyperthyroidism
(#thyrotoxicosis)
Clinical features of hyperthyroidism
1. Constitutional
2. Gastrointestinal
3. Cardiac
4. Neuromuscular
5. Ocular
6. Thyroid storm
7. Apathetic
Hyperthyroidism
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Diagnosis of hyperthyroidism
1. Low TSH
2. High T4
3. Radioiodine uptake
 In secondary hyperthyroidism, TSH is
normal or raised
 T3 toxicosis: Normal T4, High T3
Thyroid scan
Causes of hypothyroidism
 Primary
1. Postablative: surgery, radioiodine, radiation
2. Hashimoto thyroiditis*
3. I-deficiency*
4. Congenital defect (dyshormonogenetic goiter)*
5. Drugs (Li, I, p-aminosalicylic acid)*
6. Rare developmental abnormalities of thyroid
(thyroid dysgenesis)
 Secondary
Pituitary or hypothalamic failure (uncommon)
* Goiterous hypothyroidism
Hypothyroidism
 Clinical Features:
Cretinism
Myxedema
 Diagnosis:
high TSH
Low T4
Thyroiditis
Hashimoto’s thyroiditis
 F>>M, 45-65 yr
 Most common thyroiditis in I sufficeint areas
 Autoimmune: CD 4 T cells (cytokine
mediated), CD 8 cytotoxicity, Ab-dep cell
mediated cytotoxicity by NK cells
Pathogenesis of Hashimoto’s thyroiditis
Hashimoto’s thyroiditis
 F>>M, 45-65 yr
 Most common thyroiditis in I sufficeint areas
 Autoimmune: CD 4 T cells (cytokine
mediated), CD 8 cytotoxicity, Ab-dep cell
mediated cytotoxicity by NK cells
 AutoAbs: anti TG, anti PO, anti TSHR
 Genetic: HLA DR3, HLA DR5, CTLA-4
 Hypothyroidism, Hashitoxicosis
 Increased risk of B-cell non Hodgkin
lymphoma
Hashimoto’s thyroiditis
Hashimoto’s thyroiditis
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Hashimoto’s thyroiditis
Fibrosing variant
Other thyroiditis
 Infectious: Rare, painful
 Subacute granulomatous (De Quervain’s)
Painful, post-viral, enlargement
of 1 or 2 lobes, granulomatous inflammation,
sudden or gradual hyperthyroidism, self limited
 Subacute lymphocytic (Silent)
Painless, postpartum, Autoimmune, initial phase
Of hyperthyroidism followed by euthyroidism
 Reidel: Autoimmune, diffuse fibrosis
 Palpation
Granulomatous thyroiditis
Palpation
thyroiditis
Riedel
thyroiditis
Graves’ disease
 F>>M, 20-40 yr
 Most common cause of endogenous
hyperthyroidism
 Genetic: HLA-B8 and DR3, CTLA4, PTPN22
 Anti TSHR, Anti TG, anti thyroid peroxisdase
 Anti TSHR: Thyroid stimulating Ig, TGI
(growth), TBII (Inhibitory)
 Autoimmune thyroid disease span a spectrum
from Graves to Hashimoto’s
Triad of Graves
Hyperthyriodism
Ophthalmopathy
Dermopathy
Graves’ disease
Graves’ disease
Graves’ disease
Graves’ disease
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Goiter
 Most common thyroid disease
 Diffuse / nodular
 Endemic goiter (Geograhpic distribution) > 10%
 Sporadic goiter (Increased demand, substances
interfere with synthesis)
 Dyshormonogenetic goiter
 Euthyroidism, Plummer syn, hypothyroidism
 Nodularity:
Recurrent episodes of hyperplasia/involution
Variation among cells in response to external stimuli
Goiter
Goiter
Goiter
Multinodular goiter
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Goiter
Goiter
Goiter
Thyroid neoplasms
 Often present as solitary thyroid
nodule
 Very common
 Mostly benign
 Increased chance of malignancy if:
Solitary
Young
Male
Hx of radiation
Cold nodule
Thyroid FNA is a diagnostic
test
Thyroid FNA
Follicular adenoma
Solitary in a lobe
Soft to firm
Cold to hot
Activating mutations in TSH receptor
causes high cAMP
20% mutations in RAS oncogene
(Also in follicular carcinoma)
Often non functional, toxic
Follicular adenoma
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Follicular adenoma
Follicular adenoma
Follicular adenoma
Follicular adenoma
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Follicular
Adenoma
Hurthle cell adenoma
Thyroid carcinomas
 ~ 1% of CA related death
 F >M
 Mostly in adults, children (papillary CA)
 Mostly well diff
 Risk factors: Radiation in childhood, I-def
Papillary CA: 75-85%
Follicular CA: 10-20%
Meduallary CA: 5%
Anaplastic CA< 5%
Papillary carcinoma
 Most common thyroid CA
 Young age
 Genetic: MAP kinase signaling pathway
ret/PTC or NTRK1 rearrangements
BRAF oncogene point mutation
 Hx of radiation in childhood (RET
rearrangement)
 Painless mass/ cervical lymphadenopathy
 Indolent course
Papillary carcinoma
Papillary carcinoma
Papillary carcinoma
Papillary carcinoma
Papillary carcinoma
Papillary carcinoma
Papillary carcinoma
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Follicular Carcinoma
 Second most common CA
 Older age (middle age)
 I-deficiency (nodular goiter)
 RAS mutation, PAX-PPAR ϒ1
 Cold nodule
 Blood metastasis common
 LN metastasis uncommon
Follicular carcinoma
Follicular carcinoma
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Follicular carcinoma
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Medullary carcinoma
 Derived from C cells
 80% sporadic
 20%: MEN II, familial medullary CA
 RET point mutations
 > 40 yr, MEN II younger age
 Mass in thyroid , secretion of hormones
 Raised serum calcitonin, somatostatin,
serotonin, VIP
 Prophylactic thyroidectomy
Medullary carcinoma
Medullary carcinoma
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Medullary carcinoma
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Anaplastic carcinoma
• Elderly, mean=65 yr
• Rare
• Lethal
Hx of goiter
Hx of differentiated thyroid CA
Concurrent thyroid CA (papillary)
• Loss of funcrion of p53
Anaplastic carcinoma
Anaplastic carcinoma
Anaplastic carcinoma