surgical pathology diseases of the thyroid and parathyroid.docx
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Surgical Pathology Diseases of the thyroid and parathyroid.docxTRANSCRIPT
DISEASES OF THE THYROID and PARATHYROIDDr. RamosSurgical PathologyTHYROID
develops as a tubular evagination from foramen caecum at the root of the tongue
grows downward anterior to trachea and thyroid cartilage
Abnormal descent leads to aberrant lingual or substernal thyroid
weighs 20-25 gms T3 and T4 synthesized by thyroid
and released into blood bound to TBG, albumin and prealbumin
T3 and T4 – modulate cell growth and functional activity
Undergoes hyperplasia during stress
“Goitrogens” – inhibits thyroid gland function à suppress T3T4 synthesis à TSH increases à gland enlarges
Examples:a. Anti thyroid agentsb. Iodide
Thyrotoxicosis (Hyperthyroidism) hypermetabolic state, elevated T3
and T4
more common in females, hyperfunctioning gland
S/Sx: nervousness, palpitations, rapid pulse, fatigability, weakness, weight loss, good appetite, diarrhea, heat intolerance, warm skin, excess perspiration, emotional lability, menstrual changes, fine tremors, eye changes and thyroid enlargement
Morphology: eye changes - wide-eyed
stare, proptosis skin changes – peripheral
vasodilatation cardiac changes –
arrhythmias, mild lymphocytic/eosinophilic infiltrates, mild fibrosis, fatty changes in myofiber
Others: fatty infiltration in skeletal muscle, liver osteoporosis, lymphadenopathies
Most common cause: Grave’s disease – diffuse
hyperplasia Toxic Multinodular goiter Toxic adenoma
Hypothyroidism
Cretinism During development and infancy. Mental and physical growth
retardation, dry rough skin, wide set eyes, periorbital puffiness, flat broad nose, large protuberant tongue.
Endemic or sporadic cretin
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Myxedema Slow physical and mental activity,
fatigue, lethargy, cold intolerance, general listlessness and apathy,
Periorbital edema, thick dry coarse skin, tongue enlarges, peripheral edema, constipation, flabby heart and enlarged with dilated chambers with myofiber
CAUSES OF DISTURBED THYROID FUNCTION
A. THYROIDITIS 1. Hashimoto’s Thyroiditis
(Struma lymphomatosa)2. Subacute granulomatous
Thyroiditis (De Quevains)3. Subacute lymphocytic
(Painless) Thyroiditis4. Infectious Thyroiditis5. Riedel’s Fibrous
Thyroiditis (Riedel’s Struma)
Hashimoto’s Thyroiditis (Struma lymphomatosa)
most common cause of goitrous hypothyroidism in region sufficient with iodine
major cause of non-endemic goiter in children
an organ-specific autoimmune disease
o F:M (5:1), middle age ETIOLOGY:
o defect in function of thyroid-specific suppressor T cells, autosomal dominant
o associations with HLA-DR5 and DR3
o autoantibodies against thyroid peroxidases, thyroglobulin colloid Ag, TSH receptor, etc.
o patients may suffer from other autoimmune disease like sle, sjogren syndrome, ra, pa, grave’s
MORPHOLOGYo with atrophic and goitrous
varianto enlarged nodular gland,
rubberyo replacement of parenchyma
by lymphocytes, plasma cells, immunoblasts, macrophages, with germinal centers
o hurtle cell follicles (oncocytes)o atrophic variant – small gland
with fibrosis
SIGNS AND SYMPTOMSo thyroid enlargement,
hypothyroido increase TSH and decrease
T3T4 levelso demonstrate autoantibodies,
increase risk to lymphoma
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SUBACUTE GRANULOMATOUS THYROIDITIS (DE QUEVAINS)
self-limited granulomatous thyroiditis
second to fifth decade, F:M (3:1) HLA-B35 association probable viral
etiology MORPHOLOGY
o enlarged gland, aggregation of cells around damaged follicles admixed with multinucleated giant cells enclosing naked pools of colloid – granulomatous
o later CI infiltrates and fibrosis
SIGNS AND SYMPTOMSo acute febrile reactiono painful enlargement of
thyroido hyperthyroidismo self-limited in 6-8 weeks
SUBACUTE LYMPHOCYTIC THYROIDITIS (Painless Thyroiditis)
in female, post partum period 15% of hyperthyroidism enlargement of gland, foci of
lymphocytic infiltrates with occasional interstitial fibrosis
self-limited, T3&T4 levels increased
INFECTIOUS THYROIDITIS
from microbial seeding Staphyloccocus, Streptococcus,
Salmonella, TB and fungi
RIEDEL’S FIBROUS THYROIDITIS (Riedel’s Struma)
glandular atrophy, hypothyroidism, fibrosis and adhesions to surrounding structures
mistaken for malignancy
CAUSES OF DISTURBED THYROID FUNCTION
B. GRAVE’S DISEASE TRIAD:
o hyperthyroidism – diffuse hyperplasia
o ophthalmopathy – lid lag, stare, proptosis, upper lid retraction, periorbital edema
o dermopathy – localized edema at dorsa of legs and feet
INCIDENCE:o 1-2% of female, HLA-
DR3 and B8o between Grave’s and
other autoimmune diseases
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ETIOLOGY:o autoantibodies to TSH
receptor leading to hyperfunction of gland:
o Thyroid stimulating Abo Thyrotropin-binding inhibitor
Ig – inhibits TSH bindingo Ophthalmopathy – due to
lymphocytic infiltrates in EOM and retro-orbital fibrofatty tissue, glycosaminoglycans in orbital fat
o T cell-mediated action with local release of cytokines and growth factors
MORPHOLOGY:o enlarged, meaty parenchymao tall columnar epithelium,
increase number of cells (pseudopapilla buds)
o eaten-up colloido increase lymphoid tissueo morphology may be altered
by medications
SIGNS AND SYMPTOMS:o young femaleo thyrotoxicosiso ophthalmopathyo dermopathyo thyroid enlargemento increase RAIU, decrease TSH,
increase T3 & T4
CAUSES OF DISTURBED THYROID FUNCTION
C. DIFFUSE NON-TOXIC GOITER (COLLOID GOITER)
diffuse thyroid enlargement without hypo- or hyperfunction endemic goiter
deficient intake of iodine decrease T3 & T4, increase
TSH follicle hyperplasia à
euthyroid state GOITROGENS
o Calciumo Fluorideso Cabbageo Cassavao Cauliflowero Turnipso Brussel sproutso Brassica and Crucifera
plants Non-endemic/Sporadic
Goitero F:M (8:1), puberty or
young adulto either physiologic
superimposed on or hereditary defect in thyroxine synthesis
Signs and Symptomso enlarged glando euthyroid state
MORPHOLOGY:a. Hyperplastic Stage
enlarged, hyperemic follicles lined by columnar epithelium with scanty colloid
b. Colloid Stage colloid
accumulation, markedly enlarged gland (up to 500 gms or more)
distended follicles lined by flattened epithelium filled with colloid
irregular distribution of small and distended follicles, hyperplastic foci may persist
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CAUSES OF DISTURBED THYROID FUNCTION
D. MULTINODULAR GOITER (MCAG) from simple goiters with sporadic and endemic
forms toxic or non-toxic extreme enlargement F>M MORPHOLOGY:
o nodular, enlarged gland up to 2 kg, asymmetric
o nodularity created by islands of colloid-filled or hyperplastic follicles
o random irregular scarring
o focal hemorrhage and hemosiderin deposition
o focal calcificationso miocrocysts formation
SIGNS AND SYMTPOMS:o enlarged thyroid causing
cosmetic and functional impairment
o dysphagia, choking sensation, inspiratory stridor, SVC syndrome
o signs of thyrotoxicosis - RAIU & T3&T4
o cardiac manifestations
CAUSES OF DISTURBED THYROID FUNCTION
E. TUMORS: “Thyroid Nodules”GENERALIZATIONS:
1. A solitary nodule is more likely to be neoplastic than multiple nodules.
2. Functioning “hot” nodules are more likely to be benign than malignant.
3. The younger the patient (<40), the greater the likelihood of neoplasia
4. A nodule in a male is more ominous then one in a female
I. ADENOMAS
MORPHOLOGY: discrete, completely
encapsulated masses with parenchyma different from that outside the capsule, compress surrounding non-neoplastic thyroid tissue
approximately 3-10 cms soft, fleshy, may be
hemorrhagic composed of well or poorly
developed follicles; fetal, colloid or trabecular type, spindle cell (atypical), Hurthle cell adenomas (oncocytic type)
SIGNS AND SYMPTOMS:
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o must be differentiated from malignancy
o may be “cold” or “hot”o mass may suddenly enlarge
due to intralesional hemorrhage
II. MALIGNANT TUMORS:PAPILLARY Ca 75 – 85% Well-
differentiated tumors
FOLLICULAR Ca 10 – 20%MEDULLARY Ca 5%ANAPLASTIC Ca rare
PATHOGENESIS:o Irradiation to head and neck
areao Japanese survivors to atomic
bombs (7% developed thyroid
CA)o Hashimoto’s Thyroiditiso Non-toxic nodular goitero Oncogene PTC present in 20-
30% of tumors
1. PAPILLARY CARCINOMA most common 3rd to 5th decade F:M (2-3:1) MORPHOLOGY: from small to large lesions,
often multifocal gray white, firm, calcified
areas and cystic change Composed of papillae and or
follicles lined by single or several layers of columnar epithelium, papillae with fibrovascular core
“orphan-Annie” nuclei
Nuclear grooves, eosinophilic intranuclear inclusions, psammoma bodies
Encapsulated variant – 10% of tumors
Follicular variant – mostly follicular structures devoid of papilla but nuclear detail that of Papillary
SIGNS AND SYMPTOMS: Young female, mild to
moderate thyrotoxicosis 50% neck node metastasis at
time of diagnosis à 90% survival at 20 yrs.
Favorable prognostic factors include:
Female sex Less than 20 y/o Confinement to thyroid gland Well-differentiated cytologic
morphology
2. FOLLICULAR CARCINOMA 10-20% of thyroid CA 5th-6th decade F:M (3:1) SIGNS AND SYMPTOMS: Slow growing, painless
masses6
30% 5-year survival for large lesions
MORPHOLOGY: encapsulated, difficult to
distinguish from adenoma composed of uniform
microfollicular architecture of orderly cuboidal lining cells
capsular and/or vascular invasion
little propensity for lymphatic invasion
vascular invasion is common – distant metastasis
3. MEDULLARY THYROID CARCINOMA
Neuroendocrine neoplasm of parafollicular C cell origin
5th-6th decade of life, in 3rd decade if associated with MEN
MYC: 1. secrete calcitonin2. Amyloid stroma3. 20-25% occur with MEN
Syndrome IIa and II MORPHOLOGY: discrete tumors in one lobe or
numerous nodules throughout gray tan parenchyma,
infiltrative, calcification
polygonal and spindle shaped cells in organoid nests and trabeculae, separated by fibrovascular stroma with amyloid
SIGNS AND SYMPTOMS: Mass with associated pressure
symptoms or asymptomatic Paraneoplastic syndrome
(diarrhea) Prognosis: familial form – 90%
10-year survival MEN form – 30-50% 10-year
survival
4. ANAPLASTIC CARCIOMA 5% of carcinomas Rapid growth, large tumors Aggressive, metastasize widely Variants:
1. Spindle cell2. Giant cell3. Small cell
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F. MISCELLANEOUS LESIONS THYROGLOSSAL DUCT CYST
2-3 cm midline cyst from remnants of foramen caecum may occur at any age cyst with numerous secretion,
lined by squamous or columnar epithelium with trapped thyroid follicles in adjacent wall
DISEASES OF THE PARATHYROID
PARATHYROID GLANDS 4 glands derived from pharyngeal
pouches
36-40 mg Chief cells
- predominant cell- secrete PTH
PTH FUNCTIONS: Mobilizes calcium from bone. Increases renal production of
1,25(OH)2D3, active in intestinal Ca absorption.
Increases renal tubular reabsorption of Ca thereby conserving it.
Lowers serum phosphate level by enhancing phosphaturia.
I. PRIMARY HYPERPARATHYROIDISM Result to hypercalcemia Causes:
1. Adenoma – 75-80%2. Hyperplasia – 10-15%3. Carcinoma - <5%
Incidence:1. F:M (3:1), 6th decade of
life2. 25 cases/100,000
Major effects of hyperparathyroidism:o Increase bone resorption
and calcium mobilization from skeleton.
o Increase renal tubular reabsorption and retention of Ca
o Increase renal synthesis of 1,25(OH) 2D3 enhancing GIT calcium absorption
SIGNS AND SYMPTOMS:
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o Vague symptomso Weakness and easy
fatigabilityo Affective dysfunctionso Urinary complaintso Hypercalciuria
1. Adenoma Solitary, 0.5 to 5.0
gms, encapsulated, no intervening stromal fat
Usually inferior glands are affected
Composed mostly of normal-looking, enlarged chief cells in sheets, trabeculae, follicles
2. Primary Hyperplasia Sporadic or in MEN I and
IIa All 4 glands are enlarged,
asymmetric Diffuse or nodular
hyperplasia composed predominantly of chief cells, clear cells, oxyphil cells in sheets, nests, trabeculae and follicles
Interspersed fat within hyperplastic area
3. CARCINOMA Very similar to adenoma but
with features of local invasion and metastasis
SIGNS AND SYMPTOMS:o Renal – recurrent stones,
nephrocalcinosiso Skeletal – loss of bone,
osteoporosis, OFC o GIT – peptic ulcer,
pancreatitiso CNS – HA, depression,
memory loss, seizureso Muscular – generalized
weaknesso Others: skin & eye
changes, hyperCa, hypoPO4, elevated PTH
II. Secondary Hyperparathyroidism
In patients with renal failure
phosphate retention and hypocalcemia
secondary hyperparathyroidism MORPHOLOGY:
Same as primary HP
III. Hypoparathyroidism CAUSES:
1. Surgically induced9
2. Congenital absence of all glands
3. Autoimmune disease4. Familial and metabolic
syndromes SIGNS AND SYMPTOMS:
1. Increases neuromuscular excitability
2. Mental changes3. Intracranial changes4. Calcification of lens5. Cardiac conduction
abnormalities
IV. Pseudohypoparathyroidism Abnormality in PTH-receptor
complex interaction Unresponsive to PTH Increase PTH due to decrease
serum Ca
THE ENDOCRINE PANCREAS
Review of Normal PhysiologyCELL TYPE
SYNONYM
% PRODUCTS
PRODUCT ACTION
B BETA 70 Insulin AnabolicA ALPHA 20 Glucago
nCatabolic
D DELTA 5-10
Somatostatin
Vs insulin & glycogen
PP Pancreatic Polypeptide
1 GY effects
DIABETES MELLITUSTYPE I TYPE II
SYNONYMS Insulin dependent DM (IDDM)Juvenile onsetKetosis prone DM
Non-insulin dependent DM (NIDDM)Adult onset
PATHOGENESIS Absolute lack of insulin due to reduction of B cell
Impaired insulin release and end-organ insensitivity
CAUSES: TYPE I1. Genetic susceptibility
- resides in chromosome 6 (HLA-D), CI II genes
- 50% concordance in twins2. Autoimmunity
90% with islet cell antibodies (ICA)
3. Environmental factorsa. Virusesb. Chemicalsc. Cow’s milk
CAUSES: TYPE II1. Genetic but not HLA-linked2. No evidence for autoimmunity3. No evidence of viral-induced injury4. Premature cell aging5. Amylase outside cells6. Decrese number of receptors7. Impaired post-receptor signaling
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INSULITIS IN TYPE 1 DM
ISLET WITH AMYLOID CHANGE
MECHANISMS LEADING TO DIABETIC COMPLICATIONS
1. Non-enzymatic glycosylation à advances glycosylation end products (AGE)
o HbA1c – glycosylated hemoglobin
o measure of blood glucose level
2. Increased sorbitol and fructose à OSMOSIS
MORPHOLOGY of other organs:1. Diabetic microangiopathy2. AtherosclerosisCAUSES:
a. Hyperlipidemiab. Decreases HDLc. Increased platelet
adhesivenessEFFECTS:
a. Myocardial infarctionb. Cerebral strokec. Gangrene of lower extremities
3. Diabetic Nephropathy Kidneys are the most severely
affected organ Morphology: Diffuse glomerulosclerosis Nodular glomerulosclerosis
(Kimmelsteil-Wilson) Exudative lesion Necrotizing papillitis
NEPHROSCLEROSIS
PAPILLARY NECROSIS
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Kimmelsteil-Wilson Lesion
4. Diabetic Ocular complicationsa. Retinopathy
i. Non-proliferative (background retinopathy)
ii. Proliferativeb. Cataractc. Glaucoma
5. Diabetic Neuropathy Due to damage Schwann cells
an axon Sexual impotence, bladder
and bowel dysfunction
ISLET CELL TUMORS
A. INSULINOMA B cell tumor most common of
the islet cell tumors Clinical Triad:
hypoglycemia, CNS manifestations, relief with glucose
Morphology: Majority are solitary
adenomas Yellow-brown nodules
composed of B cells
5% malignanT
B. GASTRINOMA Clinical Triad: Zollinger
Ellison Syndrome (peptic ulcer disease, gastric hypersecretion, pancreatic islet cell tumor)
MORPHOLOGY: Microscopically similar
to insulinomas; need immunocytochemistry or electron microscopy to differentiate the two
Mostly malignant (60%)
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