Thyroid

Pathology 2014/2015
THYROID
DEVELOPMENTAL DISORDERS
Lingual
thyroid

Thyreoglo
ssal duct
cyst

Accessory
thyroid
THYROTOXICOSIS AND
C

HYPERTHYROIDISM
T3, T4 TSH
PATHOGENESIS
CLINICAL Hai
r CN
FEATURE S
Eye
S s
Appet
ite
Ski
n
Hea
rt
Weig
ht
GI
tract
Reproduc
tive
system
Han
ds
Extremit
ies
GRAVES (BASEDOW) DISEASE
EPIDEMIOLOGY
F>M (10:1)
Most common in 20s
and 30s
Increased incidence of
other autoimmune
diseases and in PATHOGENESIS
relatives (50%) Autoimmune disease
Associated with HLA- 3 types of antibodies:
DR3 carriers 1. Thyroid-stimulationg Ig (IgG)
2. Thyroid growth-stimulating
Ig
3. TSH-binding inhibitor Ig
GRAVES (BASEDOW) DISEASE
PATHOLOGY
Symmetrically enlarged
gland diffuse
hypertrophy and
hyperplasia
Lymphocyte infiltration
Graves triad:
1. Thyrotoxycosis
2. Ophtalmopathy
3. Pretibial myxedema
HYPOTHYROIDISM
C

T3, T4 TSH
 PATHOGENESISEPIDEMIOLOGY
Lack of thyroid parenchyma 3-5% of adults
developmental disorders F>M
Hashimoto thyrioditis In children causes
Surgical removal cretinism mostly
Damage caused by radiation associated with iodine
Disorders in thyroid hormone deficiency
production In adults causes
myxedema
idiopathic primary (Gull disease)
hypothyroidism
hereditary (genetic) defects in
biosynthesis
drugs
insufficiency of iodine
Suprathyroid causes
CLINICAL Hai
r CN
FEATURE
EyeS
S
s
Appet
ite
Ski
n
Hea
rt
Weig
ht
GI
tract
Reproduc
tive
system
Joint
s
Extremit
ies
THYROIDITIS C

Inflammation of the thyroid

HASHIMOTO THYROIDITIS
EPIDEMIOLOGY PATHOGENESIS
Most common cause of 1. CD8+ T-cells reaction
hypothyroidism 2. Macrophage reaction
F>M (10:1) 3. B-cells reaction
Mostly between ages
of 40 and 65
Mutated CTL4 gene
 HASHIMOTO THYROIDITIS
PATHOLOGY
Lymphocytic infiltrations
(with germinal centres)
symmetrically
enlarged gland
Follicle atrophy with
oxyphil (Hrthle) cells
Fibrosis

TREATMENT
Taking thyroid hormones
SUBACUTE GRANULOMATOUS (DE
QUERVAIN) THYROIDITIS
EPIDEMIOLOGY CLINICAL FEATURES
F>M (3:1) Fever, malaise, pain in
Most common the neck (particularly
between ages of 30 with swallowing)
and 50 Transient hyperthyroidism
may occur transient
hypothyroidism episode
PATHOGENESIS
leukocyte count and
Virus infection (?) erythrocyte
occurs mostly after sedimentation
upper respiratory Euthyroid state in 6
tract infection to 8 weeks
SUBACUTE GRANULOMATOUS (DE
QUERVAIN) THYROIDITIS
PATHOLOGY
Disruption of thyroid follicles extravasations of
colloid
Polymorphonuclear infiltrate mononuclear
infiltrate
Granulomatous
reaction with
giant cells
Fibrosis
RIEDEL THYROIDITIS
EPIDEMIOLOGY
Unknown etiology
F>M (3:1)
May be associated
with idiopathic fibrosis
in retroperitoneum,
mediastinum or orbit
Autoimmune disease
(?) PATHOLOGY
CLINICAL FEATURES Hard, fixed thyroid mass
Painless enlargement of thyroid Dense fibrosis with few
Signs of compression of larynx, mononuclear
oesophagus and recurrent inflammatory cells
nerve Follicle atrophy
Hypothyroidism
 GOITER C

Enlargement of the thyroid

GOITER
EPIDEMIOLOGY
Hypertrophy and hyperplasia of follicles caused by
secondary disorder of thyroid hormone synthesis (TSH)
Possible states:
1.Euthyroid metabolic state mostly
2.Hyperthyroidism
3.Hypothyroidism
. 2 types:
1.Sporadic puberty, young adults; F>M (8:1)
causes: Ca or F, some vegetables,
hereditary
enzymatic defects and other unknown
2.Endemic chronic insufficiency of iodine
. Plummer syndrome toxic multinodular goiter (10%)
 GOITER
PATHOLOGY
Diffuse and multinodular
goiter
Many colloid-filled, variably
sized and shaped follicles

CLINICAL FEATURES
Mass effects: cosmetic
problem, airway
obstruction, dysphagia,
compression of large
vessels
Toxic: hyperthyroidism
Malignancy incidence: <5%
BENIGN NEOPLASMS
C
NON-
NEOPLASTIC NEOPLASMS
CONDITION
Multiple nodules
warm/hot nodules
Older patients
Slow growth
Females Solitary nodules (1%
malignant)
cold nodule (often malignant)
Younger patients
Rapid and asymmetrical
enlargement of the gland
Males
FOLLICULAR ADENOMA
Benign neoplasm derived from follicular epithelium

EPIDEMIOLOGY
3-7% of adults
F>M (7:1)
More often in younger
people

PATHOLOGY
Mostly solitary with well-defined capsule
Multiple adenomas difference to multinodular goiter
Subtypes: microfollicular, macrofollicular, trabecular,
tubular etc.
Hrthle cell adenoma
Very similar to follicular carcinoma (capsule!)
FOLLICULAR ADENOMA
CLINICAL FEATURES
Cold vs. warm/hot nodules
Thyrotoxicosis toxic
adenoma
Excellent prognosis no recur
or metastasis

TREATMENT
Surgical removal (lobectomy)
MALIGNANT
C

NEOPLASMS
PATHOGENESIS
GENETIC FACTORS: 2 oncogenic pathways:
1. MAP kinase pathway feature of most papillary
carcinomas
mutations in RET or BRAF genes - never both!
fused RET/PTC gene in 30% of PCs
2. PI-3K/AKT pathway in 1/3 of follicular carcinomas
mutations of RAS, PIK3CA or PTEN genes
unique (2;3)(q13;p25) translocation in 1/3 of FCs
fused PAX8-PPAR gene which codes a new
oncogenic protein
. ENVIRONMENTAL FACTORS:
1. Exposure to ionizing radiation especially before 20s
2. Deficiency of dietary iodine
 4 types:
1.Papillary carcinoma (70-
80%)
2.Follicular carcinoma
(15%)
3.Anaplastic carcinoma
(<5%)
4.Medullary carcinoma
(5%)
PAPILLARY CARCINOMA
70-80% of thyroid carcinomas
Most common between ages of 25 and 45
F>M (3:1)

PATHOLOGY
Solitary or multifocal lesions
Can be encapsulated or cystic with areas of fibrosis,
calcification or lymphocyte infiltration
Papillary architecture fibrovascular stroma (with
psammoma bodies) + one or more layers of cubic to
cylindrical, atypical epithelial cells
Typical nuclear features: very finely dispersed
chromatin (optically clear ground glass or Orphan
Annie eye nuclei), pseudoinclusions (invaginations
of cytoplasm)
PAPILLARY CARCINOMA
CLINICAL FEATURES
Painless palpable nodule
Early metastasis in cervical lymph nodes
Prognosis mostly excellent (10-year survival
rate of 90%)
More aggressive in
older patients and
males
FOLLICULAR CARCINOMA
F>M (3:1)
40-60 year-olds
PATHOLOGY
2 forms:
1.Minimally invasive
encapsulated, looks like
follicular adenoma
invades blood vessels,
infiltrates capsule and
surrounding tissue
2.Widely invasive infiltrates
the thyroid parenchyma and
extrathyroid soft tissues
(not) encapsulated
FOLLICULAR CARCINOMA
CLINICAL FEATURES
Metastasizes haematogenous to bone (shoulders,
pelvis, sternum, skull), lungs and liver
MIFCa 10-year survival rate = 85%
WIFCa 10-year survival rate = barely 45%
ANAPLASTIC CARCINOMA
EPIDEMIOLOGY
20% of patients had papillary
or follicular carcinoma
F=M, ages 50 to 75
PATHOLOGY
Undifferentiated, aggressive tumour
Rapid growth into nearby neck structures
Highly anaplastic cells, pleomorphic giant cells and
spindle cells
CLINICAL FEATURES
Metastases to distant sites
Death occurs in less than 2 years (in most within 6
months)
ANAPLASTIC CARCINOMA
MEDULLARY CARCINOMA
EPIDEMIOLOGY
Derived from parafollicular cells (C cells) that secrete
calcitonin
2 types: sporadical (80%) and familial (20%)
PATHOGENESIS
RET gene mutation (both) or as a part of MEN-2 syndrome
(F)
PATHOLOGY
Solitary or multicentric (with microcarcinomas; F)
Necrosis and haemorrhage in larger lesions
Polygonal or spindle-shaped cells in nests, trabeculae or
follicles
Amyloid deposits altered procalcitonin (Kongo red +)
Immunohistochemical methods antibodies for calcitonin
MEDULLARY CARCINOMA
MEDULLARY CARCINOMA
CLINICAL FEATURES
Mass in the neck with possible compression effects
Manifestations caused by secretion of aberrant
hormones like VIP
calcitonin rarely affects calcium metabolism
Metastases to regional lymph nodes, lungs, liver
and bones
SMCa 5-year survival rate (after thyroidectomy)
50%
FMCa without MEN-2 very good prognosis
FMCa with MEN-2A relatively good prognosis
FMCa with MEN-2B very malignant, poor prognisis
 THE END! C

Thank you for your attention!