Disorders in Thyroid Development
1. Thyroglossal Duct Anomalies
Thyroglossal duct-cyst
Location
Midline of neck ant to trachea
65% infrahyoid
20% suprahyoid
15% at hyoid bone
Gross
Cyst content: watery, mucoid, gel, pasty or
purulent, 2-3 cm in diameter
Microscopic
treatment
Lining may be squamous, ciliated columnar,
transitional or cuboidal w/surrounding
lymphocytic infiltrate
Wall may contain thyroid tissue
Tract usu goes thru hyoid bone
Thyroglossal duct carcinoma
Less than 100 cases reported
Ectopic thyroid
90% base of tongue near foramen cecum (lingual thyroid)
Except medullary carcinoma all other thyroid lesions have been
reported in this location
Midline fluid filled cyst w/papillary
excrescences
Solid or cystic w/hemorrhage
70% may be patients only thyroid tissue—do thyroid scan to
confirm
Papillary structures, atypical follicles,
psammoma bodies & fibrosis w/squam
metaplasia
Benign ectopic thyroid follicles used as
exclusion from metastatic tumor
Radical excision of entire tract including
tumor and hyoid bone (sistrunk procedure)
Good prognosis
2. Lateral Aberrant Thyroid
 Most are foci of follicular carcinoma or follicular variants of papillary carcinoma metastatic to neck lymph nodes
 Tx: ipsilateral thyroid lobectomy
 Sometimes benign thyroid particles seen in skeletal ms unassociated w/a lymph node
o Migration of thyroid follicle to neck can occur in nodular goiter & Hashimotos’s
o usu a surrounding lymphocytic infiltrate w/o architecture of lymph node
Chronic Thyroiditis
Hashimoto’s
Description
Most common form of chronic thyroditis
& cause of non-endemic goitrous
hypothyroid (also major cause in kids)
45-65 y.o women
10-20:1 more common in women
Gross
Micro
Pathogenesis
course
Treatment
Subacute (granulomatous)
Women in 3rd-5th decade (3-5:1)
Enlarged thyroid, firm, tender,
unilateral in 20%
Typical: sudden painful enlgment
w/fever & viral infection
Riedel’s struma
Exceedingly rare
Unilateral; woody hard thyroid
(ligneous), nodular, densely adherent
to surrounding structures
Subacute lymphocytes (painless)
Most common in post-partum
women
Uncommon cause of goitrous
hyperthyroid, responsible for 110% of total hyperthyroid
classic
4X Symmetrically enlarged
Smooth, firm, not attached to
surrounding structures
Gray, nodular w/septae, may be friable
Fibrous (atrophic)
10%; 1/3 of parenchyma may be
replaced by bands of fibrous tissue
May resemble Riedels
Not adherent to surrounding
Classic
Extensive infiltration of parenchyma by
sm lymphocytes, plasma cells, well dev
germinal ctrs
Many thyroid follicles destroyed
Remaing follicles are sm, lined w/epith
cells w/eosinophilic cytoplasm=Hurthle
cells
Delicate fibrosis-lobular pattern
Confined w/in thyroid capsule
Hyperplastic follicles in young adults
Fibrous
Extensive fibrosis w/follicular atrophy,
few clumps of eosinophilic colloid
May not be recognized as thyroid
Hurthle cells & squam metaplasia
Autoimmune disorder both humoral &
cell mediated injury cause damage to
thyroid gland
Myxedema may develop after yrs due to
progressive destruction of parenchyma
Not precancerous, but ↑risk B cell
lymphoma
Diffuse: 2-3x enlg, firm, yellow white
areas stand out from rubbery brown
thyroid substance
Intact capsule, slightly adherent to
surroundings but can be easily
separated
Dense white scar where involuted part
of thyroid was
Mild enlargement
Early: scattered follicles replaced by
microabscesses
Late:lymphocytes aggregates. Plasma
cells, histocytes around collapsed &
damaged thyroid follicles
Multinuc giant cells enclose colloid
End stage: chronic inflamm infiltrate &
fibrosis
Thyroid tissue is completely replaced
by mature hyalinized collagen
Infiltration by small lymphocytes
with patchy disruption and
collapse of thyroid follicles.
Rare plasma cells, no germinal
centers
Waves of destruction—diff stages
found in one gland
frozen section would help diff from
carcinoma
Post viral inflamm process
Self limited
HLA-B35
Pain in neck may radiate to jaw, ears;
fever, fatigue, malaise, anorexia,
myalgia w/variable enlgment of thyroid
Some occur in pts w/idiopathic retrop
fibrosis, mediastinal fibrosis, sclerosing
cholangitis, pseudotumor of orbit
May Present w/asphyxia due to the
pressure on the trachea
Thyroid hormone
Do not do subtotal thyroidectomy
Self-limited;
almost always complete recovery
Surgery difficult
No prominent inflammation
Diff dx:
1. thyroid carcinoma
2. fibrous variant Hashimoto’s
unknown
Self-limited, no sequelae
No hx. of viral infection
Common hyperthyroid sx.
Develop over 1-2 wks, and last 28 wks.
Self-limited
Goiter



1.
any enlargement of part or whole of the thyroid gland secondary to impaired synthesis of TH and compensatory response in serum TSH
TSH response causes hyperplasia and hypertrophy of thyroid follicular cells
Two types
Endemic type – more common
 From iodine deficiency in food or water in mountainous areas of the world
2. Sporadic type
 Less common than endemic
 Females> males, 8:1
 Minimal iodine lack w/increased demand for TH
 In indiv residing in areas w/adequate iodine
 Cause unknown
o Hereditary Aut Rec enzymatic defects
o Dietary goitrogens (substances that interfere w/thyroid hormone synthesis cabbage, cauliflower, brussel sprouts, turnips)
Simple (diffuse, non-toxic, colloid)
Multinodular – premalignant to follicular carcinoma
Gross
Diffuse, moderately enlarged and vascular
Nodular enlgment involving either part or whole thyroid
Not assoc w/hyper or hypofunction
Cut surface: variegated pattern due to hemorrhage, calcification, fibrosis,
microcyst formation
May reach enormous size (up to 2000g) & show retrosternal prolongation
Micro
Early: hyperplastic stage—hypertrophy & hyperplasia of follicular epithelium Follicles of varying sizes grouped together in form of ill defined nodules
w/scant colloid
which may be separated by broad bands of fibrous tissue w/old hemorrhage
Later: if dietary iodine ↑ or demand for TH↓, the stimulated follicular epith
& calcification
involutes to form enlarged colloid rich acini lined by low cuboidal to
columnar epithelium (colloid goiter)
Focal papillary hyperplasia may not be associated w/hyperthyroidism
Course
Children: caused by congenital biosyn defect may cause cretinism
Usually follows recurrent episodes of stimulation and involution of diffuse
Adults: achieve state of euthyroidism; few hyperthyroid
goiter, causing irregular enlgment of thyroid
Most long standing simple convert to multinodular
complications
Pressure on trachea, esophagus, SVC
Hemorrhage w/rapid ↑size may lead to asphyxia
Hypethyroidism from a toxic nodular goiter (plummer’s syndrome)—not
accompanied by infiltrative ophthalmopathy & dermatopathy like graves.
Hypothyroidism is rare, typically euthyroid
Radioiodine uptake is uneven
Distinction b/t multinodular and neoplasm is difficult in dominant nodule
Hyperthyroidism & Grave’s Disease
 Common 1.5-2% women in US
 Hyperthyroidism from protracted high levels of TH which can been seen in diffuse hyperplasia, toxic nodular goiter, toxic adenoma
 Diffuse hyperplasia or Grave’s disease peak age 20-40yrs, 7:1 more common in women
Grave’s Disease
 Most common cause of endogenous hyperthyroidism
 No increased risk of cancer
 Characterized by triad
1. Hyperthyroidism
2. infiltrative ophthalmology
3. Dermatopathy (thickening and induration of skin), only in 10-15%
 Pathogenesis: autoimmune—Ab’s to TSH receptor or TSI
 Gross: diffusely enlarged vascular meaty gland w/smooth capsule
 Microscopic: small acini w/tall columnar hyperplastic cells w/papillary projections
o Acini—diminished colloid, scalloping margins
o Vascularity & lymphocytic infiltration w/follicles w/in interfollicular parenchyma
o Audible bruit due to increased blood flow
 Clinical:
o generalized lymphoid hyperplasia, hypertrophied heart, & ischemic changes if have pre-existing CAD
o Increased metabolism – weight loss, increased sweating
o Cardiovascular effects – tachycardia, increased CO, arrhythmias, cardiac failure
o Neurological effects – mood swings, tremor, myopathy
o Eye signs – exopthalmos, lid retraction
o Skin edema – pre-tibial myxedema
 Labs:
o ↑free T4 and T3
o ↓TSH
o ↑radioactive iodine uptake (b/c of follicle stimulation by thyroid stimulating immunoglobulins-TSI)
 Treatment:
o Surgical—subtotal thyroidectomy
o Medical—decrease TH synthesis by radioiodine ablation
 Course: Tx may result in control of hyperthyroidism but eye changes may remit, persist, or progress
Tumors of the Thyroid
Adenomas

Most common benign thyroid tumor, arising from the follicular epithelium

Single nodule, well defined capsule surrounding uniform epithelial cells that are diff from surrounding normal thyroid

Presents as painless mass which must be differentiated from a carcinoma

Take up less radio-iodine than normal parenchyma – cold on scans (can be exceptions)

10% of cold adenomas are malignant – use FNA to help evaluate, but definitively need microscopy

Slowly increase in size – can get pressure symptoms, remain stable, suddenly increase in size with pain due to hemorrhage
Follicular
papillary
Atypical (spindle cell)
description
Most common thyroid adenoma
No true papillary adenoma
Encapsulated tumor showing tightly packed spindle
Composed of thyroid acini of varying sizes w/zone of
Most are papillary carcinoma
cells w/↑ cellularity, mitosis, & atypia
fibrosis & hemorrhage in center
No capsular or vascular invasion
Types: Trabecular, fetal, colloid
Some w/follicular pattern w/pleomorphic nuclei
Hurthle cell
Follicular adenomas w/acini composed of
granular eosinophilic cells w/lots
mitochondria
Carcinomas
description
microscopic
Tx & prog
Papillary
Most common type of thyroid ca
Only 3.3% are pure papillary
Most mix of papillary, follicular, solid
Spreads via lymphatics
Many assoc w/prior ionizing radiation
exposure
Ave age 2nd-4th decade; females
Five forms
~Minute clinically occult (small scar,
seen in many autopsies)
~Larger infiltrating (gray, firm, can be
calcified, have cystic change, or extend
into peri-thyroidal tissue)
~Encapsulated (rare spread, excellent
prognosis)
~Follicular (nuclear features important)
~Tall cell (eosinophilic cells, vascular
invasion, metastasis, older individuals,
worse prognosis)
Follicular
10-20% of all thyroid carcinomas
50 yrs. old, more in women
Increased prevalence in iodine deficient
areas
Variable pattern w/well defined papillae
& fibrovascular cores
Cells may have
-hypochromic empty nuclei w/o nucleoli
(orphan annie eyes)
-nuclear grooves
-eosinophillic cytoplasmic invag into
nuclei
Microfollicular growth pattern, solid and
trabecular areas present.
Encapsulated form looks very normal
Can be composed entirely of Hurthle
cells
Invasive form – hematogenous spread,
lots of mitosis, necrosis, obviously
malignant
Psammoma bodies in 50%
Multifocal in 20-80%
CLN metastases in 50% at dx.
Tx varies: total thyroidectomy, ipsi
Grossly – variegated, pink with redbrown areas of hemorrhage, necrosis,
calcification, cysts formation. If invasive,
may see gross infiltration of surroundings
NO psamomma bodies, empty nuclei,
nuclear grooves, eosinophilic
intranuclear inclusions
Unilateral lobectomy
Encapsulated – slow growing, spread by
blood, hot spot. Metastases may appear years
after excision of primary
Invasive – metastatic to liver, lung, bone in
50%
More aggressive, worse prognosis than pap
Medullary
5% of all thyroid cancers
Peaks at 40-50 in sporadic, 20-30 in familial
~C cell (calcitonin secreting) tumor
~Many with amyloid in stroma
~Familial – MEN IIA and IIB
MEN IIA – Sipple syndrome.
Aut dom.
Medullary carcinoma, C-cell hyperplasia, adrenal
pheochromocytoma, adrenal med. Hyperplasia, parathyroid
hyperplasia
Ret oncogene mut. On chromosome 10
MEN IIB
Medullary carcinoma, C-cell hyperplasia, pheochromocytoma,
adrenal med. Hyperplasia, mucosal neuromas, GI
ganglioneuromas, MSK abnormalities
Very aggressive, many metastases
Neural lesions often precede medullary cancer
Gross – gray-white, solitary, firm, well-circumscribes. If familial,
may be bilateral
Tumor cells may be round, spindle shaped, plasmacytoid with a
nesting, pseudofollicular, or trabecular pattern
May be amyloid.
Foci of c-cell proliferation in familia but usually not in sporadic.
Undifferentiated (anaplastic)
Less than 5%
~Most common in elderly,
often in areas of endemic goiter
~Rapidly progressing neck
mass, which can cause
hoarseness, SOB, stridor
~Tumor infiltrates skeletal
muscle, may extend posterior
to trachea, into upper
mediastinum.
~Aggressive, with CLN and
lung metastases
~Sometimes, see foci of
papillary or follicular
differentiation, suggesting
origin from better differentiated
carcinoma
Highly anaplastic cells, with
following patterns:
~large, pleomorphic giant cells
~spindle cells with sarcomatous
appearance
~small anaplastic cells
Calcitonin is demonstrable by immunohistochemical stains.
Good if detected early enough. Malignant nodules may be very
small.
Dismal – median survival of 6
mo.