Benyamin Makes

Dept. Of Pathology
FMUI - Jakarta

The thyroid gland develops from an evagination of the

tonge anlage! termed foramen "e"m! and then
des"ends to the ne"k.

May des"end into thora# in a$normal "onditions. If the

"anal formed $y the evagination doesn%t "lose! then
thyroglossal "ysts persist.

&$errant thyroid tisse is sally fond in the midline!

anterior triangle of ne"k.

'ormally the thyroid (eighs )*-)+gm.

THYROID GLAND
THYROID GLAND

,pheroidal folli"les are formed $y a"ini lined $y "$oidal

epithelim.

The "ells possess mi"rovilli that pro-e"t into the "olloid.

The "olloid material in folli"les "ontains thyroglo$lin!

(hi"h is the "arrier mole"le for T. and T/.

The mi"rovilli are $elieved to parti"ipate in the

mo$ili0ation of thyroid hormones from thyroglo$lin! $y
the en0ymati" "leavage of T.1T/ from thyroglo$lin.

Thyroid hormone affe"ts "elllar o#idative pro"esses

throghot the $ody.


Thyroglossal duct

Thyroid derived from

evagination of the
pharyngeal epithelim

D"t or "yst is a
persisten"e of a sins
tra"t

.

Iodide trapping.

Iodide o#idation $y pero#idase! prod"ing

tyrosine resides in thyroglo$lin. Thyroid
pero#idase "onstittes! at least in part! thyroid
mi"rosomal antigen. & de"rease or a$sen"e of
pero#idase may $e a "ase for thyroid failre.

Iodination of "olloid at epithelial ape# mi"ro-

villos1"olloid interphase of gland.

.

Formation of Thyroid 2ormones3

4
MIT 5Monoiodotyrosine6
4
DIT 5Diiodotyrosine6
4
Thyro#ine 5DIT # ) 7 T/6
4
Triiodothyronine 5) DIT 8 9 MIT 7 T.6

2ormone se"retion re:ires re-entry of "olloid

into the epithelial "ell! and partial proteolysis.
;on"entri" storage of glo$lin! (ith the older
glo$lin at the "enter sggests that the ne(er
glo$lin gets tili0ed first.

<oiters is a nonspe"ifi" term denoting thyroid

gland enlargement.

,"h in"reases in gland si0e and (eight may

have a variety of "ases.

Depending on the nderlying "ase! patient

(ith an enlarged thyroid gland may $e
ethyroid! hypothyroid! or hyperthyroid.

auses o! Thyroid "nlargement

In$orn errors of thyroid hormone $iosynthesis

'tritional iodine defi"ien"y

<oitrogeni" s$stan"es

'onto#i" nodlar goiter

Diffse to#i" goiter 5<raves=s disease6

Thyroiditis

'eoplasms

Infan"y-;retinism.

&dlt- My#edema.5,ome symptoms se"ondary

to a""mlation of m"opolysa""harides in
interstitial tisses.

;ases3
4
,rgi"al.
4
&toimmne.
4
>adiation.

Signs:
4
Mental retardation!
4
Ma"roglossia.
4
Delayed fontanel
"losre
4
pot-$elly
4
delayed epiphyseal
"losre.

Lab :
4
lo( T.1T/.

Signs:
4
Fatige!
4
lethargy! "old
intoleran"e!
4
perior$ital edema.
4
Thi"k! dry skin.
4
?nlargement of the
tonge.
4
De"reased "ardia"
otpt.

Lab:
4
@o( T.1T/.
4
2ypothalami" failre-
lo( T,2.

Clinical features.

The thyroid "an rea"h a hge si0e 5p to )+*

g or more6
Patholgy and pathogenesis.

The "om$ination of nodlarity! fo"al

hyperplasia! and degenerative "hanges
"omprises the entity of nodlar goiter.

NON TO&I NOD'LAR NON TO&I NOD'LAR
GOIT"R GOIT"R

This disorder is the most "ommon "ondition

asso"iated (ith hyperthyroidism.

Other "ases of hyperthyroidism in"lde

fn"tioning thyroid adenomas or "ar"inomas!

pititary tmors that se"rete thyrotropin!

"horio"ar"inomas that se"rete thyrotropin-like

s$stan"es.

Clinical features.

Patients sally are yong females!

(ho e#hi$it nervosness! ta"hy"ardia!

s(eating! and (eight loss.

Often e#ophthalmos also is present.

Pathology

<rossly! diffse to#i" goiter is a symmetri"al

enlargement of the thyroid gland to t(o to for times
the normal si0e

Mi"ros"opi"ally3
4
The thyroid sho(s a diffse! severe hyperplasia of the
folli"lar epithelim.
4
The folli"les are small and "ontain little "olloid.
4
The folli"lar "ells are tall and "olmnar! (ith enlarged n"lei.
4
Papillary infoldings o""r and lympho"yti" infiltrates are
"ommon.


Pathogenesis.

This is nkno(n! is presma$ly "ased $y

immnologi" me"hanisms.

The overea"tivity of the thyroid is "ased $y

e#"essive stimlation of the gland $y thyroid-
stimlating immnoglo$lins.

&toimmne diseases are "ommon in patient

(ith <raves= disease.

Acute suppurative thyroiditis

4
is a $a"terial infe"tion o""rs in yong "hildren.
4
It is very rare

Subacute granulomatous! thyroiditis

4
is a self-limited disorder "hara"teri0ed $y painfl s(elling of
the thyroid gland! transient hypothyroidism! and re"overy in 9
to . months.
4
The etiology is nkno(n! $t a viral "ase is sspe"ted

Chronic thyroiditis "ashimoto#s thyroiditis$

struma lymphomatosa$ autoimmune thyroiditis!
4
is a "ommon "ase of hypothyroditism and is a "lassi"
e#ample of atoimmne disease.

%iedel#s struma %iedel#s disease!

4
is not a disorder of the thyroid gland per se $t a "onne"tive
tisse proliferation that involves the gland.
4
This disorder is a systemi" "ollagenosis.

Clinical features.

The ne"k pain $egins sddenly.

Fever and malaise may $e present.

Pathology
<rossly3 the gland is slightly enlarged.
Firm and poorly defined.
2istologi"ally3

;olloid leakage from the disrpted folli"les for the

initial hyperthyroidism and initiates an
inflammatory response! (hi"h $e"omes
granlomatos.

<land destr"tion leads to hypothyroidism.

Su+acute thyroiditis

Clinical features.

?thyroid or! more often! hypothyiroid.

2ypothyroid 5my#edematos6 patients often

are lethargi"! intolerant of "old! and have thi"k
skin! $rady"ardia! and a lo( $ody temperatre.

Pathology

<rossly3 the gland is firm and moderately enlarged!

from t(o to for times the normal si0e.

Mi"ros"opi"ally3
4
the thyroid folli"les are small and atrophi"! (ith spare or
a$sent "olloid.
4
O#yphili" 52rthle-"ell6 metaplasia of the folli"lar epithelim is
"ommon.
4
The most prominent "hara"teristi" is infiltration $y
lympho"ytes and plasma "ells! (ith formation of germinal
"enters.


Hashimoto,s thyroiditis

Clinical features.
The thyroid "ompresses the srronding str"tres and
may o$str"t $reathing.
Pathology.
4
<rossly! the thyroid gland is (oody or iron-hard
4
and the a$normal tisse is adherent to srronding
str"tresA

&ll $enign tmors of the thyroid gland arise

from the folli"lar epithelim and! ths! are
folli"lar adenomas.

The tmor sally are solitary nodles.

-enign thyroid neo#lasms
&rossly'

folli"lar adenomas have the sal (ell-

"ir"ms"ri$ed appearan"e of a $enign tmor.

they sally are demar"ated from the ad-a"ent

normal thyroid tisse and en"apslated.
Microscopically

the en"apslation and the sharp demar"ation

from the ad-a"ent thyroid tisse are evident.

The ad-a"ent thyroid tisse is "ompressed

from the e#pansive gro(th of the adenoma

Papillary adenocarcinoma is the most "ommon type of

thyroid "an"er and a""onts for appro#imated B*C to
D*C of all malignant tmors arising in the thyroid

(ollicular carcinoma: a$ot 9*C of all thyroid

"ar"inomas.

Medullary carcinoma: +C to 9*C of all thyroid "an"ers

from the parafolli"lar "ells.

Anaplastic undifferentiated! carcinoma: .C to +C

thyroid "ar"inomas. >apidly gro(ing.

)pidemiology.

&$ot +*C of patient are nder /*!

more "ommon in (omen than in men!

It has $een related to prior head and ne"k irradiation.

Clinical features.

&nterior ne"k mass that sally painless.

May present as a "ervi"al lymph node metastatis (ith

a primary tmor in the thyroid gland that is too small to
$e "lini"ally evident.

Pa#illary adenocarcinoma
Pathology
&ross appearance3
4
This varies "onsidera$ly (ith the si0e of the tmor.
4
,mall tmors 5often "alled s"lerosing! or o""lt "ar"inomas6
resem$le minte s"ars.
4
@arge tmors have ill-defined $orders! ;yst formation is
"ommonA the tmor may $e solid. Fi$rosis and "al"ifi"ation
sometimes are e#tensive.
Microscopic appearance.
4
Fi$rovas"lar stalks.
4
'"lei sho( "hara"teristi" "learing 5Egrond-glass n"leiF6.
4
&$ot /*C of "ontain psammoma $odies.
4
@ymphati" invasion $y papillary "ar"inoma is e#tremely
"ommon.

Pa#illary carcinoma o! the thyroid

Papillary "ar"inoma - Papillary "ar"inoma -
Psammoma $odies Psammoma $odies
Papillary "ar"inoma Papillary "ar"inoma
-Papillary str"tre -Papillary str"tre

Pa#illary adenocarcinoma
Prognosis.

,lo( gro(th.

The 9*-year srvival rate is a$ot G+C.

Clinical features.

&dlt (ith a slight predominan"e in females.

Invasion of $lood vessels is "ommon

;ases metastases to $rain! $ones! or lngs.

Pathology

<rossly
4
some folli"lar "ar"inomas are
indistingisha$le from folli"lar adenomas
$e"ase invasion is not e#tensive enogh to
$e seen grossly.
4
Hith other folli"lar "ar"inoma! the invasion
is grossly evident.

.ollicular carcinoma o! the thyroid

Folli"lar "ar"inoma 4 Folli"lar "ar"inoma 4
"apslar invasion "apslar invasion
Folli"lar "ar"inoma 4 Folli"lar "ar"inoma 4
vas"lar invasion vas"lar invasion

Prognosis
depends largely pon the e#tent of
invasion3
4
If invasion is so minimal that the "an"er looks
grossly like an adenoma and
4
mi"ros"opi"ally sho( limited "apslar or
vas"lar invasion!
the prognosis is very good (ith a +-year
srvival rate *f D+C.

Clinical features.

Patients over age /*

Parafolli"lar "ell normally se"rete "al"itonin

measrement of serm "al"itonin is sefl as a
diagnosti".

Medllary "ar"inoma o""rs in familial forms as (ell as

sporadi"ally. In the familial forms! it is a "omponent of
mltiple endo"rine neoplasia 5M?'6 type II 5,ipple=s
syndrome6 and type II$. In familial "ases! medllary
"ar"inoma tends to $e mltifo"al and $ilateral.

Pathology
4
<rossly! hard! grayish-(hite to yello(ish-tan mass
and sally is (ell demar"ated.
4
Mi"ros"opi"ally! tmor "ells "lstered in solid or
irreglar grops that are separated $y a hyaline!
amyloid-"ontaining stroma.
Prognosis.
4
Metastasi0e $oth $y lymphati"s and $lood vessels.
4
The overall +-year srvival rate is +*C


)pidemiology.

Over age I* and

Over +*C of patients is pre"eded $y a long history of

goiter
Clinical features.

>apidly gro(ing mass that may "ompromise $reathing

$y "ompressing the tra"hea or! on o""asion!

May l"erate throgh the skin.

Pathology

<rossly!
4
invasion into ad-a"ent areas of the thyroid gland and other
str"tres of the ne"k.
4
>emnants sggesting a pree#isting adenoma or lo(-grade
"an"er are fre:ently present.

Mi"ros"opi"ally! the tmor "ells are large! often of giant

si0e! and pleomorphism is "ommon
*he prognosis

poor

nearly al(ays fatal (ithin 9 *r ) years.

Anatomy and histology

&$ot G*C of all person have for parathyroid

glands.
(unction

Parathyroid hormone 5parathormone! PT26!

(orking in "on-n"tion (ith vitamin D!
"al"itonin plays a ma-or role in "al"im
homeostasis.

Normal #arathyroid gland
Normal #arathyroid gland

"ypercalcemia is the hallmark of primary

hyperparathyroidism.

"ypocalcemia is m"h less "ommon than

hyper"al"emia
,"reening for "al"im distr$an"es. >otinely
measred in mlti"hannel s"reening test! so
"ases of asymptomati" hypo- or hyper"al"emia
are no( $eing identified.

,ymptoms may $e a$sent (hen hyper"al"emia

is mild!

&s serm levels rise a$ove G or 9*g/dl, patients

develop gastrointestinal! ms"loskeletal!
"ardiovas"lar! neropsy"hiatri"! and rinary
symptoms.

@evels a$ove 9Dg1dl "an $e lethal.

It "an reslt from a failre of target organs

5kidneys6 to response to PT2! a "ondition
"alled psedohypoparathyroidism.

,ymptoms depend on the degree and dration

of the hypo"al"emia and are "hiefly nerologi"3
4
an#iety! depression! fn"tional psy"hoses!
neroms"lar irrita$ility.
4
,evere hypo"al"emia "ases tetany.

2yperplasia may o""r from slo( renal ;a88 loss!

heightened resistan"e to PT2! and from ne"k irradiation.

;ases 9+C of "ases of 2yperparathyroidism.

Mostly from "hief "ell hyperplasia.

Most glands are enlarged $t enlargement may $e

asymmetri".

2yperplasia may $e nodlar making the diagnosis of

adenoma diffi"lt.

;lear "ell hyperplasia is "omposed of "ells (ith many

small va"oles.

Parathyroid hy#er#lasia

Parathyroid Parathyroid
hyperplasia hyperplasia

& relatively "ommon disorder.

,poradi"ally and! less often! in familial forms! "hiefly

as a "omponent of M?' types I and II.

;lini"al featres.
4
One or more symptoms of hyper"al"emia may $e present!
4
$t many asymptomati" patient no( are identified $y mass
s"reening te"hni:es.

Pathology.
4
/*C to D*C of patients have solitary parathyroid adenomas
4
9*C to +*C have primary hyperplasia.


M)+ , medullary carcinoma M)+ , medullary carcinoma
M)+ , papillary carcinoma M)+ , papillary carcinoma

;ompensatory hyperse"retion of PT2 se"ondary

to end organ resistan"e to the hormone!
"hara"teri0ed $y hypo"al"emia.

Causes:
4
;hroni" renal insffi"ien"y 5main "ase6. >ed"tion of
ioni0ed ;a88 and retention of phosphors
4
Jitamin D defi"ien"y
4
Intestinal mala$sorption
4
2yperplasia of "hief "ells enses. If "ase is
removed! tisses may revert to normal or "ontine as
hyperplasia 5tertiary hyperparathyroidism6.

Caused by renal disease or! more rarely! $y

mala$sorption.

Clinical features3 soft tisse "al"ifi"ation and

osteos"lerosis develop.

Pathology3 the parathyroid gland sally sho( diffse

"hief "ell or "lear "ell hyperplasia.

Pathogenesis: Patients (ith renal insffi"ien"y "annot

synthesi0e a"tive vitamin D develop hypo"al"emia.
,ome mala$sorptive states also "ase hypo"al"emia.
In "onse:en"e! there is a rea"tive in"rease in PT2
se"retion! and parathyroid hyperplasia develops.

sally is an iatrogeni" "onse:en"e of

thyroid srgery! radioiodine therapy! or
radi"al ne"k disse"tion.

Un"ommonly! it is familial! idiopathi"

5possi$ly atoimmne6!

or "ased $y metastates to the

parathyroids.

Clinical features.

2ypo"al"emia and hyperphosphatemia! (ith

symptoms related to the degree and dration
of the hypo"al"emia.
Pathology!

In iatrogeni" hypoparathyroidim no parathyroid

tisse is present.

In idiopathi" hypoparathyroidism! lympho"ytes

infiltrate and destroy the gland!

Metastati" tmors also repla"e and destroy the

parathyroid glands.

Inade:ate se"retion of PT2 or ineffe"tive

hormone. 2ypo"al"emia and hyperphosphatemia
reslt.

Clinical symptoms and signs:

4
In"reased neroms"lar e#"ita$ility! de to lo(
ioni0ed ;a88. ;hvostek sign! "arpopedal spasm.
4
Mental depression! psy"hosis.
4
;ardia" "hanges-K-T prolonged! T-(ave "hanges.
4
Dental hypoplasia.


Causes:
4
Post srgi"al 5p to 9*C6.
4
&toimmne 5 hereditary or non-hereditary6!
may $e a""ompanied $y hypoadrenalism and
other endo"rinopathies.

>enal resistan"e to PT2

'ormal or LPT2 . 2ypo"al"emia and

hyperphosphatemia.

M-linked dominant 5rond fa"e! short ne"k! short

/th-+th meta"arpal-&l$right osteodystrophy6.

May respond to large doses of Jit D.

& solitary adenoma is the most "ommon primary

disorder of the parathyroid glands

;ar"inoma is very rare! appro#imately 9C of "ases of

primary hypoparathyroidism.

;lini"ally3 these tmors are fre:ently large enogh to

$e palpa$le and reslt in severe hyper"al"emia.

Pathologi"ally3 mitoses! lo"al invasion! and metastases

5sally fn"tional6 "hara"teri0e the lesion.

'eoplasms of nonparathyroid origin
5sally "ar"inomas6 sometimes "an
prod"e s$stan"es that mimi" the a"tions
of PT2 and hen"e "ase hyper"al"emia.
This "ondition is kno(n as e"topi"
hyperparathyroidism

arcinoma o! #arathyroid

;ar"inoma of parathyroid is rare!

it "an also $e the "ase of primary

hyperfn"tion.

&lmost invaria$ly are a""ompanied $y

hyperparathyroidism!

and the symptoms are more severe than in

adenomas.

Diffi"lt to diagnose! $e"ase $enign tmors "an

$e pleomorphi".


Carcinomas are diagnosed by:
4
;apslar! ad-a"ent fat or $lood vessel
invasion.
4
Tra$e"lar gro(th pattern (ith mitoses.
4
Positive nodes
4
@o"al re"rren"e follo(ing rese"tion.
4
The tmors are sally atta"hed! firmer than
adenomas


Parathyroid carcinoma