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ThyroidCytopathology
and Its
Histopathological Bases
Doc. MUDr. Jaroslava Dukov,CSc,FIAC
Inst. of Pathol. 1st Med. Faculty, Charles Univ. & Chair of Pathol. Inst. of Postgraduate Studies,
Prague, Czech Rep.
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Thyroid Gland
- embryology and fetal endocrinology
mouth epithelium, end of the 1st iu.monthductus thyreoglosus
lateral pharynx ultimobranchial bodiesC- bb.
parathyroid glands
fetal secretion starts in 12 weeks
effect on GROWTH
effect on DIFFERENTIATION
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Thyroid Gland - anatomy
Weight in adults 15-20g
over60g(7g in a neonate)struma
lobus dexter ismus a lobus pyramidalis
lobus sinister
aberant, accesory, ectopic gland
(polyclonality should help to tell from ca)
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Thyroid Gland - ectopic tissue
Parasitic thyroid nodule
Rosai (1990) - mediastinum
Assi (1996) - laterally in the neck
Shimizu et al. (1999) - onlyforlaterally on
the neck localised thyroid tissue without anyrelation to the lymph nodes
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Main Tasks
in the Thyroid Cytology
reduction of the unnecessary surgery diagnosis & follow-up of subclinical
inflammation
EARLY DIAGNOSIS of NEOPLASMS
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Thyroid Cytology
getting sample
needle 0.6-0.8mm
min. 2 punctionsaspiration
nonaspiration reduction of the blood content
cyst: evacuate and aspirate with thesecond punction the periphery
fluid: whole volume for cytology
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Thyroid Cytology - processing
Fixation
air dried
etanol / spray
(cytospin)
CYTOBLOCK
Staining:
MGG, HE
polychrom
all histo
imunocytoTGB,calcitonin,
parathormon
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Thyroid Cytology
- diagnostic groups (n20 000)
10,8
58,2
19,3
3,6
8,1 nondiag.
goitre
inflammation
benign tumor
tumor susp./malignant
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Main Tasks
in the Thyroid Histology
diagnosis of all lesions
in malignancies pTNM
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Processing of Thyroid Resecate
orientation
division lobus dx.
isthmus (+lobus pyramidalis) lobus sin.
cutting in cca 3mm thick lamellae
revision and extensive/completeblocking of the encapsulated nodulesperiphery
any suspicious focus for histology
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Benign Thyroid Nodule 1.
Histological
diagnosis
adenomatous
goitre
macrofollicular
adenoma
Cytologic features low cellularity
colloid background
phragments ofmacrofollicules
tct regular small orslightly enlarged
small and middle size
bare nucleioncocytes esp. in
elderly people
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Benign Thyroid Nodule 2.
Histological
diagnosis
adenomatoid
goitre
macrofollicular
adenoma
with regressive
changes
Cytologic features low cellularity
colloid background
phragments ofmacrofollicules
tct regular small orslightly enlarged
small and middle sizebare nuclei
pigmentedmacrophages
oncocytes esp. inelderly people
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Benign Thyroid Nodule 3.
Histologicaldiagnosismicromacrofollicular
goitre
micromacrofollicular
adenoma
cystic transformation(often with signs of older
haemorrhage)
Cytologic features low cellularity
regresively changed
erythrocytes and colloid
macrophages(abundant, pigmented) thyreocytes small or
slightly enlarged
scatterred groups
may be damaged
may be absent
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Folicular Neoplasia
(proliferating microfollicular lesion)
Histological
diagnosis
microfollicular
adenoma
follicular
carcinoma
Cytological features
highly cellular smears few colloid microfollicular
formations thyreocytes regular,
small or slightlyenlarged bare nuclei regressive changes:
mostly absent
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ThyreoiditisNON-SPECIFIC purulent non-specific granulomatose de Quervain lymphocytic (Hashimoto)
hypertrofic
atrofic focal
invasive sclerosing Riedel
SPECIFIC tbc syfilis sarcoidosis
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Non-Specific Granulomatose
Thyreoiditis de Quervain (1904)
Synonyma: Giant cell
Subacute non-purulent Clin.features: Oedema, pain, eufunction,
may be also silent
Histol. features: dispersegranulomaswith giant cells
Course: spontaneous healing by 2-4weeks
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Thyreoiditis lymphoplasmocellularis Hashimoto - HT
Hashimoto, H.:Zur Kenntniss der lymphomatsen
Vernderung der Schilddrse
(struma lymphomatosa)
Arch.f. klin. Chir. 97, 1912, 219
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Original Description of HT
(4 cases)
Macro - goitre
diffuse
parenchymatous
firm elasticgray- yellowish
Micro - inflammation
diffuse
lymphoplasmocellular
folliculesONCOCYTES
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Etiopatogenesis of HT
Etiology: unclear - viri ?
Patogenesis:
dysregulation of T lymphocytes IL-1 expression Fas molecules on the
surface
of thyreocytes (they have FasL) activation
ofapoptosis
Activity: CD44 proteoglycan influencingmigration and lymphocyte proliferation, andmetastasing
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Course of HT
a) progressive
oncocytic transformation
loss of thyreocytes
transformation to a lymph-
node-with-ca- meta image
hyperfunction folowed by
hypofunction
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Course of HT
b) regressive
loss of parenchyma,
fibrosis
hypofunction
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Course of HT
c) neoplasia
carcinoma
lymphoma (mostly B - MALT)
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Oncocytic Tumours
adenoma
architecture follicular, trabecular
cellular atypiae without predictive valuefor biological behaviour
more risky in case of solid architecture
EXCLUDE
ANGIOINVASION, CAPSULOINVASION
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Oncocytic Tumours
carcinoma
oncopapillary (may lack ground glass nuclei ?
oncofollicularmust exhibit
ANGIOINVASION and/or
CAPSULOINVASION (all capsulethickness with extracapsular expansion)
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Oncocytic Tumours- cytology
blood & colloid background, oftensiderophages
groups of oncocytes
well delineated and stained cytoplasm sometimes dark blue cytoplasmic granules
irregular large nucleus, excentric, binucleation
solitary cherry red nucleolus
anisocytosis, anisokaryosis may be striking
no signs of inflammation in the background
no inflammatory cells in the oncocytic groups
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HT - differential diagnosis
HT versus HT + lymphoma
HT versus HT + carcinoma
oncocyticpapillarymedullary
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ThyroidMalignant Lymphomas
less than 2% of primary thyroidmalignancies
most in women withHT
clinically rapid growth, often hypofunction
mostly B (MALT) with lymphoepiteliodlesion features
LG i HG
dif dg. HT
in case of uncertainty dg. excision
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Summary:
interpretation of cytology in some patientswith HT may be very difficult correlation with clinical course especially
important (rapid growth, nodule formation)
extensive histology investigation of resecates
with HT proves coincidence with latent
malignancies in the inflammatory background
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Papillary Carcinoma
- histological variants WHO (2004)
microcarcinoma
(encapsulated)
follicular
macrofollicular
diff. sclerosing
oxyphil cell
clear cell
tall cell
columnar cell
solid
cribriform
with desmopl.stroma (hyal. trabecular ca)
with focal insular component
with squamous ormucoepidermoid ca
with spindle and giantcell ca
combined papillary andmedullary ca
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Papillary Carcinoma
Cytological features
general highly cellular smears
few colloid
waxy colloid, may beabsent
architecture
phragments of papillae groups trabecular
microfollicular syncytial formations
squamous metaplasia
psammomata
NUCLEI
enlarged non - circular
overlapping
grooves pseudoinclusions
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Medullary Carcinoma
origin fom C-cells
clinical forms :
(parafollicular)
sporadic familiar
MEN 2a
MEN 2b
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Medullary Carcinoma
familiar forms
MEN 2a
medullary ca
parathyr. adenoma
pheochromocytoma
MEN 2b
MEDULLARY CA
marfanoid habitus
mucous neuromas
pheochromocytoma
parathyr. adenoma -
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Medullary Carcinoma
Histological
diagnosis
architecturemay mimicany other
thyroid ca!!!(WHO 1988)
Calcitonine + amyloid +-
argyrophilia +
VARIANTS WHO 2004: papillary, glandular- tubular, giant cell, spindle
cell, small cell, paraganglioma-like, oncocytic , clear cell, angiosarcoma-
like, squamous cell, melanin producing, amphicrine
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Medullary Carcinoma
Cytological
types large cell small cell
fusocellular
plasmocytoid
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Medullary Carcinoma
Cytological
features blood background colloid absent (amyloid +-) groups of cells
oncocytoid (granules rose!) plasmocytoid
fusocellular
small round cells
HYPERCHROMATIC NUCLEI(overlapping, oval or spindle shaped)
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highly malignant neoplasm of the old age withrapid progression
origin:
non diag. differentiated ca
hyperplastic goitre
chronic inflammation without preceeding goitre
Undifferentiated Carcinoma
(anaplastic)
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Undifferentiated Carcinoma
Histological variants (often combined)
fusocellular
small cell (?) exclude lymphoma! giant cell (monstrous cells)
squamous metaplasia
composed lmsa, rmsa,osa, chsa, hae, MFH,
classify as carcinoma!
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Undifferentiated Carcinoma
Cytological features
blood background without colloid
isolated and grouped atypical cells
fusiform polygonal giant
striking anisocytosis, anisokaryosis
HYPERCHROMATIC NUCLEI
squamous metaplasia
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Mixed Medullary-Follicular
Carcinomamixture of structures
both components in metastases provable even without meta
(differentiation, ihch, ISH, PCR
co-expression of TGB and Calcitonine)
Two own cases published in:
Acta Cytol 2003; 47 (1):71-7
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Other Types
ofPrimaryThyroid Carcinomas
epidermoid
mucoepidermoid
mixed follicular and mucoepidermoid
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Metastases to theThyroid
kidney
lung
breast
others
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Pitfalls in Thyroid FNAB
combined diagnoses
repair
medullary ca
rare tumours
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The Unified Approach to
Breast Fine NeedleAspiration Biopsy.
A synopsis.
Acta Cytol., 1996, 40, 6, 1120-6
Applicable to the Thyroid FNAB
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Triple test in Thyroid FNAB
clinical symptoms and info
(+laboratory data)ultrasonography
cytology (FNAB)
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What to do?
Listen
to the patients
history
and clin. info BUT
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Considermaterial
limitations bothquantitative and
qualitative
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evaluate
what ISon the slide
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If uncertainty
considering malignancy presencepersists
forASK
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extensive
histological
investigation
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