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ThyroidCytopathology and ItsHistopathological BasesDoc. MUDr. Jaroslava Dušková,CSc,FIAC
Inst. of Pathol. 1st Med. Faculty, Charles Univ. & Chair of Pathol. Inst. of Postgraduate Studies,
Prague, Czech Rep.
Thyroid Gland - embryology and fetal endocrinology
mouth epithelium, end of the 1st iu. month ductus thyreoglosus
lateral pharynx ultimobranchial bodies C- bb. parathyroid glands
fetal secretion starts in 12 weeks effect on GROWTH effect on DIFFERENTIATION
Thyroid Gland - anatomy
Weight in adults 15-20g
over 60g (7g in a neonate) strumalobus dexter
ismus a lobus pyramidalis
lobus sinister
aberant, accesory, ectopic gland (polyclonality should help to tell from ca)
Thyroid Gland - ectopic tissue
„Parasitic“ thyroid nodule Rosai (1990) - mediastinum
Assi (1996) - laterally in the neck
Shimizu et al. (1999) - only for laterally on
the neck localised thyroid tissue without any
relation to the lymph nodes
Main Tasks in the Thyroid Cytology
reduction of the unnecessary surgery
diagnosis & follow-up of subclinical
inflammation
EARLY DIAGNOSIS of NEOPLASMS
Thyroid Cytology getting sample
needle 0.6-0.8mm min. 2 punctions
aspirationnonaspiration – reduction of the blood content
cyst: evacuate and aspirate with the second punction the
periphery fluid: whole volume for cytology
Thyroid Cytology - processing
Fixation air dried etanol / spray
(cytospin)
CYTOBLOCK
Staining: MGG, HE polychrom all histo imunocyto
TGB,calcitonin, parathormon
Thyroid Cytology - diagnostic groups (n20 000)
10,8
58,2
19,3
3,68,1 nondiag.
goitre
inflammation
benign tumor
tumor susp./malignant
Main Tasks
in the Thyroid Histology
diagnosis of all lesions
in malignancies pTNM
Processing of Thyroid Resecate orientation division
– lobus dx.– isthmus (+lobus pyramidalis)– lobus sin.
cutting in cca 3mm thick lamellae– revision and extensive/complete blocking of
the encapsulated nodules periphery– any suspicious focus for histology
Benign Thyroid Nodule 1.
Histological diagnosis
– adenomatous goitre
– macrofollicularadenoma
Cytologic features– low cellularity– colloid background– phragments of
macrofollicules tct regular small or
slightly enlargedsmall and middle size
bare nucleioncocytes esp. in
elderly people
Benign Thyroid Nodule 2.
Histological diagnosis
– adenomatoid goitre
– macrofollicular adenoma
with regressive changes
Cytologic features– low cellularity– colloid background– phragments of
macrofollicules tct regular small or
slightly enlargedsmall and middle size
bare nucleipigmented
macrophagesoncocytes esp. in
elderly people
Benign Thyroid Nodule 3.Histological diagnosis micromacrofollicular
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 groupsmay be damagedmay be absent
Folicular Neoplasia (proliferating microfollicular lesion)
Histological diagnosis
– microfollicular adenoma
– follicular carcinoma
Cytological features
highly cellular smears– few colloid– microfollicular
formations– thyreocytes regular,
small or slightly enlarged
– bare nuclei– regressive changes:
mostly absent
ThyreoiditisNON-SPECIFIC purulent non-specific granulomatose de Quervain lymphocytic (Hashimoto)
hypertrofic atrofic focal
invasive sclerosing Riedel
SPECIFIC tbc syfilis sarcoidosis
Non-Specific Granulomatose Thyreoiditis de Quervain (1904)
Synonyma: „Giant cell“ „Subacute non-purulent“
Clin.features: Oedema, pain, eufunction, may be also silent
Histol. features: disperse granulomas with giant cells
Course: spontaneous healing by 2-4 weeks
Thyreoiditis lymphoplasmocellularis Hashimoto - HT
Hashimoto, H.:Zur Kenntniss der lymphomatösen Veränderung der Schilddrüse
(struma lymphomatosa)
Arch.f. klin. Chir. 97, 1912, 219
Original Description of HT (4 cases)
Macro - goitre
diffuse
parenchymatous
firm elastic
gray- yellowish
Micro - inflammation
diffuse
lymphoplasmocellular
follicules
ONCOCYTES
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 of apoptosis
Activity: CD44 proteoglycan influencing migration and lymphocyte proliferation, and metastasing
Course of HTa) progressive
oncocytic transformation loss of thyreocytes
transformation to a lymph- node-with-ca- meta
image hyperfunction folowed by
hypofunction
Course of HT
b) regressive loss of parenchyma,
fibrosis
hypofunction
Course of HT
c) neoplasia
carcinoma
lymphoma (mostly B - MALT)
Oncocytic Tumours
adenoma– architecture follicular, trabecular– cellular atypiae without predictive value
for biological behaviour– more risky in case of solid architecture
EXCLUDE
ANGIOINVASION, CAPSULOINVASION
Oncocytic Tumours
carcinoma– oncopapillary (may lack ground glass nuclei ?
– oncofollicular
must exhibit
ANGIOINVASION and/or
CAPSULOINVASION (all capsule thickness with extracapsular expansion)
Oncocytic Tumours - cytology blood & colloid background, often siderophages 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
HT - differential diagnosis
HT versus HT + lymphoma
HT versus HT + carcinoma oncocytic papillary
medullary
Thyroid Malignant Lymphomas
less than 2% of primary thyroid malignancies
most in women with HT clinically rapid growth, often hypofunction mostly B (MALT) with lymphoepiteliod
lesion features LG i HG dif dg. HT in case of uncertainty dg. excision
Summary: interpretation of cytology in some patients
with 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
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 or
mucoepidermoid ca with spindle and giant
cell ca combined papillary and
medullary ca
Papillary CarcinomaCytological featuresgeneral
highly cellular smears few colloid waxy colloid, may be
absent
architecture phragments of papillae groups trabecular microfollicular syncytial formations squamous
metaplasia psammomata
NUCLEI
enlarged non - circular overlapping grooves pseudoinclusions
Medullary Carcinoma
origin fom C-cells
clinical forms :
(parafollicular)
sporadic familiar
– MEN 2a
– MEN 2b
Medullary Carcinoma familiar forms
MEN 2a medullary ca parathyr. adenoma pheochromocytoma
MEN 2b MEDULLARY CA marfanoid habitus mucous neuromas pheochromocytoma parathyr. adenoma -
Medullary Carcinoma
Histological diagnosis
architecture may mimic any 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…
Medullary Carcinoma
Cytological types
large cell
small cell
fusocellular
plasmocytoid
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)
highly malignant neoplasm of the old age with rapid progression origin:
non diag. differentiated ca hyperplastic goitre chronic inflammation without preceeding goitre
Undifferentiated Carcinoma(anaplastic)
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!
Undifferentiated Carcinoma
Cytological features blood background without colloid isolated and grouped atypical cells
– fusiform– polygonal– giant
striking anisocytosis, anisokaryosis HYPERCHROMATIC NUCLEI squamous metaplasia
Mixed Medullary-Follicular Carcinoma
mixture 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
Other Types of PrimaryThyroid Carcinomas
epidermoid mucoepidermoid mixed follicular and mucoepidermoid
Metastases to theThyroid
kidney lung breast others
Pitfalls in Thyroid FNAB
combined diagnoses repair medullary ca rare tumours
The Unified Approach to Breast Fine Needle Aspiration Biopsy. A synopsis.
Acta Cytol., 1996, 40, 6, 1120-6
Applicable to the Thyroid FNAB
Triple test in Thyroid FNAB
clinical symptoms and info
(+laboratory data)
ultrasonography
cytology (FNAB)
What to do?
Listen to the patient´s history and clin. info BUT
Consider material limitations both quantitative and
qualitative
evaluate what IS on the slide
If uncertaintyconsidering malignancy presence persists
forASK
extensive histological
investigation