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