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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