Thyroid Cytopathology and Its Histopathological Bases

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ThyroidCytopathology and ItsHistopathological
Bases

• Doc. MUDr. Jaroslava Duková,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.
  month? ductus thyreoglosus
• lateral pharynx
• ultimobranchial bodies ? C- 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
• over 60g (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) - only for laterally on
  the neck localised thyroid tissue without any
  relation 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 punctions
• aspiration
• nonaspiration reduction of the blood content
• cyst evacuate and aspirate with the second
  punction the periphery
• fluid whole volume for cytology

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Thyroid Cytology - processing

• Staining
• MGG, HE
• polychrom
• all histo
• imunocyto
• TGB,calcitonin, parathormon

• Fixation
• air dried
• etanol / spray
• (cytospin)
• CYTOBLOCK

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Thyroid Cytology - diagnostic groups
(n?20 000)
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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/complete blocking of the
  encapsulated nodules periphery
• any suspicious focus for histology

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Benign Thyroid Nodule 1.

• Histological diagnosis
• adenomatous goitre
• macrofollicularadenoma

• Cytologic features
• low cellularity
• colloid background
• phragments of macrofollicules
• tct regular small or slightly enlarged
• small and middle size bare nuclei
• oncocytes 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 of macrofollicules
• tct regular small or slightly enlarged
• small and middle size bare nuclei
• pigmented macrophages
• oncocytes esp. in elderly people

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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 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 slightly enlarged
• bare nuclei
• regressive changes
• mostly absent

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Thyreoiditis

• NON-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 disperse granulomas
• with giant cells
• Course spontaneous healing by 2-4
  weeks

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Thyreoiditis lymphoplasmocellularis Hashimoto -
HTHashimoto, H.

• Zur Kenntniss der lymphomatösen Veränderung der
  Schilddrüse
• (struma lymphomatosa)
• Arch.f. klin. Chir. 97, 1912, 219

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Original Description of HT (4
cases)

• Micro - inflammation
• diffuse
• lymphoplasmocellular
• follicules
• ONCOCYTES

• Macro - goitre
• diffuse
• parenchymatous
• firm elastic
• gray- yellowish

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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 of apoptosis
• Activity CD44 proteoglycan influencing
  migration and lymphocyte proliferation, and
  metastasing

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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 value
  for 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 ?
• oncofollicular
• must exhibit
• ANGIOINVASION and/or
• CAPSULOINVASION (all capsule thickness
  with extracapsular expansion)

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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

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HT - differential diagnosis

• HT versus HT lymphoma
• HT versus HT carcinoma
• oncocytic
• papillary
• medullary

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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

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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

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Papillary Carcinoma - histological variants WHO
(2004)

• 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

• microcarcinoma
• (encapsulated)
• follicular
• macrofollicular
• diff. sclerosing
• oxyphil cell
• clear cell
• tall cell
• columnar cell

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Papillary Carcinoma

• Cytological features
• general
• 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

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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
• 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
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Medullary Carcinoma

• large cell
• small cell
• fusocellular
• plasmocytoid

• Cytological types

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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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Undifferentiated Carcinoma (anaplastic)

• highly malignant neoplasm of the old age with
  rapid progression
• origin
• non diag. differentiated ca
• hyperplastic goitre
• chronic inflammation
• without preceeding goitre

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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 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
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Other Types of PrimaryThyroid 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 Needle
Aspiration 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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Consider material limitations both quantitative
and qualitative
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evaluate what IS on the slide
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If uncertaintyconsidering malignancy presence
persists
ASK
for
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extensive histological investigation