Thyroid Cytopathology and Its Histopathological Bases

1. ThyroidCytopathology and ItsHistopathologicalBases • Doc. MUDr. Jaroslava Dušková,CSc,FIAC • Inst. of Pathol. 1st Med. Faculty, Charles Univ. & Chair of Pathol. Inst. of Postgraduate Studies, • Prague, Czech Rep.

2. 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

3. 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)

4. 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

5. Main Tasks in the Thyroid Cytology • reduction of the unnecessary surgery • diagnosis & follow-up of subclinical inflammation • EARLY DIAGNOSIS of NEOPLASMS

6. 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: wholevolume for cytology

7. Fixation air dried etanol / spray (cytospin) CYTOBLOCK Staining: MGG, HE polychrom all histo imunocyto TGB,calcitonin, parathormon Thyroid Cytology- processing

8. Thyroid Cytology - diagnostic groups(n20 000)

9. Main Tasksin the Thyroid Histology • diagnosis of all lesions • in malignancies pTNM

10. 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

11. 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 Benign Thyroid Nodule 1.

12. 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 Benign Thyroid Nodule 2.

13. 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 Benign Thyroid Nodule 3.

14. 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 Folicular Neoplasia (proliferating microfollicular lesion)

15. Thyreoiditis • NON-SPECIFIC • purulent • non-specific granulomatose de Quervain • lymphocytic (Hashimoto) • hypertrofic • atrofic • focal • invasive sclerosing Riedel • SPECIFIC • tbc • syfilis • sarcoidosis

16. Non-Specific Granulomatose Thyreoiditis de Quervain (1904) • Synonyma: „Giant cell“ • „Subacute non-purulent“ • Clin.features: Oedema, pain, eufunction, may be also silent • Histol. features: dispersegranulomas • with giant cells • Course: spontaneous healing by 2-4 weeks

17. Thyreoiditis lymphoplasmocellularis Hashimoto - HTHashimoto, H.: • Zur Kenntniss der lymphomatösen Veränderung der Schilddrüse • (struma lymphomatosa) • Arch.f. klin. Chir. 97, 1912, 219

18. Macro - goitre diffuse parenchymatous firm elastic gray- yellowish Micro - inflammation diffuse lymphoplasmocellular follicules ONCOCYTES Original Description of HT (4 cases)

19. 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

20. Course of HT a) progressive • oncocytic transformation loss of thyreocytes • transformation to a lymph- node-with-ca- meta image • hyperfunction folowed by hypofunction

21. Course of HT b) regressive • loss of parenchyma, • fibrosis • hypofunction

22. Course of HT c) neoplasia • carcinoma • lymphoma (mostly B - MALT)

23. Oncocytic Tumours • adenoma • architecture follicular, trabecular • cellular atypiae without predictive value for biological behaviour • more risky in case of solid architecture • EXCLUDE • ANGIOINVASION, CAPSULOINVASION

24. Oncocytic Tumours • carcinoma • oncopapillary (may lack ground glass nuclei ? • oncofollicular • must exhibit • ANGIOINVASION and/or • CAPSULOINVASION (all capsule thickness with extracapsular expansion)

25. 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

26. HT - differential diagnosis • HT versusHT + lymphoma • HT versusHT + carcinoma • oncocytic • papillary • medullary

27. ThyroidMalignant Lymphomas • less than 2% of primary thyroid malignancies • most in women withHT • clinically rapid growth, often hypofunction • mostly B (MALT) with lymphoepiteliod lesion features • LG i HG • dif dg. HT • in case of uncertainty dg. excision

28. 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

29. 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 Carcinoma- histological variants WHO (2004)

30. 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 Papillary Carcinoma

31. origin fom C-cells clinical forms : (parafollicular) sporadic familiar MEN 2a MEN 2b Medullary Carcinoma

32. MEN 2a medullary ca parathyr. adenoma pheochromocytoma MEN 2b MEDULLARY CA marfanoid habitus mucous neuromas pheochromocytoma parathyr. adenoma - Medullary Carcinoma familiar forms

33. Histological diagnosis architecture may mimic any other thyroid ca!!! (WHO 1988) Calcitonine + amyloid +- argyrophilia + Medullary Carcinoma VARIANTS – WHO 2004: papillary, glandular- tubular, giant cell, spindle cell, small cell, paraganglioma-like, oncocytic , clear cell, angiosarcoma-like, squamous cell, melanin producing, amphicrine…

34. Cytological types large cell small cell fusocellular plasmocytoid Medullary Carcinoma

35. 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) Medullary Carcinoma

36. 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)

37. 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!

38. Cytological features blood background without colloid isolated and grouped atypical cells fusiform polygonal giant striking anisocytosis, anisokaryosis HYPERCHROMATIC NUCLEI squamous metaplasia Undifferentiated Carcinoma

39. 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

40. Other Types of PrimaryThyroid Carcinomas • epidermoid • mucoepidermoid • mixed follicular and mucoepidermoid

41. Metastases to theThyroid • kidney • lung • breast • others

42. Pitfalls in Thyroid FNAB • combined diagnoses • repair • medullary ca • rare tumours

43. The Unified Approach to Breast Fine Needle Aspiration Biopsy. A synopsis. Acta Cytol., 1996, 40, 6, 1120-6 Applicable to the Thyroid FNAB

44. Triple test in Thyroid FNAB clinical symptoms and info (+laboratory data) ultrasonography cytology (FNAB)

45. What to do? Listen to the patient´s history and clin. info BUT

46. Consider materiallimitations both quantitative and qualitative

47. evaluate what IS on the slide

48. If uncertaintyconsidering malignancy presence persists ASK for

49. extensive histological investigation