Thyroid Cytopathology and Its Histopathological Bases

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  • Warton počítá št. žlázu mezi slinné zajišťující vlhkos laryngu.
  • Warton počítá št. žlázu mezi slinné zajišťující vlhkos laryngu.
  • Warton počítá št. žlázu mezi slinné zajišťující vlhkos laryngu.
  • Warton počítá št. žlázu mezi slinné zajišťující vlhkos laryngu.
  • Warton počítá št. žlázu mezi slinné zajišťující vlhkos laryngu.
  • Warton počítá št. žlázu mezi slinné zajišťující vlhkos laryngu.
  • Warton počítá št. žlázu mezi slinné zajišťující vlhkos laryngu.
  • Warton počítá št. žlázu mezi slinné zajišťující vlhkos laryngu.
  • Warton počítá št. žlázu mezi slinné zajišťující vlhkost laryngu.
  • Warton počítá št. žlázu mezi slinné zajišťující vlhkost laryngu.
  • Thyroid Cytopathology and Its Histopathological Bases

    1. 1. Thyroid Cytopathology and Its Histopathological Bases <ul><li>Doc. MUDr. Jaroslava Dušková,CSc,FIAC </li></ul><ul><li>Inst. of Pathol. 1st Med. Faculty, Charles Univ. & Chair of Pathol. Inst. of Postgraduate Studies , </li></ul><ul><li>Prague, Czech Rep. </li></ul>
    2. 2. Thyroid Gland - embryology and fetal endocrinology <ul><ul><li>mouth epithelium, end of the 1 st iu. month  ductus thyreoglosus </li></ul></ul><ul><ul><li>lateral pharynx </li></ul></ul><ul><ul><ul><li>ultimobranchial bodies  C- bb. </li></ul></ul></ul><ul><ul><ul><li>parathyroid glands </li></ul></ul></ul><ul><ul><li>fetal secretion starts in 12 weeks </li></ul></ul><ul><ul><ul><li>effect on GROWTH </li></ul></ul></ul><ul><ul><ul><li>effect on DIFFERENTIATION </li></ul></ul></ul>
    3. 3. Thyroid Gland - anatomy <ul><li>Weight in adults 15-20g </li></ul><ul><li>over 60g (7g in a neonate) struma </li></ul><ul><ul><li>lobus dexter </li></ul></ul><ul><ul><li>ismus a lobus pyramidalis </li></ul></ul><ul><ul><li>lobus sinister </li></ul></ul><ul><ul><li>aberant, accesory , ectopic gland </li></ul></ul><ul><ul><ul><li> (polyclonality should help to tell from ca) </li></ul></ul></ul>
    4. 4. Thyroid Gland - ectopic tissue <ul><ul><li>„ Parasitic “ thyroid nodule </li></ul></ul><ul><ul><ul><li>Rosai (1990) - mediastinum </li></ul></ul></ul><ul><ul><ul><li>Assi (1996) - laterally in the neck </li></ul></ul></ul><ul><ul><ul><li>Shimizu et al. (1999) - only for laterally on the neck localised thyroid tissue without any relation to the lymph nodes </li></ul></ul></ul>
    5. 5. Main Tasks in the Thyroid Cytology <ul><li>reduction of the unnecessary surgery </li></ul><ul><li>diagnosis & follow-up of subclinical inflammation </li></ul><ul><li>EARLY DIAGNOSIS of NEOPLASMS </li></ul>
    6. 6. Thyroid Cytology getting sample <ul><li>needle 0.6-0.8mm </li></ul><ul><li>min. 2 punctions </li></ul><ul><ul><ul><li>aspiration </li></ul></ul></ul><ul><ul><ul><li>nonaspiration – reduction of the blood content </li></ul></ul></ul><ul><li>cyst: evacuate and aspirate with the second punction the periphery </li></ul><ul><li>fluid: whole volume for cytology </li></ul>
    7. 7. Thyroid Cytology - processing <ul><li>Fixation </li></ul><ul><ul><li> air dried </li></ul></ul><ul><ul><li> etanol / spray </li></ul></ul><ul><li>(cytospin) </li></ul><ul><li>CYTOBLOCK </li></ul><ul><li>Staining: </li></ul><ul><li>MGG, HE </li></ul><ul><li>polychrom </li></ul><ul><li>all histo </li></ul><ul><li>imunocyto </li></ul><ul><ul><ul><li>TGB,calcitonin, parathormon </li></ul></ul></ul>
    8. 8. Thyroid Cytology - diagnostic groups (n  20 000)
    9. 9. Main Tasks in the Thyroid Histology <ul><li>diagnosis of all lesions </li></ul><ul><li>in malignancies pTNM </li></ul>
    10. 10. Processing of Thyroid Resecate <ul><li>orientation </li></ul><ul><li>division </li></ul><ul><ul><li>lobus dx. </li></ul></ul><ul><ul><li>isthmus (+lobus pyramidalis) </li></ul></ul><ul><ul><li>lobus sin. </li></ul></ul><ul><li>cutting in cca 3mm thick lamellae </li></ul><ul><ul><li>revision and extensive/complete blocking of the encapsulated nodules periphery </li></ul></ul><ul><ul><li>any suspicious focus for histology </li></ul></ul>
    11. 11. Benign Thyroid Nodule 1. <ul><li>Histological diagnosis </li></ul><ul><ul><li>adenomatous goitre </li></ul></ul><ul><ul><li>macrofollicularadenoma </li></ul></ul><ul><li>Cytologic features </li></ul><ul><ul><li>low cellularity </li></ul></ul><ul><ul><li>colloid background </li></ul></ul><ul><ul><li>phragments of macrofollicules </li></ul></ul><ul><ul><ul><li>tct regular small or slightly enlarged </li></ul></ul></ul><ul><ul><ul><li>small and middle size bare nuclei </li></ul></ul></ul><ul><ul><ul><li>oncocytes esp. in elderly people </li></ul></ul></ul>
    12. 12. Benign Thyroid Nodule 2. <ul><li>Histological diagnosis </li></ul><ul><ul><li>adenomatoid goitre </li></ul></ul><ul><ul><li>macrofollicular adenoma </li></ul></ul><ul><li>with regressive changes </li></ul><ul><li>Cytologic features </li></ul><ul><ul><li>low cellularity </li></ul></ul><ul><ul><li>colloid background </li></ul></ul><ul><ul><li>phragments of macrofollicules </li></ul></ul><ul><ul><ul><li>tct regular small or slightly enlarged </li></ul></ul></ul><ul><ul><ul><li>small and middle size bare nuclei </li></ul></ul></ul><ul><ul><ul><li>pigmented macrophages </li></ul></ul></ul><ul><ul><ul><li>oncocytes esp. in elderly people </li></ul></ul></ul>
    13. 13. Benign Thyroid Nodule 3. <ul><li>Histological diagnosis </li></ul><ul><li>micromacrofollicular goitre </li></ul><ul><li>micromacrofollicular adenoma </li></ul><ul><li>cystic transformation (often with signs of older haemorrhage) </li></ul><ul><li>Cytologic features </li></ul><ul><ul><li>low cellularity </li></ul></ul><ul><ul><li>regresively changed erythrocytes and colloid </li></ul></ul><ul><ul><li>macrophages </li></ul></ul><ul><ul><li>(abundant, pigmented) </li></ul></ul><ul><ul><li>thyreocytes small or slightly enlarged </li></ul></ul><ul><ul><ul><li>scatterred groups </li></ul></ul></ul><ul><ul><ul><li>may be damaged </li></ul></ul></ul><ul><ul><ul><li>may be absent </li></ul></ul></ul>
    14. 14. Folicular Neoplasia (proliferating microfollicular lesion) <ul><li>Histological diagnosis </li></ul><ul><ul><li>microfollicular adenoma </li></ul></ul><ul><ul><li>follicular carcinoma </li></ul></ul><ul><li>Cytological features </li></ul><ul><li>highly cellular smears </li></ul><ul><ul><li>few colloid </li></ul></ul><ul><ul><li>microfollicular formations </li></ul></ul><ul><ul><li>thyreocytes regular, small or slightly enlarged </li></ul></ul><ul><ul><li>bare nuclei </li></ul></ul><ul><ul><li>regressive changes: </li></ul></ul><ul><ul><li>mostly absent </li></ul></ul>
    15. 15. Thyreoiditis <ul><li>NON-SPECIFIC </li></ul><ul><li>purulent </li></ul><ul><li>non-specific granulomatose de Quervain </li></ul><ul><li>lymphocytic (Hashimoto) </li></ul><ul><ul><ul><li>hypertrofic </li></ul></ul></ul><ul><ul><ul><li>atrofic </li></ul></ul></ul><ul><ul><ul><li>focal </li></ul></ul></ul><ul><li>invasive sclerosing Riedel </li></ul><ul><li>SPECIFIC </li></ul><ul><li>tbc </li></ul><ul><li>syfilis </li></ul><ul><li>sarcoidosis </li></ul>
    16. 16. Non-Specific Granulomatose Thyreoiditis de Quervain (1904) <ul><li>Synonyma: „ Giant cell“ </li></ul><ul><li> „Subacute non-purulent“ </li></ul><ul><li>Clin.features: Oedema, pain, eufunction, may be also silent </li></ul><ul><li>Histol. features: disperse granulomas </li></ul><ul><li> with giant cells </li></ul><ul><li>Course: spontaneous healing by 2-4 weeks </li></ul>
    17. 17. Thyreoiditis lymphoplasmocellularis Hashimoto - HT Hashimoto, H.: <ul><li>Zur Kenntniss der lymphomatösen Veränderung der Schilddrüse </li></ul><ul><li>(struma lymphomatosa) </li></ul><ul><li>Arch.f. klin. Chir. 97, 1912, 219 </li></ul>
    18. 18. Original Description of HT (4 cases) <ul><li>Macro - goitre </li></ul><ul><li>diffuse </li></ul><ul><li>parenchymatous </li></ul><ul><li>firm elastic </li></ul><ul><li>gray- yellowish </li></ul><ul><li>Micro - inflammation </li></ul><ul><li>diffuse </li></ul><ul><li>lymphoplasmocellular </li></ul><ul><li>follicules </li></ul><ul><li>ONCOCYTES </li></ul>
    19. 19. Etiopatogenesis of HT <ul><li>Etiology: unclear - viri ? </li></ul><ul><li>Patogenesis: </li></ul><ul><ul><ul><li>dysregulation of T lymphocytes </li></ul></ul></ul><ul><ul><ul><li>IL-1  expression Fas molecules on the surface </li></ul></ul></ul><ul><ul><ul><li>of thyreocytes (they have FasL)  activation of apoptosis </li></ul></ul></ul><ul><li>Activity: CD44 proteoglycan influencing migration and lymphocyte proliferation, and metastasing </li></ul>
    20. 20. Course of HT <ul><li>a) progressive </li></ul><ul><ul><ul><ul><li>oncocytic transformation loss of thyreocytes </li></ul></ul></ul></ul><ul><ul><ul><ul><li>transformation to a lymph- node-with-ca- meta image </li></ul></ul></ul></ul><ul><ul><ul><ul><li>hyperfunction folowed by hypofunction </li></ul></ul></ul></ul>
    21. 21. Course of HT <ul><li>b) regressive </li></ul><ul><ul><ul><li>loss of parenchyma, </li></ul></ul></ul><ul><ul><ul><li>fibrosis </li></ul></ul></ul><ul><ul><ul><li>hypofunction </li></ul></ul></ul>
    22. 22. Course of HT <ul><li>c) neoplasia </li></ul><ul><ul><ul><li>carcinoma </li></ul></ul></ul><ul><ul><ul><li>lymphoma (mostly B - MALT) </li></ul></ul></ul>
    23. 23. Oncocytic Tumours <ul><li>adenoma </li></ul><ul><ul><li>architecture follicular, trabecular </li></ul></ul><ul><ul><li>cellular atypiae without predictive value for biological behaviour </li></ul></ul><ul><ul><li>more risky in case of solid architecture </li></ul></ul><ul><li>EXCLUDE </li></ul><ul><li> ANGIOINVASION, CAPSULOINVASION </li></ul>
    24. 24. Oncocytic Tumours <ul><li>carcinoma </li></ul><ul><ul><li>oncopapillary (may lack ground glass nuclei ? </li></ul></ul><ul><ul><li>oncofollicular </li></ul></ul><ul><li>must exhibit </li></ul><ul><li> ANGIOINVASION and/or </li></ul><ul><li>CAPSULOINVASION (all capsule thickness with extracapsular expansion) </li></ul>
    25. 25. Oncocytic Tumours - cytology <ul><li>blood & c olloid background, often siderophages </li></ul><ul><li>groups of oncocytes </li></ul><ul><ul><li>well delineated and stained cytoplasm </li></ul></ul><ul><ul><li>sometimes dark blue cytoplasmic granules </li></ul></ul><ul><ul><li>irregular large nucleus, excentric, binucleation </li></ul></ul><ul><ul><li>solitary „cherry red“ nucleolus </li></ul></ul><ul><ul><li>anisocytosis, anisokaryosis may be striking </li></ul></ul><ul><li>no signs of inflammation in the background </li></ul><ul><li>no inflammatory cells in the oncocytic groups </li></ul>
    26. 26. HT - differential diagnosis <ul><li>HT versus HT + lymphoma </li></ul><ul><li>HT versus HT + carcinoma </li></ul><ul><li> oncocytic </li></ul><ul><li> papillary </li></ul><ul><li> medullary </li></ul>
    27. 27. Thyroid Malignant Lymphomas <ul><li>less than 2% of primary thyroid malignancies </li></ul><ul><li>most in women with HT </li></ul><ul><li>clinically rapid growth, often hypofunction </li></ul><ul><li>mostly B (MALT) with lymphoepiteliod lesion features </li></ul><ul><li>LG i HG </li></ul><ul><li>dif dg. HT </li></ul><ul><li>in case of uncertainty dg. excision </li></ul>
    28. 28. Summary: <ul><li>interpretation of cytology in some patients with HT may be very difficult </li></ul><ul><li>correlation with clinical course especially important (rapid growth, nodule formation) </li></ul><ul><li>extensive histology investigation of resecates with HT proves coincidence with latent malignancies in the inflammatory background </li></ul>
    29. 29. Papillary Carcinoma - histological variants WHO (2004) <ul><ul><li>microcarcinoma </li></ul></ul><ul><ul><ul><li>(encapsulated) </li></ul></ul></ul><ul><ul><li>follicular </li></ul></ul><ul><ul><li>macrofollicular </li></ul></ul><ul><ul><li>diff. sclerosing </li></ul></ul><ul><ul><li>oxyphil cell </li></ul></ul><ul><ul><li>clear cell </li></ul></ul><ul><ul><li>tall cell </li></ul></ul><ul><ul><li>columnar cell </li></ul></ul><ul><ul><li>solid </li></ul></ul><ul><ul><li>cribriform </li></ul></ul><ul><ul><li>with desmopl.stroma </li></ul></ul><ul><ul><ul><li>(hyal. trabecular ca) </li></ul></ul></ul><ul><ul><li>with focal insular component </li></ul></ul><ul><ul><li>with squamous or mucoepidermoid ca </li></ul></ul><ul><ul><li>with spindle and giant cell ca </li></ul></ul><ul><ul><li>combined papillary and medullary ca </li></ul></ul>
    30. 30. Papillary Carcinoma <ul><li>Cytological features </li></ul><ul><li>general </li></ul><ul><ul><li>highly cellular smears </li></ul></ul><ul><ul><li>few colloid </li></ul></ul><ul><ul><li>waxy colloid, may be absent </li></ul></ul><ul><li>architecture </li></ul><ul><ul><li>phragments of papillae </li></ul></ul><ul><ul><li>groups trabecular </li></ul></ul><ul><ul><li>microfollicular </li></ul></ul><ul><ul><li>syncytial formations </li></ul></ul><ul><ul><li>squamous metaplasia </li></ul></ul><ul><ul><li>psammomata </li></ul></ul><ul><li>NUCLEI </li></ul><ul><li>enlarged </li></ul><ul><li>non - circular </li></ul><ul><li>overlapping </li></ul><ul><li>grooves </li></ul><ul><li>pseudoinclusions </li></ul>
    31. 31. Medullary Carcinoma <ul><li>origin fom C-cells </li></ul><ul><li>clinical forms : </li></ul><ul><li>(parafollicular) </li></ul><ul><li>sporadic </li></ul><ul><li>familiar </li></ul><ul><ul><li>MEN 2a </li></ul></ul><ul><ul><li>MEN 2b </li></ul></ul>
    32. 32. Medullary Carcinoma familiar forms <ul><li>MEN 2a </li></ul><ul><li>medullary ca </li></ul><ul><li>parathyr. adenoma </li></ul><ul><li>pheochromocytoma </li></ul><ul><ul><li>MEN 2b </li></ul></ul><ul><li>MEDULLARY CA </li></ul><ul><li>marfanoid habitus </li></ul><ul><li>mucous neuromas </li></ul><ul><li>pheochromocytoma </li></ul><ul><li>parathyr. adenoma - </li></ul>
    33. 33. Medullary Carcinoma <ul><li>Histological diagnosis </li></ul><ul><li>architecture may mimic any other </li></ul><ul><li>thyroid ca!!! </li></ul><ul><li>(WHO 1988) </li></ul><ul><li>Calcitonine + </li></ul><ul><li>amyloid +- </li></ul><ul><li>argyrophilia + </li></ul>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. 34. Medullary Carcinoma <ul><li>Cytological types </li></ul><ul><li>large cell </li></ul><ul><li>small cell </li></ul><ul><li>fusocellular </li></ul><ul><li>plasmocytoid </li></ul>
    35. 35. Medullary Carcinoma <ul><li>Cytological features </li></ul><ul><li>blood background </li></ul><ul><li>colloid absent (amyloid +-) </li></ul><ul><li>groups of cells </li></ul><ul><ul><li>oncocytoid (granules rose!) </li></ul></ul><ul><ul><li>plasmocytoid </li></ul></ul><ul><ul><li>fusocellular </li></ul></ul><ul><ul><li>small round cells </li></ul></ul><ul><ul><li>HYPERCHROMATIC NUCLEI </li></ul></ul><ul><li>(overlapping, oval or spindle shaped) </li></ul>
    36. 36. <ul><li>highly malignant neoplasm of the old age with rapid progression </li></ul><ul><li>origin: </li></ul><ul><ul><ul><li>non diag. differentiated ca </li></ul></ul></ul><ul><ul><ul><li>hyperplastic goitre </li></ul></ul></ul><ul><ul><ul><li>chronic inflammation </li></ul></ul></ul><ul><ul><ul><li>without preceeding goitre </li></ul></ul></ul>Undifferentiated Carcinoma (anaplastic)
    37. 37. Undifferentiated Carcinoma <ul><li>Histological variants (often combined) </li></ul><ul><li>fusocellular </li></ul><ul><li>small cell (?) exclude lymphoma! </li></ul><ul><li>giant cell (monstrous cells) </li></ul><ul><li>squamous metaplasia </li></ul><ul><li>composed </li></ul><ul><ul><ul><li>lmsa, rmsa,osa, chsa, hae, MFH, </li></ul></ul></ul><ul><ul><li>classify as carcinoma! </li></ul></ul>
    38. 38. Undifferentiated Carcinoma <ul><li>Cytological features </li></ul><ul><li>blood background without colloid </li></ul><ul><li>isolated and grouped atypical cells </li></ul><ul><ul><li>fusiform </li></ul></ul><ul><ul><li>polygonal </li></ul></ul><ul><ul><li>giant </li></ul></ul><ul><li>striking anisocytosis, anisokaryosis </li></ul><ul><li>HYPERCHROMATIC NUCLEI </li></ul><ul><li>squamous metaplasia </li></ul>
    39. 39. Mixed Medullary-Follicular Carcinoma <ul><li>mixture of structures </li></ul><ul><li>both components in metastases </li></ul><ul><li>provable even without meta (differentiation, ihch, ISH, PCR </li></ul><ul><li>co-expression of TGB and Calcitonine) </li></ul>Two own cases published in: Acta Cytol 2003; 47 (1):71-7
    40. 40. Other Types of PrimaryThyroid Carcinomas <ul><li>epidermoid </li></ul><ul><li>mucoepidermoid </li></ul><ul><li>mixed follicular and mucoepidermoid </li></ul>
    41. 41. Metastases to theThyroid <ul><li>kidney </li></ul><ul><li>lung </li></ul><ul><li>breast </li></ul><ul><li>others </li></ul>
    42. 42. Pitfalls in Thyroid FNAB <ul><li>combined diagnoses </li></ul><ul><li>repair </li></ul><ul><li>medullary ca </li></ul><ul><li>rare tumours </li></ul>
    43. 43. The Unified Approach to Breast Fine Needle Aspiration Biopsy. A synopsis. <ul><ul><ul><li>Acta Cytol., 1996, 40, 6, 1120-6 </li></ul></ul></ul>Applicable to the Thyroid FNAB
    44. 44. Triple test in Thyroid FNAB <ul><li>clinical symptoms and info </li></ul><ul><ul><ul><ul><ul><li> (+laboratory data) </li></ul></ul></ul></ul></ul><ul><li>ultrasonography </li></ul><ul><li>cytology (FNAB) </li></ul>
    45. 45. What to do? Listen to the patient´s history and clin. info BUT
    46. 46. Consider material limitations both quantitative and qualitative
    47. 47. evaluate what IS on the slide
    48. 48. If uncertainty considering malignancy presence persists for ASK
    49. 49. extensive histological investigation

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