Introduction to breast FNAC. Torill Sauer, Department of Pathology, Akershus University Hospitak

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1 Introduction to breast FNAC 1

2 Goal of FNAC of breast lesions Confirm benign clinical and radiological findings in order to avoid unnecessary surgery Confirm a clinical and/or radiological malignant lesion in order to allow definitive surgery

3 FNAC CNB Needle size (0.6) mm internal diameter Needle size > 1 mm internal diameter

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5 Microscopic assessment FNAC Amount of cell material pattern of the smear Grading (mainly by nuclear criteria) Subtyping Indirect signs of invasion evt extracellular material as mucin Stromal fragments Necrosis Microcalcifications Mitoses CNB Growth pattern (solid, tubular, indian file, cribriform) Grading (percentage tubular growth, nuclear atypia, mitoses) Subtyping Direct evaluation of invasiveness Extracellular material Necrosis Microcalcifications

6 FNAC diagnostics A diagnosis of breast carcinoma on fine needle aspiration (FNAC) is based on a number of cytological features. The pattern of the smear consists of: growth pattern tubular papillary micropapillary cribriform cell dissociation pattern arrangement of cells in clusters, sheets and aggregates an eventual component of extracellular material may give information about the tumor subtype.

7 FNAC diagnostics A general evaluation of the cellular pleomorphism is important. The nuclear criteria are critical and we carefully evaluate nuclear size irregularities of the nuclear margin chromatin pattern nucleoli

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9 Multidisciplinary work-up (triple diagnostics) Spiculating tumor ςρικθι in the milky way black star distortion рҗљ in oblique view assymetry

10 ROSE

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12 Multidisciplinary meeting

13 Patient management (screening and symptomatic) benign FNAC - probably benign mx and US = back to screening/local surgery benign FNAC - eqiovocal/suspicious mx and/or US = diagnostic biopsy (in screening 75 % will be benign) eqiovocal/suspicious FNAC diagnostic biopsy (in screening 75 % will be malignant) malignant FNAC = definitive surgery evt preoperative biopsy before preoperative chemotherapy

14 Aspirator skill Is reflected mainly in the inadequacy rate which varies from < 5 % to 40 % Some of the suspicious cases are also caused by suboptimal smear quality Sampling error (false negatives)

15 FNAC of same lesion by pathologist 1 yr later

16 Diagnostic problem areas Interpretation errors (IE) Papillary lesions DCIS Low grade carcinomas Borderline, proliferative lesions Radial scar/complex sclerosing adenosis Columnar cell lesions Atypical fibroadenomas Phyllodes tumour

17 Cytological reporting categories Insufficient material/no diagnosis/unsatisfactory (C1) Benign (C2) equivocal (probably benign)(pbd without atypia)(c3), including Columnar cell lesion/hyperplasia without atypia Intraductal hyperplasia, adenosis, sclerosing adenosis, cellular papillary lesion and some low grade CA and in situ lesions PBD with atypia (C4), including a few benign, proliferative( atypical lesions Consistent with non high-grade DCIS/ADH Columnar cell hyperplasia with atypia Consistent with papillary (intracystic) carcinoma in situ, cannot evaluate invasiveness Suspicious NOS(C4) Carcinoma NOS (C5), including High-grade DCIS, cannot evaluate invasiveness Invasive carcinoma

18 Diagnostic goals Sensitivity > 90 % Specificity > 90 % Non-diagnostic/insufficient < 10 % (preferably better) Benign Probably benign: as few as possible! Equivocal: as few as possible! > 50% will be histologically benign Suspicious approx 75 % malignant Malignant False negative < 5 % False positives < 1 % FNAC (together with radiology) should give a definitive diagnosis and management in approx % of work-up cases

19 Can we see the microcalcifications?

20 Mammographic (suspicious) microcalcifications without a tumour A number of cases may be recognisable on ultrasound DCIS?? If so, only in situ or invasive as well? Invasive lesions in or adjacent to DCIS are not always visible on mx However, the vast majority are found on US Therefore always do US also when there are microcalcifications but no tumour on mx

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22 Bondeson L, Lindholm K. Prediction of invasiveness by aspiration cytology applied to nonpalpable breast carcinoma and tested in 300 cases. Diagn Cytopathol 1997;17: Proliferation of fibroblasts (a sign of tumour induced stromal reaction) Cell poor elastoid stromal fragments Invasion of single or small groups of 2-3 carcinoma cells in stromal tissue and fatty fragments Intracytoplasmic vacuoles Tubular structures Can diagnose about 50 % of the carcinomas as invasive

23 Grading of invasive carcinomas Robinson IA, McKee G, Nicholsen A, D'Arcy J, Jackson PA, Cook MG. Prognostic value of cytologic grading of fine-needle aspirates from breast carcinomas. Lancet 1994;343: Criteria to be evaluated: Discohesion Nuclear size Nuclear contour irregularities Chromatin pattern/texture Nucleolus Cellular pleomorphism

24 Mitoses in breast FNAC

25 FNAC diagnosis in invasive breast carcinoma grade 1 Are we good enough?

26 Low-grade (G1) breast carcinomas Histological G1 breast carcinomas make up about 20 % of the symptomatic cases In the mammography screening programme they make up 45 % of the malignant lesions It is generally assumed that FNAC of low-grade carcinomas of the breast has a distinctly lower sensitivity due to discrete cellular atypia Several studies have shown a high percentage of FN FNAC in ILC, TUB und PAP. Lamd J, McGoogan E. Fine needle aspiration cytology of breast invasive carcinoma of tubular type and in radial scar/complex sclerosing lesions. Cytopathology 1994;5: Joshi A, Kumar N, Verma K. Diagnostic challenge of lobular carcinoma on aspiration cytology. Diagn Cytopathol 1998;18: Mitnick JS, Gianutsos R, Pollack AH, Susman M, baskin BL, Ko WD et al. Tubular carcinoma of the breast: sensitivity of diagnostic techniques and correlation with histopathology. AM J Roentgenol 1999;172: Rajesh L, Dey P, Joshi K. Fine needle aspiration cytology of lobular carcinoma. Comparison with other breast lesions. Acta Cytol 2003;47: Layfield LJ, Dodd LG. Cytologically low grade malignancies: an important interpretative pitfall responsible for false negative diagnoses in fine-needle aspiration of the breast. Diagn Cytopathol 1996;15:250-9

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28 FNAC from histologically G1 breast carcinomas absolute sensitivity 77.3 % complete sensitivity 92.7 % 4.8 % false negative (> 60 % SE) 2.6 % no diagnosis/insufficient/inadequate 80 % are IDC and > 80 % of these are given a definite malignant cytological diagnosis ILC and TUB make up <15 % and only 58 % of these receive a definite malignant diagnosis on a preoperative FNAC Karimzadeh M, Sauer T: Diagnostic accuracy of fine-needle aspiration cytology in histological grade 1 breast carcinomas: are we good enough? Cytopathology 2008; 19:

29 Ancillary methods in breast FNAC Immunocytochemistry (ICC) ER/PgR Ki-67 HER-2 In situ hybridisation HER-2 Top2-α

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31 CISH FNAC and cell block

32 What kind of material for ancillary methods LBC (!!) for steroid receptors Recommend LBC for all ICC (virtually no background noise ) Direct, air dried smear for ICC is ok Cell block if (very) abundant material Prefer direct smears for in situ hybridisation ICC or in situ of prestained material (PAP and/or Giemsa) is possible, but should be an exception

33 Thank you for your attention!

34 DCIS versus invasiv tumour (FNAC) If non-palpable lesion: histologically invasive in 18 % (Sauer T, Myrvold K, Lømo J, Anderssen KY, Skaane P. Fine-needle aspiration cytology in non-palpable mammographic abnormalities in breast cancer screening: results from the breast cancer screening programme in Oslo Breast 2003; 12(5): ) Palpable lesions which fulfill the criteria of high-grade DCIS are most often invasive (97 %)(Chieng DC et al. Invasive Carcinoma in Clinically Suspicious Breast Masses Diagnosed as Adenocarcinoma by Fine-Needle Aspiration. Cancer Cytopathology 2000; 90(2): )

35 DCIS versus invasiv tumour (CNB) Verkooijen HM. Diagnostic accuracy of stereotactic large-core needle biopsy for nonpalpable breast disease: results of a multicentre prospective study with 95 % surgical confirmation. Int J Cancer 2002; 99: % with a diagnosis of DCIS were invasive in the surgical specimen