Breast FNAC. 5th EFCS Tutorial Trondheim, Norway. Torill Sauer, Department of Pathology, Oslo University Hospital

Transcription

1 Breast FNAC 5th EFCS Tutorial Trondheim, Norway

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

3 Patient management Cytological results must always be put in a proper context together with the radiological and the clinical findings FNAC and radiological findings usually determine the further handling of the lesions In specialized breast centres both sensitivity and specificity of FNAC is around 90 %; somewhat higher for palpable lesions than for non-palpbale lesions Complications Hematomas: thus ALWAYS do radiology before FNAC Pneumothorax : very rare; in young and thin women Seeding of tumour cells: very rare!

4 Cytological diagnostic/reporting categories Insufficient Benign equivocal Suspicious Carcinoma material/no diagnosis/unsatisfactory (C1) (C2) (probably benign)(pbd without atypia)(c3), including Columnar cell lesion/hyperplasia without atypia Intraductal hyperplasia, adenosis, sclerosing adenosis, cellular papillary lesion NOS; PBD with atypia (C4), including Consistent with non high-grade DCIS/ADH Columnar cell hyperplasia with atypia Consistent with papillary (intracystic) carcinoma in situ, cannot evaluate invasiveness NOS (C5), including High-grade DCIS, cannot evaluate invasiveness Invasive carcinoma Torill Sauer, Department of Pathology, Oslo University Hospital

5 Problems Equivocal/borderline cytological diagnoses always require a diagnostic biopsy What represents a good/satisfactory breast FNAC < 10 % unsatisfactory/nondiagnostic A low percentage of equivocal/borderline diagnoses (10-15 %?) Aspirator skili 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) Torill Sauer, Department of Pathology, Oslo University Hospital

6 Materials Direct smears Air dried Wet fixation in alcohol (ethanol) Liquid based suspensions commercial home made PBS Staining Papanicolaou, MGG/Diff-Quick, HE, Alcian, PAS, Fite, Grocotte, Gram

7 Benign/normal findings 1 Small cohesive groups Monolayer sheets Oval nuclei with regular outlines, 8-10 nm in diameter Inconspicious nucleolus Evenly distributed chromatin Scanty cytoplasm

8 Benign/normal findings 2 Myoepithelial cells appear as ovoid, dense nuclei at the periphery of ductal sheets and groups Naked, bipolar (myoepithelial cell) nuclei in the background Occasional complete TDLU Torill Sauer, Department of Pathology, Oslo University Hospital

9 Lactation Moderately or markedly cellular Cells are single and well dispersed in a lipid rich foamy or granular background The cells (including nuclei) are large with abundant cytoplasm that is vacuolated or wispy. Bare nuclei are common Nuclei are round and uniform with active granular or vesicular, but evenly distributed chromatin. Single prominent nucleoli

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11 Gynekomastia Scanty or moderately cellular smears Small to medium sized epithelial fragments that may be hyperplastic and three dimensional Small to moderate numbers of bipolar cells Diagnostic pitfalls In florid hyperplasia there may be marked anisokaryosis that can be misinterpreted as atypia

12 Fat necrosis Foamy macrophages and multinucleate giant cells with foamy cytoplasm Small irregular groups of (reactive) histiocytic cells Fragments of normal as well as degenerate fatty tissue Variable numbers of other inflammatory cells but usually sparse Few if any epithelial cells Free lipid droplets, seen as empty spaces that may be surrounded by blood or as empty spaces in a granular background Granular background debris

13 Granulomatous Mastitis 1 Sheets or clusters of epitheloid (or sometimes more histiocytic in appearance) cells with abundant cytoplasm and elongated nuclei. Multinucleate giant cells associated with epitheloid cells.

14 Granulomatous Lesions 2 A variable number of inflammatory cells: lymphocytes, plasma cells, neutrophilic granulocytes Admixture of ductal or lobular epithelial cells which may be reactive with enlarged nuclei and distinct nucleolus Keratinised squamous cells in subareolar A

15 Fibrocystic changes 1 Scanty, often watery smear Low or moderate cellularity Apocrine cells either dominating the cellular picture or in variable numbers Sheets or fragments of ductal epithelium with bland nuclei arranged in a honeycomb pattern with admixed myoepithelial cells and dispersed bipolar nuclei Threedimensional epithelial aggregates (representing intraductal proliferations) Microcalcifications

16 Fibrocystic changes 2 Macrophages and granular debris form microscopical cysts Threedimensional epithelial aggregates representing intraductal hyperplasia Fat or fibrous stroma in variable quantities Torill Sauer, Department of Pathology, Oslo University Hospital

17 Fibroadenoma Moderate or high cellularity, though may be scanty in older or fibrotic lesions Cohesive sheets with an antler-like appearance containing recognisable myoepithelial cell nuclei Many naked bipolar cell nuclei in the background If apocrine or foamy cells are present they are few

18 Cohesive sheets, myoepithelial cell nuclei, stromal fragments Torill Sauer, Department of Pathology, Oslo University Hospital

19 Low grade Phyllodes Tumour 1 Variably cellular smears Numerous (?) plump, single stromal cells with discret cellular pleomorphism The prominence and number of bipolar cells are usually greater than in fibroadenomas Benign ductal epithelium

20 Low grade Phyllodes Tumour 2 Obvious stromal fragments, some large and with high cellularity Fragments composed entirely of bipolar cells containing pink or purple ground substance in MGG preparations Torill Sauer, Department of Pathology, Oslo University Hospital

21 borderline borderline malignant benign

22 Benign intracystic/intraductal papilloma 1 Variable cellularity with a basic benign pattern The epithelial cells are often seen as small groups Complex, folded three dimensional epitehlial aggregates Stromal fragments

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24 Benign intracystic/intraductal papilloma 2 (Micro-)papillary clusters may be preserved Papillary stromal fragments may be present numbers of bipolar cells Torill Sauer, Department of Pathology, Oslo University Hospital

25 Benign intracystic/intraductal papilloma 3 Apocrine cells may be present A small amount of debris and macrophages may be present Diagnostic pitfalls When the lesions are cellular, differentiation from a welldifferentiated papillary carcinoma may be difficult Torill Sauer, Department of Pathology, Oslo University Hospital

26 Mucocele-like Lesions Abundant mucin Scant to moderate cellularity with cohesive, monolayer clusters and sheets of epithelial cells No or up to moderate nuclear atypia No eventually few single epithelial cells

27 Lobular Neoplasia (LCIS) Loosely cohesive groups Uniform cells with occasional intracytoplasmic lumina Slightly irregular and eccentric nuclei Diagnostic pitfalls May be mistaken for benign cells More pleomorphic tumour cells may be diagnosed as carcinoma

28 General criteria of malignany Moderate or abundant cellularity (except ILC) Lack of cell-to-cell cohesion Absence of myoepithelial cell nuclei, both in the background and in the periphery of the tumour cell groups and aggregates (except TUB)

29 Nuclear size and pleomorphism 1 ½ -2 x RBC (diameter of a red blood cell) to > 5 x RBC Most low-grade carcinomas have nuclear sizes in the range of 2-3 x RBC Nuclear size pleomorphism is less distinct in low-grade carcinomas and a few may appear deceivingly monotonous ( monoclonal )

30 Nucleolar size and pleomorphism Most low-grade carcinomas have small or indistinct nucleoli Distinct or prominent/abnormal nucleoli are a feature of grade 2 and 3 carcinoma. Nucleoli and the size of the nucleoli, are a feature of active cells. This is the case in most carcinomas, but the nucleoli as such are not a feature of malignancy Atypical nucleoli with bizarre shapes and sharp edges in well preserved cells are a feature of malignancy

31 Nuclear membrane irregularity and extranuclear chromatin Small indentations as folds, grooves and clefts or projections/buds in the nuclei Box-shaped and angular nuclei are also suspicious. Extranuclear chromatin tends to be seen more commonly in higher-grade carcinomas Nuclear/cytoplasmic ratio and cytoplasmic features are of limited help in dx

32 Nuclear fragility and mitotic figures Malignant nuclei show a greater tendency to rupture under the physical pressure of being smeared These are rarely seen in breast aspirates except those of high-grade ductal carcinomas. Unless frequent and atypical, they should not be given a heavy diagnostic bias

33 Contents of the background Most high-grade DCIS and a few grade 3 invase ductal carcinomas show comedo type necrosis on the smears Necrosis is thus not pathognomic of invasiveness, and may even be more suggestive of a DCIS mass

34 Can we see the microcalcifications? Torill Sauer, Department of Pathology, Oslo University Hospital

35 Grading of invasive carcinomas mainly variants of nuclear grading good correlation with histological grading and ploidy

36 Subtypes of invasive breast carcinomas IDC 65 80% ILC 5 14% Basal and medullary - like carcinoma 5 7% TUB 2 8% MUC 2 4% PAP 1 2% Apocrine C 1 4% Other rare types <1%

37 Invasive ductal Carcinoma 1 Varying cellularity from abundant to scanty The epithelial cells present as single cells, loose aggregates and cohesive groups often threedimensional in appearance

38 Invasive ductal Carcinoma 2 Varying cellular and nuclear atypia according to histological grade G1-G3 Cells may be vacuolated and occasional signet ring cells are seen Torill Sauer, Department of Pathology, Oslo University Hospital

39 Invasive ductal Carcinoma 3 Microcalcification is quite common Mitoses are uncommon, but may be seen in high grade lesions Necrosis is not common Torill Sauer, Department of Pathology, Oslo University Hospital

40 DCIS 3 - microcalcifications

41 Invasive lobular Carcinoma Scanty aspirates are common Tumour cells are well dispersed and mainly single or in small groups of 2 to 5 cells. Occasional single file chains, usually containing only three or four cells, may be seen

42 ILC 2 Cells are small Cytoplasm is scanty nucleus eccentrically placed some cells may contain an intracytoplasmic lumen with a signet-ring appearance Nuclei show slight but definite variation in size chromatin is stippled but not coarse nucleolus inconspicuous in the classic type nuclei have an abnormal appearance with irregular outline

43 Mucinous Carcinoma On spreading, the aspirate is quite glairy, hinting at a high mucin content The smear is usually cellular Single cells, loose aggregates and cohesive groups, often threedimensional in appearance The cells are bathed in mucin of variable density. (Violet in MGG) The cells are small, with small, uniform, round nuclei, smooth nuclear outlines, bland, possibly granular, chromatin and inconspicuous nucleoli Cells may be vacuolated occasional signet ring cells Torill Sauer, Department of Pathology, Oslo University Hospital

44 Nuclei are often 1 1/2-2 x RBC slightly irregular nuclear outlines indistinct or small nucleoli. Cells may be cuboidal or columnar. The groups are usually very cohesive, but a few single cells may be found in most cases (often columnar) Monolayer sheets, often folded and with part of an intact tubular structure in one end Tubular Carcinoma

45 True tubular structures, often broken with sharp angles Slight anisonucleosis and mild hyperchromasia. The chromatin is finely granular and evenly distributed Bipolar nuclei are present in occasional cases Messy background of cell fragments and stromal elements No apocrine or foam cells present TUB 2

46 Papillary Carcinoma (in situ and invasive)1 May be cystic on aspiration The cell material is usually abundant Epithelial cells are monotonous and appear clonal Torill Sauer, Department of Pathology, Oslo University Hospital

47 Papillary Carcinoma (in situ and invasive)2 Usually G1, occasionally G2 and G3 Anisonucleose, hyperchromasia, coarse chromatin, and prominent nucleoli are uncommon Benign bipolar cells are absent from the background and myoepithelial cells are not seen within the groups Torill Sauer, Department of Pathology, Oslo University Hospital

48 Papillary Carcinoma (in situ and invasive)3 Cells often tall, columnar in shape Intracytoplasmic vacuolisation is not rare Torill Sauer, Department of Pathology, Oslo University Hospital

49 Papillary Carcinoma (in situ and invasive) 4 Large papillary cell clusters forming arborizing arrays bearing overlapping, palisaded cells on a fibrovascular core may be present as with papillomas Cells may be dispersed and the fibrovascular cores denuded Microcalcification common finding

50 Non-epithelial tumours Malignant Phyllodes tumour Angiosarcoma Liposarcoma Malignant Lymphoma (primary and sekundary)

51 Metastases Malignant Melanoma ML Lung carcinomas Ovarian carcinomas MM

52 Thank you for your attention!