Fnac breast

1. P atterns of FNAC in benign & malignant breast lesions Dr Neha Mahajan MD Pathology

2. Indications of FNAC breast Diagnosis of simple cysts The investigation of suspected recurrence or metastasis in cases of previously diagnosed cancer Confirmation of inoperable, locally advanced cancer Preoperative confirmation of clinically suspected cancer Investigation of any clinically palpable lump, clinically benign or malignant as a guide to clinical management As a complement to mammography in the screening situation To obtain tumor cells for special diagnosis

3. Adequacy of smears: Presence of at least six clusters of epithelial cells in all smears or Presence of 10 or more myoepithelial (bipolar cells) in 10 consecutive medium power viewing fields m

4. Reporting of aspirations Normal Inflammatory Benign Suspicious of malignancy Atypical/indeterminate Malignant Unsatisfactory

5. CLASSIFICATION OF LESIONS OF FEMALE BREAST INFLAMMATORY LESIONS Acute & chronic inflammatory processes LESIONS CAUSED BY TRAUMA Fat necrosis Reaction to foreign bodies Lesions resulting from breast aumentation /reduction BENIGN PROLIFERATIVE DISEASES Cysts Fibrous mastopathy & other fibrous lesions BENIGN TUMORS Fibroadenoma Lactating Adenoma Intraductal papilloma Granular cell tumor MALIGNANT TUMORS Carcinomas of various types Sarcomas Rare tumor & tumor like conditions METASTATIC TUMORS

6. Inflammatory disorders Uncommon, account for <1% of women with breast symptoms Erythematous , swollen, painful breast Inflammatory breast cancer mimics inflammation

7. Mastitis: A benign bimodal component of non neoplastic breast tissue Inflammatory cells, chronic/acute Regenerative epithelial atypia Histiocytes , epitheloid cells, multinucleated giant cells and plasma cells( granulomatous pattern) Microorganisms(infectious mastitis )

8. Breast abscess Plenty of PMN`s scattered ductal cells necrotic material

9. Subareolar abscess Young & nulliparous women Squamous metaplasia of lactiferous ducts Painful subareolar mass D.D: Contaminant squamous epithelium Ruptured Epidermoid cysts

10. Subareolar abscess Aspirate :Purulent inflammation Keratin flakes & debris Mature squamous cells

11. Fat necrosis Painless,palpable mass,thickening or retraction of skin History of breast trauma ,repeated palpation or aspiration or surgery D.D: Lipid cyst Macrophages mistaken for atypical epithelial cells Carcinoma cells with macrophage like appearance

12. Dirty background of granular debris, fat droplets & fragments of adipose tissue Foamy macrophages, multinucleated giant cells & adipocytes with bubbly cytoplasm Absence of epithelial cells Fat necrosis

13. Lipoma A well defined rounded soft mass,firm,tender Empty sensation on needling Fat only in multiple aspirates-fat vacuoles & fragments of adipose tissue

14. BENIGN EPITHELIAL BREAST LESIONS Non proliferative breast disease/fibrocystic changes Cysts with apocrine metaplasia Fibrosis Adenosis Proliferative disease without atypia Epithelial hyperplasia Sclerosing adenosis Complex sclerosing scar Papillomas Proliferative disease with atypia Atypical ductal hyperplasia Atypical lobular hyperplasia

15. Fibrocystic breast disease Clinician LUMPY BUMPY breast Radiologists Dense breast with cysts Pathologist Benign breast lesion Sequential proliferation & atrophy of ducts & lobules and fibrosis of parenchyma of breast On cytology, impossible to differentiate subgroups

16. Fibrocystic breast disease(cytology) Sheets of ductal epithelial cells of apocrine type Fragments of usual epithelial cells Scattered single bare bipolar nuclei Background of variable amounts of cyst fluid and macrophages Fibrous stroma

17. Ductal cells with apocrine features Apocrine cells

18. Foam cells Fibrous stroma Fibrocystic changes

19. Collagenous spherulosis Cytology Histopathology

20. Simple cyst Complete dissapearance of the lump after aspiration of the fluid Absence of altered blood or necrotic material in the aspirated fluid Cyst macrophages and more or less degenerate oxyphil / apocrine epithelial cells Inflammatory cells(polymorphs) variable

21. Fibroadenoma A high yield of cells, myxoid substance & some macroscopically visible tissue fragment Large ,branching sheets of bland epithelial cells( staghorn pattern of epithelial cells) Numerous single, bare bipolar nuclei Fragments of fibromyxoid stroma

22. Fibroadenoma Staghorn clusters

23. Intracanalicular Pericanalicular

24. D/D Overlap with other hyperplastic lesions( papilloma ) Epithelial atypia mimicking carcinoma(premenopausal & HRT) Fibromyxoid stroma occuring in some invasive cancers Cystic/ mucinous change Distinction from phylloides tumor

25. Lactating adenoma Solitary/multiple freely movable breast mass during pregnancy/ puerperium Numerous densely packed lobular units in clusters or as isolated structures with myoepithelial cells at the periphery

26. Lactating adenoma Cell rich smears Poorly cohesive mainly dispersed cells of acinar type Cells have abundant fragile cytoplasm,some bare nuclei Rounded vesicular nuclei & central nucleoli Background of abundant lipid secretion

27. D/D Lobular ca(alveolar variant) Ca breast during pregnancy & lactation Secretory activity unrelated to pregnancy & lactation Galactocoele with unusual features

28. Intraductal papilloma Solitary subareolar mass Bloody nipple discharge Papillary lesions cannot be distinguished on cytology, diagnosis left to histology All papillary lesions should be excised

29. Cellular smears Complex folded & branching epithelial sheets & finger like fragments True papillary fragments with stromal cores Dispersed epithelial cells with mild nuclear atypia Rows of pallisaded columnar epithelial cells Macrophages & variable amount of cyst fluid Bare bipolar nuclei Papilloma

30. D/D Low grade papillary carcinoma Cell dispersed mimicking a malignant smear pattern Pseudopapillary structures in smears of low grade invasive duct carcinoma Overlap with fibroadenoma Infarcted papilloma

31. Granular cell myoblastoma Uncommon, benign ,firm tumor of breast clinically mimics carcinoma Large cells with abundant granular cytoplasm, monotonous ,generally spherical small nuclei In smears ,break up of cytoplasm results in naked nuclei Often confuses with large cell duct carcinoma

32. Granular cell tumor

33. Phylloides tumor Cohesive fragments of highly cellular stroma composed of spindle cells with nuclear atypia and background atypical bare spindle nuclei, are highly suggestive of phylloides tumor Marked nuclear pleomorphism & mitotic activity seen in frank malignant phylloides tumor .

34. Phyllodes tumor

35. Leaf like architecture Malignant stroma

36. Dignostic dilemma Is the lesion an ordinary fibroadenoma ? Or can it quantify as a phyllodes ?? In case of marked abnormalities of stromal cells ,is it a phyllodes or carcinoma??

37. Mammary carcinomas CARCINOMAS OF MAMMARY DUCT Infiltrating duct Inflammatory Medullar Colloid/ mucinous Signet ring type Apocrine Tubular Papillary

38. INTRADUCTAL CARCINOMA(IN SITU Ca OF DUCTS ) Solid type Comedo type Solid papillary carcinoma CARCINOMA OF MAMMARY LOBULES Infiltrating lobular carcinoma Lobular carcinoma in situ MIXED TYPES RARE: Spindle cell Adenoid cystic Metaplastic Ca mimicking giant cell tumor of bone Secretoty / juvenille ca

39. General cytologic presentation in Malignancy Abundant pure population of tumor cells ,singly & in clusters Backround no inflammation/necrosis Clusters of aspirated cancer cells are 3D, either loosely arranged,cells at the periphery become detached Isolated cancer cells show N:C ratio,nuclear abnormalities Absence of myoepithelial cells

40. DCIS Diagnosis of DCIS in tissue section includes assessment of nuclear grade, growth pattern, presence or absence of necrosis & calcification Specific diagnosis or classification of DCIS cannot be made on FNAC Lesions with high nuclear grade, invasion cannot be predicted accurately

41. DCIS low grade ( cribriform,solid or micropapillary,non invasive intracystic papillary ca) Epithelial cells mainly cohesive forming large sheets,often with holes or papillary fragments Bare bipolar nuclei absent Variable ,mild to moderate epithelial atypia Necrotic debris, often calcium granules Macrophages

42. High gradeDCIS (solid or comedo growth pattern) Soft, boggy, palpable mass with highly cellular indicates significant intraductal lesion worthy of excision. Neoplastic cells in sheets, irregular aggregates and single pleomorphic cells showing obvious malignant nuclear features . Necrotic debris, granular debris, granular calcium ,lymphocytes and vacuolated cytoplasm.

43. DCIS( comedocarcinoma )

44. Predicting invasion Findings of tubular or angular epithelial structures, malignant cells adherent to fibrous stroma Presence of intracytoplasmic neolumina in malignant cells Fibroblast proliferation Fragments of elastoid stroma

45. Invasion

46. Infiltrating duct carcinoma Cell rich smears, single population of epithelial cells no myoepithelial cells,no single bare bipolar nuclei Variable loss of cell cohesion irregular clusters and single cells Single epithelial cells with intact cytoplasm Mod to severe nuclear atypia , enlargement, pleomorphism , irregular nuclear membrane& chromatin Fibroblasts & fragments of collagen( stromal desmoplasia ) a/w atypical cells Intracytoplasmic neolumina in some cases Necrosis unusual

47. Infiltrating carcinoma

48. D/D Representative sampling Smearing artefacts Fibrosclerotic lesions In situ & low grade carcinoma Nuclear atypia in other lesions

49. Medullary carcinoma Soft, fleshy well defined mass mimics benign 6 th decade L.N metastasis common Prognosis favourable

50. Highly Cellular smears Large pleomorphic ,undifferentiated malignant cells with irregular coarsely granular nuclei with v large nucleoli Many lymphocytes in background Medullary carcinoma

51. D/D Metastatic malignancy (melanoma) to axillary nodes Malignant lymphoma High grade DCIS( comedocarcinoma )

52. Colloid Carcinoma/ Mucinous carcinoma Elderly women circumscribed tumor Abundant background mucin Atypical cells in small solid aggregates, runs single files, singly Moderate nuclear atypia Benign epithelial cells & bipolar nuclei absent Chicken wire blood vessels Can confuse with mucocele like lesions

53. Colloid/ mucinous carcinoma

54. Colloid carcinoma (tumor cells floating in mucin pools)

55. D/D Lack of nuclear pleomorphism Mucinous DCIS or ADH Mucocoele like lesions Mucinous fibroadenoma Myxoid stromal matrix resembling mucin Metastatic carcinoma Ultrasound gel

56. Apocrine carcinoma Elderly women Cellular smears with large cells with eosinophilic granular cytoplasm similar to that of benign apocrine cells Nuclei are large with multiple nucleoli

57. A pocrine Ca

58. Apocrine carcinoma

59. Tubular carcinoma Moderately cellular smears Cohesive 3D complex, often branching & angulated tubular clusters of epithelial cells Single bipolar nuclei of benign type with fat in the background Nuclear abnormalities are trivial May mimic fibroadenoma

60. T ubular C a

61. D/D Fibroadenoma Mixed tubular & usual ductal carcinoma Complex sclerosing lesion/ scar , adenosis

62. Papillary Carcinoma Rare tumors Cell clusters resembling benign papillomas Nuclear enlargement & evidence of mitotic activity Definitive diagnosis cannot be made Confirmation by histopath

63. Lobular carcinoma Difficult to aspirate because of fibrosis Small monotonous cancer cells showing cytoplasmic vacuolation Cells either dispersed, clusters or singe files Nuclei granular of similar sizes Cytoplasmic vacuolation with central condensed mucus in cancer cells(air dried geimsa ) Target cells

64. Lobular carcinoma

65. Lobular carcinoma ( H&E ) L.P

66. D/D Sparse cellularity Resemblance to non neoplastic breast tissue in L.P Component of benign epithelium Lobular hyperplasia in pregnancy & lactation Distinction from low grade ductal carcinoma Intracytoplasmic neolumina in other lesions

67. Uncommon variants

68. Adenoid cystic carcinoma Aspirate shows hyaline globules surrouned by epithelial hyperplasia Have to be distinguished from collageous spherulosis Prognosis significantly better

69. Adenoid cystic carcinoma

70. Metaplastic carcinoma Highly aggressive malignant tumor combine features of carcinoma with that of well differentiated sarcoma( lipoma,oste or chondroSa,fibrosarcoma ) Diagnostic: two or more population of malignant cells Spindle cell variant resembles soft tissue sarcoma, difficult to distinguish from phyllodes

71. Metaplastic carcinoma

72. Carcinoma with neuroendocrine Smears cell rich composed of dispersed small & relatively uniform cells with coarse granular nuclear chromatin resembling carcinoid Mistaken for lymphoma,look for possibility of metatstatic neuroendocrine ca

73. Ca with neuroendocrine features

74. Angiosarcoma Aspiration : plenty of blood, few tumor cells(low grade) Tumor cells spindly, attenuated basophilic cytoplasm without distinct borders& have dark pleomorphic , elongated or plump spindle nuclei(High grade ) mistaken for sarcoma

75. Angiosarcoma

76. Gynecomastia Smears similar to fibroadenoma Sheets of cuboidal ductal cells & fragments of loose connective tissue stroma Bipolar, spindly myoepithelial cells & oncocytes Fragments of fibrous stroma & adipose tissue

77. Cytology Histopath

78. Nipple secretions in breast tumor Bloody nipple secretions are more likely to be malignant Two subtypes in spontaneous nipple secretions: 1.Solid/papillary ductal carcinoma 2.Ductal carcinoma with paget`s disease

79. Duct carcinoma Cancer cells desquamate singly or in clusters Clusters may be loosely structured, and are sometimes thick or spherical, but may show a relatively orderly arrangement of cancer cells in papillary clusters Necrosis is common comedo type DCIS

80. Paget`s disease Background of keratin, squamous cells, inflammatory cells & debris(scrape smears from nipple) Large malignant cells, single and in small groups, closely associated with squamous & inflammatory cells Abundant pale cytoplasm with distinct borders Obvious nuclear features of malignancy

81. Paget`s disease smear

82. Paget`s disease

83. Metastatic malignancy to breast If cytological pattern does not fit any of the recognised types of primary breast cancer,then possibility of metastasis need to be considered Mets are common from melanoma, SCC of cervix, bronchogenic carcinoma, mucin secreting adenocarcinoma stomach, ovarian adenoca , alveolar RMS, soft tissue sarcoma

84. Pitfalls of FNAC

85. False positive Papillary lesions Epithelial hyperplasia with nuclear atypia Radial scar/complex sclerosing lesion Fibroadenoma Regenerative epithelial atypia Pregnancy & lactation Skin adnexal tumor

86. False negative Tumors with central necrosis/sclerosis Small carcinoma next to a dominant benign lesion Complex proliferative lesion Low grade ductal carcinoma Lobular carcinoma Ca and small cell ductal Ca

87. Prognosis

88. Cytoarchitectural pattern Favourable Extremely bad Bad Tubular Lobular carcinoma Squamous cell ca Cribriform (Signet ring ca) Metaplastic Ca Medullary Carcinoma with Pure mucinous neuroendocrine Papillary Adenoid cystic Secretory / juvenille

89. As the prognosis and thereby the line of management of each group of breast lesions varies, it is important to recognize the spectrum of morphological changes seen and separate them into benign, premalignant and malignant categories.

90. Masood   et al , cytological grading system based on Cellular arrangement (relationship of cells to one another in a sheet of ductal epithelial cells), The degree of cellular pleomorphism (the variation in cell size of the ductal epithelial cells), Anisonucleosis , The presence of myoepithelial cells, Nucleoli The status of chromatin pattern like clumping of chromatin

91. 1 2 3 4

92. The prick is worth the pain!!!!

93. References: Leopald G.Koss,Myron R.Melamed`s Koss` Diagnostic Cytology and its histopathologic bases.5 th ed.New York:Lippincott & Williams & Wilkins;2006;p1148-1185.vol 2. Svante R Orell,Gregory F Sterrett,Darell Whitaker`s Fine Needle Aspiration Cytology.4 th ed.Australia:Churchilll Living An Imprint of Elsevier,2005;p165-276. Vinay Kumar,Abul.Kabbas,Nelson Fausto . Robbins & Cotran Pathological Basis of Disease.8 th ed. Chicago,Illinois:Elsevier.2010 .p. 905-969 Stephen S sternburg,Donald A.A,Daryl.Carter,Stacey.E,Oberman H.A.Diagnostic Surgicl Pathology.3 rd ed.Newyork:Lippincort Williams &Wilkins;1999.p.1701-1784. Rosai Juan.Rosai and Ackerman`s Surgical Payhology.9 ed.Milan,Italy:Elsevier;2005.p.1164-1316 Nandini NM,Rekha TS,Manjunath GV,Evalaution of scoring system in cytoloical diagnosis & management of breast lesion.Indian jounal of cancer;2011 vol28,p240 -245