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Patterns of FNAC in benign & malignant breast lesionsDr Neha MahajanMD Pathology


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


Adequacy of smears:

Presence of at least six clusters of epithelial cells in all smears orPresence of 10 or more myoepithelial (bipolar cells) in 10 consecutive medium power viewing fields

m


Reporting of aspirations

Normal Inflammatory Benign Suspicious of malignancy Atypical/indeterminate Malignant Unsatisfactory


CLASSIFICATION OF LESIONS OF FEMALE BREAST

INFLAMMATORY LESIONSAcute & chronic inflammatory processes

LESIONS CAUSED BY TRAUMAFat necrosisReaction to foreign bodiesLesions resulting from breast aumentation /reduction

BENIGN PROLIFERATIVE DISEASESCystsFibrous mastopathy & other fibrous lesions

BENIGN TUMORSFibroadenomaLactating AdenomaIntraductal papillomaGranular cell tumor

MALIGNANT TUMORSCarcinomas of various typesSarcomasRare tumor & tumor like conditions

METASTATIC TUMORS


Inflammatory disorders

Uncommon, account for <1% of women with breast symptoms

Erythematous, swollen, painful breast Inflammatory breast cancer mimics inflammation


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)


Breast abscess

Plenty of PMN`sscattered ductal cells necrotic material


Subareolar abscess

Young & nulliparous women Squamous metaplasia of lactiferous ducts Painful subareolar mass

D.D: Contaminant squamous epithelium Ruptured Epidermoid cysts


Subareolar abscess

Aspirate :Purulent inflammationKeratin flakes & debrisMature squamous cells


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


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


LipomaA well defined rounded soft mass,firm,tender

Empty sensation on needling

Fat only in multiple aspirates-fat vacuoles & fragments of adipose tissue


BENIGN EPITHELIAL BREAST LESIONS

Non proliferative breast disease/fibrocystic changesCysts with apocrine metaplasiaFibrosisAdenosis Proliferative disease

without atypiaEpithelial hyperplasiaSclerosing adenosisComplex sclerosing scarPapillomas

Proliferative disease with atypiaAtypical ductal hyperplasiaAtypical lobular hyperplasia


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


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


DUCTAL CELLS WITH APOCRINE FEATURES

Apocrine cells

Copyright © Wondershare SoftwareFoam cells Fibrous stroma

Fibrocystic changes


COLLAGENOUS SPHERULOSIS

Cytology Histopathology


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


Fibroadenoma

A high yield of cells, myxoid substance & some macroscopically visible tissue fragmentLarge ,branching sheets of bland epithelial cells(staghorn pattern of epithelial cells)Numerous single, bare bipolar nucleiFragments of fibromyxoid stroma


FIBROADENOMA

Staghorn clusters


Intracanalicular Pericanalicular


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


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


Lactating adenoma

Cell rich smearsPoorly cohesive mainly dispersed cells of acinar typeCells have abundant fragile cytoplasm,some bare nuclei Rounded vesicular nuclei & central nucleoliBackground of abundant lipid secretion


D/D Lobular ca(alveolar variant) Ca breast during pregnancy & lactation Secretory activity unrelated to pregnancy &

lactation Galactocoele with unusual features


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


Cellular smearsComplex folded & branching epithelial sheets & finger like fragmentsTrue papillary fragments with stromal coresDispersed epithelial cells with mild nuclear atypiaRows of pallisaded columnar epithelial cellsMacrophages & variable amount of cyst fluidBare bipolar nuclei

Papilloma


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


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


Granular cell tumor


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 .


Phyllodes tumor


Leaf like architecture Malignant stroma


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??


Mammary carcinomas

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


INTRADUCTAL CARCINOMA(IN SITU Ca OF DUCTS)Solid typeComedo typeSolid papillary carcinomaCARCINOMA OF MAMMARY LOBULESInfiltrating lobular carcinomaLobular carcinoma in situMIXED TYPESRARE:Spindle cellAdenoid cysticMetaplasticCa mimicking giant cell tumor of boneSecretoty/juvenille ca


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


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


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


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.


DCIS(comedocarcinoma)


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


Invasion


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


Infiltrating carcinoma


D/D

• Representative sampling• Smearing artefacts• Fibrosclerotic lesions• In situ & low grade carcinoma• Nuclear atypia in other lesions


Medullary carcinoma

Soft, fleshy well defined mass mimics benign6th decadeL.N metastasis commonPrognosis favourable


Highly Cellular smearsLarge pleomorphic ,undifferentiated malignant cells with irregular coarsely granular nuclei with v large nucleoliMany lymphocytes in background

Medullary carcinoma


D/D

Metastatic malignancy (melanoma) to axillary nodes

Malignant lymphoma High grade DCIS(comedocarcinoma)


Colloid Carcinoma/Mucinous carcinoma

Elderly women circumscribed tumorAbundant background mucinAtypical cells in small solid aggregates, runs single files, singlyModerate nuclear atypiaBenign epithelial cells & bipolar nuclei absentChicken wire blood vesselsCan confuse with mucocele like lesions


Colloid/mucinous carcinoma


Colloid carcinoma (tumor cells floating in mucin pools)


D/D

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


Apocrine carcinoma

Elderly womenCellular smears with large cells with eosinophilic granular cytoplasm similar to that of benign apocrine cellsNuclei are large with multiple nucleoli


Apocrine Ca


Apocrine carcinoma


Tubular carcinoma

Moderately cellular smearsCohesive 3D complex, often branching & angulated tubular clusters of epithelial cellsSingle bipolar nuclei of benign type with fat in the backgroundNuclear abnormalities are trivialMay mimic fibroadenoma


Tubular Ca


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


Papillary Carcinoma

Rare tumorsCell clusters resembling benign papillomasNuclear enlargement & evidence of mitotic activityDefinitive diagnosis cannot be madeConfirmation by histopath


Lobular carcinoma

Difficult to aspirate because of fibrosisSmall monotonous cancer cells showing cytoplasmic vacuolationCells either dispersed, clusters or singe filesNuclei granular of similar sizesCytoplasmic vacuolation with central condensed mucus in cancer cells(air dried geimsa) Target cells


Lobular carcinoma


Lobular carcinoma ( H&E ) L.P


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


Uncommon variants


Adenoid cystic carcinoma

Aspirate shows hyaline globules surrouned by epithelial hyperplasia

Have to be distinguished from collageous spherulosis

Prognosis significantly better


Adenoid cystic carcinoma


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


Metaplastic carcinoma


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


Ca with neuroendocrine features


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


Angiosarcoma


Gynecomastia

Smears similar to fibroadenomaSheets of cuboidal ductal cells & fragments of loose connective tissue stromaBipolar, spindly myoepithelial cells & oncocytesFragments of fibrous stroma & adipose tissue


Cytology Histopath


Nipple secretions in breast tumor

Bloody nipple secretions are more likely to be malignant

Two subtypes in spontaneous nipple secretions:1.Solid/papillary ductal carcinoma2.Ductal carcinoma with paget`s disease


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


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


Paget`s disease smear


Paget`s disease


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


Pitfalls of FNAC


False positive 1. Papillary lesions2. Epithelial hyperplasia with nuclear atypia3. Radial scar/complex sclerosing lesion4. Fibroadenoma5. Regenerative epithelial atypia6. Pregnancy & lactation7. Skin adnexal tumor


False negative1. Tumors with central necrosis/sclerosis2. Small carcinoma next to a dominant benign lesion3. Complex proliferative lesion4. Low grade ductal carcinoma5. Lobular carcinoma Ca and small cell ductal Ca


Prognosis


Cytoarchitectural patternFavourable Extremely bad BadTubular Lobular carcinoma Squamous cell caCribriform (Signet ring ca) Metaplastic CaMedullary Carcinoma withPure mucinous neuroendocrinePapillaryAdenoid cysticSecretory/juvenille


• 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.


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


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The prick is worth the pain!!!!


References:

Leopald G.Koss,Myron R.Melamed`s Koss` Diagnostic Cytology and its histopathologic bases.5th ed.New York:Lippincott & Williams & Wilkins;2006;p1148-1185.vol 2.

Svante R Orell,Gregory F Sterrett,Darell Whitaker`s Fine Needle Aspiration Cytology.4th ed.Australia:Churchilll Living An Imprint of Elsevier,2005;p165-276.

Vinay Kumar,Abul.Kabbas,Nelson Fausto. Robbins & Cotran Pathological Basis of Disease.8th ed. Chicago,Illinois:Elsevier.2010 .p. 905-969

Stephen S sternburg,Donald A.A,Daryl.Carter,Stacey.E,Oberman H.A.Diagnostic Surgicl Pathology.3rd 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

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