fnac of ductal carcinoma in situ of the breast - sbp dcis cytology.pdf · cytologic features of...

FNAC of epithelial borderline and in situ lesions of the

breast

FNAC of microcalcifications

Torill Sauer, Department of Pathology, Akershus University Hospital 1 Torill Sauer, Department of Pathology, Akershus University Hospital

Lesions included

• Ductal carcinoma in situ (DCIS)

– High grade

– Non-high grade

• Atypical ductal hyperplasia (ADH)

• Columnar cell lesions (CLL), including flat atypia

• Lobular neoplasi

– Atypical lobular hyperplasia (ALH)

– Lobular carcinoma in situ (classical)

– Pleomorphic lobular carcinoma in situ

Torill Sauer, Department of Pathology, Akershus University Hospital 2

Breast lesions associated with radiological

microcalcifications • Atrophy, inflammatory lesions

• Benign non-tumour conditions

– Adenosis

– UDH (usual ductal hyperplasia)

• Benign tumours

– papilloma

– fibroadenoma

– adenomyoepithelioma

• Borderline proliferative lesions (=

columnar cell lesions)

• PLCIS

• Ductal carcinoma in situ

• Invasive lesions

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Ductal carcinoma in situ (WHO definition)

• A neoplastic proliferation of

epithelial cells confined to the

mammary ductal-lobular

system

• A subtle to marked cytological

atypia

• An inherent but not necessarily

obligate tendency for

progression to invasive breast

cancer

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(Histologic) growth pattern subtypes of DCIS

• Solid

• Cribriform

• Micropapillary

• Papillary

• Comedo

• Non-comedo

• Apocrine

• Signet ring type

• Clear cell type

• Flat/”clinging”

All subtypes are reflected in the cytological specimens

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(Histological) grading of DCIS

• Depends primarily on the nuclear

atypia

• Low nuclear grade

– Small monomorphic cells (growing in

arcades, micropapillae, cribriform or

solid patterns)

• Intermediate grade

– Cells with mild to moderate variability

in shape, size, chromatin pattern and

variably prominent nucleoli

– Comedo type necrosis may be

present

• High nuclear grade

– Highly atypical cells

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Grading of DCIS

• Sauer T, Lømo J, Garred Ø, Næss O. Cytologic features of ductal carcinoma in situ in fine-needle aspiration of the breast mirror the histopathologic growth pattern heterogeneity and grading. Cancer Cytopathol 2005;105:21-7. (modified Van Nuy)

• Cytological grading of DCIS

– high grade DCIS – G3 (irrespective of growth pattern as well as comedo type necrosis or not): > 2 x RBC

– non-high grade DCIS: < 2 x RBC

– comedo type necrosis seen: G2

• Concordance with histology 95 %

Torill Sauer, Department of Pathology, Akershus University Hospitak

In a setting of

mammographic

microcalcifications

WITHOUT a tumour

the following features

are characteristic of

high grade DCIS:

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Threedimensional solid or cribriform aggregates

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Nuclei > 2 x RBC

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Comedo type necrosis

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Microcalcifications

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Ocassionally papillary or micropapillary

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Variable number of single cell component

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Note also the microcalcifications!

Dissociation in single cells is (still) a criterion of

malignancy, • But it is NOT a feature of invasiveness

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Diagnostic considerations high nuclear grade DCIS

• Some cases of IDC grade 3 may present cytologically with

necrosis and microcalcifications on FNAC, but the radiology will

be that of a tumour

• A few DCIS may be tumour-forming (-8 % with radiological mass

or assymetry)

• Palpable tumours with cytologic characteristics like DCIS are

invasive in 97 % of the cases

• Microinvasion will not be sampled

• Invasive lesions not recognised radiologically will not have been

sampled and about 20 % of radiological DCIS will have an

invasive component in the surgical specimen

• Single cells are not a feature of invasion

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DCIS varia

• In a setting of microcalcifications without tumour a diagnosis of

high grade DCIS may be given

• The question is not «invasive OR in situ», but «is there an

invasive component in addition to the DCIS?»

• The larger the extent of high grade DCIS, the larger the risk of an

additional invasive component

• In a setting of radiological tumor, approx 97 % of the lesions are

invasive (with or without an in situ component)

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In a setting of

microcalcifications

without tumor, the

following is

characteristic of a

none-high grade DCIS (low and intermediate grades)

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non-high grade DCIS

Very large three-dimensional aggregates;solid,

cribriform and often more cohesive than high grade lesions

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Cell monotony

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Micropapillary groups

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True papillary structures

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Monolayer (two-dimensional) sheets

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+micropapillary

Variable number of single cells

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Microcalcifications

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Occasional comedo type necrosis

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Low to moderate/intermediate nuclear atypia

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Diagnostic pitfalls and considerations in low- and

intermediate-grade DCIS

• The cytological criteria overlap with epithelial hyperplasia with

and without atypia (ADH, columnar cell lesions)

– A diagnosis suggestive of non-high grade DCIS should ONLY result

in a diagnostic biopsy for confirmation, never mastectomy or ALND

• Some of the lesions might appear deceivingly monotonous, in

contrast to some benign, hyperplastic lesions with a

polymorphous cell pattern

• Numerous single cells are not indicative of an invasive lesion

• Myoepithelial cell nuclei on the epithelial groups are no «proof» of

a benign lesion.

• Pure subtypes as to growth pattern is virtually non-exisent

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Diagnostic categories low grade DCIS

• Equivocal

• C3-C4

• proliferative with low grade atypia

• suspicious for low grade DCIS/ADH

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Columnar cell lesions (WHO)

• CCC and CCL are lesions of the

terminal-duct lobular unit (TDLU)

– enlarged, variably diated acini

lined by columnar epithelial cells

• Flat epithelial atypia is a

neoplastic alteration of the TDLU

– replacement of the native epithelial

cells by one to several layers of a

single epithelial cell type showing

low-grade (monomorphic)

cytological atypia

• Radiologically seen as grouped

microcalcifications

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Cytological features of the columnar cell lesions

have not been published in the cytological

literature, but …….

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Monolayer sheets, microcalcifications and debris

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Crowded palisading strips

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Complex sheet/aggregate

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Secretoric debris/mucous material, macrophages,

microcalcifications

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CLL diagnostics and pitfalls/caveats

• The full spectrum of cytologic features is not known

• The entity of CLL harbor a continous spectrum of architectural

and cellular/nuclear changes from «benign» to «flat atypia»

• Myoepithelial cells/nuclei are often absent

• None or low grade nuclear atypia

• Is a risk lesion for simultaneous

– ILC

– TUB

– LCIS/ALH

– Low grade DCIS/ADH

• Risk of over- and underdiagnosis

• Reporting category: proliferative, with or without atypia, and with

a reccommendation of biopsy

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Example CLL

• 65 yrs

• Group of

microcalcifications 1 cm

• US-guided FNAC

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TUB CLL

Lobular neoplasia – lobular carcinoma in situ

• several variants of lobular carcinoma in situ (LCIS)

have been recognized

–classical type

–pleomorphic LCIS (PLCIS)

–LCIS with Comedo Necrosis

–carcinoma in situ with mixed ductal and lobular

features

–clear cell variant

–signet ring cell variant

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Pleomorphic lobular carcinoma in situ (PLCIS) Sneige N et al. Mod Pathol 2002

• Cells appear dyshesive

• More pleomorphism than in

“classical” LCIS

• Usually abundant cytoplasm

• Cytoplasm may appear

eosinophilic or granular

(apocrine appearance)

• Comedo type necrosis and

microcalifications common

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PLCIS

• radiologically they appear as

suspicious microcalcifications

(almost always present)

• can be difficult to differentiate

from ductal carcinoma in situ

(on histology)

–The dyshesive

appearance of the cells is

helpful in making this

diagnosis,

–lack of E-cadherin

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Immunophenotype of PLCIS

• ER/PgR positive

• E-cadherin negative

• may show HER2 protein

overexpression/gene

amplification (particularly if

associated with invasive

carcinoma)

• may show p53 positivity

• moderate to high Ki67 labeling

index

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Cytologic features of PLCIS

• Solid three-dimensional aggregates

• Dyscohesive with loosely cohesive cells and often abundant

single cells

• Variable, but often abundant cytoplasm; often granular and

eosinophilic

• Distinct cellular pleomorphism with variable cellular size and

shape

• Often plasmacytoid

• Cytoplasmic vacuoles more common in PLCIS than in DCIS

• Distinct nuclear pleomorphism with nuclear size up in the range

of high grade DCIS (> 2x RBC)

• Comedo type necrosis and microcalcification AS IN DCIS

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Cell dissociation and pleomorphism

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Comedo necrosis and microcalcifications

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Microcalcification

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Solid, threedimensional aggregates and

myoepithelial cells

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Cytoplasmic vacuoles and amount of cytoplasm

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PAP and ThinPrep morphology

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Which means:

• Nuclear features, amount and appearance of cytoplasm,

dissociation and pleomorphism are not distinguishable from high

nuclear grade DCIS

• No cytomorphological feature(s) that definitely separates

PLCIS and high grade DCIS

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If you consider PLCIS: E-cadherin ICC

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Diagnostic considerations PLCIS

• Obviously malignant cells

• Radiological microcalcification without tumour, suspicious of high

grade DCIS

• Total overlap with cytological criteria of high grade DCIS

• Perhaps more plasmacytoid in appearance and with more

cytoplasm than most DCIS

• Cytoplasmic vacuoles more common than in DCIS

• Nuclear size > 2 x RBC, but usually not very much larger

• Previously diagnosed as DCIS in histology and cytology

• As of today: no difference in treatment

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End of session!