BREAST PATHOLOGY DR TANWEN WRIGHT

• Breast Reporting Guidelines

• B categories

• Lymph node categories

• Management of B3 lesions

WHAT WE’LL COVER

• Papillary Lesions

• Papilloma

• Papillary DCIS

• Encysted Papillary Carcinoma

• Solid Papillary Carcinoma

• Immunohistochemsitry

PAPILLARY LESIONS

• The problem with papillary lesions

• Generally identifying a breast lesion as papillary is not difficult

• Based on finding a proliferation characterised by finger-like projections or fronds

composed of a central fibrovascular core covered by epithelium

• The problem with papillary lesions

• Once identified it’s the categorisation of the lesion into benign/atypical/malignant is

often difficult

• Even when you recognise it as malignant determining whether is in-

situ/invasive/combination is difficult

• On biopsies it can be really tricky!

PAPILLOMA

• Benign

• Solitary

• Subareolar large ducts

• 40 – 60’s, rarely kids/adolescents

• Prone to nipple discharge

• Multiple

• Periphery

• Usually younger

• Synchronous , recurrent or bilateral proliferative breast lesions

• Fibrovascular cores

• Covered by an inner myoepithelial cell layer and an outer epithelital layer

• Lacks significant cytological atypia

• Mits absent or rare

• 1layer/few layers/Varying degrees of UDH (can grow contiguously between papillae)

• Can have quite a heterogenous appearance

• Varying degrees of epithelial proliferation, FCCH, stromal sclerosis

• Duct

• Myoepithelial cells surround the involved duct

IMMUNOHISTOCHEMISTRY

• CK5/6, p63, Smooth muscle myosin,

• Fibrovascular Core

• Duct space

• ER heterogenous

CK5/6

P63

CK5/6

CK5/6

ER

CK5/6

PAPILLOMA WITH ATYPIA AND PAPILLOMA WITH DCIS

• Different to papillary DCIS

• When the papilloma exhibits areas of epithelial proliferation that fulfil the

criteria for a diagnosis of ADH or DCIS

• Atypia can involve the papilloma to varying extent, usually find features of a

benign papilloma in part of the lesion

• DCIS – low/int grade, solid/cribriform/micropapillary

p63

CK5/6

Remember Papilloma with usual hyperplasia

IMMUNOHISTOCHEMISTRY

• P63

• Decreased or absent in foci of ADH/DCIS

• Remains readily identifiable in areas of residual benign papilloma and around the

periphery

• CK14 and CK5/6

• Lack of expression in atypical area, positive around duct

• ER

• Typically expressed in homogenous fashion in atypical area

RISK OF MALIGNANCY

• Breast cancer risk in atypical papilloma – similar to ADH elsewhere in the breast (4-

5X).

• Breast cancer risk particulary high (7X) if multiple papillomas with atypia

• Distinguishing between papilloma with atypia and papilloma with DCIS, may be of

questionable clinical importance

• Risk of recurrence isn’t related to the extent of atypia/DCIS in the papilloma - it’s the

presence of ADH/DCIS in the surrounding breast tissue that’s important

• Treatment - complete excision and careful follow up

• Careful examination of the surrounding breast for ADH/DCIS – this is the major feature

influencing management decision

PAPILLARY DCIS

• Not the same as papilloma with DCIS

• This is where DCIS has a papillary architecture

• Papillary proliferation itself is neoplastic – no evidence of pre-existing papilloma

• Papilloma with DCIS on the other hand – DCIS is grafted onto pre-existing benign

papilloma

• Fibrovascular cores are lined by neoplastic epithelium

• In Papillary DCIS the papillae are usually more delicate and less fibrotic than

in an intraductal papillomas

• Makes it look more blue, whilst papilloma looks more pink

• Epithelium may consist of one-several layers

• Varying degrees of stratification

• Can get more solid/cribriform/micropapillary bits

• Can get contiguous growth between papillae

IMMUNOHISTOCHEMISTRY

• Loose myoepithelial marker in papillae

• If myoeputhelial expression persists in papillae this is more likely to be extensive

involvement of a papilloma by DCIS

• BUT retain it in the surrounding duct

• ER heterogenous

SMM

ENCAPSULATED (INTRACYSTIC/ENCYSTED) PAPILLARY CARCINOMA

• Papillary carcinoma within a cystically dilated duct

• Usually present as a subareolar mass

• +/- nipple discharge

• Most frequently in elderly women

• Macro

• Friable/ bossolated mass within a cystic space

• Micro

• One/occasionally several nodules of papillary carcinoma surrounded by thick fibrous

capsule

• Central papillary carcinoma in situ surrounded by a hyalinised fibrous wall – giving it an

encysted/encapsulated appearance

IMMUNOHISOTCHEMISTRY

• Lack myoepithelial markers in the fibrovascular cores

• Large proportion lack myoepithelial markers in the surrounding duct

• Unlike papillary DCIS which shows staining in the surrounding duct

WHAT IS ITS NATURE?

• Some debate over this

• Some authors argue that the lack of myoepithelial cells indicates that it is an indolent

invasive carcinoma

• Albeit with similar behaviour to DICS

• A tiny percentage show axillary Lymph node metastasis

• However it has an excellent outcome with adequate local therapy alone

• Therefore prudent to continue to manage them as they’re currently managed – like DICS

and to avoid categorisation as frankly malignant

• B5a on biopsy

• The presence of DICS in the surrounding tissue is recognised local recurrence

and should therefore be reported

• Not uncommon to find entrapped neoplastic epithelial cells in the fibrous

capsule

• May be misinterpreted as frankly invasive carcinoma

• Areas of unequivocal invasive carcinoma can be seen – NEEDS TO BE SEEN

BEYOND THE FIBROUS CAPSULE

• Only report the size of the frankly invasive component

SOLID PAPILLARY CARCINOMA

• Also considered a variant of DCIS

• Older, postmenopausal women

• Frequent neuroendocrine differentiation

• Called solid because of the inconspicuous nature of the papillae

• Tends to involve larger central ducts

• Nipple discharge/bleeding

MICRO

• Intraluminal proliferation

• Cells often have streaming architecture (like UDH)

• Inconspicuous supportive stalks

• Can resemble UDH on low power

• But the cells show less overlapping , greater monotony, more hyperchromatic and mits easy to find

• Perivascular palisaiding of tumour cells

• Cytoplasmic/ intraluminal mucin

• Unsual

IMMUNOHISTOCHEMISTRY

• Myoepithelial markers negative in papillae, may or may not be around duct

• ER uniform

• Neuroendocrine markers

SMM

Synaptophysin

INVASIVE OR NOT INVASIVE?

• Conventional carcinoma more frequently seen in solid papillary carcinoma than in encysted papillary carcinoma

• This lesion lacks myoepithelial markers so is it an invasive carcinoma – debate rages

• Mets reported

• But regardless (again) it has an indolent clinical course

• Just to confuse you even more there are solid papillary carcinoma that are considered invasive

• WHO definition

• Geographic jigsaw pattern with more ragged and infiltrative margin and complete lack of myoepithelial cells

• But complex architecture is very subjective

• Other texts you other definitions

• Usually demonstrate mucin or neuroendocrine features

• Basically tricky!!

REPORTING GUIDELINES

COMPLICATIONS OF NEEDLE CORE BIOPSIES THAT CAN CAUSE DIFFICULTIES FOR THE PATHOLOGIST

• Removal of lesion by core biopsy

• Does happen – don’t panic!!

• Especially if lesion is small – especially if its already been extensively sampled

• Core biopsy will need to be provide info on differentiation and type

• Seeding of tumour

• May cause problems in the excision

• Cells seen out of the main lesion in fibroblastic and histiocytic tissue

B CATEGORIZATION

HOW WOULD YOU CATEGORISE THE FOLLOWING?

• Clincial details state ?lipoma, core shows fat only

• Clicical details: deformity, core shows a tiny amount of fibrocystic change

• Clincal details: Microcalcification, core shows tiny focus of microcalc (less than

0.1mm)

• Clincal Details: ?papilloma ?FA, core shows small papillary lesion which is

benign – papilloma,

CATEGORISATION

• Designed to take into account PURELY the HISTOPATHOLGICAL nature of the

specimen

• NOT the clinical and imaging characteristics

• DO NOT use B1 because the biopsy may not reflect the clinical or

radiological abnormality

• Judgement about the lesion being adequately sampled is the responsibility of

the MDT

B1- NORMAL TISSUE

• Whether or not breast glandular structures present (state it in report)

• Normal breast ducts and lobules

• Mature adipose tissue

• Stroma only

• May indicate lesion not sampled – but not necessarily (harmatomas/lipoms)

• Minor degree of fibrocystic change best categorised as B1 – MDT

• Mammograms do not demonstrate microcalc singly/in clusters less than 100um

• Role of MDT not the Pathologist alone to determine if the biopsy is adequate

• Exceptionally - uninterpretable – eg excessive crush aretfact

B2 – BENIGN LESION

• Fibroadenoma

• Fibrocystic change

• Scelrosing adenoasis

• Duct ectasia

• Abscesses

• Fat Necrosis

• Definite benign skin lesions

• Sometimes difficult to categorise lesion – eg adnexal tumour B3 it

B3 – UNCERTAIN MALIGNANT POTENTIAL

• Need to comment on the presence of ATYPIA

• Risk of malignancy at excision (upgrade) varies depending on whether or not

there is atypia

• Radial Scar

• Papillary lesions

FLAT EPITHELIAL ATYPIA

• Columnar cell change with superimposed with mild cytological atypia

• In round mildly dilated acini, typically single layer

• Architectual complexity – ADH/LG DCIS

• If there is high grade nuclei

• Limited B4

• Extensive – DCIS – B5a

• If

NON-INVASIVE LOBULAR NEOPLASIA

• Classical non-invasive lobular neoplasia

• B3

• Pleomorphic LCIS

• B5a

• LCIS with necrosis, but not pleomorphic

• B4

Pleomorphic LCIS

LCIS with necrosis

ATYPICAL EPITHELIA PROLIFERATION

• Includes ADH

B4 - SUSPICIOUS

• Technical problems such as crushed or poorly fixed cores that contain probable carcinoma but

cannot provide the definitive diagnosis

• Similarly, small groups of apparently neoplastic cells contained within blood clot or adherent

to the outer aspect of the sample

• Very small foci suspicious of invasive carcinoma in which there is insufficient material to allow

immunocytochemistry

• non-high grade intraductal

• proliferation with a significant degree of atypia probably representing intermediate or

lowgrade

• DCIS, where relatively few involved duct spaces are represented in the biopsy

• Definitive therapeutic surgery should not be undertaken as a result of a B3 or B4 core biopsy

B5 - MALIGNANT • B5a

• Ductal carcinoma in situ

• Pleomorphic LCIS

• Encysted papillary carcinoma

• B5b

• Invasive carcinoma

• Lymphoma, metastases, malignant phyllodes

• B5c

• Malignant but uncertain whether invasive or in-situ

• Rarely used

• NOT for lymphoma/mets/malignant phyllodes

MICROINVASION

• If area of invasion <1mm on biopsy, what do you do?

• DCIS + microinvasion

• B5a but mention microinvasion

• DCIS + area suspicious of microinvasion

• B5a

• No DCIS + unequivocal microinvasion

• B5b

• No DCIS + area suspicious of microinvasion

• B4

• B5c should not be used

LYMPH NODES - FNA

• LC1 inadequate

• No lymphoid cells or technically inadequate

• LC2 Benign

• LC3 atypia

• Atypical lymphoid cells or uncertain types

• LC4 Suspious

• Of met or lymphoma

• LC5 Malignant

• Carcinoma or other malignancy

LYMPH NODE - BIOPSY

• Mirrors FNA