Histopathology: disease of thebreast

These presentations are to help you identify, and to test yourself on identifying, basichistopathological features. They do not contain the additional factual information

that you need to learn about these topics, or necessarily all the images fromresource sessions.

This presentation contains images of basic histopathological features of selecteddisorders of the breast (fibrocystic change, fibroadenoma, fat necrosis, carcinoma,

gynaecomastia).Before viewing this presentation you are advised to review relevant histology, relevant

sections on neoplasia and breast in a pathology textbook, relevant lecture notes,relevant sections of a histopathology atlas and the histopathology power point

presentation on neoplasia.Copyright University of Adelaide 2011

Normal breast. Terminal portion of a breast duct (blue star) and its associated acini (yellow star). Each islined by 2 layers of cells. The layer lining the duct/acini is secretary. The basal layer comprisesmyoepithelial cells which contract to help propel the secretion.

Fibrocystic change, low power

Black stars: fibrous tissue

Blue star: small cyst

Yellow star: dilated duct

Hyperplasia of ductal epithelium(black arrows), medium power

Fibroadenoma, the edge of afibroadenoma, low power

Black arrow: well-defined margin

Yellow arrows: glandularcomponents

Blue star: paucicellular fibrousstroma

Green star: surrounding adiposetissue of breast

Fat necrosis, low power

Black star: fibrosis

Black arrows: inflammation(granulomatous in type which isdifficult to appreciate at this lowmagnification)

Other benign breast diseases in women include:

• Mastitis and breast abscess• Duct ectasia• Various sclerosing lesions• Intraduct papilloma

Gynaecomastia, medium power

Black star: fibrous stromalhyperplasia

Black arrows: glandular hyperplasia

Ductal carcinoma in situ (DCIS) of comedo type, low power. Dilated ducts (blackarrows) lined by multiple layers of epithelial cells and containing central necrosis. Thenecrotic debris frequently calcifies. DCIS may be seen on its own or in association withinvasive carcinoma.

Ductal carcinoma in situ (DCIS) of comedo type, medium power. Dilated duct lined bymultiple layers of atypical epithelial cells and containing central necrosis. The black linesoutline approximately the location of some of the epithelial basement membrane.

Ductal carcinoma in situ (DCIS) of comedo type, high power. Edge of a duct lined by multiple layers ofepithelial cells with large nuclei and focally prominent nucleoli. An atypical tripolar mitosis is seen (blackarrow). The duct contains central necrotic debris (black star). The black lines outline approximately thelocation of the epithelial basement membrane.

Area of calcification (black star) in in situ ductal carcinoma, medium power.

Paget’s disease of the nipple. Cells from a DCIS spread up along the ducts and infiltrate the epidermis of the nippleand areola resulting in inflammation. There may or may not be associated invasive carcinoma.Black arrows: malignant ductal epithelial cells infiltrating epidermis. The malignant cells are large and typically have asurrounding clear zone.Black star: inflammatory exudate on nipple

Edge of an invasive ductal carcinoma, low power. Note the irregular edge of the tumour infiltratingadipose tissue on the right and bottom of picture. This gives it a stellate appearance macroscopically.The tumour cells are darker pink/purple and are located in a paler pink fibrous (desmoplastic) stromawhich makes the tumour firm to palpation. Invasive ductal carcinomas are often very firm (scirrhous)owing to their propensity to induce desmoplasia.

Invasive ductal carcinomas of no special type,high power.Black arrows: tubule formationYellow arrows: mitosesBlack stars: tumour stroma

Invasive ductal carcinoma, high power. Nests of malignant cells can be seen infiltrating between normalterminal ducts. Note the difference in nuclear size and characteristics between the normal and malignantcells.Black stars: malignant cells. Black arrow: mitosisYellow stars: normal ducts (note normal 2 layers of cells lining the ducts)

Invasive ductal carcinoma, medium power view. This tumour shows a cellulardesmoplastic stroma (black stars).Yellow stars: malignant cells

Invasive lobular carcinoma, medium power view. In this classic type, relatively uniformtumour cells grow in an ‘Indian file’ (rows of single cells) pattern.

PathologyTissue removed from the patient is sent to

the pathology laboratory. The pathologistexamines the specimen and

• Describes and measures +/-photographs the specimen

• Orientates the specimen and inks thesurgical margins such they can be seenin the histopathology sections todetermine and document completenessof excision of the lesion

• Sections the specimen• Describes and measures the lesion and

measures how far it is from the surgicalmargins

• Describes any other features

Sectioned breast specimen with inked margins

Pathology

• Sections and selects appropriatepieces of the specimen to beexamined histologically i.e.requiring paraffin embedding,sectioning and staining

• Documents which parts of thespecimen have been selected forhistopathological examination,and in which of the labelledcassettes they have been placedfor paraffin embedding Cassettes with sectioned tissue

to be paraffin embedded

Pathology

• The pieces of tissue areembedded in paraffin, sectionedand stained with haematoxylinand eosin for histopathologicalassessment

• The macroscopic description,record of sections (block key)and histopathologic descriptionall form part of the report

Breast cancer synoptic reportMany features affect the prognosis and management of malignancy. The pathologistprovides much of this information in the pathology report of the surgically excisedspecimen with lymph nodes. This often detailed information is usually presented in aconsistent fashion in a synoptic report. These differ somewhat depending on themalignancy. The information is important for determining prognosis and for tailoringmanagement to individual patients. You don’t need to memorize the details of thefollowing synoptic report, which at this stage, is for information only. Note, however,the extent of information that is provided by the pathologist following examination ofthe specimen and sections to the referring clinician. Medical students should get intothe habit of reading the pathology reports in patient notes, as doctors you will beexpected to understand them. You should have a general understanding, however,of the features that are important in assessing the prognosis and management ofmalignancies, including some specific information about the major malignancies e.g.specific grading scheme, oestrogen and progesterone receptors, HER2 in breastcancer.

Breast cancer synoptic report

Breast:• Left

• Right

Specimen:

• Excisional (for palpable mass)

• Mammographic Localisation

• Incisional (includes core needle and FNA)

• Re-excisional

• Mastectomy

• Chest wall

Specimen Size:

Breast cancer synoptic report

Invasive carcinomaTumour size:Tumour type:• DCIS: ductal carcinoma in situ• LCIS: lobular carcinoma in situ• Infiltrating ductal (NOS)• Infiltrating lobular• Mixed NOS/ILC• Tubular• Mucinous• Medullary• Papillary• Cribriform• Other (specify)

Breast cancer synoptic report

Invasive carcinomaTumour Grade:

• (Bloom and Richardson with Elston's modification): I, II, III

• Nuclear grade: /3,

• Score for tubule formation: /3,

• Score for mitosis: /3Gross margin:• Free (specify distance)• Involved

Histologic margins of invasive carcinoma

• Free (specify distance)

• Focal

• >Focal

• Unevaluable

Breast cancer synoptic report

Peritumoural vascular invasion:

• Absent

• Probable

• Present

• Dermal

Breast cancer synoptic reportDCISExtent DCIS within invasive tumour:• Absent• Slight• Moderate marked• Tumour primarily DCIS with focal invasionExtent DCIS adjacent to invasive tumour:• Absent• Slight• Moderate markedEIC status:• EIC positive – please specify:• (DCIS comprising greater than 25% of the area delimited by the infiltrating tumour and intraductal carcinoma

of any extent outside the margin of the infiltrating tumour)• or (DCIS with foci of stromal invasion)• EIC negative• EIC indeterminate

Breast cancer synoptic reportMargins of DCIS:• Free (specify distance)• Focal• >Focal• UnevaluableDCIS nuclear morphology:• High grade• Intermediate grade• Low gradeDCIS patterns (specify all that apply):• Large areas of central necrosis (comedo)• Small areas of central necrosis• Cribriform• Solid• Micropapillary• Papillary

DCIS – presence of comedo necrosis:Calcification in in-situ:

•Absent

•Prominent in DCIS

•Focal in DCIS

•In LCIS

•Prominent in benign breast tissue

•Focal in benign breast tissue

Breast cancer synoptic reportSkin:• Not sampled• Free• Invasive• Dermal lymphaticNipple:• Not sampled• Free• Invasive• Dermal lymphatic• DCIS• Paget'sMuscle:• Not sampled• Free• Involved

Mastectomy tumour location:•1) Central•2) UOQ •3) UIQ •4) LOQ •5) LIQMultiple areas involved:•1) Central•2) UOQ•3) UIQ•4) LOQ•5) LIQ•6) Only 1 area involved

Breast cancer synoptic report

Lymph nodes:• Total• Number involved• Sentinel Node involved/not involved (state

number)• Specify if size of nodal metastases is less than

2 mmExtranodal extension:• Absent• PresentNature of nontumourous breast tissue

(describe):

Breast cancer synoptic report

Breast Markers• Date of report:• Block No:

Oestrogen receptor status:• % Tumour nuclei staining: <1%(negative) 1-10% 11-25% 26-50% 51-75% >75%• Staining intensity: weak/intermediate/strong

Progesterone receptor status:• % Tumour nuclei staining: <1% (negative) 1-10% 11-25% 26-50% 51-75% >75%• Staining intensity: weak / intermediate / strong

MIB-1 count (proliferative cell index):• <20% (low) 20-30% (intermediate) >30% (high)

Oestrogen receptors are in the nucleus. Immunohistochemistry reveals>75% of this tumour’s nuclei to be staining strongly (brown).

Breast cancer synoptic report

HER2 staining score (on immunohistochemistry):Scoring system:

• No staining is observed or membrane staining is observed in less than 10% ofthe tumour cells. Overall score for Her 2 is therefore 0 (Negative)

• A faint/barely perceptible membrane staining is observed in more than 10% ofthe tumour cells. Overall score for Her 2 is therefore 1+ (Equivocal)

• A Weak to moderate complete membrane staining is observed in more than10% of the tumour cells. Overall score for Her 2 is therefore 2+ (Equivocal)

• A strong complete membrane staining is observed in more than 10% of thetumour cells. Overall score for Her 2 is therefore 3+ (Positive)

HER2 staining (immunohistochemistry): A strong complete membrane staining is observed in more than 10% of thetumour cells (above). Overall score for HER2 is therefore 3+ (Positive). HER2 (Neu, ERB-B2) is a proto-oncogenebelonging to the family of epidermal growth factor receptors. Gene amplification resulting in increased receptorexpression (on the cell surface) is present in a proportion of breast carcinomas. Binding of specific ligands activatesthe receptor, triggering signal transduction and activating cascades that affect cell proliferation. HER2overexpression is thus involved in the pathogenesis of some tumours and such tumours have a worse prognosis.Determining the presence of HER2 overexpression is also utilised in management as these patients can be treatedwith Trastuzumab (Herceptin), a monoclonal antibody targeted to HER2 protein. Other newer methods are nowfrequently being used to detect HER2 overexpression e.g. silver in situ hybridisation

Silver In Situ Hybridization (SISH) for HER2. Each black dot represents one copy of the HER2 gene.Cases with a mean HER2 gene count of >6 per nucleus, counted in at least 40 cells, are regarded asamplified. When the HER2 gene count is between 4 and 6 per nucleus, SISH for the centromere tochromosome 17 is used to determine the HER2/CEP17 ratio, for which >2.2 is amplified.

Investigation

• Biopsy: needle core biopsy to give a piece of tissue forhistopathological assessment

Investigation

• Biopsy: fine needle aspiration to give cells for cytologicalassessment

fibrocystic

Cells from a fine needle aspiration. Sheet of cohesive epithelial cells with uniform smallnuclei (benign) (black star) and background foamy macrophages (arrows) from a cyst infibrocystic change.

Cells from a fine needle aspiration. Sheet of cohesive epithelial cells with uniformsmall nuclei (benign) (black star). Note other cells with much larger nuclei (yellowstars). These are malignant.

Cells from a fine needle aspiration.A: Low power view of a very cellular smear from a carcinoma. Malignant epithelial cells lose their cohesiondue to loss of intercellular junctions, appearing in a smear as loosely cohesive sheets and single cellscompared to the more cohesive sheets of benign and normal epithelial cells (C). Loss of cohesion in vivoenables invasion into and through tissues.B: Higher power view of malignant epithelial cells.

A B

C