Benign Breast Disease

Dr. Susan J. RobertsonDr. Carolyn NessimNovember 17,2015

Objectives• Discuss Investigations and management of benign

breast disease• Describe pathogenesis of fibrocystic breast disease• Describe the pathogenesis of fibroadenoma, breast

cyst, and breast abscesses• Compare and contrast the clinical presentation of

benign vs. malignant breast disease• Explore the relationship between benign breast disease

and breast cancer• Macro and micro features of common benign and

malignant breast pathology• Explain the pathogenesis of proliferative and non‐

proliferative fibrocystic changes of the breast.

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Breast Anatomy

Ducts and Lobules

Histology (limited)

About 12 large branching ducts leading down from the nipple ending in glands or acini arranged into lobules (terminal duct lobular unit). Two layered nature of breast ducts and lobules

Clinical Presentation – Palpable mass

• Palpable lump– Fat necrosis– Breast cyst– Fibroadenoma– Breast abscess– Sebaceous cyst and lipomas– Gynecomastia in men

Clinical Presentation – Non-palpable

• Mammographic abnormality• Stellate lesion• Microcalcifications (branching, non-branching)• Concentric mass

Clinical Presentation – Nipple Discharge

• Questions must ask:– Colour– Bilateral vs. Unilateral– Spontaneous vs. Expressed

Mammogram

• BiRADs (Breast Imaging, Reporting & Data System)• 0: Incomplete, Needs more tests• 1: Normal• 2: Benign• 3: Likely benign but needs follow up• 4a: low malignant (>2 to ≤10% likelihood of malignancy – usu DCIS) • 4b: mod malignant (>10 to ≤50% likelihood of malignancy – usu DCIS)• 4c: high malignant (>50 to <95% likelihood of malignancy – usu DCIS)• 5: Malignant (Cancer)• 6: Malignant with confirmed diagnosis

Standard vs. Digital Mammography

CC and MLO views(cranio-caudal and mediolateral-oblique)

Fibroadenoma

Invasive Ductal carcinoma

Benign Calcifications

Microcalcifications in DCIS

Ultrasound – Benign findings

• Simple cysts are well-circumscribed, rounded, or oval anechoic masses with a thin or imperceptible wall and posterior acoustic enhancement.

Ultrasound - Benign Findings

• Solid nodules are:– Pure and intensely hyperechoic texture– Elliptical shape (wider than tall)– Gently lobulated shape (3 or fewer lobulations)– Complete thin capsule

Biopsies

• US guided FNA (23G, 25G) – (US)– Node– Cyst aspiration

• US guided core (14G, 16G, 10G) (US)– Lesion in breast

• Stereotactic core biopsy (Mammogram)– Microcalcs (cannot see on US)

• MRI guided core biopsy – (Cannot see on US or Mammogram)

Breast Biopsy

Palpable lump

• Physical examination benign– Smooth, round, mobile, rubbery

• Physical examination malignant– Hard, irregular, non-mobile at times, fixed to skin

or pectoralis muscle, less well defined borders• History:

– Age at menarche and menopause, birth control pill use, hormone use, history of breast cancer in the family, parity, age of first live birth, previous biopsies and investigations

Investigations & Management

• Palpable lump:– Ultrasound and mammogram– Aspiration or biopsy– Close observation (usually every 3 to 6 months for

2 years and then back to regular screening)– Surgical excision (scar and breast deformity)

RED FLAGS!

• DESPITE IMAGING, ANY PALPABLE MASS IN A WOMAN ≥ 40 yo MUST HAVE BIOSPY!!!

• IF CYST DRAINED in Post-Menopausal Women, MUST HAVE Follow-up imaging to rule out underlying malignancy

• The Diagnosis of Fibroadenoma in a post menopausal woman should be further investigated

CATEGORIZATION OF BENIGN BREAST LESIONS – Dupont, Page and Rogers

• Nonproliferative (RR is 1.0)– Cysts ( RR is 1.5)– Papillary apocrine change– Epithelial-related calcifications– Mild hyperplasia of the usual type

• Proliferative without atypia (RR is 1.5 to 2.0)– Moderate or florid ductal hyperplasia of the usual type– Intraductal papilloma– Sclerosing adenosis– fibroadenoma

• Atypical hyperplasia (RR is 3.5 to 5)– Atypical ductal and lobular hyperplasia

Benign: Fibrocystic changes +/- Proliferation without atypia

Types1. Non proliferative (no increase relative risk)- Cysts; Apocrine metaplasia; Fibrosis; Adenosis2. Proliferative Fibrocystic changes (1.5-2 relative risk)- Epithelial hyperplasia without atypia- Sclerosing lesions including sclerosing adenosis and

complex sclerosing lesions

Breast Cysts

• Most frequently seen in women ages 40 – 49• Account for 25% of masses overall and 10% of

masses in women younger than 40.• More than 50% of women who have cysts

develop more than one during their lifetime• Complex cysts have a 0.3% risk of cancer, and

can be associated with a mass• Simple cysts can be aspirated if symptomatic

Breast Cysts

• Fluid-filled, round to ovoid structures that vary in size from microscopic to grossly evident

• Derived from the terminal duct lobular unit• Epithelium usually consists of two layers: an

inner epithelial layer and an outer myoepithelial layer

Fibrocystic Change

Clinical• Feels like plaque like thickening in the breast• More often in Asian and African American

Gross Description• "Blue-dome“ large cysts• Firm gray-white fibrous tissue

Microscopic Description (non proliferative)• Cysts containing inspissated secretions which may calcify • Cysts may also contain macrophages; lined by flattened epithelium • Apocrine metaplasia

Benign Fibrocystic Changes

cysts Apocrine metaplasia calcium

Sclerosing Adenosis

• increased number of small terminal ductules or acini

• Can have deposition of calcium

• Can be Mass forming • Can be associated with

small calcifications• Can be difficult on imaging • Can be difficult for

pathologists to differentiate from cancer

Medscape.com

Radial Scars

Gross: a mass that is irregular spiculated on imaging

• easily confused with invasive cancers on mammography although there are some differences

• For the pathologist there can also be difficulties grossly and microscopically differentiating from an invasive cancer especially on a small core biopsy.

Radial Sclerosing Lesions

From Robbins

Hyperplasia

• Mild hyperplasia of the usual type– Increase in the number of epithelial cells within a

duct that is less than four epithelial cells in depth

• Florid ductal hyperplasia– Intraductal epithelial proliferation more than four

epithelial cells in depth– Often distend the involved space

Hyperplasia without atypia (Usual )

• moderate or florid ductal hyperplasia is an increased risk for breast cancer (1.5 to 2.0 x)

• No need for chemoprevention or surgical excision after core biopsy as long as there is an agreement between pathology and the clinical/ radiological findings

Medscape.com

ATYPICAL HYPERPLASIA

the bridge to neoplasia

Pathogenesis: Atypical proliferations

Atypical proliferations have some of the features of in situ carcinomas but without filling full criteria either quantitatively or qualitatively.

*Associated with a moderate increased risk of carcinoma (4-5X relative risk)

* Associated with concurrent risk of neoplasia1. Atypical Duct Hyperplasia2. Atypical Lobular Hyperplasia

ADH & ALH

ADH characterized by small, uniform, mildly atypical hyperplastic epithelial cells that pile up on themselves and distend the ducts and acini they occupySpectrum with DCIS. ADH is small (< 2mm)

• ALH is small• involving less than half the acini

in a terminal duct lobular unit • confined to proximal ducts• and/or causing no distention• Spectrum with LCIS

ADH and ALH

• Found in 2 to 3% of biopsies done for benign breast disease

• ADH characterized by small, uniform, mildly atypical hyperplastic epithelial cells that pile up on themselves and distend the ducts and acini they occupy

• Spectrum with DCIS. ADH is small (< 2mm)• ALH is small, involving less than half the acini in a

terminal duct lobular unit and confined to proximal ducts

Atypical Duct Hyperplasia- definitionFeatures that are not qualitatively/ quantitatively enough to call

in situ carcinoma. Subjectivity in interpretation

From Robbins

Medscape.com

What’s this

Atypical Duct Hyperplasia• Epidemiology <10% of core biopsies • Presentation : Not in itself palpable lesion• A risk factor for malignancy (in both breasts).

Excision after core high yield of DCIS or even invasive cancer

• Clinically, all patients with a core biopsy identifying atypical duct hyperplasia need to have an excisional biopsy.

• but not all women will progress to carcinoma. Other risk factors are add to total risk

• Follow-up and Prevention

Estrogen as Promoter

Atypical Lobular Hyperplasia qualitatively/quantitatively not enough to call Lobular Carcinoma in

Situ

Medscape.com

Atypical Lobular Hyperplasia Epidemiology. Most between 35-55.Presentation – An incidental finding on biopsy

Risk Factor 4 X relative risk factor over 4-12 years.

Coexistence of ALH does not increase risk of ADH. Other risk factors do add on to risk.

Tendency for multifocality recognized in follow-up

BENIGN NEOPLASMS

Benign Neoplasmsmost common = Fibroadenoma

• 60% of palpable breast masses in women aged 20 or less

• Definition- Mixed biphasic tumours originate from intralobular stroma and the glands of the breast lobule

• Presentation- Palpable nodule or on imaging. Circumscribed

• Hormonally sensitive – cyclic pattern of pain

• Carries no risk of carcinoma

Fibroadenoma

• Pseudoencapsulated and sharply delimited from surrounding breast tissue

• Usually spherical or ovoid• May be multilobulated• Giant (> 5 cm), Complex and Juvenile Types• Half of all biopsies are fibroadenomas• Usually women ages 15 to 30• Occur in 10% of all women• Higher risk in Asian and African American

Fibroadenoma

Fibroadenoma• Gross Pathology

reflects clinical- circumscribed margins rubbery texture, white

• Microscopy = even distribution of epithelial and stromal components and low stromal cellularity

• Does not have to be excised.

Robbins

Fibroadenoma

• Can involute and calcify presenting on mammogram with calcification

Fibroadenomas

• ALH and ADH can be found within the fibroadenoma in 0.81% of cases

• However, presence of atypia within the fibroadenoma does not predict for atypical hyperplasia in the surrounding breast tissue, also no increased risk of subsequent Br. Ca.

• Rarely, LCIS and DCIS, and invasive lobular and ductal carcinomas can be associated with a fibroadenoma

Phyllodes Tumours (rare)• Biphasic and can be difficult to

distinguish from fibroadenoma clinically

• Suspect if more than 40 years, larger than 4 cm , history of recent growth

• Problem local recurrence after excision and very rarely, malignant transformation with metastatic potential

• Leaf-like gross and increased cellularity atypia mitosis

• With clinical and good core biopsy can triage “next step” (watch, excise or excise with wider margin)

Benign neoplasms: Papillomas

1. Solitary, large, central papilloma, more common.

Present as nipple discharge 70-80%. Can be a mass. 6th decade. Can be intracystic

2. Multiple, more peripheral micropapillomasPresent less often as nipple discharge. Younger

(40-50)3. Often associated with DCIS

Papillomas

• True polyps of epithelium-lined breast ducts• Most often located close to the areola• Usually less than 1 cm• Accompanied by bloody nipple discharge• Found with ultrasound of nipple-areolar

complex• Peripheral papillomas can sometimes be

confused with invasive papillary carcinoma

Management of Papillomas

• Duct excision with underlying breast tissue to rule out DCIS

• If smaller than 2mm – vacuum assisted biopsy for full removal with surveillance imaging

• If intracystic malignancy – treat like DCIS

Benign Intraductal papilloma

Multiple Peripheral papillomata

Medscape.com

Rosen Pathology of Breast

Papillomas as risk factor

1. If NO ATYPIA solitary single papilloma carries a relative risk of 2 X

2. IF NO ATYPIA micropapillomas have a 3- 3.5 X risk

The risk of finding invasive cancer on an excisional biopsy after finding a papilloma on a core biopsy increases with the atypia seen

Atypia can extend up to the point of DCIS (quantitative rules)

TREATMENT OF BENIGN LESIONS

• Non-proliferative• OBSERVE– Cysts – Papillary apocrine change – Epithelial-related calcifications – Mild hyperplasia of the usual type• ASPIRATE– Cyst (if symptomatic or unclear diagnosis)– Abcess (requires multiple aspirations – AVOID

SURGERY)

Breast Cysts

TREATMENT OF BENIGN LESIONS• Proliferative without atypia

• OBSERVE– Moderate or florid ductal hyperplasia of the usual type– Sclerosing adenosis – Fibroadenoma• EXCISE– Intraductal papilloma – Fibroadenoma (if symptomatic, patient preference)– Radial Scar– Phyllodes Tumour

TREATMENT OF BENIGN LESIONS

• Proliferative with atypia• EXCISE• Intraductal papilloma with atypia• Atypical ductal hyperplasia (ADH)• Atypical lobular hyperplasia (ALH)• Flat-epithelium with atypia (FEA)• PASH with atypia

Interpretation of Core Needle Biopsy Results

• Ensure biopsy results are concordant with the image

• 10% of biopsies will be inconclusive, and patient will require surgical excision, if repeat biopsy remains inconclusive

• If ADH found on core biopsy, DCIS or invasive cancer is found in 20% of the subsequent surgical specimen

• Triple test: concordance with clinical exam, radiological and pathological findings

Inflammatory Lesions

• Mastitis is usually lactation related • Fat necrosis (trauma including surgery)• Granulomatous Mastitis• Non-lactational subareolar periductal abscess (Zuska Disease)• Treatment : steroids if symptomatic but can self resolve

Further lesions for self study not covered here• Diabetic Mastopathy• Mammary Duct ectasia• PASH

Mastitis +/- Abscess

• central cavity with pus. • Inflammatory infiltration

with involvement of gland. • Foamy histiocytes in

regional dilated ducts

- Physical presentation- Red, hard, tender, hot

- Etiology- usually a bacterial infection through a nipple damaged during breastfeeding

- most often Staphylococcus aureus

- Course with Rx only about 10% of women end up with an abscess (walled of collection of pus)

- Can confuse with malignant diseases if ill-defined or overlying skin thick or there is lymphadenopathy or nipple retraction –THUS REQUIRES FOLLOW-UP

- If doesn’t resolve with Antibiotics - BIOPSY

Mayo.com

Mastitis

Usually found in breast feeding patients

Erythema, fever,Tenderness, leukocytosis,Warmth to the skin

Arise from entry of bacteria through the nipple into the duct system

Breast Abscess

Usually caused by Staphylococcus aureus or enterococci, anaerobic streptococci, Bacteroides sppTreat with Keflex or Erythromycin/ Clavulin or Erythromycin +Flagyl

neutrophils

Treatment

• Warm compresses• STOP SMOKING!• Repeated aspiration• Antibiotics• Continue breast feeding or using breast pump• Incision and Drainage – LAST RESORT (risk of

lactation fistula with surgery)• NSAIDs

Breast Abscess Drainage

Breast abscess –Periareolar infectionZuska Disease

• Usually young females , mean age 32• Smokers• Squamous metaplasia of ducts, Periductal

mastitis, duct fibrosis, and duct ectasia• Mammary Duct Fistula• Ensure no underlying DCIS or other pathology

with mammogram and US once resolved

Breast Abscess-Peripheral Non-lactational

• Associated with:– Diabetes– Rheumatoid arthritis– Immunocompromised state– Usually premenopausal– Smoking

• Mammogram recommended once resolved

Granulomatous Mastitis

Granulomatous Mastitis

• Non-caseating granulomas and microabscesses• Rule out infectious organisms• More common in Asian women• Young women, usually within five years of

pregnancy• Usually non-smokers• Antibiotics not effective• Spontaneous resolution• Steroids sometimes effective• Avoid surgery –continuous drainage

Granulomatous Mastitis

Granulomatous Mastitis

Granulomatous Mastitis

• Rule out specific infection

Fat Necrosis

Definition: Disruption of fat cells is accompanied by a histiocytic response and eventually fibrous scarring.

Etiology: trauma, surgery, radiation. Can be “spontaneous”

Gross: The clinical importance is that this may present as a hard mass that can be suspicious for carcinoma on physical examination. Can have skin retraction. Indurated. Sometimes demarcated or cystic. Can be calcified

Fat Necrosis

Histology: - Acute phase: clear lipid-

filled spaces surrounded by "foamy" histiocytes and some lymphocytes.

- Calcification- Healed phase: dense

fibrous scar Rosen breast pathology

clear lipid-filled spaces

foamy" histiocytes

Benign vs. MalignantBenign Malignant

Young age, pre-menopausal Older age, post-menopausal

Mammographic and US characteristics-smooth, well demarcated

Mammographic and US characteristics-BIRADS 4-5, spiculated lesions, ill-defined

Physical exam –smooth, round, rubbery, mobile

Physical exam – hard, irregular, less well defined borders, can be fixed to skin or chest wall

Nipple discharge: Bilateral, expressed, green

Nipple discharge: Unilateral, spontaneous, bloody or straw coloured

Can often observe Must biopsy

Often does not require surgery Always requires surgery

Evaluate family risk factors Evaluate family risk factors