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BREAST PATHOLOGY

15. BREAST PATHOLOGY

Differentiation of benign breast lesions from malignant breast cancer

15.1. BREAST CANCER

Most common cause of cancer in women


Occurs mainly in women aged 40 to 60
Large increase in incidence due to introduction of mammographic screening

ETIOLOGY
Risk Factors
Increasing Age
Uncommon before age of 25
Steady increase in risk to time of menopause
Followed by slower rate of increase

Increased Estrogen Exposure


Major contributing factors
- Early menarche
- Late menopause
- Age at first child

Increased risk for women having first child after 30 years old
Estrogen replacement therapy

Obesity
Possibly due to ectopic production of estrogen in adipocytes

Genetic Predisposition
BRCA1 and BRCA2 mutation
Account for majority of hereditary breast cancers

Preexisting Breast Diseases


Proliferative and atypical benign breast lesions
Contralateral breast cancers

MORPHOLOGY
Routes of Spread
Local Involvement
Invasion into skin, skeletal muscles and ribs
- Rare due to early detection of disease with screening
Lymph Node Metastasis
Axillary lymph node most important prognostic factor
Distant Metastasis
Bone most common site of spread
- Usually osteolytic metastasis
Liver and lungs
Gross Appearance
Usually felt as a rubbery or hard lump
Malignant features:
Tethered to the skin

BREAST PATHOLOGY
Fixation to chest wall
Retraction of nipple
HISTOPATHOLOGY
2 major variants:
Ductal carcinoma
Lobular carcinoma
Ductal Carcinoma
Most common form of breast cancer
Typical Histology of Adenocarcinoma
Atypical, pleomorphic and hyperchromatic cells
Formation of tubules
Most exhibit marked increase of dense fibrous tissue stroma

Ductal Carcinoma In Situ


Cancer cells lacking the ability to invade through the basement membrane
Large increase in incidence due to mammographic screening
- Half of mammographically detected cancers

Morphology
- Similar to ductal carcinoma without invasion through basement membrane
- With areas of calcifications and central necrosis
- Historically classified into:

Comedocarcinoma with gross dark foci of necrosis

Non-comedo ductal carcinoma in situ

Pagets Disease of the Nipple


Underlying ductal carcinoma or carcinoma in situ with invasion into the epidermis
Large mucin filled clear cells in the epithelial layer of the nipple
- Pagets cells

Uncommon Variants of Ductal Carcinoma


Better prognosis compared to ductal carcinoma of no special type
Medullary Carcinoma
- Common in BRCA1 positive women
- Soft fleshy tumor consisting of large pleomorphic cells with
- Lymphocytic infiltrate surrounding and within tumor
Mucinous Carcinoma
- Isolated neoplastic cells within large lakes of mucin
Tubular Carcinoma
- Well differentiated cancers consisting of well formed tubules

Lobular Carcinoma
5 to 10% of breast carcinomas
Tends to be bilateral and multicentric
Appearance Differs from Ductal Carcinoma
Monomorphic cells with round or oval nuclei
- Signet ring cells commonly seen
Cells lack cohesion
- Strands of infiltrating cells in the form of a single file

Indian Files
- Loosely dispersed in fibrous matrix

BREAST PATHOLOGY
Lobular Carcinoma In Situ
See Ductal Carcinoma In Situ
Monomorphic and loosely cohesive population of lobular carcinoma cells
Confined within the basement membrane of the involved lobule
CLINICAL SIGNIFICANCE

Clinical Presentation
Most patients present with a breast lump or
Mammographic abnormality detected during routine screening

Classic Descriptions of Some Breast Cancer


Peau dOrange
- Thickening of skin and lymphedema
- Due to blockage of local lymphatic drainage by tumor

Inflammatory Carcinoma
- Infiltration of majority of dermal lymphatics in the affected breast
- Causing redness and tenderness

Poor prognosis due to high incidence of metastasis

Mammographic Appearance
Density
Most tumors grow as solid masses
- Radiologically denser than surrounding connective and adipose tissues
Commonly presents as a spiculated lesion with irregular infiltration

Architectural Distortion
Diffusely infiltrating masses may distort architecture without producing discrete density

Calcifications
Due to calcified secretory material or necrotic debris

Changes Over Time


Detected examination of serial mammograms
Uncertain lesions may show malignant changes over time

Prognosis
Vastly improved due to better surgical techniques and neo-adjuvant therapy

Prognostic Factors
Axillary Lymph Node Metastases
- Most important prognostic factor

Tumor Grade
- Nuclear abnormality, tubule formation and mitotic rate
- Determines degree of differentiation of tumor

Estrogen and Progesterone Receptor Status


- Positive tumors have better prognosis

Associated with lower tumor grade


- Treated with neo-adjuvant anti-estrogen therapy

Her2/Neu Amplification
- Found in up to 20% of breast cancers

BREAST PATHOLOGY

Associated with poorer prognosis


Treated with monoclonal antibody against Her2/Neu receptor

Depth of Invasion and Tumor Size


- Not as significant due to earlier presentation of cancer with introduction of mass screening

15.2. BENIGN BREAST DISORDERS

Some lesions may confer a risk of developing breast cancer

CLASSIFICATION OF BENIGN BREAST LESIONS:


Nonproliferative lesions
No risk of breast cancer
Fibrocystic changes
Benign tumors
- E.g. Fibroadenoma, lipoma, phyllodes tumor
Infections
Traumatic lesions
Proliferative without atypia
Mild increase in risk
Usual ductal hyperplasia
Sclerosing adenosis
Papilloma
Proliferative with atypia
More than 100% increase in risk
Atypical ductal or lobular hyperplasia

CLINICAL PRESENTATION OF BENIGN BREAST DISORDERS

Presentation commonly hard to differentiate from breast cancer


E.g. Breast lumps, breast pain, nipple discharge

15.2.1. FIBROCYSTIC CHANGES

Alterations of normal breast morphology present in most women

PATHOGENESIS

Response to hormones in an exaggerated manner by the lobules and stroma in the breast

MORPHOLOGY
3 principal changes
Cyst formation
Solitary or multiple cysts lined by polygonal cells
Resembling apocrine epithelium of sweat glands
- Apocrine metaplasia
Blue-dome Cyst
Gross appearance of large solitary cyst containing brownish blue fluid
Fibrosis
Chronic inflammation and fibrosis
Due to rupture of cysts

BREAST PATHOLOGY
Adenosis
Increase in number of acinar units per lobule
Gland lumens are often enlarged

CLINICAL SIGNIFICANCE

May mimic carcinoma by presenting with


Palpable lumps, mammographic densities, nipple discharge
No increased risk of cancer

15.2.2. BENIGN BREAST NEOPLASMS

No increase in risk of breast carcinoma


Unless associated with proliferative breast disease

FIBROADENOMA

Growth composed of glandular and fibrous tissue


Neoplasm of the stromal cells, glandular elements appear to be polyclonal
Responsive to hormonal stimulation
May enlarge during pregnancy and during late phase of menstrual cycle

Morphology
Gross Appearance
Pale well-circumscribed mass
- Tumor sharply delimited by fibrous capsule
Histopathology
Fibroblastic stroma enclosing
Glandular and cystic spaces lined by glandular epithelium

PHYLLODES TUMOR

Tumor arising from intralobular stroma


Majority of tumors are benign
High-grade lesions may exhibit features of malignancy
- Cystosarcoma phyllodes

Morphology
Gross Appearance
Large lesions often have bulbous leaflike protrusions
Histopathology
Differentiated from fibroadenomas by presence of:
- Increased cellularity, mitotic rate, pleomorphism

LARGE DUCT PAPILLOMA

Solitary epithelial lesions


Present as serous or bloody unilateral nipple discharge

Morphology
Composed of multiple branching papillae
Consisting of a connective tissue axis covered by
- Myoepithelial and epithelial cells

BREAST PATHOLOGY

15.2.3. PROLIFERATIVE BREAST DISEASE

Increased risk of carcinoma development

EPITHELIAL HYPERPLASIA

Most important risk factor for cancer


Increase in layers of cells in ducts

Morphology
Usually not grossly evident
Solid masses extending into duct lumen
Fenestrations can usually be seen

Classified into:
Hyperplasia Without Atypia
No increase to small increase in risk

Atypical Hyperplasia
Cellular atypia and architectural distortion
Histologically can resemble ductal or lobular carcinoma in situ
- Atypical ductal and lobular hyperplasia respectively
More than two fold increase in risk of developing carcinoma

SCLEROSING ADENOSIS

Increase in number of distorted and compressed acini


Slight increase in risk of cancer

Morphology
Increased number of acini per terminal duct
Acini compressed by stromal fibrosis can create appearance of cords or strands of cells
Mimicking carcinoma

SMALL DUCT PAPILLOMA

Occurs deep within breast


Often associated with other proliferative breast disease

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