Pathogenesis and histopathological diagnosis of carcinoma of breast

Dr. Munazza Azam SindhuAssistant Professor Department of PathologyAziz Fatima Medical and Dental College

Carcinoma of breast

• Carcinoma of the breast is the most common non-skin malignancy in women and is second only to lung cancer as a cause of cancer deaths.

ETIOLOGY AND PATHOGENESIS

Sporadic

• The major risk factors for sporadic breast cancer are related to

• Hormone exposure• Gender

• Age at menarche and menopause

• Reproductive history• Breastfeeding• Exogenous estrogens.

Familial Breast Cancer

– Approximately 12% of breast cancers occur due to inheritance of an identifiable susceptibility gene or genes.

– Inheritance of a defective copy of a tumor suppressor gene.

– BRCA1, BRCA2, TP53, and CHEK2

– Mutations in BRCA1 and BRCA2 are responsible for 80% to 90% of “single gene” familial breast cancers and about 3% of all breast cancers.

• BRCA1-associated breast cancers:• Commonly poorly differentiated• ER-negative/HER2-negative (basal-like)

• BRCA2-associated breast carcinomas:• Relatively poorly differentiated• More often ER-positive than BRCA1 cancers.

Familial Breast Cancer

Types of biopsy procedures

• Fine needle aspiration biopsy– ultrasound-guided

• Core needle biopsy– A slightly larger, hollow needle is used to withdraw

small cylinders (or cores) of tissue from the abnormal area in the breast.

• Surgical (open) biopsy– incisional biopsy

– removes only part of the suspicious area, enough to make a diagnosis.

– excisional biopsy– removes the entire tumor or abnormal area, with or without trying to

take out an edge of normal breast tissue

MORPHOLOGY OF BREAST CARCINOMAS

DCIS

• Mastectomy is curative in greater than 95% of women

• Breast conservation is appropriate for most women but has a slightly higher risk of recurrence.

Paget disease of breast

Invasive (Infiltrating) Carcinoma

• Presents as a palpable mass.

• By the time becomes palpable, over half the patients will have axillary lymph node metastases.

• May be fixed to the chest wall or cause dimpling of the skin.

• Lymphatics may block the local area of skin drainage and cause lymphedema and thickening of the skin--- peau d'orange.

• Retraction of the nipple may develop

Invasive ductal carcinoma

Divided according to 2 major criteria;

1. Cytoarchitectural variants--- 75% NOS type & others as special types.

2. Pattern of spread--- inflammatory carcinoma & Paget’s disease.

Typical IDC, irregular crab like, white fibrous appearance,& chalky streaks, retraction of the overlying skin

Invasive ductal carcinoma

Tumor can grow in diffuse sheets, nests, cords or as individual cells showing Glandular/tubular differentiation

Medullary Carcinoma

Well circumscribed character & fleshy appearance

Medullary Carcinoma

Large tumor cells grow in a syncytial fashion, & are sharply separated from the surrounding stroma, which is heavily infiltrated by lymphocytes & plasma cells

Tubular Carcinoma

well differentiated with excellent prognosis

Cribriform Carcinoma

• Tumour has cribriform appearance similar to its in situ counterpart but with stromal invasion

Mucinous carcinoma

• Usually in post menopausal women.

• Grossly well circumscribed, crepitant to palpation

• Typical gelatinous gross appearance, sharply circumscribed quality

Balls of cancer cells floating in gelatinous secretions

Mucinous carcinoma

• Breast carcinoma with entire breast reddened & warm with widespread edema of skin simulation mastitis.

• Undifferentiated carcinoma with widespread carcinomatosis dermal lymphatics.

Inflammatory carcinoma

Large tumour embolus in a dermal lymphatic in a case of clinical appearance of inflammatory carcinoma

Inflammatory carcinoma

Invasive Lobular Carcinoma

• Palpable mass or mammographic density.

• A diffuse pattern of invasion without prominent desmoplasia--- a vaguely thickened area of the breast or subtle architectural changes on mammography.

• Greater incidence of bilaterality. • Incidence is increasing among postmenopausal

women, may be related to the use of postmenopausal hormone replacement therapy.

• Lack of accumulation of p-53, absence of E-cadherin.

Invasive Lobular Carcinoma

Tumor cells small & uniform with round nuclei & grow in indian file pattern, Signet-ring cells are common.

– Well-differentiated and moderately differentiated invasive lobular carcinomas

– Express hormone receptors, and are associated with LCIS in the majority of cases.

– HER2/neu over-expression is very rare.

– Poorly differentiated lobular carcinomas– Often lack hormone receptors, and may over-express

HER2/neu.

• If matched by grade and stage, lobular carcinomas have the same prognosis as carcinomas of NST.

Invasive Lobular Carcinoma

Scarf bloom richardson grading

Molecular Subtypes of Breast cancer

• Luminal Type A– ER+ &/or PR+, HER2-– Most common subtype– Hormone responsive– Good prognosis

• Luminal Type B– ER+ &/or PR+, HER2+– Worse outcome that Luminal A

• HER2+ (ER-)– Less common, aggressive

subtype– High grade histology– Outcome improved with

Herceptin– Risk at young age

• Basal-Like– Triple negative– Aggressive subtype– High grade histology– Risk at young age– More common in African

American women– Constitute 20% of all breast

cancers– Propensity for metastasis

PROGNOSTIC & PREDICTIVE FACTORS

INVASIVE CARCINOMA VERSUS IN-SITU DISEASE

– Treated DCIS - majority are cured – Invasive carcinoma - 50 % have local or

distant metastasis at the time of diagnosis

SIZE OF PRIMARY TUMOUR– 1cm tumor, LN - 10 years survival rate >

90%– more than 2cm with LN – it is < 77 %– EXCEPR HER2 +VE CA

LYMPH NODE INVOLVEMENT AND NO. OF LYMPH NODES INVOLVED•Most important factor•10 years survival rate

– No nodal involvement 70 - 80 %– 1-3 positive nodes 35- 40 %– More than 10 positive nodes 10-15 %

DISTANT METASTASIS– Rarely curable– Palliations achieved only in ER +ve cases

LOCALLY ADVANCED DISEASE– Invading skin and skeletal muscle are

usually large, difficult to treat surgically

INFLAMMATORY CARCINOMA– ( less than 3 %)

– Poor prognosis, dermal lymphatic involvement

– 3 years survival rate - 3-10 %

Clinical Stages

• Stage 0. DCIS or LCIS (5-year survival rate: 92%).

• Stage I. Invasive carcinoma 2 cm or less in diameter (including carcinoma in situ with microinvasion) without nodal involvement (or only metastases < 0.02 cm in diameter) (5-year survival rate: 87%).

• Stage II. Invasive carcinoma 5 cm or less in diameter with up to three involved axillary nodes or invasive carcinoma greater than 5 cm without nodal involvement (5-year survival rate: 75%).

• Stage III. Invasive carcinoma 5 cm or less in diameter with four or more involved axillary nodes; invasive carcinoma greater than 5 cm in diameter with nodal involvement; invasive carcinoma with 10 or more involved axillary nodes; invasive carcinoma with involvement of the ipsilateral internal mammary lymph nodes; or invasive carcinoma with skin involvement, chest wall fixation, or clinical inflammatory carcinoma

(5-year survival rate: 46%).

• Stage IV. Any breast cancer with distant metastases (5-year survival rate: 13%).

Clinical Stages

Recent Advances

There have been two recent advances in the breast cancer research field that have lead to paradigm shifts: first, the identification of intrinsic breast tumor subtypes, which has changed the way we think about breast cancer and second, the recent characterization of cancer stem cells (CSCs), which are suspected to be responsible for tumor initiation, recurrence and resistance to therapy. These findings have opened new exciting avenues to think about breast cancer therapeutic strategies.