breast cancer

Breast pathology

Breast cancer

Breast cancer

Malignant tumors of the breast

Primary:Epithelial: breast carcinomaMesenchymal: sarcomas

Secondary

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Breast carcinoma

Breast cancer

Epidemiology:

It is a disease of developed countries.It is a very common neoplasm constituting 20%

of cancer death in females. One third of breast cancer patients die due to the disease.

It is the second most important cancer killer for females in the USA.

One in every 9 females develops breast carcinoma in her lifetime.

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Increased incidence of early breast cancer detection due to mammographic screening , leading to detection of small early (and even non-invasive) breast cancer

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Increased detection of early pre-invasive breast cancer is balanced by increased incidence of invasive breast cancer. So mortality is slightly decreased

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Epidemiology (Gharbiah):

Breast cancer constituted 37% of cancer in women in our locality (Al-Gharbiah) in 1999, forming the most common cancer among females.

After age standardization, breast cancer formed about 50 per 100,000 per year in Al-Gharbiah females

The second most common cancer was non-Hodgkin’s lymphoma forming (8%) of all female female cancers

Breast cancer

Risk factors

Gender : Females are at higher risk than males. Race: More common in Caucasian and Jews. Age: 30-60 years. however, younger and older ages could be affected. Family history: There is family history especially in mothers and sisters (first degree relative, earlier and of the same pathology).

However, 85% of females with family history of breast cancer does not develop breast cancer Past history: Females with previous breast cancer are at increased risk of developing new breast cancer

Breast cancer

Menstruation: Early menarche and late menopause. [increased estrogen exposure]

Pregnancy & lactation: Nulliparous females, delayed first pregnancy and absence of breast feeding are important risk factors.[increased unopposed estrogen exposure]

High fat diet and obesity: Due to local synthesis of oestrogen. Risk may be decreased by beta carotene intake

Risk factors

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Risk factors - Genetic factors

Strong family oncogene (HER2/Neu) is present in some cases.

25% of familial breast cancer is attributed to BRCA1 & BRCA2 germline mutations.

Other cases of breast cancer is related to Li-Fraumini syndrome (germline TP53 mutation) and cawden syndrome (Germline PTEN mutation).

However, all these mutations accounts for only 30% of familial breast cancer, leaving about two thirds unexplained.

Breast cancer

Risk factors

Hormones: 1- Oestrogen exposure (as in late

menopause and in replacement therapy). 2- Prolactin excess (weak evidence).

Viruses:Bittner milk factor (virus) is incriminated in

the development of breast carcinoma in mice.

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Precancerous lesions:

Proliferative changes (especially atypical hyperplasia) : High risk in patient with fibrocystic disease particularly those with marked epitheliosis

Duct papilloma

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Ductography : injection of contrast material into one lactiferous duct, indicating the complex branching of a single lactiferous duct, and showing a single breast lobe (or segment)

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Classification of breast carcinoma

I- Carcinoma of ductal origin

II- Carcinoma of lobular origin

Each can be invasive and non-invasive

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I- Carcinoma of ductal origin:positive for E-Cadherin

1- Ductal carcinoma in situ (DCIS)=Intraduct carcinoma

2-Infiltrating ductal carcinoma:

a) With prominent intraductal component :1-Infiltrating papillary carcinoma 2-Infiltrating comedo carcinoma.3-Infiltrating cribriform carcinoma.

b) Without intraductal foci = Infiltrating Ductal Carcinoma-Not other wise specified (IDC-NOS) or Infiltrating Duct Carcinoma of No Special Type (IDC-NST)

Breast cancer

c) Special types of IDC :

1- Medullary carcinoma 2- Colloid carcinoma.3- Paget's disease of the nipple 4- Adenoid cystic carcinoma. 5- Tubular carcinoma6- juvenile (secretory carcinoma).7- Apocrine carcinoma8- Carcinoma with neuroendocrine

differentiation.

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II-CARCINOMA OF LOBULAR ORIGIN:Negative for E-Cadherin

1-Lobular carcinoma in situ (LCIS)

2- Infiltrating lobular carcinoma

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It is non-invasive (early) carcinoma (intact basement membrane)

Recently increased in incidence [from 5% to 30% of breast cancer] (i.e. detecteion) by mammography (microcalcification)

Gross picture: Most commonly detected as mammographic calcification, less commonly as area of increased density (periductal fibrosis).It may form a palpable small hard mass and may cause bleeding or serous discharge from the nipple. Squeezing of the mass yields necrotic pasty-like material in cases of comedo type

Ductal carcinoma in situ (DCIS) = Intraduct carcinoma

Breast cancer

Ductal carcinoma in situ (DCIS) = Intraduct carcinoma

Microscopic picture:

within a single ductal system,

spreading within the duct ,

and when this is extensive , it may involve an entire segment

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DCIS- Microscopic picture :

The ducts are enlarged and lined by several layers of malignant cells without invasion of the basement membrane. The pattern of growth of the malignant cells may be cribriform, papillary, micropapillary, solid or comedo Recently, it is comedocarcinoma and non-comedo DCIS

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The classic cribriform pattern of intraductal carcinoma of the breast. they have holes with sharp margins as though punched out by a cookie cutter.

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Neoplastic cells are still within the ductules and have not broken through into the stroma. Note that the two large lobules in the center contain microcalcifications. Such microcalcifications can appear on mammography

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This mammogram reveals multiple clusters of small, irregular calcifications in a segmental distribution. Suspicious calcifications must be biopsied, as 20% to 30% will prove to be due to DCIS.

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DCIS- Prognosis:

Rarely becomes invasive if not treated.The consensus seems to be that many cases of small, low-grade DCIS, and probably most cases of high-grade and extensive DCIS, progress to invasive carcinoma, emphasizing the importance of proper diagnosis and appropriate therapy for this condition

Breast cancer

PAGET'S DISEASE OF THE NIPPLE

Malignant cells, referred to as Paget cells, extend from DCIS within the ductal system (especially the lactiferous sinuses) into nipple skin without crossing the basement membrane .

The tumor cells disrupt the normal epithelial barrier, and this allows extracellular fluid to seep out onto the nipple surface.

The Paget’s cells are easily detected by nipple biopsy or cytologic preparations of the exudate.

Breast cancer

PAGET'S DISEASE OF THE NIPPLE

Gross picture: - Nipple eczema or ulceration. - Excoriation of the areola. -There may or may not be a palpable mass.

Microscopic picture: - The basal layer of epidermis is infiltrated by large malignant

cells with clear cytoplasm and large hyperchromatic nuclei (Paget's cells).

- There is an underlying carcinoma which may be intraduct or invasive carcinoma.

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INFILTRATING DUCTAL CARCINOMA

NOT OTHERWISE SPECIFIED (IDC-NOS)

It is the most common type of breast carcinoma (80%)

Infiltrating Duct Carcinoma of No Special Type (IDC-NST)

Skin manifestations:-The skin covering of the tumour may simulate the peel of an orange “peau d’orange” [lymphatic edema]. -There may be also nipple retraction and sometimes ulceration.-Dimpling-Tethering-Cancer en cuirase-Skin nodules

Breast cancer

This mastectomy specimen demonstrates the gross findings of "inflammatory" carcinoma of breast. This is not a specific histologic type of breast cancer, but rather it implies dermal lymphatic invasion by some type of underlying breast carcinoma. Such involvement of dermal lymphatics gives the grossly thickened, erythematous, and rough skin surface with the appearance of an orange peel ("peau d'orange" for you francophiles).

Breast cancer

Gross picture:

The tumour is non-capsulated, hard in consistency, irregular and spiky. Colour: grayish white Site: commonly in the upper outer quadrant of the breast. The cut surface is chalky and concave. The tumour gives a gritty sensation during cutting due to excessive fibrous stroma.

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The tumour is composed of diffuse sheets, well-defined nests, and cords of somewhat cohesive malignant cells separated by dense stromal fibrosis (desmoplastic reaction)

Microscopic picture:

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MEDULLARY (ENCEPHALOID) CARCINOMA

It is a soft carcinoma less common than scirrhous carcinoma.

Gross picture: The tumour forms a soft, fleshy well-circumscribed, large mass. Cut surface usually bulges and is grayish, red or yellow with areas of haemorrhage and necrosis. Skin ulceration may occur.

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Microscopic picture

cells are large, pleomorphic with large nuclei, prominent nucleoli and numerous mitoses.

with syncytial or sheet-like appearance.

scanty stroma intensely infiltrated by lymphocytes.

better prognosis than the scirrhous type.

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COLLOID (MUCINOUS) CARCINOMA

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This variant of breast cancer is known as colloid, or mucinous, carcinoma. This variant tends to occur in older women and is slower growing, and if it is the predominant histologic pattern present, then the prognosis is better than for non-

mucinous, invasive carcinomas.

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Lobular NeoplasiaE-Cadherin Negative

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LOBULAR CARCINOMA IN SITU (LCIS)

It is composed of (loosely cohesive) neoplastic lobular cell proliferations that fill one or more lobules but the basement membrane is intact.

It tends to be mutlifocal , bilateral and usually forms a palpable mass. [it is usually an incidental finding-no masses, no calcifications, no stromal reactions]

If present, the risk of invasive carcinoma increases, the associated invasive carcinoma may be lobular or ductal.

The management of LCIS is controversial ranging from follow up to bilateral mastectomy.

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It constitutes 10% of infiltrating breast carcinomas.

It is more frequently bilateral (25%) and multicentric.

It is more estrogen receptor positive than IDC.

Matched by grade and stage, Its prognosis is similar to IDC.

loss of a region on chromosome 16 (16q22.1) that includes a cluster of at least eight genes responsible for cell adhesion.

INFILTRATING LOBULAR CARCINOMA

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Gross picture: The tumour forms a poorly circumscribed rubbery to

hard mass, may be diffuse.

Microscopic picture: The tumour cells are small to medium-sized regular,

and uniform with little cytological abnormalities. They grow singly in the form of linear cords (Indian File Pattern) within a dense fibrous stroma. It may give targetoid appearence

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pattern of metastasis

Metastases to the peritoneum and retroperitoneum, the leptomeninges (carcinomatous meningitis), the gastrointestinal tract, and the ovaries and uterus.

These carcinomas are less likely to metastasize to the lungs and pleura.

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Spread of breast cancer1) Direct spread: To the overlying skin and chest wall 2) Lymphatic spread: Two methods

a- lymphatic emboli:The outer part: To the axillary lymph nodes, which may extend to

supraclavicular lymph nodesThe inner part: To the internal mammary lymph nodes, then to the

contralateral axilla.The lower part to the peritonium, falciform ligamnt, porta hepatis

and umbilicus (sister Joseph nodule of mayo clinic)

b- lymphatic permeation: It leads to lymphoedema -Skin nodularity

-Cancer en cuirasse -Peau d’orange. 3) Blood spread: To the lung, liver, bone, adrenals and ovaries

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Staging of breast cancer (TNM staging)

T4: Tumour of any size with invasion of skin or chest wall.

T3: Tumour more than 5 cm

T2: Tumour 2-5 cm

T1: Tumour 2 cm or less

Tis: (carcinoma in situ )

Tumour (T)

M1:Distant metastases

M0: No distant metastases

Metastases (M)

N3: Metastases to ipsilateral supraclavicular or infraclavicular lymph nodes or metastases to internal mammary nodes in the presence of axillary nodes.

N2: Metastases to fixed ipsilateral axillary nodes

N1: Metastases to movable ipsilateral axillary nodes

N0: No lymph node metastases

Lymph node (N)

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Clinical staging

M1Any N Any TIV

M0

M0

Any N

N3

T4

Any T III B

M0

M0

M0

M0

N2

N2

N1

N2

T1

T2

T3

T3

III A

M0

M0

N1

N0

T2

T3 II B

M0

M0

N1

N0

T1

T2 II A

M0NoT1I

M0N0Tis0

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Prognostic factors in breast cancer

1- Tumour size2- Lymph node status and number 3) Histologic grade 4) Histological type (1) Non (2) uncommonly (3) commonly metastasizing metastasizing metastasizing- Carcinoma in situ 1) colloid - IDC-NOS 2) Medullary - ILC 3) Papillary 4) Tubular

5) Adenoid cystic

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5) Estrogen and progesterone receptor status

6) Lymphovascular space invasion

7) Proliferation rate by flow cytometry

8) Presence of activated oncogenes e.g. HER2/Neu, but herceptin changed this view

9) Clinicopathologic stage

10)Ploidy [i.e. DNA contents]

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Sentinel lymph node

First in cutaneous melanoma, then in the breast, then in many other cancerApplied to avoid removal of lymph nodes which may lead to lymphatic edema and aggressive angiosarcomaInjecting a dye or a radioactive substence around the tumor before the operation, and following it during the operation to the first node.This node (the sentinel node)is examined immediately by frozen sections and if involved, axillary dissection is cariied out, if not, leave the axilla alone

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CAUSES OF BREAST MASS

Inflammatory: Chronic abscess, duct ectasia and tuberculous mastitis.

Hyperplastic: Fibrocystic disease and sclerosing adenosis.

Traumatic: Traumatic fat necrosis and haematoma.

Neoplastic: Different benign and malignant tumours of the breast.

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DISEASES OF MALE BREAST

Gynaecomastia: It means enlargement of male breast which may be unilateral or bilateral, due to:a) Oestrogen excess as in liver cirrhosis and fibrosis due to failure of detoxification of oestrogen, oestrogen forming tumours e.g. sertoli cell tumour of the testis, or oestrogen therapy for carcinoma of the prostate.

b) Drugs such as digitalis for a long time.

c) Idiopathic.

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Carcinoma of male breast:

It is a rare tumour with bad prognosis due to early invasion if the chest wall

It is stated that 1% of breast cancer occurs in males

However, this disease is common in our locality , with prevalence of the atypical proliferative lesion in cases of gynecomastia (personal observation, not yet documented)

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Important subjects

Causes of breast massFibrocystic disease of breastBenign tumors of the breastRisk factors of cancer breastMedullary carcinoma of the breastPaget’s disease of the breastPrognostic factors in cancer breast

Breast cancer

Thank you

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breast cancer