Breast Cancer

Breast pathology Breast cancer

Malignant tumors of the breast Primary:  Epithelial: breast carcinoma  Mesenchymal: sarcomas

Secondary

Breast cancer

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. Breast cancer

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

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

:)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 nonHodgkin’s lymphoma forming (8%) of all 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

Risk factors 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 Breast cancer

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 LiFraumini 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.

Breast cancer

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

Breast cancer

Breast cancer

Breast cancer

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

Breast cancer

Classification of breast carcinoma I- Carcinoma of ductal origin II- Carcinoma of lobular origin Each can be invasive and non-invasive Breast cancer

Breast cancer

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 CarcinomaNot 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 carcinoma 6- juvenile (secretory carcinoma). 7- Apocrine carcinoma 8- Carcinoma with neuroendocrine differentiation. Breast cancer

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

1-Lobular carcinoma in situ )LCIS) 2- Infiltrating lobular carcinoma

Breast cancer

Ductal carcinoma in situ )DCIS) = Intraduct carcinoma 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 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

Breast cancer

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 noncomedo DCIS Breast cancer

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

Breast cancer

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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 Breast cancer

Breast cancer

Breast cancer

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. Breast cancer

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. Breast cancer

Breast cancer

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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. Breast cancer

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:Microscopic picture The tumour is composed of diffuse sheets, welldefined nests, and cords of somewhat cohesive malignant cells separated by dense stromal fibrosis (desmoplastic reaction)

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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.

Breast cancer

MEDULLARY )ENCEPHALOID) CARCINOMA

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. Breast cancer

MEDULLARY )ENCEPHALOID) CARCINOMA

Breast cancer

COLLOID )MUCINOUS) CARCINOMA

Breast cancer

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 Breast cancer

Lobular Neoplasia E-Cadherin Negative

Breast cancer

LOBULAR CARCINOMAIN 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. Breast cancer

Breast cancer

INFILTRATING LOBULAR CARCINOMA

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. Breast cancer

INFILTRATING LOBULAR CARCINOMA 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 Breast cancer

Breast cancer

INFILTRATING LOBULAR CARCINOMA

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. Breast cancer

Spread of breast cancer 1) 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 nodes The 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 Breast cancer

)Staging of breast cancer )TNM staging Tumour )T)

Lymph node )N)

Metastases )M)

Tis: )carcinoma in

N0: No lymph node metastases

M0: No distant metastases

situ )

T1: Tumour

2 cm

N1: Metastases to movable ipsilateral M1:Distant metastases

or less

axillary nodes

T2:

N2: Metastases to fixed ipsilateral

Tumour 2-5

cm

axillary nodes

T3: Tumour more

N3: Metastases to ipsilateral

than 5 cm

supraclavicular or infraclavicular lymph nodes or metastases to internal mammary nodes in the presence of axillary nodes.

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

Clinical staging 0 I II A

Tis

N0

M0

T1

No

M0

T1 T2

N1 N0

M0 M0

II B

T2 T3

N1 N0

M0 M0

III A

T1 T2 T3 T3

N2 N2 N1 N2

M0 M0 M0 M0

III B

T4 Any T

Any N N3

M0 M0

IV

Any T

Any N

M1

Breast cancer

Prognostic factors in breast cancer 1- Tumour size 2- Lymph node status and number 3) Histologic grade 4) Histological type (1) Non (2) uncommonly metastasizing metastasizing - Carcinoma in situ 1) colloid 2) Medullary 3) Papillary 4) Tubular 5) Adenoid cystic Breast cancer

(3) commonly metastasizing - IDC-NOS - ILC

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] Breast cancer

Sentinel lymph node First in cutaneous melanoma, then in the breast, then in many other cancer Applied to avoid removal of lymph nodes which may lead to lymphatic edema and aggressive angiosarcoma Injecting 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 Breast cancer

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. Breast cancer

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.

Breast cancer

: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)

Breast cancer

Important subjects Causes of breast mass Fibrocystic disease of breast Benign tumors of the breast Risk factors of cancer breast Medullary carcinoma of the breast Paget’s disease of the breast Prognostic factors in cancer breast Breast cancer

Thank you Breast cancer