Transcript Carcinoma of the breast is the most common malignancy in women

Breast pathology II
Phyllodes tumors
• arise from intralobular stroma.
• most present in the sixth decade, 10 to
20 years later than the peak age for
fibroadenomas
• phyllodes is Greek for “leaflike”) due to
the presence of nodules of proliferating
stroma covered by epithelium
• Carcinoma of the Breast
• Carcinoma of the breast is the most common
malignancy in women
• the incidence of breast cancer began to increase in
older women
• due to the introduction of mammographic
screening in the early 1980s
• Since 1994 the breast cancer mortality rate for all
women has slowly declined from 30% to 20%
RISK FACTORS
• Age
• Menarche Age, early menarche is a risk
• First-Degree Relatives with Breast Cancer
• Breast Biopsies
• Race (caucasian the highest)
• Estrogen Exposure, prolonged, early menarche, late menopause
• Radiation Exposure
• Carcinoma of the contralateral breast or endometrium
• Obesity
• Lack of breast feeding is a risk, Lack of prior pregnancy is a risk.
Tobacco
• ETIOLOGY AND PATHOGENESIS
• The major risk factors for the development of
breast cancer are hormonal and genetic.
• Breast carcinomas can therefore be divided
into sporadic cases, probably related to
hormonal exposure, and hereditary cases,
associated with germline mutations.
• Hereditary Breast Cancer
• Mutations in BRCA1 and BRCA2 account for the
majority of cancers attributive to single gene
mutation (3% of breast cancer)
Other genes P53 , CHEK2
• Sporadic Breast Cancer
• The major risk factors for sporadic breast cancer
are related to hormone exposure: gender, age at
menarche and menopause, reproductive history,
breastfeeding, and exogenous estrogens. The
majority of sporadic cancers occur in
postmenopausal women
• Carcinogenesis and Tumor Progression
• The most likely cell type of origin for the
majority of carcinomas is the ER-expressing
luminal cell, since the majority of cancers are
ER-positive
• ER-negative carcinomas may arise from ERnegative myoepithelial cells
• CLASSIFICATION OF BREAST CARCINOMA
• divided into in situ carcinomas and invasive
carcinomas.
• Carcinoma in situ refers to a neoplastic
proliferation that is limited to ducts and
lobules by the basement membrane.
• Invasive carcinoma (synonymous with
“infiltrating” carcinoma) has penetrated
through the basement membrane into
stroma.
• Ductal Carcinoma in Situ
• DCIS has been divided into five architectural
subtypes: comedocarcinoma, solid, cribriform,
papillary, and micropapillary
Comedocarcinoma is
characterized by the
presence of solid
sheets of pleomorphic
cells with “high-grade”
hyperchromatic nuclei
and areas of central
necrosis
• Noncomedo DCIS consists of a monomorphic
population of cells with nuclear grades ranging
from low to high.
• Lobular Carcinoma in Situ (LCIS)
• LCIS, and invasive lobular carcinoma all
consist of dyscohesive cells with oval or
round nuclei and small nucleoli
• Paget disease of the nipple:
is a rare manifestation of breast cancer (1% to
4% of cases)
presents as a unilateral erythematous eruption
with a scale crust. Pruritus is common, and
the lesion may be mistaken for eczema.
Malignant cells (Paget cells) extend from DCIS
within the ductal system, via the lactiferous
sinuses, into nipple skin without crossing the
basement membrane
Apalpable mass presents in 50%-60% of paget
disease indicates presence of underlying
invasive ductal carcinoma
• DCIS with microinvasion
• is an area of invasion through the
basement membrane into stroma
measuring no more than 0.1 cm.
• most commonly seen in association
with comedocarcinoma
• Invasive (Infiltrating) Carcinoma
• presents as a palpable mass.
• Palpable tumors are associated with
axillary lymph node metastases in over 50%
of patients.
• may be fixed to the chest wall or cause
dimpling of the skin.
• retraction of the nipple may develop
• lymphedema and thickening of the skin
mimics the appearance of an orange peel, an
appearance referred to as peau d'orange.
• mammography, invasive carcinomas most
commonly present as a radiodense mass
Invasive carcinomas of no special type
Invasive Ductal Carcinomainclude the
majority of carcinomas (70% to 80%).
Ranging from well differentiated to poorly
differentiated
• five major patterns of gene expression in the
NST group: luminal A, luminal B, normal,
basal-like, and HER2 positive
Luminal A” (40% to 55% of NST cancers):
o ER positive and HER2/neu negative.
o The majority are well- or moderately
differentiated, and most occur in
postmenopausal women.
slow growing and respond well to hormonal
treatments
o only a small number will respond to standard
chemotherapy
Luminal B” (15% to 20% of NST cancers):
o expresses ER but is generally of higher grade, has a
higher proliferative rate, and often overexpresses
HER2/neu.(triple-positive cancers)
o have lymph node metastases and that may
respond to chemotherapy.
Normal breast–like” (6% to 10% of NST cancers):
well-differentiated ER-positive, HER2/neu-negative
cancers
Basal-like” (13% to 25% of NST cancers):
o absence of ER, PR, and HER2/neu (triple-negative
carcinomas)
o expression of markers typical of myoepithelial cells
(e.g., basal keratins, P-cadherin, p63, or laminin)
o progenitor cell (e.g., cytokeratins 5 and 6)
o include medullary carcinomas, metaplastic carcinomas
(e.g., spindle cell carcinoma)
o These cancers are generally high grade and have a high
proliferation rate.
o They are associated with an aggressive course,
frequent metastasis to viscera and the brain, and a poor
prognosis.
o 15% to 20% will have a pathologic complete response to
chemotherapy
HER2 positive” (7% to 12% of NST cancers):
ER-negative carcinomas that overexpress
HER2/neu protein.
These cancers are usually poorly differentiated,
have a high proliferation rate, and are
associated with a high frequency of brain
metastasis.
• Invasive Lobular Carcinoma
• Lobular carcinomas have been reported to
have a greater incidence of bilaterality
• presence of dyscohesive infiltrating tumor
cells, often arranged in single file or in loose
clusters or sheets .
• Tubule formation is absent.
• Signet-ring cells containing an
intracytoplasmic mucin droplet are
common.
• Desmoplasia may be minimal or absent.
• Medullary Carcinoma
• most common in women in the sixth
decade and presents as a wellcircumscribed mass. It may closely mimic
a benign lesion clinically and
radiologically, or present as a rapidly
growing mass.
• tumor is soft, fleshy (medulla is Latin for
“marrow”), and well circumscribed.
• Microscopically:
(1) solid, syncytium-like sheets of large cells
with vesicular, pleomorphic nuclei, and
prominent nucleoli, which compose more
than 75% of the tumor mass;
(2) frequent mitotic figures;
(3) a moderate to marked lymphoplasmacytic
infiltrate surrounding and within the tumor;
(4) a pushing (noninfiltrative) border
• Mucinous (Colloid) Carcinoma
• These carcinomas occur in older women
(median age 71)
• Morphology. The tumor is soft or rubbery
and has the consistency and appearance of
pale gray-blue gelatin.
• The borders are pushing or circumscribed.
The tumor cells are arranged in clusters and
small islands of cells within large lakes of
mucin
• Tubular Carcinoma
• These tumors consist exclusively of wellformed tubules and are sometimes mistaken
for benign sclerosing lesions
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PROGNOSTIC AND PREDICTIVE FACTORS
Invasive carcinoma versus in situ disease
Distant metastases.
Lymph node metastases
Tumor size
Locally advanced disease
Inflammatory carcinoma
Histologic grade, Estrogen and progesterone
receptors, HER2/neu, Lymphovascular
invasion