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Normal microanatomy

Major lesion sites

FIBROCYSTIC CHANGE
Characterized by following features:
i) Cystic dilatation of terminal ducts.
ii) Relative increase in inter- and intralobular fibrous tissue.
iii) Variable degree of epithelial proliferation in the terminal ducts.
Divided into two clinicopathologically groups:
A. Non-proliferative Fibrocystic Changes: Simple Fibrocystic Change
Includes 2 features: formation of cysts of varying size, and increase in fibrous stroma.
MORPHOLOGIC FEATURES.
Grossly:
❖ Usually multifocal and bilateral.
❖ They vary from microcysts to 5-6 cm in diameter.
❖ The usual large cyst is rounded, translucent with bluish color prior to opening (blue-dome
cyst).
❖ On opening, the cyst contains thin serous to haemorrhagic fluid.
Microscopically:
1. Cyst formation: The cyst lining shows a variety of appearances.
2. Fibrosis: There is increased fibrous stroma surrounding the cysts.
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B. Proliferative Fibrocystic Changes:

Epithelial Hyperplasia and Sclerosing
Adenosis.

BREAST TUMOURS
1. Benign breast tumours are fibroadenoma, phyllodes tumour (cystosarcoma phyllodes) and
intraductal papilloma.
2. Malignant tumour is Carcinoma occurs as non-invasive (carcinoma in situ) and invasive cancer.
Benign breast tumours
I FIBROADENOMA
Fibroadenoma or adenofibroma is a benign tumour of fibrous and epithelial elements. Though it
can occur at any age during reproductive life, most patients are between 15 to 30 years of age.
Clinically, fibroadenoma generally appears as a solitary, discrete, freely mobile nodule within
the breast.
Fibroadenoma may contain in situ or invasive lobular or ductal carcinoma, or the carcinoma may
invade the fibroadenoma from the adjacent primary breast cancer.
Microscopic patterns (fibrous tissue comprises most of a fibroadenoma)
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II PHYLLODES TUMOUR (CYSTOSARCOMA PHYLLODES)

❖ Cystosarcoma phyllodes was the nomenclature given by Müller in
1838 to an uncommon bulky breast tumour with leaf-like gross
appearance (phyllodes=leaf-like) having an aggressive clinical
behaviour.
❖ Most patients are between 30 to 70 years of age. Grossly, the
tumour resembles a giant fibroadenoma but is distinguished
histologically from the latter by more cellular connective tissue
❖ Phyllodes tumour can be classified into: benign, borderline and
malignantAbout 20% of phyllodes tumours are histologically
malignant and less than half of them may metastasise..
❖ Grossly, the tumour is generally large, 10-15 cm in diameter,
round to oval, and less fully encapsulated than a fibroadenoma.
❖ The cut surface is grey-white with cystic cavities, areas of haemorrhages, necrosis and
degenerative changes
III INTRADUCTAL PAPILLOMA
❖ Is a benign papillary tumour occurring in a lactiferous duct or lactiferous sinus near the nipple.
❖ Clinically, it produces serous or serosanguineous nipple discharge.
❖ Grossly, intraductal papilloma is usually solitary, small, less than 1
cm in diameter, commonly located in the major mammary ducts
close to the nipple.
❖ Histologically, an intraductal papilloma is characterized by multiple
papillae having well-developed fibrovascular stalks attached to the
ductal wall and covered by benign cuboidal epithelial cells
supported by myoepithelial cells.
❖ An intraductal papillary carcinoma is distinguished from intraductal
papilloma in having severe cytologic atypia, pleomorphism, absence
of myoepithelial cells, multilayering and presence of mitotic figures.
Malignant tumour (Cancer of the breast)
❖ Cancer of the breast is among the commonest of human cancers throughout the world.
❖ Its incidence varies in different countries but is particularly high in developed countries.
❖ In the United States, carcinoma of the breast constitutes about 25% of all cancers in females
and causes approximately 20% of cancer deaths among females.
❖ However, there has been some decline in mortality from the breast cancer in recent years in
North America, Western Europe and Australia due to both early diagnosis and modern
therapy.
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❖ Cancer of the male breast, on the other hand, is quite rare and comprises 0.2% of malignant
tumours (ratio between male-female breast cancer is 1:100).
❖ The incidence of breast cancer is highest in the perimenopausal age group and is uncommon
before the age of 25 years.
CARCINOMA OF THE BREAST
Clinically, the breast cancer usually presents as a solitary, painless, palpable lump which is
detected quite often by self-examination.
Higher the age, more are the chances of breast lump
turning out to be malignant.
Early diagnosis by mammography, xero-radiography and
thermography.
Techniques like fine needle aspiration cytology (FNAC),
stereotactic biopsy and frozen section are immensely
valuable to the surgeon for immediate pathological
diagnosis.

Etiology
1. Geography
❖ The incidence of breast cancer is about six times higher in developed countries than the
developing countries, with the notable exception of Japan.
❖ These geographic differences are considered to be related to consumption of large amount of
animal fats and high caloric diet by Western populations than the Asians (including Japanese)
and Africans.

2. Genetic factors.
Recently, much work has been done on the influence of family history and inherited mutations in
breast cancer:
i) Family history:
First-degree relatives of women with breast cancer have 2 to 6-fold higher risk of development
of breast cancer.
ii) Genetic mutations:
❖ About 10% breast cancers have been found to have inherited mutations.
❖ These mutations include the following, most important of which is breast cancer (BRCA)
susceptibility gene in inherited breast cancer:
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❖ BRCA 1 gene located on chromosome 17, a DNA repair gene, is implicated in both breast and
ovarian cancer in inherited cases.
❖ BRCA1 deletion is seen in about two-third of women with inherited breast cancer having
family history.
❖ The protein product of BRCA gene is a cell cycle regulated protein and Men who have mutated
BRCA1 have increased risk of developing cancer of the prostate but not of male breast.
❖ BRCA 2 gene located on chromosome 13, another DNA repair gene, in its mutated form, has
a similarly higher incidence of inherited cancer of the breast (one-third cases) and ovary in
females, and prostate in men.
❖ Mutation in p53 tumour suppressor gene on chromosome 17 as an acquired defect accounts
for 40% cases of sporadic breast cancer in women but rarely in women with family history of
breast cancer.
❖ Other mutations seen less frequently in breast cancer include ataxia telangiectasia gene, PTEN
(phosphate and tensin) tumour suppressor gene.
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3. Oestrogen excess.
There is sufficient evidence to suggest that excess endogenous oestrogen or exogenously
administered oestrogen for prolonged duration is an important factor in the development of breast
cancer.
Evidences in support of increased risk with oestrogen excess are as follows:
a. Women with prolonged reproductive life, with menarche setting in at an early age and
menopause relatively late have greater risk.
b. Higher risk in unmarried women than in married and multiparous women.
c. Women with first childbirth at a late age (over 30 years) are at greater risk.
d. Lactation is said to reduce the risk of breast cancer.
e. Bilateral oophorectomy reduces the risk of development of breast cancer.
f. Functioning ovarian tumours (e.g. granulosa cell tumour) which elaborate oestrogen are
associated with increased incidence of breast cancer.
g. Oestrogen replacement therapy administered may result in increased risk of breast cancer.
h. Longterm use of oral contraceptives has been suspected to predispose to breast cancer
i. Men who have been treated with oestrogen for prostatic cancer have increased risk of
developing cancer of the male breast.
Normal breast epithelium possesses oestrogen and progesterone receptors.
The breast cancer cells secrete many growth factors which are oestrogen-dependent.
In this way, the interplay of high circulating levels of oestrogen, oestrogen receptors and growth
factors brings about progression of breast cancer.
4. Miscellaneous factors
These include a host of following
Environmental influences and dietary factors associated with increased risk of breast cancer:
i) Consumption of large amounts of animal fats, high calorie foods.
ii) Cigarette smoking.
iii) Alcohol consumption.
iv) Breast augmentation surgery.
v) Exposure to ionising radiation during breast developement.
vi) Identification of a transmissible retrovirus in early 20th century
Fibrocystic change
Fibrocystic change, particularly when associated with atypical epithelial hyperplasia, has about
5-fold higher risk of developing breast cancer subsequently.
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General Features and Classification

❖ Cancer of the breast occurs more often in left breast than the right and is bilateral in about 4%
cases.
❖ Anatomically upper outer quadrant is the site of tumour in half the breast cancers; followed in
frequency by central portion, and equally in the remaining both lower and the upper inner
quadrant
❖ Carcinoma of the breast arises from the ductal epithelium in 90% cases while the remaining
10% originate from the lobular epithelium.
❖ For variable period of time, the tumour cells remain confined within the ducts or lobules
(noninvasive carcinoma) before they invade the breast stroma (invasive carcinoma).
❖ While only 2 types of non-invasive carcinoma have been described: intraductal carcinoma and
lobular carcinoma in situ, there is a great variety of histological patterns of invasive carcinoma
breast which have clinical correlations and prognostic implications.
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A. NON-INVASIVE (IN SITU) BREAST CARCINOMA

Intraductal Carcinoma
❖ Carcinoma in situ confined within the larger mammary ducts is called intraductal carcinoma.
❖ The tumour initially begins with atypical hyperplasia of ductal epithelium followed by filling
of the duct with tumour cells.
❖ Clinically, it produces a palpable mass in 30-75% of cases and presence of nipple discharge
in about 30% patients.
❖ The Breast of patients of intraductal carcinoma treated with excisional biopsy alone develop
ipsilateral invasive carcinoma during a follow-up period of 10 years while the chance of a
contralateral breast cancer developing in patients with intraductal carcinoma is far less than
that associated with in situ lobular carcinoma.
❖ Grossly, the tumour may vary from a small poorly-defined focus to 3-5 cm diameter mass.
❖ On cut section, the involved area shows cystically dilated ducts containing cheesy necrotic
material (in comedo pattern), or the intraductal tumour may be polypoid and friable
resembling intraductal papilloma (in papillary pattern).

Lobular Carcinoma in Situ

❖ Lobular carcinoma in situ is not a palpable or grossly visible tumour.
❖ Patients of in situ lobular carcinoma treated with excisional biopsy alone develop invasive
cancer of the ipsilateral breast in about 25% cases in 10 years as in intraductal carcinoma but,
in addition, have a much higher incidence of developing a contralateral breast cancer (30%).
❖ Grossly, no visible tumour is identified. Histologically, in situ lobular carcinoma is
characterised by filling up of terminal ducts and ductules or acini by rather uniform cells which
are loosely cohesive and have small, rounded nuclei with indistinct cytoplasmic margins

NON-INVASIVE (IN SITU) BREAST CARCINOMA

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B. INVASIVE BREAST CARCINOMA

Infiltrating (Invasive) Duct Carcinoma-NOS
Infiltrating duct carcinoma-NOS (not otherwise specified) is the classic breast cancer and is the
most common histologic pattern accounting for 70% cases of breast cancer.
Clinically, majority of infiltrating duct carcinomas have a hard consistency due to dense
collagenous stroma (scirrhous carcinoma).
They are found more frequently in the left breast, often in the upper outer quadrant. Retraction of
the nipple and attachment of the tumour to underlying chest wall may be present.
MORPHOLOGIC FEATURES.
Grossly, the tumour is irregular, 1-5 cm in diameter, hard cartilage-like mass that cuts with a
grating sound.
The sectioned surface of the tumour is grey-white to yellowish with chalky streaks and often
extends irregularly into the surrounding fat.
Histologically, as the name NOS suggests, the tumour is different from other special types in
lacking a regular and uniform pattern throughout the lesion. A variety of histologic features
commonly present are as under
i) Anaplastic tumour cells forming solid nests, cords, poorly-formed glandular structures and
some intraductal foci.
ii) Infiltration by these patterns of tumour cells into diffuse fibrous stroma and fat.
iii) Invasion into perivascular and perineural spaces as well as lymphatic and vascular invasion.

Infiltrating duct carcinoma-NOS.

Microscopic features include formation of solid nests, cords, gland-like structures
and intraductal growth pattern of anaplastic tumour cells. There is infiltration of
densely collagenised stroma by these cells in a haphazard manner.
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Infiltrating (Invasive) Lobular Carcinoma

Invasive lobular carcinoma comprises about 5% of all breast cancers.
This peculiar morphologic form differs from other invasive cancers in being more frequently
bilateral; and within the same breast, it may have multicentric origin.
MORPHOLOGIC FEATURES.
Grossly, the appearance varies from a well-defined scirrhous mass to a poorlydefined area of
induration that may remain undetected by inspection as well as palpation.
Histologically, there are 2 distinct features:
i. Pattern A
characteristic single file (Indian file) linear arrangement of stromal infiltration by the tumour cells
(arrangement) infiltrating the stroma and arranged circumferentially around ducts in a target-like
pattern.
Infiltrating cells may be arranged concentrically around ducts in a target-like pattern.
ii. Tumour cytology
Individual tumour cells resemble cells of in situ lobular carcinoma.
They are round and regular with very little pleomorphism and infrequent mitoses

Invasive lobular carcinoma. Characteristic histologic features are:

One cell wide files of round regular tumour cells (‘Indian file’
arrangement) infiltrating the stroma and arranged circumferentially
around ducts in a target-like pattern.