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Pathology and management of

benign breast diseases

DR BASHIRU AMINU
MODERATOR PROF LMD YUSUF
Outline

 Introduction
 Anatomy/ physiology
 Congenital anomalies
 Infectious disorders
 Non prolifarative disorders
 Proliferative disorders without atypia
 Proliferative disorders with atypia
 Complications
 Follow up
 conclusion
Introduction

 Diagnosis of any breast disorder at any age is usually


associated with much discomfort
 Both for patient and relations
 It’s a cause of frequent OPD visits
 Loss of income and man hours may be assoc with
lack of sound knowledge by the clinician to hit the
right diagnosis first time
 Some are precancerous
Anatomy and physiology

 Ectodermal modifications of sweat glands


 size and shape of the breast are dependent on age,
race, genetic or hereditary characteristics of the
individual,
 physiological states such as pregnancy and lactation
or unilateral or bilateral disease are important
Mammary milk line
Anatomy and physiology

 extends from the clavicle above to the upper border


of the rectus sheath below
 laterally from the midline to the posterior axillary
line (the anterior border of
 latissimus dorsi)
 It spans the area over the second to the sixth ribs, the
pectoralis major, serratus anterior and the upper
part of the rectus sheath.
Anatomy and physiology

 The basic unit is the acinus


 Several of which form a lobule
 15-20 lobules unite to drain via a lactiferous duct
which opens at the nipple
 Beneath the skin the superficial fascia splits into 2,
envelopes the breast
 Ligaments of cooper exist btw the 2, important in
surgery
 Deeper layer relates to the fascia over pec. Major
 Between which we have rotter nodes
Anatomy and physiology

 four perforating branches of the internal mammary


artery of which
 the 2nd intercostal branch is me largest.
 The rest of the breast is supplied by the axillary
artery, namely
- (I) the pectoral branch of the thoraco-acromial artery
( Ist part)
- (2) the lateral thoracic artery (from its 2nd part)
- (3) the subscapular artery - the largest branch of the
axillary artery to supply the breast from its 3rd part.
 Venous drainage follow arterial supply to some
extent
 Batson’s vertebral venous plexus is important in this
organ
 the veins invests the vertebrae and extends from the
base of the skull to the sacrum
 may provide a route for breast cancer metastases to
the vertebrae, skull, pelvic bones, and central
nervous system.
Anatomy and physiology

 The axillary lymph nodes usually receive >75% of the


lymph drainage from the breast
 the rest flows through the lymph vessels that
accompany the perforating branches of the internal
mammary artery
 They then enter the parasternal (internal mammary)
group of lymph nodes
 Breast development and function are initiated by a
variety of hormonal stimuli
 major trophic effects being modulated by estrogen,
progesterone, and prolactin.
 The upper outer quadrant of the breast contains a
greater volume of tissue than do the other quadrants.
 Herein lies the cause of higher freq. of pathology
here
 The breast remains undeveloped in the female until
puberty, when it enlarges in response to ovarian estrogen
and progesterone, which initiate proliferation of the
epithelial and connective tissue elements.
 However, the breasts remain incompletely developed
until pregnancy occurs.
 With the hormonal stimulation that accompanies
pregnancy and lactation, the breast becomes larger and
increases in volume and density, whereas with
senescence, it assumes a flattened, flaccid, and more
pendulous configuration with decreased volume
 Estrogen initiates ductal development, whereas
progesterone is responsible for differentiation of
epithelium and for lobular development.
 Prolactin is the primary hormonal stimulus for
lactogenesis in late pregnancy and the postpartum
period.
 It upregulates hormone receptors and stimulates
epithelial development
 is responsible for regulation of the secretion of the
hormones
 that affect the breast tissues. The gonadotropins
luteinizing hormone
 (LH) and follicle-stimulating hormone (FSH) regulate
 the release of estrogen and progesterone from the
ovaries. In
 turn, the release of LH and FSH from the basophilic cells
of the
 anterior pituitary is regulated by the secretion of
gonadotropinreleasing
 hormone (GnRH) from the hypothalamus.
 Positive and negative feedback effects of circulating estrogen
and progesterone
 regulate the secretion of LH, FSH, and GnRH. These
 hormones are responsible for the development, function, and
 maintenance of breast tissues (Fig. 17-9A). In the female
neonate,
 circulating estrogen and progesterone levels decrease
 after birth and remain low throughout childhood because of
the
 sensitivity of the hypothalamic-pituitary axis to negative
feedback
 from these hormones
 With the onset of puberty, there is a decrease in the
sensitivity of the hypothalamic-pituitary axis to
negative feedback and an increase in its sensitivity to
positive feedback from estrogen
 an increase in GnRH, FSH, and LH secretion and ultimately
an
 increase in estrogen and progesterone secretion by the
ovaries,
 leading to establishment of the menstrual cycle. At the
beginning
 of the menstrual cycle, there is an increase in the size and
 density of the breasts, which is followed by engorgement of
 the breast tissues and epithelial proliferation. With the onset
of
 menstruation, the breast engorgement subsides and epithelial
 proliferation decreases.
Inactive breast
Active breast
Congenital Anomalies

 Amazia assoc withPoland’s syndrome consists of hypoplasia or


complete absence of the breast, costal cartilage and rib defects,
hypoplasia of the subcutaneous tissues of the chest wall, and
brachysyndactyly.
 Polymazia ;Turner’s syndrome (ovarian agenesis and dysgenesis)
and Fleischer’s syndrome (displacement of the nipple and bilateral
renal hypoplasia) may have polymastia as a component.
 Polythelia occur in <1% of infants and may be associated with
abnormalities of the urinary tract (renal agenesis and cancer),
abnormalities of the cardiovascular system (conduction
disturbances, hypertension, congenital heart anomalies), and other
conditions (pyloric stenosis, epilepsy, ear abnormality and
arthrogryposis
 Symmastia is a rare anomaly recognized as webbing between the
breasts across the midline.
Gynecomastia

 Refers to enlarged breast in a male


 It may be neonatal (bilateral; placental oestrogen),
pubertal (unilateral; excess estradiol relative to
testostrones) , senescent (bilateral;due to fall in
testosterone relative to estrogen)
 In gynecomastia, the ductal structures of the male
breast enlarge, elongate, and branch with a
concomitant increase in epithelium.
 Gynecomastia is graded based on the degree of breast enlargement,
the position of the nipple with reference to the inframammary fold
and the degree of breast ptosis andskin redundancy:
Grade 1: mild breast enlargement without skin redundancy;
Grade IIa: moderate breast enlargement without skin redundancy
Grade IIb: moderate breast enlargement with skin redundancy;
Grade 3: marked breast enlargement with skin redundancy and
ptosis.
 Gynecomastia generally does not predispose the male breast to
cancer
 However, the hypoandrogenic state of Klinefelter’s syndrome
(XXY), in which gynecomastia is usually evident, is associated with
an increased risk of breast cancer.
Infectious disorders

 Usually more common in lactating


 Non lactating are intrinsic(due to underlying breast
abnormality) or extrinsic (spreadin from some other
focus)
 The common bacterial agents are staph. and strep.
Species
 The former deep while the latter assoc with
superficial
 Nonepidemic (sporadic) puerperal mastitis refers to
involvement of the interlobular connective tissue of
the breast by an infectious process.
 The patient develops nipple fissuring and milk stasis,
which initiates a retrograde bacterial infection
 Zuska’s disease, also called recurrent periductal
mastitis, is a condition of recurrent retroareolar
infections and abscesses.
 Smoking has been implicated as a risk factor for this
condition
 Blastomycosis or sporotrichosist are fungal infection
innoculated into cracked or macerated breast during
breast feeding
 Candida albicans is also implicated
 Hidradenitis suppurativa of the nipple-areola
complex or axilla is a chronic inflammatory
condition that originates within the accessory areolar
glands of Montgomery or within the axillary
sebaceous glands
 Mondor’s disease is a variant of thrombophlebitis that
involves the superficial veins of the anterior chest wall and
breast
 In 1939, Mondor described the condition as “string phlebitis,”
a thrombosed vein presenting as a tender, cord-like structure
 Frequently involved veins include the lateral thoracic vein, the
thoracoepigastric vein, and, less commonly, the superficial
epigastric vein.
 Typically, a woman presents with acute pain in the lateral
aspect of the breast or the anterior chest wall.
 A tender, firm cord is found to follow the distribution of one
of the major superficial veins.
 Rarely, the presentation is bilateral, and most women have no
evidence of thrombophlebitis in other anatomic sites.
Non proliferative disorders
ANDI

 The proponents of this classification made the ff


assumption;
-the breast passes thru phases of reproductive life to
involution
-diseases affecting the breast related to above phases fall in
a spectrum
-mild abnormality is designated disorder
-severe abnormality is designated disease
-most women to a degree express these features.
- It is often the extent or severity of the disorder that
results in a patient seeking medical help
Non proliferative disorders

 Nonproliferative disorders of the breast account for


70% of benign breast conditions
 carry no increased risk for the development of breast
cancer.
 This category includes cysts, duct ectasia, periductal
mastitis, calcifications, fibroadenomas, and related
disorders
Early Reproductive Years
fibroadenoma

 present symptomatically predominantly in younger


women aged 15 to 25 years
 Fibroadenomas usually grow to 1 or 2 cm in diameter
and then are stable but may grow to a larger size.
 Small fibroadenomas (≤1 cm in size) are considered
normal, whereas larger fibroadenomas (≤3 cm) are
disorders and giant fibroadenomas (>3 cm) are
disease.
 Similarly, multiple fibroadenomas (more than five
lesions in one breast) are very uncommon and are
considered disease.
Early Reproductive Years

 Classified as intracanalicular or pericanalicular


Pericanalicular
-occur in younger women
-grows slower
-encasulated
-oval, about 1-3cm
-multiple
-contains fibrous,acinar, ductal tissue
-conc mainly around the ducts
Early Reproductive Years

 Intracanalicular
-older women
-about 40-50yr
-larger up to 10cm
-Faster growth
-proliferation into the ducts, dilating, distorting them
-smooth surfaced, well capsulated
-sarcomatous change, rare but possible
Early Reproductive Years

 Massive adolescent breast hypertrophy


-Pathology mainly of stromal hyperplasia
- it ranges from limited to massive stromal hyperplasia
-Masive stromal hyperplasia also called gigantomastia
-unilateral
-breast are dysplastic
-no evidence of neuroendocrine abnormality
 Massive breast hypertrophy of pregnancy
-soon after conception
-background dysplasia
Usually may not regress
Later Reproductive Years
Cyclical mastalgia

 probably due to hypersensitivity of breast epithelium to


nonnal circulating hormones especially oestrogens.
 The gross appearance of a benign mammary dysplasia is
that of localized tissue masses with cysts of variable sizes
containing bluish-green or clear fluid
 Microscopically, benign mammary dysplasia is
characterized by increased stromal proliferation
(fibrosis), ductal epithelial hyperplasia (epitheliosis).
and cyst formation
 ocassionaly there is some degree of glandular
hyperplasia (adenosis) ocurring in younger pt.
Later Reproductive Years

 Cyclical mastalgia and nodularity usually are


associated with premenstrual enlargement of the
breast and are regarded as normal.
 Cyclical pronounced mastalgia and severe painful
nodularity are viewed differently than are
physiologic discomfort and lumpiness.
 Painful nodularity that persists for >1 week of the
menstrual cycle is considered a disorder.
Mgt of cyclical mastalgia

 Management
-reassurance
-NSAIDS
-oil of prim rose
-danazol inhibitors of LH,FSH
-Bromocriptine ;dopamine agonist depress prolactin
production
-tamoxifen
Involution

 Involution of lobular epithelium is dependent on the


specialized stroma around it.
 However, an integrated involution of breast stroma
and epithelium is not always seen, and disorders of
the process are common.
 When the stroma involutes too quickly, alveoli
remain and form microcysts, which are precursors of
macrocysts
Involution

 The macrocysts are common, often subclinical, and


do not require specific treatment.
 Sclerosing adenosis is considered a disorder of both
the proliferative and the involutional phases of the
breast cycle.
 Duct ectasia (dilated ducts) and periductal mastitis
are other important components of the ANDI
classification.
 Periductal fibrosis is a sequela of periductal mastitis
and may result in nipple retraction
Involution

 About 60% of women ≥70 years of age exhibit some


degree of epithelial hyperplasia
 Atypical proliferative diseases include ductal and
lobular hyperplasia, both of which display some
features of carcinoma in situ.
 Women with atypical ductal or lobular hyperplasia
have a fourfold increase in breast cancer risk
Proliferative disorders
without atypia

 Sclerosing adenosis is prevalent during the childbearing


and perimenopausal years
 has no malignant potential.
 Histologic changes are both proliferative (ductal
proliferation) and involutional (stromal fibrosis,
epithelial regression).
 Sclerosing adenosis is characterized by distorted breast
lobules and usually occurs in the context of multiple
microcysts, but occasionally presents as a palpable mass.
 Benign calcifications are often associated with this
disorder Sclerosing adenosis can be managed by
observation as long as the imaging features and
pathologic findings are concordant.
Radial scars & complex sclerosing lesions

 Central sclerosis and various degrees of epithelial


proliferation, apocrine metaplasia, and papilloma
formation
 Lesions up to 1 cm in diameter are called radial
scars
 larger lesions are called complex sclerosing lesions.
Radial scars & complex sclerosing lesions

 Radial scars originate at sites of terminal duct branching


 the characteristic histologic changes radiate from a central
area of fibrosis.
 All of the histologic features of a radial scar are seen in the
larger complex sclerosing lesions, but there is a greater
disturbance of structure with papilloma formation, apocrine
metaplasia, and occasionally sclerosing adenosis.
 Distinguishing between a radial scar and invasive breast
carcinoma can be challenging based on core needle biopsy
sampling.
 Often the imaging features of a radial scar (which can be
quite similar to an invasive cancer) will dictate the need for
either a vacuum assisted biopsy or surgical excision in order
to exclude the possibility of carcinoma.
Pathology of Proliferative Disorders
Without Atypia

 Mild ductal hyperplasia is characterized by the


presence of three or four cell layers above the
basement membrane.
 Moderate ductal hyperplasia is characterized by the
presence of five or more cell layers above the
basement membrane.
 Florid ductal epithelial hyperplasia occupies at least
70% of a minor duct lumen
Pathology of Proliferative Disorders
Without Atypia

 It is found in >20% of breast tissue specimens, is


either
 solid or papillary, and is associated with an increased
cancer risk
 Intraductal papillomas arise in the major ducts,
usually in premenopausal women.
 They generally are <0.5 cm in diameter but may be
as large as 5 cm.
 A common presenting symptom is nipple discharge,
which may be serous or bloody
Pathology of Proliferative Disorders
Without Atypia

 Grossly, intraductal papillomas are pinkish tan,


friable, and usually attached to the wall of the
involved duct by a stalk.
 They rarely undergo malignant transformation, and
their presence does not increase a woman’s risk of
developing breast cancer (unless accompanied by
atypia).
 However, multiple intraductal papillomas, which
occur in younger women and are less frequently
assoc with discharge but susceptible to malignant
transformation
Pathology of Atypical Proliferative
Diseases

 The atypical proliferative diseases have some of the


features of carcinoma in situ but either lack a major
defining feature of carcinoma in situ or have the
features in less than fully developed form.
 Atypical ductal hyperplasia (ADH) appears similar
to low grade ductal carcinoma in situ (DCIS)
histologically and is composed of monotonous
round, cuboidal, or polygonal cells enclosed by
basement membrane with rare mitoses.
Pathology of Atypical Proliferative
Diseases

 A lesion will be considered to be ADH if it is up to 2


or 3 mm in size but would be called DCIS if it is
larger than 3 mm.
 The diagnosis can be difficult to establish with core
needle biopsy specimen alone and most cases will
require excisional biopsy specimen for classification.
Individuals with a diagnosis of ADH are at increased
risk for development of breast cancer and should be
counseled appropriately regarding risk reduction
strategies
Pathology of Atypical Proliferative
Diseases

 Haagensen et al described lobular neoplasia, a


 spectrum of disorders ranging from atypical lobular
hyperplasia
 to lobular carcinoma in situ (LCIS).35Atypical lobular
hyperplasia
 (ALH) results in minimal distention of lobular units with
 cells that are similar to those seen in LCIS. The diagnosis
of
 LCIS is made when small monomorphic cells that
distend the
 terminal ductal lobular unit are noted
Pathology of Atypical Proliferative
Diseases

 . In cases of LCIS the acini


 are full and distended while the overall lobular
architecture is
 maintained (Fig. 17-12). Classic LCIS is not
associated with
 a specific mammographic or palpable abnormality
but is an
 incidental finding noted on breast biopsy. There is a
variant of
 LCIS that has been termed pleomorphic LCIS
Pathology of Atypical Proliferative
Diseases

 In pleomorphic LCIS, there can be calcifications or other


suspicious mammographic changes that dictate the need
for biopsy.
 Classic LCIS is not treated with excision as the patient is
at
 risk for developing invasive breast cancer in either breast
and therefore the patient is counseled regarding
appropriate risk reduction strategies.
 Pleomorphic LCIS can be difficult to distinguish from
high-grade DCIS
Pathology of Atypical Proliferative
Diseases

 some proponents have suggested that patients with


pleomorphic LCIS be managed similar to those with
DCIS with attention to margins and consideration for
radiation therapy in the setting of breast conserving
treatment.
 The use of immunohistochemical staining for E-cadherin
can help to discriminate between LCIS and DCIS
 In lobular neoplasias, such as ALH and LCIS, there is a
lack of E-cadherin expression whereas the majority of
ductal lesions will demonstrate E-cadherin reactivity
Pathology of Atypical Proliferative
Diseases
Pathology of Atypical Proliferative
Diseases
complications
Follow up
conclusion

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