A.

Fibroadenoma
Definition
Fibroadenomas are solid neoplasms, a benign biphasic tumour of the breast. Fibroadenomas are
often solitary masses and mobile. Fibroadenoma consisting of fibroepithelial elements.
Fibroadenomas are made both by glandular breast tissue and connective tissue stroma. Hormonal
can influence their size; it will be fluctuating with the menstrual cycle and regression in
postmenopausal women. Fibroadenoma (FA) occurs most frequently in women of childbearing
age, especially those under 30. After menopause, the tumor is generally not found anymore.

Etiology
Usually considered a neoplasm, some believe FA results from hyperplasia of normal
lobular components rather than being a true neoplasm. The exact etiology of fibroadenoma is
unknown. However, several studies show that estrogen influences the development of
fibroadenomas. In a large population study of 265,402 women, risk factors for development of
fibroadenoma include young age (<35 years old), self-breast examination, and prior history of
benign breast disease.
Exposure to an estrogen-progesterone oral contraceptive before menopause and increasing
number of live births decreases the risk of fibroadenoma .There is also a correlation between body
mass index and incidence of fibroadenoma. In a study of 1,717 patients, the incidence of
fibroadenoma peaked in the body mass index group of 25–29.9 kg/m Fibroadenomas can also be
associated with syndromes such as Beckwith-Wiedemann syndrome, Maffucci syndrome, and
Cowden syndrome. One study found that there are high incidency of fibroadenoma in monosomy
of chromosome 21, however this genetic disorder also been reported in epithelial hyperplasia.
The natural history of fibroadenoma varies from individual to individual. Some
fibroadenomas may remain dormant without any change in size. Others may grow slowly in size.
Overall, most fibroadenomas decrease in size as they lose cellularity, infarct with resultant
calcification and hyalinization. In the adolescent population, 10%–40% of fibroadenomas
spontaneously regress.

Clinical features
Fibroadenomas are typically asymptomatic but may cause discomfort over the onset of
menses. Fibroadenoma presents as a painless, solitary, firm, rubbery mass, smooth, mobile, well
defined nodule slowly growing (up to 3 cm), with distinct borders usually ranging from 1 cm to 3
cm in size, but can also be < 1 cm to greater than 10 cm in size. Less frequently it may occur as
multiple nodules arising synchronously or asynchronously in the same or in both breasts and may
grow very large (up to 20 cm) mainly when it occurs in adolescents. Such lesions, may be called
“giant” fibroadenomas. With the increasing use of screening mammography, small, non-palpable
FAs are being discovered.
 Fibroadenoma can be clasified to fibroadenoma juvenile and giant fribroadenoma.
Fibroadenoma is termed juvenile if it occurs in children and adolescents between the ages of 10–
18 years. Giant fibroadenoma (rare variant) characterized by a rapidly growing tumor with a mass
greater than 5 cm and/or weighing more than 500 g.

Macroscopy
The cut surface is solid, firm, bulging, greyish in colour, with a slightly lobulated pattern and slit
like spaces. Variations depend on the amount of hyalinization and myxoid change in the stromal
component. Calcification of sclerotic lesions is common.

Histopathology
The admixture of stromal and epithelial proliferation gives rise to two distinct growth patterns of
no clinical significance. The pericanalicular pattern is the result of proliferation of stromal cells
around ducts in a circumferential fashion; this pattern is observed most frequently during the
second and third decades of life. The intracanalicular pattern is due to compression of the ducts
into clefts by the proliferating stromal cells. The stromal component may sometimes exhibit focal
or diffuse hypercellularity (especially in women less than 20 years of age), atypical bizarre
multinucleated giant cells, extensive myxoid changes or hyalinization with dystrophic calcification
and, rarely, ossification (especially in postmenopausal women). Foci of lipomatous, smooth
muscle, and osteochondroid metaplasia may rarely occur. Mitotic figures are uncommon. Total
infarction has been reported, but rarely. The epithelial component can show a wide spectrum of
typical hyperplasia, mainly in adolescents, and metaplastic changes such as apocrine or squamous
metaplasia may be seen. Foci of fibrocystic change, sclerosing adenosis and even extensive
myoepithelial proliferation can also occur in FA. In situ lobular, and ductal carcinoma occasionally
develop within FAs. Juvenile (or cellular) fibroadenomas are characterized by increased stromal
cellularity and epithelial hyperplasia. The term giant FA has been used as a synonym for juvenile
fibroadenoma by some, but is restricted to massive fibroadenomas with usual histology by others.

Diagnosis
The steps to diagnose fibroadenoma:
1. History taking (Kaneda MJ et.al., 2013)
Patient who has Fibroadenoma mammae mostly said that they have:
a. Palpable mass (typically unilateral), that are painless, firm, solitary, mobile, or slowly
growing lump
b. Family history of breast disease (malignant or benign)
c. Early menarche (< 12 years) and obstetrical parity (nulliparity)
d. Late menopause (age >55 years)
e. Associated symptoms of pain, nipple discharge, and skin changes (eg, dimpling or
inflammation, nipple inversion)
f. Length of time present, speed of growth (Hormonally responsive, grows during
pregnancy and late luteal phase, regresses after menopause)

2. Physical Examination (Kaneda MJ et al., 2013)

After we take the patient history, we can find this on physical examination:
a. Firm mass of variable shape and size
b. Fifty percent of masses found in the upper outer quadrant of the breast
c. May have associated pain with palpation, especially right before your period, when it
may swell due to hormonal changes. But, most are painless.
d. Nipple discharge, inversion, changes, or asymmetry
e. Skin retraction or tethering
f. Axillary lymphadenopathy
g. Inflammatory changes of the skin (ie, peau d'orange)
h. Pay special attention to associated upper-extremity neurologic motor or sensory
abnormalities, as these may herald invasion of the brachial plexus—an indication for
emergent radiation therapy.
3. Diagnostic Approach
Breast mass can be assess with triple assessment which include: breast
examination, USG and/or mammogram, a core biopsy and/or fine needle aspiration biopsy
(FNAB)
a. Ultrasonography (Weissleder R et al., 2013)
Fibroadenomas appear oval on ultrasonograms, and their width is larger than
their anteroposterior diameter. Gentle lobulations (typically fewer than 4) may be
present, but the margins should be circumscribed.
Internal echogenicity may be homogeneous, and findings may range from
isoechoic to lobules of fat to hypoechoic. The through- transmission of the tumor is
variable. A thin echogenic capsule is typical of a fibroadenoma and indicates that the
lesion is benign. A vague or thick surrounding region of echogenicity may indicate
malignancy. Fibroadenomas do not have a true capsule; the thin echogenic capsule
seen on ultrasonograms is a pseudocapsule caused by the compression of adjacent
tissue.
When using color-flow Doppler or power Doppler imaging, the amount and
distribution of vascularity among fibroadenomas is highly variable. Therefore, the
vascularity of solid masses does not help distinguish a cancer from a fibroadenoma.
Cysts seen in a solid mass are suggestive of cystosarcoma phyllodes rather than
fibroadenomas. One study found that histologic type, tumor size, and patient age
significantly influence ultrasound characteristics of breast fibroadenomas.
Degree of confidence of masses with a thin, smooth echogenic capsule, 93%
are benign. Of circumscribed masses, 91% are benign. Of masses that are round or
oval, 94% are benign. Of fibroadenomas, 60% are oriented parallel to the skin (ie, they
appear oval).
False positives/negatives
Overlap may exist between the appearances of carcinomas, fibroadenomas,
cystosarcoma phyllodes, and complicated cysts.
 Figure. Ultrasonogram demonstrates a hypoechoic mass with smooth,
partially lobulated margins typical of a fibroadenoma.
b. Mammography (Parades ES, 2007)
A 50-74 years old woman suggested to check mammography every 2 years.
Fibroadenomas have a spectrum of features from the well circumscribed discrete
oval mass hypo- or isodense to the breast glandular tissue, to a mass with
macrolobulation or partially obscured margin. Involuting fibroadenomas in older,
typically postmenopausal patients may contain calcification, often producing the
classic, coarse popcorn calcification appearance. In some cases the whole lesion is
calcified. Calcification may also present as crushed stone-like microcalcification
which makes differentiation from malignancy difficult.
Figure. Mammography of Fibroadenoma of the left breast
c. Biopsy (AJR, 2010)
Needle biopsy
There are 2 types of needle biopsies:
1) Fine needle biopsy (also called fine needle aspiration)
Fine needle aspiration (FNA) uses a very thin, hollow needle attached to a syringe
to take out a small amount of fluid and very small pieces of tissue from the tumor.
The doctor can aim the needle while feeling the tumor, if it’s near the surface of
the body. If the tumor is deeper inside the body and can’t be felt, the needle can be
guided while being watched on an imaging test such as an ultrasound or CT scan.
The main advantages of FNA are that the skin doesn’t have to be cut, and in some
cases it’s possible to make a diagnosis the same day. The disadvantage is that
sometimes this needle can’t remove enough tissue for a definite diagnosis.
Although FNA is a type of biopsy, it’s also classified as a cytology test.
2) Core needle biopsy (also called core biopsy) Needles used in a core biopsy are
slightly larger than those used in FNA. They remove a small cylinder of tissue
(about 1/16 inch in diameter and 1/2 inch long). The core needle biopsy is done
with local anesthesia (drugs are used to make the area numb) in the doctor’s office
or clinic. Like FNA, a core biopsy can sample tumors that the doctor can feel as
well as smaller ones that must be seen using imaging tests.
Doctors sometimes use special vacuum tools to get larger core biopsies from breast
tissue. Processing core biopsy samples usually takes longer than FNA biopsies, so
getting the results of those tests also might take longer.
Surgical (open biopsy)
In rare cases, surgery is needed to remove all or part of the lump for testing.
This is called a surgical or open biopsy. Most often, the surgeon removes the entire
mass or abnormal area as well as a surrounding margin of normal breast tissue. There
are 2 types of surgical biopsies:
1) An incisional biopsy removes only part of the suspicious area, enough to make a
diagnosis.
2) An excisional biopsy removes the entire tumor or abnormal area, with or without
trying to take out an edge of normal breast tissue (depending on the reason for the
biopsy).
Lymph node biopsy
The doctor may also need to biopsy the lymph nodes under the arm to check them
for cancer spread. This might be done at the same time as biopsy of the breast tumor, or
when the breast tumor is removed at surgery. This is done by needle biopsy, or with a
sentinel lymph node biopsy and/or an axillary lymph node dissection.
Early prevention (ACOG, 2011)
Every woman can do self breast examination every 1 week after the first day of last menstrual
period. This is the step of self breast examination

Step 1:
Begin by looking at your breasts in the mirror with your shoulders straight and your arms on your
hips.
Here's what you should look for:
Breasts that are their usual size, shape, and color
Breasts that are evenly shaped without visible distortion or swelling
If you see any of the following changes, bring them to your doctor's attention:
Dimpling, puckering, or bulging of the skin
A nipple that has changed position or an inverted nipple (pushed inward instead
of sticking out)
Redness, soreness, rash, or swelling

Step 2: Now, raise your arms and look for the same changes.
Step 3: While you're at the mirror, look for any signs of fluid coming out of one or both nipples
(this could be a watery, milky, or yellow fluid or blood).
Step 4: Next, feel your breasts while lying down, using your right hand to feel your left breast and
then your left hand to feel your right breast. Use a firm, smooth touch with the first few finger
pads of your hand, keeping the fingers flat and together. Use a circular motion, about the size of a
quarter.

Cover the entire breast from top to bottom, side to side — from your collarbone to the top of your
abdomen, and from your armpit to your cleavage.

Follow a pattern to be sure that you cover the whole breast. You can begin at the nipple, moving
in larger and larger circles until you reach the outer edge of the breast. You can also move your
fingers up and down vertically, in rows, as if you were mowing a lawn. This up-and-down
approach seems to work best for most women. Be sure to feel all the tissue from the front to the
back of your breasts: for the skin and tissue just beneath, use light pressure; use medium pressure
for tissue in the middle of your breasts; use firm pressure for the deep tissue in the back. When
you've reached the deep tissue, you should be able to feel down to your ribcage.

Step 5: Finally, feel your breasts while you are standing or sitting. Many women find that the
easiest way to feel their breasts is when their skin is wet and slippery, so they like to do this step
in the shower. Cover your entire breast, using the same hand movements described in step 4.

Differential diagnosis
Most FAs, especially those of large size, cellular stroma and epithelial clefts need to be
distinguished from phyllodes tumours (see below). Another breast lesion, which can simulate FA,
is hamartoma.
Treatment
Many doctors recommend removing fibroadenomas, especially if they keep growing or
change the shape of the breast, to make sure that cancer is not causing the changes. The following
criteria to establish a patient as a potential candidate for cryoablation or percutaneous excision
of a fibroadenoma (Orr B, 2016) :

1. The lesion must be sonographically visible

2. The diagnosis of fibroadenoma must be confirmed histologically.

3. Lesions should be less than 4 cm in largest diameter

Sometimes these tumours stop growing or even shrink on their own, without any treatment. In this
case, as long as the doctors are sure the masses are fibroadenomas and not breast cancer, they may
be left in place and watched to be sure they don’t grow. This approach is useful for women with
many fibroadenomas that are not growing. In such cases, removing them might mean removing a
lot of nearby normal breast tissue, causing scarring that would change the shape and texture of the
breast. This could also make future mammograms harder to read. It’s important for women who
have fibroadenomas to have regular breast exams or imaging tests to make sure the fibroadenomas
are not growing.

Prognosis and predictive features

Most FAs do not recur after complete surgical excision. In adolescents, there is a tendency for one
or more new lesions to develop at another site or even close to the site of the previous surgical
treatment. The risk of developing cancer within a FA or in breasts of patients previously treated
for FA is low, although a slightly increased risk has been reported.

B. Phyllodes tumours
Definition
A group of circumscribed biphasic tumours, basically analogous to fibroadenomas, characterized
by a double layered epithelial component arranged in clefts surrounded by an overgrowing
hypercellular mesenchymal component typically organized in leaf-like struct u res. Phyllodes
tumours (PTs) are usually benign, but recurrences are not uncommon and a relatively small
number of patients will develop haematogenous metastases. Depending on the bland or overtly
sarcomatous characteristics of their mesenchymal component (also called stromal component),
PTs display a morphological spectrum lying between fibroadenomas (FAs) and pure stromal
sarcomas. Still widespread in the literature, the generic term “cystosarcoma phyllodes”, is
currently considered inappropriate and potentially dangerous since the majority of these tumours
follow a benign course. It is highly preferable to use the neutral term “phyllodes tumour”,
according to the view already expressed in the WHO classification of 1981, with the adjunction
of an adjective determining the putative behaviour based on histological characteristics.

Epidemiology
In western countries, PTs account for 0,3- 1% of all primary tumours and for 2,5% of all
fibroepithelial tumours of the breast. They occur predominantly in middle aged women (average
age of presentation is 40-50 years) around 15-20 years older than for FAs. In Asian countries, PTs
occur at a younger age (average 25-30 years). Malignant PTs develop on average 2-5 years later
than benign PTs. Among Latino whites, especially those born in Central and South America,
malignant phyllodes is more frequent. Isolated examples of PTs in men have been recorded.

Etiology
PTs are thought to be derived from intralobular or periductal stroma. They may develop de novo
or from FAs. It is possible, in rare cases, to demonstrate the presence of a pre-existing FA adjacent
to a PT.

Clinical features
Usually, patients present with a unilateral, firm, painless breast mass, not attached to the skin.
Very large tumours (>10 cm) may stretch the skin with striking distension of superficial veins, but
ulceration is very rare. Due to mammographic screening, 2-3 cm tumours are becoming more
common, but the average size remains around 4-5 cm. Bloody nipple discharge caused by
spontaneous infarction of the tumour has been described in adolescent girls. Multifocal or bilateral
lesions are rare. Imaging reveals a rounded, usually sharply defined, mass containing clefts or
cysts and sometimes coarse calcifications.

Macroscopy
PTs form a well circumscribed firm , bulging mass. Because of their often clearly defined margins,
they are often shelled out surgically. The cut surface is tan or pink to grey and may be mucoid.
The characteristic whorled pattern with curved clefts resembling leaf buds is best seen in large
lesions, but smaller lesions may have a homogeneous appearance. Haemorrhage or necrosis may
be present in large lesions.

Histopathology
PTs typically exhibit an enhanced intracanalicular growth pattern with leaf-like projections into
dilated lumens. The epithelial component consists of luminal epithelial and myoepithelial cells.
Apocrine or squamous metaplasia is occasionally present and hyperplasia is not unusual. In benign
phyllodes tumours, the stroma is more cellular than in FAs, the spindle cell nuclei are
monomorphic and mitoses are rare. The stromal cellularity may be higher in zones in close contact
with the epithelial component. Areas of sparse stromal cellularity, hyalinisation or myxoid
changes are not uncommon. Necrotic areas may be seen in very large tumours. The presence of
occasional bizarre giant cells should not be taken as a mark of malignancy. Lipomatous,
cartilagenous and osseous metaplasia have been reported. The margins are usually well delimited,
although very small tumour buds may protrude into the surrounding tissue. Such expansions may
be left behind after surgical removal and are a source of local recurrence.

Malignant PTs have infiltrative rather than pushing margins. The stroma shows frankly
sarcomatous, usually fibrosarcomatous changes. Heterologous differentiation such as
liposarcoma, osteosarcoma, chondrosarcoma or rhabdomyosarcoma may occur. Such changes
should be indicated in the diagnostic report. Due to overgrowth of the sarcomatous components,
the epithelial component may only be identified after examining multiple sections. Borderline PTs
(or low-grade malignant PTs) display intermediate features and the stroma often resembles low-
grade fibrosarcoma. Malignant epithelial transformation (DCIS or LIN and their invasive
counterparts) is uncommon.

Differential diagnosis
Benign PTs may be difficult to distinguish from fibroadenomas. The main features are the more
cellular stroma and the formation of leaf-like processes. However, the degree of hypercellularity
that is required to qualify a PT at its lower limit is difficult to define. Leaf-like processes may be
found in intracanalicular FAs with hypocellular and oedematous stroma, but the leaf-like
processes are few in number and often poorly formed. The term giant FA as well as juvenile (or
cellular) FA have often been used inappropriately as a synonym for benign PT. Although the term
periductal stromal sarcoma has been used as a synonym for PTs, it is better restricted to a very
rare non circumscribed biphasic lesion characterized by a spindle cell proliferation localized
around tubules that retain an open lumen and absence of leaf-like processes. These often low-
grade lesions may recur and r a rely progress to a classic PT. Malignant PTs may be confused with
pure sarcomas of the breast. In such case, diagnosis depends on finding residual epithelial
structures. However, the clinical impact of these two entities appears to be similar.

Grading
Several grading systems have been proposed with either two subgroups, or three subgroups. None
is universally applied since prediction of the behaviour remains difficult in an individual case.
Grading is based on semi-quantitative assessment of stromal cellularity, cellular pleomorphism,
mitotic activity, margin appearance and stromal distribution. Because of the structural variability
of P Ts, the selection of one block for every 1 cm of maximal tumour dimension is appropriate.
PTs should be subclassified according to the areas of highest cellular activity and most florid
architectural pattern. The different thresholds of mitotic indices vary substantially from author to
author. Since the size of high power fields is variable among diff e rent microscope brands, it has
been suggested that the mitotic count be related to the size of the field diameter. Stromal
overgrowth has been defined as stromal proliferation to the point where the epithelial elements are
absent in at least one low power field (40x). So defined, stromal overgrowth is not uncommon.
Prognosis and predictive factors
Local recurrence occurs in both benign and malignant tumours. Recurrence may mirror the
microscopic pattern of the original tumour or show dedifferentiation (in 75% of cases). Metastases
to nearly all internal organs have been reported, but the lung and skeleton are the most common
sites of spread. Axillary lymph node metastases are rare, but have been recorded in 10-15% in
cases of systemic disease. Recurrences generally develop within 2 years, while most deaths from
tumour occur within 5 years of diagnosis, sometimes after mediastinal compression through direct
chest wall invasion. The frequency of local recurrence and metastases correlate with the grade of
PTs but vary considerably from one series to another. The average in published data suggests a
21% rate of local recurrence overall, with a 17%, 25% and 27% rate in benign, borderline and
malignant PTs, respectively, and a 10% rate of metastases overall, with a 0%, 4% and 22% rate in
benign, borderline and malignant PTs, respectively. Local recurrence after surgery is strongly
dependent on the width of the excision margins.