Surgical

Oncology
Notes
by

Prof Dr Galal Aboul Nagah

Surgical Oncology Unit

Faculty of Medicine
Alexandria University

2021
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Benign breast diseases

At the fifth or sixth week of fetal development, two ventral bands
of thickened ectoderm (mammary ridges, milk lines) are evident
in the embryo. These ridges are not prominent in the human
embryo and disappear after a short time, except for small portions
that persist in the pectoral region.

Absence of the breast (amastia) is rare and results from an arrest

in mammary ridge development. Breast hypoplasia either
congenital or may be iatrogenically induced before puberty by
trauma, infection, or radiation therapy. mammary milk line

Accessory nipples (polythelia) occur in <1% of infants.

Supernumerary breasts may occur in any configuration along the mammary milk
line but most frequently occur between the normal nipple location and the axilla
(Accessory breasts)
Each breast develops when an ingrowth of ectoderm forms a primary tissue bud in
the mesenchyme. If there is failure of a pit to elevate above skin level, an inverted
nipple results. This congenital malformation occurs in 4% of infants.

At birth: the breasts are identical in males and females, demonstrating only the
presence of major ducts. Enlargement of infantile breast may be evident and a
secretion, referred to as witch's milk, may be produced. These transitory events occur
in response to maternal hormones that cross the placenta.
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.

ANATOMY:

The breast is composed of 15 to 20 lobes, which are each composed of several

lobules. Fibrous bands of connective tissue travel through the breast (Cooper's
suspensory ligaments), insert perpendicularly into the dermis, and provide structural
support.

Cut-away diagram of a mature resting breast.

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Each breast extends superiorly to the second rib, inferiorly to the sixth costal cartilage,
medially to para sternum, and laterally to the mid-axillary line.

Natural lines of skin tension,

known as Langerhans‟s lines,
extend circum-ferentially in a
circles around the nipple–areola
complex. The lines of
Langerhans‟s assume particular
clinical significance for the
surgeon, because it is the least
tension line where incision through
it resulted in least scar formation.

The deep or posterior surface of the breast Surface anatomy of the breast
rests mainly on the fascia of the pectoralis
major, serratus anterior.

BLOOD SUPPLY:
Arterial supply to the breast originates primarily from
(a) the internal mammary artery and (b) the lateral
thoracic artery. Lateral branches of the intercostal
arteries also share in the blood supply.

The veins of the breast and chest wall follow the course
of the arteries. The three principal groups of veins are
(a) perforating branches of the internal thoracic vein,
(b) perforating branches of intercostal veins, and (c)
tributaries of the axillary vein. Batson's vertebral
venous plexus, which 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
(mainly lumber due to gravity). Arterial supply of the breast

LYMPHATIC DRAINAGE:
95% of lymphatic drainage of the breast drain toward the axilla. Anatomically; The
axillary lymph nodes are divided into six groups:
(1) Anterior or pectoral group, lie along the lower border of the pectoralis minor
muscle and receive most of the lymph drainage from the lateral aspect of the
breast;
(2) Lateral or brachial, receive most of the lymph drainage from the upper extremity;
(3) Posterior or subscapular, contiguous with the subscapular vessels and receive
lymph drainage principally from the lower posterior neck, the posterior trunk, and
the posterior shoulder;
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(4) The central group, are embedded in the fat of the axilla and receive lymph
drainage from the previous three groups.
(5) Apical or sub clavicular, receive lymph drainage from all other groups of axillary
lymph nodes.
(6) Interpectoral group (Rotter's nodes), interposed between the pectoralis major and
pectoralis minor muscles and receive lymph drainage directly from the breast.

Surgically; Axillary lymph nodes are divided into three levels by the pectoralis minor
muscle:
Level I: located lateral and below the lower border of the pectoralis minor muscle.
Level II: located behind the pectoralis minor muscle.
Level III: located medial and above the upper border of the pectoralis minor muscle.

levels of axillary lymph nodes

BREAST PAIN (MASTALGIA)

Breast pain is the most common breast symptom
Classification
1. Cyclic mastalgia: 90%. Women with cyclic pain tended to refer to heaviness
and tenderness
2. Non-cyclic mastalgia.
a. True non-cyclic breast pain 9%
b. Other causes of chest wall pain 1%.
History-taking : include the type of pain, relationship to menses, duration, location,
and any other medical problems. The impact of the pain on the everyday activities of
the patient, particularly sleep and work should be established, to assess the need for
medication. Any drug history specially contraceptives & hormonal.
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Examination:
 Gentle palpation of the breasts to exclude discrete masses
 It may be possible to identify that pain is arising from the underlying rib or
costal cartilage.
 Nodularity can be associated with mastalgia, but the extent is unrelated to pain
severity; in younger women, the finding is so common that it should be
considered normal.
Imaging investigations:
In the absence of a discrete lump, ultrasonography and mammography is done
routinely, but any breast lump present requires triple assessment. No specific
mammogram findings are associated with breast pain.
Treatment Trials
Mastalgia usually cause patient worrying because most of the patients are afraid from
carcinoma, so they are greatly relieved when informed of the benign nature of the
condition. Then some medications could help like:
1. Reduction of caffeine or saturated fat intake.
2. Diuretics are widely used to oppose water retention in luteal phase of the cycle.
3. Unsaturated fatty acid gamma-linolenic acid, present in evening primrose oil,
provides a non-endocrine treatment. Its effect is more prominent on cyclic
mastalgia.
4. Danazol, may relieve pain in up to 93% of patients with resistant cyclic
mastalgia.
5. Supportive brassiere usually relieve mastalgia.
6. Bromocriptin, is not indicated except in mastalgia with high prolactin level.
7. Tamoxifen, a partial estrogen antagonist and agonist, in treating severe breast
pain.

Extra Mammary Pain

Pain originating within the thorax or abdomen and referred to the breast area is
managed by treatment of the underlying condition. (eg angina pectoralis)
Pain that originates from the thoracic wall (Tietze's syndrome or costochondritis), and
localized specific tender areas in the breast, (trigger spots), can be managed by
nonsteroidal analgesics have been used as topical gel applications.

Mondor's Disease: It is a rare cause of breast pain, with diagnostic clinical features of
local pain associated with a tender, palpable subcutaneous cord or linear skin
dimpling. The cause is superficial thrombophlebitis of the lateral thoracic vein. The
condition is usually self limited.
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Nipple Discharge

Nipple discharge accounts for approximately 15% of referrals to breast clinics.

Approximately 95% of women presenting to the hospital with nipple discharge have a
benign cause for the discharge. Also, 95% of women complaining of bleeding per
nipple are actually have non bloody nipple discharge.

Diagnosis and Management:

The physician must establish whether the discharge is spontaneous or induced,
whether it arises from a single or from multiple ducts, and whether it is from one or
both breasts.
The characteristics of the discharge also need to be defined: whether it is viscous or
watery and whether it is serous, sero-sanguineous, bloody, clear, milky, green, or
blue-black.
Frequency and amount of fluid also need to be assessed; It is important for milky
discharge, which should be considered to be galactorrhea if it is copious and arises
from bilateral multiple ducts. Complete physical examination to identify the presence
or absence of a breast mass. During the examination, firm pressure should be applied
around the areola to identify the site a specific dilated duct which produce the
discharge. The nipple is squeezed with firm digital pressure and, if fluid is expressed,
the site and character of the discharge are recorded.
Less than 10% of patients who have a bloodstained discharge or who have a discharge
containing moderate or large amounts of blood have an underlying malignancy. The
main cause of bloody nipple discharge is intra-ductal benign papilloma
Investigations:
1. Mammography has a high overall sensitivity for breast cancer, but not all
malignant lesions that cause nipple discharge are visible mammographically.
2. Ultrasonography can sometimes identify intra ductal papilloma and malignant
lesions in the ducts close to the nipple.
3. In large papilloma, Magnetic resonance imaging (MRI) may aid assessment of
the presence of malignancy.
4. If clinical examination demonstrates a mass lesion or mammography or
ultrasonography raises suspicion of malignancy, then core biopsy of the lesion
should be performed.

Causes of Nipple Discharge

1. Physiologic Causes
Lactation is the most common physiological cause of nipple discharge. In two-thirds
of non-lactating women, a small quantity of fluid can be expressed from the ducts of
the nipple if the nipple is cleaned, the breast massaged, and gentle suction pressure
applied.
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2. Intra-ductal Papilloma
A true intra-ductal papilloma develops in one of the major ducts and is the most
common cause of bloody or sero-sanguineous discharge. A mass may be felt on
examination in as many as one-third of cases. Which is usually due retention cyst
behind the papilloma itself. The treatment of choice is microdochectomy.
3. Multiple Intra-ductal Papilloma‟s
In approximately 10% of cases of intra-ductal papilloma, multiple lesions are found;
usually, two or three occur, often in the same duct. Multiple papilloma‟s were found
to be associated with an increased risk of breast cancer
4. Carcinoma
Only rarely does an invasive cancer cause nipple bloody discharge in absence of a
clinical mass. Discharge associated with a cancer is spontaneous, usually arises from a
single duct, is persistent, and is bloodstained or contains RBCs.
In most series, DCIS is responsible for up to 10% of unilateral nipple discharges.
Nipple discharge alone or in association with a mass or Paget's disease is the
presenting feature in approximately one-third of symptomatic in situ cancers.
5. Bloody Nipple Discharge in Pregnancy
Nipple discharge with blood present, either visibly or cytologically with pregnancy.
The likely cause is hyper vascularity of developing breast tissue; it is benign, usually
settles quickly and requires no specific treatment.
6. Galactorrhea
Galactorrhea should be diagnosed if there is copious bilateral milky discharge not
associated with pregnancy or breast-feeding. A careful drug history should be taken
because a number of drugs, particularly psychotropic agents, cause
hyperprolactinemia. Blood should be taken to test for prolactin, and if prolactin levels
are significantly elevated in the absence of any drug cause, then a search for a
pituitary tumor should be instituted.

7. Periductal Mastitis and Duct Ectasia

There is no relation between parity or breast-feeding and periductal mastitis or duct
ectasia.
 Age is an important factor in the cause of duct ectasia;
 An association between smoking and recurrent peri-areolar abscesses. Heavy
smokers are more likely to have abscess recurrence or subsequent mammary
duct fistulae than light smokers or nonsmokers. How cigarette smoking causes
peri-ductal mastitis is unclear.
The clinical features of duct ectasia include:
 Episodes of peri-areolar inflammation with or without an associated mass, a
peri-areolar abscess, and a mammary duct fistula.
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 Nipple retraction can be seen early at the site of the affected duct and is often
subtle.
 Nipple discharge is often Cheesy, viscous, toothpaste like nipple discharge,
some.
 Patients with green discharge from multiple ducts are often diagnosed as
having duct ectasia, but most of these are physiologic breast secretion.

8. Other Causes of “Nipple” Discharge

Other diseases of the nipple–areolar complex can present with “nipple” discharge,
including nipple adenoma, eczema, Paget's disease, ulcerating carcinoma, and long-
standing nipple inversion with maceration.
Treatment:
Approximately 95% of women presenting to the hospital with nipple discharge have a
benign cause. So, Surgery is indicated only in cases of spontaneous discharge from a
single duct that is confirmed on clinical examination and has one of the following
characteristics:
 Is bloodstained or contains moderate or large amounts of blood on testing
 Is persistent (occurs on at least two occasions per week)
 Is associated with a mass
 Is a new development in a woman older than 50 years of age, but is not thick or
cheesy
Discharge from multiple ducts normally requires surgery only when it causes
distressing symptoms, such as persistent staining of clothes.
Types of surgery:
1. Patients ≤ 30 years who have serous, serosanguineous, or watery discharge
could be observed every 3 months, with micro-ductectomy reserved for cases
in which discharge persists at review or bloody discharge.
2. Patients ≥45 years of age are treated by excision of major duct system on the
affected side;
3. Patients between 30 and 45 years of age are deemed suitable for either
approach.

A: slit like retraction of duct ectasia. B: nipple retraction of breast carcinoma

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Nipple Inversion or Retraction
These changes can be developmental or acquired. The acquired causes, in order of
frequency, are duct ectasia, peri-ductal mastitis, carcinoma, and tuberculosis.
Central, symmetric, transverse slit-like retraction is characteristic of benign disease;
nipple inversion occurring in association with either breast cancer or inflammatory
breast disease is more likely to involve the whole of the nipple and to be associated
with distortion of the areola when the breast is examined in different positions.
All patients with acquired nipple inversion or retraction should have a full clinical
examination and US breast. If the patient is older than 35 years, a mammogram as
well is ordered. Management depends on the presence or absence of a clinical or
mammographic abnormality.
Benign nipple retraction requires no specific treatment, but can be corrected surgically
if the patient requests it and the surgeon considers the operation appropriate. Usually,
division or excision of the underlying breast ducts (total duct division or excision) is
required; patients should be warned that they cannot breast-feed after this procedure.

Breast Infection

It is commonly affects women between the ages of 18 and 50 years. Breast infection
can be considered lactational or non-lactational. Infection can also affect the skin
overlying the breast, and occurs either as a primary event or secondary to a lesion in
the skin, such as a sebaceous cyst, or a more generalized condition, such as
hidradenitis supportive. The most common organism is S aureus.

The guiding principle in treating breast infection is to give antibiotics as early as

possible to stop abscess formation; if the infection or inflammation fails to resolve
after one course of antibiotics, then abscess formation or an underlying cancer should
be suspected.

Mastitis Neonatorum

An enlargement of the breast bud in the first 2 weeks of life occurs in approximately
60% of both males as well as females newborns, and the gland may reach several
centimeters in size before regressing. It is due to the effect of maternal feminine
hormones passed during delivery on fetal breast tissue,

The enlarged breast bud can become infected, usually by Staphylococcus aureus,
although Escherichia coli can sometimes cause this infection.

In the early stage, antibiotics (flucloxacillin) can control infection; however, if a

localized collection is evident on ultrasound, treatment is incision and drainage.
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Lactational Infection

The infection is usually caused by S. aureus, but it can also be caused by

Staphylococcus epidermidis and Streptococcus species.

Usually, the patient has a history of a cracked nipple or a skin abrasion. Infection most
commonly occurs following a first pregnancy in the first 6 weeks of breast-feeding, 6
months (age of baby teething) or during weaning.

Clinical picture

 Patients present with pain, erythema, swelling, tenderness, or systemic signs of

infection.
 The breast is swollen,
tender, and erythematous;
if an abscess is present, a
fluctuant mass with
overlying shiny, red skin
may be seen.
 Patients could be toxic with
pyrexia, tachycardia, and Lactational breast infection
leukocytosis.

Treatment
Antibiotics given at an early stage usually control the infection and stop abscess
formation. Because more than 80% of staphylococci are resistant to penicillin,
flucloxacillin or amoxicillin–clavulanate are given, except in patients with a penicillin
sensitivity, for whom erythromycin or clarithromycin is usually effective.
Patients whose condition does not improve rapidly on antibiotic therapy require
assessment with ultrasonography to determine whether pus is present and to exclude
an underlying neoplasm. Inflammatory carcinomatosis can be difficult to differentiate
from acute mastitis.
If a small abscess (less than 2 cm) is evident on ultrasonography and the overlying
skin is healthy, the abscess should be US guided aspirated to dryness following
injection of antibiotics and local anesthesia to minimize pain. The combination of
repeated aspiration and oral antibiotics is usually effective at resolving most small
local abscess formation. Aspiration should be repeated every 2 to 3 days until no
further pus is obtained.
If the skin overlying the abscess is thinned and abscess is big or multi-loculated on
ultrasonography, then under general anesthesia, a small radial incision is made over
the point of maximal fluctuation, and the pus is drained. Irrigation of the cavity with
antiseptics, and a drains or wound packing after incision is necessary.
Breast-feeding should be continued if possible because this promotes drainage of the
engorged segment and helps resolve infection.
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Non-lactational Infection
Non-lactational infections can be divided into those occurring centrally in the breast in
the peri-areolar region and those affecting peripheral breast tissues.
Peri-areolar Infection
Peri-areolar infection is most commonly seen in young women; the mean age of
occurrence is 32 years, and most are cigarette smokers. The underlying pathologic
process is peri-ductal mastitis had been described with nipple retraction before.

Mammary Duct Fistula

A mammary duct fistula is a communication between the skin, usually in the peri-
areolar region, and a major sub-areolar breast duct. It is most commonly seen after
incision and drainage of a non-lactational breast abscess, although it can occur after
spontaneous discharge of a peri-areolar inflammatory mass or after biopsy of an area
of peri-ductal mastitis. Patients usually have preceding episodes of recurrent abscess
formation and a pus-like discharge through the fistula opening.
Treatment is surgical, consisting of either opening up the fistula tract and leaving it to
granulate or excising the fistula and affected duct or ducts (a total duct excision is
usually required) and closing the wound primarily under appropriate antibiotic cover.

Peripheral Non-lactational Breast Abscess

 Peripheral non-lactational breast abscesses are less common than periareolar
abscesses and have been reported to be associated with a variety of underlying
disease states, such as diabetes, rheumatoid arthritis, steroid treatment, and trauma.
 S. aureus is the most common organism, but some abscesses contain anaerobic
organisms.
 Peripheral non-lactational breast abscesses are three times more common in
premenopausal women than in menopausal or postmenopausal women.
 Systemic evidence of malaise and fever is usually absent.
 Management is the same as for other breast abscesses.

Skin-Associated Infection
Cellulitis of the breast, with or without abscess formation, is common, particularly in
patients who are overweight, have large breasts, or have had previous surgery or
radiation therapy. It is most common in the lower half of the breast, where sweat
accumulates and intertrigo develops.
Skin-associated infection can also occur in association with sebaceous cysts in the
skin over the breast or can be seen in association with hidradenitis suppurativa. Acute
episodes of infection should be treated with appropriate antibiotics and, when an
abscess is present, aspiration or incision and drainage should be performed.
Other Rare Infections
Tuberculosis
Tuberculosis is not uncommon in Eastern countries. The breast can be the primary
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site, but tuberculosis more commonly reaches the breast through lymphatic spread
from axillary, mediastinal, or cervical nodes or directly from underlying structures,
such as the ribs. Molluscum contagiosum can affect the areola and present as wart-like
lesions.

Granulomatous Lobular Mastitis

Granulomatous lobular mastitis is characterized by non-caseating granulomata and
microabscesses confined to the breast lobule.
Clinical picture:
 The condition presents as a firm mass, or as multiple or recurrent abscesses.
 Mass is sometimes painful, tender and the overlying skin is sometimes ulcerated.
 Young women, often within 5 years of pregnancy, are most frequently affected.
 The role of organisms in the etiology of this condition is unclear
 Diagnosis is not certain by US & mammogram
 Biopsy is usually needed to exclude malignancy
 Treatment is by excision of a small affected part, or systemic steroid

Chronic breast abscess

It usually follows inadequate drainage or injudicious antibiotic treatment, is often a
very difficult condition to diagnose. When encapsulated within a thick wall of fibrous
tissue the condition cannot be distinguished from a carcinoma without histological
biopsy.

Others:
Actinomycosis of the breast is rare. Syphilis, mycotic, helminthic, and viral infections
occasionally affect the breast, but are rare.

Fibroadenomas
It is the most common benign breast tumors, usually affected young girls 17-25 years
old. On gross examination, fibroadenomas are well encapsulated by a pseudo capsule
and are clinically sharply demarcated from the surrounding breast tissue.

Grossly, fibroadenomas are usually spherical or ovoid, but may be multi-lobulated.

When cut, the tumor bulges above the level of the surrounding breast tissue. The cut
surface is most typically gray-white, and small, punctate, yellow-to-pink soft areas
and slit-like spaces are commonly observed. Occasionally, the tumor has a gelatinous,
mucoid consistency.
Microscopically, fibroadenomas have both an epithelial and stromal component. In
general, the epithelial component consists of well-defined, gland-like and duct-like
spaces lined by cuboidal or columnar cells with uniform nuclei. The stromal
component consists of connective tissue that has a variable content of acid muco poly
saccharides and collagen.
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Giant Fibroadenomas
 Some tumors that are histologically typical fibroadenomas may attain great size ≥
5 cm.
 It should still be treated adequately by enucleation.
 The major feature that distinguishes cystosarcoma phyllodes (preferably called a
phyllodes tumor) from a giant fibroadenoma is the cellularity of the stromal
component in the former.

Intra-ductal Papilloma’s
Intra-ductal papilloma‟s can be divided into two major categories: solitary (central)
papilloma and multiple (peripheral) papilloma‟s.

Solitary intra-ductal papilloma’s

 Most frequently observed in women 30 to 50 years of age.
 These lesions are generally less than halve cm in diameter, usually measuring 2 to
3 mm.
 On gross examination, solitary Intra-ductal papilloma is tan-pink, friable tumors
within a dilated duct. The tumor is usually attached to the wall of the involved duct
by a delicate stalk, but it may be sessile.

Multiple (Peripheral) Intra-ductal Papilloma’s

Compared with solitary Intra-ductal papilloma, multiple Intra-ductal papilloma‟s tend
to occur in younger patients; they are less often associated with nipple discharge, are
more frequently peripheral, and are more often bilateral. Most importantly, these
lesions appear to be particularly susceptible to the development of carcinoma.

Phyllodes tumors
Usually occur in women over the age of 40 years.
 It presents as a Bulky tumor.
 They present as a large, sometimes massive, tumor with an unevenly bosselated
surface. Despite their size they remain mobile on the chest wall.
 Rarely, ulceration of overlying skin occurs because of pressure necrosis.
 Made of proliferation of ducts & stroma.
 The stroma shows hyper cellularity, much atypia & numerous mitoses.
 Cross section: characterized by clefts & slits creating leaf-like pattern of
intervening tumor.
 Can be malignant (uncommon) or benign (common)
 Predictors of malignancy: increased cellularity, high mitotic activity, anaplasia,
overgrowth of stromal activity.
 Treatment:
- Excision with a surrounding rim of normal breast tissue for benign one.
- Mastectomy is indicated for massive or recurrent tumour and those of the
malignant type.
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Breast cysts
 These occur most commonly in the last decade of reproductive life as a result of a
non-integrated involution of stroma and epithelium. As a part of fibrocystic
changes.
 They are often multiple, may be bilateral.
 Diagnosis can be confirmed by ultrasound and/or aspiration.
 They typically present suddenly and cause great alarm; prompt diagnosis and
drainage provides immediate relief.

Treatment
 Assurance is the main line of treatment as patients are usually afraid of cancer.
 A solitary cyst can be aspirated. If they resolve completely, no residual mass, not
rapid accumulation, and if the fluid is not blood-stained, no further treatment is
required. However, 30% will recur and require repeated frequent aspiration.
 Cytological examination of cyst fluid is no longer practiced routinely. If there is a
residual lump or if the fluid is blood-stained, a core biopsy or local excision for
histological diagnosis is advisable, which is also the case if the cyst reforms
repeatedly. This will exclude cystadenocarcinoma, which is a rare tumor more
common in elderly women.

Galactocele
Galactocele, which is rare, usually presents during or just after finishing lactation, as a
solitary, oblong cyst taking a shape of a segment of the breast. It contains milk and in
longstanding cases its walls tend to calcify.

Gynecomastia

It is an enlarged breast in the male. It may be physiologic or pathologic.

Physiologic gynecomastia usually occurs during adolescence. Adolescent
gynecomastia is caused by an excess of estradiol relative to testosterone. The
condition often is unilateral but could be bilateral and typically occurs between ages
12 and 15 years.

Etiology and Pathology:

In gynecomastia, the ductal structures of the male breast enlarge, elongate, and branch
with a concomitant increase in epithelium. Mammography if possible and
ultrasonography are used to differentiate it from cancer. Dominant masses or areas of
hardness, irregularity, and asymmetry suggest the possibility of a breast cancer,
particularly in the older male.
Gynecomastia generally does not predispose the male breast to cancer. However, the
hypo-androgenic state of Klinefelter's syndrome (XXY), in which gynecomastia is
usually evident, is associated with an increased risk of breast cancer. Klinefelter's
syndrome (XXY) is manifested by gynecomastia, hyper-gonadotropic hypogonadism,
and azoospermia.
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In pathologic gynecomastia, estrogen excess results from:

1. Increase in the secretion of estradiol by tumors, endocrine disorders (suprarenal

tmors), and hepatic disease (nonalcoholic and alcoholic cirrhosis). Androgen
deficiency may initiate gynecomastia. Gynecomastia usually occurs in men aged
50 to 70 years.

 Primary testicular failure also may be caused by adrenocorticotropic hormone

deficiency, hereditary defects of androgen synthesis, and undescending or
destructed testicle.
 Secondary testicular failure may result from trauma, orchitis, and
cryptorchidism. Renal failure, regardless of cause, also may initiate
gynecomastia.

2. Drugs:

 Drugs with estrogenic activity (digitalis, estrogens, anabolic steroids,

marijuana) or drugs that enhance estrogen synthesis (human chorionic
gonadotropin) may cause gynecomastia.
 Drugs that inhibit the action or synthesis of testosterone (cimetidine,
ketoconazole, phenytoin, spironolactone, antineoplastic agents, diazepam) also
have been implicated.
 Drugs such as reserpine, theophylline, verapamil, tricyclic antidepressants, and
furosemide induce gynecomastia through idiopathic mechanisms.

Treatment:

When gynecomastia is caused by androgen deficiency, then testosterone

administration may cause regression. When it is caused by medications, then these are
discontinued if possible. When endocrine defects are responsible, then these receive
specific therapy. When gynecomastia is progressive and does not respond to other
treatments, surgical excision is considered.
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Cancer breast
Epidemiology
Breast cancer is the most common cancer among women, with one in eight in western
and one in twelve in middle east women expected to develop breast cancer over the
course of their lifetime. It is the second leading cause of cancer mortality in women
(after lung cancer). Breast cancer accounted for 25-30% of all new cancer diagnoses,
and 13% of all cancer deaths in women. With the implementation of improved
screening and management programs, breast cancer mortality has decreased by 30%
over the last decade.
In Egypt:
 Breast cancer is the most prevalent cancer among Egyptian women and
constitutes 29% of National Cancer Institute cases.
 Median age at diagnosis is one decade younger than in countries
Risk Factors
Numerous risk factors have been proven to be associated with the development of
breast cancer. The impact of each of these factors ranges considerably, with some
factors exerting a small increase in risk (RR<2) and others a much larger increase
(RR>4).

Table 1. Relative risk associated with key breast cancer risk factors

Strong risk factors Moderate risk factors Weak risk factors

 Family history in two  Old age  Obesity
or more first degree pre  Personal history  Alcohol abuse
menauposal relatives of cancer breast  High
 BRACA1/BRACA2  Typical socioeconomic
 History of LCIS hyperplasia state
 Atypical hyperpleasia  High breast  Hormonal
 Nulli para density replacement
 White race  Non lactating therapy
 Young menarche  Radiation
 Late menopause exposure

HEREDITARY BREAST-OVARIAN CANCER SYNDROME (HBOC):

BRCA1 and BRCA2 are the two most commonly identified germline mutations in
breast cancer. They are inherited in an autosomal dominant manner. The presence of
one of these mutations is associated with a 50-85% lifetime risk of developing breast
cancer. BRCA1 is also associated with a 45% risk of developing ovarian cancer by 70
years of age. These mutations are more common in the Ashkenazi Jewish population,
among whom 1/40 women are carriers.
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LI-FRAUMENI SYNDROME
A loss-of-function mutation in the p53 tumour suppressor gene results in Li-Fraumeni
Syndrome. This syndrome is associated with an increased risk of breast, prostate, and
colorectal cancer.

COWDEN SYNDROME
A loss-of-function mutation in the PTEN tumour suppressor gene results in Cowden
Syndrome. This syndrome is associated with an increased risk of breast, thyroid,
endometrial, and brain cancer.

GENETIC TESTING
Consideration should be given for referral to the BC Cancer Hereditary Cancer
Program for genetic testing if the patient‟s history is significant for:

 Family history of bilateral breast cancer

 Family history of breast cancer at age <35 years
 Multiple cases of close relatives with breast cancer
 Family or personal history of ovarian cancer
 Family history of male breast cancer
 Ashkenazi Jewish heritage

Screening
Effective screening programs can enable the detection of breast cancer before clinical
signs and symptoms appear. As with many cancers, the earlier a breast cancer is
detected and treated, the better the prognosis for the patient.

Self Breast Examination

Monthly self-breast examinations (SBEs) are recommended to patients. SBEs may
increase emotional distress in women who believe they have a positive finding. If
SBE is performed, it should be conducted in the week following the menstrual period,
and should include inspection and palpation of both breasts and axillae.

Clinical Breast Examination

The combination of mammography screening programs and CBEs have been shown
to decrease mortality from breast cancer. On the basis of this combined benefit, some
cancer agencies continue to recommend that physicians carry out CBEs.

Mammography
Mammogram is x-ray images of breasts. A standard mammogram consists of a
medial-lateral view and a cranio-caudal view of both breasts. Mammography may be
performed as either a screening or a diagnostic investigation. It is considered the gold
 18
standard screening investigation for breast cancer. Screening mammography is
undertaken in asymptomatic women to detect the presence of otherwise unsuspected
breast cancer. It is important to note that screening mammography (single oblique
view) differs from diagnostic mammography, which includes several additional
radiographic views.
Benefits of Screening
Screening mammography has been shown to reduce breast cancer mortality by 25%
among women who are screened regularly.
Risks of Screening
Mammography does not detect all breast cancers. This is especially significant in
younger women, whose denser breast tissue makes mammograms more difficult to
interpret. Conversely, false-positive mammograms can result in costly and invasive
follow-up tests, as well as distress for patients. On average, 7% of women screened
by mammography will be called back for additional testing. Of these women, more
than 95% do not have cancer. Women may express concern about radiation exposure
from mammography. However, the amount of radiation associated with a
mammogram is quite low, and is unlikely to be associated with any increased risk of
malignancy.
Ultrasound
Ultrasound is not recommended as a screening tool for the general population as it has
lower sensitivity and specificity than mammography. Ultrasound may be used in
conjunction with mammography when an abnormal finding is detected and is
especially useful for differentiating solid and cystic components of a mass. Ultrasound
may also be used to guide biopsy of breast lesions.
Magnetic Resonance Imaging (MRI)
MRI is not recommended as a screening tool for the general population. A breast MRI
has very high sensitivity (95-100%) but variable specificity (37-97%), making it a
poor screening tool due to an unacceptably high rate of false-positive. Only certain
subgroups of high-risk individuals may be screened by MRI, including young
individuals with an estimated lifetime risk of 20-25%, individuals with a history of
chest radiation exposure, and individuals with a known or suspected genetic mutation
(eg. BRCA1/2, p53, PTEN).

Histological Classification
Breast cancer is primarily classified histopathologically as seen in overview in the
flowchart below. Breast cancer may also be classified by the expression of hormone
receptors and genetic mutations that are impactful for treatment and prognosis.
 19

1) Non-Invasive Breast Malignancies

In-situ carcinomas are not invaded the basement membrane. These carcinomas, if left
untreated, can progress into invasive carcinomas.
DCIS is responsible for 20% of all abnormal mammogram findings mainly as micro-
calcification. DCIS can be classified as low, intermediate or high grade on the basis of
pathology, and this grading has prognostic value for the likelihood of post-operative
recurrence.
Lobular carcinoma in-situ (LCIS) is a pre-malignant condition arising from the cells
of the breast lobules. It often develops in multiple parts of bilateral breasts at the same
time, and is an important marker for the development of future invasive breast cancer.
As such, women with LCIS should undergo more frequent screening mammography.
2) Invasive Breast Cancers
Over 95% of all invasive breast cancers are adenocarcinomas derived from epithelial
tissue. Rarer forms of invasive breast cancer include stromal-derived malignancies,
lymphomas and metastasis of other cancers to the breast.

INVASIVE DUCTAL CARCINOMA

Invasive ductal carcinomas (IDCs) represent 80% of all invasive breast cancers. IDC
can be further classified into subtypes defined by characteristic histopathological
features.
 Not-Otherwise-Specified is a diagnosis of exclusion, and remains the most
common form of IDC (more than 95%).
 20
 Medullary carcinomas account for 5-10%. They are associated with a good
prognosis.
 Tubular carcinomas account for 2-3% of invasive breast
cancers. Histopathologically, they are well-differentiated and resemble benign
lesions. They are associated with a good prognosis.
 Mucinous carcinomas account for 2% of invasive breast cancers and are found
more frequently in women 60-70 years of age. Histopathologically, they are
characterized by large pools of mucin. They are associated with a good prognosis.
 Papillary carcinomas account for 1-2% of invasive breast cancers and occur more
frequently in postmenopausal women. Histopathologically, they are characterized
by papillae and may be surrounded by a fibrous pseudocapsule. They generally
have a favourable prognosis.

INVASIVE LOBULAR CARCINOMA (ILC)

Invasive lobular carcinomas are the second most common form of invasive breast
cancer and represent 10-15% of all invasive breast cancers. They are characterized by
a single-file of infiltrating cells that invade into breast stromal tissue. On gross
specimen, they have a rubbery hard consistency with irregular borders.

INFLAMMATORY BREAST CARCINOMA

Inflammatory breast carcinoma is a rare but highly aggressive form of breast
cancer. It is more common in young women. It usually presents as a red, warm,
swollen breast. The overlying skin may appear pitted, which is known as „peau
d‟orange‟ due to its resemblance to the texture of an orange peel. At the time of
diagnosis, the cancer has often already spread to involve the lymph nodes and even
distant organs. Prognosis is poor, with an estimated five-year survival of 34%.

PAGET’S DISEASE OF BREAST

Paget‟s disease of breast is another rare form of invasive breast cancer derived from
epithelium of the major lactiferous ducts. It is more common in women over 50 years
of age. It commonly presents clinically, with crusting and scaling of skin of the nipple,
burning, pruritus, nipple bleeding or discharge, and new nipple retraction. A lump
may be felt near or under the nipple. Histologically, it is characterized by large
dendritic neoplastic cells (Paget cells) within the epidermis.

CYSTOSARCOMA PHYLLOIDES
It is a rare locally malignant tumour derived from breast stroma. It does not send
metastasis to lymph nodes. There grading varies from low, intermediate to high
grading according to number of mitosis in microscopic field. Clinically it usually
presented by huge mass not fixed to skin nor underlying muscles. Treatment is by
local wide excision except in malignant form where it's treated by simple mastectomy.
It represents less than 1% of all breast cancers.
 21

Molecular Classification
A additional classification scheme is used an adjunct to the histopathological
classification model. This scheme divides cancers based on their expression of certain
hormone receptors and genes that have significance for both management and
prognosis.

1) Hormone Receptor Status

A malignancy can be classified according to the presence or absence of estrogen and
progesterone receptors. About 75% of breast cancers are hormone receptor positive
meaning that the cancer will grow in the presence of estrogen and/or
progesterone. Both estrogen and progesterone receptor positive cancers are associated
with a more favorable prognosis, including higher disease-free survival and reduced
mortality. Estrogen-receptor positive cancers can be treated using anti-estrogen
(hormonal) therapy. Estrogen-receptor positive cancers are more common in post-
menopausal women.

2) HER2 Status
Human epidermal growth factor receptor 2 (HER2) is a proto-oncogene for a
transmembrane growth factor receptor. HER2 is present in normal breast epithelial
cells, but is overexpressed in 20-25% of all breast cancers. Cancers that overexpress
HER2 are considered to be HER2 positive, and are associated with a higher grade and
more aggressive rate of spread. Targeted therapies are available for HER2 positive
cancers, including Herceptin (transtuzumab) & Perjetta.

Distribution of breast cancer in

different breast quadrants
Signs & Symptoms

Breast Mass
The most common presentation of breast cancer is a painless breast mass or
lump. Malignant breast masses are usually hard, irregular and not tender. Masses that
are fixed to the skin or chest wall are more suspicious of malignancy, as are lesions
with overlying skin changes. Breast tissue thickening, mastalgia (breast pain), and
changes in mass size throughout the menstrual cycle are features more typical of
benign breast conditions.
 22
Skin manifestation of cancer breast:
 Skin retraction: due to tumour infiltration to cooper's ligaments.
 Peau d'orange : due to dermal lymphatic obstruction.
 Skin ulceration.
 Nipple retraction.
 Payet's disease of the nipple.
 Inflammatory carcinomatosis.

Nipple Changes
Nipple discharge may be seen in both benign and malignant conditions. However,
spontaneous nipple discharge that is unilateral, blood stained, or associated with a
mass is suspicious for breast cancer. Changes in the nipple‟s appearance, such as new
inversion of the nipple, are also concerning for possible malignancy.
PAGET’S DISEASE OF THE BREAST:
Paget‟s disease often presents with unilateral erythema, pruritis and scaling of the
nipple and areola areas. These symptoms are sometimes mistaken for eczema in the
early stages of the disease.
INFLAMMATORY BREAST CANCER:
Inflammatory breast cancer is an aggressive form of breast cancer that presents
similarly to infectious mastitis. Skin on the breast may appear erythematous, pruritic,
and warm to touch. As cancer cells invade and block lymphatic vessels, the breast
and overlying skin can become edematous. This gives rise to a skin condition known
as „Peau d‟orange,‟ in which the skin appears dimpled like an orange peel.

Left breast with inflammatory breast cancer

Axillary Lymphadenopathy:
Masses felt in the axilla may represent lymphadenopathy caused by malignant spread
to the lymph nodes. These masses are typically hard and painless.
 23
Jaundice, confusion and headache. Additionally, metastatic spread can be associated
with non-specific symptoms including weight loss, loss of appetite, and nausea.

Distant Metastases

 At approximately the twentieth cell doubling, breast cancers acquire their own
blood supply (neovascularization). Thereafter, cancer cells may be shed directly
into the systemic venous blood to seed the pulmonary circulation via the axillary
and intercostal veins or the vertebral column via Batson's plexus of veins, which
courses the length of the vertebral column.
 Common sites of involvement, in order of frequency, are bone, lung, pleura, soft
tissues, and liver. Symptoms of metastatic spread can therefore include bone pain,
cough, shortness of breath.

Diagnostic Approach

Any new breast lesions should be investigated using the ‘triple assessment.’ This is a
combined use of clinical exam, imaging, and biopsy to assess breast lesions.

History
Taking a good history is an important initial step in the diagnosis process of breast
cancer, and can provide valuable information to begin distinguishing between breast
malignancy and benign forms of breast disease including mastitis, breast cysts,
fibroadenomas, and intraductal papillomas.
Characteristics of the breast mass, including duration, current size of the mass, rate of
growth and any changes in the appearance of the breast, nipple or skin. Associated
features of the breast mass should also be elicited, including breast pain, changes in
the mass throughout the menstrual cycle, and the presence of nipple discharge.
Additional information to be elicited includes the presence of any signs or symptoms
of lymphatic spread or metastatic disease.
Any prior history of breast disease should be elicited, including any history of breast
hyperplasia, LCIS, or breast cancer. Other significant past medical history includes
any history of any risk factors for breast cancer, and any prior history of other
malignancies.
Family history should include any history of relatives with breast cancer or ovarian
cancer. If a positive history is present, details should be elicited including the age of
the relative at diagnosis and basic characteristics of their disease course.
Any current use of hormone-replacement therapy or oral contraceptive pills should be
assessed.
 24

Physical Exam
The breast exam should begin with the patient seated and naked from the waist up to
the head. The breasts should be inspected for any visible bulge, asymmetry or notable
skin changes. The patient should be asked to slowly abduct their arms above their
head, and then slowly lower them back down, while the clinician observes for any
signs of a breast mass tethering to the skin or muscle. The patient should also be asked
to place their hands on their hips and press down in order to elicit any fixation of a
breast mass to the pectoralis major muscle.

The next portion of the exam is examination of the

breasts by palpation. The patient should be asked to
lie in a supine position with both hands behind her
head, as this results in the breast tissue being spread
more evenly over the chest. Each breast should be
palpated separately starting with normal side, using
the palmer surface of examiner‟s fingers. Palpation
should be performed in a systematic manner and
should include all tissue from the sternal border to the Speculated mass in mammogram
axillary tail. Any abnormal masses should be proven to be invasive carcinoma
described in terms of their location, size, depth,
mobility or fixation, consistency, contours, tenderness and any overlying skin
changes.

The clinician should next examine the axilla and supraclavicular region by palpation
for the presence of any lymphadenopathy descripting its character‟s. If suspicious of
advanced disease, examination of the chest, abdomen, and skeleton should be
performed to assess for signs of distant metastasis.

Imaging

1) Bilateral Mammogram
Diagnostic mammography is the recommended initial investigation of choice for
women over the age of 30 years who present with a breast complain. Bilateral
diagnostic mammography provides additional views to further characterize the
abnormality and allows for a more thorough inspection of both breasts.

2) Ultrasound
Ultrasound is the initial investigation of choice for women under the age of 30 years
who present with a breast abnormality. It may also be indicated to further evaluate an
abnormality on screening mammography, or to evaluate women with dense breasts.
Usually combined with any mammogram imaging to increase its accuracy.
 25
3) MRI
MRI is uncommonly used. In the case of axillary lymph nodes found to be positive for
breast cancer in the absence of a known breast tumor, MRI may be useful to identify
the location of the primary occult tumour.

Biopsy

1) FINE-NEEDLE ASPIRATION (FNA)

FNA is most often used for benign breast masses or cysts. A thin needle is inserted
into the lump, and fluid and cells are aspirated. The sample is then sent to pathology
to rule out the presence of malignant cells.

2) CORE NEEDLE BIOPSY

It is therefore the method of choice to assess solid breast masses. A large gauge
hollow doubled needle is inserted into the lump to obtain core of tissue.

3) GUIDED BIOPSY
Stereotactic biopsies are similar to core needle biopsies except they are performed
with the aid of either mammogram or ultrasound imaging. These biopsy techniques
are useful when a breast abnormality is seen on mammography but cannot be palpated
(non palpable masses).

Other methods for biopsy

1) Excisional biopsy
If a breast mass has a high probability of being or previous methods of biopsies failed
to prove malignancy, an incisional of a part or more often excisional biopsy may be
performed. A surgeon will attempt to excise the entire abnormal mass with a margin
of normal tissue. The excised mass is then sent to pathology.

2) Wire-localized biopsy
If a breast mass is highly suspicious for malignancy but not easily palpated, under X-
ray guidance, a radiologist inserts a thin wire to identify the location of the mass. The
surgeon is then able to use the wire guide as well as the x-ray films to excise the
suspicious area. After the procedure, the specimen could be imaged to ensure that the
entire lesion was excised.

Metastatic workup

These are done when the lump proved to be malignant these include:
1. Plain chest x ray or better chest CT with contrast to exclude presence of lung
metastases. CT chest has a better diagnostic yield it diagnoses with accuracy
lung, subpleural deposits, effusion or mediastinal LN affection.
 26
2. Abdominal & pelvic US or CT with contrast: to exclude hepatic deposits.
3. Skeletal isotope scan: bone metastases show 'hot spots'

Staging: TNM Staging

This system stages breast cancer according to three primary features. The first feature
is the tumor size, represented by „T‟. The second feature is the extent of spread to
regional lymph nodes, represented by „N‟, The third feature used to classify breast
cancer is the presence of any distal metastasis, represented by „M‟. which can be
determined either clinically or pathologically. On the basis of these features, breast
cancer is assigned a TNM status, which correlates to a certain stage of breast cancer
according to the table below.

Primary tumor (T) Definitions for classifying the primary tumor (T) are the same for
clinical and for pathologic classification. If the measurement is made by physical
examination, the examiner will use the major headings (T1, T2, or T3); if other
measurements, such as mammographic or pathologic measurements, are used, the
subsets of T1 can be used. Tumors should be measured to the nearest 0.1-cm
increment.
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ
Tis Ductal carcinoma in situ
(DCIS)
Tis Lobular carcinoma in situ
(LCIS)
Tis Paget's disease of the nipple with no tumor (NOTE: Paget's disease
(Paget's) associated with a tumor is classified according to the size of the tumor)
T1 Tumor 2 cm in greatest dimension
T1mic Microinvasion 0.1 cm or less in greatest dimension
T1a Tumor >0.1 cm but not >0.5 cm in greatest dimension
T1b Tumor >0.5 cm but not >1 cm in greatest dimension
T1c Tumor >1 cm but not >2 cm in greatest dimension
T2 Tumor >2 cm but not >5 cm in greatest dimension
T3 Tumor >5 cm in greatest dimension
T4 Tumor of any size with direct extension to (a) chest wall or (b) skin, only as
described below
T4a Extension to chest wall, not including pectoralis muscle
T4b Edema (including peau d'orange), or ulceration of the skin of the breast, or
satellite skin nodules confined to the same breast
T4c Both T4a and T4b
T4d Inflammatory carcinoma
 27
Regional lymph nodes—Clinical (N)
NX Regional lymph nodes cannot be assessed (e.g., previously removed)
N0 No regional lymph node metastasis
N1 Metastasis to movable ipsilateral axillary lymph node(s)
N2 Metastases in ipsilateral axillary lymph nodes fixed or matted, or in
clinically apparenta ipsilateral internal mammary nodes in the absence of
clinically evident axillary lymph node metastasis
N2a Metastasis in ipsilateral axillary lymph nodes fixed to one another (matted)
or to other structures
N3 Metastasis only in clinically apparenta ipsilateral internal mammary nodes
and in the absence of clinically evident axillary lymph node metastasis;
metastasis in ipsilateral infraclavicular lymph node(s) with or without
axillary lymph node involvement, or in clinically apparenta ipsilateral
internal mammary lymph node(s) and in the presence of clinically evident
axillary lymph node metastasis; or metastasis in ipsilateral supraclavicular
lymph node(s) with or without axillary or internal mammary lymph node
involvement
N3a Metastasis in ipsilateral infraclavicular lymph node(s)
N3b Metastasis in ipsilateral internal mammary lymph nodes(s) and axillary
lymph node(s)
N3c Metastasis in ipsilateral supraclavicular lymph node(s)

Locally advanced breast cancer (LABC):

 Any patient with one of the following is considered to have LABC:
 Tumor size ≥ 5 cm
 Tumor fixed to chest wall
 Fixed ipsilateral lymphadenopathy
 Supra-clavicular lymphadenopathy
 Extensive skin manifestations (≥ 1/3 of skin of the breast)
 Inflammatory carcinomatosis
 28

Management of cancer breast

Surgery

Surgery is a core component of breast cancer treatment. For non-metastatic breast

cancer, surgery is considered the primary treatment. Several surgical procedures are
employed in the management of breast cancer.

Breast conserving surgery (BCS), also known in the past as a „lumpectomy‟ or

partial mastectomy, is a procedure in which the surgeon aims to remove the breast
tumour along with a margin of healthy tissue all around, while sparing the remaining
healthy breast tissue. When BCS is performed in patients with localized DCIS or early
invasive breast cancer, and followed by external beam radiation therapy, it has been
shown to achieve survival rates equal to those of patients treated with mastectomy.
Contraindications to BCS include multicentric tumours, inflammatory breast cancer,
persistent positive margins after localized surgical resections, and contraindications to
radiation such as pregnancy or history of previous breast irradiation. BCS is also not a
good option for women with large tumour size relative to breast volume, as a good
cosmetic result may not be achieved under these conditions.

Mastectomy is a surgical procedure in which the whole breast glandular tissue is

removed. In a modified radical mastectomy, the breast tissue, nipple, axillary lymph
nodes and pectoralis fascia are all removed. This procedure continues to be performed
in patients for whom BCS is contraindicated. In a simple mastectomy, only the breast
tissue is removed, with the surrounding musculature and lymph nodes remaining in
place. This procedure is performed only in patients with diffuse DCIS and as a
palliative in metastatic breast cancer. Some women at a very high risk of developing
further invasive breast cancer may choose to undergo prophylactic bilateral simple
mastectomy. This is not commonly performed as it is considered to be an aggressive
surgery.

Surgical management also includes management of the axilla; basically to assess

lymph nodes affection for use in cancer staging and determine further treatment
needed. A sentinel lymph node biopsy is usually recommended for patients with no
clinically palpable nor imaging detected lymph nodes (N0). In this procedure, the first
axillary lymph nodes to which cancer is most likely to spread is removed and sent for
pathology. If the sentinel lymph node is negative, the cancer is unlikely to have spread
to other lymph nodes. If the sentinel lymph node is positive, the patient should
undergo complete axillary lymph node dissection to remove the remaining axillary
lymph nodes and allow assessment of the extent of the cancer‟s lymphatic spread.
Patients should proceed immediately to axillary lymph node dissection if they have
clinically or radiologically node positive disease.
 29
Radiation
Radiation therapy is offered to breast cancer patients following breast-conserving
surgery in order to reduce the risk of cancer recurrence. For early invasive breast
cancer, the use of external beam radiation therapy results in a 20% absolute reduction
in 10 years risk of recurrence, which in turn results in a 5% reduction in breast cancer
mortality. Radiation treatment is usually not performed in patients who have
undergone modified radical mastectomy for early invasive breast cancer. However,
radiation therapy may be offered to these patients if certain high-risk features are
present, including lymph-node positive disease. The schedule for radiation therapy
typically involves treatments being given five days per week for a duration of five to
seven weeks.
External beam radiation may also be considered for palliation. It may be used to
control pain and other symptoms arising from localized metastases, such as bone
metastases, spinal cord metastases, metastases causing bronchial obstruction, and
large or painful chest wall metastases.
Hormonal therapies
Hormonal therapies are offered as adjuvant therapies to patients with hormone-
receptor positive of any stage. The duration of recommended use ranges from five
years to ten years. Options for hormonal therapy include selective-estrogen receptor
modulators (SERMs), aromatase inhibitors (AIs), ovarian suppression with luteinizing
hormone-releasing hormone (LHRH) agonists, and surgical removal of the ovaries.
In pre-menopausal women, Tamoxifen is the most commonly used SERM, and has
been shown to reduce the risk of breast cancer recurrence by 30-50% in
premenopausal women. Tamoxifen is also the most commonly used agent in post-
menopausal women, in whom it reduces the risk of breast cancer recurrence by 40-
50%. However, in post-menopausal women with stage 4 breast cancer, AIs are
considered first-line due to their greater efficacy in this population.
Tamoxifen is associated with an increased risk of endometrial cancer, DVT/PE and
stroke. It is therefore relatively contraindicated in women with a personal history of
venous thromboembolism or endometrial cancer. AIs are associated with an increased
risk of osteoporosis and dyslipidemia, and caution should be therefore be used when
prescribing AIs to women with a history of these conditions.
Chemotherapy
Chemotherapy is most often used as an adjuvant therapy for breast cancers that are
stage II or greater. It is particularly important for breast cancers that are ER and PR
negative, as these malignancies do not qualify for hormonal therapy. The age, medical
comorbidities, and general health of the patient should be considered prior to starting
any chemotherapy regimen. Chemotherapy may also be used as a neoadjuvant therapy
to reduce the size of the tumor prior to surgery. This may render previously non-
 30
operable tumors operable or allow breast-conserving surgery in a patient for whom
this was not previously feasible goal. Multi-agent chemotherapy regimens are usually
employed due to their greater efficacy & to decrease each drug specific complications.
Herceptin (trastuzumab) is a monoclonal antibody against the HER2 receptor that is
used in the treatment of HER2 positive breast cancer
 31
Prognosis
As demonstrated in the table below, the prognosis of breast cancer is determinedly
largely by the stage of disease. Stage 0 and Stage 1 disease has a 5-year survival of
98-100%, while Stage 4 disease has a median survival of 18-24 months. Within
staging, the presence or absence of spread to lymph nodes is the most important
prognostic factor. Higher numbers of positive lymph nodes are associated with a
worse prognosis. The second most important prognostic factor within staging is the
size of the tumour, with larger tumours having a worse prognosis.

Additional factors also have an influence on prognosis and may guide treatment
decisions. Positive hormone-receptor status is associated with a better prognosis, as
these tumours are usually less aggressive and respond well to hormonal therapies.
Triple negatives & HER2 positive status is associated with a worse prognosis, as these
tumours are usually more aggressive and more likely to metastasize. Younger age at
diagnosis (age < 35 years) is also associated with more aggressive, higher-grade
tumours, and local recurrence.

Follow-up

Following up is essential as it allows the health care team to assess and monitor any
side effects of the treatment. In addition, follow-up care is critical for early detection
of recurrent breast disease. Follow-up appointments are usually recommended to
occur every 3-6 months for the first 5 years, and annually thereafter. Each follow-up
appointment should include a history, physical examination, which include a clinical
breast exam, axillary node palpation, and an examination of the chest and abdomen.

Diagnostic mammography is the appropriate investigation for follow-up of breast

cancer. It should be performed six-months after the end of treatment, and annually
thereafter. Blood tests, chest x-rays, liver and bone scans are not indicated unless there
is suspicion of metastasis or new onset of symptoms suggesting recurrence.

Breast Cancer in Men

Male breast cancer is rare, accounting for less than 1% of all breast cancers. Risk
factors for breast cancer in men include a family history of breast cancer, presence of
BRCA mutations, Klinefelter syndrome, and exposure to chest radiation.
 32

Soft Tissue Neoplasms

The term soft tissue is used to describe all non-epithelial tissue arise from any
mesoderm derivative tissue except: bone, cartilage, brain & its coverings,
hematopoietic cells & lymphoid tissue.

CLASSIFICATION
Benign Tumors (more common):
- Adipose tissue: Lipoma.
- Fibrous tissue: Keloid, Fibroma, Nodular fasciitis
- Fibrohistocytic: Fibrous histocytoma
- Muscle origin: Rhabdomyoma, leiomyoma
- Lymphatic system: Cystic hygroma, Lymphangioma simplex, lymphangioma
- Vascular system: Hemangioma, Pyogenic granuloma, Glomus body tumor
- Nervous system: Neuroma, Neurofibroma, Schwannoma
- Uncertain (combined) origin: Hamartoma.

Locally Malignant (infiltrates locally but do not metastasize)

- Desmoid tumor.
- Dermatofibrosarcoma protuberans

Malignant (fortunately rare):

- Liposarcoma - Fibrosarcoma
- Malignant fibrous histocytoma - Rabdomyosarcoma
- Leiomyosarcoma - Lymphangiosarcoma
- Hemangiosarcoma - Malignant Schwannoma
- Kaposi sarcoma - Malignant hamartoma
- Synovial sarcoma - Epithelioid sarcoma

Benign to malignant transformation

Certain BTs are prone to undergo malignant changes, and it is important for both R/ &
prognosis to realize when this occurs. Some or all of the following may be recognized:
- Rapid ↑ in size - ↑ vascularity - Fixity
- Involvement of nearby structure: e.g. facial palsy
- Dissemination: to LNs or remote secondary's

BENIGN TUMORS
Lipoma
It is the most common soft tissue neoplasm. It may occur anywhere in the body except
where there is no adipose tissue (eye lid, glans penis). Head & neck, shoulder,
abdominal wall & thighs are particularly favoured sites. It is usually solitary but may
present in families as multiple subcutaneous (SC) lipomatosis all over the body
(Dercum disease).
 33
Types
- Pathological: pure lipoma, fibrolipoma, hemangiolipoma, angiolipoma (painful).
- Anatomical (in order of frequency): subcutaneous, inter-muscular, retro peritoneal,
sub-fascial, sub-serous, sub-mucous, sub-synovial, intra-articular, para-osteal,
CNS, intra-glandular.

Clinical picture & differential diagnosis (DD)

- History: A slowly growing, painless lump
- Examination: A lipoma is not tender. It is well-defined, with a smooth or lobulated
surface & slippery edges, soft, freely mobile, pseudo-fluctuant & regional LNs are
not enlarged.
- Investigations (diagnosis is usually on clinical base but if needed)
1. FNAC → benign fat cells
2. US → well-circumscribed, capsulated, solid swelling
- Differential diagnosis: Sebaceous cyst, fibroma, organized haematoma, ganglion

Complications
- Sarcomatous changes (especially in certain sites: retroperitoneal, back & thigh)
- Myxomatous degeneration - Calcification
- Pressure on nearby structures
- Inflammation - Disfigurement

Treatment
- Excisional biopsy is standard treatment. Liposuction could be helpful in cosmetic
areas.
- In case of multiple tumors; excise the symptomatizing or complicating one.
Fibroma
- Pure fibroma is rare, most fibromas are combined: fibromyoma, fibrolipoma,
neurofibroma, etc
- It is either soft or hard depending on the proportion of fibrous to other cellular
tissue.
- Some reactive fibroblastic proliferation may mimic BT such as nodular fasciitis
(eg. Dipteran contracture), which is usually a painless, small (< 3 cm), slowly-
growing mass, in the upper extremities & trunk.
Neurofibromatosis
- It is caused by autosomal dominant (AD) gene.
- There are two types:
1. Type 1 (90%): It was previously known as Von Recklinghausen disease.
Characterized by multiple pedunculating nodules as well as pigmented skin
discoloration (café-au-lait spots).
2. Type 2: It was previously called bilateral acoustic neurofibromatosis.
Clinically, there is pain, numbness, or pressure manifestation, tenderness &
limitation of mobility along the axis of nerve where it originates from.
 34

LOCAL MALIGNANT TUMORS

A. Desmoid Tumor
- It is an uncommon tumor that arises from musculo-aponeurotic structure.
- Site: The most common site is the anterior abdominal wall, which usually presents
as a slowly growing, hard, mass in the anterior abdominal wall below the level of
the umbilicus (more common in multipara women). Special intra-abdominal type is
usually associated with familial polyposis coli (Gardner syndrome). It also occurs
at the head & neck, thigh & shoulder.
- Pathology: formed of fibrous tissue with multinucleated plasmoidal masses, un-
capsulated, infiltrate neighborhood muscle. Metastasis does not occur & no
sarcomatous change happened.
- Treatment: wide excision with 1 inch safety margins all around. Muscular defect
should be repaired with prosthetic mesh. Radiotherapy could be used as adjuvant or
in cases where total excision is not possible.

B. Dermatofibrosarcoma protuberans
- Pathology: It is an intermediate type between benign fibrohistocytoma & malignant
fibrohistosarcoma. It is composed of a mixture of fibroblast & phagocytes (lipid
laden cells with histocytic appearance).
- Clinical Picture: It is a rare tumor, which occurs in young age usually in trunk &
shoulders. It appears as slowly growing, bluish, dermal nodule. Suddenly it grows
fast, ulcerates & infiltrates surrounding structures. Rarely, it gives metastasis to
lungs.
- Treatment: Wide local excision in all direction including depth.

SOFT TISSUE SARCOMAS (STS)

They are rare (1% of human cancer) & arise from mesenchymal tissue (mesoderm in
origin). Although they have been traditionally classified according to tissue of origin,
it is now evident that histological grade & clinical stage are more important as
prognostic indicators & in determining the management approach.

They differ from carcinomas by

- Younger age - Rapid rate of growth
- Rapid local invasion - Blood born metastasis is commoner
- Worse prognosis - Less sensitive to radio & chemotherapy
Etiology
Unknown but there are some predisposing factors like:
1. Radiation exposure
2. Post mastectomy arm lymphedema
3. Von Recklinghausen disease
 35
Grading
G1 Well differentiated
G2 Moderately differentiated
G3 Poorly differentiated
G4 Undifferentiated
Staging
T1 5 cm or less
T2 > 5 cm
N0 No regional LN metastasis
N1 Regional LN metastasis
M0 No distant metastasis
M1 Distant metastasis

Differential diagnosis
1. Benign soft tissue tumors
2. Organized hematoma
3. Vascular aneurysm & AV fistula
4. Lymphadenopathy
5. Myositis ossificans
Prognostic factors (the following make the tumour worst)
1. Type: Malignant histocytoma is worst
2. Grading: bad with undifferentiating
3. Staging: Distant metastases are usually fatal
4. Site: retro peritoneal is more fatal
5. Local recurrence: predisposes to further recurrence
6. Biological expression of tumor: e.g. p53
Clinical picture
Rapidly growing painless swelling, hot surface, ill-defined border, variable in
consistency, fixed, dilated subcutaneous veins, enlarged LN in special types.
Investigations
1. CT: Best in abdominal & thoracic lesions
2. MRI: Better in neurological, muscular & bony lesions
3. PET: Gives an idea about the metabolic function of sarcoma & surrounding tissue.
4. Biopsy: Either open incisional or better to be taken by FNAC or core tissue biopsy
under US or CT guidance. (core biopsy is the prefers method)
Treatment
1. Surgical
- En-bloc wide excision in all directions should be performed, even if it includes
major neurovascular structures, which need further reconstruction.
 36
- Amputation is indicated in very huge, aggressive or recurrent cases.
- Excision of localized solitary metastases could be curative in some patients.
- LN block dissection is needed only in certain types of STSs (angiosarcoma
synovial, Rhabdomyosarcoma, epithelioid)
2. Radiotherapy
- Preoperative: may ↓ size to facilitate surgical removal & ↓ local recurrence.
- Post-operative: as adjuvant in cases of suspected surgical margin involvement.
3. Chemotherapy
- Best results are achieved with childhood malignancy.

Characters of individual's ST tumours

Liposarcoma
- It is the commonest sarcoma in general, age of 50-60 y, most frequent in retro
peritoneal region & extremities.
- Types: well differentiated, myxoid, fibroblastic, lipoplastic, pleomorphic (arranged
from better to worst prognosis).
Malignant fibrohistosarcoma (pleomorphic undifferentiated sarcoma)
- It is the most common sarcoma in young adult age, with 2nd peak between 50-70 y.
- It usually arises in the deep muscular tissue of extremities or in retroperitoneal
space.
- It is a highly aggressive tumor that usually recurs locally & sends metastasis in >
50% of patients.
Fibrosarcoma
- Incidence: It is the 2nd most common sarcoma at the age of 35-50 ys, higher
incidence in the thigh & arm.
- Clinically: Firm, rubbery, painless nodule of long duration.
- Histologically: Low grade or high grade (worst prognosis).
Rhabdomyosarcoma
- It is predominantly a neoplasm of infancy & childhood.
- The most common histological variant is embryonal rhabdomyosarcoma with good
response to variant therapeutic tools (others are alveolar & pleomorphic types).
- It arises usually in head & neck area, genitourinary tract & retro peritoneum.
Leiomyosarcoma
- It is the most common sarcoma of the uterus & GIT.
- It is distinguished from leiomyoma by the infiltrate growth, great cellularity,
pleomorphism, greater mitotic activity & the presence of metastasis.
 37
Kaposi sarcoma
- It is a rare malignancy characterized by flat purplish-red skin lesions particularly
lower limb that may affect also mucous membrane, GIT & other visceral organs.
- There is well known two types:
1. Non-aggressive form, affecting mainly Central European Jews.
2. Aggressive form, affecting mainly immuno-suppressant patients (AIDS, organ
transplantation). Characterized by fever, chills, internal organ involvement &
lymphadenopathy.
- Treatment: AZT & interferon (IFN) to raise the immunity of AIDS patients,
radiotherapy, surgery is limited to small localized lesion & for R/ of intestinal
complications.
Synovial sarcoma
- This tumor accounts for 10% of all STSs, known also as spindle cell tumor.
- Despite of the name, it does not arise from synovial cells; rather, it derives from
mesenchymal cells about joint cavities & sometimes in sites totally remote from
joint.
- It has a variable histological grading but the high grade one is an aggressive tumor
with high recurrence rate (RR).

RETR-PERITONEAL TUMORS
Anatomy
- The space between the posterior abdominal muscular wall & peritoneum is termed
retoperitoneal space, which extends from the diaphragm above to the pelvic brim
below.
- It contains: Aorta, IVC, cysterna chili, para-aortic LNs & vessels, lumber plexus &
chain of sympathetic ganglia. The kidneys, ureters, adrenals & pancreas are also
within this space. The term retro peritoneal tumor is usually confined to tumors
arises in retro peritoneal space with exclusion of kidneys, adrenals and pancreatic
swellings.
Classification & examples
- Cystic: Teratoma, remnant of Wolffian ducts, dermoid, parasitic, lymphogenous.
- Solid benign (20%): lipoma, leiomyoma, neurofibroma.
- Malignant (80%): lymphoma, Liposarcoma, fibrosarcoma, neurofibrosarcoma.
Diagnosis
- History: Vague symptoms: abdominal discomfort, back pain, anorexia, fatigue &
weight loss.
 38
- Examination: Abdominal mass: In most cases, a mass could be palpated. In some
huge tumors obstruction of IVC leads to edematous legs, dilated abdominal veins &
ascites.
- Imaging: CT and MRI are the investigations of choice.
- CT guided core biopsy: has to be done in all cases

Treatment
- Surgical excision is the gold standard R/. However, only 25% of tumors could be
completely resected.
- In unrespectable cases: Excision of as much as possible from the tumor (de-
bulking) combined with radio/chemotherapy carries a better prognosis than either
alone.
 39

Surgery of Lymph Nodes

Lymph nodes (LN) are accumulations of lymphatic tissue varying in size from 1 mm
up to 1 cm. They are about 500 to 1000 LN in each person.
1. Anatomy
Lymph nodes are located along the course of lymphatic vessels, whose contents pass
through the regional nodes to the main drainage system of the thoracic and right
lymphatic duct. (Figure 1)

The main groups of lymph nodes in human body

Cervical groups of LNs

The neck is a small area but contain a large number of Lymph nodes up to 200. As
each group drain certain areas in head & neck, further anatomical subdivision is
needed, they subdivided clinically into superficial and deep group, each of them
subdivided into circular & longitudinal one (Figure 4):
Superficial circular groups:
Sub-mental, sub-mandibular, parotid (pre-auricular), retro-auricular (post-
auricular), and occipital. (Figure 2)
Superficial longitudinal chain:
Anterior chain (Para-midline): along superficial jugular veins.
Lateral chain: along external jugular vein.
Posterior chain: along spinal accessory nerve.
Deep Circular chain (Waldeyere’s ring):
Lingual anterior anteriorly, palatine tonsils on both sides and nasopharyngeal
(adenoid) in the middle posteriorly. (Figure 3)
Deep Longitudinal chain:
 Midline chain (small): Pre-laryngeal (Delphian), pre-tracheal and supra-
sternal.
 40
 Lateral chain (Main stem): lies along the internal jugular vein extending from
the base of the skull to the root of the neck. Crossed obliquely & divided by
sterno mastoid muscle into upper (anterior), middle and lower (posterior)
group:
o Upper anterior: in front & above the sterno mastoid muscle (drain
tongue and tonsil).
o Middle: under cover by sterno-mastoid muscle(drain Thyroid and
Larynx)
o Lower posterior: including supra calvicular (Virchow‟s: left
supraclavicular)

Deep Circular cervical lymph nodes (Waldeyere’s ring)

Superficial Circular & Vertical Cervical Lymph nodes

Surgeons preferred to classify Cervical Lymph nodes into groups (Figure 4). Each
group drain certain area which the surgeon is concerning about clearing this area
during lymph nodes dissection (removal) during excision of head & neck tumors.

Surgical groups of cervical lymph nodes

 41
Axillary group of LNs
Axillary group of LNs include 5 anatomical groups that drain from the level of the
clavicle down to the umbilicus, including the upper limb:
1. Pectoral (Anterior): drains the breast and the anterior abdominal wall above
umbilicus. Rotter’ s LN (Inter-pectorals LN) is a part of it
2. Subscapular (Posterior): drains the back till the level of the iliac crests.
3. Brachial (Lateral): felt against the humorous; drains mainly the upper limb.
4. Central: felt against the chest wall; drains the above groups.
5. Apical: related to the apex; drains all above groups.
Surgically, they are divided in relation to pectorals minor muscle into three levels:
1. Level I: below pectorals minor muscle
2. Level II: behind pectorals minor muscle
3. Level III: Above pectorals minor muscle
Inguinal group of LNs
Inguinal group of LNs drain he trunk from the level of the umbilicus downwards
including he genitalia and lower limbs, divided into superficial and deep:

Superficial group:
Transverse chain: below and parallel to the inguinal ligament:
Lateral LN: drain the buttocks
Medial LN: drain below umbilicus, perineum, external genitalia, lower
½ of anal canal & anterior urethra
Vertical chain: along the long saphenous vein; drains the lower limb

Deep group:
Drains the superficial group and directly the clitoris and the glans penis and the
bladder; Cloquet LN in the femoral canal is a part of it.

Pre-aortic & Para-aortic group of LNs

Pre-aortic: over the descending aorta; celiac, superior and inferior mesenteric group
Para-Aortic: on both sides of the aorta; renal, gonadal & common iliac
NB: Rarely could be clinically felt as epigastric mass when pathologically affected

Histology:
LNs are kidney-shaped structures with a hilum on one side containing an efferent
lymphatic running along with blood vessels. Afferent lymphatic‟s enter the node at
multiple sites over its convex surface. (Figure 5)
 42

Histological structure of lymph nodes

Lymph vessels
 Also called lymphatics
 Lymph vessels form a complicated, spidery network of fine tubes
 The smallest vessels, called lymph capillaries, have closed ends

Lymph flow
 Lymphatics carry lymph in one direction toward the heart
 Lymph flows into one of two lymph ducts:
- Right lymph duct drains right arm, shoulder & right side of the head and neck
- Left lymph duct (thoracic duct) drains rest of the body
 These two ducts drain into subclavian veins where they join internal jugular
veins to form brachiocephalic veins

Lymph flows due to:

1) Lymphatic pressure gradient
2) Muscular and respiratory pumps
3) Semilunar valves

Lymphangitis:
It is acute inflammation of the lymphatics usually by bacteria, more common in
extremities. Clinically it appears as a painful red strikes under skin of upper or lower
limbs with fever & malaise. Treated by: treating the infected primary spot, proper
systemic antibiotics & analgesic antipyretics.

Lymphedema:
Definition: Lymphedema is a condition that results from impaired flow of the
lymphatic system. It is caused by absence, malfunction or blockage of the lymph
vessels.
Lymphatic system is damaged or blocked causes accumulation of high protein fluid in
tissues. These swelling decreases oxygenation of the tissues, and makes them heal
slowly. Also protein stimulates chronic inflammation & formation of excess fibrous
tissue.
 43
The stagnant protein & water provides perfect site for bacterial growth & fungal
infections. These infections have greater loads on lymphatics, and worsen
lymphedema. (Figure 6)

Lymphedema of upper & lower limbs

Clinical picture:
Early:
 Tightness and heaviness in the limb
 Aching buttocks or shoulder
 Pins and needles in the limb
 A feeling of 'tightness' and tenderness in the elbow or back of the knee.
 Early lymphedema pits if pressed by thumb

Late:
 Edema is no longer pits (none pitting edema)
 The skin may get very thick, with huge folds and warts – elephantiasis
 loss of hair and alterations of nails
 Skin may get very thick, with huge folds and warts – elephantiasis
 Sometimes lymph leaks through skin & leads to superadded infection

Causes of Lymphedema:
1. Primary Lymphedema
Caused by deficient in lymphatic system either due to: Anaplesia, Hypoplasia or
even none functioning Hyperplasia
According to the time of presentation it is either:
 At birth (lymphedema congenita)
 During puberty (lymphedema praecox)
 Later in life (lymphedema tarda)
2. Secondary (blocked or cut lymphatics)
 Surgery: removal of lymph nodes
 Radiotherapy: destroys the lymph nodes
 44
 Trauma: tear lymphatics
 Parasites: filarial worms
 Paralysis, venous insufficiency, lipodema
Grades of Lymphedema
 Grade 1: pitting and reduced if the limb is elevated.
 Grade 2: does not pit, and is not much reduced by elevation
 Grade 3 (Elephantiasis): has gross changes to the skin
Treatment: (usually very difficult)
 Reduce risk of infection (keeping skin healthy, limit cuts, burns or insect bites)
 Gentle exercise
 Physiotherapy
 Elastic bandage
 Diuretics
 Limb elevation
 There is no cure for lymphedema and once it develops, it can be a long-term,
uncomfortable, and sometimes painful condition requiring daily treatment
 45

Tumor Markers

Definition
Tumor markers are substances expressed or secreted by tumor cells, which can be
used to discriminate between tumor & normal tissue

Characters of ideal tumor marker

- Specific Sensitive
- Rapid correlation Cheap & easy test

Clinical application of tumours marker

- Diagnosis (site, staging)
- Assessment of response to treatment
- Detection of relapse or recurrence
- Screening
- Therapeutic (targeted therapy)

Classification of TMs
1. Specific e.g. Philadelphia chromosome in chronic myeloid leukaemia (CML)
2. Non-specific, expressed by many different types of cancer e.g. carcinoembryonic
antigen (CEA) & alpha-feto protein (AFP)

Clinical Types
Tumor markers can be detected in the following:
1. Tissue: e.g. Chromose, ER (estrogen receptor)
2. Serum: e.g. CEA, Ca++
3. Body secretions: e.g. Cortisol in urine

Origin
- Oncofetal ..................
- Eutropic ...................
- Ectopic .....................
- Mutational .................
Fetal tissue (AFP)
Normal originating (Cortisol, thyroglobulin)
Specialized outside tumor (ACTH, HCG)
Mutated chromosome, oncogene (P53)

Laboratory Methods for detecting TMs

1. ELISA
2. IHC (Immunohistochemistry)
3. FISH
4. RT-PCR (Polymerase chain reaction)
5. MoAbs (Monoclonal antibodies)
 46
INDIVIDUAL TUMOR MARKERS

CEA (Carceno Embrionic Antigen)

- Oncofetal
- Half-life = 10 days , hepatic clearance
- Ca colon (GIT) (Not specific)
- ↑ in cancer of lung, liver, pancreas, breast
- ↑ also in benign Ulcerative colitis, Crohn‟s disease, trauma, smoking

AFP (Alfa Feto Protien)

- Fetal form of albumin, yolk sac derivatives
- N = <20 ug/L, half-life = 4.5 d
- ↑ in Hepatocellular carcinoma (HCC)., seminoma
- ↑ also in benign Lung, GIT, liver cirrhosis

HCG
- Syncytiotrophoblast
- ↑ pregnancy
- Half- life = 1 day
- ↑ mainly in Germ cell tumors of testis & ovary
- ↑ also in cancer Liver, pancreas stomach, lung, breast
 47
PSA
- ↑ in Prostatic cancer
- Half-life = 3 days
- ↑ also in benign BPH (benign prostatic hyperplasia), cystoscopic exam, biopsy,
digital exam, ejaculation

MoAbs
- CA125: ↑ in Cancer Ovary in 80% of cases
- CA19-9: ↑ in Cancer Pancreas in 87% of cases
- CA15-3: ↑ in Cancer Breast in 50% of cases

CLINICAL APPLICATIONS
Colorectal carcinoma
- CEA is related to Duke staging A (4%), B (26%), C (44%), D (65%)
- Screeing in High risk population (eg ulcerative colitis)
- Assess the Response to R/
- Detect Recurrence 4-6 months earlier than clinically manifested
Pancreatic carcinoma
- CA19-9, and CEA
- 87% specific
- Good correlation Response to surgery in stage I
- Another TMS are: CA50, CA242 (1993)
 48
Hepatic tumors
- AFP
- Screeing in High risk population (eg schirrosis & Hepatitis C)
- Triad stigmata (known hepatitis C + New focal lesion by imaging + ↑ AFP)
- Good in monitoring response to R/
- Antibody imaging (targeting imaging eg lipidol CT scan)
- Chemo-targeting therapy
Germ cell tumors
- HCG: ↑ in Teratoma
- AFP: ↑ in Seminoma
- LDH: ↑ in Seminoma
- Elevated in 85%
- Relapse up to 10 y
Breast cancer
- Very weak sensitivity & specificity
- CA15-3, CEA
- Detection of relapse
- Metastasis: ↑ CA15-3 (75%)
- Recurrence 6-18 m earlier (50%)
Other tumors
- Tyrosinase: ↑ in Melanoma
- Circulating melanoma cells
- Thyroglobulin: ↑ in Medullary carcinoma of the thyroid (MCT)
- PTH (Parathyroid hormone): ↑ in Parathyroid carcinoma
- VMA (Vinyl Mandelic Acid) in urine: Neuroblastoma
 49

Screening programs
Disease characters to be suitable for screening
A serious disease, High prevalence, Better results with early detection

Characters of ideal screening test

- Simple Non- invasive Easy to interpret Cheap
- Widely available High sensitivity & specificity

Types of screening
1. Generalized (for the whole population)
- Breast Cervical Prostate Melanoma Colon
2. Specific (for high risk people)
- Hepatitis C (among health cares) - Cancer Colon (patients with ulcerative
colitis)
- HCC (patients with viral hepatitis) - Melanoma (Albinos)

 See also page 16-17

 50

Review MCQs
Choose the only one correct answer
1) Cancer cachexia means:
a) Anaemia & toxeaemia
b) Wight loss & loss of muscle bulk
c) All of the above
d) Non of the above

2) Breast conservation surgery is indicated in:

a) Diffuse lobular carcinoma
b) Multicenteric ductal carcinoma
c) Very small breast
d) Tumor less than 4 cm in size

3) Appropriate treatment of cystosarcoma phylloides in 35-years female is:

a) Wide local excision with rim of normal tissue
b) Lumpectomy & axillry lymphadenectomy
c) Modified radical mastectomy
d) Excision & post operative chemo-radiotherapy

4) Fibrocystic disease of the breast is associated with increase blood level of:
a) Testosterone
b) Estrogen
c) Progesterone
d) Both B & C

5) Blood born metastasis from breast cancer most common affects:

a) Liver
b) Lung
c) Bone
d) Brain

6) In breast cancer, bilaterality and multicentericity is most expected in:

a) Infiltrating ductal carcinoma
b) Infiltration lobular carcinoma
c) Paget's disease of the breast
d) Mucinous carcinoma of the breast

7) Neo-adjuvant chemotherapy is indicated in:

a) Early breast carcinoma
b) Locally advanced breast cancer
c) In presence of distant metastasis
d) In patients with age more than 50 years
 51
8) Following are constitutional manifestations of Hodgkin's lymphoma, EXCEPT:
a) Persistent vomiting
b) Relapsing fever
c) Loss of weight
d) Anemia

9) The most specific imaging procedure to diagnose a retro-peritoneal tumor is:

a) Multi-slice CT
b) IVU
c) Ultra-Sonography
d) Aortic angiography

10) Following statements regarding benign breast disease are true EXCEPT:
a. Cyclical mastalgia is the commonest reason for referral to the breast clinic
b. Atypical lobular hyperplasia is associated with an increased risk of breast cancer
c. Lactational breast abscesses are usually due to Staph aureus
d. Duct ectasia is more common in smokers

11) Tamoxifen in the treatment of breast cancer which of the following is FALSE:
a. 20 mg per day is as effective as higher doses
b. Treatment for longer than 5 years has been proven to be beneficial
c. d. Reduces the risk of contralateral breast cancer by 40%
e. Is effective in both pre and post menopausal women

12) Breast fibroadenoma is:

a. A benign monoclonal neoplasms
b. Most commonly present in late adolescence or the early 20s
c. Should be diagnosed by mammogram in all cases
d. Can be disappeared by conservative measures

13) Serum alpha fetoprotein is:

a. Is increased in testicular tumours
b. In suprarenal tumours is produced by trophoblastic elements
c. Is increased in over 70% patients with hepatocellular carcinoma
d. In hepatocellular carcinoma levels correlate well with size of the tumour

14) Retroareolar duct ectasia is:

a. Can be adequately treated with a microdochectomy
b. The incidence is reduced in smokers
c. May present with a reddish or watery nipple discharge
d. May present with nipple inversion.
 52
15) Hodgkin's disease is not characterized by:
a. Reed-Sternberg cells are a diagnostic feature
b. Usually presents as painless lymphadenopathy
c. The Pel-Epstein fever is often a characteristic feature
d. Stage III disease is confined to one side of the diaphragm

16) Differential diagnosis of hard breast lump includes:

a) ANDI
b) Lipoma
c) Traumatic fat necrosis
d) Giant fibroadenoma

17) Commonest presentation of cancer breast is:

a) Bleeding per nipple
b) Painless lump
c) Pathological fracture of humorous neck
d) Mastalgia

18) Manifestations of locally advanced cancer breast include:

a) 2 cm painless lump
b) Skin nodules
c) Large hard mobile axillary lump
d) Hepatic fibrosis

19) Treatment of acute breast abscess doesn’t include:

a) Incision & drainage
b) Mastectomy
c) Antibiotics
d) Evacuation of milk

20) The term epithelial dysplasia in breast biopsy means:

a) Cyst formation
b) Leukoplakia
c) Abnormal epitheliosis
d) Abnormal adenosis

21) In lactating women presented with pain, swelling & redness of breast:
a) The probable cause is breast engorgement
b) Absence of palpable lesion suggests acute mastitis
c) Presence of palpable lesion means malignancy
d) She is in high risk of develop cancer breast in future
 53
22) Locally advanced breast cancer presents with:
a) Lung metastasis
b) Massive pau d‟orange
c) Lump < 5 Cm
d) Loss of weight

23) Assessment of breast lump includes all of the following EXCEPT:

a) Mammogram & Ultrasound breast
b) Fine needle aspiration cytology
c) History taking
d) CT scan of breast

24) Characters of subcutaneous lipoma includes:

a) Firm in consistency
b) Free mobile except to skin overlying
c) Pseudofluctuant
d) Transilluminant

25) Soft tissue neoplasm includes:

a) Bone & cartilage
b) Peripheral nerves tumors
c) Brain & its coverages
d) Hematopoietic & lymphoid
e) Carcinoid tumors of GIT

26) Most common soft tissue neoplasm is:

a) Liposarcoma
b) Fibrocystic sarcoma
c) Subcutaneous Lipoma
d) Spindle cell tumors
e) Cancer breast

27) All are clinical features of Lipoma except:

a) Slowly growing painless lump
b) Fixed to muscle if intramuscular
c) Well define
d) Tender
e) Pseudo fluctuant

28) Most serious complication of Lipoma is:

a) Inflammation
b) Sarcomatous changes
c) Calcification
d) Pressure on nearby structures
 54
29) Most common complication of Lipoma is:
A. Sarcomatous changes
B. Myxomatous degeneration
C. Calcification
D. Unsighteness

30) All are true regrade Dermatofibrosarcoma protuberans except:

a) Slowly growing bluish dermal nodule
b) Grow fast, ulcerate denote malignant transformation
c) Favorable sites are trunk & shoulders
d) It usually metastasis to lung

31) Sarcoma differs from carcinomas by:

a) Affects older age group
b) less local invasion
c) Better sensitive to radio & chemotherapy
d) Worse prognosis

32) Ideal treatment of liposarcoma of the lower limb should be:

a) Always amputation
b) Radiotherapy is the only treatment
c) Hormonal therapy
d) Wide local excision

33) Desmoid tumor is characterized by:

a) High rate of recurrence after excision
b) Malignant tumor of the anterior abdominal wall
c) Affect males only
d) Always associated with Gardener's syndrome

34) About soft tissue sarcoma:

a) Tumor grading is not of value as a prognostic factor
b) The tissue of origin is the most important prognostic factor
c) Excision without safety margin increase the liability of recurrence
d) Angiosarcoma is never associated with lymph node metastasis

35) Lymph nodes in post triangle neck considered to be area:

a) I
b) III
c) V
d) VII
 55
36) Tubercular lymphadenitis characterized by:
a. Short history of painless swelling
b. 90% involve single nodal groups
c. Common sites are cervical & inguinal
d. Rubbery in consistency

37) Cold abscess of TB characterized with:

a) Central fibrosis of cervical LN
b) It is felt cold
c) If secondary infected could be hot
d) Aspiration or surgical excision is the main way of treatment

38) Head and neck occult carcinoma sites include all except:
e. pharynx
f. Anterior third of tongue
g. Thyroid gland
h. Airway sinuses.

39) Characters of none specific Ch LN-it is:

a) Common in boys
b) Common site is cervical
c) Painful
d) Discrete & mobile

40) Treatment of none specific Ch lymphadenitis includes all except:

a) Surgical excision biopsy
b) Assurance
c) R the primary cause
d) Hot fomentation
e) Re-examination after 10 days

41) In cases of generalized lymphadenopathy which of the following is the

investigation of choice:
a) CBC
b) Excisional biobsy
c) Ultra-sound abdomen and pelvis
d) CT neck

42) Hodgkin's lymphoma

a) Often presents as painless cervical lymphadenopathy
b) About 50% of patients have splenomegaly at presentation
c) The nodular sclerosing type has the best prognosis
d) Stage 1 disease has a 5-year survival of over 90%
 56

43) Histopathological revised European-American classification of Hodgkin’s disease

include:
a) lymphocyte rich classical Hodgkin‟s disease
b) Mixed cellularity
c) Lymphocyte predominance
d) All of the above

44) Hodgkin‟s lymphoma that carry a more favorable prognosis is :

a) Nodular lymphocytic varieties only
b) Histocytic varieties only
c) Nodular lymphocytic and histocytic varieties
d) Nodular and diffuse lymphocytic varieties

45) The following are Systemic manifestations of lymphoma EXEPT:

a) Loss of weight > 10% in 12 months
b) Excessive sweating
c) Persistent fever >380C
d) Pruritis

46) Metastatic involvement of left Cloquet LN may denotes a:

a) Melanoma in the right big toe
b) Squamous carcinoma in the anal verge
c) left testicular neoplasm
d) left cancer breast

47) Epstein Barr virusis a carcinogen that play role in occurrence of:
a) heptaocellular carcinoma
b) bladder cancer
c) lymphoma
d) carcinoma of the cervix

48) Stony hard inguinal lymphadenopathy reveals metastases from:

a) Kaposi sarcoma
b) Malignant melanoma
c) Dermatofibrosarcoma protuberance
d) All of the above
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Answers key

1 c 9 a 17 b

2 d 10 b 18 b

3 a 11 b 19 b

4 d 12 b 20 c

5 c 13 c 21 b

6 b 14 d 22 b

7 b 15 d 23 d

8 a 16 c 24 c

25 b 33 a 41 b

26 c 34 c 42 a

27 d 35 c 43 d

28 b 36 b 44 d

29 d 37 c 45 c

30 d 38 b 46 b

31 d 39 d 47 a

32 d 40 a 48 d