morphology and location of breast …

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Qaddoori et al. World Journal of Pharmacy and Pharmaceutical Sciences

MORPHOLOGY AND LOCATION OF BREAST

MICROCALCIFICATION AS TYPE DESCRIPTORS TO STRATIFY

RISK OF MALIGNANCY DEMOGRAPHIC BASED STUDY

Dr. Tameem Akram Qaddoori* and Dr. Zinah Saeed Mahmood

MBChB MDR.

INTRODUCTION

Breast cancer is the most frequently diagnosed non-skin cancer in

women and has become one of the leading causes of death in women

over the age of 40 years. Clustered micro calcifications are often an

early sign of breast cancer but are not breast-cancer-specific. The

characteristics of clustered micro calcifications are the main

parameters for classifying lesions on mammograms. A key diagnostic

feature for mammography, seen in 30% to 50% of women with biopsy-

confirmed breast cancer, is micro calcification (Morgan et al., 2005).

Whereas benign calcifications are typically composed of calcium oxalate, malignant

calcifications are typically composed of hydroxyapatite deposited in specific patterns (Haka

et al., 2002). Hydroxyapatite micro calcifications range in size from 100 um single crystals to

clusters up to centimeters in diameter (Gong et al., 2004). In addition to malignant lesions,

many non-malignant processes also produce dystrophic micro calcifications in breast tissue.

The form, size, polymorphism and distribution of the calcifications provide clues to the

underlying pathology.

Clustered micocalcifications are often an early sign of breast cancer but are not breast -

cancer-specific. The characteristics of clustered microcalcifications are the main parameters

for classifying lesions on mammograms. Microcalcification was a risk factor for upgrading to

cancer, independent of age (Li et al., 2012).

Aim of the work

This study aims to assess the morphology and location of breast microcalcification as type

descriptors to stratify risk of malignancy.

WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

SJIF Impact Factor 7.632

Volume 10, Issue 10, 2102-2150 Research Article ISSN 2278 – 4357

*Corresponding Author

Dr. Tameem Akram

Qaddoori

MBChB MDR

Article Received on

19 August 2021,

Revised on 09 Sept. 2021,

Accepted on 29 Sept. 2021

DOI: 10.20959/wjpps202110-20213


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Anatomy of breast

The breast or mammary gland is a modified sweat gland that has the specific function of milk

production (De Paredes, 2007)

Figure 1: The glandular parenchyma of the breast (Quoted from Nagin., 2008).

Gross anatomy of the breast

The breasts have a conical shape and are located, one on each side, within the subcutaneous

layer of the thoracic wall, anteriorly to the pectoralis major muscle. They extend superiorly as

far as the level of the second rib, inferiorly as far as the level of the six or seventh ribs,

laterally as far as the anterior axillary line (sometimes as far as the middle axillary line) and

medially they reach the lateral margin of the sternum. Posteriorly, they make contact with the

fascia of the pectoralis major, serratus anterior and obliquus externus muscles and the most

cranial portion of the rectus abdominis muscle (Figure 1) (Macea and Fregnani, 2006).

The epidermis of the nipple-areola complex is pigmented and is variably corrugated. The

areola contains sebaceous glands, sweat glands and accessory glands which produce small

elevations on the surface of the areola (Montgomery's tubercles) (Brunicardi et al., 2010).

The breast is composed of three major structures: skin, subcutaneous tissue, and breast tissue

(parenchyma and stroma) (Figure 2). The parenchyma is divided into 15 to 20 lobes or

segments that converge at the nipple in a radial arrangement. The ducts from the lobes

converge into 6 to 10 major collecting ducts that have openings at the nipple and connect to

the outside. Each of these major ducts arborizes back from the nipple and forms a lobe or

segment of glandular tissue that is supported by surrounding connective or stromal tissue.


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The distribution of lobes is not even as there is a preponderance of glandular tissue in the

upper outer quadrant of the breast (Morris et al., 2005).

Figure 2: Normal anatomy of the nipple-areolar complex (Quoted from Moore et al.,

2007).

Beneath the nipple openings, the lactiferous sinus is visible. The lactiferous sinus is a slight

dilation of the ampullary portion of the major duct. The major ducts that converge below the

nipple and drain each segment are 2mm in diameter. Each duct drains a lobe made up of 20 to

40 lobules. Each lobule contains 10 to 100 alveoli or acini. Each lobule also consists of

branching ducts that divide into sub segmental structures and terminate in the terminal duct

lobular unit. The terminal duct lobular unit consists of the terminal duct and the acinus. The

glandular tissue and ducts are surrounded by fat and supported by Cooper’s ligaments, which


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are connective tissue elements that arise from stromal tissue and attach to the prepectoral

fascia and dermis and support and suspend the breast tissue (Morris et al., 2005).

Figure 3: The breast profile (Quoted from Moore et al., 2007).

A Ducts

B Lobules

C Dilated section of duct to hold milk

D Nipple

E Fat

F Pectoralis major muscle

G Chest wall/rib cage

The Tail of Spence (Spence's tail, axillary process, axillary tail) is an superolateral extension

of the mammary gland (Figure 4) (Iris, 2012).

Figure 4: The axillary tail of the breast (Quoted from Moore et al., 2007).


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Arterial supply

The blood supply to the breast is provided mainly by the anterior medial branches (Arise

from the first 4 intercostal spaces, just medial to the sternum and split into cutaneous and

breast branches). This is in addition to, the posterior medial branches (arise laterally from the

intercostal spaces through the pectoralis fascia and supply the deep portion of the breast

tissue) of the internal mammary artery (supplies 60% of the breast medially /centrally) and

the lateral mammary branch of the lateral thoracic artery (supplies about 30% of the breast in

the upper outer quadrant). Vessels enter via superolateral, superomedial and deep aspect of

the breast. The reminder of the vascular supply to the breast is variable via posterior

intercostal arteries, the pectoral branch of the thoracoacromial artery ,the subscapular artery

and thoracodorsal artery (Berg et al., 2006) ( Figure 5). Smaller sources of arterial blood

include the posterior intercostal arteries and the pectoral branch of the thoracoacromial artery.

There is wide variation in the proportion of blood supplied by each artery between women

and little evidence of symmetry between breasts. Moreover, the course of the arteries does

not appear to be associated with the ductal system of the breast (Geddes, 2007).

Figure 5: The arterial supply of the breast (Quoted from Berg et al., 2006).


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Venous drainage

The venous drainage of the breast is divided into the deep and superficial systems (figure 6)

which are joined by short connecting veins. Both systems drain into the internal thoracic,

axillary, and cephalic veins. The deep venous drainage of the breast parallels the arterial

supply with three principle routs via the internal mammary veins into the subclavian vein,

lateral thoracic vein into axillary vein and posterior intercostal vein branches into vertebral

plexus (Berg et al., 2006). While the superficial plexus consists of subareolar veins that arise

radially from the nipple and drain into the periareolar vein which circles the nipple and

connects the superficial and deep plexus (Geddes, 2007).

Figure 6: The venous drainage of the breast (Quoted from Berg et al., 2006).

Lymphatic drainage of the breast

The lymph in the breast is drained by two main pathways; to the axillary and internal

mammary nodes. The axillary nodes have been reported to receive more than 75% of the

lymph from both the medial and lateral portions of the breast. Whereas, the internal

mammary nodes receive lymph from the deep portion of the breast. Nevertheless there is a

wide variation in the drainage of lymph from the breast and less common pathways have

been demonstrated. Lymph may occasionally pass through either the interpectoral nodes or

lymph nodes in the breast parenchyma. Sometimes direct drainage of lymph occurs to the

supraclavicular nodes and infrequently lymph may pass retrosternally into the contralateral

internal mammary nodes. In addition lymph has been shown to drain into the posterior and

anterior intercostal nodes (Geddes, 2007).


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The lymphatic vessels from the breasts may also occasionally drain to the liver and

subdiaphragmatic plexus by means of the abdominal lymphatic vessels (Macea and

Fregnani, 2006).

Axillary lymph nodes (Figure 7)

Classically, five axillary lymph node groups are described: pectoral (anterior), subscapular

(posterior), central (intermediate), humeral (lateral) and apical (subclavicular).

Pectoral (anterior) lymph nodes: This is formed by three to five lymph nodes that are

located along the medial wall of the axilla, around the lateral thoracic vein and the lower

margin of the pectoralis minor muscle.

Subscapular (posterior) lymph nodes: This consists of six to seven lymph nodes located

along the margin of the posterior axillary wall and the subscapularis vessels.

Humeral (lateral) lymph nodes: This is formed by a group of four to six lymph nodes

located medially and posteriorly to the axillary vein, in the proximal segment of the vein,

close to the lateral wall of the axilla.

Central lymph nodes (intermediate): This is formed by three or four large lymph nodes

located deeply in relation to the pectoralis minor muscle, close to the base of the axilla ,in

relation to the second portion of the axillary artery .Because of its location ,this group

receives the lymph from the pectoral, subscupular and humeral nodes .All the lymph from

this group drains to the apical lymph nodes.

Apical lymph nodes (subclavicular): This is formed by all the lymph nodes located at the

axillary apex, which are located along the medial side of the distal part of the axillary vein

and the first portion of the axillary artery (Macea and Fregnani, 2006).

The internal mammary lymphatic vessels were identified alongside the internal mammary

artery and vein, deep to the parietal pleura, with lymph nodes present in the intercostal space

(Suami et al, 2008).


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Figure 7: The lymphatic drainage of the breast (Quoted from Suami et al., 2008).

Nerve supply

The superior breast is innervated by branches from cervical plexus and the reminder of the

breast by intercostal branches from the brachial plexus (Berg et al., 2006). The 2nd to 6th

intercostal nerves supply the breast (Figure 8). The distribution and course of these nerves

are complex and variable. The anterior nerves take a superficial course in the subcutaneous

tissues, while, the lateral nerves travel a deep course through the breast. The nipple and areola

are supplied by the anterior and lateral cutaneous branches of the 3rd to 5th intercostal nerves

most commonly the 4th intercostal nerve (Geddes et al., 2007).

Figure 8: The nerve supply of the breast (Quoted from Berg et al., 2006).


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Radiological anatomy of the breast

The mammographic examination may show the following normal anatomical structures:

• Skin

• Nipple and areola

• Fatty tissue

• The breast tissue proper or corpus mammae

• Blood vessels

Skin

The skin appears as a thin, continuous, radiopaque rim homogeneous in density,

approximately 1 mm thick and readily visible against the radiolucency of the underlying

subcutaneous premammary fatty tissue. If the breast is very dense because of the higher

density of the underlying parenchymal structure, however, the skin may occasionally not

show up clearly even on a correctly exposed mammogram (Lattanzio and Simonetti, 2005).

Nipple and areola

The skin surrounding the nipple - the areola – can be up to 3-5 mm thick, with a central

opacity, roughly cylindrical in shape and of variable size and density, corresponding to the

nipple. Posteriorly, there is a generally triangular, heterogeneous trabecular area, the

retroareolar region (Figure 9). Under normal conditions, the lactiferous ducts and sinuses are

not seen.

Figure 9: The nipple, subcutaneous fat and coppers ligament of the breast (Quoted from

Harjit et al., 2012).


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Fatty tissue

Varying amounts of fatty tissue may be present forming anything from a thin subcutaneous

layer to "islets" of various sizes that may occupy the whole breast depending on the

characteristics and age of the individual woman.

The parenchymal cone is surrounded by fatty tissue which constitutes the premammary fat

anteriorly and the retromammary fat posteriorly. Anteriorly, subcutaneous fat appears as a

radiolucent layer of variable thickness traversed by planar sheets of fibrous tissue, the crests

of Duret which accommodate Cooper's ligaments. The superficial extensions of Cooper's

ligaments come to peaks attached to the skin, which anchor the body of the breast to the

subcutaneous tissues, known as retinacula cutis, which separates the breast from the

prepectoral fascia Posteriorly, adipose tissue outlines the retromammary space (the bursa of

Chassaignac) overlying the pectoralis major muscle (Lattanzio and Simonetti, 2005).

Breast tissue proper or corpus mammae

The body of the mammary gland is roughly cone-shaped with the floor resting on the chest

wall and the tip projecting towards the nipple. The shape and density of breast structures vary

from individual to individual.

The concept of mammographic "density" as being strictly related to advancing age is

obsolete, so adipose tissue is not synonymous with a senile breast, and, similarly, the so-

called "dense breast" is not necessarily a young breast.

The variety in the mammographic appearance of the "individual" types of mammary

structures is in all likelihood related to differences in the normal processes of development

and involution, more than to pathological conditions. Therefore, the American College of

Radiology (ACR) Imaging Reporting and Data System (BIRADS) is becoming a standard on

the assessment of mammographic images. Breast density is classified in four categories:

I. The breast is almost entirely fatty (Figure 10).

II. There is some fibroglandular tissue.

III. The breast is heterogeneously dense.

IV. The breast is extremely dense (Figure 11) (Oliver et al., 2005).


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Figure 10: The mediolateral oblique view of fatty breast tissue (Quoted from Harjit et al.,

2012).

Figure 11: The mediolateral oblique of dense breast tissue (Quoted from Harjit et al.,

2012).

Pectoralis muscle

The pectoralis muscle is homogeneously radiopaque; it is located in front of the chest wall

and is shaped like an upside-down triangle in the lateral and mediolateral oblique views. In

the craniocaudal view it is crescent-shaped and variably visible depending on the anatomy of

the chest and the position and compression of the breast. The pectoralis muscle can be

visualized in about 30% of patients on the CC view (Figure 12) (William et al, 2007).


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Figure 12: The pectoralis muscle on the craniocaudal view (black arrow) (Quoted from

William et al, 2007).

Generally, a correctly executed mediolateral oblique projection shows the lower margin of

the pectoralis muscle following an imaginary line that runs anteriorly through the nipple

(Figure 13).

Figure 13: The pectoralis muscle on the mediolateral oblique view (Quoted from William

et al., 2007).


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Blood vessels

Vessels are more readily visible in breasts that contain plentiful fatty tissue, and appear as

thin ribbon-like opacities that may be more or less tortuous; vessel walls may be calcified, in

which case they give typical "railwayline" images. In the early stages of calcification, only

scattered elongated "casts" are seen, in a linear pattern, reflecting partial, fragmentary

calcification of the vascular wall (Figure 14) (Lattanzio and Simonetti, 2005).

Figure 14: The vascular calcifications on mammography (Quoted from Adam et al.,2013).

Technique of mammography

Mammography is an effective imaging tool for the detection of early–stage breast cancer,

detection about 75% of cancers at least a year before they can be felt (Badgwell et al, 2008).

There are two main types of mammography: film-screen mammography and digital

mammography, also called full-field digital mammography or FFDM. The technique for

performing them is the same. What differs is whether the images take the form of

photographic films or of digital files recorded directly on to a computer. In recent years, there

have been major advances in mammographic technology with the development of full field

digital mammography (FFDM) (Adam et al., 2008).


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Figure 15: The mammogram machine (Quoted from Gur et al., 2009).

Digital mammography is replacing conventional film-screen mammography in most

departments. The greatest advantage of digital mammography is its ability to provide

improved image quality. In addition, the digital images can be electronically manipulated,

which has resulted in fewer repeat images being required for technical reasons. The ability to

control images on a computer makes digital mammography a more accurate screening tool

for some women. In general, digital mammography is better at finding cancer in women who

fall into one or more of the following groups:

Women who are premenopausal

Women who are under age 50

Women who have dense breast tissue

In addition, digital mammography allows images to be sent via teleradiology, facilitating

mammography services in areas that do not have radiologists (William E and Clyde A, 2013).

Full-field digital mammography (FFDM) refers to a mammography system where in solid-

state detectors are used in place of an x-ray film. The detectors facilitate the conversion of x-

http://www.radiology-info.org/mammography.html


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rays into electrical signals. These signals are utilized for creating images of breasts which can

be printed over a special film or seen on the computer screen.

Full-field digital mammography uses low dose X-rays, achieved by using targets made of low

atomic weight alloys (e.g. molybdenum and rhodium). Filters made of aluminum,

molybdenum beryllium, rhodium, or palladium is used. It uses high contrast, high resolution

(with single-sided emulsion) film to demonstrate microcalcifications smaller than 100 mm

(Saslow et al., 2006).

Because both high contrast and high spatial resolution are needed for optimal mammography,

standard radiographic equipment can not be utilized for this examination. Mammography

must be performed on a unit dedicated to this purpose. Mammographic equipment and

technique differ from standard radiography in several ways. The anode material utilized to

generate the x-rays in most dedicated mammography units is molybdenum. This allows the

production of lower-energy x-rays, which in turn produces greater contrast between soft

tissue structures. The structures of the breast do not differ greatly in their inherent contrast, so

these low-kilovolt are extremely important in producing a high contrast image. Some units

also have rhodium anodes that can be used to increase the contrast in denser breasts, while

keeping radiation dose and time of exposure low (William E and Clyde A, 2013).

During mammography, the breast is compressed using a dedicated mammography unit.

Parallel-plate compression evens out the thickness of breast to increase image quality by

reducing the thickness of tissue that X-rays must penetrate, decreasing the amount of

scattered radiation (scatter degrades image quality), reducing the required radiation dose , and

holding the breast still (preventing motion blurs) (Miller et al., 2005). Some women find

breast compression uncomfortable, but most can tolerate it once the benefits are explained.

During routine mammography, the breast is compressed for a few seconds while each film is

taken. Many units are equipped with automated compression devices so the technologist can

release the tension immediately after the film is exposed (William et al, 2013).


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Figure 16: Breast compression in crainocaudal view (Quoted from Gur et al., 2009).

Exposure factors

The kVp output of mammographic machines is adjustable between 25 and 35 kVp. The tube

current is kept as high as possible to minimize exposure times and should be at least 100 mA,

with the 0.3- mm2 focus commonly used for routine mammography. The exposure time

should be less than two seconds and the focal spot 0.6mm2 or less. A 0.3-mm2 focal spot is

used routinely to reduce geometric unsharpness. A 0.1-mm2 focal spot is used for magnified

projections. The detector for this must be moveable so that it can be positioned behind the

most dense part of the breast, which typically lies 2 cm behind the nipple. This allows a range

of breast sizes to be imaged satisfactorily (Whitley et al., 2005).

Positioning

Mammography can be performed with the patient seated or standing. Most screening

practices prefer the standing position because it allows faster throughput and is less

cumbersome. Patients are able to lean into the unit to a greater degree when standing, thus

allowing more of the posterior breast tissues to be imaged. Recumbent imaging is possible,

but quite difficult; its use should be restricted to problem-solving situations (William E and

Clyde A, 2013).

Before the examination begins, the technologist asks the patient to put on a gown, preferably

one designed for mammography, which allows exposure of only the breast that is being

examined. The patient is instructed to remove any jewelry, talcum powder, or antiperspirant

that may cause artifacts on the radiographic image.


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Certain lotions, especially lotions with sparkles or glitter, can cause artifacts as well on the

image.

The technologist explains the procedure and documents any relevant patient history as per

departmental protocol (Bontrager L and Lampignano P, 2014).

There are two standard mammographic projections: a craniocaudal (CC) view and a

mediolateraloblique (MLO) view (Adam et al., 2008).

The craniocaudal projection will best visualize the subareolar, central, medial, and

posteromedial aspects of the breast and is one of two complementary projections that make

up the routine mammographic study (Andolina F and Lillé L, 2011).

For the CC view, the X-ray beam travels from superior to inferior. Positioning is achieved by

pulling the breast up and forward away from the chest wall, with compression applied from

above. A well-positioned CC view should demonstrate the nipple in profile. It should

demonstrate virtually all of the medial tissue and the majority of the lateral tissue with the

exclusion of the axillary tail of the breast (Adam et al., 2008).

The MLO projection best visualizes the posterior and upper-outer quadrants of the breast.

This is intrinsic to the anatomy of the breast, which lies anterior to and follows the line of the

obliquely coursing pectoral muscle. By positioning the breast parallel to this oblique line,

which is the natural course of the tissue, it is possible to demonstrate most of the glandular

tissue (Andolina F and Lillé L, 2011).

The MLO is taken with the X-ray beam directed from superomedial to inferolateral, usually

at an angle of 30–60°, with compression applied obliquely across the chest wall,

perpendicular to the long axis of the pectoralis major muscle. The MLO projection is the only

projection in which all the breast tissue can be demonstrated on a single image. A well-

positioned MLO view should demonstrate the inframammary angle, the nipple in profile and

the nipple positioned at the level of the lower border of the pectoralis major, with the muscle

across the posterior border of the film at an angle of 25–30° to the vertical (Adam et al.,

2008).


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(A) (B)

Figure 17: A standard set of mammograms consists of the (A) and the craniocaudal

(CC) view (B) mediolateral oblique (MLO) view (Quoted from Adam et al., 2013).

(A) (B)

Figure 18: Breast positioning. Positioning for the (A) craniocaudal views and (B)

mediolateral oblique (Quoted from Adam et al., 2008).

In the majority of cases, a two-view screening mammogram will provide a conclusive

interpretation, but when the results of mammography are indeterminate, further evaluation is

necessary; additional mammographic views (Table 1), US and, infrequently, MR may be

required for clarification (Andolina F and Lillé L, 2011).

Further characterization of an abnormality can be accomplished with spot compression and

magnification views. The compression plate used is much smaller than that used in standard

views;


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therefore, greater force can be applied, which results both in further spreading of any

overlying tissue and in bringing the abnormality closer to the film for increased detail.

Magnification also produces finer detail, which allows more accurate assessment of the

morphology of microcalcifications and the borders of masses (William E and Clyde A ,

2013).

Indications

§ Evaluation of symptomatic women with a dominant breast mass, persistent discomfort, skin

dimpling, or nipple discharge should have a thorough breast examination that includes

mammography and any other diagnostic study (ultrasound and sometimes MRI) to determine

if cancer is present. These studies should be performed regardless of the patient’s age

(Richard and Matthew, 2014).

§ Breast cancer screening (Table 1)

§ Follow-up of breast cancer patients

§ Guidance for biopsy or localization of lesions not visible on ultrasound (Adam et al., 2013).

Table 1: American cancer society guidelines for breast cancer screening in average-risk

women (Quoted from William E and Clyde A, 2013).

Limitations of mammography

However, there are limitations of mammography and clinicians must be aware of them. They

should remember that the mammogram, physical exam, and ultrasound of the breast are

complementary.

Patients with palpable masses and an unremarkable mammogram should undergo ultrasound

examination of the breast (Richard and Matthew, 2014).

Routine mammograms in young women increase the risk for future breast cancer due to

direct radiation exposure to breast tissue. For young women who have a high risk of breast


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cancer because of genetic mutations, the radiation from yearly mammograms may make the

risk even higher. It is quite possible that women who may never have developed breast cancer

in their lifetime may get this disease in their 50s, 60s, or later, from having routine yearly

mammograms in their 30s or 40s. High-risk women, especially those under 30, may want to

consider switching to an alternative screening method such as magnetic resonance imaging

(MRI) which does not involve exposure to radiation. The premenopausal breast is very

sensitive to radiation, each rad of exposure increasing breast cancer risk by 1 percent,

resulting in a cumulative 10 percent increased risk over ten years of premenopausal

screening, usually from ages 40 to 50. Risks are even greater for "baseline" screening at

younger ages, for which there is little or no evidence of any future relevance. Statistically,

some women have approximately as much chance of getting breast cancer from repeated

mammograms as they have of the testing finding earlier cancers (Sahelian, 2013).

These theoretical risks should be weighed against the risk of dying from spontaneous breast

cancer, which would be approximately 700 per million in women aged 40 to 49 years and

1000 per million in women aged 50 to 59 years. This risk increases steadily with advancing

age (William E and Clyde A, 2013).

Pathology of breast cancer

The vast majority of the lesions that occur in the breast are benign. Much concern is given to

malignant lesions of the breast because breast cancer is the most common malignancy in

women in Western countries; however, benign lesions of the breast are far more frequent than

malignant ones (Guray and Sahin, 2006).

"Breast cancer is the most common type of malignancy recorded in the cancer registries of

almost all countries within the Eastern Mediterranean Region. In Iraq, the continuous rise in

the incidence rate is associated with an obvious trend to affect premenopausal women.".

Breast cancer incidence and mortality are increasing in developing countries. It's the most

common malignancy among Iraqi women and comprises more than 30% of the registered

female cancer (according to Iraqi cancer registry), and tend to affect young age group. The

obvious rise in incidence rates and the prevalence of advanced stages at presentation

associated with more aggressive tumour behaviour resulting in greater fatality rates.


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Malignant breast lesions

Breast cancer is the most common site specific cancer in women and is the leading cause of

death from cancer for women aged 20 to 59 years. It accounts for 26% of all newly diagnosed

cancers in females and is responsible for 15% of the cancer-related deaths in women

(Brunicardi et al., 2010).

Malignant microcalcification seen on mammogram associated with Invasive breast cancer

and DCIS (Adam et al., 2013).

*Epidemiology

Incidence by age :- Breast cancer is extremely rare through the second decade of life, The

incidence begins to increase rapidly around age 35, and this increase continues throughout

life (Kapson, 2007).

Incidence by location :- Breast cancer is commonly affects the left breast more frequent than

the right one. 4%of the cases of breast cancer have bilateral primary tumors .50% of the

breast cancer occur in the upper outer quadrant (Kumar, 2010).

*Risk factors to breast cancer

Breast cancer is an extremely heterogeneous disease caused by interactions of both inherited

and environmental risk factors (Conzen et al., 2008).

Being female: Approximately 1.500 cases (less than 1%) occur in males each year (Kapson,

2007).

Hormonal status: Early Menarche and Late Menopause: Women who have an early

menarche and a late menopause are at somewhat higher risk that is probably related to the

duration and type of hormonal effects on the breast (Kapson, 2007).

Geographic variations

Therisk for this form of neoplasia is significantly higher in North America and northern

Europe than in Asia and Africa (Kumar, 2010).


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Genetics and Family history

About 5% to 10% of breast cancers are related to specific inherited mutations. About half of

women withhereditary breast cancerhave mutations in geneBRCA1 (on chromosome

17q21.3), and anadditional one-thirdhave mutations in BRCA2 (on chromosome 13q12-13)

(Kumar, 2010).

Prior history of breast cancer :- A woman who has already had abreast canceris atgreater

risk of developing a second cancer than a woman without such a prior history (Kapson,

2007).

Age at First Full-Term Pregnancy: Nulliparous women are at increased risk, andlate parity

(after age 30) further increases risk (Kapson, 2007).

Lonizing radiation: lonizing radiation to the chest increases the risk of breastcancer. The

magnitude of the risk depends on the radiation dose, the time since exposure, andage. Only

women irradiated before age 30 seemto be affected (Kumar, 2010).

Exogenous hormone use

Prolonged exposure to exogenous estrogens postmenopausally, according to recent studies,

relatively short-term use of combined estrogen plus progestin hormone therapy is associated

with an increased risk of breast cancer (Kumar, 2010).

Alarge, well-designed study provides solid evidencethatbirth control pills not increase the

risk of breastcancer even inwomen Who have taken the pill for a long time and in women

with a family history of breast cancer (Kumar, 2010).

Lactation: Lactation has been shown in some studies to have a weak protective effect but

this appears to be related to the total length of time a woman lactates. The benefit from

lactation, if any, likelyoccursbecausewhile lactating the individual is probably not ovulating,

and her risk could be influenced by reducing her exposure to her own hormones (Kapson,

2007).

Others

Many other less well-established risk factors, such as obesity, alcohol consumption, and a

diet high in fat, have been implicated in the development of breast cancer on the basis of


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population studies. Obesity is a recognized risk factor in postmenopausal women (Kumar,

2010).

Breast cancers are classified into those that have not penetrated the limiting basement

membrane (noninvasive) and those that have (invasive) (Kumar, 2010). The chief forms of

carcinoma of the breast are classified as follows

Ductal carcinoma in situ (DCIS) including paget disease

Ductal carcinoma in situ (DCIS), the earliest neoplastic stages of human breast cancer

progression, is characterized by a proliferation of epithelial cells that is confined within the

basement membrane of the mammary- ductal network. DCIS represents a diverse group of

tumors that are detected in women undergoing screening mammography (Moulis and Sgroi,

2008).


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The detection of ductal carcinoma in situ has increased markedly secondary to the

widespread use of screening mammography, and it accounts for 25%-40% of

mammographieally detected breast cancers, although most patients are asymptomatic, some

present with nipplerelated disease (nipple discharge or Paget disease) or have palpable

abnormalities (Harris, 2006).

Grossly, DCIS may be associated with microcalcifications within the lumens, gross findings

may be of fibrocystic change, may form mass, in comedo variant cysts dilated ducts are filled

with granular, yellow white material, on squeezing necrotic material come out of its cut

surface like toothpaste, may be associated with invasive carcinoma (Harris, 2006).

DCIS markedly increases from less than 5% of breast cancers in unscreened populations up

to 40% of those screened by mammography, primarily because of the detection of

calcifications (Kumar, 2010).


Paget's disease of the breast

Paget's disease of the breast is characterized by Paget cells. Paget cells are large cells with

clear cytoplasm and eccentric, hyperchromic nuclei found throughout the epidermis.

Paget disease accounts for less than 5% of all breast cancers and is thought to most likely

arise from preexisting DCIS or invasive ductal cancer. Paget disease typically manifests with

symptoms limited to one breast, including nipple discharge (serous or sanguineous), nipple

inversion, a palpable mass, or an eczema-type rash involving the nipple. The diagnosis is

made with skin biopsy. Most of these patients have an underlying malignancy, either DCIS or

invasive carcinoma. In a minority of cases, these lesions may manifest as an intraductal

finding, although at times diagnostic evaluation does not result in identification of the

primary breast lesion (Ferris James et al., 2012).

The malignant cells disrupt the normal epidermal barrier, which allows extracellular fluid to

be extruded on to the surface (Kumar, 2010).

As many as 50% of patients with Paget's disease may have an underlying cancer (Abeloff et

al., 2008).

Lobular Carcinoma in situ (LCIS)


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It is of Unknown aetiology, LCIS occurs predominantly in women with a mean age of 45

years old, approximately 10 to 15 years younger than the mean age when invasive breast

carcinoma occurs, more frequent in women of low parity with first child after 30, increased in

obesity, in women with history of atypical hyperplasia, in women with history of breast

carcinoma, and Increased in women with mother with breast cancer (Stein et al., 2004).

The natural history of LCIS is difficult to define, as it generally has no specific clinical or

mammographie findings. It is usually incidentally identified histologically in breast tissue

biopsied for other reasons. Therefore, its reported incidence depends on the frequency of

biopsy (Stein et al., 2004).

LCIS is a high-risk marker for the future development of invasivecarcinomahowever, some

investigators have speculated that individual foci of LCIS progress to invasive disease.

Regardless of the mechanisms involved, a woman with LCIS has approximately a 15%

chance of developing an infiltrating ductal or lobular carcinoma in the breast in which the

LCIS is discovered, but also has a similar risk (15%) for contra lateral development of cancer

over the next 30 years. 18-25% of the cases diagnosed with LCIS at core needle biopsy were

upgraded to more invasive cancer pathologies at surgical excision (Stein et al., 2004).

Invasive ductal carcinoma

Carcinomas of "no special type" or"not otherwise specified"(NOS)are synonyms for ductal

carcinomas (Kumar, 2010). Most common form of breast cancer (80%). Probably arises from

DCIS and typically measures about 2 cm at diagnosis. Infiltration of tumor occurs into.

Dermal lymphatics, which leads to inflammation and skin thickening ? Perivascular and

perineural spaces (Weissleder et al ., 2011).

In the absence of breast screening the great majority of invasive carcinomas are detected

because patients usually present with a palpable breast mass, varies in size from one to

several centimetres in diameter, the mass in most cases presents in the upper outer quadrant.

The average age of patients is about 50 years (Kishimoto et al., 2004).

Invasive lobular carcinoma

Lobular carcinomas, more frequently than ductal carcinomas metastasize to cerebrospinal

fluid, serosal surfaces, gastrointestinal tract, ovary and uterus, and bone marrow. Lobular

carcinomas are also more frequently multicentric and bilateral (10% to 20%) (Kumar, 2010).


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A significant subgroup may have a diffusely invasive pattern without a desmoplastic response

and may be clinically occult, it is often seen as an ill-defined mass or an area of

asymmetrically dense breast tissue (Brunicardi et al., 2010).

Medullary carcinoma

Medullary carcinoma, also called circumscribed carcinoma, accounts for up to 7% of all

mammary carcinomas, and 11% of breast carcinomas diagnosed in women 35 years of age or

younger. These tumors are often characterized by large size, gross circumscription, and a

tendency to hemorrhage, and become necrotic (Liberman et al., 2008).

Medullary carcinoma represent 4% of all invasive breast cancers and is a frequent phenotype

of BRCA1 hereditary breast cancer (Brunicardi et al., 2010) .The cancer is soft and

hemorrhagic. A rapid increase in size may occur secondary to necrosis and haemorrhage.

Bilaterality is reported in 20% of cases.

Mucinous (Colloid) carcinoma

Mucinous carcinoma is a tumor containing large amounts of extracellular epithelial mucin

surrounding and within tumor cells (Paramo et al., 2005).

Mucinous carcinoma usually presents in postmenopausal women and it is characterized by

mucus production. But its locally aggressive growth to form a large skin ulcer is rarely seen

(Ishikawa et al., 2004).

Mucinous carcinoma account 2% of all invasive carcinoma like medullary carcinomas, they

often present as well-circumscribed masses and can be mistaken for fibroadenomas. The

tumors are usually soft and gelatinous (Brunicardi et al., 2010).

Adenoid cystic Carcinoma (ACC)

Adenoid cystic carcinoma of the breast is a rare neoplasm, accounting for less than 0.1% of

all breast carcinomas .Nevertheless, its early recognition is mandatory as it has a favorable

prognosis.

Adenoid cystic carcinoma occurs predominantly in women at mean age of 50-60 years

(Aithala et al., 2009).


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The clinical features are, a well circumscribed palpable mass, occasionally tender on

palpation, the tumor is rarely fixed to the overlying skin, nipple and pectoral muscle.

Although any part of the breast may be involved, most ACCs are centrally located (Figure

18) (Aithala et al., 2009).

ACC can be confused with other more common breast carcinomas, as ductal carcinoma with

cribriform pattern. It is important to distinguish ACC from others, as it has excellent

prognosis (Aithala et al., 2009).

This is a very rare tumor in which the invasive component is predominantly in the form of

papillary structures. Fibro vascular stalks may be seen and there is usually slight stromal

fibrosis. Foci of intraductal papillary carcinoma are often seen nearby (Aithala et al., 2009).

Inflammatory Breast Cancer (IBC)

IBC due to tumour emboli within dermal lymphatics (Adam et al., 2013) and patients ranged

in age at diagnosis from 35 to 72 years (mean age, 51). Inflammatory breast cancer (IBC)

accounts for approximately 6% of new breast cancers. It is the most aggressive and lethal

form of locally advanced breast cancer, with a mean 5-year disease-free survival rate of

<45%.

Clinically, patients present with skin erythema and nodularity. Pathologically, IBC is highly

angiogenic and angioinvasive, with numerous tumor emboli filling the dermal lymphatics.

These tumor emboli are responsible for the striking clinical picture of skin edema that arises

from lymphatic obstruction (Kleer et al., 2007) Staging of breast cancer.

Once the pathologic diagnosis of breast cancer is established, the clinician should promptly

obtain the staging information necessary to make therapeutic recommendations and

decisions, which are important for medical, psychological, and economic reasons. The

primary goal of staging evaluation is to assess whether the patient is has operable disease and

is potentially curable by one or more therapy modalities, which most frequently include

surgery plus radiation therapy (if breast conservation and if higher risk factors) plus systemic

therapy (before or after surgery and according to predictive and prognostic factors) (Abeloff

et al., 2008).


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The American College of Radiology has developed the Breast Imaging Reporting and Data

System or BI-RADS. This is a quality assurance tool published and trademarked by the ACR

(Daffner and Hartman, 2014).

The BI-RADS assessment categories are:

0: Incomplete (The mammogram or ultrasound didn't give the radiologist enough information

to make a clear diagnosis; followup imaging is necessary)

1: Negative (There is nothing to comment on; routine screening recommended).

2: Benign finding(s) (A definite benign finding; routine screening recommended).

3: Probably benign (Findings that have a high probability of being benign (>98%); six-month

short interval follow-up).

4: Suspicious abnormality (Not characteristic of breast cancer, but reasonable probability of

being malignant (3 to 94%); biopsy should be considered)

5: Highly suggestive of malignancy (Lesion that has a high probability of being malignant

(>= 95%); take appropriate action).

6: Known biopsy-proven malignancy (Lesions known to be malignant that are being imaged

prior to definitive treatment; assure that treatmentis completed).

All mammogram reports list the BI-RADS category at the end (Daffner and Hartman, 2014).

TNM classifications according to American Joint

Committee on Cancer Staging

Primary tumor (t)

TX: Primary tumor cannot be assessed.

TO: No evidence of primary tumor.

Tis: Intraductal carcinoma, lobular carcinoma in situ, or Paget's disease of the nipple with no

associated invasion of normal breast tissue.

Tis (DCIS): Ductal carcinoma in situ.

Tis (LCIS): Lobular carcinoma in situ.

Tis (Paget's): Paget's disease of the nipple with no tumor.

[Note: Paget's disease associated with a tumor is classified according to the size of the tumo.]

Ti: Tumor not larger than 2.0 cm in greatest dimension.

Timic: Microinvasion not larger than 0.1 cm in greatest dimension.

Tia: Tumor larger than 0.1 cm but not larger than 0.5 cm in greatest dimension.


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Tib: Tumor larger than 0.5 cm but not larger than 1.0 cm in greatest dimension.

Tie: Tumor larger than 1.0 cm but not larger than 2.0 cm in greatest dimension.

T2: Tumor larger than 2.0 cm but not larger than 5.0 cm in greatest dimension.

T3: Tumor larger than 5.0 cm in greatest dimension.

T4: Tumor of any size with direct extension to (a) chest wall or (b) skin.

T4a: Extension to chest wall, not including pectoralis muscle.

T4b: Oedema (including peaud'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.

Regional lymph nodes (N)

NX: Regional lymph nodes cannot be assessed (e.g. previously removed).

NO: No regional lymph node metastasis.

N1: Metastasis to movable ipsilateral axillary lymph node(s).

N2: Metastasis to ipsilateral axillary lymph node(s) fixed or matted, or in clinically apparent

ipsilateral internal mammary nodes in the absence of clinically evident lymph node mtastasis.

N2a: Metastasis in ipsilateral axillary lymph nodes fixed to one another (matted) or to other

structures.

N2b: Metastasis only in clinically apparent ipsilateral internal mammary nodes and in the

absence of clinically evident axillary lymph node metastasis.

N3: Metastasis in ipsilateral infraclavicular lymph node(s) with or without axillary lymph

node involvement, or in clinically apparent 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 node(s) and axillary lymph node(s).

N3c: Metastasis in ipsilateral supraclavicular lymph node(s).

Distant metastasis (m)

MX: Presence of distant metastasis cannot be assessed.

MO: No distant metastasis.

M1: Distant metastasis (Conzen et al., 2008).


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Patients and methods

Patients

This retrospective study was conducted from 15/9/2013 to 1/2/2014 in which 20 women

enrolled. The inclusion criteria were women with known breast cancer with malignant

microcalcifications on mammography. Women with known breast tumors with absent

malignant microcalcifications on mammography were excluded from our study.

These patients were recruited from early detection of breast cancer clinic, Al-Kadmia hospital

A-Nahrin Teaching in Baghdad, Iraq during 2013, Baghdad, Iraq. The study was approved by

the Institutional Scientific Committee and apermission obtained from the registration office

of the hospital to review the patient's record who admitted to the hospital.

Methods

Complete history taking was obtained including the following:

Age:

Marital status : Single: Married History of smoking


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History of Oral contraceptive pills intake:

History of previous pregnancy:

Family history of breast cancer:

Full general and local examination was performed.

The malignant microcalcifications on mammography were evaluated regarding:

Site:

Distribution = clustered linear segmental

Shape : branching pleomorphic .amorphous

Presence of mass:

The histopathological examination was used as the diagnostic standard of reference.

RESULTS

A total number of 20 patients with malignant microcalcifications on mammography and

histopathology were included in this study ;mean age (55 years), age range from 42 years to

78 years, 14 of cases were married (70%) and 6 were single (30%) (figure 1).

Figure 1: Pie chart represent marital status.

The most common age group was (40-50 years) with 10 cases (50%) followed by (51-60

years) with 6 cases (30%).

Table 2: Distribution of breast cancer patients with different age groups.

Age Group 40-50 years 51-60 years Above 61 years Total

No (%) 10(50%) 6(30%) 4(20%) 20(100%)


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Figure 2: Par chart represent age group.

Among 20 patients, 8(40%) have family history of breast cancer, 7(35%) had history of

taking oral contraceptive pills, 7(35%) with no evidence of pregnancy (6 were single and 1

were nulliparous) and 3(15%) were smokers .

Table 3: Association between breast cancer and risk factor.

Risk factor Number (%)

Family history 8(40%)

Oral contraceptive pills 7(35%)

Absence of pregnancy 7(35%)

Smoking 3(15%)

Figure 3: Cylindrical chart represent risk factors.


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In this study, breast lump is the common presenting symptom of breast cancer (50%),

followed by breast pain (40%), while both nipple discharge and retraction of nipple account

(5%).

Table 4: Current clinical presentations related to breast cancer.

Presenting signs/symptom Number (%)

Breast lump 10(50%)

Nipple discharge 1(5%)

Retraction of nipple 1(5%

Breast pain 8(40%)

Figure 4: Pie chart represent presenting illness.

According to mammographic findings in this study ,the most common location of

mirocalcifications are upper outer quadrant in 13(65%) patients followed by upper inner

quadrant in 4(20%) patients, while lower outer quadrant account for 2(10%)patients, and

retroareolar region in 1(5%) patient.

Pleomorphic shape of microcalcifications mostly encountered in 14(70%) patients followed

by branching shape in 5(25%), and amorphous shape in 1(5%).

The most common microcalcifiions distribution are segmental in 12(60%) patients followed

by cluster distribution in 5(25%) patients and linear distribution in 3(15%).


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Table 5a: Findings of mammaography image (Site of microcalcifications.

Site of microcalcifications Number (%)

UOQ 13(65%)

UIQ 4(20%)

LOQ 2(10%)

Retroareolar 1(5%)

Figure 5a: Bar chart represent site of microcalcifications.

Table 5b: Findings of mammaography image (Shape of microcalcifications).

Shape of microcalcifications Number (%)

Pleomorphic 14(70%)

Amorphus 1(5%)

Branching 5(25%)

Figure 5b: Bar chart represent shape of microcalcifications.


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Table 5c: Findings of mammaography image (Distribution of microcalcifications).

Distribution of

microcalcifications

Number (%)

Linear 3(15%)

Segmental 12(60%)

Cluster 5(25%)

Figure 5c: Pie chart represent distribution of microcalcifications.

In this study, invasive ductal carcinoma was the most common type in 14(70%) patients (6 of

14 patients are associated with breast mass) ,followed by ductal carcinoma in situ in 5(25%)

patients (only one patient of 5 was associated with breast mass), while invasive lobular

carcinomas constitute in 1(5%)patient (associated with mass).

Table 6: Histopathological findings and their relation to presence or absence of mass.

Breast

malignancies Number (%)

associated

mass Non Total

IDC 14(70%) 6( 42,9) 8(57,1) 14(100)

DCIS 5(25%) 1(20%) 4(80%) 5(100%)

ILC 1(5%) 1(100%) 0 1(100%)

Total 20(100%)


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Figure: Bar chart represent histopathological findings percent (%) in relation to

presence or absence of mass.


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DISCUSSION

Breast cancer incidence and mortality are increasing in developing countries.[9,10]

It’s the

most common malignancy among Iraqi women and comprises more than 30% of the

registered female cancer (according to Iraqi cancer registry), and tend to affect young age

group.[11]

The obvious rise in incidence rates and the prevalence of advanced stages at

presentation associated with more aggressive tumor behaviour resulting in greater fatality

rates.[12]

A total of 20 patients with malignant microcalcifications, 14 were married (13 have history of

pregnancy and 1 patients were nulliparous) and 6 of cases were single.

In this study the most common age group was (40-50 years) with 10 cases (50%) followed by

(51-60 years) with 6 cases (30%) Invasive ductal carcinoma is the most common histological

type and invasive lobular carcinomas constitute (5-10%), in most series its represent the

second most frequent type of invasive breast cancer[4,17-19]

in comparison to our study the

invasive ductal carcinoma was the most common type account for (70% ), followed by ductal

carcinoma in situ (25%), while invasive lobular carcinomas constitute (5%).

Breast lump is the common presenting symptom of breast cancer (50%), followed by breast

pain (40%), while both nipple discharge and retraction of nipple account (5%).

In this study 8 patients (40%) have family history of breast cancer.

Breast tissue microcalcifications observed radiologically are frequently employed as a marker

for breast pathology type as they can act as a strong differentiator between benign and

proliferative (type I and type II, respectively) breast lesions and as an indicator of the

presence of an early breast cancer. It is often the presence of type II calcification on

mammography that leads to further investigations. However, to date it has not been possible

to clearly distinguish between the proliferative lesions on the basis of the presence of type II

calcium hydroxyapatite. Around 86% of mammograms have been shown to contain visible

microcalcifications in women aged 76–79 years (DH, 2005). Survival of patients with

mammographic microcalcifications is significantly shorter than those without (Ketcham and

Muffat, 1990; Holme et al, 1993) and a significantly larger number of lymph nodes are

involved in patients with tumours showing microcalcifications than those without (

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2965876/#bib6





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They are extremely and common can be present in ~ 85 % of mammograms.[8]

Their

frequency increases with age. Up to 50% of breast cancers can be associated with

calcification while ~ 15-30% of calcifications biopsied for various reasons tend to be

malignant in asymptomatic patients.[10]

RESULTS

Mammographic calcifications associated with breast carcinoma had the final pathologic

diagnoses of pure ductal carcinoma in situ (DCIS) in 65% of patients, DCIS with a focus of

invasion in 32%, and invasive carcinoma only in 4%. Invasive foci were more likely

associated with mammographic calcification size of 11 mm and greater (40%, 77/194)

compared with 1-10 mm (26%, 29/110; p = 0.019). Invasive foci were also more likely

associated with linear calcifications (44%, 55/126) compared with granular calcifications

(29%, 51/178; p = 0.007). The frequency of invasion did not increase with calcification

extents greater than 10 mm. The frequency of invasion ranged from 22% for less than or

equal to 5-mm granular calcifications to 45% for linear calcifications of 11 mm and greater.

Only 11% of cancers characterized by fine granular calcifications were associated with

invasion as compared with 32% of those with coarse and mixed granular calcifications (p =

0.002).

CONCLUSION

Mammographic calcification features of malignant lesions cannot predict the absence of

invasion with greater than 90% predictive value or predict the presence of invasion with

greater than 45% predictive value. Increased extent of calcifications greater than 10 mm was

not associated with greater likelihood of invasion.

Mammographic manifestations of breast cancer

Cancer incidence is increasing all over the world (Curado et al., 2007). Despite new

advances in cancer research, the etiology of many types of cancer is still unknown.

Mammographic detection of microcalcification in breast carries clinical significance.

The detection and identification of elementary mammographic signs form the basis for

correctly interpreting breast pathologies and describing them accurately in the

mammographic report. The specific features are the basis for classifying the lesions as either

benign or malignant (Lattanzio and Simonetti, 2005).


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Mammographical features to look for in breast carcinoma are:

• Ill-defined or spiculated mass

• Parenchymal distortion

• Overlying skin thickening

• Malignant microcalcifications

• Enlarged axillary lymph nodes (David and Brain, 2004).

Calcifications are amorphous, radiopaque, acellular entities produced by calcium deposits.

They vary widely in density, shape and size, reflecting the secretary or degenerative

processes of the breast. Malignant calcifications may be caused either by cellular secretion or

by calcification of necrotic cancer cells.

The detection of calcium deposits in a suspicious opacity, or more often, isolated calcified

clusters, is only possible with mammography, and has made it possible to recognize many

cancers at a very early stage, permitting conservative surgery and reducing the mortality rate

for breast cancer. Calcifications are among the most frequent mammographic signs and can

also be amongst the most difficult to define and interpret (Lattanzio and Simonetti, 2005).

Clustered pleomorphic microcalcifications, with or without an associated soft tissue mass, are

a primary mammographic sign of breast cancer. Such calcifications are seen in more than half

of all mammographically discovered cancers; about one third of all non palpable cancers are

manifest by calcifications alone, without an associated mass (William et al., 2007).

Probably malignant microcalcifications are

Casting calcifications are linear and irregularly shaped, giving a high-density image. They

fill the ducts and their branches, giving a distinctive linear or fragmented pattern. The

necrotic cellular fragments give rise to the cast of the dilated ductal lumen.

Granular type calcifications have irregular shape/ high density and may look like gravel/

crushed stones iron filings/ or fine grains of salt. They generally have a clustered

distribution, sometimes multiple groupings. When they are scattered segmentally or

diffusely they are not readily distinguishable from dysplastic calcifications.

Mixed calcifications present variably as granular type formations or casting type

(pleomorphic). Their distribution is generally diffuse or segmental. They are diagnostic of

a malignant process (Lattanzio and Simonetti, 2005).


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DCIS is most often detected mammographically as a result of microcalcifications. Groups of

pleomorphic calcifications that are more linear in appearance are more commonly associated

with high-nuclear-grade intraductal carcinomas that have luminal necrosis

(comedocarcinomas). The lower-grade (cribriform and micropapillary) types are often

manifest by more punctate or granular appearing calcifications. The morphology of the

calcification cannot, however, be used to predict the subtype of DCIS (William et al, 2007).

Shapes of DCIS Calcification

• Granular

• Irregular rods

• Casting

• Irregular

Branching

Comma shaped

Arrow shaped or pointed (Angela et al., 2007).

Mammogram in Paget's disease is negative in 50% nipple, areolar thickening ,dilated duct,

linearly distributed microcalcifications and retroareolar soft-tissue mass.

Calcifications become specific finding of LCIS and not just an indirectly associated regional

abnormality. Two forms of distinctly sized calcifications are found, a small calcification is

identical in morphology to calcifications also present in surrounding benign tissue. Pathogenesis

of the calcifications was unknown. This form of lobular carcinoma in situ is the classic form of

lobular carcinoma in situ with small, uniform cells. In contrast, large calcifications that are

formed in central necrosis are found; the cells in this type of lobular carcinoma in situ are larger

and more pleomorphic (Smith and Lawton, 2005).

Invasive lobular carcinoma may be difficult to detect as it diffusely infiltrates fatty tissue and

often seen as an ill-defined mass or an area of asymmetrically dense breast tissue

(microcalcifications are less common) (Adam et al., 2013).

Medullary carcinoma may appear as new or enlarging multilobulated masses and may be well

defined (simulating a benign lesion) (Adam et al., 2013).


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Imaging is essential for accurate breast diagnosis and the early detection of breast cancer.

Population screening with mammography is the only intervention proven to reduce mortality

from breast cancer through early detection (Adam et al, 2008).

Summary

Breast cancer is most prevalent and is the leading cause of cancer related deaths among

women worldwide. The early and accurate diagnosis of breast cancer is crucial for successful

treatment and to improve the quality of life. There are several imaging modalities for

diagnosis of breast lesions. The commonest are mammography and ultrasonography.

Breast tissue microcalcifications observed radiologically are frequently employed as a marker

for breast pathology type as they can act as a strong differentiator between benign and

malignant breast lesions and as an indicator of the presence of an early breast cancer.

There are a lot of factors that consider to be related to malignant breast cancer. Simply being

a woman is the main risk factor for developing breast cancer. This is probably because men

have less of the female hormones estrogen and progesterone, which can promote breast

cancer cell growth. Women with dense breasts have a higher risk of breast cancer than

women with less dense breasts. Unfortunately, dense breast tissue can also make

mammograms less accurate.

IDC and DCIS are most common malignancy in breast associated with pleomorphic

microcalcifications followed by ILC.

CONCLUSION

Detection of microcalcification in conventional mammography is a suitable procedure for

diagnosis of breast cancer. It is simple, safe and low cost method of detection.

Malignant microcalcification had important value in diagnosis of ductal type breast cancer.

The most common location of malignant microcalcifications are upper outer quadrant

probably because of presence of high glandular tissue. Regarding the shape and distribution

of miicrocalcifications pleomorphic segmental should arise the strong possibility of breast

cancer. In patients where a mass was found on mammography (with microcalcifications),

there is a higher risk of malignancy. Invasive or infiltrating lobular carcinoma (ILC) accounts


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for 5% of invasive breast cancers, composing the second most common type of invasive

breast lesions after infiltrating ductal carcinoma and mostly multifocal at presentation.

REFERENCES

1. Abeloff MD, Wolff AC, Weber BL, Zaks TZ, Sacchini V, and McCormick B: Abeloff's

Clinical Oncology, Chapter Cancer of the Breast, 4: 14.

2. Conzen SD, Grushko TA, and Olopade OI: Devita, Hellman & Rosenberg's Cancer:

Principles & Practice of Oncology, 8th Edition Chapter 43 - Cancer of the Breast, 2008;

1596- 1654.

3. DeParedes ES: Atlas of Mammography, 3rd Edition, Lippincott Williams & Wilkins, Chapter

1 - Anatomy of the Breast, 2007.

4. Geddes DT: Inside the Lactating Breast: The Latest Anatomy Research. J Midwifery

Women’s Health, 2007; 52: 556 –563.

5. Iglehart JD, and Smith BL: Sabiston Textbook of Surgery, Section VII. chapter

34 Diseases of the Breast, 2008; 18.

6. Kopans DB: Epidemiology of breast cancer in Breast imaging. 3rd edition Lippincott

Williams &Wilkins, 2007; 78-120.

7. Kumar R, and Abbas A: Robbins basic Pathology, The female genital system and breast,

Saunders, an imprint of Elsevier, 2010; 8(19): 739-750.

8. Morris E, and Liberman L: Breast MRI: diagnosis and intervention Springer, New York,

2005; 1.

9. Smith RA, Saslow D, and Sawyer KA: American Cancer Society guidelines for breast

cancer screening: update. CA Cancer J Clin, 2003; 53(3): 141-69.

10. Brunicardi FCH, Andersen DK, Billiar TR, Dunn DL, Hunter JG, Matthews JB, and

Pollock RE: Schwartz's Principles of Surgery Chapter 17. The Breast Book ISBN, 2010;

978-0-07-1547703.

11. Berg WA, Birdwell RL, Gombos E C, Parkinson BT, Raza S, Green GE, Kennedy A, and

Kettler MD: Diagnostic imaging breast, 2006; 1.

12. Guray M and Sahin A: Benign Breast Diseases: Classification, Diagnosis, and

Management. The Oncologist, 2006; 11(5): 435-49.

13. Adam A, Dixon AK, Grainger RG, Allison DJ, Aslam S, Sohaib A, Rockall A, Bomanji

JB, Evanson J, and Reznek RH : Grainger & Allison's Diagnostic Radiology, 5th ed.

section six–Woman’s imaging, chapter –, Churchill Livingstone, An Imprint of Elsevier,

2008.

mk:@MSITStore:F:/radiology/Books/Grainger%20&%20Allison's%20Diagnostic%20Radiology,%205th%20Edition/GADR5.chm::/HTML/about/book/churchill.html


2149


14. Macea JR, and Fregnani JHTG: Anatomy of the thoracic wall, axilla and breast. Int. J.

Morphol, 2006; 24(4): 691-704.

15. Nagin MK: Breast Anatomy and Development Britannica online encyclopedia, 2008.

Available at: http// www. britannica online encyclopedia.com.

16. Gong X, Vedula AA, Glick SJ: Microcalcification detection using cone-beam CT

mammography with a flat-panel imager. Phys Med Biol, 2004; 49: 2183–2195.

17. Haka AS, Shafer-Peltier KE, Fitzmaurice M, et al. Identifying microcalcifications in

benign and malignant breast lesions by probing differences in their chemical composition

using Raman spectroscopy. Cancer Res, 2002; 62: 5375–5380.

18. Holme TC, Reis MM, Thompson A, Robertson A, Parham D, Hickman P, Preece PE. Is

mammographic microcalcification of biological significance? Eur J Surg Oncol, 1993;

19(3): 250-253.

19. Lehman C, Holt S, Peacock S, White E, Urban N. Use of the American College of

Radiology BI-RADS®

guidelines by community radiologists: concordance of assessments

and recommendations assigned to screening mammograms. AJR Am J Roentgenol, 2002;

179: 15–20.

20. Morgan MP, Cooke MM, McCarthy GM. Microcalcifications associated with breast

cancer: an epiphenomenon or biologically significant feature of selected tumors? J

Mammary Gland Biol Neoplasia, 2005; 10: 181–187.

21. Li X, Weaver O, Desouki MM, Dabbs D, Shyum S, Carter G, Zhao C. Microcalcification

is an important factor in the management of breast intraductal papillomas diagnosed on

core biopsy. Am J Clin Pathol, 2012; 138(6): 789-795.

22. Seo BK, Pisano ED, Kuzmiak CM, Koomen M, Pavic D, McLelland R, Lee Y, Cole EB,

Mattingly D, Lee J. The positive predictive value for diagnosis of breast cancer full-field

digital mammography versus film-screen mammography in the diagnostic

mammographic population. Acad Radiol, 2006; 13(10): 1229-1235.

23. Iris Chu: BRS Anatomy (axilla), updated, 2012; 10.

http://www.studyblue.com/notes/note/n/brs-anatomy-axilla/deck/3305986

24. William E. Brant, Clyde A. Helms: Fundamentals of Diagnostic Radiology, 3rd ed. Section

IV, Breast Radiology, Chapter, Lippincott Williams & Wilkins, 2007; 1416: 20.

25. Oliver A, Freixenet J and Zwiggelaar R: Automatic classification of breast density, 2005; (2):

1258-1261.

26. Macea J.R and Fregnani J.H: Anatomy of the thoracic wall, axilla and breast .Int. J. Morphol,

2006; 24(4): 691-704.

http://www.ncbi.nlm.nih.gov/pubmed?term=Holme%20TC%5BAuthor%5D&cauthor=true&cauthor_uid=8390947

http://www.ncbi.nlm.nih.gov/pubmed?term=Reis%20MM%5BAuthor%5D&cauthor=true&cauthor_uid=8390947

http://www.ncbi.nlm.nih.gov/pubmed?term=Thompson%20A%5BAuthor%5D&cauthor=true&cauthor_uid=8390947

http://www.ncbi.nlm.nih.gov/pubmed?term=Robertson%20A%5BAuthor%5D&cauthor=true&cauthor_uid=8390947

http://www.ncbi.nlm.nih.gov/pubmed?term=Parham%20D%5BAuthor%5D&cauthor=true&cauthor_uid=8390947

http://www.ncbi.nlm.nih.gov/pubmed?term=Hickman%20P%5BAuthor%5D&cauthor=true&cauthor_uid=8390947

http://www.ncbi.nlm.nih.gov/pubmed?term=Preece%20PE%5BAuthor%5D&cauthor=true&cauthor_uid=8390947

http://www.ncbi.nlm.nih.gov/pubmed/?term=Holme+1993+and+breast

http://www.ncbi.nlm.nih.gov/pubmed?term=Li%20X%5BAuthor%5D&cauthor=true&cauthor_uid=23161711

http://www.ncbi.nlm.nih.gov/pubmed?term=Weaver%20O%5BAuthor%5D&cauthor=true&cauthor_uid=23161711

http://www.ncbi.nlm.nih.gov/pubmed?term=Desouki%20MM%5BAuthor%5D&cauthor=true&cauthor_uid=23161711

http://www.ncbi.nlm.nih.gov/pubmed?term=Dabbs%20D%5BAuthor%5D&cauthor=true&cauthor_uid=23161711

http://www.ncbi.nlm.nih.gov/pubmed?term=Shyum%20S%5BAuthor%5D&cauthor=true&cauthor_uid=23161711

http://www.ncbi.nlm.nih.gov/pubmed?term=Carter%20G%5BAuthor%5D&cauthor=true&cauthor_uid=23161711

http://www.ncbi.nlm.nih.gov/pubmed?term=Zhao%20C%5BAuthor%5D&cauthor=true&cauthor_uid=23161711

http://www.ncbi.nlm.nih.gov/pubmed/23161711




http://www.studyblue.com/notes/note/n/brs-anatomy-axilla/deck/3305986


2150


27. Moore K. L and Agur A. M: Anatomy of breast, In: Essential clinical anatomy, Baltiman:

Lippincott, William and Wilkins. Philadelphi, a: WB Sunders, 2007; 2: 392-393.

28. Richard H. Daffner, Matthew S. Hartman: Clinical Radiology The Essential, Chapter 6:

Breast Imaging, Lippincott Williams & Wilkins, 2014; 4: 209.

29. Vincenzo L. and Giovanni S. :Mammography Guide to Interpreting , Reporting and Auditing

Mammographic Images, 3 rd ed. Part 1, Spinger, 2005; 4-6.

30. Angela D, Ellen M, Jeffrey R, Kelly K, Mark D, Paula J : Radiological Pathology,

Volume 1, Ductal Carcinoma in Situ, American Registry of Pathology Armed Forces

Institute of Pathology Washington, 2007; 5: 241.

31. Sahelian R: Mammography benefit and risk, danger, caution, side effects, controversy of

testing, 2013, http://www.raysahelian.com/mammography.html.

32. Science Daily :Breast cancer incidence among Iraqi women profiled

http://www.sciencedaily.com/releases/2010/03/100311074127.htm

33. British Journal of cancerhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2965876/,28 sept

2010.

34. http://radiopaedia.org/articles/breast-calcifications

35. STOMPER Paul C; GERADTS Joseph; EDGE Stephen B.; LEVINE Ellis G.

36. Mammographic predictors of the presence and size of invasive carcinomas associated

with malignant microcalcification lesions without a mass

37. Author(s) STOMPER ; GERADTS ; EDGE ; ...

38. American journal of roentgenology, 1976, 2003; 181: 1679 – 1684.

39. American journal of roentgenology, 1976, 2003; 181(6): 1679-1684.

http://www.raysahelian.com/mammography.html

http://www.sciencedaily.com/releases/2010/03/100311074127.htm

morphology and location of breast …

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