Review Article: Breast Calcifications on Mammography

mucin accumulating in the duct, lobular acini or cavities associated with the lesion. These calcifications can appear in low to intermediate grade DCIS or benign conditions such as sclerosing adenosis and ductal hyperplasia. They take a round or hazy/amorphous shape with size of the calcification depending on the size of the duct. Calcifications within the ducts and lobules can also be formed by the calcium deposition within cell debris and Abstract Breast calcifications are the most common finding on mammograms and can show significant morphological variability. With the help of the BIRADS (Breast Imaging Reporting and Data System) lexicon they can be divided into benign and malignant types but there remains overlap between these two categories. Micro calcifications which fall in the ‘suspicious’ category can occur without the presence of an associated mass or architectural distortion. Micro- calcifications are also one of the first features to be seen on mammograms in DCIS (Ductal Carcinoma In Situ ), leading to early diagnosis and prompt treatment. With the advent of newer technologies in imaging, more information regarding the radiological extent of disease and cancer type associated with the calcification can be determined. This review aims to cover the BIRADS fifth edition descriptors and lexicons of breast calcifications on mammography. Calcifications are a common entity on mammograms, with most being benign. With the evolution in mammogram technology and screening programmes, microcalcifications have become easier to detect with reporting of DCIS increasing, thereby reducing patient mortality. With this review paper, we aim to review the imaging descriptors of benign and malignant calcifications seen on mammograms with a pictorial representation and brief literature review.


Introduction
Calcifications are a common finding in the breast, and they can appear as unequivocally benign, unequivocally malignant, or indeterminate. Around 50% of invasive cancers are associated with microcalcifications and nearly a third of women recalled in screening programs, have only calcifications as a sign of cancer [1,2]. Hence identification and characterization of these calcifications is essential for assessing risk of malignancy and early detection of cancer. Mammography continues to be the most sensitive modality for the detection and differentiation of calcifications. The introduction of DBT (Digital Breast Tomosynthesis) along with FFDM (Full Field Digital Mammography), has further increased sensitivity and resolution. The use of BIRADS lexicon for assessing morphology, size and distribution of calcifications standardizes the reporting and enables better communication between radiologists and referring physicians. Our review covers the BIRADS descriptors for calcifications, their varied imaging appearances, and suitable recommendations.

Breast Calcifications: Pathogenesis
In the ducts and lobules of the breast, calcifications are formed by calcium deposition within mucin accumulating in the duct, lobular acini or cavities associated with the lesion.
These calcifications can appear in low to intermediate grade DCIS or benign conditions such as sclerosing adenosis and ductal hyperplasia. They take a round or hazy/amorphous shape with size of the calcification depending on the size of the duct. Calcifications within the ducts and lobules can also be formed by the calcium deposition within cell debris and

Abstract
Breast calcifications are the most common finding on mammograms and can show significant morphological variability. With the help of the BIRADS (Breast Imaging Reporting and Data System) lexicon they can be divided into benign and malignant types but there remains overlap between these two categories. Micro calcifications which fall in the 'suspicious' category can occur without the presence of an associated mass or architectural distortion. Micro-calcifications are also one of the first features to be seen on mammograms in DCIS (Ductal Carcinoma In Situ), leading to early diagnosis and prompt treatment. With the advent of newer technologies in imaging, more information regarding the radiological extent of disease and cancer type associated with the calcification can be determined. This review aims to cover the BIRADS fifth edition descriptors and lexicons of breast calcifications on mammography.
secretions within the lumen taking the shape of the duct as linear or sometimes granular microcalcifications, commonly seen in high grade lesions [3]. Calcifications can also occur in the stroma of fibrous lesions, such as in a fibroadenoma or in the stromal change of a malignant process [3]. And finally, calcifications can also result from calcium deposition within collagen as response to post-traumatic or post therapeutic steatonecrosis and within a hematoma. Calcium deposition in the breast can be categorized according to their chemical composition into Type I and Type II.
In Type I, the calcific deposits are made of calcium oxalate and are mostly found in benign conditions. In Type II, the calcific deposits are made of calcium phosphate, and these are found in both benign and malignant conditions [4].

Imaging Appearances of Calcifications
Calcifications on mammography are characterized as either benign or suspicious and based on their distribution (Table 1).
Benign calcifications are typically larger, coarser, round and have smooth margins. They are more commonly and easily seen than calcifications associated with malignancy. On the other hand, malignant calcifications are typically small and frequently need the use of magnification to be identified. When a typical benign aetiology cannot be assigned, description of calcifications should include their morphology and distribution.

Definition of micro calcifications
Calcifications are categorized as microcalcifications when the diameter of the calcification is <1mm [3]. These are frequently associated with a malignant process. All macro-calcifications start as micro-calcifications and differentiation between benign and malignant types in the early stages can be difficult.

Skin
Commonly seen along the infra-mammary fold, parasternal region or over the axilla they are round with central lucency, <5mm in size and appearing in tight groups. Additional mammographic views tangential to the skin may be required when they mimic suspicious calcifications near the skin surface [5]. Digital Breast Tomosynthesis, due to its quasi-3D nature can help make the identification of skin calcifications easier since the skin appears at the first and the last three images of the sequence.

Large rod-like or secretory
These benign calcifications are seen in about 3 % of mammograms and appear as smooth, large, linear discontinuous rod like calcifications measuring more than 0.5mm. They can be intra-ductal, appearing solid or periductal showing a central lucency with a characteristic ductal or ductal branching distribution radiating towards the nipple. These are commonly seen in the elderly and involving both the breasts. They can sometimes cause a diagnostic dilemma when seen unilaterally as few calcific particles [5][6][7]. Differentiation from malignancy is typically straightforward since in DCIS, the calcifications although linear are more irregular, do not have lucent centres, are thinner and more discontinuous [8]; ( Figure 4).  although with some heterogeneity and should be carefully assessed [7] ( Figure 5).

Figure 5:
The above LMLO view of a 56-year-old woman shows diffuse punctate/ round calcifications (long arrows). Image courtesy: HCG Hospitals, Bangalore.

Rim calcifications
Previously called 'Eggshell/Lucent centred', they are benign, non-grouped, thin and appear as 'calcium deposited on the edge of a sphere'. Initially these lesions are seen as round or oval lucent lesions that eventually develop a calcified spherical surface with a lucent centre. The calcific deposits when viewed on edge measure less than 1mm in thickness but can range in size from less than 1mm to more than a centimetre. They occur more commonly in a superficial location along with a history of trauma or surgery but are also known to occur spontaneously in large breasts [5,6].
On DBT, these thin calcifications which are curvilinear are better depicted on the walls of oil cysts along with associated fat density [10]; (Figure 6).

Dystrophic calcifications
These calcifications are large, thick, and irregular in shape

Sutural
Commonly occurring at surgical and biopsy sites of an irradiated breast as seen in many studies [11]. (Although they can also rarely occur in a non-irradiated post-surgical breast), they are categorized as benign due to their typical appearance (knotted configuration). In their early development they can be confusing with their vague and non-characteristic morphology and might be mistaken for possible recurrence. Additional magnification views showing the presence of calcifications along a sutural plane will help in diagnosis [8,12]; (Figure 9).

Breast infarcts
Breast infarcts occur due to a variety of reasons and settings.
For example, due to anti-coagulant therapy, in coronary artery bypass grafting using internal mammary artery, in pregnancy, in breast lesions like phyllodes tumour and fibroadenoma etc.
In mammograms, they may appear as microcalcifications with a grouped distribution arousing suspicion for malignancy and need to be thoroughly evaluated [13]; (Figure 10).  Figure 11: RMLO image of a 39-year-old woman showing radio-dense opacities in the axillary region, most likely caused by radio-opaque containing material like antiperspirant (long arrows). Image courtesy: HCG Hospitals, Bangalore.

Artifacts
NACS.000632. 6(2).2021 587 Many compounds which contain radio-opaque material like zinc, aluminium, magnesium can mimic calcifications on mammography causing concern to the patient and the radiologist. They can also mask the true underlying abnormalities. Some examples of substances which form pseudo-calcifications are various ointments, deodorants, and talc. Patients should be informed not to wear deodorants, ointments etc. before the mammogram [14]; ( Figure 11).

Amorphous
They are small and hazy in appearance without a specific shape.
When they occur in a grouped, linear, or segmental distribution, they are deemed suspicious and commonly warrant biopsy. But when they appear in both breasts and are diffuse, they can be assigned a benign BIRADS category. According to ACR BIRADS, amorphous calcifications have a positive predictive value of 20 % and are therefore assigned the BIRADS 4b category [5]. Many studies have been done on assessing the efficiency of mammography imaging techniques in the characterization of amorphous calcifications and the utility of biopsy of these calcifications.
In a study by Ferreira et al. [15] 78 patients with suspicious grouped amorphous calcifications on mammography and categorized as BIRADS 4 were retrospectively analysed with their histopathology results with samples having been obtained via VABB. Their conclusion was that amorphous calcifications of a suspicious nature showed a correlation more with precursor lesions, than with malignancy with a ratio of 3:1.
In another study by Oligane et al. [16] published in 2018, they retrospectively analysed 497 lesions from 494 patients that underwent stereotactic biopsies based on the presence of amorphous calcifications. In their study, they found that 10.5% lesions were malignant with an association of the invasive cancers and hormone receptor positivity ( Figure 12). These are more conspicuous than the hazy amorphous calcifications and tend to have discrete shapes and measuring <0.5mm in diameter. These calcifications are irregular and vary in size and shape. They have a higher positive predictive value of 29% for malignancy and are therefore categorized as BIRADS 4b [5]; (Figure 13).

Coarse heterogeneous
These irregular calcifications are generally larger than pleomorphic calcifications measuring between 0.5mm-1mm; commonly seen in fibroadenomas, fibrosis or areas of trauma eventually becoming dystrophic calcifications. When bilateral, groups of these calcifications, can be categorized as benign. When a single group of these calcifications is seen, they can be associated with malignancy and have a Positive predictive value of <15%, and hence are categorized as BIRADS 4b [5]; (Figure 14).

Linear and fine linear branching
As the name suggests they are fine, linear, thin, and irregular measuring < 0.5mm. They appear sometimes as discontinuous calcifications, as well as in a branching pattern, developing due to the filling in of the lumen of a duct/ducts which are involved by carcinoma. They have the highest positive predictive value amongst the suspicious calcifications (70%). They are categorised as BIRADS 4C [5]; (Figure 15).

Distribution of Calcifications
The distribution of calcifications is as equally important as the morphology of calcifications.
A. Diffuse -Where calcifications are distributed randomly throughout the breast. They are almost always benign. B. Regional -where >2cm (lower limit) of breast tissue is occupied. Malignancy is less likely since they do not have a ductal distribution.
C. Grouped (previously known as clustered) -Calcifications which are present in a small portion of breast tissue -lower limit is 5 calcifications within 1cm and upper limit is a larger number of calcifications within 2cm.
D. Linear-arranged linearly along a duct. They can increase suspicion for malignancy when thin and irregular.
E. Segmental-deposits in a duct and their branches-they are twice as likely to be associated with malignancy [5,[17][18][19]. for not just radiologists, but also pathologists and surgeons dealing with breast disease.