Breast Calcifications - Differential diagnosis and BIRADS Atoosa Adibi MD. Isfahan University Of Medical Scienses

Ductal carcinoma-in-situ (DCIS) represents 25-30% of all reported breast cancers. Approximately 95% of all DCIS is diagnosed because of mammographically detected microcalcifications.

Terminal ductal lobular unit The basic functional unit in the breast is the lobule, also called the terminal ductal lobular unit (TDLU). The TDLU consists of 10-100 acini, that drain into the terminal duct. Most invasive cancers arise from the TDLU. It also is the site of origin of ductal carcinoma in situ (DCIS), lobular carcinoma in situ, fibroadenoma and fibrocystic disease, like cysts, apocine metaplasia, adenosis and epitheliosis.

Most calcifications in the breast form either within the terminal ducts (intraductal calcifications) or within the acini (lobular calcifications). LEFT: Lobular calcifications: punctate, round or 'milk of calcium' RIGHT: Intraductal calcifications: pleomorph and form casts in a linear or branching distribution.

Lobular calcifications These calcifications fill the acini, which are often dilated. This results in uniform, homogeneous and sharply outlined calcifications, that are often punctate or round. When the acini become very large, as in cystic hyperplasia, 'milk of calcium' may fill these cavities. However when there is more fibrosis, as in sclerosing adenosis, the calcifications are usually smaller and less uniform. In these cases it can be difficult to differentiate them from intraductal calcifications. Lobular calcifications usually have a diffuse or scattered distribution, since most of the breast is involved in the process that forms the calcifications. Lobular calcifications are almost always benign.

Intraductal calcifications These calcifications are calcified cellular debris or secretions within the intraductal lumen. The uneven calcification of the cellular debris explains the fragmentation and irregular contours of the calcifications. These calcifications are extremely variable in size, density and form (i.e. pleomorphic). Sometimes they form a complete cast of the ductal lumen. This explains why they often have a fine linear or branching form and distribution. Intraductal calcifications are suspicious of malignancy and are classified as BI-RADS 4 or 5.

Diagnostic Approach The diagnostic approach to breast calcifications is to analyze the morphology, distribution and sometimes change over time. The form or morphology of calcifications is the most important factor in deciding whether calcifications are typically benign or not. If not, they are either suspicious (intermediate concern) or of a high probability of malignancy. Usually biopsy in these cases is needed to determine the etiology of these calcifications.

Distribution Diffuse or Scattered: diffuse calcifications may be scattered calcifications or multiple similar appearing clusters of calcifications throughout the whole breast. Regional: scattered in a larger volume (> 2 cc) of breast tissue and not in the expected ductal distribution. Clustered : at least 5 calcifications occupy a small volume of tissue (< 1 cc). Linear: calcifications arrayed in a line, which suggests deposits in a duct. Segmental: calcium deposits in ducts and branches of a segment or lobe.

Diffuse or scattered distribution is typically seen in benign entities Diffuse or scattered distribution is typically seen in benign entities. Even when clusters of calcifications are scattered throughout the breast, this favors a benign entity. Regional distribution according to the BI-RADS atlas would favor a non-ductal distribution (i.e. benignity), while Segmental distribution would favor a ductal distribution (i.e. malignancy). Sometimes this differentiation can be made, but in many cases the differentiation between 'regional' and 'segmental' is problematic, because it is not clear on a mammogram or MRI where the boundaries of a segment (or a lobe) exactly are.

Clustered calcifications are both seen in benign and malignant disease and are of intermediate concern. When clusters are scattered throughout the breast, this favors a benign entity. A single cluster of calcification favors a malignant entity. Linear distribution is typically seen when DCIS fills the entire duct and its branches with calcifications.

Change over time There are conflicting data concerning the value of absence of change over time. It is said that the absence of interval change in microcalcifications that are probably benign on the basis of morphologic criteria is a reassuring sign and an indication for continued mammographic follow-up .

On the other hand in a retrospective study that included indeterminate and suspicious clusters of microcalcifications, stability could not be relied on as a reassuring sign of benignancy In group of patients with biopsy proven malignancy, 25% of patients had stable microcalcifications for 8-63 months. It seems that the morphology of calcifications is far more important than stability and stability can only be relied on if the calcifications have a probably benign form.

The odds for invasive carcinoma versus DCIS are statistically significantly higher among patients with increasing or new microcalcifications. The likelihood that carcinoma will be invasive increases significantly when a suspicious or indeterminate cluster of calcifications is new or increasing.

At six month follow up they had increased in number and DCIS was found at biopsy

Benign Calcifications Skin Calcifications These are usually lucent-centered deposits. Atypical forms may be confirmed by tangential views to be in the skin. Usually they are located along the inframammary fold parasternally and in the axilla and areola.

This cluster calcifications was presented for biopsy This cluster calcifications was presented for biopsy. When you look at the oblique and craniocaudal view, notice that the calcifications look exactly the same in configuration. This is called the tattoo sign . Spot views subsequently proved that these were dermal calcifications.

Vascular Calcifications These are linear or form parallel tracks, that are usually clearly associated with blood vessels. Vascular calcifications noted in women < 50 years suggest potential risk of coronary artery disease. On the left typical vascular calcifications. If only one side of a vessel is calcified (arrow), the calcification may simulate intraductal calcification, but usually the diagnosis is straight forward

Coarse or 'Popcorn-like The classic large 'popcorn-like' calcifications are produced by involuting fibroadenomas. When the calcifications in an fibroadenoma are small and numerous, they may resemble malignant-type calcifications and need a biopsy.

Large Rod-like, Plasma cell mastitis These benign calcifications form continuous rods that may occasionally be branching. They are different from malignant-type fine branching calcifications, because they are usually > 1 mm in diameter. They may have lucent centers if the calcium is in the wall of the duct. These calcifications follow a ductal distribution, radiating toward the nipple and are usually bilateral. These secretory calcifications are most often seen in women older than 60 years. Sometimes it is difficult to differentiate these from linear calcifications as seen in DCIS.

Round and punctate calcifications Round calcifications are 0.5-1 mm in size and frequently form in the acini of the terminal duct lobular unit. When smaller than 0.5 mm, the term 'punctate' is used. Round and punctate calcifications can be seen in fibrocystic changes or adenosis, skin calcifications, skin talc and rarely in DCIS. Suspect DCIS when the calcifications are small, i.e. punctate , and show some heterogeneity especially when in cluster, linear or segmental distribution.

Round and punctate calcifications are classified as: Bi-RADS 2: when scattered round calcifications. Bi-RADS 3 or 4: when in isolated cluster or if new or ipsilateral to a cancer.

Lucent-Centered These are round or oval calcifications that range from under 1 mm to over a centimeter. They are the result of fat necrosis, calcified debris in ducts, and occasional fibroadenomas

Eggshell or Rim Calcification These are very thin benign calcifications that appear as calcium is deposited on the surface of a sphere. These deposits are usually under 1 mm in thickness when viewed on edge. Although fat necrosis can produce these thin deposits, calcifications in the wall of cysts are the most common 'rim' calcifications.

Milk of Calcium The most important feature of these calcifications is the apparent change in shape of the calcific particles on different mammographic projections (craniocaudal versus oblique or 90° lateral)

Suture calcifications They are typically linear or tubular in appearance and knots are sometimes visible

Dystrophic calcifications These are coarse irregular 'lava-shaped' calcifications. These calcifications are larger than 0.5 mm and often have a lucent center. They are seen in irradiated breast or following trauma. They develop 3-5 years after treatment in about 30% of women. These calcifications are also described as fat necrosis

Suspicious Calcifications These calcifications have either an amorphous or coarse heterogeneous form. Usually these calcifications are biopsied to determine their exact nature.

Amorphous calcifications Amorphous or indistinct calcifications are defined as 'without a clearly defined shape or form'. These calcifications are usually so small or hazy in appearance, that a more specific morphologic classification cannot be determined. About 20% of amorphous calcifications turn out to be malignant. Usually it is low grade DCIS.

Based on the morphology these calcifications were classified as BI-RADS 4. Biopsy revealed fibrocystic changes (FCC)

Amorphous calcifications BI-RADS 2: when diffuse and bilateral BI-RADS 3: when multiple bilateral clustered BI-RADS 4: when unilateral clustered or new on follow up or in a patient with a cancer in the contralateral breast

This was classified as Bi-RADS 4 (3-95% chance of malignancy) This was classified as Bi-RADS 4 (3-95% chance of malignancy). Biopsy revealed DCIS with invasive ductal carcinoma

Coarse Heterogeneous larger than 0.5 mm. They are considered to be of intermediate concern, They have to be differentiated from fine pleomorphic microcalcifications, formerly called fine granular, that vary in size and shape, are usually less than 0.5 mm in diameter and are considered to be of higher probability of malignancy, along with the fine linear microcalcifications .

coarse heterogeneous calcifications They were classified as Bi-RADS 4 coarse heterogeneous calcifications They were classified as Bi-RADS 4. Biopsy revealed DCIS.

The differential diagnosis of coarse heterogeneous calcifications includes: Fibroadenoma Fibrosis Post-traumic representing evolving dystrophic calcifications (fat necrosis) DCIS. Multiplicity and bilaterality of such calcifications favors a benign etiology. DCIS is considered when these calcifications have a clustered, linear or segmental distribution.

a patient in whom new calcifications were detected during follow up for breast cancer in the contralateral breast: coarse heterogeneous calcifications in a segmented distribution. These calcifications were classified as Bi-RADS 4. Biopsy showed calcifications within fibrous stroma. There was no sign of malignancy

High Probability of Malignancy Calcifications with a higher probability of malignancy are fine pleomorphic and fine linear or fine linear branching.

Fine Pleomorphic These calcifications vary in size and shapes and are usually < 0.5 mm in diameter. They are more conspicuous than the amorphic calcifications. There is a 25-40% risk of malignancy.

fine pleomorphic calcifications in a segmental and linear distribution fine pleomorphic calcifications in a segmental and linear distribution. These were classified as BI-RADS 5. Biopsy revealed high grade DCIS.

There are some round typically benign calcifications There are some round typically benign calcifications. The most conspicious calcifications however are the fine pleomorphic calcifications. They have a segmental distribution. .

Amorphous and fine pleomorphic calcifications (Bi-RADS 4) Biopsy: fibrocystic changes

New calcifications were detected during follow up in a screening program. These are fine pleomorphic calcifications in a cluster. These calcifications were classified as Bi-RADS 4.This proved to be DCIS.

The message is that with these calcifications you cannot tell whether they are malignant or not and they have to be biopsied.

Fine Linear or Fine Linear Branching These are thin, linear or curvilinear irregular calcifications. They may be discontinuous. Usually they are < 0.5 mm in width. Their appearance suggests filling of the lumen of a duct, i.e. 'casting' calcifications. These calcifications are classified as Bi-RADS 5.

calcifications in a segmental distribution calcifications in a segmental distribution. Some have a linear distribution and some have a branching morphology. This is highly suggestive of malignancy (Bi-RADS 5).

fine linear and branching calcifications in a segmental distribution highly suggestive of malignancy (Bi-RADS 5). Extensive high grade DCIS was found at biopsy.

The morphology and distribution these calcifications were classified as BI-RADS 5. At biopsy this was high grade DCIS

The image on the left shows the same artifacts The image on the left shows the same artifacts. On the image on the right DCIS.

Category 2 Central lucent Rod like Skin Coarse Chunky Vascular Punctate Round