Applied Radiology

Dr. Picca is an Instructor in Radiology and Dr. Shaw de Paredes is a Professor of Radiology and the Section Chief of Breast Radiology at the Medical College of Virginia of Commonwealth University, Richmond, VA.

Breast cancer is the most common malignancy in women in the United States and is the second leading cause of cancer-related mortality. ¹ Each year nearly 200,000 American women develop invasive breast cancer and more than 45,000 will die from the disease. ¹ The lifetime risk of developing breast cancer in American women is approximately 12%. ¹ The survival rate from breast cancer is significantly improved in women in whom breast cancers are clinically occult and are detected by mammography alone. A majority of breast cancers are associated with microcalcifications; ductal carcinoma in situ (DCIS), in particular, presents as microcalcifications alone in the majority of cases. ² Often, the identification of these fine microcalcifications is the key to early detection of breast cancer.

Most mammograms demonstrate some type of calcification in the breast. Many forms of calcifications are identified on standard mammographic views as being clearly benign and do not necessitate recalling the patient for additional imaging. Microcalcifications can be present in benign conditions, particularly fibrocystic changes; however, they also are present in breast cancers. Typically, the presence of focal microcalcifications on a screening study should prompt a recall for magnification views ³ to assess their morphology and distribution. Many microcalcifications are biopsied because of their association with breast cancer.

Approach to assessment of calcifications

Calcifications are found with great frequency on mammography, and radiologists must determine if they are likely benign, malignant, or indeterminate. The characteristics that help to distinguish between the categories include: morphology, distribution, size, number, variability, and stability from prior mammograms. ⁴ Morphology is the most important characteristic indicative of the likely histologic origin of the calcifications. Irregular, pleomorphic, fine linear branching, or amorphous microcalcifications are most likely within ducts and are suspicious in nature; whereas round, smooth, and punctate microcalcifications are more likely in lobules and therefore benign. Distribution of calcifications is the second most important analysis point. Grouped clustered or segmentally distributed calcifications are more typical of malignancy because of their ductal orientation. Although malignant calcifications are most often small (<200 µm in diameter), the size of the calcifications is much less important than their morphology and distribution in determining whether they have a benign or malignant appearance. Coarse, lucent-centered, eggshell, and dystrophic calcifications are usually stromal in origin and also benign. Stability of greater than 2 years suggests, but does not confirm, a benign etiology. Certainly, calcifications having a suspicious morphology should not be ignored because of lack of interval change. Conversely, many new calcifications need not be biopsied if their morphology is benign.

Benign patterns of calcifications

The American College of Radiology (ACR) BI-RADS ⁵ Lexicon describes mammographic findings using a standard nomenclature. Benign calcifications (those categorized as BI-RADS category 2) include the following types: skin, coarse, large rod-like, milk-of-calcium, round, lucent-centered, egg-shell or rim, dystrophic, vascular calcifications, sutural, and punctate.

Skin calcifications, which are located in the sebaceous glands, are small, very well demarcated calcifications with lucent centers that should not cause concern. Dermal calcifications are usually related to a chronic inflammatory process such as folliculitis and are most often located in sebaceous glands. Often, these calcifications are in groups as they extend into small glands in the skin. Occasionally, tangential views are performed to verify that questionable calcifications are located in the skin.

Lucent-centered calcifications (Figure 1), as well as the larger eggshell and rim calcifications (Figure 2), are the result of fat necrosis. These represent the calcifications of oil cysts, which may be small (liponecrosis microcystica) or up to several centimeters in diameter. ⁶ Fat necrosis calcifications may disappear and, thus, develop a crumbled, more irregular appearance (Figure 3). A history of blunt trauma or surgery is often present in patients with lucent-centered or eggshell calcifications.

Milk-of-calcium calcifications are a specific group of microcalcifications that occur in cystic hyperplasia, part of the spectrum of fibrocystic changes. Mammographically, they appear as round or smudged microcalcifications on the craniocaudal (CC) image and are more prominent or linear on the mediolateral oblique (MLO) image (Figure 4). The cross-table lateral, or mediolateral (ML), magnification view is used to verify their etiology. On the ML view, the heavier calcium sediments layer in the bases of the microcysts of the breast, causing a classic tea cup or meniscoid appearance. ⁷

Arterial calcifications are generally a result of calcified atherosclerotic plaques in arterial walls. Arteries within the breast may calcify as they do elsewhere, appearing as long, hollow, parallel streaks of calcium that follow a tortuous course along the path of the vessel (Figure 5). Occasionally, early calcifications in a portion of vessel wall may be difficult to define with standard views, and magnification mammography is utilized to verify the presence of the vessel and the type of calcifications. Coarse calcifications typically occur in fibroadenomas, which are benign tumors found commonly in young women. If a fibroadenoma is not removed, it may degenerate and calcify with a typical benign pattern. In the early stages of degeneration of a fibroadenoma, a few punctate peripheral microcalcifications (Figure 6) are seen on mammography. With time, the calcifications become more dense and coarse, giving the fibroadenoma its classic popcorn appearance (Figure 7).

Secretory disease or plasma cell mastitis is an aseptic inflammation of the breast thought to be the result of extravasation of intraductal secretions into the periductal connective tissue. The condition is associated with duct ectasia and periductal fibrosis, which may cause chronic bilateral nipple retraction. Calcifications associated with secretory disease are large, rod-like ⁸ and are diffuse and bilateral, radiating toward the nipples (Figure 8).

Changes from trauma, surgery, or radiation therapy can be visualized on the mammogram in the form of dystrophic calcifications. These cal-cifications are typically small macro-calcifications with irregular morphology (Figure 9) and are most commonly located in the stroma or fatty tissue of the breast. Dystrophic calcifications tend to be relatively smoothly marginated and coalescent, in contrast to malignant pleomorphic calcifications, which are more jagged and irregular. Other unusual causes of benign dystrophic type calcifications of the breast are associated with silicone or paraffin injections for augmentation of the breasts, ⁹ extensive calcification from secondary hyperparathyroidism, ¹⁰ and dermatomyositis.

Pseudocalcifications and artifacts include gold deposits in lymph nodes ¹¹ from intramuscular gold therapy for rheumatoid arthritis (Figure 10), adhesive tape, deodorant, and numerous film-screen artifacts. The radiologist and technologist must be cognizant of these artifacts, as they can be confused with true parenchymal calcifications. It is important that the technologist ask the patient to remove any powder, deodorant, or creams from the skin of her breast prior to mammography to avoid unnecessary recalls for pseudocalcifications (Figure 11).

Punctate microcalcifications are small, round, pearl-like, and uniform in appearance. They typically occur with breast lobules, and therefore are more often associated with fibrocystic changes rather than malignancy. These calcifications are often diffuse and scattered in both breasts. However, grouped punctate microcalcifications may require magnification views for better assessment of their morphology and uniformity (Figure 12).

Calcifications of intermediate suspicion

Indeterminate calcifications account for the majority of mammographically generated biopsies of calcifications. These microcalcifications are faint, amorphous, and indistinct and are sometimes described as granular in appearance. Magnification mammography, utilizing a microfocal spot and an air gap, is necessary in the evaluation of amorphous calcifications. Often, only a few faint calcific deposits are evident on routine views, but magnification may demonstrate many more calcifications and considerable variation in their morphology. Most often, these calcifications are associated with fibrocystic changes, including fibrosis, adenosis, sclerosing adenosis (Figure 13), epithelial hyperplasia, and atypical hyperplasias. They may occur in lobular carcinoma in situ (LCIS) incidentally. ¹² These calcifications are also seen with DCIS (Figure 14), and, for this reason, they are usually biopsied. ¹³ The BI-RADS assessment category for these calcifications is suspicious (category 4) and the likelihood of malignancy is approximately 25% to 30%. The entire clinical picture, including breast cancer risk factors, must be thoroughly considered when evaluating these calcifications. Clustering or segmental distribution or an interval change from prior mammography are more worrisome than a diffuse bilateral pattern of amorphous microcalcifications. The bilateral pattern is often mixed with smooth, punctate, and/or milk-of-calcium calcifications, which are benign and also part of the spectrum of fibrocystic changes.

Malignant calcifications

Invasive breast cancers are associated with malignant calcifications in about 50% of cases. ¹⁴ Ductal carcinoma in situ accounts for about one-fourth of all breast cancers and is most frequently clinically occult and found by mammography alone. Ductal carcinoma in situ presents as microcalcifications in at least 90% of cases. ² The formation of microcalcifications is thought to be the result of active secretion by the epithelial cells, ¹⁵ as well as by calcification of necrotic debris in comedocarcinoma. Malignant calcifications are typically heterogeneous or pleomorphic, varying in shape and size, and are often jagged and irregular (Figures 15 and 16). Each calcification tends to be small (<500 µm), and they tend to occur in clusters or in a linear or segmental distribution.

Ductal carcinoma in situ is also associated with fine, linear, and/or branching calcifications (Figure 17) as a result of intraductal calcification of necrotic debris in comedocarcinoma. The presence of fine linear branching calcifications is categorized as BI-RADS-5 (highly suspicious for malignancy) and is associated with a positive predictive value >90%.

The greater the number of microcalcifications in an area, the more suspicious for malignancy. Malignant calcifications tend to occur in clusters of an area ¾1 cm ² . However, it is important that one not exclude malignant-appearing calcifications as being suspicious if they are not tightly clustered or numerous. Malignant calcifications can involve a large area, even an entire quadrant or more of the breast (Figure 18), where the tumor may occur extensively throughout the ductal system. Because breast cancer has a tendency to be multifocal or multicentric, additional clusters of microcalcifications in the same breast must be identified and biopsied. As more and more women undergo breast conservation therapy to treat breast cancer, it becomes even more important that the radiologist identify all residual tumor before therapy is initiated. In a series of cases of DCIS, Dershaw et al ² found that 65% were multifocal. When one area of suspicious microcalcifications is identified, the radiologist must search carefully for other foci that might indicate multicentric disease.

Conclusion

We have reviewed the various patterns of calcifications observed on mammography. The authors hope that this article guides the reader toward the proper approach to analysis and diagnosis of calcifications. However, other factors such as knowledge of the patient's clinical history and physical examination and comparison with prior studies are also important in achieving the appropriate diagnosis.

Attention to detail is paramount in the correct identification and assessment of microcalcifications on mammography. Excellent quality images of high contrast and spatial resolution are a necessity. Magnification mammography is needed to completely assess the number and morphology of microcalcifications. There is also increasing evidence for the value of computer-aided detection of microcalcifications and potential malignancies as an aid to the radiologist as a second reader. Proper detection and diagnosis through percutaneous or excisional biopsies for calcifications of suspicion is key to the early detection of breast cancer and the reduction in deaths from this disease. AR

Acknowledgment

The authors gratefully acknowledge the assistance of Ms. Louise Logan in the preparation of this manuscript.