Residents Section Pattern of the Month Chen et al. Segmental reast Calcifications Residents Section Pattern of the Month Residents inradiology Po-Hao Chen 1 Erica T. Ghosh 1,2 Priscilla J. Slanetz 1,2 Ronald L. Eisenberg 1,2 Chen PH, Ghosh ET, Slanetz PJ, Eisenberg RL Keywords: breast, calcifications, lesions, mammography, segmental calcifications DOI:10.2214/JR.11.8198 Received November 3, 2011; accepted after revision December 26, 2011. 1 Harvard Medical School, oston M. 2 Department of Radiology, eth Israel Deaconess Medical Center, 330 rookline ve, oston M 02115. ddress correspondence to P. J. Slanetz (pslanetz@bidmc.harvard.edu). WE This is a Web exclusive article. JR 2012; 199:W532 W542 0361 803X/12/1995 W532 merican Roentgen Ray Society Segmental reast Calcifications reast calcifications related to both benign and malignant causes are commonly seen on screening mammography. dditional views, such as spot magnification craniocaudal and 90 lateral, are typically required to further characterize these calcifications. Depending on their morphology and distribution, calcifications can be stratified into different risk categories: benign (I-RDS 2), with recommendation for continued routine screening; probably benign (I-RDS 3), warranting follow-up imaging to assess for stability; and suspicious morphology or distribution (I-RDS 4 or 5), which necessitates core biopsy for definitive diagnosis. The distribution of calcifications within the breast, which has an important association with relative risk of malignancy, can be described as scattered, regional, grouped, or segmental. Diffuse calcifications throughout both breasts have a low association with malignancy. Regional calcifications occur in a volume of tissue greater than one quadrant, do not correspond with the expected distribution of a ductal unit, and are not typically associated with malignancy. Depending on morphology, grouped calcifications may be characterized as benign, although in many cases they may have suspicious morphology warranting biopsy. Segmental calcifications are best described as calcium deposits that conform to the expected distribution of one or more ducts and their branches, usually radiating toward the nipple. They can have a branching appearance or cover a triangular region, with the most acute angle pointing to the nipple. Whereas segmental calcifications often can be characterized as benign, microcalcifications following a segmental distribution are often suspicious for malignancy because of their anatomic relationship with the ductal system. This article focuses on both benign and malignant causes of segmental calcifications (Table 1). enign Causes of Segmental Calcifications Secretory Secretory calcifications arise from benign calcium deposits in the lumen of the ductal system. They are sometimes referred to as plasma cell mastitis because of the presence of plasma cells in the periductal stroma on histology. Secretory calcifications are seen in both pre- and postmenopausal women and are associated with prior pregnancy and duct ectasia. They have the classically benign appearance of dense, large tubular, or intact rodlike linear deposits (Fig. 1). Typically more than 0.5 mm in thickness and 3 10 mm in length, secretory calcifications occasionally have a diffuse branching configuration because of their ductal origin. Dermal Dermal calcium deposits are typically secondary to an inflammatory process, such as chronic folliculitis. They also can be seen in such conditions as lbright hereditary osteodystrophy, osteoma cutis, and skin tumors. Dermal TLE 1: Differential Diagnosis of Segmental Calcifications on Mammography enign Secretory (plasma cell mastitis, duct ectasia) Dermal Milk of calcium/fibrocystic changes Fat necrosis Sclerosing adenosis Malignant Ductal carcinoma in situ Invasive ductal carcinoma (IDC) IDC with extensive intraductal components W532 JR:199, November 2012
Segmental reast Calcifications Fig. 1 Secretory calcifications. and, Craniocaudal () and mediolateral oblique () images of left breast in 66-year-old woman show dense large tubular linear calcifications representing benign calcium deposits in lumen of ductal system. calcifications are commonly located in the parasternal region, inframammary fold, axilla, or periareolar region. They can be spherical or polygonal and classically show lucent centers. When viewed en face, dermal calcifications may appear to follow a grouped or segmental distribution (Fig. 2). Tangential views are sometimes required to definitively localize these calcifications within the skin, thus allowing them to be accurately classified as benign. Milk of Calcium Milk of calcium is a benign condition that is associated with apocrine metaplasia and fibrocystic changes in the breast and typically represents sedimentation of calcium in cystic fluid. Milk of calcium can be clearly distinguished from other types of calcification by its amorphous appearance on the craniocaudal view and a fluid-calcium level on the lateral view (Fig. 3). t times, however, a delayed lateral view or pendent imaging, in which the patient s hip is flexed at a right angle to allow the breast to fall naturally as though in a prone position, may provide better visualization in some patients. Fat Necrosis Fat necrosis is a benign finding arising from blunt trauma, radiation therapy, surgery, ductal ectasia, or breast infection. Seatbelt injury from a motor vehicle accident can cause fat necrosis that appears to follow a segmental distribution on mammography. The calcifications of fat necrosis arise from calcified cellular debris within the breast parenchyma or ductal system. Fat necrosis typically appears as either round radiolucent oil cysts or irregular dystrophic calcifications along the path of injury (Fig. 4). Occasionally, fat necrosis may present with fine pleomorphic calcifications that can be difficult to distinguish from malignancy. Sclerosing denosis Sclerosing adenosis of the breast is a benign proliferative disease that most frequently develops in the perimenopausal period. rising from fibrotic changes in the ductal unit, it sometimes can resemble malignancy on mammography. However, sclerosing adenosis has not been associ- JR:199, November 2012 W533
Chen et al. C Fig. 2 Dermal calcifications. and, Craniocaudal () and mediolateral oblique () images of right breast in 48-year-old woman show dermal calcification. lthough mediolateral oblique view may suggests intraparenchymal location, craniocaudal view localizes these calcifications to skin of inner breast. C and D, Enlarged images of craniocaudal (C) and mediolateral oblique (D) views highlight calcifications (circle). ated with an increased risk of malignancy. On mammography, sclerosing adenosis can be associated with calcifications as well as architectural distortions. These calcifications are classically fine, smooth, and bilateral (Fig. 5) and can be localized or spread across a large area. Malignant Causes of Segmental Calcifications Microcalcifications seen in association with ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) develop from calcification of necrotic cells or secretion of calcium salts into the ductal lumens. Suspicious calcifications typically are more irregular, lack lucent centers, and are more subtle. Regardless of their morphology, a segmental or linear ductal distribution of calcifications is twice as likely as any other pattern to be associated with malignancy. lthough amorphous and coarse heterogeneous calcifications are usually morphologies of intermediate concern, their arrangement in a segmental pattern increases the risk for malignancy and warrants a I-RDS 4 categorization. Fine pleomorphic, linear, or linear branching D W534 JR:199, November 2012
Segmental reast Calcifications Fig. 3 Milk of calcium. and, Craniocaudal () and mediolateral oblique () images of right breast in 46-year-old woman show classic appearance. Due to effects of gravity on calcium sedimentation, calcium-fluid levels are poorly seen in craniocaudal view but easily visualized in mediolateral oblique view. This patient has incidental simple cyst in retroareolar region. calcifications in a segmental distribution are highly suspicious for malignancy, generally reflect underlying DCIS or IDC, and are categorized as I-RDS 4 or 5. Malignant calcifications, particularly in a segmental distribution, increase the risk for extensive intraductal components (EICs). EIC-positive malignancies are associated with a higher probability of residual cancer after breast-conservative therapy and therefore a higher probability of local recurrence. In patients without EIC, suspicious calcifications associated with a primary malignancy also increase the risk of residual disease at reexcision, regardless of other mammographic findings and the status of the margin at initial surgery. Calcifications associated with DCIS or IDC can have variable morphologies, some of which are more typically associated with benign conditions. However, when they have a segmental distribution or an associated mass (Fig. 6), these calcifications become concerning for malignancy. The two classic morphologies associated with malignancy are fine pleomorphic linear and linear branching calcifications. Fine pleomorphic calcifications are small (< 0.5 mm) irregular calcifications of different shapes and sizes. They are highly suspicious for DCIS or IDC and require biopsy even if unchanged from prior studies. The cause of malignant pleomorphic calcifications differs depending on whether the DCIS belongs to comedo or noncomedo subtypes. The comedo subtype is caused by intraductal necrotic cells, whereas the noncomedo subtype consists of JR:199, November 2012 W535
Chen et al. Fig. 4 Fat necrosis. and, Craniocaudal () and mediolateral oblique () images of left breast in 59-year-old woman show spherical calcified cysts, classic for fat necrosis. This patient sustained seat belt injury after motor vehicle accident. Fig. 5 Sclerosing adenosis. and, Craniocaudal () and mediolateral oblique () images in 75-year-old woman show innumerable fine smooth calcifications representing fibrotic changes within breast. Subtle postsurgical changes are also seen. W536 JR:199, November 2012
Segmental reast Calcifications Fig. 6 Ductal carcinoma in situ (DCIS). and, Craniocaudal () and mediolateral oblique () images of left breast in 39-year-old woman with palpable lump show segmental disease with fine pleomorphic calcifications extending along upper inner quadrant immediately posterior to suspicious mass and along ductal segment (arrows). iopsy of mass showed highgrade invasive ductal carcinoma. dditionally, biopsy of calcifications posterior to mass revealed high-grade DCIS with focal necrosis and ductal and pleomorphic lobular features. calcium-containing secretions in the cribriform space. Comedo DCIS is generally considered more aggressive and is associated with rapidly proliferating cells that have an increased risk of invasion of the basement membrane. This type is also more likely to be associated with the ER2 (formerly HER2) oncogene and less likely to contain estrogen receptors. Fine linear or linear branching calcifications are small discontinuous or dot-dash, sometimes branching, calcifications that often have a segmental ductal distribution. Occasionally, Fig. 7 Invasive ductal carcinoma. and, Craniocaudal () and mediolateral oblique () images of right breast in 53-year-old woman show large segmental area of fine pleomorphic calcifications. (Fig. 7 continues on next page) JR:199, November 2012 W537
Chen et al. C Fig. 7 (continued) Invasive ductal carcinoma. C and D, Enlarged views of craniocaudal (C) and mediolateral oblique (D) images show numerous Y-shaped and V-shaped calcifications due to duct casting with calcified cellular debris. E, Sonogram shows large underlying hypoechoic mass at least 7 cm in length with internal echogenic foci consistent with calcifications. iopsy showed high-grade invasive ductal carcinoma. there may be a Y- or V-shaped calcification, which is due to duct casting and is associated with DCIS with comedo necrosis caused by calcification of necrotic cellular debris within the ductal system. The presence of linear or linear branching calcifications within a mass also suggests central necrosis (Fig. 7). Fine linear calcifications in a segmental or grouped distribution are nearly universally due to high-grade malignancy (I-RDS 5) and warrant biopsy. iopsy-proven DCIS with an area of involvement by calcifications > 2.5 cm is associated with increased risk of invasion. lthough most coarse heterogeneous calcifications are typically benign, up to 20% of biopsies of these lesions reveal underlying malignancy. The coarse heterogeneous calcifications tend to be larger (> 0.5 mm) and vary in size and shape (Fig. 8). When seen in a segmental distribution, this finding should raise concern, and biopsy should be considered (although the association between coarse heterogeneous calcifications and cancer may not be causal because malignancies seldom produce this appearance). Occasionally, fine pleomorphic calcifications produced by a malignancy can be obscured by nearby and overlying coarse heterogeneous calcifications (Fig. 9). morphous calcifications are calcium deposits that lack a well-delineated shape and often appear fuzzy and indistinct on mammography. morphous calcifications in a segmental distribution are concerning for malignancy. pproximately 20% of amorphous calcifications are associated with high-risk breast lesions, such as atypical ductal hyperplasia or atypical lobular D E W538 JR:199, November 2012
Segmental reast Calcifications hyperplasia. n additional 20% are associated with low-grade DCIS or IDC. However, in many cases, amorphous calcifications represent fibrocystic or other benign changes in the breast. morphous calcifications can be difficult to distinguish from milk of calcium on the craniocaudal view, but layering or a teacup configuration on the lateral view suggests that diagnosis. similar appearance of amorphous calcification may be secondary to sclerosing adenosis due to a benign increase in the number of lobular acini. Regardless of the cause of amorphous calcifications, the distribution significantly affects the patient s risk profile. lthough diffuse and bilateral amorphous calcifications are almost always benign, those with segmental distribution are suspicious for malignancy. Conclusion Calcifications in the breast are commonly seen on routine screening mammography. Despite a variety of different morphologic appearances, segmental distribution of breast calcifications raises concern for malignancy and often requires a biopsy to confirm the diagnosis. Fig. 8 Ductal carcinoma in situ (DCIS). and, Craniocaudal () and mediolateral oblique () images of right breast in 55-year-old woman show segmental areas consisting of coarse granular and lucent-centered calcifications in segmental distribution that slowly increased over 6-month period. (Fig. 8 continues on next page) JR:199, November 2012 W539
Chen et al. Fig. 8 (continued) Ductal carcinoma in situ (DCIS). C E, Sonograms from evaluation along area of calcification 1 cm (C), 2 3 cm (D), and 1 8 cm (E) from nipple show dilated ductal system containing echogenic debris consistent with calcifications. Vacuum-assisted biopsy showed low- to intermediate-grade DCIS with calcifications and focal necrosis. C D E W540 JR:199, November 2012
Segmental reast Calcifications C Fig. 9 Ductal carcinoma in situ (DCIS). and, Craniocaudal () and mediolateral oblique () images of left breast in 51-year-old woman show large segmental area consisting of predominantly coarse granular calcifications. C and D, Same-day sonographic images show multiple dilated ducts containing echogenic intraductal material with prominent shadowing (C) and more focal hypoechoic area (cursors, D). iopsy showed high-grade DCIS with calcifications and focal necrosis. D JR:199, November 2012 W541
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