Breast Calcifications: The Focal Group

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1 Residents Section Pattern of the Month reast alcifications Residents Section Pattern of the Month Downloaded from by on 01/08/18 from IP address opyright RRS. For personal use only; all rights reserved Residents inradiology manda Demetri-Lewis 1, 2 Priscilla J. Slanetz 1 Ronald L. Eisenberg 1 Demetri-Lewis, Slanetz PJ, Eisenberg RL Keywords: breast, calcification DOI: /JR Received September 6, 2010; accepted after revision June 10, Department of Radiology, eth Israel Deaconess Medical enter, Harvard Medical School, 330 rookline ve, oston, M ddress correspondence to R. L. Eisenberg (rleisenb@bidmc.harvard.edu). 2 Present address: reast are enter, York Hospital, York, ME. WE This is a Web exclusive article. JR 2012; 198:W325 W X/12/1984 W325 merican Roentgen Ray Society reast alcifications: The Focal Group reast calcifications are common findings on mammography and may reflect both benign and malignant causes (Fig. 1). The detection of breast calcifications often necessitates further imaging evaluation. Magnification mammography is the primary technique used for further analysis of calcifications in the breast. Typically, magnified mammographic views in the craniocaudal and mediolateral projections are obtained because this permits differentiation of benign milk of calcium, a form of fibrocystic change, from other worrisome deposits. Magnification mammography decreases noise and increases image sharpness, permitting clearer analysis of the morphology and the distribution of the calcifications. Evaluation of breast calcification morphology and distribution as well as assessing for any interval changes can aid in determining patient management. The morphology and size of calcifications are the most important factors in deciding whether calcifications are typically benign, indeterminate and warranting follow-up imaging or biopsy, or suspicious and requiring biopsy. Macrocalcifications are defined as larger (typically > 2 mm) calcium deposits in the breast tissue that are generally associated with a benign process, such as those related to fat necrosis, involuting fibroadenomas, radiation therapy, or plasma cell mastitis. Microcalcifications are calcific particles smaller than 0.5 mm that can be associated with a malignant process, such as ductal carcinoma in situ or invasive carcinoma. nalysis of the morphology of breast calcifications is helpful in determining the likelihood that the calcifications are benign, probably benign, or malignant (Fig. 2). The distribution of breast calcifications is also useful in differentiating benign from indeterminate and malignant causes (Fig. 3). Diffuse or scattered calcifications, most often bilateral, are distributed randomly throughout the breasts and are typically benign, such as skin TLE 1: Differential Diagnosis calcifications and calcifications associated of Focal Group of with fibrocystic change. Regional calcifications are scattered in a larger volume (> 2 enign causes alcifications cm 3 ) of breast tissue; often involve most of rtifact (ointment/antiperspirant) the breast or more than a single quadrant but not in an expected ductal distribution; and Skin calcification favor a benign cause, such as seen with sclerosing adenosis or fibrocystic change. Fibroadenoma Fibrocystic change/milk of calcium Grouped (or clustered) calcifications, which Papilloma are defined as at least five calcifications within 1 cm 3 of tissue, are most often of intermediate concern for malignancy of the breast. Sclerosing adenosis Fat necrosis Linear calcifications, which suggest deposits typia (DH, pleomorphic LIS, LH) in a duct, are suspicious for malignancy. Segmental calcifications, which are deposited in reast infarct one or more ducts and branches of a segment Malignancy or lobe, are typically suspicious for multifocal breast cancer. Invasive cancer, most commonly ductal DIS Most breast calcifications form either Note DH = atypical ductal hyperplasia, LIS = within the terminal ducts (intraductal) or lobular carcinoma in situ, LH = atypical lobular within the acini (lobular), both of which hyperplasia, DIS = ductal carcinoma in situ. JR:198, pril 2012 W325

2 Downloaded from by on 01/08/18 from IP address opyright RRS. For personal use only; all rights reserved enign Dystrophic Eggshell Fat necrosis Milk of calcium Plasma cell mastitis Popcorn Round/punctate Skin Sutural Vascular alcification Morphology Intermediate concern morphous Granular oarse heterogeneous Fig. 1 Various appearances of clustered calcifications in 54-year-old woman who had abnormal screening mammography results., Right mediolateral oblique image shows three clusters of calcifications (arrows)., Magnification mediolateral image shows cluster of pleomorphic calcifications (arrow) in superior anterior right breast, which represented biopsyproven ductal carcinoma in situ., Magnification mediolateral image shows two posterior clusters of calcifications (arrows), which represented fibroadenomas at different stages of hyalinization. Malignant Fine linear branching Fine pleomorphic Fig. 2 Flowchart shows morphology of breast calcifications. [1] W326 JR:198, pril 2012

3 reast alcifications Fig. 3 Flowchart shows calcification differentiation. alcification Distribution enign Intermediate concern Malignant Diffuse Regional Grouped Linear Segmental Downloaded from by on 01/08/18 from IP address opyright RRS. For personal use only; all rights reserved compose the terminal duct lobular unit (TDLU), the basic functional unit of the breast. The ducts and lobules are lined by breast epithelium. onsequently, most breast disorders, including fibrocystic change and malignancies, arise from the TDLU. Lobular calcifications, which are located within the acini of the breast, tend to be uniform, homogeneous, and sharply defined and are often punctuate or round. When the acini become very large, as in cystic hyperplasia, calcium oxalate may precipitate out in the concentrated fluid contained within the distended acinus, most often referred to as milk of calcium. When there is more fibrosis, as Fig. 4 Skin ointment artifact in 63-year-old woman. and, Left mediolateral oblique () and magnification mediolateral () images from screening mammography show cluster of pleomorphic calcific densities in axilla (arrow, )., Tangential compression image with radiopaque marker on skin lesion shows calcific densities seen mammographically (arrow). Further discussion with patient revealed that she had applied zinc oxide cream to her axilla. JR:198, pril 2012 W327

4 Downloaded from by on 01/08/18 from IP address opyright RRS. For personal use only; all rights reserved Fig. 5 ntiperspirant artifact in 47-year-old woman. and, Mediolateral oblique () and magnification mediolateral oblique () images of left breast show cluster of pleomorphic multiple densities in axilla (arrow, ). and D, Repeat mediolateral oblique images without () and with (D) magnification obtained after patient was called back and axilla was washed show no evidence of previous clustered densities, consistent with antiperspirant that was removed. D in sclerosing adenosis, the calcifications are usually smaller and less uniform, making them difficult to differentiate from intraductal calcifications. Lobular calcifications usually have a diffuse or scattered distribution and are often benign. Intraductal calcifications represent calcified cellular debris or secretions within the distal aspect of the TDLU and typically vary in size, density, and shape. Intraductal calcifications may form complete casts of the duct, ap- W328 JR:198, pril 2012

5 reast alcifications Downloaded from by on 01/08/18 from IP address opyright RRS. For personal use only; all rights reserved pearing as fine linear or branching calcifications or appearing more fragmented and irregular, both appearances suspicious for malignancy. Most breast calcifications are deposits of calcium phosphate, usually in the form of hydroxyapatite. These stain dark blue to purple on routine H and E stains. alcium phosphate is found in a spectrum of entities that includes fibrocystic changes (cysts, usual ductal hyperplasia, adenosis, and sclerosing adenosis), fibroadenomas, and in situ and invasive carcinomas. alcium oxalate crystals are much less common; colorless on H and E staining; and predominantly found in benign fibrocystic epithelium, usually accompanied by apocrine epithelial metaplasia. This type of calcification is uncommon in malignant epithelium. The remainder of this article focuses on benign and malignant causes of grouped calcifications (Table 1), which often pose a diagnostic challenge. When properly evaluated with additional mammographic views, some groups of calcifications can be definitively characterized as benign, whereas others may still require follow-up imaging or biopsy. enign Lesions Presenting as Grouped Microcalcifications rtifacts reast calcifications may be simulated by a wide array of artifacts, including radiopaque material on the skin such as antiperspirants, deodorants, powders, and salves, many of which contain metals such as aluminum, magnesium, iodine, or zinc oxide (Fig. 4). Radiopaque Fig. 6 Skin calcifications in 60-year-old woman. and, Screening craniocaudal () and mediolateral oblique () images of right breast show cluster of calcifications (arrow) in posterior inferior medial breast., Magnification craniocaudal image shows cluster of calcifications (arrow) lies within skin and some of calcifications have lucent centers. JR:198, pril 2012 W329

6 densities projecting over the axilla suggest antiperspirant on the skin, which will not persist on repeat imaging after the patient washes the axillary region (Fig. 5). Downloaded from by on 01/08/18 from IP address opyright RRS. For personal use only; all rights reserved Skin alcifications Dermal calcifications usually have lucent centers and are located along the inframammary fold, in the parasternal region, in the axilla, and around the areola (Fig. 6). Dermal calcifications may appear on mammography as a group of calcifications and simulate intraparenchymal calcifications on multiple projections. Tangential views can confirm that the calcifications lie within the skin and are therefore of no clinical concern. Fibrocystic hange Fibrocystic change refers to a constellation of benign entities in the ducts and the stroma that most commonly present as cysts and may have calcifications (Figs. 7 and 8). Sedimented calcium deposits within benign cysts are often referred to as milk of calcium (Fig. 9). Milk of calcium has a very characteristic appearance mammographically and, when present, can be readily recognized as a benign process. On the mediolateral or the lateromedial projection, milk of calcium has the characteristic appearance of crescent-shaped calcium deposits, corresponding to the calcifications conforming to the curve in the inferior aspect of the cyst. On the craniocaudal projection, the calcifications are indistinct, sometimes referred to as smudgy. Other proliferative fibrocystic changes include usual ductal hyperplasia, adenosis, and sclerosing adenosis, all of which may present as grouped calcifications on mammography. Fig. 7 Fibrocystic changes in 61-year-old woman. and, raniocaudal () and mediolateral oblique () images reveal cluster of calcifications in central upper right breast (arrow)., Spot compression magnification craniocaudal image of right breast shows predominantly punctuate group (arrow), which on biopsy were shown to be fibrocystic change. W330 JR:198, pril 2012

7 reast alcifications Downloaded from by on 01/08/18 from IP address opyright RRS. For personal use only; all rights reserved D Fig. 8 Fibrocystic change in 44-year-old woman who had abnormal screening mammography., raniocaudal spot compression magnification image of left breast shows cluster of calcifications medially (arrow)., luster of numerous fine pleomorphic calcifications (arrow) on this magnified craniocaudal image was considered suspicious, and stereotactic core biopsy was recommended., Image shows stereotactic core biopsy of this suspicious cluster of calcifications in left breast, which was performed with superior to inferior approach in craniocaudal projection. D, Specimen radiograph of biopsied calcifications (arrows) confirms adequate sampling and histopathology confirms fibrocystic change. Fibroadenoma Fibroadenomas are benign masses of stroma (fibroblasts and collagen) that distort the native duct epithelium. They most commonly occur in women younger than 30 years but can be seen at any age. On mammography, a fibroadenoma usually appears as an oval or lobulated mass with a density equal to that of breast parenchyma. Involution of a fibroadenoma typically leads to calcification, which initially may appear small and irregular and prompt biopsy. Eventually, the calcification progresses to a dense more popcornlike appearance that confirms its benign cause (Fig. 10). Fat Necrosis Fat necrosis may develop in patients who have sustained trauma or undergone previous surgery or radiation. Fat necrosis usually appears as rimlike or eggshell calcifications with fat-containing radiolucent centers, termed oil cysts (Fig. 11). Occasionally, fat necrosis can appear as a group of indeterminate microcalcifications that may warrant biopsy (Fig. 12). JR:198, pril 2012 W331

8 Downloaded from by on 01/08/18 from IP address opyright RRS. For personal use only; all rights reserved Fig. 9 Milk of calcium in 55-year-old woman with abnormal screening mammography who presented for diagnostic workup., Two-minute delayed lateral image of left breast shows cluster of calcifications in upper breast (arrow)., Magnification image of 2-minute delayed lateral view shows layering of calcifications within tiny cysts, consistent with milk of calcium (arrow)., raniocaudal image of left breast shows same cluster of calcifications in lateral breast (arrow). D, On magnification craniocaudal image, calcifications appear rounded, fuzzy, and amorphous, typical of milk of calcium (arrow) on this projection. iopsy is not indicated. D W332 JR:198, pril 2012

9 reast alcifications Downloaded from by on 01/08/18 from IP address opyright RRS. For personal use only; all rights reserved Fig. 10 Hyalinized fibroadenoma in 51-yearold woman who presented for annual screening mammography., raniocaudal image of right breast shows cluster of coarse calcifications in central posterior breast (arrow)., Mediolateral oblique image shows cluster in superior right breast (arrow)., On magnification mediolateral image, calcifications have popcornlike appearance that is typical of hyalinized fibroadenoma. iopsy is not indicated. Fig. 11 Oil cysts in fat necrosis in 74-year-old woman who had undergone lumpectomy for invasive ductal carcinoma., Mediolateral oblique image of right breast with lumpectomy marker and four clips shows cluster of calcifications in lumpectomy bed (arrow)., Magnification mediolateral image shows cluster of calcifications with lucent-centered calcifications in lumpectomy bed, consistent with oil cysts seen with fat necrosis. No further imaging or workup is necessary. JR:198, pril 2012 W333

10 Downloaded from by on 01/08/18 from IP address opyright RRS. For personal use only; all rights reserved E Fig. 12 Fat necrosis in 29-year-old woman who had undergone prior lumpectomy and radiation therapy for invasive ductal carcinoma and ductal carcinoma in situ and presented for annual mammography., Mediolateral oblique image of right breast shows cluster of calcifications in lumpectomy bed (arrow)., Lateral magnification compression image of lumpectomy bed confirms cluster of pleomorphic calcifications., ompression magnification craniocaudal image of same breast shows cluster of calcifications in lateral breast (arrow). D, Magnified craniocaudal view shows cluster of pleomorphic calcifications (arrow), which were considered suspicious and therefore biopsied. E, Specimen radiograph (with gray scale inverted) after stereotactic-guided core biopsy of calcifications (arrows) in lumpectomy bed confirmed calcifications in biopsy specimen. Histopathology showed fat necrosis. Diagnosis was considered concordant with imaging findings. D W334 JR:198, pril 2012

11 reast alcifications Downloaded from by on 01/08/18 from IP address opyright RRS. For personal use only; all rights reserved Fig. 13 alcified suture material in radiated breast in 67-year-old woman with prior radiation treatment for invasive carcinoma 1 year ago who presented for annual mammography. and, raniocaudal () and mediolateral oblique () images of right breast show group of linear calcifications (arrow). and D, Magnification craniocaudal () and lateral (D) images show linear calcifications in configuration of suture material (arrow) that have knots consistent with calcified suture material, which can occur after radiation therapy and rarely after benign breast biopsy. Sutural alcifications alcifications occurring in the operative site of a resected malignancy are challenging to assess. omparing the current study with pre- and postbiopsy images and specimen radiographs can help to determine whether the calcifications represent residual tumor or a benign finding. alcifications of suture material can occur in a radiated breast and, rarely, at the site of a prior benign surgical biopsy (Fig. 13). D reast Infarct Hemorrhagic breast infarct has been described as a complication of anticoagulant therapy, during pregnancy and lactation, and after harvesting of the internal mammary artery for JR:198, pril 2012 W335

12 Downloaded from by on 01/08/18 from IP address opyright RRS. For personal use only; all rights reserved Fig. 14 reast infarction in 89-year-old woman who had abnormal screening mammography., Mediolateral oblique image of left breast shows cluster of calcifications in anterior slightly superior breast (arrow)., Magnification compression craniocaudal image shows cluster of heterogeneous calcifications (arrow) in this patient, who was on anticoagulation therapy. This cluster was considered suspicious, and biopsy revealed breast infarction. coronary artery bypass grafting. Infarction of breast masses, such as fibroadenoma and phyllodes tumor, has also been reported. reast infarction may manifest mammographically as a group of calcifications that is indistinguishable from the appearance associated with malignant disease (Fig. 14). Sclerosing denosis Sclerosing adenosis is a condition characterized by lobular calcification and associated fibrosis. Lobular calcifications filling the acini are typically uniform, homogeneous, and sharply defined, appearing mammographically as punctate or round. When grouped, they can be difficult to differentiate from suspicious calcifications and thus warrant biopsy (Fig. 15). Fig. 15 Sclerosing adenosis in 77-year-old woman who presented for screening mammography., raniocaudal image of left breast shows cluster of calcifications in lateral breast (arrow)., Magnified craniocaudal image of area shows cluster of pleomorphic calcifications in lateral breast (arrow), for which biopsy was recommended. (Fig. 15 continues on next page) W336 JR:198, pril 2012

13 reast alcifications Downloaded from by on 01/08/18 from IP address opyright RRS. For personal use only; all rights reserved Fig. 15 (continued) Sclerosing adenosis in 77-year-old woman who presented for screening mammography., Postbiopsy radiograph shows calcifications within specimen (arrows). D, Magnified specimen radiograph shows calcifications (arrow), which were shown at biopsy to represent sclerosing adenosis. Fig. 16 Papilloma in 48-year-old woman who presented with bloody nipple discharge. and, raniocaudal () and magnified craniocaudal () images of right breast show cluster of about nine rounded calcifications in retroareolar region (arrow)., Ultrasound image of area shows discrete lesion (cursors) containing calcifications (arrows), which was biopsied under ultrasound guidance and shown to be papilloma. D JR:198, pril 2012 W337

14 Downloaded from by on 01/08/18 from IP address opyright RRS. For personal use only; all rights reserved High-Risk Lesions Presenting as Grouped alcifications Papilloma Papillomas are intraductal lesions composed of a fibrovascular core capped by epithelial and fibroepithelial cells. They are often solitary, occurring in one of the large ducts within 3 cm of the nipple, and typically present with spontaneous clear or bloody discharge. Papillomas are typically not seen on mammograms because of their relatively small size, infrequently associated calcifications, and subareolar location. lmost 60% of patients with papillomas have normal mammograms. Mammographic findings associated with papillomas include benign-appearing circumscribed masses of various sizes and solitary dilated retroareolar ducts. The rare calcifications identified mammographically within a papilloma may be rounded, crescentic, coarse, or eggshell. However, calcifications associated with papillomas may have other appearances that are indistinguishable from the grouped microcalcifications seen in malignant lesions (Fig. 16). Papillomas containing calcifications are believed to have previously undergone infarction with hemorrhage. Papillary lesions of the breast with atypical ductal hyperplasia should be excised because of the significant upgrade rate to malignancy. In some centers, even benign papillomas diagnosed on core needle biopsy are surgically excised, although this is controversial. typical Ductal Hyperplasia typical ductal hyperplasia (DH) is a high-risk marker because women with atypical proliferative changes are 4 5 times more likely to develop breast cancer than those with nonproliferative changes. typical proliferative change in association with a family history of breast cancer elevates the risk to 11 times that of the general population. The risk is increased in both the ipsilateral and the contralateral breasts. Mammographically, DH may appear as a group of amorphous, indistinct, or fine granular calcifications that are difficult to differentiate from a malignant cause (Fig. 17). Fig. 17 typical ductal hyperplasia in 69-year-old woman who presented for screening mammography., Magnification compression craniocaudal image shows cluster of calcifications in left retroareolar breast (arrow)., Magnified craniocaudal image of area shows cluster of pleomorphic calcifications (arrow), which were considered suspicious. iopsy showed atypical ductal hyperplasia and excision was performed. W338 JR:198, pril 2012

15 reast alcifications Downloaded from by on 01/08/18 from IP address opyright RRS. For personal use only; all rights reserved Fig. 18 Lobular carcinoma in situ in 43-year old woman who presented with abnormal screening mammography., Magnified craniocaudal image of left breast shows cluster of calcifications in central posterior breast (arrow)., Magnified craniocaudal image of area shows cluster of pleomorphic calcifications (arrow). ecause of patient s small breast with compression thickness of 14 mm, excisional biopsy after needle localization was performed, revealing pleomorphic lobular carcinoma in situ containing microcalcifications. Lobular arcinoma in Situ Lobular carcinoma in situ (LIS), also termed lobular neoplasia, is an incidental histologic diagnosis with no clinical or mammographic findings except in the pleomorphic variant where calcifications may be seen (Fig. 18). The pleomorphic variant appears to be more aggressive than conventional LIS, with up to 30% having an associated malignancy on surgical excision. For most cases in which LIS is found on a biopsy specimen obtained for grouped calcifications, most centers recommend surgical excision, although the management of LIS remains somewhat controversial. ll forms of LIS are considered a significant risk marker for the development of subsequent breast cancer in either breast, elevating the lifetime risk by 8 10 times. Fig. 19 typical lobular hyperplasia in 51-year-old woman who presented for screening mammography., raniocaudal image of right breast shows cluster of calcifications in lateral central breast (arrow)., Magnified craniocaudal image of area shows cluster of pleomorphic calcifications (arrow), which were considered suspicious. iopsy showed atypical lobular hyperplasia. JR:198, pril 2012 W339

16 Downloaded from by on 01/08/18 from IP address opyright RRS. For personal use only; all rights reserved Fig. 20 Ductal carcinoma in situ (DIS) in 62-year-old woman who presented for screening mammography., Mediolateral oblique image of right breast shows cluster of linear calcifications in superior breast (arrow)., Magnification mediolateral image shows linear calcifications with associated density (arrow). iopsy showed DIS with microinvasion. Fig. 21 Ductal carcinoma in situ (DIS) in 45-year-old woman who presented for screening mammography., raniocaudal image of right breast shows cluster of calcifications in outer breast (arrow). and, Magnified craniocaudal () and lateral () images of area show suspicious cluster of coarse heterogeneous calcifications. iopsy confirmed grade 2 DIS. W340 JR:198, pril 2012

17 reast alcifications Downloaded from by on 01/08/18 from IP address opyright RRS. For personal use only; all rights reserved typical Lobular Hyperplasia Women with atypical lobular hyperplasia (LH) have a 4 5 times increased risk for developing breast cancer in their lifetime. Mammographically, LH is thought to be a serendipitous finding that may result when a biopsy is performed for calcifications. The management of LH is controversial. LH is considered by some to require surgical excision if found on core biopsy to exclude an associated malignancy. Others think that LH does not require surgical excision (Fig. 19). Malignant Lesions Presenting as Grouped alcifications Ductal arcinoma In Situ Ductal carcinoma in situ (DIS) is confined within the TDLU because of its intact basement membrane. The tumor grows within and along the duct, expanding the duct and assuming its D Fig. 22 Ductal carcinoma in situ (DIS) in 40-year-old woman who presented for baseline screening mammography., raniocaudal image of both breasts shows cluster of heterogeneous calcifications in lateral right breast (arrow)., ilateral mediolateral oblique image shows cluster of heterogeneous calcifications in anterior superior right breast (arrow)., Magnification compression craniocaudal image shows cluster or innumerable heterogeneous calcifications (arrow), considered suspicious and prompting biopsy. D, Magnified lateral image shows suspicious cluster of heterogeneous calcifications (arrow), shown to be DIS on stereotactic core biopsy. JR:198, pril 2012 W341

18 Downloaded from by on 01/08/18 from IP address opyright RRS. For personal use only; all rights reserved Fig. 23 Grade 1 invasive ductal carcinoma in 53-year-old woman who presented for screening mammography. and, raniocaudal () and mediolateral oblique () images of right breast show cluster of calcifications in upper outer quadrant (arrow). and D, Magnified craniocaudal () and lateromedial (D) images of area show suspicious group of calcifications. iopsy revealed grade 1 invasive ductal carcinoma. shape. alcifications form within DIS either from calcifying secretions or from cell death with necrosis. The classic appearance of DIS includes linear, branching, or fine pleomorphic calcifications in a ductal distribution. The calcifications in DIS may have a dot-dash appearance with both round and linear shapes, or they may appear as broken needles. However, DIS occasionally may present as a focal group of fine pleomorphic or coarse heterogeneous calcifications, which on histopathology reflect the rounded, tiny, and irregular calcifications that form in necrotic tumors and are most often seen in the micropapillary or cribriform subtypes (Figs ). Invasive arcinoma Most calcifications developing in breast cancer are fine pleomorphic, meaning that they vary in size, shape, and density. These calcifications are concerning for malignancy and warrant biopsy. alcifications in invasive carcinoma typically are due to cell death and necrosis, which occur as the cancer outgrows its blood supply (Fig. 23). Typically seen with invasive ductal cancer, calcifications are rarely associated with invasive lobular malignancies. D onclusions grouped distribution of calcifications carries an intermediate concern for malignancy and therefore warrants further imaging evaluation. reast calcifications should be classified W342 JR:198, pril 2012

19 reast alcifications Downloaded from by on 01/08/18 from IP address opyright RRS. For personal use only; all rights reserved on the basis of their morphology and distribution. Imaging with additional spot compression magnification views in the craniocaudal and the true lateral projections helps further characterize the morphology of calcifications within a group. Those calcifications that are thought to be definitely benign should be managed with routine yearly follow-up mammography. alcifications thought to be probably benign (< 2% chance of malignancy) should be managed with follow-up mammography in 6 months (and placed in the I-RDS 3 category). Periodic follow-up at 6 months for 2 years or follow-up imaging at 6 months, 1 year, 2 years, and 3 years can be undertaken in these probably benign calcifications if they are round or punctuate, have no malignant features, and are stable. Grouped calcifications characterized as suspicious (new, increasing in number, or pleomorphic) warrant further intervention with stereotactic core needle, vacuum-assisted ultrasound-guided, or surgical biopsy. Reference 1. Radiology ssistant Website. alcifications morphology ce38e6d1d7T-calcifications.png. ccessed December 19, 2011 Suggested Reading 1. goff SN, Lawton TJ. Papillary lesions of the breast with and without atypical ductal hyperplasia: can we accurately predict benign behavior from core needle biopsy? m J lin Pathol 2004; 122: merican ollege of Radiology. reast imaging reporting and data system (I-RDS), 4th ed. Reston, V: merican ollege of Radiology, anik S, runt. Haemorrhagic breast infarction complicating anticoagulant therapy. Postgrad Med J 1982; 58: arder PJ, Shaaban, lizadeh Y, Kumarasuwamy V, Liston J, Sharma N. Screen-detected pleomorphic lobular carcinoma in situ (PLIS): risk of concurrent invasive malignancy following a core biopsy diagnosis. Histopathology 2010; 57: De Lafontan, Daures JP, Salicru, et al. Isolated clustered microcalcifications: diagnostic value of mammography series of 400 cases with surgical verification. Radiology 1994; 190: Esserman LE, Lamea L, Tanev S, Poppiti R. Should the extent of lobular neoplasia on core biopsy influence the decision for excision? reast J 2007; 13: Kopans D. reast imaging, 3rd ed. Philadelphia, P: Lippincott Williams & Wilkins, 2007:73 75, 443, 444, , Mahoney M, Robinson-Smith TM, Shaughnessy E. Lobular neoplasia at 11-gauge vacuum-assisted stereotactic biopsy: correlation with surgical excisional biopsy and mammographic follow-up. JR 2006; 187: Sickles E. reast calcifications: mammographic evaluation. Radiology 1986; 160: Sigfúson F, ndersson I, spegren K, Janzon L, Linell F, Ljungberg O. lustered breast calcifications. cta Radiol Diagn (Stockh) 1983; 24: Tavassoli R. Pathology of the breast, 2nd ed. Hong Kong: ppleton and Lange, 1999: Wellings SR, Jensen HM, Marcum RG. n atlas of subgross pathology of the human breast with special reference to possible precancerous lesions. J Natl ancer Inst 1975; 55: Winchester DJ, ernstein JR, Jeske JM, et al. Upstaging of atypical ductal hyperplasia after vacuum-assisted 11-gauge stereotactic core needle biopsy. rch Surg 2003; 138: Jiang Y, Nishikawa RM, Wolverton DE, et al. Malignant and benign clustered microcalcifications: automated feature analysis and classification. Radiology 1996; 198: JR:198, pril 2012 W343