CDIS: what's beyond microcalcifications? - Pictorial essay

Transcription

1 CDIS: what's beyond microcalcifications? - Pictorial essay Poster No.: C-1096 Congress: ECR 2014 Type: Educational Exhibit Authors: R. N. Lucas, C. A. S. Ruano, I. Oliveira, J. M. G. Lourenco, Z Seabra ; Lisbon/PT, Lisboa/PT Keywords: Breast, Mammography, MR, Diagnostic procedure, Cancer DOI: /ecr2014/C-1096 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 30

2 Learning objectives To make a comprehensive review of the spectrum of ductal carcinoma in situ (DCIS) using mammography and magnetic resonance (MR). To outline the imaging features that can help radiologists to consider this diagnosis in the setting of screening mammography and complementary MR evaluation, as to ensure optimal therapeutic approach. Page 2 of 30

3 Background First described almost a century ago by Dr. Joseph Bloodgood, DCIS of the breast represents a spectrum of abnormal clonal proliferation of malignant epithelial cells originating in the terminal ductal lobular unit, with no histologic evidence of invasion of the basement membrane. Some DCIS represent a precursor to invasive breast cancer, and it is thought to be part of invasive carcinoma disease spectrum, as these entities are often found in association. However the diagnosis and management of DCIS is not straightforward and the proportion of DCIS that will progress to invasive tumors is still a matter of debate [1]. DCIS may involve multiple locations in the same ductal system or in different ductal systems with normal breast parenchyma interposed [2]. DCIS is most often asymptomatic and affects mainly woman from age 40 to 50 and its etiology is presumably heterogeneous. Most studies suggest that the risk factors for DCIS are the same as those for invasive breast cancer, including high mammographic density, family history of breast cancer (e.g. BRCA positive), increasing age, menopausal hormone replacement therapy, late age at menopause, nulliparity and high postmenopausal body mass index. The natural history of DCIS is still quite unclear, making assessment of prognosis based on pathology and imaging highly variable. In the past, mastectomy was performed when DCIS was detected, nowadays consensus guidelines agree that the goal of treatment is breast conservation and, for this to became achievable, it is mandatory to determine the DCIS extent precisely. Pathological Features Tumor characteristics besides size include the histological pattern of ductal proliferation, which have been organized in several classification systems based mainly upon architecture, nuclear grade and the presence of central or punctate necrosis. In the 1997 Consensus Conference on the Classification of DCIS, nuclear grade was considered the most reproducible and relevant feature in all the classification systems discussed [3]. Nuclear grade Appearance Page 3 of 30

4 High grade (NG3) Markedly pleomorphic Intermediate grade (NG2) Neither NG 1 nor NG 3 Low grade (NG1) Monotonous (monomorphic) Concerning the architecture, DCIS has been divided into the following types: comedo, solid, cribriform, micropapillary and papillary. Architectural pattern comedo-type frequently associated with central necrosis and microcalcifications cribriform appearing to have open spaces or small holes papillary having fingerlike projections micropapillary having smaller fingerlike projections solid The most aggressive form is the comedo-type, which is often associated with local recurrence and progression to invasive carcinoma, however the "noncomedo" subtypes are more frequent. Many DCIS cases include at least two different architectural types in the same breast [1]. Imaging Role With the development of diagnostic imaging capable of identifying breast lesions before they become palpable, DCIS detection rate increased significantly, especially with the widespread application of screening mammography since the 1980s. Paralleling the rising number of screening mammography worldwide, the incidence of DCIS grew significantly, accounting for about 27% of all newly diagnosed breast cancers.[4]. Nowadays, MRI is being increasingly used to evaluate the local extent of the known DCIS, which is essential for successful breast conservation treatment, but also to identify multicentric tumors and additional disease in the contralateral breast. [4,5]. Most of the published studies state that MRI is more sensitive than mammography for detecting multicentric disease, however more data concerning MRI specificity in this setting is still needed. [5]. Page 4 of 30

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6 Findings and procedure details MAMMOGRAPHIC FEATURES OF DCIS Mammography is the most important method for detecting DCIS, with a reported sensitivity between 87-95% [5]. DCIS is typically depicted at conventional mammography as calcifications, although it may also appear in a noncalcified form [4]. The mammographic findings include: 1. Microcalcifications The most frequent mammographic finding of DCIS, found in 50%-75% of cases [5]. Several attempts have been made to correlate mammographic with histopathologic findings, however there is still great controversy since there is a considerable overlap between the imaging appearances of the different histologic subtypes. a) Fine pleomorphic or fine-linear branching (FIG. 1-5) Usually associated with high-grade lesions and the presence of necrosis. b) Amorphous or indistinct (FIG. 6-9) c) Round calcification Usually associated with low-grade DCIS. 2. Mass (FIG. 10,11) In about 10% of cases, DCIS manifests as a dominant mass [5]. This appearance may be a manifestation of an existing soft-tissue mass, or a result of periductal fibrosis/elastosis producing an irregular or spiculated margin around a nonmasslike lesion. This pattern is more frequently associated with low-grade DCIS without necrosis than with higher-grade lesions. Page 6 of 30

7 3. Architectural distortion (FIG. 12) Observed in 7%-13% of cases, may be related to the presence of sclerosing adenosis, radial scarring and sclerosis in the interstitium around the DCIS [5]. MR IMAGING FEATURES OF DCIS The reported sensitivity of MR imaging for the detection of DCIS ranges between 77%-96% [5]. Dynamic contrast-enhanced MR imaging is the most useful sequence as DCIS is not usually visible on T2-weighted images (with or without fat-suppression) or unenhanced T1-weighted images, in which DCIS either mimics normal breast parenchyma or, less commonly, appears hypointense in relation to normal parenchyma [2]. Contrast-enhanced dynamic MRI of the breast has complementary role to mammography in the detection of DCIS because mammography detects only DCIS associated with microcalcifications and may underestimate the extent of disease in a substantial percentage of patients, resulting in additional interventions such as re-excision or mastectomy to obtain negative surgical margins. With dynamic MRI, enhancement may be seen in areas already depicted in mammography by the presence of microcalcifications as well in mammographically occult DCIS [2]. Diffusion-weighted MR imaging also may be useful, but its role is not yet clear. Breast MR imaging features have also been correlated with histopathologic findings/grades of DCIS without consistent results [6]. 1. Nonmasslike enhancement Accordingly to the Breast Imaging Reporting and Data System (BIRADS) MR lexicon [7], the nonmasslike enhancement is characterized by its distribution and internal enhancement patterns: - Distribution (FIG.13) may be defined as: focal, linear (FIG.14), ductal (FIG.15), segmental (FIG. 16,17), regional (FIG.18), multiregional or diffuse (FIG. 19). The segmental distribution is the more frequent; Page 7 of 30

8 - The internal enhancement pattern may be classified as clumped ("cobblestone") (FIG.14,15), homogeneous, heterogeneous, stippled (punctate) (FIG.17, 18) or reticular. Nonmasslike enhancement is the most common MR imaging finding of DCIS, seen in 60%-80% of cases, although the interpretation of nonmass enhancement lesions is not always straightforward so correlation with mammography is recommended [5]. 2. Enhancing mass (FIG. 20, 21) The BI-RADS lexicon [7] describes masses as space-occupying lesions, round, oval, lobular or irregular in shape. The margins may be smooth, irregular or spiculated. Seen in 14%-34% of cases [5], homogeneous or heterogeneous internal enhancement are equally frequent. 3. Focal enhancement The BI-RADS lexicon [7] describes focus as a spot of enhancement that is too small (< 5 mm) to allow further morphologic characterization. It is the least common finding, seen in about 1%-12% of cases [5]. Kinetic Curves The enhancement kinetics of DCIS lesions at dynamic breast MR imaging are variable and no kinetic pattern is know to be pathognomonic or consistently associated with a particularly nuclear grade [5]. During the initial period after contrast material administration (the first 2 minutes), enhancement is usually rapid in the majority of the lesions. [2]. At delayed imaging, washout is frequently observed (type III curve) but many lesions show plateau enhancement (type II curve, FIG. B) or persistent increase in enhancement (type I curve), so these lesions are considered to have less suspicious kinetic findings compared with invasive cancers [5,8]. Taking into account the great variety of kinetic patterns, the image interpretation is best based on the morphologic enhancement characteristics instead of the enhancement kinetics [2,9]. Page 8 of 30

9 Correlation between Mammographic and MR There seems to be a correlation between the kinetic curves and the mammographic findings: - masslike lesions at mammography tend to have strong washout at MR imaging. (FIG.22) - pleomorphic, fine linear, or fine linear-branching calcifications at mammography tend to have plateau enhancement at MR imaging. (FIG.23) - amorphous calcifications at mammography tend to exhibit persistent delayed enhancement [6,8]. (FIG. 24) ULTRASOUD Ultrasound (US) has a limited role in pure DCIS detection, being sometimes helpful in detecting DCIS without calcifications. The main advantage of identifying an US abnormality in women with mammographically detected DCIS is to guide interventional procedures (eg: needle biopsy, needle localization) [10,11] (FIG.25). Page 9 of 30

10 Images for this section: Fig. 1: Grouping and fine pleomorphic microcalcifications classified as BIRADS 5. Biopsy revealed high grade DCIS. Page 10 of 30

11 Fig. 2: Grouping of thin, branching pleomorphic microcalcifications classified as BIRADS 5. Biopsy revealed high nuclear grade DCIS. Page 11 of 30

12 Fig. 3: Grouping and fine pleomorphic microcalcifications classified as BIRADS 5. Biopsy revealed high grade DCIS. Page 12 of 30

13 Fig. 4: Grouping of thin and branched pleomorphic microcalcifications classified as BIRADS 5. Biopsy revealed high grade DCIS. Page 13 of 30

14 Fig. 5: Cluster of fine pleomorphic and amorphous calcifications microcalcifications classified as BI-RADS 5. The biopsy revealed DCIS of intermediate nuclear grade. Page 14 of 30

15 Fig. 6: Cluster of amorphous coarse heterogeneous microcalcifications and pleomorphic microcalcifications, classified as BIRADS 4C. Biopsy revealed high grade DCIS. Page 15 of 30

16 Fig. 7: Cluster of amorphous microcalcifications classified as BIRADS 4. Biopsy revealed low nuclear grade DCIS. Page 16 of 30

17 Fig. 8: Grouping of amorphous and heterogeneous microcalcifications classified as BIRADS 4. Biopsy revealed intermediate nuclear grade DCIS. Page 17 of 30

18 Fig. 9: Grouping of amorphous and heterogeneous microcalcifications classified as BIRADS 4. Biopsy revealed low nuclear grade DCIS. Page 18 of 30

19 Fig. 10: Nodule with spiculated margins classified as BIRADS 5. Biopsy revealed intermediate nuclear grade DCIS with cribiform pattern. Page 19 of 30

20 Fig. 12: Architectural distortion in mediolateral oblique mammogram of the left breast. Biopsy revealed DCIS with papillary and cribriform pattern. Page 20 of 30

21 Fig. 13: DCIS MR Distribution patterns. Adapted from Esserman LJ et al, J Clin Oncol Oct 1;24(28): Page 21 of 30

22 Fig. 14: MR early subtraction image postcontrast showing an area of linear clumped enhancement on the left breast (A) and correspondent Maximum Intensity Projection image of subtracted images (B). Page 22 of 30

23 Fig. 15: Magnetic resonance subtraction image 2 min postcontrast showing area of ductal clumped persistent enhancement in left upper outer quadrant. Fig. 16: MR early subtraction image postcontrast showing an area of segmental heterogeneous enhancement on the right breast. Page 23 of 30

24 Fig. 17: Magnetic resonance early subtraction image postcontrast showing segmental stippled enhancement of pure DCIS on the left breast. Biopsy revealed DCIS cribriform and solid types, intermediate nuclear grade, with central necrosis. Fig. 18: Magnetic resonance early subtraction image postcontrast showing regional stippled enhancement of pure DCIS on the left breast. Page 24 of 30

25 Fig. 19: Magnetic resonance early subtraction image post contrast showing diffused non-mass enhancement distributed almost uniformly throughout the right breast. Biopsy revealed cribriform and micropapillary DCIS without central necrosis of intermediate nuclear grade. Fig. 20: Magnetic resonance early subtraction image postcontrast showing 1-cm oval mass with irregular margins and heterogeneous enhancement. Biopsy revealed DCIS with marked periductal fibrosis. Page 25 of 30

26 Fig. 21: Magnetic resonance early subtraction image postcontrast (A) and Maximum Intensity Projection image of subtracted images (B) showing a 12-mm oval mass with regular margins and heterogeneous enhancement. Fig. 22: Nodule with irregular borders in mammography (A); corresponding MR early postcontrast subtraction image (B) and kinetic curve - type III curve - with rapid initial uptake and rapid washout in delayed phase (C). Page 26 of 30

27 Fig. 23: Grouping of fine pleomorphic microcalcifications in mammography (A); corresponding MR early postcontrast subtraction image (B) and kinetic curve type II curve (C) with signal intensity not increasing after initial rise, reaching plateau. Fig. 24: Amorphous calcifications at mammography (A); corresponding MR early postcontrast subtraction image (B) and kinetic curve with persistent delayed enhancement - type I curve (C). Page 27 of 30

28 Fig. 25: Partially circumscribed 8 mm nodule in the retroareolar area of the left breast seen on mammography (A). Ultrasound scan demonstrates a round circumscribed hypoechogenic nodule (B) and ultrasound guided core needle biopsy is represented with needle inside the lesion (C). Biopsy revealed DCIS micropapillary and cribiform of Intermediate grade. Fig. 11: Mediolateral oblique mammogram of the left breast showing a spiculated mass projecting in the retroglandular fat (A) and the corresponding ultrasound evaluation showing an ill-defined hypoechoic mass classified as BIRADS 5 (B). Page 28 of 30

29 Conclusion DCIS is a well-know entity with a wide spectrum of imaging features. Almost a century after its first description, nowadays DCIS is generally detected long before a palpable lump becomes evident. Even thought the histologic features of this entity have been the subject of many studies, a precise radio-pathologic correlation is still missing. The implementation of mammographic screening contributed to the rise in the incidence of DCIS worldwide and MR imaging is being progressively adopted to try to define more precisely the pretreatment extent of DCIS and to exclude multifocal or contralateral breast disease. Microcalcifications in mammography and segmental or ductal nonmasslike enhancement in contrast enhanced MR are well-known hallmarks of DCIS, although other features may also be observed. The kinetic contrast uptake evaluation is still a matter of great debate and there seems to exist a correlation with the mammographic findings. Page 29 of 30

30 References [1] NIH State-of-the-Science Conference: Diagnosis and Management of Ductal Carcinoma in Situ (DCIS). September 22-24, 2009 Bethesda, Maryland, consensus.nih.gov/2009/dcisstatement.htm [2] Raza S, Vallejo M, Chikarmane SA, Birdwell RL, Pure Ductal Carcinoma in Situ: A Range of MRI Features. AJR 2008; 191: [3] Consensus Conference on the Classification of Ductal Carcinoma In Situ, April 25-28, 1997, ACS [4] Baur A et al. Breast MRI of pure ductal carcinoma in situ: Sensitivity of diagnosis and influence of lesion characteristics. Eur.J Radiol. 2013; 82(10); [5] Yamada T et al, Radiologic-Pathologic Correlation of Ductal Carcinoma in Situ. RadioGraphics 2010; 30: [6] Jansen SA, Newstead GM, Abe H, Shimauchi A, Schmidt RA, Karczmar GS. Pure ductal carcinoma in situ: kinetic and morphologic MR characteristics compared with mammographic appearance and nuclear grade. Radiology 2007;245(3): [7] American College of Radiology (ACR). ACR BI-RADS-ACR Breast Imaging Reporting and Data System, Breast Imaging Atlas. Reston, VA: American College of Radiology, [8] Esserman LJ et al, Magnetic resonance imaging captures the biology of ductal carcinoma in situ. J Clin Oncol Oct 1;24(28): [9] Facius M et al, Characteristics of ductal carcinoma in situ in magnetic resonance imaging. Clinical Imaging 31 (2007) [10] Barreau B, de Mascarel I, Feuga C, et al. Mammography of ductal carcinoma in situ of the breast: review of 909 cases with radiographic-pathologic correlations. Eur J Radiol 2005;54(1): [11] Moon WK et al, US of Ductal Carcinoma In Situ. Radiographics March : Page 30 of 30