MRI Occult Invasive Breast Cancer

MRI Occult Invasive Breast Cancer Poster No.: C-1573 Congress: ECR 2015 Type: Educational Exhibit Authors: R. Patel, N. Chhaya, K. Stafford, B. Holloway, D. Tsukagoshi, A. Malhotra; London/ Keywords: Cancer, Localisation, Ultrasound, MR, Mammography, Breast DOI: 10.1594/ecr2015/C-1573 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. www.myesr.org Page 1 of 31

Learning objectives To analyse the negative magnetic resonance imaging (MRI) studies of all patients who had histologically proven invasive breast cancer and to correlate these with their respective mammographic and ultrasound findings. Page 2 of 31

Background The availability and utilisation of dedicated breast MR imaging has increased exponentially over the past decade. MRI has shown high sensitivity(1) for detecting multifocal/multicentric and contralateral disease(2) and high specificity in women at increased risk of mammographically occult lesions. In cases of metastatic axillary nodal disease, MRI can help localise the primary malignancy in 60% of women. Page 3 of 31

Findings and procedure details Retrospective analysis of the histological findings of all newly diagnosed invasive breast cancers over a 3 year period (January 2009 through to October 2011 inclusive). Inclusion criteria: local staging of beast cancer performed - diagnosis known. Exclusion criteria: non breast cancer patients - implants/screening. follow up of systemic treatment assessment (chemotherapy/endocrine). Analytical imaging-review was performed in cases found to have MRI-occult invasive breast cancer. Imaging review performed by specialist breast Radiologists. Histology and cytological analysis by a specialist breast Histopathologist CASE 1 76 year old woman presenting to symptomatic clinic: short history of a palpable lump 2 x 2 cms in the left breast lower outer quadrant graded clinically as P4 Refer to Figures 1-3. DISCUSSION Page 4 of 31

Histology: Grade 2 invasive lobular cancer (ILC) measuring 40 x 20 x 13mm. Tumour admixed with LCIS but no DCIS. Mammogram: Bilateral BI-RADS 1. Ultrasound: BI-RADS 2. MRI: Identified no definite abnormality on either pre- or post-contrast sequences and no lesion in the left lower outer quadrant. There are no specific histological characteristics described that would explain the lack of enhancement. Of note ILC is a known cause of negative contract enhanced MRI. CASE 2 43 year old woman presenting in symptomatic clinic with: palpable, diffuse thickening in the right breastlower inner quadrant?aberrations in the Normal Development and Involution of the breast (ANDI). Refer to Figures 4-11. DISCUSSION Histology: Grade 3 invasive carcinoma measuring 8 x 4 x 1.6 mm. Infiltrative margins with some medullary features. Background breast shows fibrocystic change with apocrine metaplasia. Mammogram: Bilateral BI-RADS 1. Ultrasound: hyperechoic focus thought to represent benign pathology (BI-RADS 2). Page 5 of 31

MRI: demonstrated simple cysts but nodiscrete lesion on pre- or post-contrastsequences. Histology reveals multiple tiny foci of highgrade malignancy scattered through an area o fdense lymphocytic infiltrate. Specific immunostaining was required for adequate characterisation. CASE 3 45 year old woman presenting in symptomatic clinic: 10 day history discrete lump in the right breast lower inner quadrant. Refer to Figures 12-17. DISCUSSION Histology: Grade 1 invasive lobular carcinoma measuring 20 x 16 x 11mm. No LCIS, DCIS or lymphovascular invasion. Surrounding the spiculate mass were macroscopic areas of firm fibrosis showing fibroadenomatoid and fibrocystic changes. Mammogram: Bilateral BI-RADS 1 Ultrasound: Right Breast BI-RADS 2 -microcysts noted. However persistence of clinical symptoms led to further intervention and biopsy. MRI: Identified the area of microcyst formation but no accompanying discrete mass lesion or sinister enhancement demonstrated (BI-RADS 2). It is debatable whether the surrounding fibrotic process may be involved in reducing the degree of contrast uptake to levels that are not detected on MRI. Page 6 of 31

CASE 4 55 year old woman referred from a District General Hospital with: biopsy-proven metastatic ductal carcinoma Refer to Figures 18-21. DISCUSSION MASTECTOMY PEFORMED Histology: Intermediate-grade invasive carcinoma measuring 7 x 6 x 4 mm with marked involution with desmoplasia and host response corresponding to left breast 12 o' clock Separate area of intermediate-grade DCIS measuring 21mm (corresponding to the area of MCC in the left breast upper outer quadrant). No abnormal histology from the left breast upper inner quadrant. Despite the invasive carcinoma in the left breast at the 12 o' clock position being identified on mammogram and ultrasound it was MR-occult. The area of DCIS within the left breast upper outer quadrant seen on mammogram was also MR-occult. The area of high signal intensity on DWI resulted in normal histology and was therefore considered to be a false positive result on MRI. Lack of MR enhancement may be attributable to the degree of desmoplasia and involution demonstrated microscopically. Page 7 of 31

Images for this section: Fig. 1: Initial mammogram reveals the breast parenchyma to be predominantly adipose in nature, with no suspicious features identified (Bilateral BI-RADS 1). Page 8 of 31

Fig. 2: Ultrasound reveals an oval hyperechoic lesion in the left breast 4 o'clock position thought to represent a benign lesion i.e. hamartoma but due to rapidity of onset a core biopsy was performed. A single axillary lymph node was identified with benign morphology and no eccentric cortical thickening (BI-RADS U2). Fig. 3: Note made of hamartomatous-type lesion described on conventional imaging. No definite mass lesion identified on pre-contrast imaging and no sinister dynamic contrast enhancement in either breast as evidenced by the subtraction and MIP image (BI-RADS 2). Page 9 of 31

Fig. 4: Mixed fatty density breast parenchyma. No suspicious features (Bilateral BI-RADS 1) Page 10 of 31

Fig. 5: No abnormality at site of clinical concern in right lower inner quadrant. A lobulated, principally solid abnormality is identified in the right 7 o'clock position with fluid-filled areas within it. This was believed to represent a benign entity such as fibroadenoma with cystic degeneration or fibrocystic change (BI-RADS 2). Page 11 of 31

Fig. 6: Several simple cysts present bilaterally, largest at 9 o'clock position of right breast. Page 12 of 31

Fig. 7: Several cysts are noted on the pre-contrast T1/T2w images, the largest centrally in the right breast (circle). No lesion is seen at the site of clinical concern in the right breast lower inner quadrant but a parenchymal abnormality is seen in the region suggested by targeted ultrasound. No other suspicious solid mass lesion in either breast. (BI-RADS 2) Page 13 of 31

Fig. 8: Several cysts are noted on the pre-contrast T1/T2w images, the largest centrally in the right breast (circle). No lesion is seen at the site of clinical concern in the right breast lower inner quadrant but a parenchymal abnormality is seen in the region suggested by targeted ultrasound. No other suspicious solid mass lesion in either breast. (BI-RADS 2) Page 14 of 31

Fig. 9: Following dynamic contrast administration, no discrete mass lesion or differential enhancement on the subtraction sequences is seen. Several sub-3mm foci of enhancement are noted which are too small to characterise by MRI (BI-RADS 2). Page 15 of 31

Fig. 10: The focus of carcinoma was surrounded by dense inflammation and the true extent was only highlighted by the cytokeratin stain. It may either be that there are such tiny tumoral foci or the background fibrocystic change affects the degree of contrast enhancement expected of such an invasive tumour. Page 16 of 31

Fig. 11: The focus of carcinoma was surrounded by dense inflammation and the true extent was only highlighted by the cytokeratin stain. It may either be that there are such tiny tumoral foci or the background fibrocystic change affects the degree of contrast enhancement expected of such an invasive tumour. Page 17 of 31

Fig. 12: Right breast shows no suspicious abnormality. Low-density opacity in the upper outer quadrant of the left breast, measuring 12mm (BI-RADS 2). Page 18 of 31

Fig. 13: No abnormality in right breast lower inner quadrant, but focal microcystic lesion identified at 12 o'clock position of right breast. Benign appearance hence no intervention performed (BI-RADS 2). However patient re-presents to clinic six weeks later with persistent 1.5cm lump in 12 o'clock position. Clinical FNA and subsequent US-guided core biopsy performed. Page 19 of 31

Fig. 14: Tiny high T2 signal foci scattered through both breasts and at site seen on ultrasound in keeping with microcysts (circled). Fig. 15: Following dynamic contrast administration however, no discrete mass lesion or differential enhancement on the subtraction sequences is seen. Several sub-3mm foci of enhancement noted which are too small to characterise by MRI (Bi-RADS 2). Page 20 of 31

Fig. 16: This is a non-mass like lobular carcinoma confirmed histologically after specific cytokeratin immunostaining. The discohesive cells are populating the existing fibrous tissue septa of the breast and are also infiltrating the breast lobules. Page 21 of 31

Fig. 17: This is a non-mass like lobular carcinoma confirmed histologically after specific cytokeratin immunostaining. The discohesive cells are populating the existing fibrous tissue septa of the breast and are also infiltrating the breast lobules. Page 22 of 31

Fig. 18: Ill-defined opacity (arrow) in the left breast at the 12 o' clock position with adjacent focus of fine microcalcification (MCC) [circled] in the left breast upper outer quadrant (BIRADS 3). Page 23 of 31

Fig. 19: Corresponding to the mammographic abnormality in the left breast at the 12 o' clock position ultrasound demonstrates a suspicious 13mm hypoechoic lesion (BI-RADS 4). Page 24 of 31

Fig. 20: A linear area of high signal (circle), measuring 22 x 11 mm, is also seen in the left breast upper inner quadrant on the DWI sequence. This does not correspond to the focal abnormality at the 12 o' clock position in the left breast or the area of MCC in the left breast upper outer quadrant identified on mammography and is a separate finding on MRI (R BI-RADS 1, L BI-RADS 3). Page 25 of 31

Fig. 21: A linear area of high signal (circle), measuring 22 x 11 mm, is also seen in the left breast upper inner quadrant on the DWI sequence. This does not correspond to the focal abnormality at the 12 o' clock position in the left breast or the area of MCC in the left breast upper outer quadrant identified on mammography and is a separate finding on MRI (R BI-RADS 1, L BI-RADS 3). Page 26 of 31

Conclusion Discussion Within these four patients, histology identified: 2 low-grade invasive lobular cancers (one having admixed foci of LCIS). 1 invasive ductal cancer with an adjacent area of DCIS within the mastectomy specimen. 1 high-grade invasive cancer. Of these patients: 3 had unremarkable mammograms with benign features identified on respective ultrasound imaging. 1 patients mammogram revealed a suspicious dense abnormality with adjacent fine microcalcification. Respective ultrasound demonstrated a suspicious hypoechoic lesion. No MRIs detected suspicious features or malignant-type dynamic contrast enhancement. Invasive breast cancers can be mammographically occult and can present with benign features on ultrasound. Breast MRI detects most invasive breast cancers but it is important to recognise that there are a small number of false negatives. Various studies have shown the incidence of non-enhancement with MRI. Page 27 of 31

Schnall et al reported 16% of DCIS and 3% of invasive cancer were not detected.17 Teifke et al found 8.4% of 334 invasive cancers18 were not detected - although the study was of a relatively small cohort. Generally malignant tumours show an increased capillary network with increased permeability leading to an earlier and stronger enhancement than surrounding parenchyma.19 However reasons cited for false-negativity include: non mass-like enhancement very small tumour size diffuse pattern of spread Our incidence of MR-occult breast malignancy is 2.7% which correlates with other reported series.16 We have identified potential causes for the lack of expected enhancement on MRI for invasive carcinoma: The presence of particularly small foci of disease (which has previously been proposed as a cause) which results in insufficient tumour angiogenesis which is required for contrast pooling to be detected. Additionally whilst the presence of a surrounding desmoplastic or fibrotic host response may assist detection by conventional imaging it may also negatively influence the degree of contrast enhancement achieved within the tumour. These findings support the belief that surgical planning cannot be based on MRI findings alone and in fact a combination of multimodality imaging features along with clinical and histological correlation must be performed in all suspected breast masses. Conclusion Whilst mammography remains the primary diagnostic tool, MRI should be considered a valuable complementary aid to facilitate delineation of tumour size and extent whilst Page 28 of 31

detecting additional foci or contralateral disease as well as effectively interrogating mammographically-dense breast tissue.20 Page 29 of 31

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