CNB vs Surgical Excision

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Update on Core Needle Biopsy of Non-palpable Breast Lesions Nour Sneige, M.D. UT MD Anderson Cancer Center Houston, Tx Image-Guided CNB of Breast Lesions An alternative to surgical biospy CNB vs Surgical Excision Same accuracy (1-2% delayed false neg) less invasive, less expensive Spares most patients (benign) unnecessary surgery Empowers patient to decide on treatment options 1

CNB of Breast Lesions 1. Technical considerations 2. Diagnostic problems 3. Controversies: to excise or not to excise Imaging Guidance Systems Ultrasound Stereotactic mammography Magnetic resonance (MRI) Ultrasound Guidance System System of choice (lesion imaged with US) Less expensive More readily available No radiation exposure Lesions not amenable to stereo (tail of axilla, close to chest wall) Less time consuming 2

Stereotactic Guidance System Can be used for wider range of lesions: masses and calcifications Breast and lesion are immobilized accurate sampling + 2 mm MRI Demonstrates cancers not detected on mammography or sonography Sensitivity 100% Specificity 37-97% Needle Biopsy Devices Automated (spring loaded gun) Directional Vacuum Assisted (DVAB) 3

Directional Vacuum Assisted Biopsy 1. Probe is placed into the breast adjacent to the tissue requiring sampling 2. 3. VACUUM Vacuum suction is applied, tissue is pulled into the cutting apeture A rotating mechanism cuts and encloses the tissue that has been pulled into the cutting aperture Advantages: DVAB vs Automated Faster (1.4 min. vs. 17 min.) Twice the weight (34 vs. 17 mg) Tissue shift by bleeding, avoided Contiguous sampling 4

Schematic Representation of Breast Biopsy Techniques Microcalcification Core biopsy Random sampling Contiguous sampling Advantages: DVAB vs Automated Underestimation of ADH 41% Automated needle 15% DVAB (Mammotome) Calcs retrieval 99-100% Reynolds et al. Am J Roentgenol 1998;171:611-3 5

CNB Size Gauge: 18, 16, 14, 11, 8-g Calcs: 11-g V more accurate than 14-g V/A Optimal Numbers of CNB Solid masses: 4-5 cores Calcifications: > 10 cores % of Lesions 100% 98% 98% 99% 99% 95% 90% 91% 85% 84% 80% 75% 1 2 3 4 5 >6 X-Core # Diagnostic yield from sequential core biopsy specimens for all masses (n=93) 6

% of Lesions 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 92% 87% 79% 74% 62% 47% 1 2 3 4 5 >6 X-Core # Diagnostic yield from sequential core biopsy specimens for calcifications without mass (n=53) Specimen Radiography - CNB Confirm Calcs Calcs must correspond to those on mammography Segregation of Cores with and without Calcs on Specimen Radiographs Diagnostic yield of malignancy (DVAB): Cores with calcs: 84% Cores without calcs: 71% Same diagnosis: atypical /malignant in 76% Equally careful attention should be given to cores with no calcs Margolin et al, Radiology 2004; 233: 251-254 Easley et al, The Breast Journal 2007;13: 486-489 7

Radiologic-Pathologic Correlation Pathologist should review specimen radiograph (calcs) Pathologist should be provided with: 1) Specimen radiograph 2) BI-RADS category 8

Imaging-Histologic Discordance 0.9-6% of cases Discordance is an indication for surgical excision (24% malignant) Diagnostic Problems- CNB Tubular lesions (tubular CA vs. adenosis) Papillary lesions (pap CA vs. papilloma) Mucinous lesions (mucocele vs. muci CA) Fibroepithelial lesions (FA vs. PT) In situ vs invasive Ductal vs lobular carcinoma in situ Diagnostic Problems- CNB 1. Benign or malignant? 2. In situ or invasive? 3. In situ lobular or ductal? 9

Breast Biopsy Claims from 1998-2003 Total Claims 42 (15.5%) False Negative 20 (48%) False Positive 22 (52%) 21% of all breast bx claims involved CNB Troxel: Errors in Surgical Pathology, Am J Surg Pathol, 2004;28:1092-1095 Diagnostic Errors in Stereotactic/ Palpable CNB of Breast 1. Misdiagnosis of DCIS, SA and adenosis as invasive ductal carcinoma. 2. Misdiagnosis of LCIS as low-grade DCIS. 3. Failure to recognize small, easily over-looked foci of invasive lobular carcinoma. Troxel: Int J Surg Pathol 8(4):335-337, 2000 10

CNB misdiagnosed as IC 11

Carcinoma In Situ: lobular or Ductal? Diagnosis: 1. LCIS 2. Ca in situ 3. ADH/DCIS E-cadherin Deeper cut 12

Indeterminate Lesions at CNB Ancillary studies If in doubt, second opinion / defer to surgical excision Controversies: To Excise or Not to Excise? Lobular Neoplasia Papilloma Mucocele Radial Scar Flat epithelial atypia ADH Consensus Meeting on Image Detected Breast Cancer The American College of Surgeons 2005 Patients with high-risk lesions, including ADH, ALH and LCIS found on percutaneous biopsy may have DCIS or invasive cancer at the same site and should generally undergo surgical excision. This incidence of missing such important findings is markedly reduced with the use of vacuum assisted biopsy and large gauge needles 13

Consensus Meeting on Image Detected Breast Cancer The American College of Surgeons For some individuals with high-risk histologic findings, in whom careful correlation of imaging and histologic findings is concordant, or breast MRI is normal, follow-up without surgical excision may be reasonable. Lobular Neoplasia: To Excise or Not to Excise? 1% of all breast biopsies Marker of inc. risk in excisional biopsy Lobular Neoplasia Diagnosed at CNB Does Not Mandate Surgical Excision 328 Surgical Excision 504 Subjects (19 studies) 176 No Surgical Excision 23.2% upgrade. 7 studies included 101 HRL Exc HRL, 16.7% upgrade Bowman et al, Journal of Surgical Research 2007, 275-280 14

Outcomes for All Patients Undergoing Surgical Excision or Observation (504 Subjects) 328 Surgical Excision 176 No Surgical Excision 94 LCIS 124 ALH 76 HRL 34 LIN 62 F/U 111 No. F/U 3 Lost 6 DCIS 14 IC 21% 13 DCIS 5 IC 14.5% 34 CA 2 DCIS 2 IC 11.7 3 CA 4.7% Bowman et al, Journal of Surgical Research 2007, 275-280 Recommendations Regarding Management of LIN Diagnosed at CNB Bowman et al, J Surg Res 2007, 275-280 Routine surgical excision 9 Surgical excision for specific circumstances 7 Only for LCIS (not ALH) 1 LIN with residual Calcs 2 LIN with synchronous mass 1 LIN with asso with a high risk lesion 1 Pleomorphic LCIS 1 Cases of diagnostic confusion 1 Clinical follow-up 1 No firm recommendations 2 LCIS and ALH on CNB Limitations of published reports 1) Marked variation in the clinical, methodological, and radiological details. 2) Inconsistency regarding inclusion criteria for surgical excision vs observation /selection bias 3) Inclusion of subjects with other high-risk lesions 4) Inclusion of cases with overlapping diagnoses (PLCIS). 5) Small numbers, the retrospective nature, and nearly half were nonconsecutive series. Bowman et al., Journal of Surgical Research 2007, 275-280 15

LN in CNB is Associated With a Low Risk of DCIS/IC 92 LCIS/ALH on CNB - 7 cancers on excision 3 (3%) in area of bx site (1 DCIS; 2 IDC)* 2 away from bx site 2 after negative bx site excision *One interpretive error (ADH on core) Renshaw et al. AJCP 2006; 126: 310-313 LN in CNB is Associated With a Low Risk of DCIS/IC Rate of DCIS/IC found is well within the reported false-negative rate for NLB (1.2%- 9.1%). In centers with appropriate f/u info, routine excision of all biopsy sites for LN may not always be necessary. Renshaw et al. AJCP 2006; 126: 310-313 38 CNB upgrade on excision 3(8%) 18 ALH 1 (6%) 20 LCIS 2 (10%) Problems: 8 associated with mass/density 9-11 V or 14 G auto (S or US) Cangiarella et al:arch Pathol Lab Med. 2008, 132: 979-983 16

LCIS/ALH on CNB- MDACC Multidisciplinary approach No excision required: if 1. Calcs only 2. Completely removed by DVAB 3. Classic LCIS 17

Post interventional imaging LCIS and CCC with calcs by imaging completely excised 18

Papillary lesions on CNB: to Excise or Not to Excise? < 5% of breast biopsies Include benign atypical and malignant 19

Atypia in a Papilloma 10% focal, <30% atypia, 30-90% DCIS (Tavassoli) 3 mm area ADH/DCIS in papilloma (Page) Atypical papilloma on CNB require excision to R/O Ca Papillary lesions on CNB 1063 subjects (16 series) with benign or atypical papillary lesions 138 (23%, R 6-39%) upgraded to carcinoma on excision Arora et al. Am J Surg 194, 444-449, 2007 Reliability of CNB in the diagnosis of papilloma (no atypia)? 20

Reliability of CNB in the Diagnosis of Papilloma? Papilloma with no atypia 345 cases (15 series) 8 series: 0% upgrade to cancer 7 series: 2-20% upgrade to cancer Papillary lesions on CNB Limitations of published series: Small number of patients Selection bias for excision 2 largest studies used cases diagnosed on FNA Relationship of Mode of Biopsy of the Papillary Lesion With Malignancy at Surgical Excision Mode of percutaneous biopsy Stereotactic US- core US- FNA N Malignant % 33 17 30 4 6 9 12 35 30 Valdes E, et al. Annals of Surg Onc. 2006; 13:480-82. 21

Relationship of Pathologic Characteristics of Papillary Lesions With Malignancy at Surgical Excision Pathologic Diagnosis bx Papilloma/papillomatosis Atypical papillomatosis/ papilloma with ADH Pure papillary lesion Papillary lesion with atypia Ca/cases 6/36 2/7 9/28 2/9 % 17 29 32 22 Valdes, et al. Annals of Surg Oncol. 2006; 13(4):480-82 Department of surgery and radiology. Lesions Yielding a Benign, Concordant Diagnosis of Papilloma at Percutaneous Biopsy May Warrant Surgical Excision 35 papillomas on CNB 25 excised, 10 mammo F/U> 2 yrs Excision: 5 Cancers (14%) Liberman, et al. 2006 AJR 186:1328-1334 Lesions Yielding Benign Papilloma at Percutaneous Biopsy and Cancer at Surgery Type Size (cm) Guidance/N eedle # of Cores Target Interval (mo) Surgical Pathology 1 Calcs 1.2 St/ 11 V 29 Excised 1 DCIS 1cm from bx site 2 Mass 1.2 St /14 A 4 Sampled 7 ICPC with DCIS at periphery of pap lesion. 3 Mass 0.8 US/ 14 A 3 Sampled 25 DCIS at periphery of papilloma 4 Mass 0.6 US/ 14 A 4 Sampled 21 DCIS in papilloma 5 Mass 0.8 St/ 11 V 14 Excised 22 IDC, gr 3 and DCIS 1.8cm; admixed with pap. 22

Lesions Diagnosed As Papilloma on CNB - MDACC No excision: Small (up to 1.5 cm) DVAB samples Concordant imaging and histologic findings (size) Mucinous Lesions < 1% of CNB specimens Range: Mucocele-like to mucinous carcinoma Mucocele-like Lesions Imaging: Indeterminate calcs (majority) Well-circumscribed lobulated mass 23

Mucocele- like lesion, CNB 24

CNB MLL with ADH and mucinous ca (20% of cases) 25

Mucocele-like Tumors- CNB Among 20 cases of MLL with no atypia, no carcinoma was found on excision. CNB is highly reliable for accurate Dx of mucinous lesions Wang et al AJCP 2007 Carder et al Histopath 2004 Renshaw AJCP 2002 Mucocele with no atypia on CNB, Calcs completely removed. Exicision is no required Radial Scars Stellate Radiating central fibroelastic stroma Nonpro/prolif.e pith. 26

Results of Surgical Excision of Radial Scars Without Atypia Diagnosed on CNB Authors Biopsy Technique # cases DCIS/IC at Excision Dershaw 14 A 1 0 Lee 14 A 4 1 DCIS Jackman 14 A 5 2 1IDC, 1 DCIS Philpotts 14 A; 11 M 8 0 Kirwan 14 A 30 0 Cawson 14 A 27 0 Total 75 3 (4%) Radial Scar on CNB Brenner et al. AJR 2002; 179: 1179-1184 198 lesions (11 institutions) 157 lesions (102 excised, rest f/u 24 m) CA at excision: RS with ADH on CNB 28% RS no ADH 4% Radial Scar on CNB Dx of RS on CNB is likely to be reliable when: No associated ADH >12 cores obtained VAD used Brenner et al. AJR 2002; 179: 1179-1184 27

Radial Sclerosing Lesion 80 patients (9 or 11 SDVAB) 19 excised, 2 upgraded to atypia 61 mammographic surveillance Conclusions: more extensive sampling by 9/11-g device followed by meticulous correlation of radiological-pathological and close f/u could obviate surgical excision in the majority of RSL. Resetkova et al. Breast Cancer Res Treat:2008 ADH at CNB: MDACC Approach ADH limited to < 2 foci (DVAB) had no worse lesion on excision, provided that most of calcs are removed Ely et al., AJ S P 2001; 25, 1017-1021 Sneige et al., AJCP 2003;119:248-253 ADH in DVAB of Microcalcifications 140 patients (86.4% excision) ADH associated with calcs in the absence of a mass can be categorized into 2 different risk groups. Nguyen, Albarracin, Whitman, Lopez, Sneige Ann Surg Oncol: (2011) 18: 752-761 28

ADH in DVAB of Microcalcifications 1. ADH associated with significant atypia and/or necrosis are most likely to be associated with carcinoma and should excised Nguyen, Albarracin, Whitman, Lopez, Sneige Ann Surg Oncol: (2011) 18: 752-761 ADH with significant cytologic atypia 29

ADH with necrosis ADH in DVAB of Microcalcifications 2. ADH without these features, regardless of extent of involvement, and with >95% removal of the targeted calcs, is associated with a minimal risk (<3%) of carcinoma and may undergo mammographic f/u only Nguyen, Albarracin, Whitman, Lopez, Sneige Ann Surg Oncol: (2011) 18: 752-761 ADH without significant atypia and /or necrosis 30

Image-guided CNB of Breast Lesions- Conclusions Important for the diagnosis Awareness of the diagnostic problems associated with CNB Best managed using a multidisciplinary approach (clinician, radiologist, pathologist, and surgeon involved) 31

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