Mara Rendi, MD, PhD

All Publications

• DCIS-like Invasive Carcinoma of the Breast with Tumor-Associated Microvasculature Mimicking Myoepithelium: A Diagnostic Pitfall Salisbury, T., Rendi, M., Bhalli, R., Bean, G., Allison, K., Troxell, M. ELSEVIER SCIENCE INC. 2024: S254-S255

  View details for Web of Science ID 001302363400212

• HER2 Testing: Insights From Pathologists' Perspective on Technically Challenging HER2 FISH Cases APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY Grimm, E., Allison, K. H., Hicks, D. G., Swenson, K. K., Krueger, J., Yaziji, H., Downs-Kelly, E., Rendi, M. H., Susnik, B., Tsai, M. L., Lillemoe, T. J. 2021; 29 (9): 635-642

  View details for Web of Science ID 000756939300002

• HER2 Testing: Insights From Pathologists' Perspective on Technically Challenging HER2 FISH Cases. Applied immunohistochemistry & molecular morphology : AIMM Grimm, E. V., Allison, K. H., Hicks, D. G., Swenson, K. K., Krueger, J., Yaziji, H., Downs-Kelly, E., Rendi, M. H., Susnik, B., Tsai, M. L., Lillemoe, T. J. 2021

  Abstract

  OBJECTIVE: College of American Pathologists and the American Society of Clinical Oncology guidelines provide straightforward criteria for HER2 interpretation in breast carcinomas; however, a subset of cases present unusual diagnostic dilemmas.MATERIALS AND METHODS: Ten challenging HER2 fluorescence in situ hybridization (FISH) cases were selected for analysis. The study included a variety of problematic cases such as those with discordant immunohistochemistry (IHC) and FISH results, cases with high intratumoral variability in HER2 copy number, a case with a highly amplified clone in 5% to 10% of the tumor sample, and a case with tumor cells containing tightly clumped HER2 signals. Six high volume HER2 FISH laboratories performed and interpreted HER2 FISH (adding HER2 IHC if necessary). Interpretation strategies were discussed.RESULTS: There was 100% concordance between laboratories in 4/10 cases. Tumors with increased intratumoral variability (tumors with high variability in HER2 copy number per cell but which otherwise do not fulfill College of American Pathologists and the American Society of Clinical Oncology criteria for heterogeneity) exhibited 100% concordance in 3/4 cases, but 1 case had only 50% agreement. Low positive HER2 cases (group 1 cases with <6 average HER2 copies/cell) had 1 laboratory disagreeing with the majority in 4/4 cases, and this was the only category with discordance between IHC and FISH methodologies. All laboratories identified the case with heterogeneity and interpreted it as positive. Five of the 6 laboratories interpreted the case with tightly clustered HER2 signals as positive.CONCLUSIONS: This study offers specific observations and interpretation strategies that laboratories can use when confronted with difficult HER 2 cases. It then highlights communication strategies a laboratory may use to discuss these unusual HER2 results with the clinical team.

  View details for DOI 10.1097/PAI.0000000000000946

  View details for PubMedID 34282066

• Pathology of Senegalese breast cancers PAN AFRICAN MEDICAL JOURNAL Fitzpatrick, M., Rendi, M., Kiviat, N., Toure, P., Dem, A., Sow, P., Hawes, S., Feng, Q., Allison, K. 2019; 34: 67

  Abstract

  Breast cancer is among the most common cancers among women in most of Africa. However, features of histologically confirmed breast cancers presenting in specific regional populations is limited. Our study describes the clinic-pathologic features of invasive breast cancer diagnosed in women undergoing biopsy for a clinically apparent mass in Senegal, West Africa.A prospective cohort of 522 Senegalese women presenting consecutively to Dantec Hospital (University of Dakar Tumor Institute) with a breast mass were included in the study cohort. Demographic data was collected by survey and 197 (37.7%) core needle biopsy-confirmed invasive breast cancers available for review were subsequently centrally reviewed at the University of Washington in Seattle to further to characterize the pathologic features and to perform immunohistochemistry for ER/PR and HER2.Seventy six (76.1%) of the 522 Senegalese women presenting for biopsy of a clinically apparent breast mass were diagnosed with invasive breast cancer. The average age of a woman with invasive cancer was 46 years old, and most (83%) presented with Stage III or IV disease. The predominant histologic subtype among the 197 biopsy-confirmed cancers was invasive ductal carcinoma (98%), with few cases of invasive lobular carcinoma (2%). Cancers were classified into four clinically relevant treatment IHC groups by combined ER/PR status and HER2 status as follows: ER-/PR-, HER2- (n=92; 46.7%), ER-/PR-, HER2+ (n=20; 10.1%), ER+/PR+, HER2- (n=76; 38.6%) and ER+/PR+, HER2+ (n=9; 4.6%). Age at time of diagnosis was similar between these four subgroups although more HER2 positive cases were pre-menopausal (p=0.05). Stage of disease at presentation differed by IHC group (p=0.008), with HER2+ cancers significantly more likely to present with stage IV disease than other IHC groups, including ER-/PR-, HER2-. There were no significant differences between groups by age group, ethnicity, place of residence or birth, or parity.Our analysis of breast cancer cases in Senegal shows a distribution of clinically relevant IHC groups like that seen in the few prior studies of breast cancer in West Africa, with higher frequencies of triple negative cancers than in most United States and European populations. Mean age at presentation, delayed presentation, and genetic/regional risk factors likely influence these differences. A better understanding of the frequencies of the pathologic features of breast cancers in the West African population may help guide future genetic studies as well as appropriate clinical management of breast cancer in these populations.

  View details for DOI 10.11604/pamj.2019.34.67.17993

  View details for Web of Science ID 000499128100002

  View details for PubMedID 31819783

  View details for PubMedCentralID PMC6884722

• HER2 testing: Insights from pathologists' perspective on challenging HER2 cases. Grimm, E. V., Swenson, K. K., Krueger, J., Hicks, D. G., Allison, K. H., Yaziji, H., Rendi, M., Susnik, B., Downs-Kelly, E., Tsai, M. L., Lillemoe, T. J. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for DOI 10.1200/JCO.2019.37.15_suppl.e12512

  View details for Web of Science ID 000487345800114

• Breast Cancer Prognostic Factors in the Digital Era: Comparison of Nottingham Grade using Whole Slide Images and Glass Slides. Journal of pathology informatics Davidson, T. M., Rendi, M. H., Frederick, P. D., Onega, T., Allison, K. H., Mercan, E., Brunye, T. T., Shapiro, L. G., Weaver, D. L., Elmore, J. G. 2019; 10: 11

  Abstract

  Background: To assess reproducibility and accuracy of overall Nottingham grade and component scores using digital whole slide images (WSIs) compared to glass slides.Methods: Two hundred and eight pathologists were randomized to independently interpret 1 of 4 breast biopsy sets using either glass slides or digital WSI. Each set included 5 or 6 invasive carcinomas (22 total invasive cases). Participants interpreted the same biopsy set approximately 9 months later following a second randomization to WSI or glass slides. Nottingham grade, including component scores, was assessed on each interpretation, providing 2045 independent interpretations of grade. Overall grade and component scores were compared between pathologists (interobserver agreement) and for interpretations by the same pathologist (intraobserver agreement). Grade assessments were compared when the format (WSI vs. glass slides) changed or was the same for the two interpretations.Results: Nottingham grade intraobserver agreement was highest using glass slides for both interpretations (73%, 95% confidence interval [CI]: 68%, 78%) and slightly lower but not statistically different using digital WSI for both interpretations (68%, 95% CI: 61%, 75%; P= 0.22). The agreement was lowest when the format changed between interpretations (63%, 95% CI: 59%, 68%). Interobserver agreement was significantly higher (P < 0.001) using glass slides versus digital WSI (68%, 95% CI: 66%, 70% versus 60%, 95% CI: 57%, 62%, respectively). Nuclear pleomorphism scores had the lowest inter- and intra-observer agreement. Mitotic scores were higher on glass slides in inter- and intra-observer comparisons.Conclusions: Pathologists' intraobserver agreement (reproducibility) is similar for Nottingham grade using glass slides or WSI. However, slightly lower agreement between pathologists suggests that verification of grade using digital WSI may be more challenging.

  View details for PubMedID 31057980

• Pathologic Features and Clinical Outcomes of Breast Cancers with HER2/CEP17 ratio < 2.0 and mean HER2 signals /cell > 6.0 by FISH; A Multi-Institutional Study Ballard, M., Toukatly, M., Bean, G., Jalikis, F., Krings, G., Schmidt, R., Chen, Y., Rendi, M., Dintzis, S., Troxell, M., West, R., Sibley, R., Allison, K. NATURE PUBLISHING GROUP. 2018: 48

  View details for Web of Science ID 000429308600140

• Clinicopathologic Features, Management and Outcomes of Breast Secretory Lesions with and without Atypia Mooney, K., Lin, C., Sibley, R., Rendi, M., Allison, K. NATURE PUBLISHING GROUP. 2018: 92

  View details for Web of Science ID 000459341000260

• Pathologic Features and Clinical Outcomes of Breast Cancers with HER2/CEP17 ratio < 2.0 and mean HER2 signals /cell > 6.0 by FISH; A Multi-Institutional Study Ballard, M., Toukatly, M., Bean, G., Jalikis, F., Krings, G., Schmidt, R., Chen, Y., Rendi, M., Dintzis, S., Troxell, M., West, R., Sibley, R., Allison, K. NATURE PUBLISHING GROUP. 2018: 48

  View details for Web of Science ID 000459341000140

• Potential Impact of Proposed HER2 FISH Guideline Updates on FISH results; A Multi-Institutional Study Ballard, M., MacKerricher, W., Jalikis, F., Krings, G., Schmidt, R., Chen, Y., Rendi, M., Dintzis, S., Troxell, M., West, R., Sibley, R., Allison, K. NATURE PUBLISHING GROUP. 2018: 48

  View details for Web of Science ID 000459341000139

• Clinicopathologic Features, Management and Outcomes of Breast Secretory Lesions with and without Atypia Mooney, K., Lin, C., Sibley, R., Rendi, M., Allison, K. NATURE PUBLISHING GROUP. 2018: 92

  View details for Web of Science ID 000429308600260

• Potential Impact of Proposed HER2 FISH Guideline Updates on FISH results; A Multi-Institutional Study Ballard, M., MacKerricher, W., Jalikis, F., Krings, G., Schmidt, R., Chen, Y., Rendi, M., Dintzis, S., Troxell, M., West, R., Sibley, R., Allison, K. NATURE PUBLISHING GROUP. 2018: 48

  View details for Web of Science ID 000429308600139

• Surgical implications and variability in the use of the flat epithelial atypia diagnosis on breast biopsy specimens. Breast Samples, L. S., Rendi, M. H., Frederick, P. D., Allison, K. H., Nelson, H. D., Morgan, T. R., Weaver, D. L., Elmore, J. G. 2017; 34: 34-43

  Abstract

  Flat epithelial atypia (FEA) is a relatively new diagnostic term with uncertain clinical significance for surgical management. Any implied risk of invasive breast cancer associated with FEA is contingent upon diagnostic reproducibility, yet little is known regarding its use.Pathologists in the Breast Pathology Study interpreted one of four 60-case test sets, one slide per case, constructed from 240 breast biopsy specimens. An electronic data form with standardized diagnostic categories was used; participants were instructed to indicate all diagnoses present. We assessed participants' use of FEA as a diagnostic term within: 1) each test set; 2) 72 cases classified by reference as benign without FEA; and 3) six cases classified by reference as FEA. 115 pathologists participated, providing 6900 total independent assessments.Notation of FEA ranged from 0% to 35% of the cases interpreted, with most pathologists noting FEA on 4 or more test cases. At least one participant noted FEA in 34 of the 72 benign non-FEA cases. For the 6 reference FEA cases, participant agreement with the case reference FEA diagnosis ranged from 17% to 52%; diagnoses noted by participating pathologists for these FEA cases included columnar cell hyperplasia, usual ductal hyperplasia, atypical lobular hyperplasia, and atypical ductal hyperplasia.We observed wide variation in the diagnosis of FEA among U.S. pathologists. This suggests that perceptions of diagnostic criteria and any implied risk associated with FEA may also vary. Surgical excision following a core biopsy diagnosis of FEA should be reconsidered and studied further.

  View details for DOI 10.1016/j.breast.2017.04.004

  View details for PubMedID 28475933

• 'Non-classical' HER2 FISH results in breast cancer: a multi-institutional study MODERN PATHOLOGY Ballard, M., Jalikis, F., Krings, G., Schmidt, R. A., Chen, Y., Rendi, M. H., Dintzis, S. M., Jensen, K. C., West, R. B., Sibley, R. K., Troxell, M. L., Allison, K. H. 2017; 30 (2): 227-235

  Abstract

  The 2013 CAP/ASCO HER2 Testing Guidelines Update modified HER2 FISH categories such that some cases with 'monosomy', 'co-amplification/polysomy', low-level increased HER2 signals or clustered heterogeneity now are considered amplified or equivocal. This study examines the frequency and clinico-pathologic characteristics of breast cancers with equivocal or 'non-classical' HER2 FISH results. Breast cancers (2001-2014) with HER2 FISH results, HER2 immunohistochemistry, ER, grade, and age from three institutions (Stanford, UCSF, UWMC) were collected. HER2 FISH was interpreted using the updated recommendations. Amplified cases with non-classical results were grouped into the following categories: (1) 'monosomy' (ratio ≥2.0, mean HER2/cell<4.0); (2) 'co-amplified' (ratio<2.0, mean HER2/cell ≥6.0); (3) 'low amplified' (ratio ≥2.0, mean HER2/cell 4.0-5.9). Heterogeneous cases with clustered HER2-positive cells were also included. Of 8068 cases, 5.2% were equivocal and 4.6% had a 'non-classical' HER2 amplified result; 1.4% 'monosomy', 0.8% 'co-amplified', 2.1% 'low amplified', and 0.3% clustered heterogeneity. These cancers had a high frequency of ER positive (80.4%), Nottingham grade 3 (52.1%) results. The highest percentage of grade 3 cancers (66.7%) and positive HER2 immunohistochemistry (31.7%) was in the 'co-amplified' group. The 'monosomy' group had the highest percent grade 1 cancers (13.3%) and was most frequently HER2 immunohistochemistry negative (30.1%). Equivocal cases had very similar characteristics to the 'low-amplified' category. Cases with non-classical HER2 amplification or equivocal results are typically ER positive, higher grade cancers. 'Co-amplified' cases have the highest frequencies of aggressive characteristics and 'monosomy' cases the highest frequencies of lower risk features. With little clinical outcomes data currently available on these non-classical HER2 results, these results support the current classification scheme for HER2 FISH, with case-by-case correlation with additional clinical-pathologic factors when evaluating whether to offer HER2-targeted therapies in these non-classical cases.Modern Pathology advance online publication, 14 October 2016; doi:10.1038/modpathol.2016.175.

  View details for DOI 10.1038/modpathol.2016.175

  View details for Web of Science ID 000393257400007

• Comparison of Breast Carcinoma Nottingham Grading by Glass Slides versus Digital Whole Slide Images: Variability Increases Using Digital Format Davidson, T. M., Rendi, M. H., Frederick, P. D., Onega, T., Allison, K. H., Mercan, E., Brunye, T. T., Shapiro, L. G., Weaver, D. L., Elmore, J. G. NATURE PUBLISHING GROUP. 2017: 505A

  View details for Web of Science ID 000393724402513

• Comparison of Breast Carcinoma Nottingham Grading by Glass Slides versus Digital Whole Slide Images: Variability Increases Using Digital Format Davidson, T. M., Rendi, M. H., Frederick, P. D., Onega, T., Allison, K. H., Mercan, E., Brunye, T. T., Shapiro, L. G., Weaver, D. L., Elmore, J. G. NATURE PUBLISHING GROUP. 2017: 505A

  View details for Web of Science ID 000394467302603

• 'Non-classical' HER2 FISH results in breast cancer: a multi-institutional study. Modern pathology Ballard, M., Jalikis, F., Krings, G., Schmidt, R. A., Chen, Y., Rendi, M. H., Dintzis, S. M., Jensen, K. C., West, R. B., Sibley, R. K., Troxell, M. L., Allison, K. H. 2016

  Abstract

  The 2013 CAP/ASCO HER2 Testing Guidelines Update modified HER2 FISH categories such that some cases with 'monosomy', 'co-amplification/polysomy', low-level increased HER2 signals or clustered heterogeneity now are considered amplified or equivocal. This study examines the frequency and clinico-pathologic characteristics of breast cancers with equivocal or 'non-classical' HER2 FISH results. Breast cancers (2001-2014) with HER2 FISH results, HER2 immunohistochemistry, ER, grade, and age from three institutions (Stanford, UCSF, UWMC) were collected. HER2 FISH was interpreted using the updated recommendations. Amplified cases with non-classical results were grouped into the following categories: (1) 'monosomy' (ratio ≥2.0, mean HER2/cell<4.0); (2) 'co-amplified' (ratio<2.0, mean HER2/cell ≥6.0); (3) 'low amplified' (ratio ≥2.0, mean HER2/cell 4.0-5.9). Heterogeneous cases with clustered HER2-positive cells were also included. Of 8068 cases, 5.2% were equivocal and 4.6% had a 'non-classical' HER2 amplified result; 1.4% 'monosomy', 0.8% 'co-amplified', 2.1% 'low amplified', and 0.3% clustered heterogeneity. These cancers had a high frequency of ER positive (80.4%), Nottingham grade 3 (52.1%) results. The highest percentage of grade 3 cancers (66.7%) and positive HER2 immunohistochemistry (31.7%) was in the 'co-amplified' group. The 'monosomy' group had the highest percent grade 1 cancers (13.3%) and was most frequently HER2 immunohistochemistry negative (30.1%). Equivocal cases had very similar characteristics to the 'low-amplified' category. Cases with non-classical HER2 amplification or equivocal results are typically ER positive, higher grade cancers. 'Co-amplified' cases have the highest frequencies of aggressive characteristics and 'monosomy' cases the highest frequencies of lower risk features. With little clinical outcomes data currently available on these non-classical HER2 results, these results support the current classification scheme for HER2 FISH, with case-by-case correlation with additional clinical-pathologic factors when evaluating whether to offer HER2-targeted therapies in these non-classical cases.Modern Pathology advance online publication, 14 October 2016; doi:10.1038/modpathol.2016.175.

  View details for DOI 10.1038/modpathol.2016.175

  View details for PubMedID 27739440

• Histological features associated with diagnostic agreement in atypical ductal hyperplasia of the breast: illustrative cases from the B-Path study. Histopathology Allison, K. H., Rendi, M. H., Peacock, S., Morgan, T., Elmore, J. G., Weaver, D. L. 2016

  Abstract

  This study examined the case-specific characteristics associated with interobserver diagnostic agreement in atypical ductal hyperplasia (ADH) of the breast.Seventy-two test set cases with a consensus diagnosis of ADH from the B-Path study were evaluated. Cases were scored for 17 histological features, which were then correlated with the participant agreement with the consensus ADH diagnosis. Participating pathologists' perceptions of case difficulty, borderline features or whether they would obtain a second opinion were also examined for associations with agreement. Of the 2070 participant interpretations of the 72 consensus ADH cases, 48% were scored by participants as difficult and 45% as borderline between two diagnoses; the presence of both of these features was significantly associated with increased agreement (P < 0.001). A second opinion would have been obtained in 80% of interpretations, and this was associated with increased agreement (P < 0.001). Diagnostic agreement ranged from 10% to 89% on a case-by-case basis. Cases with papillary lesions, cribriform architecture and obvious cytological monotony were associated with higher agreement. Lower agreement rates were associated with solid or micropapillary architecture, borderline cytological monotony, or cases without a diagnostic area that was obvious on low power.The results of this study suggest that pathologists frequently recognize the challenge of ADH cases, with some cases being more prone to diagnostic variability. In addition, there are specific histological features associated with diagnostic agreement on ADH cases. Multiple example images from cases in this test set are provided to serve as educational illustrations of these challenges.

  View details for DOI 10.1111/his.13035

  View details for PubMedID 27398812

  View details for PubMedCentralID PMC5115948

• Characterization of Breast Cancers With Equivocal and Non-Classical HER2 FISH Results - A Multi-Institutional Study Ballard, M., Jalikis, F., Krings, G., Schmidt, R., Chen, Y., Rendi, M., Dintzis, S. M., Jensen, K., West, R., Sibley, R., Allison, K. NATURE PUBLISHING GROUP. 2015: 35A

  View details for Web of Science ID 000348948000129

• Histologic Features Associated With Diagnostic Disagreement in Atypical Ductal Hyperplasia of the Breast: Results From the B-Path Study Allison, K., Rendi, M., Weaver, D., Elmore, J. NATURE PUBLISHING GROUP. 2015: 32A

  View details for Web of Science ID 000348948000120

• Histologic Features Associated With Diagnostic Disagreement in Atypical Ductal Hyperplasia of the Breast: Results From the B-Path Study Allison, K., Rendi, M., Weaver, D., Elmore, J. SPRINGERNATURE. 2015: 32A

  View details for Web of Science ID 000349502200120

• Characterization of Breast Cancers With Equivocal and Non-Classical HER2 FISH Results - A Multi-Institutional Study Ballard, M., Jalikis, F., Krings, G., Schmidt, R., Chen, Y., Rendi, M., Dintzis, S. M., Jensen, K., West, R., Sibley, R., Allison, K. NATURE PUBLISHING GROUP. 2015: 35A

  View details for Web of Science ID 000349502200129

• A framework for evaluating diagnostic discordance in pathology discovered during research studies. Archives of pathology & laboratory medicine Feng, S., Weaver, D. L., Carney, P. A., M Reisch, L., M Geller, B., Goodwin, A., Rendi, M. H., Onega, T., Allison, K. H., Tosteson, A. N., Nelson, H. D., Longton, G., Pepe, M., Elmore, J. G. 2014; 138 (7): 955-961

  Abstract

  Little is known about the frequency of discordant diagnoses identified during research.To describe diagnostic discordance identified during research and apply a newly designed research framework for investigating discordance.Breast biopsy cases (N = 407) from registries in Vermont and New Hampshire were independently reviewed by a breast pathology expert. The following research framework was developed to assess those cases: (1) compare the expert review and study database diagnoses, (2) determine the clinical significance of diagnostic discordance, (3) identify and correct data errors and verify the existence of true diagnostic discrepancies, (4) consider the impact of borderline cases, and (5) determine the notification approach for verified disagreements.Initial overall discordance between the original diagnosis recorded in our research database and a breast pathology expert was 32.2% (131 of 407). This was reduced to less than 10% after following the 5-step research framework. Detailed review identified 12 cases (2.9%) with data errors (2 in the underlying pathology registry, 3 with incomplete slides sent for expert review, and 7 with data abstraction errors). After excluding the cases with data errors, 38 cases (9.6%) among the remaining 395 had clinically meaningful discordant diagnoses (κ = 0.82; SE, 0.04; 95% confidence interval, 0.76-0.87). Among these 38 cases, 20 (53%) were considered borderline between 2 diagnoses by either the original pathologist or the expert. We elected to notify the pathology registries and facilities regarding discordant diagnoses.Understanding the types and sources of diagnostic discordance uncovered in research studies may lead to improved scientific data and better patient care.

  View details for DOI 10.5858/arpa.2013-0263-OA

  View details for PubMedID 24978923