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15. Limited Reporting of Histopathologic Details in a Multi-Institutional Academic Cohort of Phyllodes Tumors: Time for Standardization

Author

Rosenberger, Laura H, Quintana, Liza M, Thomas, Samantha M, Nimbkar, Suniti N, Hieken, Tina J, Ludwig, Kandice K, Jacobs, Lisa K, Miller, Megan E, Gallagher, Kristalyn K, Wong, Jasmine, Neuman, Heather B, Tseng, Jennifer, Hassinger, Taryn E, King, Tari A, Jakub, James W, Bentley, Rex C, and Schnitt, Stuart J

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Rare Diseases, Cancer, Clinical Research, Breast Neoplasms, Female, Humans, Margins of Excision, Phyllodes Tumor, Reference Standards, Stromal Cells, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundPhyllodes tumors are rare fibroepithelial neoplasms that are classified by tiered histopathologic features. While there are protocols for the reporting of cancer specimens, no standardized reporting protocol exists for phyllodes.MethodsWe performed an 11-institution contemporary review of phyllodes tumors. Granular histopathologic details were recorded, including the features specifically considered for phyllodes grade classification.ResultsOf 550 patients, median tumor size was 3.0 cm, 68.9% (n = 379) of tumors were benign, 19.6% (n = 108) were borderline, and 10.5% (n = 58) were malignant. All cases reported the final tumor size and grade classification. Complete pathologic reporting of all histopathologic features was present in 15.3% (n = 84) of cases, while an additional 35.6% (n = 196) were missing only one or two features in the report. Individual details regarding the degree of stromal cellularity was not reported in 53.5% (n = 294) of cases, degree of stromal atypia in 58.0% (n = 319) of cases, presence of stromal overgrowth in 56.2% (n = 309) of cases, stromal cell mitoses in 37.5% (n = 206) of cases, and tumor border in 54.2% (n = 298) of cases. The final margin status (negative vs. positive) was omitted in only 0.9% of cases, and the final negative margin width was specifically reported in 73.8% of cases. Reporting of details was similar across all sites.ConclusionIn this academic cohort of phyllodes tumors, one or more histopathologic features were frequently omitted from the pathology report. While all features were considered by the pathologist for grading, this limited reporting reflects a lack of reporting consensus. We recommend that standardized reporting in the form of a synoptic-style cancer protocol be implemented for phyllodes tumors, similar to other rare tumors.

Published
2021

17. Contemporary Multi-Institutional Cohort of 550 Cases of Phyllodes Tumors (2007-2017) Demonstrates a Need for More Individualized Margin Guidelines.

Author

Rosenberger, Laura H, Thomas, Samantha M, Nimbkar, Suniti N, Hieken, Tina J, Ludwig, Kandice K, Jacobs, Lisa K, Miller, Megan E, Gallagher, Kristalyn K, Wong, Jasmine, Neuman, Heather B, Tseng, Jennifer, Hassinger, Taryn E, King, Tari A, and Jakub, James W

Subjects
Cancer, Adult, Breast Neoplasms, Clinical Decision-Making, Female, Humans, Margins of Excision, Mastectomy, Middle Aged, Neoplasm Recurrence, Local, Neoplasm, Residual, Phyllodes Tumor, Practice Guidelines as Topic, Retrospective Studies, Risk Assessment, Risk Factors, Time Factors, Treatment Outcome, Tumor Burden, United States, Clinical Sciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

PurposePhyllodes tumors (PTs) are rare breast neoplasms, which have little granular data on margins. Current guidelines recommend ≥ 1 cm margins; however, recent data suggest narrower margins are sufficient, and for benign PT, a negative margin may not be necessary.MethodsWe performed an 11-institution contemporary (2007-2017) review of PT practices. Demographics, surgical, and histopathologic data were captured. Logistic regression was used to estimate the association of select covariates with local recurrence (LR).ResultsOf 550 PT patients, the majority underwent excisional biopsy (55.3%, n = 302/546) or lumpectomy (wide excision) (38.5%, n = 210/546). Median tumor size was 30 mm, 68.9% (n = 379) were benign, 19.6% (n = 108) borderline, and 10.5% (n = 58) malignant. Surgical margins were positive in 42% (n = 231) and negative in 57.3% (n = 311). A second operation was performed in 38.0% (n = 209) of the total cohort, including 51 patients with an initial negative margin (82.4% with < 2 mm), and 157 with an initial positive margin, with residual disease only found in six (2.9%). Notably, 32.0% (n = 74) of those with an initial positive margin did not undergo a second operation, among whom only 2.7% (n = 2) recurred. Recurrence occurred in 3.3% (n = 18) of the total cohort (n = 15 LR, n = 3 distant), at median follow-up of 36.7 months. LR (all PT grades) was not reduced with wider negative margin width (≥ 2 mm v < 2 mm: odds ratio [OR] = 0.39; 95% CI, 0.07 to 2.10; P = .27) or final margin status (positive v negative: OR = 0.96; 95% CI, 0.26 to 3.52; P = .96).ConclusionIn current practice, many patients are managed outside of current guidelines. For the entire cohort, a wider margin width was not associated with a reduced risk of LR. We do not recommend re-excision of a negative margin for benign PT, regardless of margin width, as a progressively wider surgical margin is unlikely to reduce LR.

Published
2021

18. Germline Genetic Mutations in a Multi-center Contemporary Cohort of 550 Phyllodes Tumors: An Opportunity for Expanded Multi-gene Panel Testing

Author

Rosenberger, Laura H, Thomas, Samantha M, Nimbkar, Suniti N, Hieken, Tina J, Ludwig, Kandice K, Jacobs, Lisa K, Miller, Megan E, Gallagher, Kristalyn K, Wong, Jasmine, Neuman, Heather B, Tseng, Jennifer, Hassinger, Taryn E, and Jakub, James W

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Genetic Testing, Prevention, Cancer, Clinical Research, Genetics, Breast Neoplasms, Cohort Studies, Female, Genetic Predisposition to Disease, Germ-Line Mutation, Humans, Phyllodes Tumor, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundA paucity of data exists regarding inherited mutations associated with phyllodes tumors (PT); however, some are reported (TP53, BRCA1, and RB1). A PT diagnosis does not meet NCCN criteria for testing, including within Li-Fraumeni Syndrome (TP53). We sought to determine the prevalence of mutations associated with PT.MethodsWe performed an 11-institution review of contemporary (2007-2017) PT practice. We recorded multigenerational family history and personal history of genetic testing. We identified patients meeting NCCN criteria for genetic evaluation. Logistic regression estimated the association of select covariates with likelihood of undergoing genetic testing.ResultsOf 550 PT patients, 59.8% (n = 329) had a close family history of cancer, and 34.0% (n = 112) had ≥ 3 family members affected. Only 6.2% (n = 34) underwent genetic testing, 38.2% (n = 13) of whom had only BRCA1/BRCA2 tested. Of 34 patients tested, 8.8% had a deleterious mutation (1 BRCA1, 2 TP53), and 5.9% had a BRCA2 VUS. Of women who had TP53 testing (N = 21), 9.5% had a mutation. Selection for testing was not associated with age (odds ratio [OR] 1.01, p = 0.55) or PT size (p = 0.12) but was associated with grade (malignant vs. benign: OR 9.17, 95% CI 3.97-21.18) and meeting NCCN criteria (OR 3.43, 95% confidence interval 1.70-6.94). Notably, an additional 86 (15.6%) patients met NCCN criteria but had no genetic testing.ConclusionsVery few women with PT undergo germline testing; however, in those selected for testing, a deleterious mutation was identified in ~ 10%. Multigene testing of a PT cohort would present an opportunity to discover the true incidence of germline mutations in PT patients.

Published
2020

25. Genomic landscape of malignant phyllodes tumors reveals multiple targetable opportunities.

Author

Rosenberger, Laura H, Riedel, Richard F, Diego, Emilia J, Nash, Amanda L, Grilley-Olson, Juneko E, Danziger, Natalie A, Sokol, Ethan S, Ross, Jeffrey S, and Sammons, Sarah L

Subjects
BREAST tumors, IMMUNOTHERAPY, FISHER exact test, TUMOR markers, CANCER patients, DESCRIPTIVE statistics, GENE expression profiling, GENETIC mutation, CASE studies
Abstract

Background Malignant phyllodes tumors (MPT) are rare fibroepithelial breast cancers with no known effective systemic therapy; metastatic progression portends a dismal prognosis. We sought to describe the genomic landscape of MPTs through genomic profiling and immunotherapeutic biomarker analysis. Materials and methods Cases of sequenced MPT were identified from a Clinical Laboratory Improvement Amendments-certified, College of American Pathologists-accredited laboratory (Foundation Medicine). All cases underwent genomic profiling using adaptor ligation-based, next-generation sequencing assay of 324 genes. Tumor agnostic immunotherapy biomarkers, microsatellite instability, tumor mutational burden (TMB), and programmed death-ligand 1 (PD-L1) expression were evaluated. Fisher's Exact Tests and analysis of variance were used to test for differences between groups and for continuous variables as appropriate. Results Of 135 MPT cases identified; 94 (69.6%) were localized/locally recurrent and 41 (30.4%) were metastatic. Median age was 54 years (range 14-86). The median TMB was 2.5 mut/Mb and 3 were TMB-high (≥10 mut/Mb). 21.4% were PD-L1+ via Dako 22C3 assay (CPS ≥1). Most commonly altered genes included TERT- promoter (69.7%) , CDKN2A (45.9%), TP53 (37.8%), NF1 (35.6%), CDKN2B (33.3%), MED12 (28.9%), MTAP (27.7%), KMT2D (22.2%), PIK3CA (20.0%), PTEN (18.5%), and RB1 (18.5%). Several tumors harboring genomic alterations with US Food and Drug Administration-approved indications in other tumor types were found including NF1 , PIK3CA, EGFR Exon 19/20 insertions, and BRAF V600E mutations. Conclusions In the largest genomic evaluation of MPT to date, multiple clinically actionable mutations were found. Routine sequencing of metastatic MPT may provide additional information to guide treatment decisions and clinical trial enrollment. [ABSTRACT FROM AUTHOR]

Published
2024
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26. Breast Surgery

Author

Greenup, Rachel Adams, Rosenberger, Laura H., Kao, Lillian, Series Editor, Chen, Herbert, Series Editor, Wang, Tracy S., editor, and Beck, Adam W., editor

Published
2020
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30. The Incidence of Adjacent Synchronous Invasive Carcinoma and/or Ductal Carcinoma In Situ in Patients with Intraductal Papilloma without Atypia on Core Biopsy: Results from a Prospective Multi-Institutional Registry (TBCRC 034)

Author

Nakhlis, Faina, Baker, Gabrielle M., Pilewskie, Melissa, Gelman, Rebecca, Calvillo, Katherina Z., Ludwig, Kandice, McAuliffe, Priscilla F., Willey, Shawna, Rosenberger, Laura H., Parker, Catherine, Gallagher, Kristalyn, Jacobs, Lisa, Feldman, Sheldon, Lange, Paulina, DeSantis, Stephen D., Schnitt, Stuart J., and King, Tari A.

Published
2021
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33. Relapsing malignant phyllodes tumour presenting as isolated acrometastases.

Author

Reason, Ellery H., Aiduk, Michael D., Eward, William C., and Rosenberger, Laura H.

Abstract

Malignant phyllodes tumours (PTs) are aggressive neoplasms with high rates of local recurrence and distant metastasis. With no known effective chemotherapy and no approved targeted therapy in the setting of metastatic disease, prognosis is limited with an often-relapsing course of disease. We report a case of a woman in her late 30s with a diagnosis of recurrent metastatic malignant PT who was found to have acrometastases of the malignant PT to the right distal index and small digits. We emphasise the potential for atypical patterns of metastases in patients with malignant PT and the need to recognise acrometastasis as an unusual but morbid manifestation of disease. Given the high growth rate of malignant PTs, the lack of systemic treatment options, and the ensuing distress for patients, prompt diagnosis and early intervention is crucial. [ABSTRACT FROM AUTHOR]

Published
2024
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44. Omission of Axillary Dissection Following Nodal Downstaging With Neoadjuvant Chemotherapy.

Author

Montagna, Giacomo, Mrdutt, Mary M., Sun, Susie X., Hlavin, Callie, Diego, Emilia J., Wong, Stephanie M., Barrio, Andrea V., van den Bruele, Astrid Botty, Cabioglu, Neslihan, Sevilimedu, Varadan, Rosenberger, Laura H., Hwang, E. Shelley, Ingham, Abigail, Papassotiropoulos, Bärbel, Nguyen-Sträuli, Bich Doan, Kurzeder, Christian, Aybar, Danilo Díaz, Vorburger, Denise, Matlac, Dieter Michael, and Ostapenko, Edvin

Published
2024
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48. ASO Visual Abstract: Limited Reporting of Histopathologic Details in a Multi-Institutional Academic Cohort of Phyllodes Tumors: Time for Standardization

Author

Rosenberger, Laura H., Quintana, Liza M., Thomas, Samantha M., Nimbkar, Suniti N., Hieken, Tina J., Ludwig, Kandice K., Jacobs, Lisa K., Miller, Megan E., Gallagher, Kristalyn K., Wong, Jasmine, Neuman, Heather B., Tseng, Jennifer, Hassinger, Taryn E., King, Tari A., Jakub, James W., Bentley, Rex C., and Schnitt, Stuart J.

Published
2021
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