VIRTUAL TUMOR BOARD - A patient with newly diagnosed breast cancer found to have mosaic TP53 likely pathogenic variant

Sep 30, 2026

Uploaded by ahduag

A 36-year-old nulligravid woman with controlled eosinophilic esophagitis, asthma, and very dense fibrocystic breasts was evaluated after abnormal screening mammography. Imaging showed bilateral suspicious calcifications and a left-sided mass; biopsies identified high-grade DCIS in both breasts and a separate spindle cell tumor consistent with malignant phyllodes, triple-negative with elevated Ki-67. Germline testing found a TP53 likely pathogenic variant, prompting concern for Li-Fraumeni syndrome and evaluation of whether the variant was mosaic versus a true germline finding via multidisciplinary virtual tumor board review.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Case Overview

Imaging and Biopsy Findings

Genetic Evaluation and TP53 Variant Interpretation

Multidisciplinary Management Considerations

DOI: 10. 3322/caac.70034 VIRTUAL TUMOR BOARD A patient with newly diagnosed breast cancer found to have mosaic TP53 likely pathogenic variant Hetal D. Mistry MD 1,2 | MacKenzie R. Adams MD2,3 | Charu Taneja MD2,4 | Lauren J. Massingham MD 1,2,5 | Elizabeth H. Dibble MD2,6 | Kara L. Leonard MD, MS7 | Jesse Hart DO8 | Galina G. Lagos MD 1,2 | Mary Anne Fenton MD 1,2 1Department of Hematology/Oncology, Brown University Health Cancer Institute, Providence, Rhode Island, USA 2Warren Alpert School of Medicine, Brown University, Providence, Rhode Island, USA 3Department of Medicine, Brown University Health, Providence, Rhode Island, USA 4Department of Surgery, Brown University Health, Providence, Rhode Island, USA 5Division of Genetics and Genomics, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA 6Department of Radiology, Brown University Health, Providence, Rhode Island, USA 7Department of Radiation Oncology, Brown University Health, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA 8Department of Pathology and Laboratory Medicine, Brown University Health, Rhode Island Hospital, Warren Alpert School of Medicine, Brown University, Providence, Rhode Island, USA Correspondence Mary Anne Fenton, Department of Hematology/Oncology, Brown University Health Cancer Institute and Warren Alpert School of Medicine, 222 Richmond Street, Providence, RI 02903, USA. [Email:](Email: mfenton@brownhealth.org)[ mfenton@brownhealth.org](Email: mfenton@brownhealth.org) CASE OVERVIEW A 36-year-old, nulligravid woman with a history of controlled eosinophilic esophagitis, asthma, and dense fibrocystic breasts was referred to the Breast Health Center after abnormal screening mammography. She reported recent fatigue and intermittent diarrhea but had a negative colonoscopy and food allergy testing this year. Her family history was significant for a maternal grandmother with a question of uterine cancer, a maternal grandfather who died of renal cancer at age 62 years, a paternal grandmother who died of brain cancer at age 56 years, a paternal grandfather who died of brain cancer at age 80 years, and a history of premalignant changes in the esophagus in her father. She has never smoked tobacco and consumes zero to three drinks of alcohol weekly. She has been physically active in multiple sports, including biking and swimming, and played the cello. Mammography demonstrated extremely dense breast tissue with new calcifications in both breasts. Diagnostic mammography demonstrated indeterminate grouped calcifications spanning 19 mm in the right breast at 5 o'clock and 7 mm in the left breast 12 o'clock. She subsequently underwent stereotactic needle biopsies of both areas, which revealed right breast ductal carcinoma in situ (DCIS), nuclear grade 3, with 90% estrogen receptor (ER) expression; and left ductal carcinoma, nuclear grade 3, with 95% ER expression, 40% progesterone receptor (PR) expression, negative human epidermal growth factor receptor 2 (HER-2) status, and a Ki- 67 index of 40%. Within the left breast biopsy there was an absence of myoepithelial cells, raising concern that the findings reflected an unusual type of invasive carcinoma. She then underwent bilateral breast magnetic resonance imaging (MRI), which revealed the known areas of DCIS in the bilateral breasts and also revealed a 1.0-cm mass inferior to the left breast DCIS at 12 o'clock that was considered suspicious. On subsequent ultrasound, it corresponded to an 8-mm mass in the left breast at 10 o'clock. A biopsy of the mass demonstrated a spindle cell tumor, favoring malignant phyllodes tumor with pleomorphic liposarcomatous differentiation that This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is no

FAQs

What abnormal findings led to the initial breast evaluation?

Abnormal screening mammography showed extremely dense breast tissue with new calcifications in both breasts, followed by diagnostic mammography demonstrating grouped indeterminate calcifications in the right and left breasts.

What did the biopsies show in both breasts?

The right breast biopsy revealed high-grade ductal carcinoma in situ (DCIS) with high estrogen receptor expression. The left breast biopsy showed high-grade ductal carcinoma features with high ER expression, progesterone receptor expression, negative HER-2, high Ki-67, and absence of myoepithelial cells, raising concern for an unusual invasive process.

Why was the TP53 likely pathogenic variant clinically important?

The identified TP53 likely pathogenic variant raised concern for Li-Fraumeni syndrome; however, determining the variant’s origin was essential because detection can result from clonal hematopoiesis, mosaicism, or a true germline finding.

Sep 30, 2026

Uploaded by ahduag