Rapid assessment of breast tumor margins using deep ultraviolet fluorescence scanning microscopy.

Tongtong Lu,Tina Yen,Renee Fisher,Bing Yu,Mollie Patton,Taly Gilat Schmidt,Amanda Emmrich,Dong Hye Ye,Julie M Jorns,Todd Doehring

doi:10.1117/1.jbo.25.12.126501

Tongtong Lu, Tina Yen + Show 8 more

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https://doi.org/10.1117/1.jbo.25.12.126501

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Abstract

.Significance: Re-excision rates for women with invasive breast cancer undergoing breast conserving surgery (or lumpectomy) have decreased in the past decade but remain substantial. This is mainly due to the inability to assess the entire surface of an excised lumpectomy specimen efficiently and accurately during surgery.Aim: The goal of this study was to develop a deep-ultraviolet scanning fluorescence microscope (DUV-FSM) that can be used to accurately and rapidly detect cancer cells on the surface of excised breast tissue.Approach: A DUV-FSM was used to image the surfaces of 47 (31 malignant and 16 normal/benign) fresh breast tissue samples stained in propidium iodide and eosin Y solutions. A set of fluorescence images were obtained from each sample using low magnification () and fully automated scanning. The images were stitched to form a color image. Three nonmedical evaluators were trained to interpret and assess the fluorescence images. Nuclear–cytoplasm ratio (N/C) was calculated and used for tissue classification.Results: DUV-FSM images a breast sample with subcellular resolution at a speed of . Fluorescence images show excellent visual contrast in color, tissue texture, cell density, and shape between invasive carcinomas and their normal counterparts. Visual interpretation of fluorescence images by nonmedical evaluators was able to distinguish invasive carcinoma from normal samples with high sensitivity (97.62%) and specificity (92.86%). Using N/C alone was able to differentiate patch-level invasive carcinoma from normal breast tissues with reasonable sensitivity (81.5%) and specificity (78.5%).Conclusions: DUV-FSM achieved a good balance between imaging speed and spatial resolution with excellent contrast, which allows either visual or quantitative detection of invasive cancer cells on the surfaces of a breast surgical specimen.

Highlights

Breast cancer afflicts millions of women in the United States and worldwide, of whom about a half to two-thirds will undergo breast conserving surgery (BCS) or lumpectomy.[1,2] The goal of BCS is to completely remove the tumor with a narrow rim/margin of normal, unaffected breast tissue while preserving as much normal tissue as possible
We purposefully focused on detecting invasive cancer cells on sample surfaces based on the 2014 Society of Surgical Oncology (SSO) and American Society for Radiation Oncology (ASTRO) Guidelines that support “no tumor cells at the inked margin” are adequate for women with stage I/II invasive cancers who undergo BCS followed by whole-breast radiation.[47]
The study resulted in stitched Microscopy with UV surface excitation (MUSE) images and formalin-fixed paraffin-embedded (FFPE) hematoxylin and eosin (H&E) images obtained from 47 breast specimens

Summary

Introduction

Breast cancer afflicts millions of women in the United States and worldwide, of whom about a half to two-thirds will undergo breast conserving surgery (BCS) or lumpectomy.[1,2] The goal of BCS is to completely remove the tumor with a narrow rim/margin of normal, unaffected breast tissue while preserving as much normal tissue as possible. Radiologic examination of the resected specimen with two-dimensional (2D) mammography is largely available and rapid It has low sensitivity and variable accuracy compared to other techniques and does not improve re-excision rates.[13,14] Pilot studies evaluating intraoperative specimen radiograph using digital breast tomosynthesis may be promising (sensitivity 77% to 93% and specificity 78% to 98%), but it requires further investigation.[15,16] Frozen section analysis is an involved pathological technique that typically samples only a portion of the surgical margin, performs poorly on fatty breast tissue, and has variable false-negative rates.[17] In addition, this technique is extremely labor- and time-intensive, costly, requires on-site or telepathology, and significantly lengthens operating room (O.R.) time (20 to 30 min).[13] Cytologic imprint prep analysis by touch preparation or scrape preparation is less labor-intensive (about 13 min); this technique requires a specialized cytopathologist.[18]

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