Imaging of lumpectomy surface with large field-of-view confocal laser scanning microscopy 'Histolog® scanner' for breast margin assessment in comparison with conventional specimen radiography

Abstract

Purpose: The Histolog® Scanner (SamanTree Medical SA, Lausanne, Switzerland) is a large field-of-view confocal laser scanning microscope designed to allow intraoperative margin assessment by the production of histological images ready for assessment in the operating room. We evaluated the feasibility and the performance of the Histolog® Scanner (HS) to correctly identify infiltrated margins in clinical practice of lumpectomy specimens. It was extrapolated if the utilization of the HS has the potential to reduce infiltrated margins and therefore reduce re-operation rates in patients undergoing breast conserving surgery (BCS) due to a primarily diagnosed breast cancer including ductal carcinoma in situ.

Methods: This is a single-center, prospective, non-interventional, diagnostic pilot study including 50 consecutive patients receiving BCS. The complete surface of the specimen was scanned using the HS intraoperatively. The surgery and the intraoperative margin assessment of the specimen was performed according to the clinical routine consisting of conventional specimen radiography as well as the clinical impression of the surgeon. Three surgeons and an experienced pathologist assessed the scans produced by the HS for cancer cells on the surface. The potential of the HS to correctly identify involved margins was compared to the results of the conventional specimen radiography alone as well as the clinical routine. The histopathological report served as the gold standard.

Results: 50 specimens corresponding to 300 surfaces were scanned by the HS. The mean sensitivity of the surgeons to identify involved margins with the HS was 37.5% ± 5.6%, the specificity was 75.2% ± 13.0%. The assessment of resection margins by the pathologist resulted in a sensitivity of 37.5% and a specificity of 81.0%, while the local clinical routine resulted in a sensitivity of 37.5% and a specificity of 78.2%.

Conclusion: Acquisition of high-resolution histological images using the HS was feasible in clinical practice. Sensitivity and specificity were comparable to clinical routine. With more specific training and experience on image interpretation and acquisition, the HS may have the potential to enable more accuracy in the margin assessment of BCS specimens.

Keywords: Breast cancer; Breast conserving surgery; Confocal microscopy; Conventional specimen radiography; Fresh tissue imaging; Margin assessment.

Fig. 1

Simplified explanation of a specimen's orientation.

Fig. 2

Histolog®Scanner (HS) setting in the operating room a setting of the HS in the operation room. b acquisition of a digital histopathological image of one surface of a specimen.

Fig. 3

Images produced by the Histolog®Scanner of non-cancerous breast lumpectomy margins a Surface of the lumpectomy is presenting artifacts affecting overall image quality and limiting proportion of the tissue in contact with the sensor. These artifacts are supposedly due to use of electric knife and to a superficial drying of the specimen surface. Insert: high magnification of the artifacts that are masking cellular details useful for identification. b Surface of the lumpectomy is presenting no artifacts with good image quality and good contact. Insert: high magnification of a benign lobule, where acini and small ducts could be appreciated. Scale bars in the main images and in the inserts represent 2 mm and 250 μm respectively.

Fig. 4

Images produced by the Histolog®Scanner of cancerous breast lumpectomy margins Main images are showing cancerous areas encircled in red color: cancerous areas are often easily detected because they appear darker than both fibrous stroma and adipose tissue, due to a higher content of nuclei. Inserts: high magnification of the lesions. a ductal carcinoma in situ: one solid nodule with well-defined border is recognizable in the fat, composed of neoplastic cells with enlarged nuclei. b, c invasive carcinoma: normal lobular architecture is not present, whereas a nodule composed of haphazardly distributed cords and large aggregates of neoplastic cells is shown (b), and small nests of neoplastic cells infiltrating into connective tissue are recognizable (c) Scale bars in the main images and in the inserts represent 2 mm and 250 μm respectively. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)