Digital morphometry illustrates a relationship between percentage of ductal carcinoma in-situ in breast needle core biopsy and margin status at lumpectomy

Abstract

Candidates for breast conserving surgery are selected based on imprecise variables and there is uncertainty surrounding the risk of complicated margins. Earlier estimates made with light microscopy revealed the correlation between percentage of needle core biopsy ductal carcinoma in-situ and positive lumpectomy margin status. We now study this association utilizing the precision of digital pathology. One hundred and seventy-nine lumpectomy specimens of pure ductal neoplasia were identified and their pathological, clinical, and radiological parameters retrieved. Each lumpectomy had a corresponding needle core biopsy for histological review. Virtually all cases exhibited a luminal A phenotype. Eighty-three cases showed positive margins and ninety-six cases, negative margins. We used the 2019 American College of Breast Surgeons Lumpectomy Consensus Guidelines to define margin status. For each case, by analog microscopy, we selected a single needle core biopsy slide with the greatest absolute quantity of carcinoma in-situ; each selected slide was submitted for digital whole slide imaging. Digital images were manually annotated for carcinoma in-situ, invasive carcinoma, stroma, and fat strictly based on morphology. Morphometric variables were compiled and compared to the corresponding lumpectomy margin status. Increases in percent ductal carcinoma in-situ are associated with greater odds of positive lumpectomy margins (P < 0.05). Above 10% carcinoma in-situ all but one case showed positive margins. This prediction was more precise compared to the association between pre-operative radiological studies and margin status, particularly in cases of pure ductal carcinoma in-situ. Our work suggests that needle core biopsy percentage of ductal carcinoma in-situ maybe clinically useful in assessing the risk of a positive lumpectomy margin in select patients. A larger, multi-institutional study can further elucidate if pathological reporting of needle core biopsies with pure ductal breast neoplasia should include a percentage needle core biopsy ductal carcinoma in-situ.

Keywords: Breast conserving surgery; DCIS; Digital pathology; Lumpectomy; Whole slide imaging.

Fig. 1

Sample image of a single annotated needle core biopsy with ductal carcinoma in-situ admixed with invasive ductal carcinoma (Green – ductal carcinoma in-situ, Red – invasive ductal carcinoma, Yellow – adipose tissue, Magenta – total surface area), 5×, hematoxylin and eosin. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

Grouped histogram of percentage needle core biopsy DCIS by positive margins (black) and negative margins (hatched).

Fig. 3

Logistic regression of probability of positive margins on percentage needle core biopsy DCIS (Black – DCIS alone, Aqua – DCIS with invasive ductal carcinoma). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 4

Grouped histogram of biopsied radiological lesion size by positive margins (black) and negative margins (hatched).

Fig. 5

Logistic regression of probability of positive margins on biopsied radiological lesion size (Black – DCIS alone, Aqua – DCIS with invasive ductal carcinoma). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)