Abstract
Simple SummaryOvertreatment which means providing a patient with unnecessary medical intervention has recently become the center of attention in breast diseases. One of these lesions is low-risk ductal carcinoma in situ (DCIS), for which the standard of treatment is wide local excision/mastectomy, with or without radiation therapy, with or without hormonal therapy. There are many worldwide ongoing clinical trials aiming to de-escalate this therapy by examining whether active surveillance (AS) is sufficient. These trials vary in pathology inclusion and exclusion criteria. There is lack of consensus on the definition of low-risk DCIS, in particular the overlap with atypical ductal hyperplasia (ADH), DCIS grading, and lack of definition of comedonecrosis. This review discusses AS trial from pathology standpoint and provides few recommendations.Intraepithelial mammary ductal neoplasia is a spectrum of disease that varies from atypical ductal hyperplasia (ADH), low-grade (LG), intermediate-grade (IG), to high-grade (HG) ductal carcinoma in situ (DCIS). While ADH has the lowest prognostic significance, HG-DCIS carries the highest risk. Due to widely used screening mammography, the number of intraepithelial mammary ductal neoplastic lesions has increased. The consequence of this practice is the increase in the number of patients who are overdiagnosed and, therefore, overtreated. The active surveillance (AS) trials are initiated to separate lesions that require active treatment from those that can be safely monitored and only be treated when they develop a change in the clinical/radiologic characteristics. At the same time, the natural history of these lesions can be evaluated. This review aims to evaluate ADH/DCIS as a spectrum of intraductal neoplastic disease (risk and histomorphology); examine the controversies of distinguishing ADH vs. DCIS and the grading of DCIS; review the upgrading for both ADH and DCIS with emphasis on the variation of methods of detection and the definitions of upgrading; and evaluate the impact of all these variables on the AS trials.
Highlights
Introduction iationsAtypical ductal hyperplasia (ADH) belongs to the low-grade pathway of estrogen receptor (ER)-positive/luminal type invasive breast carcinoma [1], and it is one of the earliest steps in this pathway [2]
atypical ductal hyperplasia (ADH) bordering bordering on ductal neoplasia arranged in in cribriform pattern involving more than two spaces and measuring slightly more than 2 mm (H&E, cribriform pattern involving more than two spaces and measuring slightly more than 2 mm (H&E, scanning magnification); (B) Similar finding but with larger size, some pathologists may designate scanning magnification); (B) Similar finding but with larger size, some pathologists may designate this as Ductal carcinoma in situ (DCIS) (H&E, scanning magnification)
(A)LG-DCIS: LG-DCIS:small smallmonophonic monophonic cells arranged a cribriform patFigure cells arranged in aincribriform pattern tern (H&E, 10×); (B) IG-DCIS: ductal cells with moderate variability in size arranged in a cribriform (H&E, 10×); (B) IG-DCIS: ductal cells with moderate variability in size arranged in a cribriform patpattern (H&E 20×); (C) HG-DCIS: Marked nuclear pleomorphism with many mitotic figures, apoptern (H&E 20×); (C) HG-DCIS: Marked nuclear pleomorphism with many mitotic figures, apoptotic totic bodies and central necrosis arranged in a solid growth pattern (H&E 20×)
Summary
There are at least four AS trials worldwide, including Comparison of Operative to Monitoring and Endocrine Therapy (COMET) in the United States [15], the low risk DCIS trial (LORIS) in United Kingdom [16], the “LOw Risk Dcis” (LORD) in the Netherlands [17], and LORETTA in Japan [18]. The COMET trial amended the inclusion criteria to add patients whose surgical resection margin was positive for DCIS, and patients with a diagnosis of ADH bordering on DCIS. They removed comedonecrosis as one of the exclusion criteria. Ipsilateral iBC-free percentage at 5 and Integrating clinical, imaging, morphological and molecular data to distinguish harmless from aggressive screen-detected
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