Ductal Carcinoma in Situ: State-of-the-Art Review

Abstract

Ductal carcinoma in situ (DCIS) is a nonobligate precursor of invasive cancer, and its detection, diagnosis, and management are controversial. DCIS incidence grew with the expansion of screening mammography programs in the 1980s and 1990s, and DCIS is viewed as a major driver of overdiagnosis and overtreatment. For pathologists, the diagnosis and classification of DCIS is challenging due to undersampling and interobserver variability. Understanding the progression from normal breast tissue to DCIS and, ultimately, to invasive cancer is limited by a paucity of natural history data with multiple proposed evolutionary models of DCIS initiation and progression. Although radiologists are familiar with the classic presentation of DCIS as asymptomatic calcifications at mammography, the expanded pool of modalities, advanced imaging techniques, and image analytics have identified multiple potential biomarkers of histopathologic characteristics and prognosis. Finally, there is growing interest in the nonsurgical management of DCIS, including active surveillance, to reduce overtreatment and provide patients with more personalized management options. However, current biomarkers are not adept at enabling identification of occult invasive disease at biopsy or accurately predicting the risk of progression to invasive disease. Several active surveillance trials are ongoing and are expected to better identify women with low-risk DCIS who may avoid surgery.

Graphical abstract

Figure 1:

Photomicrograph (hematoxylin-eosin stain; low-power view) shows low-grade ductal carcinoma in situ with cribriform architecture. If only the boxed area is visible to the pathologist, then the diagnosis would be atypical ductal hyperplasia because fewer than two involved ducts are visible and the extent of disease is less than 2 mm.

Figure 2:

Evolutionary models of invasion in ductal carcinoma in situ (DCIS). (A) Independent evolution model shows DCIS (clones A and B) and invasive cancer (C) evolving from separate normal cells (N₁ and N₂). (B) Evolutionary bottleneck model shows DCIS evolving from a single ancestral cell (N₁) and a single clone (C) evolves to invade and expand to form the invasive carcinoma. (C) Multiclonal invasion model shows DCIS evolving from a single ancestral cell (N₁), and then multiple clones (A, B, and C) each evolve to form invasive cancer and comingle. Reprinted, with permission, from reference .

Figure 3:

Images in three different patients demonstrate classic imaging appearance of ductal carcinoma in situ (DCIS). (A) Mammogram shows DCIS as fine pleomorphic calcifications. (B) US scan shows DCIS as hypoechoic irregular mass without posterior features (arrow). (C) MRI scan shows DCIS as nonmass enhancement in a segmental distribution (triangle).

Figure 4:

Images in a patient with pure ductal carcinoma in situ. (A) Low-energy mammogram shows an asymmetry (arrow). (B, C) Contrast-enhanced mammograms obtained in early (B) and late (C) phases show nonmass enhancement (arrow). Reprinted, with permission, from reference .