New Treatments for Breast Cancer 2
Papillary and Micropapillary
Papillary or micropapillary DCIS is a low- to moderate-grade subtype of intraductal carcinoma composed of a uniform population of cells that forms papillary extensions into the ductal spaces. These projections may coalesce to create an “arcuate” or “Roman bridge” pattern. This subtype is well-differentiated and is only rarely seen in conjunction with cellular necrosis.
Cribriform
The cribriform subtype is the most commonly encountered architectural pattern of DCIS and is identified by ductal epithelium organized into extracellular lumina, often creating a “lacy” appearance. The cells are usually of uniform size and shape with a large, centrally placed nucleus. Occasionally, the cribriform pattern may be associated with cellular necrosis, and the nuclear grade can range from well- to poorly differentiated.
Solid
The solid pattern of DCIS is characterized by complete obliteration of the ductal lumen by cellular proliferation. Although the cellular pattern is often monotonous, the tumor grade can range from very well-differentiated lesions to the more frequently seen high-grade neoplasms.
Comedocarcinoma
Comedocarcinoma has been shown to carry the worst prognosis among all architectural subtypes. It is identified by the presence of necrotic cellular debris within the ductal lumen. Although the presence of comedo histology was once thought to be the most important histologic determinant of prognosis, it has recently been realized that nuclear grade is probably the more important factor. In comedocarcinoma, the cells are typically large, with marked nuclear atypia, and calcifications are often present in association with the necrosis. Microinvasion, when present, is most likely to occur in conjunction with dense, high-grade, comedo-type lesions, and often necessitates treatment as a T1a invasive carcinoma.
Multicentricity in Ductal Carcinoma In Situ
Multicentricity is defined as disease present in more than one quadrant of the breast and was historically used to justify mastectomy for DCIS. Serial sub gross analysis of breast specimens following mastectomy for intraductal carcinomas has, however, demonstrated a low incidence of true multicentricity. Holland’s data showed that only 1 patient in 60 had multiple foci of tumor separated by 4 or more cm. The incidence of multifocal disease, defined as distinct tumor foci separated by at least 1 cm of intervening tissue, was somewhat higher, at 8%. Interestingly, the well-differentiated DCIS were more likely to demonstrate a multifocal distribution pattern than the poorly differentiated tumors (70% versus 10%). It has been postulated that this finding may reflect a field-defect phenomenon in well-differentiated DCIS that may not apply to poorly differentiated intraductal cancers or to invasive disease.
In the literature, estimates of multicentricity in DCIS range widely, from 2% to 78%. This discrepancy is attributable to differences in both the definition and mode of detection, with some authors defining multicentric disease as foci of tumor found in more than one quadrant, regardless of proximity to the index lesion. What has become clear, however, is that, contrary to initial dogma, treatment of DCIS with breast-conserving surgery can be oncologically appropriate in many patients, and higher grade intraductal lesions may be more amenable to lumpectomy because of their lower likelihood of multifocality. This question has not been specifically addressed in the large prospective randomized trials, which have excluded patients with either large or high-grade tumors. Some higher grade DCIS lesions, however, are still more optimally treated with mastectomy, as poorly differentiated intraductal cancers are often larger at diagnosis and frequently span more than one quadrant.