DCIS, cytokeratins, and the theory of the sick lobe

Abstract

We postulate that ductal carcinoma in situ (DCIS), and consequently breast carcinoma in general, is a lobar disease, as the simultaneously or asynchronously appearing, often multiple, in situ tumor foci are localized within a single lobe. Although the whole lobe is sick, carrying some form of genetic instability, the malignant transformation of the epithelial cells may appear localized to a part or different parts of the sick lobe at the same time or with varying time difference. It may be confined to terminal ductal lobular units (TDLUs), to ducts or both. The malignant transformation is often associated with aberrant branching and/or aberrant lobularization within the sick lobe. Involvement of a single individual TDLU or of a group of adjacent TDLUs generates a unifocal lesion. Multifocal lesions appear if distant TDLUs are involved. Diffuse growth pattern in DCIS indicates involvement of the larger ducts. The extent of the involved area in multifocal or diffuse cases varies considerably. Diffuse growth pattern with or without evidence of aberrant arborisation within the sick lobe seems to characterize a subgroup of DCIS with unfavourable prognosis. In this paper, we discuss the anatomical, embryological and pathological background of the theory of the sick lobe and present supporting evidence from modern radiological breast imaging, long-term follow-up studies and from our own series of 108 DCIS cases.

Clinical relevance of the distribution of the lesions in 500 consecutive breast cancer cases documented in large‐format histologic sections

“…Defining the extent by the dimensions of the involved area also proved to be a sensitive approach in our previous study regarding in situ breast carcinomas, showing a nearly 10-fold difference in the local recurrence rate between extensive (area > 2 cm) and nonextensive ductal in situ breast carcinomas. 13 Our hypothesis, the theory of the sick lobe, 13 defines breast carcinoma as a lobar disease originating in a single breast lobe in the majority of cases. In situ carcinoma may appear in the ducts and the lobules of the sick lobe simultaneously in large areas or with time differences involving small parts of it.…”

“…Despite the well-recognized importance of the distribution of cancer within the breast for optimizing breast-conserving surgery, 4 there are conflicting results in the related literature regarding the significance of breast cancer multifocality, depending on the methodologic limitations and the various definitions used lacking a wide international consensus. [1][2][3][5][6][7][8][9][10][11][12][13][14] The diffuse growth pattern of some highly aggressive breast carcinomas 10 remains mainly unrecognized.…”

“…Extensive lesions recur significantly more often that those of limited extent, both with regard to invasive 11 and in situ tumors. 12,13 The routine use of large-format histologic sections in diagnostic breast pathology allows the observer to properly document and demonstrate the extent and distribution of the lesions in a case of malignant tumors and to compare these parameters with the surgical margins. [15][16][17] Detailed radiologic/ pathologic correlation in the workup of the specimen further enhances the sensitivity of this method.…”

“…When involving the larger ducts and not (only) the TDLUs, in situ carcinoma forms a diffuse network of tubes, which are hard to delineate and measure. 13,14 This type of tumoral growth frequently characterizes high-grade ductal cancer in situ, which has been identified as a negative morphologic prognostic parameter with survival as endpoint. [35][36][37] The current study appears to be unique in its detailed analysis of the growth pattern and demonstration of the heterogeneity of tumoral growth in breast carcinomas, with 16 possible different combinations of the distribution of in situ and invasive tumor components.…”

Micropapillary ductal carcinoma in situ of the breast: an inter-institutional study

“…Another possibility for the wide spreading of this lesion is that micropapillary structures may develop simultaneously on a large area of a breast lobe. 40 The extensive nature of the micropapillary in situ cancer was first reported by Patchefsky et al 22 and confirmed by other authors. 20,21 Bellamy et al 32 described that micropapillary growth, more likely than other growth patterns of in situ carcinoma, involves multiple quadrants, regardless of nuclear grade or necrosis.…”