DCIS, cytokeratins, and the theory of the sick lobe

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.