Lobular cancerization in biopsy-diagnosed ductal carcinoma in situ (DCIS) of the breast: a detailed histopathological evaluation and reproducibility study

The role of lobular cancerization in ductal carcinoma in situ (DCIS) of the breast is poorly described to date. A precise definition is lacking. We explored the association between lobular cancerization in biopsy-diagnosed DCIS and different other histopathological features, as well as its predictive value for the upstaging risk to invasive breast carcinoma (IBC). Additionally, we evaluated its diagnostic reproducibility. The following morphological characteristics were evaluated quantitively or semi-quantitatively by two observers in 323 DCIS biopsies: nuclear grade, architecture, myxoid stroma, tumor-infiltrating lymphocytes, comedonecrosis, calcifications and lobular cancerization. Immunohistochemistry for estrogen receptor (ER), progesterone receptor (PR) and human epidermal grow factor receptor 2 (HER2) were assessed in accordance with the ASCO/CAP guidelines for IBC. Nine pathologists analyzed the presence or absence of lobular cancerization in 148 photographs of DCIS. Percentage agreement, Krippendorff’s alpha (KA) and Cohen’s kappa values were determined to objectify the interobserver variability. Twenty-nine percent (93 of 323) of DCIS biopsies showed lobular cancerization. Multivariate analysis demonstrated that DCIS with lobular cancerization presented significantly more often with myxoid stroma and HER2 non-3+ expression, occurred more frequently in younger patients (< 50 years), and presented significantly less often with comedonecrosis. Lobular cancerization in biopsy-diagnosed DCIS was not predictive for upstaging to IBC in the subsequent resection. The high interobserver variability indicated low diagnostic reproducibility: Kappa values ranged from -0.044 to 0.715 and KA was 0.3549. Lobular cancerization in biopsy-diagnosed DCIS seems of limited clinical relevance as it is age-dependent, poorly reproducible and not associated with upstaging to IBC.