Axillary Lymph Node Status in Unifocal, Multifocal, and Diffuse Breast Carcinomas: Differences Are Related to Macrometastatic Disease

Abstract

Multifocality in breast carcinoma is associated with an increased propensity to metastasis. However, it is not clear whether this propensity manifests in the form of macrometastases or as presumably less-significant low-volume metastatic disease. A total of 948 cases of invasive breast carcinoma documented in large-format histology sections and assessed with detailed radiologic-pathologic correlation were categorized as unifocal, multifocal, or diffuse on the basis of the subgross distribution of the invasive component. Rates of macrometastases (>2 mm), micrometastases (0.2-2 mm), and isolated tumor cells (<0.2 mm) in these categories were compared. The influence of tumor size and histology grade on lymph node positivity rates was also tested. Macrometastases were present in 20.4% (112 of 550) of unifocal, 48.3% (172 of 356) of multifocal, and 61.9% (26 of 42) of diffuse cases (P < 0.0001). Among the macrometastatic cases, more than three nodes were involved in 18.9% (21 of 112) of unifocal, 35.5% (61 of 172) of multifocal, and 50.0% (13 of 26) of diffuse cases. The rates of micrometastases (5.1, 5.1, and 2.4% unifocal, multifocal, and diffuse, respectively) and isolated tumor cells (4.5, 3.7, and 2.4% unifocal, multifocal, and diffuse, respectively) were low and similar in all examined categories. The relative risk (RR) of having macrometastatic disease was approximately doubled (RR 2.3726, P < 0.0001) in multifocal and tripled (RR 3.0562, P < 0.0001) in diffuse compared to unifocal cases. The findings were similar for all size categories, tumor grade categories, and sentinel lymph nodes, as well as all examined lymph nodes. The significantly increased lymph node positivity rates in multifocal and diffuse invasive breast carcinomas results from large-volume macrometastatic disease.