Axillary lymph node status in unifocal, multifocal, and diffuse breast carcinomas: differences are related to macrometastatic disease.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: The significantly increased lymph node positivity rates in multifocal and diffuse invasive breast carcinomas results from large-volume macrometastatic disease.