Perivascular infiltration reflects subclinical lymph node metastasis in invasive lobular carcinoma

Invasive lobular carcinoma (ILC) is characterized by discohesive cells due to irreversible loss of E-cadherin expression and multiple satellites, where individual cell migration is evident without disturbance of the stroma. Neoplastic cells sometimes infiltrate the surrounding vessel in satellites. Here, we aimed to clarify the specific role of perivascular infiltration (PVI) and ameboid migration, characterized by nondisturbance of the background stromal structure, in ILCs. A total of 139 cases with ILC and 122 cases with invasive breast carcinoma of no special type (IBC-NST) were evaluated retrospectively. PVI was significantly more common in ILC than in IBC-NST (50% [70 of 139 cases] vs. 9% [11 of 122 cases], p < 0.001). ILC cases with PVI showed a larger pathological tumour size than clinical tumour size (p < 0.01), a higher frequency of pathological node status pN2-pN3 when limited to clinically node-negative cases (p < 0.01) and lower circularity of tumour morphology on imaging (p < 0.01) than ILC cases without PVI. In the pathological evaluation, the intensity and occupancy of tumour cells expressing phospho-myosin light chain 2, which is a hallmark of ameboid migration, were significantly higher in ILC cases with PVI than in those without PVI at the tumour margins (p < 0.05). ILC with PVI is associated with irregular, poorly defined tumour margins and lymph node metastasis without adenopathy, which is difficult to assess using imaging. PVI may be caused by ameboid migration, as shown by the positive expression of phospho-myosin light chain 2. The presence of PVI may be a predictor for clinically node-negative pN2-pN3 in ILC patients.