Invasive Micropapillary Breast Carcinoma

Abstract

Invasive micropapillary morphology is associated with clinically meaningful staging and outcome implications in patients with breast cancer. The characteristic micropapillary morphology is seen focally in the tumor in most cases. In contrast to other special subtypes of breast cancer, any proportion of invasive micropapillary growth confers to the tumor a “special” aggressive behaviour characterised by lymphovascular invasion, high propensity for lymph node metastases and high stage at presentation. At the molecular and immunohistochemical level, tumors with mixed invasive micropapillary and invasive carcinoma NST display striking similarities to those with pure invasive micropapillary carcinomas. Moreover, these tumors are classified in most cases in the category of luminal B molecular subtype. Invasive micropapillary carcinoma has been described in other organ systems, although less frequently as in breast. In the urinary tract, gastrointestinal tract, lungs and salivary glands, this tumor pattern is in general admixed with a more conventional tumor growth pattern, and same as in breast, presents as a locally advanced disease and is associated with an aggressive behaviour. To date there are few molecular studies performed on IMPCa of the breast. None of them shows characteristic genetic alteration that could explain the special morphology of the tumor or its aggressive course. In other terms, IMPCa is not defined by highly recurrent specific mutations or fusion genes. In few cases reported in the literature as well as in the study that we presented, hotspot point mutations of the PIK3CA gene, and the TP53 gene were identified however at a rate similar to that seen in invasive breast carcinoma NST. In addition we saw in one of our IMPCa cases a MET-T1010I germline mutation, which is usually very rare in breast cancer, occurring in 2% of patients with metastatic breast carcinoma. Because of the therapeutic consequences (with MET inhibitors) we suggest a more extensive testing of the MET gene in this aggressive type of breast cancer.