Tumor histology in lymph vessels and lymph nodes for the accurate prediction of outcome among breast cancer patients treated with neoadjuvant chemotherapy

Abstract

The present study investigated fibrotic foci (FFs), the grading system for lymph vessel tumor emboli (LVTEs), and the histological characteristics of nodal metastatic tumors that were significantly associated with the outcomes of 115 patients with invasive ductal carcinoma (IDC) who had received neoadjuvant chemotherapy. We compared the outcome predictive power of FFs, the grading system for LVTEs, and the histological characteristics of metastatic tumors in lymph nodes with the well-known clinicopathological characteristics of tumor recurrence and tumor-related death in multivariate analyses. The presence of FFs, as assessed by a biopsy performed before neoadjuvant chemotherapy, significantly increased the hazard rates (HRs) for tumor-related death in all the cases and in cases with nodal metastasis. The grading system for LVTEs, which was assessed using surgical specimens obtained after neoadjuvant chemotherapy, was significantly associated with increasing hazard rates (HRs) for tumor recurrence and tumor-related death in all the cases and in cases with nodal metastasis. Moderate to severe stroma in nodal metastatic tumors and five or more mitotic figures in nodal metastatic tumors were significantly associated with elevated HRs for tumor recurrence and tumor-related death among all the cases. These results indicated that FFs, the grading system for LVTEs, and the histological characteristics of tumor cells in lymph nodes play important roles in predicting the tumor progression of IDCs of the breast in patients treated with neoadjuvant chemotherapy.

Figure 1

Histological characteristics of fibrotic foci (FFs), lymph vessel tumor emboli, and nodal metastatic tumors. (a) An FF measuring 8.4 × 6.2 mm is visible within the tumor (arrows) in a surgical specimen. The FF has the appearance of a scar‐like feature, and it is surrounded by invasive ductal carcinoma cells. The FF area consists of fibroblasts and collagen fibers arranged in a storiform pattern with tumor cell nests. (b) A core‐needle biopsy specimen shows an FF consisting of fibroblasts and collagen fibers in a storiform arrangement intermingled with invasive tumor cells (fibrosis grade 3). (c) One large lymph vessel tumor embolus and five lymph vessel tumor emboli are shown. A necrotic tumor focus is visible in the large lymph vessel tumor embolus. (d) Several apoptotic bodies and apoptotic tumor cells are visible (arrowheads), and six mitotic tumor cells (arrows) can be seen in the lymph vessel tumor embolus. The apoptotic bodies are small, variously shaped pyknotic bodies that resemble sesame seeds, and the apoptotic tumor cells were identified as tumor cells containing eosinophilic or amphophilic cytoplasm and irregularly shaped pyknotic nuclei. (e) Metastatic tumor in the lymph node exhibiting dense stromal fibrosis. (f) Tumor cells with light eosinophilic cytoplasm and irregularly shaped nuclei exhibiting scattered growth in dense fibrous stroma of a metastatic tumor in a lymph node.

Figure 2

(a–d) Overall survival curves and disease‐free survival curves of invasive ductal carcinoma (IDC) patients who received neoadjuvant chemotherapy. (a) Patients with IDCs exhibiting fibrotic foci (FFs) assessed using biopsy specimens obtained before neoadjuvant chemotherapy have a significantly shorter overall survival period than patients with IDCs that do not exhibit FFs, as assessed using biopsy specimens obtained before neoadjuvant chemotherapy. (b) The disease‐free survival of IDC patients classified according to a grading system for lymph vessel tumor emboli assessed using surgical materials obtained after neoadjuvant chemotherapy decreases significantly according to the grade. Ly, lymph vessel tumor embolus or emboli. (c) The disease‐free survival of IDC patients with nodal metastatic tumors containing five or more mitotic figures is significantly shorter than that of IDC patients without nodal metastasis or those with nodal metastatic tumors containing less than five mitotic figures. N0, no nodal metastasis; NTMF, mitotic figures in nodal metastatic tumor. (d) The disease‐free survival of IDC patients classified according to the tumor stroma of nodal metastatic tumors decreases significantly according to the degree of fibrosis in the nodal metastatic tumors. NTStr, nodal metastatic tumor stroma.