Quantitation of the Regional Lymph Node Metastatic Burden and Prognosis in Malignant Mammary Tumors of Dogs

Abstract

Background: As in women, regional lymph node status impacts survival in dogs with malignant mammary tumors. However, few studies have evaluated regional lymph node metastases in dogs with malignant mammary gland tumors.

Objectives: To estimate overall survival based on the assessments of the lymph node status and the morphologic and morphometric features in female dogs with malignant mammary gland tumors.

Materials and methods: In total, 178 lymph nodes from 97 female dogs were assessed and reviewed, and after confirmation by immunohistochemistry (IHC), 161 lymph nodes were selected for analysis of metastases. Animals were considered metastasis-free (negative lymph nodes) only after IHC analysis for cytokeratin AE1/AE3. The number of positive lymph nodes, the number of metastatic foci, the maximum diameter and the area of metastasis were analyzed, and estimates of overall survival were made.

Results: Dogs with metastasis had lower mean survival than those with metastasis-free regional lymph nodes, showing a direct relationship between the number of affected lymph nodes and shorter survival. However, histologic analysis of the lymph nodes identified lower survival rates in animals with macrometastases and isolated tumor cells, areas of metastasis >20.11 mm², and metastatic diameters >7.32 mm.

Conclusion: The identification of ≥1 lymph nodes positive for metastasis and morphometric characterization of lymphatic metastases indicate the prognostic relevance of lymph nodes status in dogs with mammary tumors.

Keywords: Canine; Lymph node; Mammary tumors; Metastasis; Survival.

Figure 1

(A) Neoplastic proliferations characterized by numerous structures resembling acini contain significant fibrosis replacing part of the lymphoid parenchyma (macrometastases). 400x. Hematoxylin‐eosin (H&E). (B) Neoplastic proliferation characterized by structures resembling acini localized in the subcapsular sinus (micrometastases). 200x. H&E. (C) Multiple deposits of isolated epithelial neoplastic cells (arrows) in the subcapsular sinus. The size of the largest metastatic deposit, measuring 0.06 mm, was used to classify lymph node metastasis as isolated tumor cells (ITC). 400x. H&E.

Figure 2

(A) Kaplan–Meier survival curve for the animals according to the histologic types: MTC (carcinoma in mixed tumor; n = 32); PTC (papillary and tubular carcinoma; n = 11); SC (solid carcinoma; n = 16; median, 195 days); RTMT (rare type malignant mammary tumors; n = 18; median, 180 days); and CSS (carcinosarcoma; n = 7; median, 185 days). Animals with MTC and PTC not did reach median survival (P < .0001). (B) Kaplan–Meier survival curve for the animals with metastasis (n = 53, median, 275 days) and without metastasis (n = 31, not reaching median survival) (P < .0001).(C) Kaplan–Meier survival curve for the animals according to the number of lymph nodes involved: 0 (no metastatic lymph nodes; n = 31, not reaching median survival), 1 (1 metastatic lymph node; n = 37; median, 348 days), and ≥2 (≥2 metastatic lymph nodes; n = 16; median, 130 days) (P < .0001). (D) Kaplan–Meier survival curve for the animals according to the classification of metastasis: A (absence of metastasis; n = 31), B (macrometastases; n = 11; median, 240 days), C (micrometastases; n = 14), D (isolated tumor cells; n = 8; median, 262 days), and E (no measurable metastasis; n = 20; median, 180 days) (P < .01). The animals in groups A and C did not reach median survival.

Figure 3

(A) Kaplan–Meier survival curve for the animals according to the area of metastasis: <20.11 mm² (n = 28; not reaching median survival) and >20.11 mm² (n = 5; median, 86.5 days) (P = .0457). (B) Kaplan–Meier survival curve for the animals according to the number of metastatic foci: <28 foci (n = 30; median, 404 days) and >28 foci (n = 3, not reaching median survival) (P = .629). (C) Kaplan–Meier survival curve for the animals according to the maximum diameter of metastasis: <7.32 mm (n = 27; not reaching median survival) and >7.32 mm (n = 6; median, 63 days) (P = .0068). (D) Kaplan–Meier survival curve for the animals according to the total metastatic area (TMA): <88.92 mm² (n = 21; not reaching median survival) and >88.92 mm² (n = 3; median, 110 days) (P = .3329).