Columnar cell lesions of the canine mammary gland: pathological features and immunophenotypic analysis

Abstract

Background: It has been suggested that columnar cell lesions indicate an alteration of the human mammary gland involved in the development of breast cancer. They have not previously been described in canine mammary gland. The aim of this paper is describe the morphologic spectrum of columnar cell lesions in canine mammary gland specimens and their association with other breast lesions.

Methods: A total of 126 lesions were subjected to a comprehensive morphological review based upon the human breast classification system for columnar cell lesions. The presence of preinvasive (epithelial hyperplasia and in situ carcinoma) and invasive lesions was determined and immunophenotypic analysis (estrogen receptor (ER), progesterone receptor (PgR), high molecular weight cytokeratin (34betaE-12), E-cadherin, Ki-67, HER-2 and P53) was perfomed.

Results: Columnar cell lesions were identified in 67 (53.1%) of the 126 canine mammary glands with intraepithelial alterations. They were observed in the terminal duct lobular units and characterized at dilated acini may be lined by several layers of columnar epithelial cells with elongated nuclei. Of the columnar cell lesions identified, 41 (61.2%) were without and 26 (38.8%) with atypia. Association with ductal hyperplasia was observed in 45/67 (67.1%). Sixty (89.5%) of the columnar cell lesions coexisted with neoplastic lesions (20 in situ carcinomas, 19 invasive carcinomas and 21 benign tumors). The columnar cells were ER, PgR and E-cadherin positive but negative for cytokeratin 34betaE-12, HER-2 and P53. The proliferation rate as measured by Ki-67 appeared higher in the lesions analyzed than in normal TDLUs.

Conclusions: Columnar cell lesions in canine mammary gland are pathologically and immunophenotypically similar to those in human breast. This may suggest that dogs are a suitable model for the comparative study of noninvasive breast lesions.

Figure 1

Canine mammary biopsies with columnar cell change without atypia (CCC) H&E stain. 1A Low-power view, showing dilated mammary acini in a TDLU lined with a single layer of epithelial columnar cells with underlying myoepithelial cells, many of which contain intraluminal secretions and many hyperplastic foci, 200×; 1B, 1C e 1D At higher magnification, the lining columnar cells with uniform ovoid to elongated nuclei and nucleoli absent. Many contain intraluminal secretions (1B) and show a small apical snout (1C) and intraluminal calcifications (1D), 600×.

Figure 2

Canine mammary biopsies with columnar cell hyperplasia without atypia (CCH) H&E stain. 2A Low-power view, terminal duct lobular unit with cellular stratification, more than two cell layers, 100×. 2B Higher power view; columnar cells with uniform ovoid to elongated nuclei, observed hobnail cells with nucleoli absent or inconspicuous, 600×.

Figure 3

Canine mammary biopsies with flat epithelial atypia (FEA) H&E stain. 3A Low-power view; terminal duct lobular unit shows larger acini with cellular atypia, prominent apical cytoplasmic snouts, to be lined by >2 cell layers. 200×; 3B Higher power view; the columnar epithelial cells (> 2 layers) lining the acini with intraluminal secretions show cytological atypia, characterized by apical cytoplasmic snouts and enlarged, uniform nuclei; the nuclear/cytoplasmic ratio is increased. Nucleoli are evident in some of the nuclei, 600×.

Figure 4

Canine mammary biopsies with immunohistochemical staining of columnar cell lesion (CCL). Columnar cell change without atypia showing intense immunostaining for estrogen receptor (4A) and progesterone receptor (4B). Flat epithelial atypia with moderate membrane E-cadherin reactivity (4C) and nuclear expression for Ki-67 (4D), 600×.