Development, Anatomy, Histology, Lymphatic Drainage, Clinical Features, and Cell Differentiation Markers of Canine Mammary Gland Neoplasms

Abstract

Mammary neoplasms are the most common neoplasm in female dogs. This article describes the embryologic development, normal anatomy, and histology of the canine mammary gland from the onset of first estrous and the changes that occur in the mammary gland during the estrus cycle. The clinical features of canine mammary gland tumors and their relation to prognosis are discussed, including age, hormones, breed, diet, and obesity. Additional clinical prognostic factors including clinical presentation, tumor size, and lymph node status at the time of presentation are discussed in relation to diagnosis and tumor staging. Immunohistochemical evaluation of the cell differentiation markers of the normal and neoplastic canine mammary gland is described and compared with similar studies in humans; the ways these markers may be used to assist with the prognosis of canine mammary neoplasms are discussed. Keywords reproductive, tissue, dog, domestic mammals, speciesThe mammary gland is a modified apocrine sweat gland found only in mammals. It consists of a network of ducts surrounded by a fibrovascular and adipocyte-rich stroma. The development of this gland is unique, as the last stages of development occur in the adult female only during pregnancy. With each pregnancy there is proliferation of the ductal tissue, differentiation to milk-producing acini, secretion of milk by the acinar cells, and, at the end of lactation, involution of the secretory component of the gland with preservation of the ductal structures. Development of the Mammary GlandMammary development can first be recognized during embryologic development by the appearance of 2 ventral linear thickenings (ridges) of ectoderm, below which are specialized regions of mesoderm. The ridges, also referred to as milk lines, extend from the axillary to the inguinal region. The ectodermal cells migrate along each milk line and coalesce to form a placode, which eventually becomes individual mammary glands. The formation of the placode is a complex interaction, involving several signal pathways between the epithelial cells of the ectoderm and mesenchymal cells of the mesoderm.The epithelial cells of the placode form a solid cord of cells that grow into the underlying mesenchyme to form the mammary buds, which subsequently branch to form a mammary sprout. Within each sprout a lumen forms via a process of cavitation, which communicates externally via a region of specialized epithelium called the nipple sheath and which becomes the raised teat in the adult dog. Each mammary sprout will eventually form the papillary duct of the adult mammary gland.Most dogs develop 5 pairs of mammary glands, although 4 or 6 pairs have been found in a few animals. There are 2 thoracic (M1 and M2), 2 abdominal (M3 and M4), and 1 inguinal (M5) pair of mammary glands. 86 Each teat has between 7 and 16 duct openings, and each of these ducts will eventually form a lobe of the adult gland and act as an independent functional unit within the gland. The mammary glands continue to grow in proport...

Clinicopathological significance of caspase-3 and Ki-67 expression in canine mammary gland tumours

“…These results are in agreement with the findings of previous studies on human breast cancer and on CMGT (Lipponen et al, 1994;Labelle et al, 2004;Nowak et al, 2008;Pathmanathan and Balleine, 2013). These findings highlight the crucial role of Ki-67 in tumour progression, as reported by several authors (Pena et al, 1998;Labelle et al, 2004;Sorenmo et al, 2011). For Ki-67 expression there was a statistically significant association with larger tumour size, histological type, mitotic index, nuclear grade, histological grade of malignancy, and the presence of lymph node metastasis.…”

Immunohistochemical detection of tumour cell proliferation and intratumoural microvessel density in canine malignant mammary tumours

“…The age of the patient is one of the most important risk factors since it has been well-documented that the incidence of canine mammary tumours is directly correlated with advancing age (11,17,28). In the present study, the average age was 9.5 years (ranging from 4 to15 years) in dogs with malignant tumours, which was similar to that reported in previous studies (2,27).…”

Histologic Evidence of the "Sick Lobe" Carcinogenesis Theory and the Frequency of Intraepithelial Lesions in the Mammary Glands of Female Canines with no Clinical Signs of Neoplasia

“…Ten individuals with this condition had the largest number of IELs, which is in contrast with other studies in which pure-bred canines appeared to be more predisposed to these pathologies [9]. A higher frequency of these neoplasms has been documented for pure breeds, such as Shih Tzu, which develop malignant mammary tumors at young ages and overexpress BRCA1, a gene involved in the carcinogenesis of mammary tumors.…”

“…The differences might be due to differences in the classification criteria used in the two works. In our case, the physiological stages of the canine estrus (reproductive cycle) such as proestrus, estrus, and diestrus, as proposed by Sorenmo, et al [9] were taken into account. However, Mouser, et al [17] used inclusion criteria of human breast pathologies and thus considered UDH when more than two cell layers were present; [38] according to those criteria, the primary criterion for classifying a lesion as UDH is several epithelial cell layers with regular proliferation within the duct lumen without any other sign of abnormal cell growth [9,[24][25][26].…”