The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

Mammary neoplasms are the most common neoplasm in female dogs. Two histologic classification systems for canine mammary tumors and dysplasias have been published: the first in 1974 and a modification in 1999. This article provides a brief overview of the two histologic classification systems. Since the publication of the second system, several new histologic subtypes of canine mammary neoplasms have been described. These have been incorporated into the proposed new classification system. This article also compares the grading systems for canine mammary carcinomas and their use for prognosis, along with the histologic classification.

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...

Histopathology is considered the gold standard diagnostic method for canine mammary tumors. In 2011, a new histologic classification for canine mammary tumors was proposed. The present study was a 2-year prospective study that validated the 2011 classification as an independent prognostic indicator with multivariate analysis in a population of 229 female dogs, identifying subtype-specific median survival times (MST) and local recurrence/distant metastasis rates. Dogs with benign tumors and carcinoma arising in benign mixed tumors all had an excellent prognosis. Dogs with complex carcinoma and simple tubular carcinoma also experienced prolonged survival. Those with simple tubulopapillary carcinoma, intraductal papillary carcinoma, and carcinoma and malignant myoepithelioma had a more than 10-fold higher risk of tumor-related death. The prognosis was even worse for adenosquamous carcinoma (MST = 18 months), comedocarcinoma (MST = 14 months), and solid carcinoma (MST = 8 months). The most unfavorable outcome was for anaplastic carcinoma (MST = 3 months) and carcinosarcoma (MST = 3 months), which also had the highest metastatic rates (89% and 100%, respectively). Adenosquamous carcinoma exhibited the highest local recurrence rate (50%). In the same canine population, the tumor diameter was recognized as a strong predictor of local recurrence/distant metastasis and an independent prognosticator of survival in the multivariate analysis. Excision margins were predictive only of local recurrence, whereas lymphatic invasion and histologic grade were predictive of local recurrence/distant metastasis and survival, although only in univariate analyses. In conclusion, this study validated the 2011 classification scheme and provided information to be used in the clinical setting and as the basis for future prognostic studies.

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