Does TLS Exist in Canine Mammary Gland Tumours? Preliminary Results in Simple Carcinomas.

Neoplastic progression is influenced by the expression of tumour antigens that activate an anti-tumour immune response. Human medical studies show that this body defence is carried out in secondary lymphoid organs (SLOs) but also directly in the tumour through organized cellular aggregates that are called tertiary lymphoid structures (TLSs). However, their occurrence has different meanings in different tumour types. For example, the presence of TLSs in breast cancer is associated with the most aggressive subtypes. This paper aimed to study TLSs in canine mammary simple carcinomas. A morphological assessment of the inflammatory infiltrate was performed on H&E sections of fifty cases. Immunohistochemistry was then carried out to typify the inflammatory cells in the tumour microenvironment. Results showed that, sometimes, inflammatory infiltrates were organized in follicles close to high-grade carcinomas, simulating a lymphoid organization, as in breast cancer. Therefore, we can assume that even in canine mammary tumours, TLSs exist and they are entities to consider due to their presence in the most aggressive histotypes or tumours with a high degree of malignancy.

Genotype data not consistent with clonal transmission of sea turtle fibropapillomatosis or goldfish schwannoma.

Recent discoveries of transmissible cancers in multiple bivalve species suggest that direct transmission of cancer cells within species may be more common than previously thought, particularly in aquatic environments. Fibropapillomatosis occurs with high prevalence in green sea turtles ( Chelonia mydas) and the geographic range of disease has increased since fibropapillomatosis was first reported in this species. Widespread incidence of schwannomas, benign tumours of Schwann cell origin, reported in aquarium-bred goldfish (Carassius auratus), suggest an infectious aetiology. We investigated the hypothesis that cancers in these species arise by clonal transmission of cancer cells. Through analysis of polymorphic microsatellite alleles, we demonstrate concordance of host and tumour genotypes in diseased animals. These results imply that the tumours examined arose from independent oncogenic transformation of host tissue and were not clonally transmitted. Further, failure to experimentally transmit goldfish schwannoma via water exposure or inoculation suggest that this disease is unlikely to have an infectious aetiology.

Bovine besnoitiosis in a cattle herd in Sicily: an isolated outbreak or the acknowledgment of an endemicity?

Bovine besnoitiosis is a debilitating infectious disease caused by Besnoitia besnoiti (Apicomplexa; Sarcocystidae). The disease is mainly characterized by cutaneous and systemic signs, infertility in bulls, and abortion in cows. The current study describes an autochthonous outbreak of bovine besnoitiosis in Sicily, Southern Italy, being the first report of B. besnoiti infection in the island so far. In a cattle farm located in Syracuse province, a 4-year-old Belgian blue bull born in Sicily displayed typical clinical signs of the sub-acute/chronic disease phase with thickening of the skin of the scrotum and testicular degeneration. Histological examination of scrotal biopsies revealed the presence of several tissue cysts of B. besnoiti. The serological analysis of the herd using a commercial ELISA revealed a high seroprevalence (45 out of 55; 82%) of antibodies against B. besnoiti. Few seropositive animals (5 out of 45; 11%) showed clinical signs, cysts in vestibulum vaginae (1 out of 31; 3.2%), and testicular degeneration (4 out of 14; 28.6%) assessed by ultrasonographic investigations. The paucity of clinical signs associated with the high seroprevalence in the farm led to hypothesize that bovine besnoitiosis is endemic in the area though further studies are needed. Local practitioners should be more aware of the disease to facilitate the early detection of cases, prevent the spread of infection, and avoid economic losses and animal health problem.

Constant Rate Infusion of Lidocaine, Tumescent Anesthesia and Their Combination in Dogs Undergoing Unilateral Mastectomy.

Tumescent anesthesia (TUM) is a technique that was initially used to perform liposuction under local anesthesia, which consists of the injection of such large volumes of local anesthetic until to produce swelling and firmness (tumescence) of the surgical area. The aim of this study was to compare the intraoperative analgesic efficacy of lidocaine (LID) constant rate infusion (CRI), of TUM, or their combination (LID/TUM) and the postoperative pain and analgesic requirement in dogs undergoing unilateral mastectomy. Twenty-four dogs were premedicated with dexmedetomidine (3 µg/kg) and methadone (0.2 mg/kg) intravenously (IV). After induction with propofol IV to effect, dogs were randomly allocated to receive a loading dose of lidocaine (2 mg/kg) followed by a CRI of 100 µg/kg/min (Group LID) in addition to an equivalent volume of lactated Ringer's solution instead of local TUM; a loading dose of lactated Ringer's solution followed by a CRI of Ringer's solution in addition to TUM (Group TUM); a loading dose of lidocaine (2 mg/kg) followed by a CRI of 100 µg/kg/min in addition to TUM (Group LID/TUM). Anesthesia was maintained with isoflurane in oxygen. Postoperative pain scores were assessed once the dogs had fully recovered from the sedative effects, and following 15, 30, 45 and 60 min. The results of the current study allow us to assert that all three treatments provided satisfactory intraoperative antinociceptive effects but administration of LID/TUM induced greater inhibition on sympathetic stimulating effect up to 60 min from recovery, thus, providing better early postoperative pain relief in dogs undergoing mastectomy.

Imaging of Canine Neoplastic Reproductive Disorders.

Diagnostic imaging plays an essential role in the diagnosis and management of reproductive neoplasia in dogs and cats. The initial diagnosis, staging, and planning of surgical and radiation treatment and the response to therapy all involve imaging to varying degrees. Routine radiographs, ultrasound, nuclear medicine, and cross-sectional imaging in the form of computed tomography (CT) and magnetic resonance imaging (MRI) are routinely used in canine reproductive disorders. The choice of imaging modality depends on many factors, including the level of referral and the pathological information required. The biological behaviour of the tumour also guides the choice of imaging in cancer staging, and imaging may play an important role in guiding serial tumour biopsy during the course of therapy. The sophistication of imaging modalities is increasing exponentially. Each modality has advantages and disadvantages in terms of cost, availability, sensitivity, specificity, and qualities of anatomic versus functional imaging.

Immune Cells and Immunoglobulin Expression in the Mammary Gland Tumors of Dog.

Inflammatory cells have a role in tumor progression and have prognostic and therapeutic potential. The immunohistochemical expression for Mast Cell Tryptase, Macrophage Marker, CD79a, IgA, IgM and IgG on 43 cases of canine mammary gland lesions was analyzed. In hyperplasia, a few B cells (BCs) and Tumor-Associated Macrophages (TAMs) were observed, while the number of Tumor-Associated Mast Cells (TAMCs) was the highest. In the peritumoral stroma of malignant lesions, low number of TAMCs and a high number of TAMAs and BCs were present. Immune cells of each type were always lower in the intratumoral than peritumoral stroma. Positivity to CD79a was also detected in the epithelial cells of simple and micropapillay carcinomas. Immunoglobulin reactivity was mainly located in the epithelial cells where an intense positivity to IgA and IgG and a weak positivity for IgM were detectable. On the basis of our preliminary results and literature data, we suggest that such cells and molecules could be directly involved in the biology of canine mammary gland tumors. In breast cancer, stromal inflammatory cells and cancer derived immunoglobulins have been correlated with the progression, malignancy and poor prognosis of the tumor. The results herein reported show that the dog's mammary gland epithelium also expresses immunoglobulins, and they mostly show a direct relationship with the infiltration of macrophages. In addition, this study shows that the infiltration of mast cells, B-cells and macrophages varies depending on the degree of malignancy of neoplasia.

Pseudo-Placentational Endometrial Hyperplasia in the Bitch: Case Series.

Canine pseudo-placentational endometrial hyperplasia differs from the classical form of cystic endometrial hyperplasia for the well-organized tissue architecture resembling the canine placenta. After the discovery, it has been inconstantly reported. The present work reports the clinicopathological details of six spontaneous cases retrieved retrospectively from a large database. The lesion was found in young non-pregnant female dogs (median 2.0 years) at the end of dioestrus. It could be imaged by ultrasound and was always grossly detectable as single or multiple uterine enlargements of 2-3 cm in diameter with a villous whitish tissue growing on the mucosa and occluding the lumen. Histology confirmed the tissue architecture of the canine placenta with a basal glandular layer, a connective band, a spongy layer and a tortuous and compact labyrinth, often poorly recognizable. The pseudo-placentational hyperplasia is a non-inflammatory proliferative lesion although numerous mast cells inhabit the connective band, and a superimposed inflammatory infiltrate was seen in a case. Canine pseudo-placentational endometrial hyperplasia has very peculiar features, and it is a model for canine placentation and may help to better understand the cystic endometrial hyperplasia/pyometra complex.

Conservative treatments for feline fibroadenomatous changes of the mammary gland.

BACKGROUND: Fibroadenomatous changes (FAC) of the mammary gland in cats represents a benign, progesterone-associated fibroglandular proliferation of one or more mammary glands that may occur in intact female cats at the time of puberty, during pregnancy or pseudopregnancy, or in female and male cats of any age under progestin treatment. Nowadays, the elective treatment of FAC is based on the progesterone antagonist aglepristone. This study aimed to report the treatment of FAC with a combination of drugs designed to preserve mammary gland integrity, even in pregnant cats. CASE DESCRIPTION: Eight sexually intact female cats with FAC showed mammary glands that were symmetrically enlarged and inflamed in all cases, and the skin was ulcerated in six cats. Four cats were on days 25-32 of pregnancy at presentation. Non-pregnant cats were treated with aglepristone and with a dietary supplement containing maltodextrin and bromelain. The mammary glands were massaged daily with an Aloe vera emollient gel. If the gland was inflamed or ulcerated, broad-spectrum antimicrobial, and anti-inflammatory treatments were given, and the ulcers were treated topically with a hypericum and neem-based cream. Two of the four pregnant cats were treated with the same therapeutic schedule plus cloprostenol to facilitate uterine emptying. Two pregnant cats underwent the same protocol except for aglepristone, which was not administered to safeguard the litter and see if the adjuvant therapy worked independently. At term, they delivered four and three kittens, respectively, that were normally nursed and weaned after 40 days. In all the studied cases, the mammary gland reduced in size 2-3 weeks after the start of the treatment and completely remitted after 4-5 weeks. CONCLUSION: This case series encourages adjuvant therapy in the course of FAC to preserve mammary gland integrity and functionality. Exploiting the natural decline of progesterone at the end of pregnancy (or pseudopregnancy), the therapy may also be used without aglepristone, when its use has other limitations.

Somatic evolution and global expansion of an ancient transmissible cancer lineage.

The canine transmissible venereal tumor (CTVT) is a cancer lineage that arose several millennia ago and survives by "metastasizing" between hosts through cell transfer. The somatic mutations in this cancer record its phylogeography and evolutionary history. We constructed a time-resolved phylogeny from 546 CTVT exomes and describe the lineage's worldwide expansion. Examining variation in mutational exposure, we identify a highly context-specific mutational process that operated early in the cancer's evolution but subsequently vanished, correlate ultraviolet-light mutagenesis with tumor latitude, and describe tumors with heritable hyperactivity of an endogenous mutational process. CTVT displays little evidence of ongoing positive selection, and negative selection is detectable only in essential genes. We illustrate how long-lived clonal organisms capture changing mutagenic environments, and reveal that neutral genetic drift is the dominant feature of long-term cancer evolution.

Molecular Signatures of Regression of the Canine Transmissible Venereal Tumor.

The canine transmissible venereal tumor (CTVT) is a clonally transmissible cancer that regresses spontaneously or after treatment with vincristine, but we know little about the regression mechanisms. We performed global transcriptional, methylation, and functional pathway analyses on serial biopsies of vincristine-treated CTVTs and found that regression occurs in sequential steps; activation of the innate immune system and host epithelial tissue remodeling followed by immune infiltration of the tumor, arrest in the cell cycle, and repair of tissue damage. We identified CCL5 as a possible driver of CTVT regression. Changes in gene expression are associated with methylation changes at specific intragenic sites. Our results underscore the critical role of host innate immunity in triggering cancer regression.

Mitochondrial genetic diversity, selection and recombination in a canine transmissible cancer.

Canine transmissible venereal tumour (CTVT) is a clonally transmissible cancer that originated approximately 11,000 years ago and affects dogs worldwide. Despite the clonal origin of the CTVT nuclear genome, CTVT mitochondrial genomes (mtDNAs) have been acquired by periodic capture from transient hosts. We sequenced 449 complete mtDNAs from a global population of CTVTs, and show that mtDNA horizontal transfer has occurred at least five times, delineating five tumour clades whose distributions track two millennia of dog global migration. Negative selection has operated to prevent accumulation of deleterious mutations in captured mtDNA, and recombination has caused occasional mtDNA re-assortment. These findings implicate functional mtDNA as a driver of CTVT global metastatic spread, further highlighting the important role of mtDNA in cancer evolution.

Transmissible [corrected] dog cancer genome reveals the origin and history of an ancient cell lineage.

Canine transmissible venereal tumor (CTVT) is the oldest known somatic cell lineage. It is a transmissible cancer that propagates naturally in dogs. We sequenced the genomes of two CTVT tumors and found that CTVT has acquired 1.9 million somatic substitution mutations and bears evidence of exposure to ultraviolet light. CTVT is remarkably stable and lacks subclonal heterogeneity despite thousands of rearrangements, copy-number changes, and retrotransposon insertions. More than 10,000 genes carry nonsynonymous variants, and 646 genes have been lost. CTVT first arose in a dog with low genomic heterozygosity that may have lived about 11,000 years ago. The cancer spawned by this individual dispersed across continents about 500 years ago. Our results provide a genetic identikit of an ancient dog and demonstrate the robustness of mammalian somatic cells to survive for millennia despite a massive mutation burden.

Sertoli cell tumors associated with feminizing syndrome and spermatic cord torsion in two cryptorchid dogs.

The association of cryptorchidism, functional Sertoli cell tumors, and spermatic cord torsion has been rarely reported in the literature. Two dogs were admitted for bilateral skin alopecia and weight loss. Both animals were cryptorchid and displayed a pendulous preputial sheath, prostate hypertrophy, and increased levels of circulating oestrogen. Transabdominal palpation and ultrasonography revealed the presence of neoplastic retained gonads. During surgery, spermatic cord torsion was also detected in the enlarged neoplastic testes of both dogs. Histologic examination confirmed the presence of Sertoli cell tumors that were primarily responsible for the feminizing syndrome. Complete remission of all symptoms occurred within 3 months after orchiectomy.