Canine histiocytic neoplasia: an overview

Canine histiocytic neoplasms include cutaneous histiocytoma, as well as localized and disseminated histiocytic sarcoma. These tumors have variable biologic behavior, although the malignant disorders often have a poor prognosis. Immunohistochemistry plays an essential role in differentiating histiocytic tumors from other neoplasias that may have similar histological appearances. This allows a definitive diagnosis to be established and provides a more accurate prediction of prognosis. This article reviews the biologic behavior, diagnosis, and treatment of histiocytic tumors in the dog.     

Canine obesity – an overview

Canine patients are generally regarded as being clinically obese when their body weight is at least 15% above ideal. The incidence of obesity in dogs is thought to be in the range of 20–40% of the general population and, since obesity is known to predispose or exacerbate a range of serious medical conditions, its importance cannot be overstated. Management of obesity through dietary restriction and increased exercise is often difficult to achieve and dependent upon owner compliance. Until recently there has been no authorized therapeutic medication available for weight reduction in dogs, and drugs used in people have proved unsuitable. However, with the development of microsomal triglyceride transfer protein inhibitors for canine use, such as dirlotapide, the veterinarian has a novel method with which to augment traditional weight control programmes. This approach has the additional advantage that weight loss is achieved without dietary restriction or change in exercise regimen, providing encouragement for the owner to comply with subsequent dietary and exercise recommendations, thereby increasing the likelihood for long-term success.     

Canine mammary cancer

Microscopic examination showed that mammary cancer in the dog, especially the more infiltrating types, had often been removed (±50%) in an incomplete way. Local recurrence, detected clinically or at post mortem examination, is frequent.
Metastasis is the most frequent cause of death. Dyspnoea is often, but not always, associated with pulmonary metastasis. Lymphogenous and haematogenous metastasis are common.
By-passing of regional lymph nodes and lungs is extremely uncommon. Pleural metastasis was only found in combination with pulmonary metastasis.
Tumours in the posterior glands had more frequently spread to the lungs and liver than those in the anterior glands. Haematogenous spread to other mammary glands was not detected. Multiple malignant mammary tumours were found to be rare (4%).
Mammary cancer should be treated both surgically and systemically.     

Canine mammary cancer

From a follow-up study of dogs surgically treated for mammary cancer the associations of fourteen tumour and host characteristics with prognosis were analyzed. Size, mode of growth, type of tumour and histological grade of malignancy were found to be associated with prognosis. Localization, type of surgical treatment, growth in lymph vessels, involvement of regional lymph nodes and delay were found not to be associated with prognosis.
The results of the present study are compared with those in the literature, particularly with Bostock's study.     

Canine mammary tumours: protective effect of late ovariectomy and stimulating effect of progestins

Ovariectomy, even when performed at an advanced age, was found to be to some extent protective against mammary tumour development in dogs. Bitches treated with progestins had a slightly higher risk for mammary tumours (all types, benign and malignant) than controls. Progestin treatment did not increase the risk of mammary cancer. Benign tumours in (treated and untreated) dogs appeared earlier than malignant ones. Progestin treatment resulted in earlier appearance of both benign and malignant tumours than in controls. The ratio solitary/multiple mammary tumours was not significantly different between treated and untreated dogs.     

Canine mammary mixed tumours: immunohistochemical expressions of EGFR and HER‐2

Background Benign mixed tumours (BMTs) are frequently found in the mammary glands of female dogs, but the factors determining malignant transformation in these tumours are unknown. Objective To evaluate the expression of the oncoproteins, human epidermal growth factor receptor 2 (HER‐2) and epidermal growth factor receptor (EGFR), in 46 carcinomas in BMTs (CBMTs) and to verify their possible association with the malignancy of the tumours. Methods Immunohistochemical expression was analysed in benign and malignant components separately, and then compared with 74 cases of BMTs. Results Among the CBMTs, positivity for HER‐2 was found in the benign histological component of 4.3% (2/46), in the malignant epithelial non‐invasive component of 14.8% (4/27) and in the malignant invasive epithelial component of 13.6% (6/44) of cases. Two of the 24 (8.3%) BMTs were positive for HER‐2. There was no relationship between HER‐2 and the tumour components. There was no significant difference between BMTs and CBMTs. Positivity for EGFR was found in the benign component of 17.4% (8/46) of the CBMTs, in the malignant epithelial non‐invasive component of 40.7% (11/27%) and in the invasive epithelial malignant component of 45.4% (20/44). EGFR positivity was significantly associated with the invasive component of CBMTs. Conclusion EGFR may contribute to malignant epithelial transformation of BMTs. In contrast, HER‐2 overexpression may not be associated with the acquisition of a malignant epithelial phenotype.     

Canine mammary gland tumors

An understanding of the known biologic facts of this disease and methodical evaluation of the individual patient are necessary prerequisites for outlining rational courses of therapy for dogs afflicted with mammary tumors. Because of the common occurrence of multiple tumors arising at various stages of development simultaneously and the heterogeneity of histology of the complex (mixed tissue types) tumors, presurgical biopsy is recommended only in cases in which mast cell tumor or anaplastic carcinoma is suspected. Although investigative work is being performed regarding the efficacy of chemotherapy, radiation therapy, and immunotherapy, surgery still remains the mainstay in treatment of this condition. No one surgical procedure fits the needs of all patients, although it seems logical to remove as much breast tissue as is reasonable in each circumstance owing to the multicentric nature of the disease. Ovariohysterectomy has not been demonstrated to be of value in treatment of dogs with mammary tumors, but it is a markedly effective method of preventing mammary tumors if it is performed before puberty; it is moderately effective if performed before the dog is 21/2 years of age.     

Feline mammary tumours

Fifty-five tumours (fifty malignant, five benign) of the mammary gland of cats were found among 2296 feline diagnostic accessions submitted over a 10-year period. Twenty-seven were adenocarcinomas, nineteen papillary adenocarcinomas, two scirrhous carcinomas, and two anaplastic carcinomas. The majority of the cats were between 10 and 14 years of age. No breed predilection was noted. Résumé. Parmi 2296 diagnostics effectués chez des chats au cours d'une période de 10 ans ont été notées 55 tumeurs de la glande mammaire. Les tumeurs (dont 50 malignes et 5 bénignes) comprenaient 27 adénocarcinomes, 19 adénocarcinomes papillaires, 2 carcinomes squirrheux et 2 carcinomes anaplasiques. L'âge des sujets atteints se situait pour la plupart entre 10 et 14 ans, sans prédominance d'aucune race déterminée. Zusammenfassung. 55 Tumoren (50 maligne, 5 benigne) der Brustdrusen von Katzen wurden bei 2296 diagnostischen Vorfühmngen von Katzen innerhalb von 10 Jahren gefunden. 27 waren Adenocarcinome, 19 papillare Adenocarcinome, 2 Szirrhuscarcinome und 2 anaplastische Carcinome. Die Mehrzahl der Katzen war 10 bis 14 Jahre alt. Es wurde keine Bevorzugung einer Rase festgestellt.     

Canine mammary gland tumors.

The National Consensus Group recommends that all women with tumors larger than 1 cm be offered chemotherapy regardless of tumor histology of lymph node status. This recommendation is to ensure that everyone at risk for failing, even though the risk may be low in women with relatively small tumors and favorable histology, has a choice and receives the benefit of adjuvant chemotherapy. This type of treatment recommendation may also be made in dogs based on recognized, well-accepted prognostic factors such as tumor size, stage, type, and histologic differentiation. Based on the limited clinical information available in veterinary medicine, the drugs that are effective in human breast cancer, such as cyclophosphamide, 5-fluorouracil, and doxorubicin, may also have a role in the treatment of malignant mammary gland tumors in dogs. Randomized prospective studies are needed, however, to evaluate the efficacy of chemotherapy in dogs with high-risk mammary gland tumors and to determine which drugs and protocols are the most efficacious. Until such studies are performed, the treatment of canine mammary gland tumors will be based on the individual oncologist's understanding of tumor biology, experience, interpretation of the available studies, and a little bit of gut-feeling. Table 2 is a proposal for treatment guidelines for malignant canine mammary gland tumors according to established prognostic factors, results from published veterinary studies, and current recommendations for breast cancer treatment in women.     

Canine haemangiopericytomas--a survey of 200 tumours

Abstract— —Of 200 canine haemangiopericytomas examined, most were slow-growing, lobulated tumours which occurred principally in dogs between 6 and 14 years of age. Haemangiopericytomas were found more often in females (69 per cent) and in two sites, the forelegs (26 per cent) and thighs (26 per cent). The next most common locations were the chest (11 per cent) and shoulders (8 per cent). Compared to the normal canine population, the haemangiopericytoma is more prevalent in Boxer dogs, German Shepherd dogs, Cocker and Springer Spaniels. Résumé— —Parmi 200 hemangiopéricytomes examinés chez le chien, la plupart sont des tumeurs lobuées à croissance lente, qui apparaissent chez des animaux âgés de 6 à 14 ans. Les hémangio-péricytomes sont rencontrés plussouvent chez les femelles (69 p. 100) et selondeux localisations: sur les pattes postérieures (26 p. 100) et sur les cuisses (26 p. 100). Ensuite, les leiux d'élection les plus communs sont la poitrine (11 p. 100) et les épaules (8 p. 100). Compte-tenu de la répartition des races dans la population canine, l'hémangiopericytome est plus fréquent chez les boxers, les bergers allemands. les cockers et les épagneuls. Zusammenfassung— —200 Hämangioperizytome von Hunden wurden untersucht. Die mcisten erwiesen sich als lobuläre Tumoren von langsamer Wachtumsgeschwindigkeit, die hauptäschlich bei Hunden im Alter zwischen 6 und 14 Jahren gefunden wurden. Hämangioperizytome wurden mit größerer Häufigkeit bei Hündinncn (69 Prozent) und in 2 Körperteilen, dem Vorderbein (26 Prozent) und dem Oberschenkel (26 Prozent), gesehen. Die beiden nächsthäufigen Vorkommensorte waren die Brust (11 Prozent) und die Schultern (8 Prozent). Im Verhältnis zur normalen Hundebe-völkerung erscheint sin Hämangioperizytom mit größerer Frequenz bei Boxern, Deutschen Schäfer-hunden, Cocker- und Springerspanieln.     

Canine oral mucosal mast cell tumours

Mast cell tumours (MCTs) are the most common cutaneous tumours of dogs, however rarely they can arise from the oral mucosa. This subset of MCT is reported to demonstrate a more aggressive clinical course than those tumours on the haired skin and the authors hypothesised that dogs with oral, mucosal MCT would have a high incidence of local lymph node metastasis at presentation and that this would be a negative prognostic factor. An additional hypothesis was that mitotic index (MI) would be prognostic. This retrospective study examines 33 dogs with MCTs arising from the oral mucosa. The results suggest that oral mucosal MCTs in the dog have a high incidence of lymph node metastasis at diagnosis (55%) which results in a poor prognosis. MI and nodal metastasis is highly prognostic. Loco‐regional progression is common in these patients and dogs with adequate local control of their tumour had an improved outcome. Despite a more aggressive clinical course, treatment can result in protracted survivals, even when metastasis is present.     

Canine mammary gland tumours; a histological continuum from benign to malignant; clinical and histopathological evidence*

This study describes the clinical and histopathological findings in dogs with mammary gland tumours, and compares the histopathological and clinical evidence consistent with progression from benign to malignant to human breast cancer epidemiology. Clinical and histopathological data on 90 female dogs with 236 tumours was included. Dogs with malignant tumours were significantly older than dogs with benign tumours (9.5 versus 8.5 years), P = 0.009. Malignant tumours were significantly larger than benign tumours (4.7 versus 2.1 cm), P = 0.0002. Sixty‐six percent had more than one tumour, and evidence of histological progression was noted with increasing tumour size. Dogs with malignant tumours were significantly more likely to develop new primary tumours than dogs with benign tumours, P = 0.015. These findings suggest that canine mammary tumours progress from benign to malignant; malignant tumours may be the end stage of a histological continuum with clinical and histopathological similarities to human breast carcinogenesis.     

Xenobiotic-metabolizing enzymes in canine mammary tumours

Mammary tumours are the most common neoplasms in female dogs. The present study was designed to evaluate the relationship between different clinical stages with activities of phase I and phase II carcinogen-metabolizing enzymes in canine mammary tumours. The levels of cytochrome P450 and cytochrome b5 and the activities of glutathione S-transferase (GST), gamma-glutamyl transpeptidase (GGT), DT-diaphorase (DTD) and NADPH diaphorase in tumour tissues of 25 bitches was estimated. Enhanced levels of cytochrome P450 and b5 and phase II enzyme activities were observed in tumour tissues compared to the corresponding uninvolved adjacent tissues. The magnitude of the changes in phase I and phase II enzyme status was, however, more pronounced in stages I and II compared to stages III and IV. The results suggest that the balance between phase I carcinogen activation and phase II detoxification systems may play an important role in canine mammary tumour development.     

Estrogen receptors in canine mammary gland tumours

The aim of the present study was to establish the relationship between estrogen receptor expression in neoplastic parenchymal cells and the type of canine mammary gland tumour. The research material included mammary gland tumours obtained from 66 dogs. Paraffin sections were stained with hematoxylin-eosin and immunohistochemically with monoclonal antibodies and LSAB/Peroxidase/Universal Kit. The estrogen receptor expression was observed in nuclei of neoplastic cells in about 59% of the cases and in the cytoplasm in about 89% of the cases. In about 20% of the cases the expression in the nuclei and in the cytoplasm was extremely weak. No correlation was found between the expression of estrogen receptors and the value of mitotic indexes in the neoplasms investigated.