ISRAEL JOURNAL OF VETERINARY MEDICINE TRANSMISSIBLE VENEREAL TUMORS DETECTED IN THE EXTRAGENITAL ORGANS OF DOGS Vol. 57 (2) 2002 A. Gurel1, B. Kuscu1, E. G. Gulanber2 and S. S. Arun1 1. Department of Pathology, and, 2. Department of Surgery, University of Istanbul, Faculty of Veterinary Medicine, Avcilar-Istanbul, Turkey. Abstract Transmissible venereal tumors detected in the extragenital regions of eight dogs of various ages, breeds and sex were evaluated clinically and pathologically. Seven of these tumors were found to be of primary origin.Only in one case, was TVT diagnosed also in the vagina of the animal. Biopsies collected from the extragenital tumor foci of 6 male and 2 female dogs were fixed in formalin and histology sections were prepared from these specimens and examined under light microscope. Three of these tumors were located in the nasal mucosa, 3 on the dorsal side of the thorax, 1 in gingiva and one in gluteal region. These tumors were approximately 0,5 X 2 cm. in size and appeared as a unique mass or two solitary masses. They were soft in consistency. All tumor cases involving the nasal mucosa were accompanied by a bloody nasal discharge. The microscopical appearance of all tumors detected in various regions was histologically similar to the appearance of TVT in the genital regions. In this study, 8 extragenital localisation of these tumors out of a total of 90 TVT cases suggest that although they are not as frequent, it is possible to encounter them in other parts of the body. Introduction Transmissible venereal tumor (TVT) is the only encountered tumor in dogs that can be transmitted by mating and also experimentally. Sticker was the first to perform detailed studies on this tumor, in the first decade of the 20th century. Since then, the tumors are known as Sticker’s sarcoma. They are also known as transmissible venereal tumor, venereal granuloma, canine condyloma or infectious sarcoma (1-3). The tumor is recognized in all dog breeds in various parts of the world, especially in tropical and subtropical zones. However, it is particularly common in stray dogs, which mate without any control after reaching sexual maturation. TVT can be experimentally transmitted to wolves, jackals, coyotes and red foxes (1,3). In reports from Turkey concerning canine tumors, these tumors are most frequently encountered (4-11). Sticker’s tumors are most common in sexually mature dogs aged 2 to 5 years (1-3). The tumor is transmitted by direct contact of the mucous membranes, damage to the mucous membrane may enhance transmission (1,3). Because the genital mucosae of both sexes are most vulnerable to injury at the time of mating, this predisposes them to tumor formation (16,11). Although it is rare, these tumors can be encountered in extra-genital regions (1-3,1218). TVT is composed histologically by round, ovoid or polyhedral cells. These cells have large, round hyperchromatic nuclei and centrally situated unique nucleoli. Also, they have moderately abundant eosinophilic cytoplasm. A notable number of mitotic figures can be observed in parenchymal cells that make up these tumors. The tumor is rich in cells, the stroma which contains the blood vessels is relatively narrow and can be observed as thin lines within the clusters of tumor cells (1-5,19,20). In this study, we have performed a clinical and pathological evaluation of extra-genital TVT cases from various biopsy materials sampled from 8 dogs of variable age, breed and sex, presented to our department. Materials and Methods Various biopsy specimens taken from extra-genital tumoral masses of 8 dogs that were sent to our laboratory from various clinics between the years 1997 to 2000. The biopsy specimens were routinely fixed in 10 % neutral buffered formaline solution and then embedded in paraffin wax, sections of 5-7 µm, stained with haematoxyline and eosin (21), and examined under a light microscope. Results Table 1 describes the signalment, location of the tumor, its characteristics, and clinical findings of 8 cases with extra-genital TVT. Table 1: Specifications and some clinical characteristics of the biopsy used in the study. No Breed Age (Y) Sex Location of the Lesion Size Characteristics Clinical Findings 1 Dalmatian* 3 M Nasal 1x1 cm Brownish, Bloody nasal soft discharge, consistency deformation of mucosa nasal bone 2 Collie 2 M Nasal 0.5x1 cm Soft Bloody nasal mucosa 2 pieces. consistency discharge for 1,5-2 month. Deformation of nasal bone 3 Crossbred 8 F Slightly hard Developed in Gluteal 1 cm in consistency, approx. 3 region diameter round months shaped 2 pieces 4 5 Terrier Boxer 10 6 M M Maxillar approx. Slightly hard, Grew 2-fold in gingiva 0.5x0.5 xm oval mass 1 month 1 pieces; Mucosa is Nasal approx. filled with Bloody nasal Mucosa 0,5 cm in this mass discharge diameter Pendular, 2 pieces, TVT 6 Crossbred 3,5 F Dorsal skin 1,5x2 cm Pate-like also of thorax in consistency, diagnosed in diameter pendular vagina. Poor general condition 7 German 5 M Shepherd Thorax; sub- 1 piece; White, Soft cutaneous 4x4,5 cm consistency Dorsal of 8 Boxer 6 F thorax, sub cutaneous - Developed in 2 1x2 cm White, soft, 2 pieces months. Poor general condition * Also refer to figure1 Histopathological examination of the specimen excised from the gingiva revealed large areas of erosion. Inflammatory cell infiltrations, mainly neutrophils were noted in some parts of the mucosa. Moreover, it was noticed that the basal cells of the stratified squamous epithelium had formed papillary projections towards the muscular layer. Atypical tumoral cells, round or polygonal in shape, with large nuclei that contain unique nucleoli and a slight pinkish cytoplasm infiltrated throughout the sub mucosal muscular layer. This infiltrate had destroyed and replaced the muscle fibers. The majority of the cells were hyperchromatic, and numerous mitotic figures were seen. A fine stromal fibrovascular network proliferated between these cells (Fig. 2). In biopsies excised from the nasal regions, the mucosae and deeper layers were seen to be infiltrated by tumor cells with similar characteristics to those described above. In some areas, focal necrosis with haemorrhage was also present (Fig. 3). In the tumors that were taken from the skin, a thick muscular “knob” was detected, while small groups of muscle cells could be observed particularly within the tumor cell foci located at the periphery. The tumor parenchyma was composed of numerous cells having similar structures as those described. Various stages of mitosis were prominent in these cells. The stromal tissue of thin fibrous filaments that was located between the parenchymal cells were determined to be more extensive compared to the others. The parenchyma was composed of various cell groups that contained different number of cells. Fig. 1: MRI (Magnetic Resonance Imaging) of dorsoventral-saggital plane of cranium. TVT localized in the left nasal lumen. Fig. 2: Tumor cell infiltration in the mucosa of the gingiva. H&E X 100. Fig. 3: Tumor cell infiltration in the nasal mucosa. Hyperchromatic cells with vesicular nuclei and abundant mitotic figures. H&E X 250. Discussion Transmissible veneral tumor is a frequently encountered tumor type in Turkey (4-10) and other countries (1-3,14,19,20). This tumor mostly develops in the genital organs of both sexes and is generally considered as a benign tumor (1-6,11). However, metastases may also occur in some of the cases and lesions may sometimes be observed in extra-genital region of some animals.The incidence of metastasis is quite low and occurs in 5 % or less of the cases. It is reported that metastases may occur in regional lymph nodes and internal organs such as the spleen, liver, kidney and brain (1-3,16,17,22,25). It is also reported that metastases may rarely occur in ocular, nasal or gingival regions due to activities such as smelling, licking and scratching (1-3,12-18). In this study, eight TVT cases were detected, of which 3 were in nasal, 3 in thoracic, 1 in the gingival and 1 the in gluteal region. According to anamnesis, clinical and microscopical examinations, all tumors except the one detected on the dorsal side of the thorax were concluded to be primary tumors. In this period, a total of 90 TVT diagnoses were recorded among the dogs or canine biopsies that were received by the clinics and laboratory of our faculty (4,12). The extra-genital location of tumors in the eight patients suggests that although it is quite infrequent, these tumors may be encountered at different sites. The destruction or the erosions of the mucosa has an important impact on tumor formation in extra-genital regions (1-3). The identification of individuals by smelling the genital areas is a common type of behaviour of canine species. The location of transmissible veneral tumors on the nasal mucosa is explained by inspiration during the action of smelling. Also, the proliferation of TVT on gingivae are explained by implantation of tumor cells on erosions already present on the gingivae. Transmission of tumors to the eyes and various regions of the skin are facilitated during the action of scratching (1-3,13-15,18,23,25). Due to the excessive number of stray dogs, the incidence of TVT in Turkey is high (4-10). The incidence of genital and extra-genital TVT has not yet been determined. In our search of the literature, 5 case reports, each describing 1 case were located (12,16,17,22,24). We suggest that our diagnosis of 8 extra-genital TVT cases out of a total of 90 patients with TVT which were received over a period of 3 years of observation may give an estimate about the incidence of extra-genital TVT cases. In a report from Nairobi, Kenya TVT was diagnosed in 181 patients out of a total of 1535 tumor cases at a small animal clinic. Of these cases, only 8 were reported as having extra-genital involvement (15). In addition, metastatic TVT was reported in the eye of a 5 year old Pointer which had TVT on its penis (16). Perez et. al. (13) have reported 3 primary TVT cases in the maxillary and nasal sinuses, which is quite similar to our findings. As explained in this report, a bloody nasal discharge at the onset and deformation of the nasal bone in the preceeding period was noted (3,13,14,18,25). According to these observations, we assume that TVT should also be considered in the etiology of a particular pathology associated with permanent nasal discharge. Although 6 of the 8 TVT cases were diagnosed in males and 2 in females, there is no evidence of a particular predilection associated with sex and breed in detailed studies. Moreover, ages between 2 and 5 years are indicated to be the most common time for the incidence of these tumors (1-3). Also in our study, it was seen that all dogs involved in our report were sexually mature and all were within these age limits. TVT which proliferate in genital organs have a variable size and width, a cauliflower-like appearance and are generally in the form of a mass bearing a stalk or in the form of small nodules. Generally, their outer surface is ulcerated. 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