INTRODUCTION
Transmissible venereal tumor (TVT) in dogs is a malignant tumor transmitted due to the transplantation of tumor cells. Although it is most common in female and male external genitalia, extragenital localization has been also reported. It may occur in areas such as the oral mucosa, lips, nasal cavity, eyes, and skin due to the implantation of tumor cells during mating movements, and it has been also less frequently reported in tonsils, liver, pancreas, spleen, lung, kidney and mesenterial lymph nodes[1]. Dogs of both sexes and all ages can be affected, but the tumor is more common in young and sexually active dogs. Macroscopically, they are usually multilobular, but may also consist of a single mass. With this nodule, there may be multi-lobed masses up to 15 cm in diameter and may also invade surrounding tissues. It grows rapidly at first and then remains static for a while. The histogenesis of tumor cells has not been fully defined. The location of the tumor plays an important role in diagnosis. However, in extragenital TVT cases, if there is no genital lesion, a differential diagnosis should be made with histiocytoma, lymphoma, poorly differentiated mast cell tumors, and amelanotic melanomas. Although surgical excision is not preferred in the treatment, it is known that treatment with radiotherapy is also effective when using single-agent or combined chemotherapy protocols[2]. In this case, we aimed to present the histopathological and immunohistochemical findings and the treatment of the tumor with combined radiotherapy and chemotherapy in a 7-year-old male dog of the Siberian Husky breed diagnosed with intranasal TVT.
MATERIAL METHOD
It has been reported that rhinoscopy was performed on 7 years and 7 months old male Siberian Husky dog, who was brought to a veterinary clinic in Lebanon with acutely formed unilateral nasal hemorrhage and stertor symptoms, and a neoplastic mass located in the nasal cavity was observed. Adenocarcinoma was diagnosed as suspicious histopathologically from biopsy samples taken from the mass. Although it was observed that the symptoms decreased when high-dose cortisone treatment was started, it was observed that the symptoms reappeared when the cortisone treatment was terminated. Thereupon, it was reported that the case was suspected to be nasal lymphoma. It was reported that immunohistochemical marking was performed with CD3, CD20, and NSE markers in a pathology laboratory (Laboratoire d’Histopathologie Animale) in France for differential diagnosis, and only NSE positivity was detected, and accordingly, the case was rediagnosed as carcinoma. At the end of the 5 months of the diagnostic investigation, the patient was referred to our clinic for oncological counseling. In the clinical examination, unilateral hemopurulent rhinorrhea, reverse sneezing and exercise intolerance findings were observed. Monocytosis and mild anemia were observed in the hematological examination, and no abnormal findings were found in the echocardiography, electrocardiography, and thorax X-rays performed in the cardiological examination. Contrast-enhanced computed tomography (CT) of the lesion was performed for surgery and radiotherapy planning, and thoracic and abdominal CT scans were performed to evaluate metastasis. Due to the inconsistency in the clinical course of the patient who was referred with the suspicion of possible carcinoma, clinicopathological consultation was made to Istanbul University-Cerrahpasa Faculty of Veterinary Medicine, Department of Pathology. Sections of 3-4 μm thickness from ready-made paraffin blocks were stained with Hematoxylin-Eosin (H&E) and examined under a light microscope. Immunohistochemical marking was performed with the Streptavidin-Biotin method in order to determine the differential diagnosis, prognosis, and appropriate treatment approach. The antibodies applied and the dilution rates are shown in Table 1.
In the clinical examination of the case, a unilateral hemopurulent discharge from the left nasal cavity was observed. Difficulty in breathing and exercise intolerance were observed due to the obstruction caused by the mass. Wheezing and reverse sneezing were detected due to this situation. Although there was no abnormal finding in the cardiological examination, monocytosis and mild anemia was detected as a result of the complete blood count. CT scan was performed under general anesthesia after pre-anesthetic controls to create a radiotherapy protocol, determine lesion borders, and control metastasis. In the head and neck sections in the examination area, a soft tissue density appearance was observed in the left nasal cavity, which completely filled the cavity, could not be distinguished from the turbinates, showed minimal contrast enhancement after intravenous contrast agent (Omnipaque 300mg/100ml) administration, and caused irregularity in the nasal septum in the anterior. In addition, soft tissue density that completely prevented aeration was observed in the left paranasal sinuses (Figure 1).
Figure 2 H&E. A. Tumor tissue separated by thin fibrous stroma. 100X, Bar=100μm B. Neoplastic cells with basophilic cytoplasm, with a centrally located round nucleus without distinct cell borders (arrowhead), numerous mitotic figures (arrow). 400X, Bar=10 μm
Figure 3 Immunohistochemistry. 200X, Bar=50 μm A. Vimentin positive staining in the cytoplasms of the cells. B. Lysozyme positive staining of the cytoplasms of neoplastic cells in different intensity
TREATMENT Treatment was started for monocytosis and anemia detected in the complete blood count at the first examination of the patient. First of all, the dose of cortisone, which was used at high doses, was tried to be reduced gradually. After premedication, a weekly session of Vincristine sulfate at a dose of 0.6mg/m2, a total recommended 6-8 week chemotherapy session was targeted. However, as a result of severe neutropenia attacks after vincristine sulfate administration, radiotherapy was added to the treatment protocol based on the literature[2].
Although TVT is rarely seen in household dogs, it can occur frequently in stray animals. Extragenital nasal location without genital lesions has been reported[3]. This atypical behavior may result from regression of the primary tumor or tumor cells directly implanted in the nasal mucosa. The biological behavior and pathogenesis of the extragenital forms of TVT are still not fully elucidated because the number of cases is low in all relevant reports. The fact that the case we are presenting is located primarily intranasally rather than in the regions where the tumor is frequently localized, and distinguishing it from tumors seen in this region, such as lymphoma, histiocytoma, poorly differentiated mast cell tumors, amelanotic melanomas, and poorly differentiated carcinomas, makes the diagnosis difficult. In this case, vimentin positivity and cytokeratin negativity were detected immunohistochemically. These findings are compatible with the literature. Cytokeratin and vimentin can be used in the differential diagnosis of extragenital TVT and carcinomas. S-100 negativity has been reported in TVT cases in the literature. S-100 is usually expressed in melanomas. Since S-100 negativity was detected in our case, it was differentiated from melanomas. CD-3 and CD-79a negativity enabled differential diagnosis with lymphomas. It is reported in the literature that lysozyme is a reliable marker that can be used in the differential diagnosis of TVT. In this case, the heterogeneous lysozyme positivity was thought to be due to the differentiation observed in the cells. The case was diagnosed as extragenital TVT due to the positivity of vimentin and lysozyme together with the light microscopy findings. While radiotherapy and chemotherapy are seen as the most effective approaches in treatment, surgery is not preferred because of both recurrence and difficult approaches. Likewise, the presence of neoplasia in the nasal region creates difficulties in treatment and may cause complications. We think that the rare diagnosis of intranasal TVT and the combined radiotherapy and chemotherapy treatment without any relapse afterward contributed to veterinary oncology. REFERENCE [1] Agnew W. and MacLachlan J. Tumors of the Genital Systems. In: Meuten D, ed. Tumors in Domestic Animals. Ames, IA: John Wiley; 2017: 718-721 [2] Thrall D.E. Orthovoltage Radiotherapy of Canine Transmissible Venereal Tumors. American College of Veterinary Radiology Vol. 23, no. 5, 1982; 217-219. [3] Wilson W.D. Tumors of the Respiratory Tract. In: Meuten D, ed. Tumors in Domestic Animals. Ames, IA: John Wiley; 2017: 467-477
