Signalment:  

5-year-old, male, Labrador retriever, canineOn June 5, 2004 the dog was presented with a serosanguineous discharge form the prepuce. It was reported by the owner that these signs had started a week ago. On physical examination, a large mass (10 cm in diameter) could be palpated in the prepuce. The owner reported that the growth was noticed two years ago. Extrusion of the penis revealed an 8x10 cm lobulated and verrucous mass involving the caudal aspects of the penile shaft. On cytologic examination of samples obtained of fine needle aspiration the mass (Fig. 1), a diagnosis of transmissible venereal tumor (TVT) was made. The dog was placed on chemotherapy (vincristine, 4 weekly injections of 0.5 mg/m2 body weight). The tumor had regressed somewhat but an enlargement was noticed in the inguinal lymph node one month after the start of the therapy. The penis was amputated and the lymph node excised. At the histopathological examination TVT was confirmed as the primary tumor and metastatic TVT was diagnosed in the lymph node. The dog was sent home with no further treatment. Two months later it returned to the Veterinary Teaching Hospital for check-up when a mass in the abdominal cavity was palpated. An ultrasound of the abdominal cavity revealed an enlarged left kidney which was excised and sent to the pathology laboratory. The dogs condition seemed to have somewhat improved and it was sent home again. A couple of weeks after surgery the dog started to progressively loose weight and after two months it was euthanatized. The owner did not permit a necropsy.

Gross Description:  

The surgical specimen was that of an enlarged kidney (12.0x7.0x5.5 cm) which presented large multifocal white masses protruding from the capsular surface. At cut surface the pelvis and calices were marked dilated and large amounts of clear fluid oozed from the pelvis. Three large homogenous white coalescing masses (Fig. 3) involved cortex, medulla pelvis and ureter. In some places sparse hemorrhagic and necrotic foci could be observed in the neoplastic mass.

Morphologic Diagnosis:  

Kidney, metastatic transmissible venereal tumor, 5-year-old, male, Labrador retriever, canine

Lab Results:  

Cytology performed in sample collected by fine needle aspiration of the penile tumor revealed clusters of round cells with high nucleus:cytoplasm ratio and moderate anisocytosis. The nucleus of these cells was round or oval and formed by loose chromatin with one irregularly shaped conspicuous nucleolus. The cytoplasm of these cells was scant, slightly basophilic, and occasionally revealed multiple small vacuoles. There were multiples cells in mitosis, occasionally binucleated cells and moderate numbers of small lymphocytes.

Condition:  

Transmissible venereal tumor

Contributor Comment:  

Canine transmissible venereal tumor (TVT), also referred to as Sticker tumor, infectious sarcoma, venereal granuloma, canine condyloma, transmissible lymphosarcoma, transmissible tumor of reticular cells, transmissible histiocytoma and hemoblastoma was described in the 19th century and reportedly is one of the major canine diseases in underdeveloped countries, mainly in those with temperate, tropical or subtropical climates.¹³ The tumor affects exclusively dogs and is considered always potentially malign;¹² the cell of origin of the tumor is still unknown, although iummunohistochemical studies support an histiocytic lineage.⁹ Attempts on viral isolation from TVT tissues have consistently failed in the past; more recently viral particles have been isolated from TVT fragments but the inoculation of theses particles in dogs failed to reproduced the disease;⁸ despite of these negative findings, the viral etiology is favored by some researchers. 

In one study, the neutering of bitches affected by the neoplasm resulted in rapid regression of TVT suggesting that the tumor is somewhat hormone-dependant. Additionally, TVTs reportedly tend to be benign in males and frequently metastatizing in females.^5,8,12 While the number of chromosomes in somatic canine cells is 76, the number of chromosomes in the cells of TVT is consistently 58. Such a disparity led, in the past, to the belief that the neoplasm had been acquired from another animal species. The analysis of the MHC molecules on cells of TVT from dogs of different geographic origins revealed that all have the same surface antigens.⁸

The transmission of TVT occurs by allogenic transplantation of viable neoplastic cells from an affected dog to a susceptible one, normally during copulation; however other means of transmission are possible and include licking, biting, and scratching.^5,8,12 The neoplasms affect the external genitalia (penis and vagina) and the skin adjacent to these areas.^5,8,13 Less commonly affected sites include nasal cavity, eyes, lips and other skin regions.^8,12 Dogs of both sexes and all ages are affected but the disease is more prevalent in sexually active dog (average age 4-5-year-old) living in areas with large populations of stray dogs.^12,13

Gross aspects of TVT are variable but most are either firm or friable verrucous papillary or nodular masses protruding from the surface of penis or vulva.⁵ The tumors can be small single nodules or multilobulated masses up to 15 cm in diameter.⁵ The surface of these neoplasms are smooth, granular and commonly ulcerated from where bleeding is frequent.⁸

Histologically, TVTs consist of round to oval cells which are closely similar to macrophages and are arranged in ribbons or pallisades; their nuclei are large, round, centrally located in the cell displaying clusters of chromatin and a single prominent, centrally located nucleolus. The cytoplasm of TVT cells is moderate in amount, faintly basophilic and vacuolated. Mitotic index is high and the tumor parenchyma is infiltrated by variable numbers of lymphocytes, plasm cells and macrophages. In regressing TVTs, inflammation, necrosis and fibrosis are frequently seen. ^5,8

The prognosis for TVTs is guarded as these tumors are self limiting in most of the cases,⁸ but not uncommonly metastasize to regional lymphnodes, spleen, liver, kidney, peritoneum, lungs and central nervous system.^8,12 Furthermore, surgical excision only results in recurrence which in some reports is close to 60% of the cases.¹² In a study carried out in a dog colony, the neoplasm was transmitted through 40 generations in a total number of 564 dogs, 68% of which developed the disease and 87% had spontaneous regression of the tumor within 180 days. When dogs are submitted to specific chemotherapy, the prognosis is good in the majority of cases. Dogs recovering from this neoplasm acquire cellular and humoral immunity.¹

In the case of this report, necropsy was not allowed and thus was not possible to determine the route of metastasis. It is not possible to ascertain if metastasis foci were present in other organs but the surgeon reported only the tumor in the left kidney. The presence of neoplastic tissue in the pelvis and ureter raises the possibility that dissemination of the tumor might have occurred by ascending the urinary tract.

JPC Diagnosis:  

Kidney: Transmissible venereal tumor, metastatic, Labrador retriever (Canis familiaris), canine.

Conference Comment:  

The contributor gives an excellent description of canine transmissible venereal tumors (TVT). Currently the TVT is the only known naturally transmitted neoplasm. However, it has been proposed that the recently described Devil facial tumor disease may be transmitted in a similar manner.⁷

It is not known how the tumor evades the host immune system. Class I and II major histocompatibility antigens are not expressed by the tumor cells until regression occurs.¹¹ Cells of TVTs secrete TGF-β1 and IL-6 which suppress the expression of major histocompatibility antigens.¹⁴

The histologic appearance of the neoplasm can vary greatly depending on the stage of growth or regression. During regression, TVT cells express major histocompatibility complex class II antigens, and therefore the neoplasms are often infiltrated by inflammatory cells, particularly T lymphocytes. The effect of vincristine administration on the cytomorphology and level of regression in this tumor is difficult to assess.

References:

1. AFIP (Armed Forces Institute of Pathology). Washington: AFIP, 2001c. 26th Wednesday Slide Conference, Case I, 18/04/01. University of Texas (Houston, USA). Available at: WSC Conf 26 2000
2. Foster RA: Female reproductive system. In: Pathologic Basis of Veterinary Disease, eds. McGavin MD, Zachary JF, 4th ed., pp. 1306-1307. Elsevier, St. Louis, MO, 2007
3. Foster RA: Male reproductive system. In: Pathologic Basis of Veterinary Disease, eds. McGavin MD, Zachary JF, 4th ed., pp. 1346-1347. Elsevier, St. Louis, MO, 2007
4. Foster RA, Ladds PW: Male genital system. In: Jubb, Kennedy, and Palmers Pathology of Domestic Animals, ed. Maxie MG, 5th ed., vol. 3, pp. 618-619. Elsevier Limited, St. Louis, MO, 2007
5. Goldschmidt MH, Hendrick MJ: Tumors of the skin and soft tissues. In: Tumors in Domestic Animals, ed. Meuten DJ, 4th ed., pp. 115-117, Iowa State Press, Ames, IA, 2002
6. Kennedy PC, Cullen JM, Edwards JF, Goldschmidt MH, Larsen S, Munson L, Nielsen S: Histological classification of tumors of the genital system of domestic animals. In: World Health Organization Histological Classification of Tumors of Domestic Animals, 2nd series, volume IV, p. 23-38, 69, Armed Forces Institute of Pathology, Washington DC, 1998
7. Loh R, Hayes D, Mahjoor A, OHara A, Pyecroft S, Raidal S: The immunohistochemical characterization of devil facial tumor disease (DFTD) in the Tasmanian devil (Sarcophilus harrisii). Vet Pathol 43:896-903, 2006
8. MacEwen EG: Transmissible venereal tumor. In: Small Animal Clinical Oncology, eds. Wintrow SJ, Macewen EG, 3rd ed., pp. 651-656. Saunders, Philadelphia, PA, 2001
9. Mozos E, M+�-�ndez A, G³mez-Villamandos JC, de las Mulas JM, P+�-�rez J: Immunohistochemical characterization of canine transmissible venereal tumor. Vet Pathol 33:257-263, 1996
10. Park MS, Kim Y, Kang MS, Oh SY, Cho DY, Shin NS, Kim DY: Disseminated transmissible venereal tumor in a dog. J Vet Diagn Invest 18:130- 133, 2006
11. Schlafer DH, Miller RB: Female genital system. In: Jubb, Kennedy, and Palmers Pathology of Domestic Animals, ed. Maxie MG, 5th ed., vol. 3, pp. 547- 548. Elsevier Limited, St. Louis, MO, 2007
12. Susaneck S: Canine transmissible venereal tumor. In: Veterinary Oncology Secrets, ed. Rosenthal RC, pp. 207-209. Hanley & Belfus, Philadelphia, PA, 2001
13. van Heerden J: Problemas dos animais de pequeno porte nos pa+�-�ses em desenvolvimento. In: Tratado de Medicina Interna Veterin+�-�ria: Mol+�-�stias do C+�-�o e do Gato, ed. Ettinger SJ, 3rd ed., pp. 225-234. Manole, S+�-�o Paulo, SP, 1992
14. von Holdt BM, Ostrander EA: The singular history of a canine transmissible tumor. Cell 126:445-447, 2006

A virtual slide is not available for this case.

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