Three-year-old, male, English setter mix, (Canis familiaris).The three-year-old intact male English setter mix was picked up by county animal control when it was found roaming freely in a small rural community in Southern Arizona.  Aspirate cytology from the preputial mass and several cutaneous masses were submitted.

Gross Description:  

The dog had a large ulcerated circumferential mass effacing the preputial mucosa and numerous variably sized cutaneous masses throughout the caudal dorsum, right and left flank, and inguinal regions.  The superficial cervical lymph nodes were enlarged.

Histopathologic Description:

The aspirate preparations from the dermal masses all revealed the same process.  The preparations have high cellularity with large numbers of intact cells for evaluation.  There is minimal hemodilution. The nucleated cell population consists of round cells with moderate anisokaryosis and anisocytosis.  The nuclei are round with coarse “ropey” chromatin and often have a single large pale lightly basophilic nucleolus.  The cytoplasm is lightly basophilic and contains small to moderate numbers of discrete round vacuoles.  Mitotic figures are common and atypical mitoses are seen.  There are occasional neutrophils and small lympho-cyte seen intermixed with the neoplastic round cells. The cytology preparations from the prepuce showed the same cytological findings.

Morphologic Diagnosis:  

Transmissible venereal tumor (TVT) metastatic to skin.

Lab Results:  

The dog was positive for Ehrlichia canis using in-house ELISA testing.


Transmissible venereal tumor

Contributor Comment:  

Transmissible venereal tumor is a transplantable neoplasm that affects members of the canid family (domestic dogs, coyotes, foxes, and wolves).3 The tumor has a global distribution and highest prevalence in regions with limited canine population control. The tumor spreads by sexual contact and is usually localized to the mucosal surface of the external genitalia of both male and female dogs.  However, masses have been reported in the mucosal surfaces of the nasal passage, oral mucosa, anus, and conjunctival surfaces of the eye.3,7 Metastatic disease is not common but has been documented. In most cases, metastasis is to the regional lymph nodes, but extension of the neoplasm to skin, kidney, brain, bone, peritoneum, and other tissues has been reported.1,3 The tumor cells are aneuploid and have a unique long interspersed nuclear element (LINE-1) that may be useful to confirm TVT origin in cases involving tumors in unusual sites.10,12

While TVT is a relatively uncommon tumor in most of the United States, rural areas that have higher numbers of intact dogs, such as many parts of Southern Arizona, cases are seen on a regular basis.  The histological and cytological characteristics of the neoplastic cells along with the location of the mass in association with the external genitalia make the diagnosis of this tumor relatively straight forward.  In this case, the cytological and histological findings from the skin lesions and the preputial lesion were identical supporting metastatic disease.  There is one report of a prepubertal female dog without any genital involvement.4 It is proposed that the tumor cells were transplanted from the dam by cohabitation and grooming/social behaviors.  While multicentric disease cannot be ruled out, it is unlikely that multiple sites of transplantation through intact haired skin would explain the presence of the skin lesions in this adult male dog with a concurrent preputial mass.

JPC Diagnosis:  

Fine needle aspirate, cutaneous mass: Transmissible venereal tumor, English setter mix, Canis familiaris.

Conference Comment:  

Canine trans-missible venereal tumor (TVT), also known as Sticker tumor or venereal granuloma, is an extremely old and remarkably stable transmissible cancer that first arose in canids approximately 11,000 years ago.2,5 Based on genetic studies, the founder breed is thought to be closely related to wolves or ancient Eastern Asian dog breeds.1 TVT dispersed across several continents about 500 years ago and is currently found on every continent in the world other than Antarctica.5,12 It is the oldest known continuously passaged somatic cell lineage.5 As mentioned by the contributor, TVT is mainly transmitted during coitus, but can also be transmitted by licking, biting, or rubbing behaviors.2,8 The infecting cells are physically transplanted and grow as a xenograft in host tissue. Neoplastic cells are thought to be of histiocytic origin and are immune-positive for vimentin, lysozyme, alpha-1-antitypsin, glial fibrillary acidic protein, and are immune-negative for cytokeratin, S100, and muscle markers.1,2,9

Typical gross findings of TVT include solitary or multiple papillary, nodular, ulcerated, and inflamed masses on the mucous membranes of the penis, prepuce, vulva, and vagina, and/or skin and subcutis of the head, neck, limbs, trunk, scrotum, and perineum. There is occasional extension to the uterus and cervix.2,9 A recent study demonstrated ocular lesions as the single manifestation of TVT with extension to the adjacent conjunctiva and nictitating membrane, presumably by extra-genital inoculation.3 As mentioned by the contributor, metastasis uncommonly occurs in the draining lymph node.9

After transmission, tumorous lesions typically appear within two months. Conference participants discussed the patho-genesis of the tumor growth, stabilization, and regression phases. The initial growth stage is called the progressive phase (P). During the P phase, almost all TVT cells lack expression of major histocompatibility complex (MHC) I and II due to production of inhibitory cytokine transforming growth factor-beta (TGF-beta). This allows the TVT cells to grow and evade immune destruction by cytotoxic T-lymphocytes. After three to nine months, the tumor stabilizes and begins to spontaneously regress. During the regression (R) phase, interleukin-6 (IL-6) from infiltrating lymphocytes is thought to work in conjunction with interferon-gamma (IFN-gamma) to antagonize TGF-beta and increase MHC I and II expression on TVT cells.1,8-10

In addition to TVT, conference participants also discussed the devil facial tumor disease (DFTD), which is an emerging rapidly fatal transmissible tumor that is decimating the wild Tasmanian devil population.8,11 This tumor is of Schwann cell origin and is spread through biting. Tumors occur primarily in the mouth, head, and neck. DFTD cells evade immune destruction via production of TGF-beta and down regulation of MHC-I and II expression, similar to TVT. However, unlike TVT, spontaneous regression has not been reported in DFTD, and mortality occurs in all affected animals via starvation and frequent metastasis.8 Other transmissible tumors include clam leukemia of soft shell clams and the contagious reticulum cell sarcoma of Syrian hamsters first described in the 1960’s.6,8,11


1. Ganguly B, Das U, Das AK. Canine transmissible venereal tumor: A review. Comp Oncol. 2016; 14(1):1-12.
2. Gross TL, Ihrke PJ, Walder EJ, Affolter VK. Skin Diseases of the Dog and Cat. 2nd ed. Oxford, UK: Blackwell Publishing; 2005:800-803.
3. Komnenou AT, Thomas AL, Kyriazis AP, et al. Ocular manifestations of canine trans-missible venereal tumor: A retrospective study of 25 cases in Greece. Vet Rec. 2015; 176(20):523-527.
4. Marcos R, Santos M, Marrinhas C, et al. Cutaneous transmissible venereal tumor without genital involvement in a prepubertal female dog. Vet Clin Pathol. 2006; 35:106–109.
5. Murchison EP, Wedge DC, et al. Transmissible dog cancer genome reveals the origin and history of an ancient cell lineage. Science. 2014; 343:437-440.
6. Ostrander EA, Davis BW, Ostrander GK. Transmissible tumors: Breaking the cancer paradigm. Trends Genet. 2016; 32:1-15.
7. Park MS, Kim Y, Kang MS, et al., Disseminated transmissible venereal tumor in a dog. J Vet Diagn Invest. 2006; 18(1):130-133.
8. Pye RJ, Woods GM, Kreiss A. Devil facial tumor disease. Vet Pathol. 2016; 53(4):726-736.
9. Schlafer DH, Foster RA. Female genital system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. St. Louis, MO: Elsevier; 2016:448-449.
10. Setthawongsin C, Techangamsuwan S, Tangkawattana S, et al. Cell-based polymerase chain reaction for canine transmissible venereal tumor (CTVT) diagnosis. J Vet Med Sci. 2016; 78(7):1167-1173.
11. Siddle HV, Kaufman J. A tale of two tumours: Comparison of the immune escape strategies of contagious cancers. Mol Immunol. 2013; 55:190-193.
12. VonHoldt BM, Ostrander EA. The singular history of a canine transmissible tumor. Cell. 2006; 126(3):445-447.

Click the slide to view.

4-1. Preputial mass, dog.

4-2. Preputial mass, dog.

4-3. Preputial mass, dog.

4-4. Preputial mass, dog.

4-5. Preputial mass, dog.

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