Presentation and Biological Behavior

Transmissible venereal tumors (TVTs) were the first described transplantable neoplastic process. They are more commonly seen in more tropic urban areas where there are large numbers of free-roaming dogs. Young sexually active dogs are most commonly affected because of direct contact and transplantation of neoplastic cells; external genitalia are most commonly affected. The typical social behavior of dogs licking and sniffing result in transplantation in other locations including the oral and nasal cavities. The TVT is considered mostly to be a benign neoplastic process that, with the aid of a competent immune system, will often spontaneously regress; however, metastatic disease, particularly to the intraocular space, may rarely occur.^10,26

Cytologic Presentation

Aspirates and touch preparations of a TVT generally yield a large number of neoplastic cells. The typical TVT cell is the epitome of the discrete round cell neoplasm group. The distinctive discrete round cells have eccentric round nuclei with uniform granular chromatin patterns and, oftentimes, a single round prominent nucleolus. Mitotic figures are common and abnormal mitotic figures may be present, but these abnormal figures are not useful in predicting biological behavior. Neoplastic cells range from 12 to 24 μm in diameter and they have moderate amounts of granular and moderately blue staining cytoplasm. Distinguishing cytoplasmic granules are not present; however, low to moderate numbers of TVT cells have distinguishing, clear, distinct, punched-out cytoplasmic vacuoles. These vacuoles are commonly similar in size and arranged in a linear array along the inner surface of the cell membrane (Figure 4-1).^20,22

Figure 4-1 Transmissible venereal tumor. Aspirates of a transmissible venereal tumor on the prepuce of a dog. A, Highly cellular specimen containing a monotonous population of discrete round mononuclear cells mixed with small amounts of peripheral blood. (Wright’s stain.) B, Higher magnification of a similar field of view demonstrating the discrete round nature of the cells, the eccentric round to slightly oval nuclei, the uniform chromatin patterns and the moderate amounts of pale blue cytoplasm with multiple, discrete, clear vacuoles at the periphery of the cell. (Wright’s stain.)

In addition to the neoplastic cells, normal-appearing small lymphocytes, few well-differentiated plasma cells, and rarely seen histiocytes/macrophages are commonly present.²⁰ These cells tend to increase in relative numbers during spontaneous regression of the neoplastic process; a localized immune response is the cause for the regression.

Presentation and Biological Behavior

Mast cell tumors are among the most common cutaneous neoplasms of dogs and cats; however, they may occur at any anatomic location both as primary and secondary neoplastic disease.²⁶ They are most commonly seen in middle aged dogs and cats, but any age animal is susceptible. In the dog, mast cell tumors are considered malignant with potential of wide-spread dissemination. A histologic grading scheme has been used to help predict biological behavior; however, even well-differentiated Grade I mast cell tumors have the potential for dissemination. Cytologic identification of metastatic or disseminated mast cell tumor, regardless of degree of differentiation, is of great value. Recently, investigators have suggested that detection of agyrophilic nucleolar organizer regions (AgNORs), which are an indirect measurement of cellular proliferation, may prove more subjective in predicting biological behavior. This staining process can be applied to both cytologic specimens and formalin-fixed and paraffin-embedded tissue sections. High AgNOR counts correlate well with poor prognosis.

The general features of the histologic grading system with canine cutaneous mast cell tumors are outlined next:^10,20

Feline mast cell tumor has multiple presentations. Isolated cutaneous mast cell tumor is generally considered a benign lesion in the cat and complete excision typically proves curative; however, dissemination may even be seen in cases with suspected isolated cutaneous mast cell tumor.^6,12,25 A guarded prognosis with short median survival times is reported in cats with multiple cutaneous mast cell tumors, recurring mast cell tumors and primary splenic disease. Degree of differentiation is commonly considered a poor prognostic finding; however, the literature is contradictive related to the more poorly differentiated mast cell tumor in the cat. One study found no correlation between degree of cell differentiation and prognosis.^3,13

Cytologic Presentation

The diagnosis of mast cell tumor in the dog and cat is relatively straightforward in most cases. Cytologic specimens are commonly very cellular and peripheral blood contamination is common. In addition to the distinctive discrete round cell characteristics, mast cell tumors have distinguishing fine to coarse purple granules when stained with a Romanowsky-type stain (Figure 4-2).³ These granules allow a definitive diagnosis in most cases; however, it is reported that one of the most commonly used stains in practice, Diff-Quik, often fails in staining these granules making accurate identification of mast cell tumor from other discrete round cell tumors difficult or impossible. Anecdotal reports suggest that approximately 15% of canine mast cell tumors will not stain with Diff-Quik (Figure 4-3). In reality, if one examines the specimen very carefully, although staining may be significantly less with Diff-Quik, there are still identifiable purple granules in neoplastic cells. Additional anecdotal reports suggest that prolonged fixation of mast cell tumors in the first solution of the Diff-Quik stain improves staining of mast cell granules.

Figure 4-2 Mast cell tumor. Aspirates of two well-differentiated mast cell tumors on the skin of two different dogs. A, Moderately cellular specimen with significant peripheral blood contamination, which is common with mast cell tumor aspirates. The neoplastic cells are uniform and well differentiated. Nuclei are almost obscured from view because of the many coarse purple granules. Note the one eosinophil in the center left of the field of view. (Wright’s stain.) B, Highly cellular preparation with densely packed sheets of mast cells where neoplastic cell nuclei are stained very pale blue because of the heavy degree of granulation and lack of stain penetration to the nucleus. (Wright’s stain.)

Figure 4-3 Aspirates of a cutaneous mast cell tumor on a dog. The image on the left is from a Wright’s-stained preparation, and the image on the right is from a Diff-Quik–stained preparation from the same aspirate. Based upon the Wright’s-stained preparation (left), the tumor is characterized as moderately well differentiated with neoplastic cells containing variable numbers of fine to coarse, purple to pink granules. On the Diff-Quik–stained preparation (right), only extremely few cytoplasmic granules are distinguishable. The eosinophil in the center of the field of view gives a possible clue to an underlying poorly differentiated mast cell tumor or one of those mast cell tumors that do not stain well with Diff-Quik stain.

Although canine mast cell tumor grading is based upon histologic evaluation where comments on degree of tissue invasion becomes an important criterion, degree of differentiation of mast cell tumor cells is possible cytologically and correlation to histologic grading is good. The less differentiated cells are less granulated and have greater variability of cell size, nuclear size, and nuclear-to-cytoplasmic ratios. Prognosis should be considered guarded for the less differentiated canine neoplasms; however, it should be noted that well-differentiated mast cell tumors may disseminate also. Identification of metastasis to possible regional lymph nodes or parenchymal organs) proves most beneficial in characterizing the biological behavior of mast cell tumors in the dog and cat (Figure 4-4). With the feline mast cell tumor, the distribution of neoplasms (isolated or multiple or disseminated) and the degree of circumscription of the neoplasm is potentially more predictive on biological behavior than degree of differentiation (Figure 4-5).

Figure 4-4 Aspirate of a popliteal lymph node from a cat with multiple cutaneous mast cell tumors. Note the mixture of moderately well-differentiated mast cells mixed with many normal appearing small lymphocytes, which represent a population of residual normal lymphoid elements in the lymph node. A single eosinophil is noted in the top right region of the field of view; eosinophils are not as commonly seen in as feline mast cell tumor as in the canine counterpart. (Wright’s stain.)

Figure 4-5 Aspirate of an isolated and well-defined cutaneous mast cell tumor in the skin of a cat. Intermixed with moderate amounts of peripheral blood, there are many poorly granulated mast cells. There is marked cytomorphologic atypia; however, upon complete surgical excision, this animal was disease free with no recurrence of neoplastic disease. (Wright’s stain.)

Mast cell tumor cell nuclei are generally round to slightly oval and paracentral in location. If discernable, nuclear chromatin patterns are finely stippled and uniform; however, irregularly clumped chromatin patterns may be seen in less differentiated mast cell tumors. Nuclei are often obscured from view with heavily granulated mast cells or they are extremely pale staining due to the high affinity of the cytoplasmic granules to the stain. Eosinophils may be present in the background and these are more commonly seen in canine mast cell tumors than feline mast cell tumors (Figure 4-6). They are not predictive of biological behavior. Low numbers of normal appearing small lymphocytes may be seen in feline cutaneous mast cell tumors.

Figure 4-6 Aspirates from cutaneous mast cell tumors on two different dogs. A, Wright’s-stained specimen. B, Diff-Quik–stained specimen. The samples are highly cellular, containing a mixture of poorly granulated mast cells and numerous eosinophils. The high number of eosinophils may help in suggesting that the underlying discrete cell neoplastic process is a poorly differentiated mast cell tumor.

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