Page 375 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

CHAPTER 19 Tumors of the Skin and Subcutaneous Tissues 353

TABLE 19.1 Most Common Canine Skin Tumors a The association of canine oral PPV with the development of
oral papillomas has been studied since the 1950s. 29,30 The associa-
tion of viral infection with the development of SCC has evolved
SKIN TUMOR INCIDENCE IN DOGS N = 8901 SKIN TUMORS
VetBooks.ir Tumor Type Overall (No.) Overall (%) from a combination of evidence, including the detection of canine
PPV in oral and cutaneous SCCs and the induction of cutaneous
Mast cell tumor
16.8
1494
SCC in 10 beagles out of 4500 vaccinated with a live oral PPV
Lipoma 758 8.5 vaccine. 31–33 Canine oral PPV has also been detected in multiple
32
cases of cutaneous SCC. A novel PPV with malignant potential
Histiocytoma 752 8.4
34
was cloned from a dog with footpad papillomas. Dogs persis-
Perianal gland adenoma 692 7.8 tently infected with this novel virus developed invasive and meta-
static SCC. Several additional novel canine PPVs were detected
35
Sebaceous gland hyperplasia/ 577 6.5 in SCC from a variety of locations, including four dogs with cuta-
adenoma
neous tumors. 36
Squamous cell carcinoma 531 6.0 Case reports support the correlation between PPV infection
Melanoma 500 5.6 and the development of invasive SCC, including lesions of mixed
histology. 33,37,38 Similar to the epidemiologic studies in immu-
Fibrosarcoma 478 5.4 nosuppressed people, a case report of a patient on ongoing che-
Basal cell tumor 445 5.0 motherapy developing cutaneous PPV infection and multiple
papillomas supports the concept of immunosuppression allow-
Malignant peripheral nerve sheath 381 4.3 ing persistent infection of PPV. Susceptibility to infection may
39
tumor
also be breed dependent. 40,41 Recently a dog with multiple viral
Papilloma 251 2.8 plaques developed more than 20 invasive cutaneous SCCs over a
3-year period, with no evidence of underlying immunosuppres-
Sweat gland adenocarcinoma 101 1.1
sion. A novel PPV was sequenced from these lesions.
42
Sebaceous adenocarcinoma 42 0.5 In cats, PPVs are associated with viral plaques and feline fibro-
papillomas (also known as feline sarcoids). 43,44 PPV can be detected
Miscellaneous 1899 21.3
with IHC in most feline viral plaques; as these plaques progress
Total 8901 100 to SCC, the ability to detect PPV antigens decreases. However,
45
when polymerase chain reaction (PCR) is used to amplify PPV
a Overall incidence of the most common canine skin tumors as determined from the collation DNA, up to 76% of “UV-protected” SCCs are positive, com-
of 10 worldwide studies. 1,3,7–14
26
pared with 42% of SCC in regions exposed to UV irradiation.
In people, it has been suggested that UV exposure and PPV infec-
46
tion may act as cofactors in the development of SCC. In a large
retrospective study that tested for the presence of PPV in SCCs,
SCCs in situ, or Bowen’s in situ carcinomas (BISCs) in 84 cats,
TABLE 19.2 Most Common Skin Tumors in Cats a no correlation was found with PPV infection and UV exposure.
47
SKIN TUMOR INCIDENCE IN CATS N = 1,225 SKIN TUMORS A novel feline PPV has been sequenced from three feline BISC
lesions. Twenty-five percent of the 73 cutaneous lesions were
48
Tumor Overall (No.) Overall (%)
positive for PPV by PCR. Human PPVs 5, 21, and 38 were iden-
Basal cell tumor 282 23.02 tified in approximately half of the virus-positive cats.
Mast cell tumor 202 16.49 A second study evaluated the levels of p16 in 60 cats; tissues
tested included 14 viral plaques, 14 BISCs, 18 invasive SCCs,
Squamous cell carcinoma 127 10.37 and 14 trichoblastomas (controls). Eleven of the invasive SCCs
26
Fibrosarcoma 219 17.88 were solar induced, and seven were classified as non–solar-induced
tumors. P16 protein levels were compared with the trichoblasto-
Apocrine adenoma 41 3.35 mas and solar-induced SCCs and were found to be elevated in all
Lipoma 40 3.27 viral plaques, BISCs, and nonsolar invasive SCCs, consistent with
26
the presence of PPV infection. Most recently, the presence of
Hemangiosarcoma 35 2.86 E6 and E7 RNA was demonstrated in preneoplastic and neoplas-
Sebaceous adenoma 34 2.78 tic feline cells in a pattern similar to that seen with PPV-induced
SCC in people. Taken together, this data supports the possibility
49
Fibroma 33 2.69
of a role for PPV in the development of SCC in cats.
Hemangioma 21 1.71
Melanoma 21 1.71 Immune Status
Malignant fibrous histiocytoma 9 0.73 Immunosuppressed people have a greatly increased risk of skin can-
cer; organ transplant recipients have up to a 100-fold increased risk
Miscellaneous 124 10.12
for development of SCC. Although this may reflect susceptibil-
50
Total 1225 100 ity to persistent PPV infection in some instances, it is also thought
to reflect loss of normal immune surveillance, with resulting lack
a Relative incidence of the most common skin tumors in cats collated from four studies. 2,6,7,15 of an immune response against early neoplasia. A case report of

the development of multiple cutaneous hamartomas and SCCs in