Joint Pathology Center Veterinary Pathology Services WEDNESDAY SLIDE CONFERENCE 2013-2014 Conference 15 12 February 2014 CASE I: T2319/13 (JPC 4035545). testing revealed an infection with feline lentivirus (FIV virus). Kept in an animal shelter, the Signalment: Juvenile male castrated domestic condition of the cat improved with still occasional shorthair cat (Felis catus). episodes of stomatitis. In summer 2012, a pedunculated mass on a forepaw was removed History: A juvenile stray cat was found in surgically. In spring 2013, the cat showed severe neglected condition in the spring of 2012. The facial dermatitis, otitis, and the mass at the paw animal had diarrhea and an ulcerative stomatitis had recurred. Suspecting a malignant neoplasm, as well as many endoparasites and a marked the tumor tissue, including the claw, was resected ectoparasitosis (fleas and mites). Serological and submitted for histopathological examination. 1-1. Footpad, cat: A polypoid mesenchymal neoplasm arises from the 1-2. Footpad, cat: The moderately cellular neoplasm is composed of haired skin and pawpad. (HE 0.63X) spindle cells arranged in vague bundles. The overlying epithelium is moderately hyperplastic and forms deep rete ridges. There is mild orthokeratotic hyperkeratosis overlying the neoplasm. (HE 38X) 1 WSC 2013-2014 1-3. Footpad, cat: Neoplastic spindle cells are spindled to stellate with a small amount of eosinophilic cytoplasm on a moderately dense fibrous stroma. Rarely, spindle cells are oriented perpendicularly to the epidermis. (HE 260X) Gross Pathology: A 2.5 x 2 x 1.5 cm mass close eosinophilic cytoplasm. Nuclei are oval to to a claw, partially covered by skin, was elongated with finely stippled, occasionally submitted. The mass had an irregular cauliflower- vesicular chromatin and a single, variably distinct like surface. The consistency was firm and the nucleolus. Mitotic rate is very low (<1 per 10 color on the cut surface was grey-white high power fields). Cells show mild anisocytosis throughout. and anisokaryosis. Occasionally, neoplastic cells are arranged perpendicular to the dermal- Laboratory Results: Detection of papillomaviral epidermal interface. Interspersed within the DNA (PCR): positive spindle cells, there are moderate numbers of well- [Institute of Hygiene and Infectious Diseases of differentiated mast cells (3-4 per high power Animals, Justus Liebig University Giessen] field). The overlying epidermis is hyperplastic Detection of FeSarPV (PCR): positive with occasional papillary projections, acanthosis [Institute of Virology, Justus Liebig University and spongiosis, elongated, thin, often branching Giessen] rete ridges, and moderate orthokeratotic and parakeratotic hyperkeratosis. Histopathologic Description: Skin, claw: Protruding from the superficial dermis and Contributor’s Morphologic Diagnosis: Skin elevating the overlying epidermis, there is a and claw: Feline sarcoid, feline, (Felis moderately cellular, well-demarcated, lobular and domesticus). pedunculated, expansively growing, unencapsulated neoplasm composed of spindle Contributor’s Comment: Feline sarcoids are cells arranged haphazardly in interweaving also known as feline fibropapillomas. They most bundles and streams within moderate amounts of often occur in young male cats at various sites of collagen and sparse vessels. Neoplastic cells are the skin (e.g. pinna, lip, nose, digits, tail, gingiva). spindle shaped, have indistinct cell borders, and a They can be ulcerated and cats can harbor one or moderate amount of fine fibrillar, pale several of these tumors. Recurrence often occurs; 2 WSC 2013-2014 metastasis has not yet been described.3,4,5 Feline trauma.6 Interestingly, as in the presented case, sarcoids share many similarities with sarcoids in FIV infection is reported in cases of feline equine species regarding their etiology, clinical sarcoids21 and can play a role in the pathogenesis outcome, morphology, and prognosis.3,4,10 of the disease. Different papillomaviruses are suspected to be Tumors most often occur in young male cats. responsible for feline sarcoids. The feline sarcoid They are solitary or multiple skin nodules that associated papillomavirus (FeSarPV) is similar to measure up to 2 cm and they can be pedunculated BPV-1, OvPV-1 and BPV-2. The genome of or ulcerated. Predilection sites are the skin at the FeSarPV shows high homology with the genome ears, lips, tail or paws. Their consistency is firm. of papillomaviruses of different ruminants.22 3,4,18 Some of these papillomaviruses are classified as members of the genus Deltapapillomavirus. In Histomorphology of feline sarcoids is identical to contrast, the host specific papillomaviruses of equine sarcoids. Characteristically they show cats, causing papillomatous plaques and real proliferating fibroblasts covered by hyperplastic papillomas, are members of the genus epidermis.18 Differentials are fibrosarcoma, Lambdapapillomavirus.9 Infection of horses or histiocytic sarcoma, other spindle cell sarcomas, cats by ruminant papillomaviruses is therefore peripheral nerve sheath tumor and amelanotic regarded as cross-species papillomavirus melanoma.3,4 infection. Feline sarcoids often show local recurrence after For a recent classification of animal surgery. Often, relapses show a marked increase papillomaviruses, see Rector and van Ranst, in growth rate.4 2013.16 The presented case shares most of the Sarcoids are also described in lions. A possible characteristics described for that entity. Three mode of infection of large felids may be the months after surgery, the health status of the cat consumption of bovine carcasses that had not was good, and there were no signs of tumor been skinned.15,17 recurrence. Viral papillomas caused by feline papillomavirus JPC Diagnosis: Haired skin and footpad: Feline (FdPV-1) are rarely found in domestic cats.22 fibropapilloma (sarcoid). These lesions are most likely associated with different forms of immunodeficiency in stray cats Conference Comment: Papillomavirus (PV) often in association with FIV infection.2,11 Feline belongs to the family Papillomaviridae (formerly papillomatous plaques, often caused by FdPV-28, Papovaviridae); it is a non-enveloped, icosahedral sometimes undergo malignant transformation to virus with double stranded DNA that is resistant squamous cell carcinoma (SCC).4,8,19 In one to high temperatures, low pH, lipid solvents and report, Human papillomavirus type 9 was detergents. Infection occurs via direct/indirect identified using molecular biology.13 contact with entry through cutaneous abrasions, and virus replication is intimately linked to the Predisposing factors of feline sarcoids are the growth and differentiation of epidermal and behavior of rural cats. Contact with ruminants is mucosal squamous epithelial cells. occasionally mentioned. Numerous cases of Papillomaviruses are divided into 16 genera sarcoids are reported from areas with dairy (Alpha, Beta, Gamma, Delta, Epsilon, Zeta, Eta, industry (e.g. New Zealand, Minnesota).3,5,12,18 Theta, Iota, Kappa, Lambda, Mupa, Nupa, Xipa, However, many interspecies contacts or modes of Omikron and Pipapapillomvirus) on the basis of virus transmission are possible. A recent study DNA sequence/genome, host range and biological demonstrated detection of feline sarcoid PV properties. The most important genera in genome sequences within different bovine skin veterinary medicine include the following:7,10 samples.12 Additional factors that favor the development of sarcoids in cats are in discussion, for example, 3 WSC 2013-2014 • Alpha (α): Oncogenic “high risk” cytoskeleton and cell–cell/cell–matrix mucosal types that cause benign mucosal/ interactions, ultimately contributing to cutaneous lesions uncontrolled cellular proliferation. This is in • Beta (β): Cutaneous PVs that rarely cause contrast to Human papillomavirus (HPV) E6 lesions without immunosuppression protein, which acts by stimulating degradation of • Delta (δ): Cause benign fibropapillomas p53.1,14 Furthermore, there is some evidence to in ungulates; unique ability to infect suggest that co-expression of BPV E5 and E7 is multiple species (e.g. Bovine necessary for neoplastic transformation in horses. papillomavirus (BPV)-1 and -2 affects In human mucosal alpha-PVs (e.g. HPV-16, -17), both cattle and horses) E7 binds and inactivates the tumor suppressor Rb, • Epsilon (ε): BPV-5 and -8; cause both promoting cell cycling.10 In addition to equine fibropapillomas and true papillomas sarcoids induced by BPV-1 and -2, Equus • Lambda (λ): Associated with skin lesions caballus papillomavirus-2 (EcPV-2) has recently in the dog and cat; Felis domesticus PV1 been identified in equine genital papillomas, in 6 (FdPV-1) and canine oral PV (COPV) situ carcinomas (ISC) and ISCCs. • Xipa (ζ): Bovine papillomaviruses (BPV)-3, -4, -6, -9 and -10; restricted to In cats, FdPV-1 and -2 infection, in combination cattle and cause true, cutaneous squamous with solar-induced p53 mutation and papillomas papillomavirus-induced inhibition of keratinocyte apoptosis, may lead to uncontrolled cell Papillomaviruses are usually host specific, with a proliferation, progressing to Bowenoid in situ strong tropism for cutaneous and mucosal carcinoma (BISC) and, less commonly, SCC. squamous epithelium, where they typically induce Additionally, as noted by the contributor, the formation of benign squamous papillomas or papillomavirus DNA has been localized to fibropapillomas. These tumors tend to proliferating fibroblasts suggesting an association between feline