Bilateral subcutaneous fibrosarcomas in a cat following feline parvo-, herpes- and calicivirus vaccination

Abstract

A crossbred cat developed a subcutaneous fibrosarcoma on the left side of the thorax at the site of previous administration of a feline parvo-, herpes- and calicivirus vaccine. A few months later the cat developed a second mass on the right side of the thorax after a booster vaccine had been administered at this site. This unique case of bilateral fibrosarcomas in a cat shortly after vaccination with parvo-, herpes- and caliciviruses suggests an individual disposition for the development of vaccine-associated sarcomas and a possible triggering of this type of pathological response which could have precipitated the development of the second tumour. To the authors' knowledge, this is the first case of vaccine-induced fibrosarcomas occurring bilaterally after injection of a feline parvo-, herpes- and calicivirus containing vaccine at different sides of the thorax.

On 1 August 2003 an 8-year-old neutered male crossbred cat was presented with a subcutaneous mass located on the left side of the thorax. He was vaccinated annually at the left side of the thorax with a combined feline parvo-, herpes- and calicivirus vaccine (Feliniffa-P, Corifelin-HC, Merial SA, Brussel, Belgium and on one occasion 3 years previously Felocell-CVR, Pfizer Animal Health SA, Louvain-La-Neuve, Belgium).

A presumptive diagnosis of a fibrosarcoma was suggested but additional cytological or histopathological examination was refused by the owner. A booster vaccination was not advised because of the possibility that the mass was a vaccine-associated sarcoma (VAS), but as the owner insisted the booster vaccination was given. This was injected subcutaneously on the right side of the thorax.

The mass was surgically removed 2 months later because it was still increasing in size. No ribs were removed. Histological examination of the mass revealed a poorly demarcated cell dense tumour located in the subcutis and infiltrating in the underlying muscle. The tumour consisted of fusiform cells arranged in bundles. In some areas there were round cells and multinucleate giant cells. There was marked anisokaryosis. At the periphery of the tumour several large aggregates of lymphoid cells were found. On immunohistochemistry the tumour cells stained positive for vimentin with variable intensity. Immunohistochemical staining for feline leukaemia virus (FeLV)-antigen was negative. Desmin immunohistochemistry revealed positive staining in the smooth muscle cells of arterial and arteriolar walls and in the striated muscle cells around the tumour. The tumour cells were desmin negative. Scattered small round cells, representing approximately 0.5% of the cell population in the tumour, were CD3 (T lymphocytes) positive. Also a large proportion of cells in lymphoid aggregates around the tumour were CD3 positive. Finally, very few scattered round cells in the tumour and a large proportion of the cells in the lymphoid aggregates were CD20 and CD79b (B lymphocytes) positive.

Two-and-a-half months after the booster vaccination, the cat developed another subcutaneous mass, this time on the right side of the thorax at the site of the booster inoculation. The owner requested euthanasia. There were no metastases detected on radiographs. There was clinically, and on autopsy, no evidence of regrowth of the mass that had been removed from the left side of the thorax.

On the right side of the thorax a large, poorly demarcated tumour was found. Histological examination revealed a high cell density with large areas of necrosis. Most viable areas in the tumour were composed of fusiform cells (Fig 1). Some areas in the tumour contained a high number of histiocytoid multinucleated giant cells. Anisokaryosis was marked. Immunohistochemically, the tumour cells were vimentin positive; desmin and FeLV and MAC 387 negative. Few CD3 positive cells were found scattered in the tumour, CD20 and CD79b positive cells were not observed.

Fig 1.

Haematoxylin and eosin staining of second tumour showing fusiform cells arranged in bundles (bar=200 μm).

The immunohistochemical profiles in the present bilateral tumours support a fibroblastic origin: as the tumour cells were vimentin positive and desmin negative. All tumours were positive for vimentin in the cases reported by Vascellari et al (2003) and Couto et al (2002). Based on the histological and immunohistochemical characteristics, both of these tumours were diagnosed as VAS in agreement with the description by Gross et al (2005), Madewell et al (2001) and Couto et al (2002). Goldschmidt and Shofer (1992) and Stiglmair-Herb and Ortmann (1986) reported sarcomas at multiple sites in 1.4% and 5.8% of cats, respectively.

Lester et al (1996) and Burton and Mason (1997) reported sarcoma formation after administration of vaccine containing panleukopenia, herpes- and calicivirus.

A direct role for a virus (feline immunodeficiency virus, FeLV, papillomavirus, polyomavirus, herpesvirus) has not been shown (Ellis et al 1996, Kidney et al 2001). These studies decreased the concerns of a retroviral aetiology for VAS. The tumours in the present case were also FeLV negative on immunohistochemistry.

Considerable differences have been reported in lymphoid cell distribution among VAS (Couto et al 2002). A high proportion of T lymphocytes occurs within tumour-associated lymphoid follicles in many specimens, in spite of the fact that follicular formations are primary B cell areas. This was also observed in the case described here.

It has been suggested that inflammatory mediators play a critical role in providing the ideal environment for oncogene activation that leads to tumour development (Ogilvie 2004). Post-vaccination inflammation and granuloma development have been postulated as important early factors in the pathogenesis of VAS (Richards 2005). In the present case, there was no apparent clinical evidence that this cat had developed an inflammation or a granuloma after any of his routine vaccinations.

Published information indicates a role for oncogenes in this disorder (Goad et al 1999). The bilateral development of tumours after booster vaccinations in this case suggests a genetic predisposition to oncogene activation.

As the cat had a history of suspect injection site sarcoma that had not recurred but then developed a similar tumour at the site of booster vaccination, it may be suggested that booster vaccination was contraindicated in this case.