FISS Research Articles

Computed tomography characteristics of fibrosarcoma -- a histological subtype of feline injection-site sarcoma.

Feline injection-site sarcoma (FISS) may be a consequence of subcutaneous injection. In the present study, the medical records and the computed tomography (CT) features of 22 cats with a FISS, histopathological subtype fibrosarcoma, were used. The majority of the fibrosarcomas (45%) were located in the interscapular region. All fibrosarcomas, except one with mild enhancement, showed strong contrast uptake, characterised as ring (42%), heterogeneous (36%), homogeneous (9%), heterogeneous/ring (6.5%) or mixed heterogeneous/homogeneous enhancement (6.5%). The longest axis of the mass was in a cranio-caudal (68%) or dorso-ventral (32%) direction. The median volume calculated on CT was 7.57 cm(3). Common features were a marked local invasiveness of the musculature and heterogeneity of the tissue in the periphery of the neoplasia. When the fibrosarcoma was interscapular, performing an additional post-contrast scan with the forelimbs positioned caudally along the body, in addition to the standard protocol with the forelimbs extended cranially, allowed better evaluation of the actual relationship between the tumour and the surrounding tissues. The mean number of muscles involved with the tumour was 2.09 with extended and 1.95 with flexed forelimbs. When a lower number of structures was considered infiltrated through the double positioning, a less invasive surgical approach to underlying muscles and scapula was performed.

The incidence of feline injection site sarcomas in the United Kingdom

BackgroundFeline injection site sarcomas (FISS) are aggressive neoplasms that have been associated with vaccination. In North America the incidence estimates have varied from 1 case of FISS per 1,000-10,000 cats vaccinated. The aim of this study was to estimate the incidence of FISS in the United Kingdom (UK) in 2007. The ratio of FISS to vaccines sold in the UK was also estimated.Fourteen FISS were diagnosed by a convenience sample of 34 small animal veterinary practices in the United Kingdom in 2007 and were used as the numerator for the incidence estimates. Denominator data was obtained from the computer systems of each practice. Considering that a single cause relationship with vaccination is not proven, three different denominators (number of cats registered, the number of cat consultations undertaken and the number of vaccination visits for cats at the practices) were used to express the potential variation in risk.ResultsThe incidence risk of FISS per year was estimated to be 1/16,000 -50,000 cats registered by practices, 1/10,000-20,000 cat consultations and 1/5,000-12,500 vaccination visits.ConclusionWhen interpreting these findings, it needs to be taken into consideration that this sample of practices and their cats may not be representative of veterinary practices and cats at risk of FISS in the UK. However it can still be concluded with reasonable certainty that the incidence of FISS in the UK is very low.

猫ワクチン関連肉腫に対して根治的切除手術を行った7例

Feline vaccine-associated sarcoma(FVAS)is a locally aggressive tumor with high rates of local recurrence after incomplete excision. Radical tumor excision with 5 cm lateral margins and 2 fascial planes deep to the tumor was performed in 7 cats(median: 11 years old)with FVAS. Three cats had preoperative radiation treatment(RT), and three cats had local recurrence after previous surgeries. The surgical margins were 5-8 cm from the palpable edges of the tumor, and the suture line in the recurrent cases, or from the RT range. Osteotomy of spinous processes(six cases), partial scapulectomy(two cases), and front limb amputation(one case)were also performed. Complete excision as determined by histologic examination of surgical margins was achieved in five cats, and in the remaining two cats, it was suggestive that the deep surgical margins were not adequate. One cat died of nontumor-related causes within 10 days of surgery. Median survival time of the other six cats was 15. 5 months(3-52 months), and five of them had no evidence of local tumor recurrence at the time of death. Radical excision appeared to be a valuable method of attaining improved outcome with a longer survival time without local recurrence in the treatment of FVAS.

Lack of association between p53SNPand FISSin a cat population from Germany

One recent study indicates a significant association between certain single nucleotide polymorphisms (SNPs) in the genomic sequence of feline p53 and feline injection-site sarcoma (FISS). The aim of this study was to investigate the correlation between a specific nucleotide insertion in p53 gene and FISS in a German cat population. Blood samples from 150 German cats were allocated to a control group consisting of 100 healthy cats and a FISS-group consisting of 50 cats with FISS. All blood samples were examined for the presence of the SNP in the p53 gene. Results found the T-insertion at SNP 3 in 20.0% of the cats in the FISS-group and 19.2% of cats in the control-group. No statistically significant difference was observed in allelic distribution between the two groups. Further investigations are necessary to determine the association of SNPs in the feline p53 gene and the occurrence of FISS.

Feline vaccination practices and protocols used by veterinarians in the United Kingdom

Vaccination is an important aspect of disease control in the feline population, as it prevents disease or reduces its severity in individual cats. However the types of antigens that should be administered to cats, the frequency of administration of certain antigens and the anatomical location at which vaccines should be administered are controversial. Various groups have developed guidelines to help veterinarians decide vaccine protocols for cats in their care. The aim of this study was to survey veterinarians in the United Kingdom about the vaccination protocols used in 2007-2008. A questionnaire about aspects of feline vaccination was distributed to a 431 veterinary practices taking part in a case-control study of feline injection site sarcomas. A response rate of 72% was achieved. The majority of veterinarians who responded administered the commonly used antigens annually (84-96% of practices). Most of the veterinarians administered most vaccines in the interscapular region (90-96% of practices depending on the antigen). The vaccination practices of the veterinarians were not consistent with the published vaccination guidelines at that time.

Musculoskeletal neoplasia: an important differential for lumps or lameness in the cat.

Musculoskeletal neoplasia is an uncommon but Important differential diagnosis for cats presenting with lameness, pain or swellings associated with bones and/or soft tissues. The most common tumours of soft tissue origin are the sarcomas (in particular feline injection site sarcomas [FISSs]); the most common bone tumour of the cat is osteosarcoma (OSA). FISSs present a clinical challenge in terms of their local invasiveness, difficulty in obtaining complete surgical excision and high risk of local recurrence. Axial and extraskeletal OSAs pose similar challenges, whereas appendicular OSA is usually easy to remove via limb amputation and can, therefore, carry a good prognosis in many cases. Cats of any age, gender or breed may be affected, although bone tumours predominantly affect middle- to old-aged cats. Vaccination of cats is of global importance in preventing feline diseases; hence, any possible significant consequences of vaccination such as neoplasia, even of a low incidence, are of huge concern to cat owners and veterinarians alike. This review is based on current literature relating to pathogenesis, pathology, presentation, diagnosis, staging, treatment and prognosis. It aims to summarise feline musculoskeletal neoplasia for clinicians in general practice.

P53 Gene Alterations and Outcome in Feline Injection Site Sarcomas

P53 Gene Alterations and Outcome in Feline Injection Site Sarcomas

Phase II clinical evaluation of lomustine chemotherapy for feline vaccine‐associated sarcoma

Treatment of feline vaccine-associated sarcoma (VAS) is challenging, in part due to the high likelihood of tumour recurrence despite aggressive local therapy. Lomustine is potentially an attractive agent to add to the current treatment armamentarium. In this de-escalating phase I/II prospective trial, 28 cats with measurable VAS were treated at target dosages of 38-60 mg m(-2) every 3 weeks until disease progression. The overall response rate was 25%, with a median progression-free survival and median duration of response of 60.5 and 82.5 days, respectively. Haematologic toxicity, specifically cumulative neutropenia, was significant, and dose reductions and treatment delays were common. Although these data support further investigation of lomustine for the treatment of VAS, safe, multidosing protocols must first be determined.

Methodologic Approaches to Histologically Distinguishing Vaccine versus Nonvaccine-Associated Sarcomas Using Validated Time and Location Vaccination Histories in Cats

Epidemiologic studies of feline vaccine-associated sarcoma (FVAS) require accurate sarcoma case definitions free from unverified assumptions for valid causal inference. This study developed methodologic approaches to improve reliable differentiation of vaccine versus nonvaccine-associated sarcomas on histologic characteristics using time windows of vaccine histories and body geographic information. Four case and five control definitions were used to classify 124 sarcomas. Results showed presence in the subcutis versus dermis, increased nuclear pleomorphism, more granulation tissue, and higher presence of inflammation in FVAS than presumptive non-FVAS. Correctly classifying sarcomas using stringent classification criteria as employed in this study will help reduce misclassification of FVAS in future epidemiologic studies of comparative risk.

Masitinib demonstrates anti‐proliferative and pro‐apoptotic activity in primary and metastatic feline injection‐site sarcoma cells*

Dysregulation of platelet-derived growth factor receptor (PDGFR) may play a role in feline injection-site sarcoma (ISS) cell growth and viability. Masitinib, a tyrosine kinase inhibitor approved for treatment of canine mast cell tumours, is highly selective for the PDGFR signalling pathway and may offer a new therapeutic approach for this disease. The in vitro effects of masitinib on growth, apoptosis and PDGFR signalling in two novel ISS cell lines were investigated. PDGFR expression was confirmed by Western blot in cell lines derived from a primary ISS tumour (JB) and a corresponding, histologically confirmed ISS lung metastasis (JBLM). Masitinib inhibited cell growth and PDGFR phosphorylation in both cell lines. Higher drug concentrations were required to inhibit growth than to modulate ligand-induced autophosphorylation of PDGFR. These in vitro data suggest that masitinib displays activity against both primary and metastatic ISS cell line and may aid in the clinical management of ISS.

Radical excision with five-centimeter margins for treatment of feline injection-site sarcomas: 91 cases (1998–2002)

To evaluate outcomes of radical excision of feline injection-site sarcomas (ISS) via assessment of local recurrence and metastasis rates, survival times, and complications associated with surgery. Retrospective case series. 91 cats with ISS. Medical records of cats that had radical excision of ISS without adjunctive treatment were reviewed. Information extracted included sex, type of surgical procedure, histologic tumor grade, tumor diameter, time from tumor detection to definitive surgery, complications associated with surgery, whether tumors recurred locally or metastasized, and survival times. Diagnosis of ISS was histologically confirmed, and additional follow-up was performed. Overall median survival time was 901 days. Thirteen of 91 (14%) cats had local tumor recurrence; 18 (20%) cats had evidence of metastasis after surgery. Median survival time of cats with and without recurrence was 499 and 1,461 days, respectively. Median survival time of cats with and without metastasis was 388 and 1,528 days, respectively. Tumor recurrence and metastasis were significantly associated with survival time, whereas other examined variables were not. Major complications occurred in 10 cats, including 7 with incisional dehiscence. Radical excision of ISS resulted in a metastasis rate similar to rates reported previously; the local recurrence rate appeared to be substantially less than rates reported after less aggressive surgeries, with or without adjuvant treatment. Major complication rates were similar to rates reported previously after aggressive surgical resection of ISS. Radical excision may be a valuable means of attaining an improved outcome in the treatment of feline ISS.

Origins of injection-site sarcomas in cats: the possible role of chronic inflammation-a review.

The etiology of feline injection-site sarcomas remains obscure. Sarcomas and other tumors are known to be associated with viral infections in humans and other animals, including cats. However, the available evidence suggests that this is not the case with feline injection-site sarcomas. These tumors have more in common with sarcomas noted in experimental studies with laboratory animals where foreign materials such as glass, plastics, and metal are the causal agent. Tumors arising with these agents are associated with chronic inflammation at the injection or implantation sites. Similar tumors have been observed, albeit infrequently, at microchip implantation sites, and these also are associated with chronic inflammation. It is suggested that injection-site sarcomas in cats may arise at the administration site as a result of chronic inflammation, possibly provoked by adjuvant materials, with subsequent DNA damage, cellular transformation, and clonal expansion. However, more fundamental research is required to elucidate the mechanisms involved.

Changes in characteristics of feline injection-site sarcomas

Changes in characteristics of feline injection-site sarcomas

Feline injection-site sarcoma: Past, present and future perspectives

Feline injection-site sarcomas (FISS) have been known since the early 1990s. After an initial correlation with rabies and feline leukaemia virus vaccination, subsequent studies have demonstrated that an abnormal reaction of feline tissues to chronic inflammation was mainly responsible for the disease. The low incidence of FISS in the population is explained by its multifactorial aetiology, since individual genetic characteristics are also implicated. FISS is an infiltrative tumour with low metastatic potential but local recurrence is common. Multimodal treatment (extensive surgery, radiotherapy, chemotherapy) is recommended. The use of sophisticated imaging techniques can improve diagnosis and help in surgical planning. After the initial enthusiasm in understanding the disease, only few advances have been made in the last few years. New promising therapies may arise from a better knowledge of the molecular pathogenesis of FISS and the successful development of drugs modulating the immune system.

Orbital extraskeletal osteosarcoma following enucleation in a cat: a case report

We present a unique case of a feline orbital extraskeletal osteosarcoma that developed 5 years post-enucleation. In 2002, an ophthalmologist enucleated the left eye of a 2-year-old neutered male DSH and submitted it to the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW). COPLOW diagnosed the left eye with feline diffuse iris melanoma. In June 2007, the cat presented to another veterinarian for moderate swelling of the enucleation site. Palpation suggested a firm mass along the lateral orbital rim and an exploratory orbitotomy revealed a cyst with a mass adhered to it and the ventrolateral orbital rim. The cyst and mass were excised by the veterinarian and submitted to COPLOW. COPLOW diagnosed the tissue as an orbital conjunctival inclusion cyst and an acquired orbital osteosarcoma. Following the enucleation, retained conjunctival epithelium became embedded in the connective tissue of the orbit and caused a cyst to develop. The cyst wall consisted of a myofibroblastic collagen-rich matrix and acted as a nidus of chronic irritation and tumor growth. This orbital osteosarcoma resembles feline vaccine-associated sarcomas (VAS), feline post-traumatic ocular sarcomas, and microchip-associated sarcomas in terms of it histopathology and its hypothesized pathogenesis related to exposure to antigenic material such as implanted epithelium, lens protein, vaccine components, and microchips as foreign bodies.

Proteasomes are not a Target for Doxorubicin in Feline Injection-Site Sarcoma

The potent anti-cancer agent doxorubicin (DOX) induces apoptosis of rapidly proliferating cells by inhibiting cellular proteasomes. The aim of the present study was to determine whether DOX modulates the level of expression and function of proteasomes in feline injection-site sarcoma (FISS). Tissue extracts from primary sarcoma lesions and the related healthy subcutis of 18 cats affected by FISS were investigated. Nine of these cats had received neoadjuvant DOX treatment and nine cats did not receive this therapy. There was enhanced proteasome expression in FISS, but this was not affected by administration of DOX. This finding may account for the low clinical effectiveness of DOX therapy in FISS and provides the rationale for developing new therapeutic protocols aimed at achieving better proteasomal inhibition in FISS and other tumours that respond poorly to DOX therapy.

Feline injection-site sarcoma: Recurrence, tumour grading and surgical margin status evaluated using the three-dimensional histological technique

The three-dimensional histology technique is used in human medicine for the evaluation of complete lateral and deep surgical margins. In this study, the technique was applied to 48 excised feline injection-site sarcoma specimens. The predictive value of the histological margin status and tumour grading on local recurrence was investigated. In 32/48 cases, the margins were non-infiltrated, whilst in the remaining 16 cases, they were infiltrated. Overall, 6/32 (19%) tumours with non-infiltrated margins and 11/16 (69%) with infiltrated margins recurred. Tumours with infiltrated margins recurred about 10 times more frequently compared to tumours with non-infiltrated margins (P=0.0011). No statistically significant correlation was observed between grading and recurrence. The assessment of margin status using the 3D histology technique showed a good predictivity for post-surgical tumour recurrence. Extensive application of the 3D histology technique is recommended to standardise the evaluation of histological margins and to allow comparison between results from different laboratories.

Successful treatment of feline vaccine-associated sarcoma in a 10-year-old cat using extensive initial surgery

Successful treatment of feline vaccine-associated sarcoma in a 10-year-old cat using extensive initial surgery

A retrospective analysis of radiation therapy for the treatment of feline vaccine‐associated sarcoma*

We retrospectively evaluated predictive prognostic factors in 73 cats with vaccine-associated sarcoma given postsurgical curative (n = 46, most with clean margins) or coarse fractionated radiotherapy (n = 27, most with either macroscopic disease or dirty margins). The former animals displayed a median survival of 43 months and a median progression free interval (PFI) of 37 months, the latter reached a median survival of 24 months and a median PFI of 10 months. In cats undergoing coarse fractionated therapy, factors predictive of a better outcome included lack of visible mass (n = 10) as opposed to macroscopic disease (n = 17, survival: 30 versus 7 months, P = 0.025; PFI: 20 versus 4 months, P = 0.01), adjuvant chemotherapy for gross disease (n = 5/17, survival: 29 versus 5 months, P = 0.04) and a smaller number of surgeries preceding radiation therapy (coeff = 0.41, P = 0.03). The Ki67 index was not predictive for survival. We concluded that postsurgical curative and coarse fractionated radiotherapy are effective legitimate options for managing vaccine-associated sarcomas.

Temporal changes in characteristics of injection-site sarcomas in cats: 392 cases (1990–2006)

To evaluate changes in characteristics of feline injection-site sarcomas (ISSs) from 1990 through 2006. Retrospective case series. 392 cats with a histologic diagnosis of soft tissue sarcoma, osteosarcoma, or chondrosarcoma at potential injection sites. Classification and anatomic location of tumors and signalment of affected cats were compared between ISSs diagnosed before and after publication of the Vaccine Associated Feline Sarcoma Task Force vaccination recommendations in 1996. From before to after publication of the vaccination recommendations, proportions of ISSs significantly decreased in the interscapular (53.4% to 39.5%) and right and left thoracic (10.2% to 3.6% and 9.1% to 1.3%, respectively) regions. On the other hand, proportions of ISSs significantly increased in the right thoracic limb (1.1% to 9.5%) and the combined regions of the right pelvic limb with right lateral aspect of the abdomen (12.5% to 25.0%) and the left pelvic limb with left lateral aspect of the abdomen (11.4% to 13.8%). Patterns of tumor classification and signalment did not change. Despite publication of the vaccination recommendations, a high proportion of tumors still developed in the interscapular region. There was also an increase in lateral abdominal ISSs, which are more difficult to treat and are likely attributable to aberrant placement of injections intended for the pelvic limbs. Veterinarians are complying with vaccination recommendations to some extent, but they need to focus on administering vaccines as distally as possible on a limb to allow for complete surgical margins if amputation of a limb is required.