FISS Research Articles

Feline Injection Site Sarcomas: Data from Switzerland 2009–2014

Feline injection site sarcomas (FISS) were first described in the early 1990s. Despite extensive research, the pathogenesis of these tumours has not been elucidated conclusively. Their appearance and the marked increase in their incidence has been mainly connected to the injection of vaccines,and it is assumed that a chronic inflammatory reaction at the injection site triggers subsequent malignant transformation. The role of alum-based adjuvants has been discussed, but is controversial. The present study of the Swiss Feline Cancer Registry (SFCR) with data from 2009 to 2014 revealed a marked decrease of the incidence of fibrosarcomas compared with the previous observation period. Notably, this drop occurred after a non-adjuvanted feline leukaemia virus vaccine was introduced in Switzerland in 2007. This observation, together with the previous findings of the SFCR, further supports the notion that alum-adjuvanted vaccines are involved in the genesis of FISS and that non-adjuvanted vaccines might be safer for cats.

Feline injection site sarcoma: immunohistochemical characteristics.

Feline injection site sarcoma (FISS) is a rapid growing locally aggressive tumor with a low metastatic rate. Its histologic features are clearly defined, but there are few studies regarding its immunohistochemical characteristics. The present study investigated the immunohistochemical characteristics of 21 cases of FISS. FISSs from 12 male and nine female cats, 20 mixed-breed and one Siamese, were included in the study. After histopathological diagnosis, additional histologic sections were immunostained for vimentin, cytokeratin, desmin, S100 protein, viral feline leukemia virus (FeLV) particles, cyclooxygenase 2 (COX-2) and c-KIT. Positive and negative controls were adopted accordingly. Immunostainings were classified as positive or negative according to the number of positive cells from a total of 1000 cells per tumor section. Histopathologic diagnosis of the tumors revealed 18 (85.7%) fibrosarcomas and three (14.3%) other sarcomas; four fibrosarcomas (22.2%) were grade III, five (27.8%) were grade II and nine (50.0%) were grade I. Two sarcomas were grade III and one was grade II. Seventeen (81%) tumors were negative for desmin. All samples were positive for vimentin. Twenty tumors (95.2%) were positive for S-100 protein. Positivity for c-KIT was observed in four (19%) samples; COX-2 was positive in 13 (61.9%) and FeLV viral particles were positive in nine (42.9%) FISSs. Immunohistochemical findings of FISSs revealed positive immunostainings for desmin, vimentin, S-100 protein, c-KIT, COX-2 and FeLV viral particles.

Distribution of Glutathione-Stabilized Gold Nanoparticles in Feline Fibrosarcomas and Their Role as a Drug Delivery System for Doxorubicin-Preclinical Studies in a Murine Model.

Feline injection site sarcomas (FISS) are malignant skin tumors with high recurrence rates despite the primary treatment of radical surgical resections. Adjunctive radiotherapy or chemotherapy with doxorubicin is mostly ineffective. Cellular and molecular causes of multidrug resistance, specific physio-chemical properties of solid tumors impairing drug transport, and the tumor microenvironment have been indicated for causing standard chemotherapy failure. Gold nanoparticles are promising imaging tools, nanotherapeutics, and drug delivery systems (DDS) for chemotherapeutics, improving drug transport within solid tumors. This study was conducted to assess the distribution of 4-nm glutathione-stabilized gold nanoparticles in FISS and their influence on kidney and liver parameters in nude mice. The role of gold nanoparticles as a doxorubicin DDS in FISS was examined to determine the potential reasons for failure to translate results from in vitro to in vivo studies. Grade III tumors characterized by a large area of necrosis at their core displayed positive immuneexpression of tumor-associated macrophages (TAM) at both the periphery and within the tumor core near the area of necrosis. Gold nanoparticles did not cause necrosis at the injection site and had no negative effect on liver and kidney parameters in nude mice. Gold nanoparticles accumulated in the tumor core and at the periphery and co-internalized with TAM—an important observation and potential therapeutic target warranting further investigation. The large area of necrosis and high immunoexpression of TAM, indicating “pro-tumor macrophages”, may be responsible for FISS tumor progression and therapeutic failure. However, further studies are required to test this hypothesis.

Proteomic Differences in Feline Fibrosarcomas Grown Using Doxorubicin-Sensitive and -Resistant Cell Lines in the Chick Embryo Model.

Proteomic analyses are rapid and powerful tools that are used to increase the understanding of cancer pathogenesis, discover cancer biomarkers and predictive markers, and select and monitor novel targets for cancer therapy. Feline injection-site sarcomas (FISS) are aggressive skin tumours with high recurrence rates, despite treatment with surgery, radiotherapy, and chemotherapy. Doxorubicin is a drug of choice for soft tissue sarcomas, including FISS. However, multidrug resistance is one of the major causes of chemotherapy failure. The main aim of the present study was to identify proteins that differentiate doxorubicin-resistant from doxorubicin-sensitive FISS using two-dimensional gel electrophoresis (2DE), followed by matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS) analysis. Using the three-dimensional (3D) preclinical in ovo model, which resembles features of spontaneous fibrosarcomas, three significantly (p ≤ 0.05) differentially expressed proteins were identified in tumours grown from doxorubicin-resistant fibrosarcoma cell lines (FFS1 and FFS3) in comparison to the doxorubicin-sensitive one (FFS5): Annexin A5 (ANXA5), Annexin A3 (ANXA3), and meiosis-specific nuclear structural protein 1 (MNS1). Moreover, nine other proteins were significantly differentially expressed in tumours grown from the high doxorubicin-resistant cell line (FFS1) in comparison to sensitive one (FFS5). This study may be the first proteomic fingerprinting of FISS reported, identifying potential candidates for specific predictive biomarkers and research targets for doxorubicin-resistant FISS.

Description of a Feline Injection-Site Fibrosarcoma with Metastasis in the Cerebellum

Abstract Feline injection-site sarcomas were initially described by Hendrick and Goldschmidt (1991). The link between vaccination site and sarcoma occurrence suggested the term of vaccine-associated sarcomas. Our paper describes an unusual feline injection-site fibrosarcoma with cerebellar metastasis. A 7-year-old female domestic short-hair cat was submitted to the Pathology Department (Faculty of Veterinary Medicine Cluj- Napoca, Romania) for necropsy. A subcutaneous tumor (relapse) in the interscapular region and multiple metastatic masses in the lungs, kidneys, subcutaneous tissue (scapular and thigh regions) and cerebellum were observed. Cytological, histological and immunohistochemical (for vimentin, desmin, multi-cytokeratin, α-smooth muscle actin, S100 and CD45) analyses from all tumors were performed. Cytological examination identifi ed highly pleomorphic spindle-shaped cells admixed with neoplastic multinucleated giant cells. Histologically, all neoplastic masses were composed of numerous spindle cells arranged into interlacing bundles. Extensive intratumoral areas of necrosis along with a neutrophilic infiltrate were also detected. A fibrillary material was present among neoplastic cells (green stained by Masson’s trichrome method), suggesting a collagenous structure. In all tumors assessed, immunohistochemistry showed an intense reaction only for vimentin in numerous neoplastic cells. Based on the history, gross, cytological, histological and immunohistochemical data, the final diagnosis was recurrent feline injection-site fibrosarcoma, with multiple metastases (including in the cerebellum). Overall, an uncommon case of feline injection-site fibrosarcoma has been reported. This is the first consistent record of an injection site sarcoma in a cat with cerebellar metastasis.

Gold nanoparticles enhance radiation sensitization and suppress colony formation in a feline injection site sarcoma cell line, in vitro

Injection Site Sarcomas (ISS) are highly invasive feline malignant tumors that are frequently associated with routine vaccination. Current treatment modalities include chemotherapy, radiation, and radical surgery. ISS have been shown to be one of the most treatment resistant of feline cancers with high rates of recurrence. Previous studies have shown that gold and other high atomic number nanoparticles have the ability to increase the dose of radiation deposited into tissue by generating secondary electrons. The focus of the current study was to assess the effects of gold nanoparticles (AuNP) on ISS cytotoxicity and colony formation both as a standalone treatment and in combination with electron beam radiation. Cells from an established ISS cell line were co-cultured with 15nm AuNP at 0.0, 0.25, 0.5, 1.0, 2.0 and 4.0mM. AuNP cytotoxicity was evaluated by assessing changes in cellularity, cell proliferation, cell cycle and viability/apoptosis/necrosis. The radiosensitizing potential of AuNP on ISS replication was assessed by the clonogenic assay. AuNP were found to significantly decrease cellular proliferation. However, the acute viability and cell cycle of ISS was not significantly altered. Interestingly, AuNP alone were shown to significantly impair colony formation. In the presence of 9MeV electron radiation, AuNP numerically decreased colony formation in ISS cells compared to cells treated with radiation only. AuNP may have efficacy as a long term therapeutic agent for decreasing ISS growth.

Feline injection site sarcoma: computed-tomographic density and assessment of tumor dimensions by different methods

ABSTRACT: Feline injection site sarcoma is a malignant neoplasm with digitiform projections into muscular planes that are ill recognized during physical examination and may compromise tumor margin demarcation. This study compared tumoral size of 32 cats measured by different methods, and evaluated the CT density of 10 tumoral tissues (Hounsfield unit) based on histograms. Tumor axes were measured by physical examination and CT images. Larger craniocaudal axis measurements were obtained following multiplanar reconstruction of pre- and post-contrast CT images (p=0.049 and p=0.041 respectively); dorsoventral axis measurements taken from post-contrast CT images were also larger (p=0.010). Tumor volume estimates increased following contrast-enhancement. Histograms tended to produce two peaks: one in the fat and another in the soft tissue attenuation range. Multiplanar reconstructed post-contrast CT images provided clearer definition of tumor margins and more judicious determination of tumor size. A tendency of common FISS attenuation profile could be described.

Feline vaccine-associated sarcomagenesis: Is there an inflammation-independent role for aluminium?

Aluminium has been found in feline vaccine-associated sarcomas. In this study, we investigated the potential for aluminium to contribute directly to tumourigenesis. Our results indicated that an aluminium hydroxide adjuvant preparation was cytotoxic and mutagenic in human-Chinese hamster ovary (CHO) hybrid cells in vitro. Moreover, CHO cells deficient in DNA double strand break (DSB), but not single-strand break (SSB), repair, were particularly sensitive to aluminium exposure compared with repair proficient cells, suggesting that aluminium is associated with DSBs. In contrast to CHO cells, primary feline skin fibroblasts were resistant to the cytotoxic effects of aluminium compounds and exposure to an aluminium chloride salt promoted cell growth and cell cycle progression at concentrations much less than those measured in particular feline rabies vaccines. These findings suggest that aluminium exposure may contribute, theoretically, to both initiation and promotion of tumours in the absence of an inflammatory response.

Curative-intent radical en bloc resection using a minimum of a 3 cm margin in feline injection-site sarcomas: a retrospective analysis of 131 cases.

Objectives Owing to its highly infiltrative growth, feline injection-site sarcoma (FISS) carries a significant risk of local tumour recurrence. Parameters of possible prognostic significance (eg, tumour size and location, resection of de novo vs recurrent tumours, and achievement of tumour-free surgical margins) were examined with regard to their influence on recurrence rate (RR), disease-free interval (DFI) and survival time (ST). Methods This was a retrospective analysis of cats with FISSs located on the chest or abdominal wall or the interscapular region treated in a single institution using a standardised radical resection technique with 3 cm lateral margins and full-thickness body wall resection (tumours over chest/abdominal wall) or a minimum of two fascial planes (interscapular tumours). Results Median postoperative DFI and ST of 131 cats with FISSs was 21 and 24 months, respectively. Patients operated on for recurrent tumours were significantly more likely to die from tumour-related reasons compared with patients with de novo tumours ( P <0.001). RR and DFI in the different tumour locations were comparable ( P = 0.544 and P = 0.17, respectively). Local tumour recurrence occurred in 38.1% of the cats. Cats operated on for tumour recurrences had a significantly higher chance of another recurrence (RR 55.5% vs 33.3%; P = 0.005). Completeness of excision was determined by taking tumour bed biopsies. Tumour bed biopsies that did not contain tumour cells were associated with a significantly lower RR compared with those with tumour cells (30.5% vs 76.2%). Conclusions and relevance Depending on prognostic factors such as surgery for primary vs recurrent tumour, tumour-free resection margins and tumour location, the RR in FISS ranges from 33-55%, despite curative intent radical surgery. This study may help in identifying patients at risk for recurrence.

Dynamic tomographic studies of interscapular feline injection-site sarcoma: essential or useless practice?

Objectives Feline injection-site sarcomas (FISSs) are soft tissue tumours typically characterised by an interscapular location and highly infiltrative behaviour. CT is considered the modality of choice for FISS staging and double positioning (dynamic approach) was reported to successfully detect the exact extent of infiltration into the muscles. The aim of the present study was to investigate the utility of the dynamic approach in feline patients referred for preoperative staging of interscapular FISS. Methods Tumour volume estimates were compared between the ellipsoid and the semi-automated segmentation methods. Two radiologists blinded to the patient coding used images from each position to assess the extent of muscular infiltration. The distance between the neoplasm and the adjacent skeletal structures (scapulae, spinous processes) was recorded in both positions by a single radiologist. Results Fifty-nine of 84 neoplasms invaded the adjacent muscular structures, with up to 15 muscles infiltrated. Between the extended and flexed position the average estimated numbers of muscles infiltrated were 1.9 (extended) and 1.84 (flexed) for observer A and 1.89 (extended) and 1.85 (flexed) for observer B. Good agreement between observers was established, with higher tumour volumes detected via the ellipsoid method. Moreover, tumours with smaller volumes showed slightly decreased muscular infiltration. Marked difference in the recorded distance between the skeletal structures and the neoplasm in the two different positions was established (mean ± SD difference spinous processes: 9.74 ± 9.57 mm; mean ± SD difference scapulae: 15.15 ± 11.76 mm). Conclusions and relevance A dynamic approach should be used for a complete evaluation of the invasiveness of FISS along with appropriate methodology for tumour volume measurement, which could potentially alter the tomographic estimation of the real dimension of the neoplasms.

SY-26 Where Does the Research on LGBT Goes? An Overview (FISS Symposium)

SY-26 Where Does the Research on LGBT Goes? An Overview (FISS Symposium)

Anti-proliferative effect of metformin on a feline injection site sarcoma cell line independent of Mtor inhibition

Metformin is an oral hypoglycemic drug that has been shown to inhibit cancer cell proliferation via up-regulation of AMPK (AMP-activated protein kinase), and possibly inhibition of mTOR (mammalian target of rapamycin). The purpose of this study was to evaluate the effects of metformin on a feline injection site sarcoma cell line. Cells from a feline injection site sarcoma cell line were treated with metformin at varied concentrations. A dose-dependent decrease in cell viability following metformin treatment was observed, with an IC50 of 8.0mM. Using flow cytometry, the mechanism of cell death was determined to be apoptosis or necrosis. To evaluate the role of mTOR inhibition in metformin-induced cell death, Western blot was performed. No inhibition of mTOR or phosphorylated mTOR was found. Although metformin treatment leads to apoptotic or necrotic cell death in feline injection site sarcoma cells, the mechanism does not appear to be mediated by mTOR inhibition.

Doxorubicin Conjugated to Glutathione Stabilized Gold Nanoparticles (Au-GSH-Dox) as an Effective Therapeutic Agent for Feline Injection-Site Sarcomas-Chick Embryo Chorioallantoic Membrane Study.

Feline injection-site sarcomas are malignant skin tumours with a high local recurrence rate, ranging from 14% to 28%. The treatment of feline injection-site sarcomas includes radical surgery, radiotherapy and/or chemotherapy. In our previous study it has been demonstrated that doxorubicin conjugated to glutathione-stabilized gold nanoparticles (Au-GSH-Dox) has higher cytotoxic effects than free doxorubicin for feline fibrosarcoma cell lines with high glycoprotein P activity (FFS1, FFS3). The aim of the present study was to assess the effectiveness of intratumoural injection of Au-GSH-Dox on the growth of tumours from the FFS1 and FFS3 cell lines on chick embryo chorioallantoic membrane. This model has been utilized both in human and veterinary medicine for preclinical oncological studies. The influence of intratumoural injections of Au-GSH-Dox, glutathione-stabilized gold nanoparticles and doxorubicin alone on the Ki-67 proliferation marker was also checked. We demonstrated that the volume ratio of tumours from the FFS1 and FFS3 cell lines was significantly (p < 0.01) decreased after a single intratumoural injection of Au-GSH-Dox, which confirms the positive results of in vitro studies and indicates that Au-GSH-Dox may be a potent new therapeutic agent for feline injection-site sarcomas.

Vaccine-associated feline sarcoma: current perspectives.

Feline injection site sarcomas (FISS; also known as vaccine-associated sarcomas) have been recognized for >20 years. Although uncommon, these tumors are iatrogenic, and vaccination against rabies and feline leukemia virus is perhaps the most common inciting cause. The exact etiopathogenesis is unknown, but it is widely accepted that inflammation induced by vaccines or other injections likely plays a critical role in tumor development. Injection site sarcomas are extremely locally invasive. Multimodal therapy, incorporating combinations of surgery, radiation therapy, and sometimes chemotherapy or immunotherapy, is recommended. However, tumor recurrences are common even with aggressive treatment, and many cats with FISS ultimately succumb to this devastating disease. While vaccination protocols play an important role in the management and control of infectious disease, veterinarians must be diligent in following established vaccination guidelines to minimize individual patient risk of FISS development. Early tumor detection and client education are also vital in the successful treatment of FISS.

Feline Injection-Site Sarcoma.

Feline injection-site sarcoma (FISS) is an aggressive tumor believed to arise from the proliferation of fibroblasts and myofibroblasts in areas of chronic inflammation, particularly at sites of injection. Local recurrence is frequent after surgical excision. Gelatinases (MMP-2 and MMP-9) and their inhibitor (TIMP-2) are endopeptidases pivotal in extracellular matrix remodeling and therefore in tumor invasiveness. The aim of this study was to investigate the immunohistochemical expression of MMP-2, MMP-9, and TIMP-2 in FISS to assess their usefulness as prognostic factors. Size, soft tissue sarcoma (STS) grading system, depth of infiltration, surgical margins, and Ki-67 index were evaluated as additional prognostic markers. Twenty-four cases of primary FISS were classified according to clinical follow-up as nonrecurrent (NR, n = 14; 58.3%) and recurrent (R, n = 10; 41.7%). MMP-2, MMP-9, and TIMP-2 were variably expressed in the FISS examined, confirming their role in tumor invasiveness, yet they did not show significant differences between the R and NR groups. These results could be due to different tumor stages or to the multiple activities of these enzymes, not limited to ECM remodeling. The immunohistochemical expression of these enzymes considered alone does not seem to be useful as a prognostic marker. STS grading system, depth of infiltration, surgical margins, and Ki-67 index did not relate to recurrence. Instead, the size of the tumor, measured after formalin fixation, with an optimal cutoff of 3.75 cm (accuracy = 86%; P < .05), and the mitotic count, with an optimal cutoff of 20 mitoses/10 HPF (accuracy = 80%; P < .05), could be evaluated as useful prognostic markers.

Quantification of surgical margin length changes after excision of feline injection site sarcomas-A pilot study.

To evaluate degree length change of lateral surgical margins at various stages of processing for histological examination and quantify the length change between grossly normal surgical margins (GNSM) and pathologist-reported histologic tumor-free margin (HTFM) in widely resected feline injection site sarcoma (FISS) specimens. Prospective clinical study. Five client-owned cats with injection site sarcomas. All cats underwent wide surgical excision (35-55 mm gross lateral margins, 2 fascial planes deep). Gross normal lateral margin measurements from tumor edge were recorded in 4 directions (cranial, caudal, dorsal, ventral) at 5 time points: intra-op (in vivo GNSM); immediately following excision (ex vivo GNSM); following formalin fixation (post-fixation GNSM); after trimming and mounting on glass slides (on-slide GNSM); and HTFM at the narrowest point from the HTFM from the same slides used for on-slide GNSM. Percent change in lateral margin length from in vivo measurements was quantified at each time point and compared using 1-way repeated measures ANOVA. The largest mean decrease in percent GNSM length occurred immediately after excision (in vivo to ex vivo GNSM = 29%; P = .016). Formalin fixation, trimming, and mounting on slides did not result in additional significant changes in length. Mean HTFM length was significantly decreased compared to both in vivo GNSM (33%; P = .014) and on-slide GNSM (7%; P = .024). Significant decreases in surgical margin length in FISS specimens occur immediately following excision (prior to formalin fixation). Subgross evaluation of tumor-free margins from on-slide GNSM to HTFM overestimates the actual (histologic) tumor-free margins.

Recurrent and non-recurrent feline injection-site sarcoma: computed tomographic and ultrasonographic findings.

This study describes the sonographic and computed tomographic (CT) characteristics of primary and recurrent feline injection-site sarcomas (FISSs). Between 2005 and 2013, 32 cats were selected for prospective and retrospective studies. Tumor shape and margins, presence of thickening of the adipose tissue, muscular and bone involvement, pre- and postcontrast attenuation, blurring of fat planes, calcification and liquefactive necrosis, intratumoral areas and skip metastasis were analyzed in CT scans. Echogenicity, echotexture, tumor margins and peritumoral tissue characteristics were analyzed by ultrasound (US). Irregular shape (62.5%) with digitiform projections (100.0%), mixed (peripheral and intratumoral) contrast enhancement (67.7%), blurring of fat planes (68.8%) and signs of liquefactive intratumoral necrosis (68.8%) were the prevailing CT findings. Ultrasonography revealed irregular tumor margins, peripheral hyperechoic capsule-like rim, heterogeneous echotexture, and hyperechoic tissue contiguous with the formations and thickening of adjacent subcutaneous tissues in all cases. Mixed echogenicity with areas suggestive of tumor liquefactive necrosis was documented in 83.3% of cases. Skip metastases were highly correlated with tumor recurrence (P = 0.001). The incidence of muscular involvement tended to be higher (P = 0.003) in tumors presenting with thickening of adjacent adipose tissue. CT and US features common to FISS lesions were highlighted in this study. The imaging modalities employed allowed assessment of peritumoral inflammation, particularly adipose tissue inflammation. Imaging data may contribute to FISS diagnosis, therapeutic planning and patient follow-up.

Changes in the dimension and volume of feline injection-site sarcomas following formalin fixation as determined by use of the ellipsoid volume formula and three-dimensional computed tomography software.

OBJECTIVE To evaluate changes in the dimension and volume of feline injection-site sarcomas (FISSs) before (in vivo) and after surgical excision and formalin fixation (ex vivo) as determined by measurements obtained from 2-D and 3-D CT images. SAMPLE 10 excised FISSs. PROCEDURES The maximum length, width, and depth of each FISS were measured on contrast-enhanced 2-D CT images of the tumor obtained in vivo and ex vivo. Those measurements were used to estimate tumor volume with the standard ellipsoid formula. Tumor volume was also calculated from 3-D CT images with software that used a volume-rendering algorithm. Student paired t tests were used for comparisons between the in vivo and ex vivo assessments. RESULTS Small decreases were detected in maximum tumor length, width, and depth between the in vivo and ex vivo assessments; however, tumor length was the only dimension that decreased significantly between the 2 assessments. Median tumor volume decreased significantly between the in vivo and ex vivo assessments regardless of the method used to estimate it. Tumor volume estimated by the ellipsoid formula was significantly lower than that estimated by the 3-D CT software at both assessments. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that shrinkage of FISSs following excision and formalin fixation was small and may be less than that of grossly normal tissue. Tumor volume estimated by the ellipsoid formula was consistently less than that estimated by 3-D CT software and should not be used when accuracy of tumor volume is of particular concern and advanced CT imaging is available.

Feline injection site sarcoma: current paradigms and future directions

Feline injection site sarcoma (FISS) is an uncommon but important tumour in cats due to its locally aggressive biologic behaviour, poor prognosis and link to routinely-administered vaccinations, which raises ethical questions regarding vaccine practices. Post-vaccinal granulomas commonly occur in cats, therefore client education is vital and careful monitoring should be adopted. Incisional biopsy is recommended to confirm diagnosis of FISS, and full staging is recommended prior to determination of a treatment strategy. Tumour palpation has been shown to vastly underestimate the extent of tumour infiltration, therefore prospective treatment planning with advanced imaging is highly recommended. Although further studies are required to determine the most effective combination of treatment modalities for definitive treatment, a multi-modal approach is often required, based on expeditious and aggressive surgery in combination with radiotherapy ×/− chemotherapy. Importantly, early detection by careful post-vaccination monitoring as well as a shift in vaccination practices is key to improving the outcome of FISS.

Feline injection site sarcomas

Feline injection site sarcoma (FISS), formerly known as vaccine associated sarcoma (VAS), is a rare but life-threatening disease. The incidence estimates have varied from one case of FISS per 1000–10 000 cats vaccinated in North America and between one per 5000–12 500 vaccination visits in UK. It has been primarily associated with vaccine administration, but several other injectable materials/substances have been implicated as aetiologic agents, namely lufenuron, penicilin, metilprednisolone, meloxicam, non-absorbable suture material and microchip. FISS can have a long latency period (3 months to 13 years), but 8 years old is the average age of onset. FISS are tumours that arise subcutaneously, reaching a variable number of layers beneath the skin (muscle, bone). They are firm, not painful, solid and variable in size. Clinical assessment and biopsy are the basis for FISS diagnosis. In order to prevent FISS, vaccination should be carefully planned and be provided in easily resectable regions. Hind legs, tail and flanks, are preferable regions for vaccine administration.