FISS Research Articles

Comparison of MMP-2, MMP-9, COX-2, and PGP Expression in Feline Injection-Site and Feline Noninjection-Site Sarcomas-Pilot Study.

Feline injection-site sarcomas (FISSs) are aggressive neoplasms that have been associated mostly with vaccination. Feline noninjection-site sarcomas (non-FISSs) are less frequently observed in cats and may arise in any anatomic site. This study aimed to determine the differences in the expression of the selected proteins (matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), cyclooxygenase-2 (COX-2), and P-glycoprotein (PGP)) and their correlation with the mitotic count in FISS and non-FISS, in order to characterize their immunohistochemical features. A preliminary study of eleven samples of FISS and eight samples of non-FISS was performed using immunohistochemistry. Among all the tested sarcomas, 80.4% of the tumors were positive for COX-2, 90.2% were positive for MMP-9, and 100% were positive for PGP. The results showed that the expressions of COX-2, MMP-9, and PGP were significantly higher in FISS than in non-FISS (COX-2-p ≤ 0.001; MMP-9-p ≤ 0.05; and PGP-p ≤ 0.05). A Spearman rank correlation analysis showed a moderate negative correlation between the expression of COX-2 and MMP-9 in FISS (r = -0.52). A strong negative correlation between COX-2 and PGP (r = -0.81), a moderate positive correlation between MMP-2 and MMP-9 (r = +0.69), and a moderate negative correlation between MMP-2 and PGP (r = -0.44) were observed in non-FISS. In summary, our study presents the immunohistochemical profile of the proteins involved with inflammation and carcinogenesis in FISS and non-FISS, which can contribute to expanding the knowledge of tumor biology.

Bilateral scapular luxation, and subsequent stabilisation, following surgical excision of recurrent interscapular feline injection site sarcoma

AbstractA 14‐year‐old cat presented with multifocal local recurrence of an interscapular feline injection site sarcoma. Aggressive surgical excision of the initial neoplasm had been performed 16 months previously. Distant metastasis was not identified on repeat staging, and the recurrent gross disease was surgically removed with a 2‐cm peripheral margin and one deep tissue plane, resulting in clear histopathological margins. Bilateral dorsal scapular luxation occurred following this surgery, causing significant patient morbidity. A further procedure was performed to stabilise the scapulae by re‐attaching the serratus ventralis muscles and placing scapulo‐costal sutures. The cat regained excellent function and quality of life and is free of gross disease at the time of writing this report, 9 months following surgery for feline injection site sarcoma recurrence.

Presumptive injection-site sarcoma in a white tiger (Panthera tigris tigris): A case report

A 6-year-old female White Tiger (Panthera Tigris Tigris) was presented with a history of a recurrent ulcerating mass on the right lumbar wall which initially, was removed by surgery one year before presentation. Cytological and histological findings were consistent with a cutaneous injection site sarcomas. Immunohistochemistry results revealed that the neoplastic cells were strongly positive for vimentin and weakly positive for alpha-smooth muscle actin (SMA), but negative for Cytokeratin AE1/AE3, s100, and Desmin. Positive staining for vimentin and SMA is consistent with myofibroblast reactivity and reflects a continuous inflammatory response seen in feline injection-site sarcomas. Feline injection-site sarcomas are the most serious adverse effect following injection of the vaccine or some other pharmaceutical substances and should be considered in the differential diagnosis of skin swelling in injection sites in the Felidae family. Limited data are available for these tumors in animals outside of domesticated cats. To the best of our knowledge, there exists no available published information on the injection-site sarcoma in tigers. Similar to domestic felids, this case highlights the importance of considerations and management options in vaccination schedules for the reduction of sarcoma risk in wild felids.

Use of wound infusion catheters for postoperative local anaesthetic administration in cats.

The present study aimed to document the use of the wound infusion catheter (WIC) following a variety of surgical procedures in cats, investigating complications and risk factors associated with catheter placement or local anaesthetic (LA) administration. A retrospective, multicentric study was performed. Medical databases of eight veterinary referral hospitals from 2010 to 2021 were searched to identify records of cats where WICs were used. Information regarding signalment, type of surgery, size and type of WIC placed, and LA protocol used, as well as postoperative complications, were retrieved. One hundred and sixty-six cases fulfilled the inclusion criteria. Feline injection site sarcoma resection was the most common surgery. Overall complications were identified in 22/166 cats (13.2%). Thirteen cats (7.8%) experienced wound-related complications, whereas nine cats (5.4%) experienced drug-delivery complications. The only factor associated with an increased risk of complications was the amount of a single dose of LA delivered through the catheter (P <0.001). An amount higher than 2.5 ml of LA delivered at each administration was associated with an increased risk of complications. All complications were minor and self-limiting. WICs were used for a large variety of surgical procedures with different protocols of LA administration as part of a multimodal analgesic plan in cats. The risk of complications was relatively low and self-limiting, suggesting its safe use in cats. Further prospective studies are required to evaluate efficacy of postoperative analgesia and to determine the suitable protocol for WIC handling and maintenance.

Feline Injection-Site Sarcoma and Other Adverse Reactions to Vaccination in Cats.

Vaccine-associated adverse events (VAAEs), including feline injection-site sarcomas (FISSs), occur only rarely but can be severe. Understanding potential VAAEs is an important part of informed owner consent for vaccination. In this review, the European Advisory Board on Cat Diseases (ABCD), a scientifically independent board of feline medicine experts, presents the current knowledge on VAAEs in cats, summarizing the literature and filling the gaps where scientific studies are missing with expert opinion to assist veterinarians in adopting the best vaccination practice. VAAEs are caused by an aberrant innate or adaptive immune reaction, excessive local reactions at the inoculation site, an error in administration, or failure in the manufacturing process. FISS, the most severe VAAE, can develop after vaccinations or injection of other substances. Although the most widely accepted hypothesis is that chronic inflammation triggers malignant transformation, the pathogenesis of FISS is not yet fully understood. No injectable vaccine is risk-free, and therefore, vaccination should be performed as often as necessary, but as infrequently as possible. Vaccines should be brought to room temperature prior to administration and injected at sites in which FISS surgery would likely be curative; the interscapular region should be avoided. Post-vaccinal monitoring is essential.

Effects of selective cyclooxygenase-2 inhibitor robenacoxib on primary cells derived from feline injection-site sarcoma.

Feline injection-site sarcomas (FISSs) are highly invasive malignant mesenchymal neoplasms that arise from injection sites in cats. Although the tumorigenesis of FISSs is still uncertain, there is a consensus that FISS is associated with chronic inflammation caused by irritation of injection-related trauma and foreign chemical substances. Chronic inflammation can provide a proper microenvironment for tumour development, which has been known as one of the risk factors of tumorigenesis in many tumours. To investigate the tumorigenesis of FISS and screen for its potential therapeutic targets, cyclooxygenase-2 (COX-2), an inflammation-enhancing enzyme, was selected as a target for this study. In vitro experiments using FISS- and normal tissue-derived primary cells and robenacoxib, a highly selective COX-2 inhibitor, were performed. The results demonstrated that expression of COX-2 could be detected in formalin-fixed and paraffin-embedded FISS tissues and FISS-derived primary cells. Cell viability, migration and colony formation of FISS-derived primary cells were inhibited, and cell apoptosis was enhanced by robenacoxib in a dose-dependent manner. However, susceptibility to robenacoxib varied in different lines of FISS primary cells and was not completely correlated with COX-2 expression. Our results suggest that COX-2 inhibitors could be potential adjuvant therapeutics against FISSs.

Histotripsy ablation for the treatment of feline injection site sarcomas: a first-in-cat in vivo feasibility study

Purpose Feline soft tissue sarcoma (STS) and injection site sarcoma (fISS) are rapidly growing tumors with low metastatic potential, but locally aggressive behavior. Histotripsy is a non-invasive focused ultrasound therapy using controlled acoustic cavitation to mechanically disintegrate tissue. In this study, we investigated the in vivo safety and feasibility of histotripsy to treat fISS using a custom 1 MHz transducer. Materials and Methods Three cats with naturally-occurring STS were treated with histotripsy before surgical removal of the tumor 3 to 6 days later. Gross and histological analyses were used to characterize the ablation efficacy of the treatment, and routine immunohistochemistry and batched cytokine analysis were used to investigate the acute immunological effects of histotripsy. Results Results showed that histotripsy ablation was achievable and well-tolerated in all three cats. Precise cavitation bubble clouds were generated in all patients, and hematoxylin & eosin stained tissues revealed ablative damage in targeted regions. Immunohistochemical results identified an increase in IBA-1 positive cells in treated tissues, and no significant changes in cytokine concentrations were identified post-treatment. Conclusions Overall, the results of this study demonstrate the safety and feasibility of histotripsy to target and ablate superficial feline STS and fISS tumors and guide the clinical development of histotripsy devices for this application.

Feline injection-site sarcomas (FISSs): could the assessment of tumour-infiltrating lymphocytes (TILs) help in prog-nostic evaluations?

Feline injection-site sarcomas (FISSs): could the assessment of tumour-infiltrating lymphocytes (TILs) help in prog-nostic evaluations?

Injection-Site Sarcoma in Three Village Weaver Birds (Ploceus cucullatus) Associated with Autogenous Yersinia pseudotuberculosis Vaccination

Post-vaccinal sarcomas have been reported in cats and rarely in other domestic mammals, but not in birds. Three village weaver birds (Ploceus cucullatus) presented with poor flying ability and abnormal wing carriage attributable to large, unilateral pectoral masses. All had received at least one dose of autogenous Yersinia pseudotuberculosis vaccine into the affected pectoral muscle 74-408 days previously. Following euthanasia, gross post-mortem examination revealed locally invasive subcutaneous tumours extending through the sternum into the coelomic cavity. Cytology and histology revealed neoplasms of pleomorphic spindloid neoplastic cells with foci of coagulative necrosis and cavitation, sometimes containing faintly refractile non-polarizing granular material, both extracellularly and after phagocytosis by surrounding cells, including multinucleated giant cells. Immunohistochemistry in one bird supported a striated muscle cell origin. Findings of anaplastic sarcoma with intralesional foreign crystalline material resembled typical injection-site sarcomas in cats. This is the first report of presumptive vaccine-associated sarcoma in a non-mammalian species.

Feline Soft Tissue Sarcomas: A Review of the Classification and Histological Grading, with Comparison to Human and Canine.

Simple SummarySoft tissue sarcomas are a common form of cancer arising in the skin and connective tissues of domestic cats. Soft tissue sarcomas encompass a group of different histological subtypes of tumours, which can behave in a range of different ways in the patient. In dogs and in humans, this group of tumours can be given a histological score (“grade”) at the time of diagnosis, which is prognostic, but there is no equivalent, well-established grading system for these tumours in cats. This review looks at soft tissue sarcomas in terms of which histological subtypes of tumour should be included in this group, and how pathologists approach their grading, comparing feline tumours with their human and canine counterparts.Soft tissue sarcomas are one of the most commonly diagnosed tumours arising in the skin and subcutis of our domestic cats, and are malignant neoplasms with a range of histological presentations and potential biological behaviours. However, unlike their canine and human counterparts, there is no well-established histological grading system for pathologists to apply to these tumours, in order to provide a more accurate and refined prognosis. The situation is further complicated by the presence of feline injection site sarcomas as an entity, as well as confusion over terminology for this group of tumours and which histological types should be included. There is also an absence of large scale studies. This review looks at these tumours in domestic cats, their classification and histological grading, with comparisons to the human and canine grading system.

Feline Injection-Site Sarcoma Complete Remission After Treatment with Isopathic medicine: a Case Report

This is a case report of a feline injection-site sarcoma generated by the rabies vaccine in a 13 year old mix breed spay cat tretaed with isopathic medicine.

Canine and feline core vaccinations: US veterinarians' concerns and perceived impact of COVID-19 antivaccination views on veterinary medicine.

Assess US veterinarians' perceptions regarding vaccine concerns (their own and owners') and the association between owners' vaccine concerns and COVID-19 antivaccination sentiments. Members of the Veterinary Information Network. An electronic survey distributed via the Veterinary Information Network data collection portal. 1,341 US veterinarians completed the survey. Top veterinarian concerns for vaccinating a healthy adult dog were anaphylaxis, soreness at injection site, and lethargy; for cats, these concerns included vaccine-associated sarcoma, lethargy, and soreness at injection site. Veterinarians reported that the most common concerns mentioned by owners included that the pet does not go outside, that vaccinations are unnecessary, that vaccinations can lead to chronic or severe illness, and cost. Veterinarians reported an increased number of dog and cat owners reluctant about or resistant to the idea of rabies vaccines and core vaccines since the time that COVID-19 vaccines became widely available. There was an association between veterinarians' perceptions of local COVID-19 antivaccination sentiments and the increase in the number of vaccine-resistant or -concerned clients. There appears to be little overlap between veterinarians' primary concerns related to vaccinations and their perception of dog and cat owners' primary concerns. The fact that the number of resistant clients is positively associated with the presence of veterinarians' perceptions of a local COVID-19 antivaccination sentiment suggests that human antivaccination sentiments impact pet owners' views of companion animal vaccinations. A better understanding of the cognitive biases that impact owners' vaccine decisions can help veterinarians better communicate with vaccine-reluctant clients and increase vaccination compliance rates.

Investigating the role of signal transducer and activator of transcription 3 in feline injection site sarcoma

BackgroundFeline injection-site sarcomas (FISSs) are malignant mesenchymal tumors of different histotypes. The pathogenesis of FISS has been correlated with chronic inflammation, resulting in neoplastic transformation. Activation of the Janus kinase-signal transducer and activator of transcription 3 (STAT3) have been demonstrated to play a critical role in tumor development by regulating signaling pathways involved in cell proliferation, survival, metastasis, and angiogenesis in human medicine. To characterize the role of STAT3 in FISS, we first detected STAT3 and phosphorylated STAT3 in formalin-fixed and paraffin-embedded (FFPE) FISS tissues using immunohistochemical staining.ResultsSTAT3 was detected in 88.9% (40/45) of FISS cases, and phosphorylated STAT3 was detected in 53.3% (24/45) of cases. However, the expression levels of both forms of STAT3 were not correlated with tumor grade. To study the role of STAT3 in tumor survival, two primary cells derived from FISSs of two cats exhibiting consistent immunophenotypes with their parental FFPE tissues were established. A dose-dependent inhibitory effect on cell proliferation was observed in both primary FISS cells treated with the STAT3 inhibitor, 5-hydroxy-9,10-dioxo-9,10-dihydroanthracene-1-sulfonamide.ConclusionsThe STAT 3 may play an important role in the tumorigenesis of FISS and be a potential molecular therapeutic target for FISS.

Bortezomib inhibits the proteasome, leading to cell death via apoptosis in feline injection site sarcoma cells in vitro.

To determine the in vitro effects of the proteasome inhibitor bortezomib in feline injection site sarcoma (FISS) cell lines. In vitro cultures of the FISS cell lines Ela-1, Hamilton, and Kaiser. Cells were treated with increasing doses of bortezomib or vehicle alone (dimethyl sulfoxide) and evaluated for cell viability via an adenosine triphosphate concentration assay, proteasome activity via a commercially available proteasome assay, accumulation of ubiquitinated proteins via Western blot, and apoptosis via flow cytometry. All 3 cell lines were sensitive to bortezomib with a 50% inhibitory concentration after 48 hours of treatment at 17.46 nM (95% CI, 15.47 to 19.72 nM) for Ela-1, 19.48 nM (95% CI, 16.52 to 23.00 nM) for Hamilton, and 21.38 nM (95% CI, 19.24 to 23.78 nM) for Kaiser. In the Ela-1 cell line, 20 nM bortezomib inhibited 20S proteasome activity by 90.9% compared with the vehicle-only control. In the Kaiser cell line, 20 nM bortezomib decreased 20S proteasome activity by 70%, compared with the untreated vehicle-only control. Last, treatment with bortezomib (25 and 40 nM) resulted in statistically significant decreases in viable cells accompanied by a statistically significant increase in apoptotic cells. Treatment options for FISS, especially nonresectable FISS, are currently very limited. These results support further investigation of bortezomib either alone or in combination with other treatments in such cases.

Feline Injection-Site Sarcoma (FISS): Does the Growth Pattern Predict Local Recurrence?

Feline Injection-Site Sarcoma (FISS): Does the Growth Pattern Predict Local Recurrence?

Injection site sarcomas in other species than the domestic cat

Injection site sarcomas (ISS) are tumours of tissues of mesenchymal origin that occur at an injection site. These tumours have been mainly described in cats as Feline injection-site sarcoma (FISS), but suspected cases have also been described in other species such as dogs. In other species than the domestic cat, these tumours are however much rarer. As a result, the body of literature is limited. This review aims to summarize the knowledge regarding ISS in species other than the domestic cat. In general, it seems that ISS can occur in a wide range of animals and that similar treatment strategies are employed as in cats. Like in cats, it seems that the benefit of the reasons for injection (such as vaccination and microchip implantation) could outweigh the risk of ISS development in other species.

Diagnostic accuracy of optical coherence tomography for surgical margin assessment of feline injection-site sarcoma.

The invasive, locally aggressive nature of feline injection-site sarcomas (FISSs) poses a unique challenge for surgeons to obtain complete margins with surgical excision. Optical coherence tomography (OCT), an imaging technology that uses light waves to generate real-time views of tissue architecture, provides an emerging solution to this dilemma by allowing fast, high-resolution scanning of surgical margins. The purpose of this study was to use OCT to assess surgical margins of FISS and to evaluate the diagnostic accuracy of OCT for detecting residual cancer using six evaluators of varying experience. Five FISSs were imaged with OCT to create a training set of OCT images that were compared with histopathology. Next, 25 FISSs were imaged with OCT prior to histopathology. Six evaluators of varying experience participated in a training session on OCT imaging after which each of the evaluators was given a dataset that included OCT images and videos to score on a scale from cancerous to non-cancerous. Diagnostic accuracy statistics were calculated. The overall sensitivity and specificity for classification of OCT images by evaluators were 78.9% and 77.6%, respectively. Correct classification rate of OCT images was associated with experience, while individual sensitivities and specificities had more variation between experience groups. This study demonstrates the ability of evaluators to correctly classify OCT images with overall low levels of experience and training and also illustrates areas where increased training can improve accuracy of evaluators in interpretation of OCT surgical margin images.

First reported case of a histiocytic sarcoma in an Armenian hamster (Cricetulus migratorius).

A 14-month-old male Armenian hamster (Cricetulus migratorius) presented with a spontaneous, subcutaneous, firm mass (4.0 × 2.0 × 1.5 cm) on the ventral neck extending towards the cheek pouch causing multifocal small oral ulcerations. This animal was immunized subcutaneously on the dorsal neck for the development of monoclonal antibodies seven months before presentation. The animal was euthanized and necropsy was performed. Histopathology of the mass showed a well demarcated, multilobulated, unencapsulated, highly cellular, neoplastic mass composed of spindle cells arranged in interlacing streams and bundles, with a moderate amount of fibrovascular stroma. The neoplastic cells exhibited indistinct cell borders and a moderate to large amount of eosinophilic, fibrillar cytoplasm, marked anisocytosis and anisokaryosis, binucleated and multinucleated cells, and high mitotic rate. Based on the histomorphologic features of the mass, and the presence of renal tubular hyaline globules and myeloid hyperplasia in the bone marrow, a diagnosis of histiocytic sarcoma was made. The presumptive diagnosis was confirmed by immunohistochemistry, upon which the neoplastic cells showed strong immunoreactivity for the histiocytic cell markers Iba1 and CD11b. Histiocytic sarcomas have been reported in Syrian (Mesocricetus auratus) and Siberian dwarf (Phodopus sungorus) hamsters but, to our knowledge, the current report represents the first case of histiocytic sarcoma described in an Armenian hamster. It is plausible to consider the animal's experimental immunization history and the development of the histiocytic sarcoma to be related. An association between adjuvanted vaccines and soft-tissue sarcomas has been described in cats and referred to as feline injection-site sarcomas.

Ventilatory failure in a cat following radical chest wall resection for feline injection site sarcoma

Case summaryA 12-year-old spayed female domestic shorthair cat presented for chest wall resection and radiation therapy following incomplete surgical excision of a feline injection site sarcoma. A CT scan for surgical planning was performed under general anesthesia and showed extensive tumor infiltration of the soft tissues of the right thorax. The cat recovered uneventfully from this anesthetic event. Nineteen days later, the patient was reanesthetized for forequarter amputation plus radical chest wall resection, including ribs 3–8 and all associated soft tissues plus adjacent spinous processes. Postoperatively, the patient developed acute respiratory failure secondary to hypoventilation. The cat was mechanically ventilated for 12 h prior to being successfully weaned from the ventilator. However, the improvement was transient and mechanical ventilation was reinitiated 6 h later owing to respiratory fatigue. On the second day, the cat developed unexplained central nervous system signs and was euthanized.Relevance and novel informationTo our knowledge, this is the first case report to describe ventilatory failure secondary to radical chest wall resection in a cat. Hypoventilation with subsequent need for mechanical ventilation is a potential complication that should be considered during preoperative planning in patients requiring extensive chest wall resections.

Targeting Peritumoral Lesions Identified by Computed Tomography and Magnetic Resonance Imaging in Feline Injection-Site Sarcomas for Microscopic Examination

Peritumoral lesions identified during in vivo imaging of feline injection-site sarcoma (FISS) are frequently interpreted as neoplastic. We recently showed that most peritumoral imaging-identified lesions (PTIILs) in FISS are non-neoplastic. In this article, we describe a protocol to target PTIIL for microscopic examination and report on the protocol's performance. Ten client-owned cats with FISS were prospectively enrolled. A fiducial marker sutured onto the skin, centered on the palpable mass, served as reference point throughout the study. Each FISS and surrounding tissue was imaged in vivo by dual phase computed tomography angiography and multiple magnetic resonance imaging pulse sequences and each PTIIL documented. Subgross measurements obtained during trimming aided localization and identification of PTIIL during microscopy. Histologic findings were categorized by descending clinical relevance: neoplastic, equivocal, non-neoplastic, within normal limits (WNL). Based on in vivo imaging resolution limits, histologic findings were ≥3 mm in at least one dimension and ≥3 mm apart. Surgical margins served as control tissue for PTIILs. Eighty-one of 87 PTIIL were examined histologically; 13 were neoplastic, 16 equivocal, and 28 non-neoplastic; 24 had no identified histologic correlate. Two neoplastic and 10 equivocal findings were located outside of PTIILs but none of them were located in sections of surgical margins. Computation of a simple confusion matrix yielded fair sensitivity (70.4%) and low specificity (59.7%) for prediction of PTIIL by histologic findings. After combining instances of normal microanatomy with non-neoplastic histologic findings, specificity increased (85.1%) and sensitivity decreased (35.8%). The protocol is a blueprint for targeting PTIIL for microscopic examination but may benefit from further refinement.