Subcutaneous fluid port-associated soft tissue sarcoma in a cat

Abstract

A 20-year-old male castrated domestic longhair cat was evaluated for assessment of its chronic kidney disease (CKD) and a non-healing ulcerated mass at the site of a previously placed and subsequently removed GIF tube. The cat had been diagnosed with CKD 10 years prior and two GIF tubes had been placed over a 5-year period, the second of which was associated with secondary infection. Biopsy of the non-healing ulcerated mass was consistent with grade 2 soft tissue sarcoma. At necropsy there was a discrete, serpentine, subcutaneous mass measuring approximately 8 mm in diameter that extended approximately 20 cm along the dorsum to the caudal thorax, following the path of the GIF tube, from the main intrascapular, ulcerated mass where the fluid port injection site was located. This is the first report of a fibrosarcoma arising at the site of a subcutaneous fluid port in a cat. Although the cat’s owners were pleased with the 4 years of quality of life provided by this device, this complication should be considered when a decision to place ports for long-term management of disease is made.

Case Report

Administration of subcutaneous fluids is a common therapy in the management of chronic kidney disease (CKD) in cats. ¹ The willingness of the patient to tolerate this therapy sometimes impedes administration. Subcutaneous fluid ports are surgically-placed fenestrated silicone tubings that are designed for a more efficient, needleless, and, hence, less stressful long-term alternative to daily subcutaneous fluid injections. This report describes a poorly differentiated soft tissue sarcoma that developed at the site of a subcutaneous (SC) fluid port of 5 years’ duration. To the best of our knowledge this has not been reported previously and should be considered a risk factor in using such ports for SC fluids administration in chronically ill patients.

A 20-year-old male castrated domestic longhair cat was evaluated at the Colorado State University James L Voss Veterinary Teaching Hospital for assessment of its CKD and a non-healing wound at the site of a previously placed and subsequently removed GIF tube (PractiVet). The cat was first diagnosed with CKD in 2001, approximately 10 years prior to presentation. At initial diagnosis the cat’s creatinine level was 3.1 mg/dl. Over a 10-year period the cat’s creatinine level ranged from 1.9 mg/dl to 9.0 mg/dl and was 2.3 mg/dl a few days prior to presentation. Initially, the cat was maintained at home with SC injections until a GIF tube was surgically placed in February 2007. The GIF tube was placed in accordance to the manufacturer’s specifications at the dorsal cervical area approximately 6.4 cm distal to the base of the skull. ² For 4 years fluids were administered through the GIF tube with minimal complications. Recorded complications during this period included pocket formation around the tube, slow flowing fluid through the tube during administration, kinking of the tube and patient discomfort. Enrofloxacin 5 mg/kg (Baytril injectable solution; Bayer Healthcare) was used initially after GIF tube placement for 10 days, as well as intermittently in each dose of SC fluids when significant pockets formed or fluid flow rate slowed. No growth was found on intermittent bacterial aerobic and anaerobic culture, and sensitivity flush tests performed during this 4-year period. Owing to slow flow the tube was removed in February 2011 and, 1 week later at the recommendation of the manufacturer, another GIF tube was placed surgically slightly caudal to the original port site in the interscapular region. At the end of March 2011 fluid administration through the tube became painful and difficult owing to a slow flow rate. The tube was flushed and cultured. Heavy growth of opportunistic bacteria Alcaligenes xylosixidans and Sphingomonas paucimobilis were cultured from the tube. Infection was treated with enrofloxacin 5 mg/kg (Baytril injectable solution; Bayer Healthcare) in the fluids and oral amoxicillin/clavulanic acid, 13 mg/kg q12h (Clavamox; Pfizer Animal Health), according to the performed sensitivity. The cat re-presented in June 2011 owing to poor flow of fluids through the tube and discomfort. The tube was once again flushed and cultured yielding Achromobacter species, susceptible to amoxicillin/clavulanic acid. In addition, the cat became markedly anemic with a packed cell volume of 18% (normocytic, normochromic, non-regenerative). Soon after, in July 2011, a firm mass was noted in the location of the cutaneous port insertion point. The device was removed entirely, and purulent exudate and granulation tissue was noted where the GIF tube port had been located. The cat was then referred to Colorado State University Internal Medicine Service for consultation.

On physical examination the cat was thin (body condition score 4/9) with a large, firm, adhered mass between the scapulae measuring 3 × 5 cm with an open, exudative wound at the cranial margin which was approximately 1.5 cm in diameter. Additional examination findings included a unilateral, palpable thyroid nodule and a gallop rhythm on auscultation. Amoxicillin/clavulanic acid (14.5 mg/kg orally q12h) was prescribed and daily wet-to-dry tie over bandage changes were performed for 1 week. Wound closure did not respond as rapidly as anticipated and a needle core biopsy revealed a grade 2 soft tissue sarcoma underlying the wound site. Histopathology could not rule out osteosarcoma. To pursue surgical options, a computed tomography (CT) scan was recommended to evaluate tumor extent and assist with surgical planning. Owing to the likelihood of an extensive resection and a lengthy surgical recovery period, the owner declined CT and surgery, and elected to continue with open management of the wound. The cat began to vomit, owing to the amoxicillin/clavulanic acid, and, alternatively, was given an injection of cefovecin (8 mg/kg SC) (Convenia; Pfizer Animal Health). Daily wound care was performed at home and SC injections of cefovecin were repeated every 2 weeks. The wound continued to contract and was approximately 0.5 cm in diameter when, owing to declining health at home, humane euthanasia was performed.

At necropsy there was a discrete, serpentine, SC mass measuring approximately 8 mm in diameter that extended approximately 20 cm along the dorsum to the caudal thorax, following the path of the GIF tube, from the main intrascapular, ulcerated mass where the fluid port injection site was located (Figure 1a). The mass was firm, tan and homogenous with a central hollow core where the tube resided surrounded by a thin circumferential rim of soft, necrotic tissue. Additional findings included bilaterally enlarged, nodular and cystic thyroid glands with parathyroid hypertrophy. Multiple compressive, well demarcated, homogenous, tan and umbilicated masses that measured up to 3 cm in diameter were found throughout the lungs. The left medial liver lobe contained a heterogenous, multi-cystic mass measuring 3.75 cm in diameter. The kidneys were shrunken and pitted, with the left more severely affected. Tissues from all systems were fixed in 10% neutral-buffered formalin solution, embedded in paraffin, sectioned and stained with haemotoxylin and eosin solution. Sections were examined by light microscopy by us (SM and BP). The SC mass was composed of a partially encapsulated, compressive, highly cellular mesenchymal neoplasm. Neoplastic cells were spindloid-to-stellate, arranged into streams and bundles separated by variable amounts of stroma (Figure 1b). Nuclei were plump oval with finely stippled chromatin and a single variably distinct nucleolus. Pleomorphism was moderate-to-marked characterized primarily by anisokaryosis. Mitoses were approximately six per 10 high powered fields. Centrally, there was a region of coagulation necrosis with neutrophils scattered through this region. Additional histologic findings included bronchioalveolar carcinoma, unilateral parathyroid carcinoma with contralateral adenoma, biliary cyst adenoma and gastric papillotubular adenoma. Renal sections were consistent with CKD with infarctions. Immunohistochemistry to further characterize the neoplastic cell population revealed strong immunopositivity for vimentin, which is consistent with a mesenchymal neoplasm (Figure 1c). There were scattered CD3 positive cells (T lymphocytes) at the periphery of the mass. Neoplastic cells were negative for smooth muscle actin, thus excluding a smooth muscle tumor (Figure 1d).

Figure 1

Subcutaneous mass extending caudally from the intrascapular region (a). Mesenchymal neoplastic cells are spindloid, arranged into streams and bundles with plump, oval nuclei and mitotic figures (hemotoxylin and eosin 200×) (b). Strong cytoplasmic expression of vimentin and negative expression of smooth muscle actin is observed (200×) (c, d)

This is the first report of a fibrosarcoma arising at the site of a SC fluid tube implant in a cat. The exact cause for malignancy in this case is unknown although similar foreign body reactions leading to neoplasia have been reported.^3–8 For example, fibrosarcomas developing secondary to microchips in both cats and a dog have been reported.^4–6 Typically, the microchip device is embedded or immediately adjacent to a firm mass composed of neoplastic mesenchymal cells. An intra-abdominal fibrosarcoma arising within a mass of retained surgical sponge material and fibrosis has been reported in a cat from a previous ovariohysterectomy. ³ In this case report the cat presented 6 years after the procedure with clinical signs unrelated to the intra-abdominal mass. Similarly, a dog developed extraskeletal osteosarcoma related to a retained surgical sponge, as well as reports of osteosarcomas associated with internal fixation devices to correct limb fractures.^7,9 Additionally, malignant transformation has been demonstrated in laboratory animals with implantation of various polymers, cellophane, glass and plastics. ¹⁰ In this particular case report the long-standing presence of a large foreign body may have been a risk factor for neoplasia. Although the manufacturer states that implants can be placed indefinitely, and typically function for many months to over a year with minimal complications, it is not known if the devices were tested for several years of use. ²

Although no previous information regarding complications of SC fluid tubes exists, smaller SC vascular access ports in dogs and cats have been used previously and studies of complications do not include neoplasia.^11–14 Dogs and cats with SC vascular access ports that received fractionated radiotherapy had several associated complications, which included sepsis, abscesses, edema at the port site, port occlusion, seroma formation, breakage at the port–catheter junction, port migration, port suture breakage and port erosion, but no reports of malignancy aside from that which they were being treated. ¹¹ In a separate study, vascular ports were used in feline blood donors for blood collection. Ports were in place for 6 months and complications included self-traumatic excoriations, edema, seroma formation and infections. ¹⁴ No evidence of neoplasia at the port site was reported.

Conclusions

Although the exact cause for neoplastic transformation was not identified definitively in this case a general link between chronic inflammation and malignancy has been made in the literature.^10,15–18 This has been shown in humans with Crohn’s disease and increased risk for colonic cancer, chronic gastric inflammation due to Helicobacter pylori and gastric carcinoma, as well as asbestos exposure and mesotheliomas.^19–25 Chronic inflammation, increased cellular turnover, cytokine release, growth factors and reactive oxygen species may result in angiogenesis, fibroplasia and DNA damage.^10,15,17 Collectively, these processes could contribute to malignant transformation. In this case of fibrosarcoma associated with a SC fluid tube implant there were repeated episodes of inflammation, as well as opportunistic bacterial contamination, with evidence of inflammatory infiltrates at the periphery of the mass and subsequent fibrosis, which occluded the tubing. The GIF tube manufacturer recommends that fluid administration sets and fluid bags are not reused to prevent contamination. ² In this case, the owners were aware of this recommendation and declined owing to cost and inconvenience. Reusing the same fluid bag and administration set could potentially have contributed to the ultimate GIF tube failure and infection; however, it is notable that no major complications or infection occurred for several years. This chronic inflammatory nidus likely contributed to the development of fibrosarcoma in this cat. Although malignancy associated with other SC ports has not been reported in companion animals this complication should be considered especially when in conjunction with protracted local infections.