Abstract
Histopathologic changes found in a grade III fibrosarcoma in a 12-yr-old captive-raised tiger (Panthera tigris) resemble those reported in vaccine-associated sarcomas in domestic cats. However, these changes are also compatible with foreign body-associated sarcomas and a broken dart needle was found near the tumor. Because the histopathologic changes are non-specific, it cannot be definitively determined whether this lesion was vaccine-induced or dart-induced; however, the changes are characteristic enough to suggest that the vaccinations, the metallic foreign body, or both, contributed to this tumor’s development. Because of the potential risk (albeit low) in developing sarcomas, the frequency of vaccinating exotic felids and the leaving of broken dart needles (or other foreign bodies) in exotic felids, may need to be re-evaluated.
Case Report
A 12-yr-old captive-raised female tiger (Panthera tigris) was anesthetized for examination of a large circular swelling on its right hip just caudal to the right ischial tuberosity. According to zoo personnel, the fluctuant mass had suddenly appeared and had reached its current size over a period of 2–3 days. Using ketamine and midazolam, the tiger was anesthetized for biopsy, culture and sensitivity, and survey radiography of the mass. A fine needle aspirate of the mass revealed clear yellow fluid. Surgical exploration of the mass was performed and revealed deep invasion of the mass into the leg musculature. Removal of the mass was aborted when it became apparent that complete removal would not be possible without irreparable damage to the leg. Additional incisional biopsies were taken; these revealed a hollow, necrotic-appearing core within a hard fibrous mass. Because of the tumor’s size and location, closure could not be accomplished without incorporating the tissue of the mass into the incision line. Consequently, dehiscence was anticipated as a likely complication. The tiger was administered procaine penicillin s.c. Recovery from anesthesia was uneventful and a course of oral amoxicillin was begun the following day.
Histopathologic findings were consistent with fibrosarcoma with up to two mitotic figures per high power field. Multifocal areas of coagulative necrosis were also evident. Culture results revealed an alpha-streptococcal sp. that was responsive to most antibiotics. Radiographs revealed a 3-cm, barbed, tubular metal structure (consistent with a barbed dart needle) to be present in the soft tissues caudal and ventral to the left acetabulum. Full delineation of the soft tissue mass could not be determined, however the needle appeared to be 2 cm cranial to the cranial extent of the mass.
The tiger did well post-surgically with no gait abnormalities and minimal drainage from the incision site. Four days after surgery, however, a small 2-cm dehiscence in the ventral aspect of the incision was noted; the following day the incision completely dehisced with exposure of tumor and muscle. Dehiscence was exacerbated by the tiger’s constant licking of the wound. The tiger was re-anesthetized, the tumor was debulked and flushed with 2 L of sterile saline, and the wound was closed again. Suture tension was minimal; however, dehiscence was anticipated because of the large size of the tumor and presumptive wound infection.
Two days after the second surgery (7 days following the initial surgery), the incision again completely dehisced. Closure of the incision was not attempted as euthanasia was being strongly considered. The tiger was euthanatized on the following day and a postmortem examination was performed.
At necropsy, the tumor measured 20×14×8 cm. The tumor was multinodular and extremely firm to palpation. A broken needle from a dart was found within the musculature, 2 cm anterior and dorsal to the neoplasm. The dart was close to, but not directly associated with, the body of the neoplasm. The lungs contained multiple, 2–5 mm diameter, firm, palpable nodules.
Histopathology revealed the primary tumor to be a grade III fibrosarcoma. Histopathologic changes were consistent with those found in vaccine-associated fibrosarcomas in domestic cats. Muscle tissue from around the area of the needle revealed the tumor to infiltrate between muscle bundles in sheets of spindle cells. The lungs revealed lesions of metastatic fibrosarcoma with cells identical to those in the primary lesion. Two, 3-mm diameter lesions were detected with cellular changes consistent with bronchoalveolar carcinoma.
Vaccine-Associated Sarcomas
The neoplastic changes that occurred in this tiger were clinically and histologically comparable to those seen in domestic cats with vaccine-associated sarcoma. Such changes are also consistent with tumors induced by foreign bodies. Over this tiger’s 12-yr lifespan, it was vaccinated at least ten times with several killed vaccine products. Unfortunately, medical records were not specific regarding dart injection sites; however, the hip and thigh muscles are likely sites, as six of the 10 vaccinations were administered via blow-dart.
Associations have been demonstrated between vaccination with killed vaccine and fibrosarcoma development at the vaccination site.6 Numerous investigators have concluded that in a low number of feline patients (1:10,000), vaccinations can lead to fibrosarcomas at injection sites, particularly when vaccination is repeatedly given at the same location.4 One study determined that the risk for developing a fibrosarcoma was 50% higher in cats that received a vaccination compared to those that did not; the risk in cats with two vaccinations was 127% higher and 175% higher in cats with three to four vaccinations.6 A single vaccine brand has not been singled out or excluded from suspicion. Presently, vaccination-site sarcoma formation appears to be unique to cats.3
Electron probe x-ray microanalysis has revealed that material within many of the vaccine-associated sarcomas is composed of aluminum and oxygen.5 Whether the aluminum is oncogenic, or merely a marker of the neoplastic reaction, remains to be determined.7 Histologically, vaccine-associated sarcomas are enveloped in dense, fibrous connective tissue and infiltrated with inflammatory lymphocytes and macrophages.8 Bluish foreign material has been present in macrophages of many vaccine-associated sarcomas.4 The tumor in this animal did not have such material, but did have other histologic changes consistent with vaccine-associated sarcomas. Necrosis has been found to be more common in vaccine-induced fibrosarcomas than in non-vaccine induced fibrosarcomas, with 25% of the vaccine-associated tumors having cavitated centres.3 The tumor in this tiger was highly necrotic with a large cavitated core.
Vaccine-induced sarcomas appear to be fast-growing and very invasive locally with infrequent metastasis; however, failure to recognize metastatic lesions may be due to short survival time of animals with these tumors.7 Post-vaccinal sarcomas often appear within 3–9 mo of vaccination; tumors not associated with vaccination are typically slower growing.7 Vaccine-associated sarcomas occur more frequently in the subcutis, while non-vaccine-associated sarcomas occur more frequently in the dermis. The tumor in this tiger was predominantly in the subcutaneous space with deep invasion of the muscles of the leg.
The histologic similarities of the tiger’s lesion to vaccine-associated sarcomas in domestic cats raise some interesting issues. Considering that there is currently a great deal of research and debate focused on vaccination recommendations in domestic cats, perhaps it would be wise to apply some of the same discussion to vaccination of exotic felids. We recognize that no vaccines are approved in exotic felids, that vaccine-associated sarcomas are relatively rare events (even in domestic cats), and that protection of exotic felids for infectious diseases is an important component of preventative health programs. However, we should examine the following recommendations regarding vaccination of domestic cats and apply them, as appropriate, to exotic felids. Current recommendations hold that none of the killed vaccines should be given in the interscapular space. The location, manufacturer, and serial number should be recorded in the medical record. Previous vaccination sites should be avoided when giving booster vaccinations.7 Cats should not be unnecessarily vaccinated and vaccination protocols should be dictated by risk of infection and prevalence of disease.
Foreign Body-Associated Sarcomas
The broken dart needle’s close proximity to the tumor site, however, also suggests that the tumor may have been caused by chronic irritation by this foreign-body. In addition to being darted for vaccinations, the tiger was also anesthetized multiple times, with five anesthetic procedures prior to those associated with treatment of the fibrosarcoma. Anesthetic records do not document all sites of anesthetic injection, however an episode in 1989 noted that a dart needle broke off in the right hip area. At that time, the hip was radiographed and the broken needle was found within the soft tissue of the hip. However, the object could not be externally palpated and no further treatment was pursued.
Tumors induced by foreign bodies have been studied in animals;10 physical factors that influence the foreign body response of inflammation and fibrosis appear to influence tumorigenesis and latency.2 Critical factors defined in the induction of sarcomas include the configuration of the implant (smooth, intact, large foreign bodies are more tumorigenic than roughened, perforated, smaller ones) and a period of latency long enough to allow progression to neoplasia of atypical elements arising within this perturbed environment.1 In a 1976 report, several tumors were described that were associated with metallic implants.10 Of the eight animals reported, only one was a felid (domestic cat); this animal developed a fibrosarcoma adjacent to a Jonas intramedullary splint of the right femur.10 A case report in a human described an aggressive soft tissue sarcoma that was detected in association with an aluminum oxide ceramic total hip implant; this tumor was detected 15 mo after implantation of the device.9
This information suggests that careful consideration should be given before any foreign object is left within an animal. Although there are situations in which it is necessary to leave metallic foreign bodies inside of animals (i.e., treatment for a fracture), or where surgical removal of foreign bodies is not a viable option, the chronic presence of these materials may induce abnormal changes in surrounding cells and these changes may promote tumor formation. Aluminum, in particular, causes persistent inflammatory and immunologic reactions that may predispose cats to a derangement of the fibrous connective tissue repair response which may lead to neoplasia.5
Discussion
It is unclear whether the tumor in this cat was associated with the previous vaccinations, with the broken dart needle, with both events, or with neither. However, it is hoped that this case will stimulate others to report their experiences with tumors that occur near sites of previous vaccination or adjacent to metallic foreign bodies, to gain a more accurate interpretation of the presence, incidence, and etiology of such tumors. Because of the potential risk (albeit low) in developing sarcomas, the frequency of vaccinating exotic felids and the leaving of broken dart needles (or other foreign bodies) in exotic felids, may need to be re-evaluated.
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