Subcutaneous hemangiosarcoma induced by a foreign body (steel staple) in a cat

Abstract

An 8-year-old, female domestic shorthair cat was presented with a ventral abdominal subcutaneous mass. A radiograph showed that the center of the mass contained what appeared to be steel sutures, presumed to be from an ovariohysterectomy performed 7 years earlier. The excised mass was irregular and contained numerous pockets filled with friable necrotic material and hemorrhages that were dissected by fibrous connective tissue bands. Multiple tangled and fragmented pieces of steel staples were deeply embedded within the mass. Histologically, the mass was non-encapsulated, densely cellular, and infiltrative. Neoplastic cells lined caverns and channels and were factor VIII-positive by immunohistochemistry. The neoplastic cells were oval to round with granular cytoplasm and vesicular nucleus and exhibited moderate cellular and nuclear pleomorphism. A diagnosis of subcutaneous hemangiosarcoma was made. To our knowledge, this is the first report of foreign body associated hemangiosarcoma and the first case of steel staple associated neoplasm in domestic animals.

There are numerous reports of foreign body-associated neoplasms in domestic and laboratory animals. Among the reported foreign bodies are vaccine adjuvants (1), drugs (2), sponge (3), nonabsorbable sutures (4), intramedullary pin (5), and microchip (6). To our knowledge, this is the first report of foreign body induced hemangiosarcoma and the first case of steel staple induced neoplasm in domestic animals.

Case description

An 8-year-old, spayed female, domestic shorthair cat was presented with a history of a ventral abdominal subcutaneous mass that had been present for an unknown period of time. The cat had been adopted at approximately 1 y of age, and was ovariohysterectomized almost immediately. On presentation, a radiograph showed a soft tissue density mass with steel suture profiles at the center of the mass. The steel suture was presumed to be from the ovariohysterectomy procedure that was performed 7 years previously, as no other surgery was noted in the animal’s medical records and history. Three chest radiographs were also done, with no evidence of neoplasia. Clinical examination revealed a firm, rough, and irregular, approximately 7 × 6 cm subcutaneous mass involving the caudal ventral abdomen. Abdominal ultrasound did not show evidence of neoplasia, but revealed a large cavitated mass of mixed echogenecity in the mid-ventral abdomen just cranial to the bladder, measuring approximately 6 × 4 cm. A fine-needle aspirate of the mass was inconclusive, revealing a predominant population of erythrocytes and platelet clumps. A complete blood (cell) count (CBC) revealed a regenerative anemia with a packed cell volume (PCV) of 16% (reference range: 30% to 40%). Leukemia and FIV tests were negative; and the results of a chemistry panel were within normal limits as was a coagulation profile. Meanwhile the bruising along the left side had progressed in the day since the cat’s visit.

The cat was presented 1 wk later for a surgical consultation, with improvement of the bruising lesion. Contrast-enhanced computed tomography revealed a large soft tissue mass arising from the ventral abdominal wall (Figure 1). There was evidence of stainless steel sutures (hyperechoic lines) along the caudal abdominal wall extending into the mass. Approximately 50% of the mass was intra-abdominal and there was a small amount of free peritoneal fluid. Pre-operatively, the PCV was 23%. During surgery to remove the mass, the abdominal wall cranial to the mass was incised, and an elliptical incision was made around the mass through the body wall with approximately 1 cm margin of normal tissue surrounding the mass. The mass had 1 small adhesion of omentum in the center, but otherwise was unassociated with any abdominal structures. Bleeding was controlled with a combination of coagulation electrocautery and sutures. No evidence of metastasis was noted during surgery. The incision was closed with 2-0 polydioxanone suture (PDS) in a routine fashion with a routine subcuticular (SQ) and skin closure. Approximately 1 h after surgery, the cat had a seizure and suffered both cardiac and respiratory arrest. The cat was intubated and cardiopulmonary resuscitation (CPR) was initiated. The cat was given a bolus of hetastarch and feline packed red blood cells (PRBC’s) after the PCV was measured at 13%. Supportive efforts included warmth and a belly wrap. Stabilization of the cat’s vitals with voluntary breathing was obtained within 5 min of initiating CPR. The cat’s cardiovascular parameters continued to stabilize overnight, but she began exhibiting neurological signs consisting of head pressing and an inability to right and move her legs properly. Due to continued complication and non-responsiveness, the owner elected humane euthanasia the next morning.

Figure 1.

Computed tomography scan of the ventral abdominal mass. Subcutaneous mass (open arrow) with hyperechoic stainless steel sutures in the center (filled arrow).

Pathologic examination

Upon extrication of the mass, it was noted to be not adherent to the skin. The excised subcutaneous mass was approximately 8 × 8 × 8 cm, and was covered by adipose tissue (Figure 2A). On the cut surface, the mass was irregular with numerous soft, dark red, cystic (blood-filled) spaces, and contained numerous pockets filled with friable material (necrosis), and hemorrhages that were dissected by connective tissue bands. Multiple tangled and fragmented pieces of steel staples, measuring 0.1 cm in diameter and of variable lengths were deeply embedded within this mass (Figure 2B).

Figure 2.

A — Gross picture of the ventral abdominal subcutaneous mass. The subcutaneous mass is approximately 8 × 8 × 8 cm, and is covered by adipose tissue. B — Cut surface of the ventral abdominal subcutaneous mass. On the cut surface, the mass is irregular with numerous soft, dark, cystic (blood-filled) spaces, and contains numerous pockets filled with friable material (necrosis) and hemorrhages that are dissected by connective tissue bands. Multiple tangled and fragmented pieces of steel staples, measuring 0.1 cm in diameter and of variable lengths are deeply embedded within this mass.

Histologically, the subcutaneous adipose tissue and skeletal muscle bundles were effaced by an unencapsulated, poorly demarcated, infiltrative, and densely cellular neoplasm. The neoplastic cells were lining erythrocyte-containing caverns and channels, and were supported by anastomosing islands of fibrous connective tissue stroma. The individual neoplastic cells were oval to round, with ill-defined borders, and contained variable amounts of eosinophilic homogeneous granular cytoplasm. The neoplastic cells had a vesicular nucleus with fine chromatin and single to multiple eosinophilic nucleoli. Mitotic figures were approximately 3 per 10 high power fields (400×). Focally, some neoplastic cells partially occluded the lumen of a vessel. Adjacent connective tissue had foci of lymphoplasmacytic inflammation (Figure 3). Extensive areas of coagulative necrosis, fibrin thrombi, and hemorrhages were scattered within the tumor. Pockets of degenerate and viable neutrophils admixed with nuclear debris and fibrin were also scattered within the tumor. The neoplastic cells stained positively for factor VIII related antigen and CD31 by immunohistochemistry (Figures 4 and 5, respectively). Based on the gross and microscopic morphology, a diagnosis of subcutaneous hemangiosarcoma was made.

Figure 3.

Photomicrograph of the ventral abdominal subcutaneous mass. The subcutaneous adipose tissue and skeletal muscle bundles are effaced by an unencapsulated, poorly demarcated, infiltrative, sparsely cellular neoplasm. The neoplastic cells are lining erythrocyte-containing caverns and channels, and are supported by anastomosing islands of fibrous connective tissue stroma/trabeculae. Adjacent to this neoplastic tissue are small foci of lymphoplasmacytic inflammation and aggregates of hemosiderophages. Hematoxylin & eosin stain. 100×.

Figure 4.

Photomicrograph of the ventral abdominal subcutaneous mass. Diffusely, neoplastic endothelial cells have strong intracytoplasmic staining. Factor VIII related antigen is stained by immunohistochemistry.

Figure 5.

Photomicrograph of the ventral abdominal subcutaneous mass. Diffusely, neoplastic endothelial cells have strong intracytoplasmic staining. CD31 immunohistochemistry stain.

Discussion

Hemangiosarcomas are malignant neoplasms of vascular endothelial cells. Among the recognized variants of hemangiosarcomas in domestic animals, only the solar-induced variant has a defined cause (7). There are 3 types of foreign bodies associated neoplasms reported in domestic animals, namely: those induced by introduced foreign biological materials (in particular, live vaccines); those induced by implanted, foreign, non-biological materials (i.e., vaccine adjuvants, sponge, microchip, suture); and those induced by native but hidden antigen (pseudo-foreign material), such as lens epithelium. Reported cases of foreign body associated neoplasms in domestic animals include canine oral papillomavirus (COPV) vaccine-associated cutaneous neoplasms in dogs (8), vaccine-associated sarcoma (fibrosarcoma, rhabdomyosarcoma, myxosarcoma, chondrosarcoma, undifferentiated sarcoma, malignant fibrous histiosarcoma) in cats, dogs, and ferrets (1,6), microchip-associated fibrosarcoma and liposarcoma in dogs and laboratory rodents (6), lufenuron-associated fibrosarcoma in a cat (5), lens epithelium-associated intraocular sarcoma in cats (9), sponge-associated osteosarcoma in a dog (3), orthopedic implants (intramedullary pin, osteosynthesis plate, hip arthroplasty stem) associated sarcomas in dogs and cats (2), and nonabsorbable suture-associated mesenchymoma in a ferret and a cat (4).

Unlike natural mucous membrane neoplasms induced by COPV, the unattenuated vaccine caused cutaneous neoplasms that don’t spontaneously regress (8). Unattenuated COPV vaccine also induced several proliferative lesions (hyperplasia, cysts) in addition to neoplasm (benign and malignant) (8). It is postulated that the pathogenesis of these neoplasms involves the transformation of the basal cells at the inoculation site (8). Vaccine-associated sarcomas are suspected to be due to the chronic inflammation to aluminum adjuvant used in vaccines (1). This is supported by the presence of macrophages laden with smudgy gray materials, suspected to be adjuvant material (1). Although causal association was not proven, one of the suspected causes of chronic irritation due to embedding microchips is the antimigration capsule made up of bioglass (6). Using immunohistochemistry, it was determined that, at least for a subset of trauma-associated ocular sarcomas, the origin of the neoplastic cells was anterior lens epithelium (9). The cotton fibers of gauze and the microenvironment produced by the fibrous capsule reaction to the gauze are suspected to be the cause of sponge-associated osteosarcomas in dogs (3). Inflammation due to bone infarcts, implant corrosions, and infection complications have been implicated as the cause of neoplastic transformation in orthopedic implant associated neoplasms (3). Persistent remodeling of extracellular matrix as a reaction to non-absorbable suture material is suspected to be the cause of suture associated mesenchymomas (4).

Previous cases of foreign body associated hemangiosarcomas have been reported in humans (10,11). To the the authors’ knowledge, this has not been reported in domestic animals.

Mechanisms of foreign body associated neoplasms include reactivation of modified live viral vaccine (8), chronic inflammation to foreign inert material (12), and transformation of exposed hidden host antigen (lens epithelium) induced by trauma (9). The mechanism of carcinogenesis induced by chronic inflammation secondary to persistence of foreign inert material centers on macrophages and multinucleated giant cells in the inflammatory focus (12). Macrophages produce mutagenic oxygen-free radicals which serve as tumor initiator and at the same time they produce stimulatory cytokines such as TNF-α and IL-1 which serve as tumor promoters (12). Additionally, TNF-α induces MMP (matrix metalloproteases) production which promotes tumor invasiveness and metastasis (12). Macrophages also produce VEGF, which can stimulate angiogenesis and hence tumor growth, by providing oxygen and nutrient-rich blood supply and conduits for metastasis (12). Although the mechanism remains unknown, we speculate that a similar carcinogenic mechanism might have been responsible in this case. CVJ