History
A 5-year-old 1.05-kg (2.31-lb) male guinea pig was evaluated because of signs of depression and anorexia of 2 days' duration, associated with progressive weight loss (approx 0.1 kg) over a period of a few months.
Clinical and Gross Findings
On physical examination, the guinea pig had signs of depression, and slight signs of pain were elicited by abdominal palpation. Radiography revealed the presence of ureteral calculi bilaterally. After preanesthetic assessment and stabilization of the animal's condition, the guinea pig was sedated; induction of anesthesia was performed for subsequent surgical removal of the calculi. Unfortunately, during preoperative preparation of the abdominal surgery site, the guinea pig suddenly developed severe hypotension due to copious abdominal hemorrhage followed by cardiac arrhythmia, respiratory arrest, and death despite resuscitation efforts and attempts to stop the bleeding. The abundant hemoperitoneum was associated with the rupture of a clinically unidentified mass involving the cranial pole of the right kidney (Figure 1). The mass measured approximately 2 × 1.5 × 1 cm, had a diffuse hemorrhagic appearance with admixed multifocal greyish areas on cut section, and was adherent to the external surface of the right adrenal gland. The owner gave consent for a complete necropsy during which no other gross abnormalities were observed.
Photographs of the abdominal cavity (A) and right kidney (B) of a 5-year-old guinea pig that had signs of depression and anorexia of 2 days' duration, progressive weight loss over a period of a few months, and urinary calculi. The guinea pig died during preparation for surgery. Necropsy revealed hemoperitoneum due to rupture of a hemorrhagic mass in the right kidney; the brown-reddish mass involved the cranial pole.
Citation: Journal of the American Veterinary Medical Association 250, 11; 10.2460/javma.250.11.1251
Photographs of the abdominal cavity (A) and right kidney (B) of a 5-year-old guinea pig that had signs of depression and anorexia of 2 days' duration, progressive weight loss over a period of a few months, and urinary calculi. The guinea pig died during preparation for surgery. Necropsy revealed hemoperitoneum due to rupture of a hemorrhagic mass in the right kidney; the brown-reddish mass involved the cranial pole.
Citation: Journal of the American Veterinary Medical Association 250, 11; 10.2460/javma.250.11.1251
Photographs of the abdominal cavity (A) and right kidney (B) of a 5-year-old guinea pig that had signs of depression and anorexia of 2 days' duration, progressive weight loss over a period of a few months, and urinary calculi. The guinea pig died during preparation for surgery. Necropsy revealed hemoperitoneum due to rupture of a hemorrhagic mass in the right kidney; the brown-reddish mass involved the cranial pole.
Citation: Journal of the American Veterinary Medical Association 250, 11; 10.2460/javma.250.11.1251
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page→
Histopathologic and Immunohistochemical Findings
Samples of the renal mass and adjacent adrenal gland were fixed in neutral-buffered 10% formalin and wax embedded; 5-μm-thick sections were stained with H&E stain. Additional sections underwent immunohistochemical analysis with primary antibodies directed against pancytokeratin (1:100 dilution),a vimentin (1:100 dilution),b and von Willebrand factor (1:800 dilution).c Immune complexes were treated with secondary biotinylated goat anti-mouse or anti-rabbit antibody (1:200 dilution)d and subsequently detected by use of an avidin-biotin complex method.e Peroxidase activity was detected with 0.1% hydrogen peroxide in 3,3′-diaminobenzidine solution.f Sections were finally counterstained with Mayer hematoxylin stain.g
Histologic examination of sections of the renal mass revealed a proliferation of pleomorphic plump to spindle-shaped mesenchymal cells with admixed irregular islands and spicules of focally mineralized, osteoid matrix (Figure 2). Neoplastic cells had a variable amount of pale amphophilic cytoplasm, round to oval and often eccentric hypochromatic nuclei with 1 or more prominent nucleoli, and a mitotic index of 10 to 11/10 hpfs (400×). Some neoplastic cells were located within osteoid lacunae. Small and large blood-filled spaces lined by tumor cells were present throughout the tumor. Scattered osteoclast-like multinucleated giant cells were also observed. The central area of the neoplastic mass was occupied by irregular, focally connected, partially calcified, lamellar bone trabeculae with fatty and hematopoietic marrow; cells in the trabecular lacunae had histologic features of well-differentiated osteocytes. Histologic examination of the sections of the right adrenal gland adjacent to the renal mass revealed that neoplastic cells did not infiltrate the adrenal gland parenchyma.
The renal tumor cells were positive for vimentin. However, the cells were negative for pancytokeratin and von Willebrand factor.
Morphologic Diagnosis and Case Summary
Morphologic diagnosis and case summary: renal extraskeletal osteosarcoma with marrow-containing bone in a guinea pig.
Photomicrographs of sections of the renal mass from the guinea pig in Figure 1. A—Notice the proliferation of pleomorphic mesenchymal cells admixed with irregular islands of osteoid matrix. H&E stain; bar = 45 μm. B—In this view, one of many large, blood-filled spaces lined by tumor cells within the mass is visible. H&E stain; bar = 45 μm. C—In this view, the interface between marrow-containing bone (lower right) and osteosarcomatous proliferation (in the center) surrounding a large blood-filled space (upper left) is evident. H&E stain; bar = 100 μm. D—Higher-magnification image of focally mineralized bone trabeculae containing hematopoietic marrow within the mass. H&E stain; bar = 45 μm.
Citation: Journal of the American Veterinary Medical Association 250, 11; 10.2460/javma.250.11.1251
Photomicrographs of sections of the renal mass from the guinea pig in Figure 1. A—Notice the proliferation of pleomorphic mesenchymal cells admixed with irregular islands of osteoid matrix. H&E stain; bar = 45 μm. B—In this view, one of many large, blood-filled spaces lined by tumor cells within the mass is visible. H&E stain; bar = 45 μm. C—In this view, the interface between marrow-containing bone (lower right) and osteosarcomatous proliferation (in the center) surrounding a large blood-filled space (upper left) is evident. H&E stain; bar = 100 μm. D—Higher-magnification image of focally mineralized bone trabeculae containing hematopoietic marrow within the mass. H&E stain; bar = 45 μm.
Citation: Journal of the American Veterinary Medical Association 250, 11; 10.2460/javma.250.11.1251
Photomicrographs of sections of the renal mass from the guinea pig in Figure 1. A—Notice the proliferation of pleomorphic mesenchymal cells admixed with irregular islands of osteoid matrix. H&E stain; bar = 45 μm. B—In this view, one of many large, blood-filled spaces lined by tumor cells within the mass is visible. H&E stain; bar = 45 μm. C—In this view, the interface between marrow-containing bone (lower right) and osteosarcomatous proliferation (in the center) surrounding a large blood-filled space (upper left) is evident. H&E stain; bar = 100 μm. D—Higher-magnification image of focally mineralized bone trabeculae containing hematopoietic marrow within the mass. H&E stain; bar = 45 μm.
Citation: Journal of the American Veterinary Medical Association 250, 11; 10.2460/javma.250.11.1251
Comments
On the basis of the histopathologic and immunohistochemical findings and the lack of skeletal involvement or other primary tumor sites (established by means of radiographic and necroscopic examinations), a diagnosis of renal extraskeletal osteosarcoma with marrow-containing bone was made for the guinea pig of the present report. Extraskeletal osteosarcoma is a very rare soft tissue tumor in humans and other animals, and is characterized by a proliferation of malignant osteoid-producing cells that lacks an association with the skeletal system. Although unusual, it predominantly develops in dogs and cats, whereas it is extremely rare in other species.1,2 To our knowledge, only 1 report3 of a multicentric extraskeletal osteogenic sarcoma in a guinea pig is available. Neoplasia is also generally uncommon in guinea pigs and usually develops in animals > 3 years of age.4
In the case described in the present report, histopathologic features and immunohistochemical findings (ie, absence of von Willebrand factor immunostaining in tumor cells lining blood-filled spaces) were indicative of a diagnosis of telangiectatic osteosarcoma.1 Blood-filled spaces surrounded by fibroblasts, rather than neoplastic cells, were also excluded because the sections of the renal mass did not have histopathologic features of organizing hematomas, necrosis, or hemosiderin deposition. The telangiectatic subtype of osteosarcoma has been very rarely described in extraskeletal sites, particularly the mesentery, in humans,5 whereas it does not appear to have been reported in the veterinary medical literature. The osteoblastic variant was the most common histologic type of tumor identified among canine cases of extraskeletal osteosarcoma in 1 study.6 There is only a single report7 of bone marrow production in the context of a human retroperitoneal extraskeletal osteosarcoma.
In the guinea pig of the present report, osseous trabeculae containing bone marrow were characterized by histologically mature osteocytes, whereas neoplastic cells only surrounded and partially infiltrated the periphery of this area. Such histologic findings are suggestive of previous heterotopic bone formation in the renal parenchyma, which subsequently became enclosed in the tumor mass. Heterotopic bone, also defined as osseous choristoma or metaplasia, refers to the development of dense, lamellar bone with variable degrees of calcification in tissues where bone would not usually exist. It may include functional, well-differentiated bone marrow.8 There are reports8,9 regarding the presence of heterotopic bone in the eyes and lungs of otherwise clinically normal guinea pigs, particularly in aged animals, although kidney involvement has not been described. Whether heterotopic bone formation is a normal age-related process or a pathological change in guinea pigs is unclear,8 although no evidence has been found concerning a relation between ectopic bone and the occurrence of disease.9
In the case described in the present report, one might speculate that the extraskeletal osteosarcoma originated from osteoblast-like cells of heterotopic origin. In fact, the potential for neoplastic transformation of heterotopic bone is supported by in vitro experiments that revealed differing behaviors of osteoblasts derived from normal bone and those derived from heterotopic bone; cells of heterotopic origin had greater metabolic activity and a greater proportion of mitotically active cells.10 In addition, development of osteosarcoma from preexisting mature heterotopic ossification in humans has been described.11,12 A canine meningeal osteosarcoma with colocalized dural mineralization and ectopic ossification has also been reported,13 although the nature of this relationship remained unclear. To our knowledge, this is the first report on a renal extraskeletal osteosarcoma associated with marrow-containing heterotopic bone in a guinea pig.
Acknowledgments
The authors declare that they have no conflicts of interest.
Footnotes
Monoclonal mouse anti-human cytokeratin, Clone AE1/AE3, DAKO, Glostrup, Denmark.
Monoclonal mouse anti-vimentin, CloneV9, DAKO, Glostrup, Denmark.
Polyclonal rabbit anti-human von Willebrand Factor, DAKO, Glostrup, Denmark.
Vector Laboratories Inc, Burlingame, Calif.
Vectastain ABC Kit, Vector Laboratories Inc, Burlingame, Calif.
Sigma-Aldrich Corp, St Louis, Mo.
Merck, Darmstadt, Germany.
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