History
An 8-year-old 43-kg (94.6-lb) castrated male Labrador Retriever was evaluated at the University of Georgia Veterinary Teaching Hospital because of stranguria of 4 days’ duration. The dog was only able to expel a few drops of urine after straining for a prolonged time, although the urine produced was normal in appearance. The dog had no other notable medical history.
Clinical and Gross Findings
When the dog was first presented to the referring veterinarian, no abnormalities were identified on physical examination, and the results of routine hematologic and serum biochemical analyses were unremarkable. A urinary catheter was placed to allow for micturition. Urinalysis revealed a specific gravity of 1.015, 15 to 20 RBCs/hpf (40×), 2 to 5 WBCs/hpf, and rare epithelial cells. The dog received a single SC injection of carprofen (4.4 mg/kg [2 mg/lb]) and was referred to the veterinary teaching hospital because the presence of a urinary bladder mass was suspected.
At the referral evaluation, abdominal ultrasonography revealed a 2-cm-diameter mass arising from the dorsal wall of the urinary bladder at the trigone. Mild blood flow within the mass was detected during color Doppler ultrasonographic examination. There was no evidence of extension of the mass into the urethra or of ureteral obstruction in the form of hydroureter. Additionally, thoracic radiography revealed no important abnormalities.
Flexible video cystoscopy confirmed the presence of a broad-based, exophytic, pale pink mass in the trigone region of the urinary bladder (Figure 1). The mass was irregularly multinodular in appearance; the adjacent mucosa, extending distally into the proximal portion of the urethra and proximally into the region of the ureterovesicular junctions, appeared abnormal and roughened. Samples of the mass and the surrounding abnormal mucosa were obtained with endoscopic biopsy forceps and submitted for histologic analysis.
Endoscopic image obtained during cystoscopicguided collection of biopsy specimens from a urinary bladder mass in an 8-year-old castrated male Labrador Retriever. A pale pink, polypoid mass with a broad base is seen extending from the dorsal surface of the urinary bladder at the level of the trigone, where it partially obstructs the proximal portion of the urethra. The left ureterovesicular junction was visualized just proximal to the mass, but the right ureterovesicular junction was not identified.
Citation: Journal of the American Veterinary Medical Association 257, 11; 10.2460/javma.2020.257.11.1137
Endoscopic image obtained during cystoscopicguided collection of biopsy specimens from a urinary bladder mass in an 8-year-old castrated male Labrador Retriever. A pale pink, polypoid mass with a broad base is seen extending from the dorsal surface of the urinary bladder at the level of the trigone, where it partially obstructs the proximal portion of the urethra. The left ureterovesicular junction was visualized just proximal to the mass, but the right ureterovesicular junction was not identified.
Citation: Journal of the American Veterinary Medical Association 257, 11; 10.2460/javma.2020.257.11.1137
Endoscopic image obtained during cystoscopicguided collection of biopsy specimens from a urinary bladder mass in an 8-year-old castrated male Labrador Retriever. A pale pink, polypoid mass with a broad base is seen extending from the dorsal surface of the urinary bladder at the level of the trigone, where it partially obstructs the proximal portion of the urethra. The left ureterovesicular junction was visualized just proximal to the mass, but the right ureterovesicular junction was not identified.
Citation: Journal of the American Veterinary Medical Association 257, 11; 10.2460/javma.2020.257.11.1137
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page→
Histopathologic and Immunohistochemical Findings
Multiple small, 0.1- to 0.2-cm-diameter, pale pink, soft tissue biopsy specimens of the urinary bladder mucosa and mass were fixed in neutral-buffered 10% formalin and submitted for histopathologic examination. Sections were routinely processed and stained with H&E stain.
Histologically, the submucosa of the urinary bladder wall was markedly expanded by a well-demarcated, moderately cellular neoplasm. Two morphologically distinct populations of neoplastic cells were present. In 1 population, neoplastic cells were arranged in short, interwoven bundles and streams supported by scant, fibrous stroma (Figure 2). These cells were elongated and spindle shaped with indistinct cell borders and moderate amounts of fibrillar, eosinophilic cytoplasm. Each cell contained a single elongated, ovoid nucleus with finely stippled chromatin and 0 or 1 nucleolus.
Photomicrographs of histologic sections of biopsy specimens obtained from the bladder wall mass in the dog in Figure 1. A—Large numbers of monomorphic spindle-shaped neoplastic cells expand the submucosa of the urinary bladder. H&E stain; bar = 20 μm. B—A large number of neoplastic cells with round, distinct borders have expanded the submucosa; these cells have increased pleomorphism (anisocytosis, anisokaryosis, and multinucleation), compared with the more spindle-shaped neoplastic cells. H&E stain; bar = 20 μm. C—Neoplastic cells of both morphologies have strong cytoplasmic immunoreactivity for vimentin. Vimentin-specific immunohistochemical stain; bar = 20 μm. D—The round, multinucleated neoplastic cells have strong cytoplasmic immunoreactivity for desmin, whereas the spindle-shaped neoplastic cells have patchier immunoreactivity for desmin. Desmin-specific immunohistochemical stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 257, 11; 10.2460/javma.2020.257.11.1137
Photomicrographs of histologic sections of biopsy specimens obtained from the bladder wall mass in the dog in Figure 1. A—Large numbers of monomorphic spindle-shaped neoplastic cells expand the submucosa of the urinary bladder. H&E stain; bar = 20 μm. B—A large number of neoplastic cells with round, distinct borders have expanded the submucosa; these cells have increased pleomorphism (anisocytosis, anisokaryosis, and multinucleation), compared with the more spindle-shaped neoplastic cells. H&E stain; bar = 20 μm. C—Neoplastic cells of both morphologies have strong cytoplasmic immunoreactivity for vimentin. Vimentin-specific immunohistochemical stain; bar = 20 μm. D—The round, multinucleated neoplastic cells have strong cytoplasmic immunoreactivity for desmin, whereas the spindle-shaped neoplastic cells have patchier immunoreactivity for desmin. Desmin-specific immunohistochemical stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 257, 11; 10.2460/javma.2020.257.11.1137
Photomicrographs of histologic sections of biopsy specimens obtained from the bladder wall mass in the dog in Figure 1. A—Large numbers of monomorphic spindle-shaped neoplastic cells expand the submucosa of the urinary bladder. H&E stain; bar = 20 μm. B—A large number of neoplastic cells with round, distinct borders have expanded the submucosa; these cells have increased pleomorphism (anisocytosis, anisokaryosis, and multinucleation), compared with the more spindle-shaped neoplastic cells. H&E stain; bar = 20 μm. C—Neoplastic cells of both morphologies have strong cytoplasmic immunoreactivity for vimentin. Vimentin-specific immunohistochemical stain; bar = 20 μm. D—The round, multinucleated neoplastic cells have strong cytoplasmic immunoreactivity for desmin, whereas the spindle-shaped neoplastic cells have patchier immunoreactivity for desmin. Desmin-specific immunohistochemical stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 257, 11; 10.2460/javma.2020.257.11.1137
In the other population, neoplastic cells were rounded to polygonal with more distinct cell borders and often eccentric nuclei (Figure 2). Occasionally, these cells were binucleated or multinucleated with < 4 nuclei. Rarely, karyomegalic nuclei with prominent nucleoli were present in both uninucleated and multinucleated cells. Compared with the spindle-shaped cell population, anisocytosis and anisokaryosis in this second population were greater. One mitotic figure was seen in more than 10 hpf (400×). The adjacent submucosa was infiltrated by low numbers of lymphocytes, plasma cells, and fewer neutrophils. One examined section had a large, submucosal aggregate of fibrin and hemorrhage. The overlying transitional epithelium was multifocally thickened, with frequent intracellular edema.
Immunohistochemically, both populations of neoplastic cells had strong, cytoplasmic immunopositivity for vimentin (Figure 2). Interestingly, staining for desmin differed between the 2 populations of neoplastic cells; the round, multinucleated cells had strong, widespread cytoplasmic immunopositivity for desmin, whereas the spindle-shaped neoplastic cells had patchier immunopositivity. Following phosphotungstic acid–hematoxylin staining, no skeletal muscle cross striations were evident within the cytoplasm of neoplastic cells. Neoplastic cells were diffusely immunonegative for cytokeratin, smooth muscle actin, and myoglobin.
Morphologic Diagnosis and Case Summary
Morphologic diagnosis: pleomorphic myogenic sarcoma consistent with botryoid embryonal rhabdomyosarcoma.
Case summary: botryoid rhabdomyosarcoma at the trigone of the urinary bladder of an 8-year-old Labrador Retriever with urinary obstruction.
Comments
Tumors of the urinary bladder account for fewer than 1% of all neoplasms in dogs.1–3 In general, older animals tend to develop lower urinary tract neoplasms.1 However, rhabdomyosarcoma of the urinary bladder is unique among urinary tract tumors in that younger animals, generally 1 to 2 years of age, are affected. Female large-breed dogs are primarily affected, with an overrepresentation of Saint Bernards and Basset Hounds. When rhabdomyosarcoma develops in the urinary bladder, it most commonly originates in the trigone area and projects into the bladder as botryoid (grape-like) masses.2
Rhabdomyosarcoma is a primary tumor of skeletal muscle and is uncommon in any anatomic location in veterinary species.4 There are 3 subclassifications of rhabdomyosarcoma: embryonal, alveolar, and pleomorphic. Botryoid rhabdomyosarcoma is regarded as a variant of the embryonal subclass. Embryonal rhabdomyosarcomas characteristically consist of neoplastic cells with 1 of 2 morphologies, namely either round, myoblast-like cells or elongated, myotube-like cells. Additionally, these cells can be either uninucleated or multinucleated.5 The exact cell of origin of botryoid rhabdomyosarcomas is uncertain. Although skeletal muscle can be found in the urethra and fundus, embryonal rhabdomyosarcomas are believed to originate from pluripotent stem cells arising from an embryonic rest in the urogenital ridge, leading to its frequent development in younger animals.2
The clinical, histologic, and immunohistochemical findings for the dog of the present report were consistent with a final diagnosis of urinary bladder rhabdomyosarcoma. The neoplastic cells had strong cytoplasmic immunopositivity for both vimentin and desmin consistent with a mesenchymal and myogenic origin, respectively. The lack of smooth muscle actin immunopositivity differentiated these neoplastic cells from those of other myogenic sarcomas, such as leiomyosarcoma, yielding a final diagnosis of rhabdomyosarcoma. Additionally, the location of the tumor, growth pattern visible during cystoscopy, and biphasic population of neoplastic cells were most consistent with the botryoid variant. The case described in the present report was unusual in that the affected dog was 8 years of age.
Immunohistochemical analysis of tissue sections containing the neoplastic cell population in question is the preferred diagnostic technique for confirmation of rhabdomyosarcoma.4,5 Additionally, electron microscopic examination of tissue specimens for the presence of myofilaments can aid in diagnosis.4 With regard to botryoid rhabdomyosarcoma, various antigens are expressed differentially, depending on the degree of differentiation of the neoplastic cells. As muscle cells mature, they sequentially begin to express vimentin, desmin, actin, myosin, and myoglobin.6 Consequently, a poorly differentiated embryonal rhabdomyosarcoma, such as the botryoid variant in the dog of the present report, may express desmin but lack myoglobin expression.4 In the case described in the present report, the round, often multinucleated cells strongly expressed both vimentin and desmin; thus, these cells likely represented the myoblast-like cell component of the neoplasm. The spindle-shaped, uninucleated neoplastic cells strongly expressed vimentin, but had patchy immunopositivity for desmin; thus, these cells were thought to comprise the myotube-like component.
On the basis of the relatively few reported cases of urinary bladder rhabdomyosarcoma, the prognosis for affected dogs is guarded to poor. Complete excision is difficult to achieve, and recurrence and metastasis are expected to occur in more than half of cases.6 Without surgical removal, clinical signs of urinary obstruction will most likely persist. Most animals are euthanized at or near the time of diagnosis.
The dog of the present report recovered well from anesthesia following cystoscopy and debulking of the mass. The urinary catheter was replaced and then removed approximately 18 hours later. However, the dog was subsequently unable to urinate, and the urinary catheter was again replaced. The dog was discharged from the hospital the following morning with the urinary catheter in place, and the owners were to administer piroxicam (0.3 mg/kg [0.14 mg/lb], PO, q 24 h).
Treatment with piroxicam is often initiated in dogs with urinary bladder urothelial (transitional cell) carcinoma because the drug is thought to induce apoptosis of tumor cells.7 Two weeks after discharge from the hospital, the dog was presented to a local veterinarian for urinary catheter removal. Following catheter removal, the dog was able to successfully void urine. The owners were instructed to have the dog's renal status checked with a serum biochemical panel 2 weeks after catheter removal and then every 4 to 6 weeks for the duration of piroxicam treatment to monitor for potential renal toxicosis. To date, the direct effects of piroxicam on rhabdomyosarcomas (if any) remain undermined.
References
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