Pollakiuria and Stranguria in a Labrador Retriever with Penile HSA
An approximately 8 yr old castrated male Labrador retriever presented for evaluation of weight loss, stranguria, and pollakiuria. Lysis of the proximal one-third of the os penis was diagnosed on abdominal radiographs, and a positive contrast urethrography revealed a smoothly marginated filling defect along the dorsal aspect of the urethra at the level of the radiographically observed osteolysis. Regional ultrasound revealed an echogenic mass at the proximal aspect of the os penis with a severely irregular and discontinuous periosteal surface. A penile hemangiosarcoma (HSA) was confirmed on histopathologic evaluation after a penile amputation and scrotal urethrostomy were performed. Although HSA is a common malignant neoplasm in dogs, lysis of the os penis has not previously been documented. Adjunctive chemotherapy, although recommended, was declined, and the patient survived 236 days postoperatively. That survival time is considerably longer than the average survival time for patients with HSA, other than cutaneous forms of HSA. Although an uncommon presentation, HSA of the penis should be considered a differential diagnosis in older canines with signs of lower urinary tract disease, especially in breeds that have been documented to be predisposed to HSA.
Introduction
Hemangiosarcoma (HSA) is a malignant neoplasia arising from the vascular endothelium and is associated with a high metastatic rate and overall poor prognosis.1–5 Splenic HSA is the most common diagnosis, with HSA representing 51% of all splenic tumors.6 Other locations of visceral HSA have been documented and include the liver, right atrium or auricle, left ventricle, skin or subcutaneous tissue, kidney, urinary bladder, prostate, urethra, penis, lung, muscle, bone, peritoneum or retroperitoneum, oral cavity, conjunctiva, and central nervous system.1–4,7–12 Clinical signs and physical exam findings associated with HSA can be vague and nonspecific and may vary significantly depending on tumor location. A definitive diagnosis of HSA requires histopathologic evaluation, but suspicion can be raised based on tumor location, presence of intracavitary hemorrhage, gross appearance of the tumor, and presence of distant metastatic disease at the time of diagnosis. A modified World Health Organization staging system has been developed for canine HSA, in which stage 1 disease is limited to a tumor confined to the primary site, stage 2 disease is a tumor that has either ruptured or spread to regional lymph nodes, and stage 3 disease includes a primary tumor with either metastatic or multicentric disease. Patients with splenic HSA most commonly present with stage 2 disease and evidence of intracavitary hemorrhage.8
Advanced stage of disease at the time of presentation and rapid development of metastasis results in death within 6 mo of initial diagnosis for most patients. Dogs with splenic HSA treated with splenectomy alone are reported to have a 1 yr survival rate of 6.25%.13 Therefore, surgical resection combined with adjunctive chemotherapy is the treatment of choice for all forms of HSA. A variety of chemotherapy protocols have been described, with variable outcomes contingent upon the stage of disease and tolerance to treatment. Doxorubicin-based protocols reportedly have a modest improvement in survival time, with little to no prolonged survival in those protocols deficient in doxorubicin.1,8,15 Cutaneous HSA is still regarded to have a guarded long-term prognosis; however, survival times are considerably longer than visceral forms of HSA even in the absence adjunctive chemotherapy.
The purpose of this report is to describe an atypical from of HSA. The tumor resulted in lysis of the os penis, and the patient demonstrated a longer than expected survival in the absence of adjunctive chemotherapy.
Case Report
An approximately 8 yr old castrated male Labrador retriever was referred to the authors for evaluation of a 3 wk history of weight loss (approximately 4.5 kg), pollakiuria, stranguria, a smaller than normal urine stream, and prolonged urination. Initial evaluation by the referring veterinarian included observation of the patient urinating and a urinalysis performed on a urine sample obtained by cystocentesis. The urinalysis revealed a slight hazy appearance to the urine, a pH of 7, a specific gravity of 1.040, occasional red blood cells, occasional WBCs, Ca oxalate crystals, and bacteria (2+ cocci). No urine culture was submitted at that time, and a 14 day course of cefpodoxime proxetila (5.15 mg/kg per os [PO] q 24 hr) was prescribed. The owner was also instructed to continue the current dose of deracoxibb (2.9 mg/kg PO q 24 hr), which was being used for chronic management of osteoarthritis. Initially, the owner reported very minimal improvement, but by the second wk of antimicrobial therapy, the patient’s clinical signs had improved.
Fifteen days after the initial evaluation and 1 day after completion of the antimicrobial therapy, the pollakiuria, stranguria, abnormal urine stream, and prolonged urination returned. An additional 14 day course of cefpodoxime proxetil (5.15 mg/kg PO q 24 hr) was prescribed. The patient returned to the referring veterinarian 5 days after starting the second course of antimicrobial therapy due to persistent clinical signs. Diagnostic testing performed by the referring veterinarian at that time included abdominal radiographs, a urinalysis, and the veterinary bladder tumor antigen (V-BTA) testc. Abdominal radiographs (right lateral and ventrodorsal views) revealed a large urinary bladder, but were otherwise unremarkable. No signs of urolithiasis were visible; however, a small portion of the urethra was excluded in that imaging series. Cystocentesis was performed under ultrasound guidance, and the ultrasound revealed neither shadowing defects nor evidence of a mass. A urinalysis performed on the second urine sample revealed a slight hazy appearance to the urine, a pH of 7, a specific gravity of 1.039, 1+ protein, and 3+ red blood cells. Urinary catheterization was performed and the patient’s bladder was evacuated. The type and size of catheter used and the amount of urine evacuated was not recorded. However, slight resistance was noted near the last 1–2 inches of the catheter placement. Immediately after the catheterization, there was significant improvement in the patient’s stranguria, and the urine stream was back to normal. Within 24 hr, the clinical signs returned and the patient was referred for further evaluation.
On presentation to the referral hospital, the patient appeared alert and well hydrated. Heart rate, temperature, and respiratory rate were all within normal limits. The patient weighed 39 kg, which was consistent with the reported 5 kg weight loss. The physical examination revealed mild periodontal disease and possible prostatomegaly palpable on abdominal palpation, but was otherwise relatively unremarkable. A small, flaccid urinary bladder was palpable, and the patient postured to urinate voluntarily. Stranguria and a small urine stream were noted. A rectal exam was performed, but the prostate was not palpable. The prepuce and penis were examined and revealed no significant abnormalities.
A complete blood count (CBC), serum biochemical analysis, urinalysis, urine culture, and an abdominal ultrasound were performed. Results of the CBC and serum biochemical analysis were within normal limits. The urinalysis performed on a urine sample obtained by cystocentesis revealed a cloudy appearance, a pH of 7, a specific gravity of 1.038, trace protein, and 3+ red blood cells (21–50/high-power field). After 48 hr, the urine culture yielded no growth and was considered negative at that time. The initial abdominal ultrasound revealed no abnormalities. Specifically, the urinary bladder, prostate, and prostatic urethra were all within normal limits.
Based on those findings, the patient was hospitalized overnight for observation. Retrograde urinary catheterization using a 10 French urethral catheterd was performed without sedation, and no areas of resistance were detected. In total, 250 mL of urine was evacuated. Reflex dyssynergia, although uncommon, was a differential diagnosis, and phenoxybenzaminee (.25 mg/kg PO q 12 hr) was initiated overnight. Otherwise, no specific treatment was administered. The patient’s stranguria resolved overnight and a normal urine stream was observed over the next 12 hr.
The following morning, abdominal radiographs (right lateral and ventrodorsal views), to evaluate the proximal urethra (previously excluded from the imagining study) and a urethrocystogram were performed. The right lateral abdominal radiograph revealed moderate to severe expansile osteolysis of the proximal one-third of the os penis (Figure 1). A positive contrast urethrogram using approximately 30 mL of a nonionic iodinated contrast agentf (240 mgI/mL) was injected through a 12 French urethral catheter placed in the distal most aspect of the urethra. An elongated, smoothly marginated filling defect causing severe narrowing of the urethral lumen was seen along the dorsal aspect of the urethra in the region of the proximal one-third of the os penis, corresponding to the region of the radiographically observed osteolysis (Figure 2). Regional ultrasound examination revealed an elongated although a somewhat ill-defined hypoechoic and mixed echogenic mass lesion with intralesional echogenic foci consistent with mineral within the proximal aspect of the os penis. The periosteal surface of the lesion was also markedly irregular and discontinuous, and apparent deviation of the urethra was noted in this location. Based on the imaging findings, an aggressive, expansile, osteolytic lesion originating within the proximal one-third of the os penis causing extraluminal compression of the membranous urethra and secondary partial obstruction was suspected. Differential diagnoses included neoplasia (e.g., osteosarcoma, multilobular osteochondrosarcoma, HSA) or another soft-tissue sarcoma. Less likely differential diagnoses included either epithelial neoplasia (e.g., transitional cell carcinoma, squamous cell carcinoma) or a benign lesion such as osteomeyelitis of the os penis. With neoplasia as the primary differential diagnosis, thoracic radiographs were obtained (right lateral and ventrodorsal views), which revealed no abnormalities.
Citation: Journal of the American Animal Hospital Association 50, 2; 10.5326/JAAHA-MS-5984
Citation: Journal of the American Animal Hospital Association 50, 2; 10.5326/JAAHA-MS-5984
Multiple fine-needle aspirates of the mass were performed and consisted of hemodilution in the presence of anaplastic neoplasia. The samples were of low cellularity, and the neutrophils present were consistent with peripheral blood. There were also loosely scattered cohesive clusters of degenerate cells with round nuclei and limited amounts of basophilic cytoplasm. Many of the cells exhibited multiple prominent nucleoli and multinucleation. Naked nuclei were detected as well. Some dysplastic cells appeared spindle shaped. Given the nature of the atypia present, a sarcoma was considered the top differential diagnosis. Bone phase nuclear scintigraphy to evaluate for osseous metastasis due to the possibility of an osteosarcoma was recommended prior to proceeding with surgery but was declined. A penile amputation with scrotal urethrostomy was performed 1 wk after presentation to the referral hospital (Figure 3). The patient recovered well from surgery and was discharged 2 days later. Aside from a small amount of incisional bruising and swelling, no postoperative complications were reported. Hematuria was reported intermittently during the recovery period, but had resolved by the time of suture removal 2 wk postoperatively.
Citation: Journal of the American Animal Hospital Association 50, 2; 10.5326/JAAHA-MS-5984
The excised tissue was submitted for histopathologic evaluation and revealed polygonal to spindle forming cells arranged in densely cellular streams and bundles. The cells had vacuolated eosinophilic cytoplasm, ovoid nuclei, vesicular chromatin, and prominent nucleoli. Anisokaryosis was present, and the nuclei from the neoplastic cells protruded into the lumina. The mitotic index was 28, and resident bone was disrupted. The histopathologic diagnosis was HSA of epithelial origin with disruption of pre-existing bone.
Adjunctive chemotherapy was recommended but declined. The patient was maintained on deracoxib (2.9 mg/kg PO q 24 hr), gabapenting (3.5 mg/kg PO q 24 hr), polysulfated glycosaminoglycanh injections, and fatty acid supplementation for the osteoarthritis. Tramadoli was also used intermittently for pain control. A follow-up examination was performed approximately q 70 days and included three-view thoracic radiographs and an abdominal ultrasound to monitor for metastatic lesions. At the first re-examination, 63 days postsurgically, the patient was reported to be doing well and had no abnormalities associated with the physical examination. The thoracic radiographs revealed a 7 mm soft-tissue density overlying the sixth rib on the left lateral view. That finding was consistent with pulmonary metastatic disease, but the abdominal ultrasound was unremarkable.
At the second postsurgical examination, 116 days after surgery, the patient continued to do well. No abnormalities were noted on the physical examination. The thoracic radiographs, however, revealed multiple variably sized pulmonary nodules. The largest was 1.2 cm summating over the cardiac silhouette between the sixth and seventh ribs on the left and right lateral views. The abdominal ultrasound was unremarkable. A CBC and serum biochemical analysis obtained at that time revealed a mild alkaline hyperphosphatemia (136 µkat/L; reference range, 5–131 µkat/L), mild hypomagnesemia (1.4 mmol/L; reference range, 1.5–2.5 mmol/L), mild neutrophilia (12.4 × 109/L; reference range, 2.1–10. 6 × 109/L), and a monocytosis (1.2 × 109/L; reference range, 0–0.84 × 109/L).
At the third follow-up examination, 193 days postsurgically, it was reported that the patient had developed a cough. The cough was characterized as dry and nonproductive and occurred about twice to thrice weekly. No abnormalities were noted on physical examination. Thoracic radiographs revealed an increase in the number of pulmonary nodules present, the largest of which measured 1.8 cm. The abdominal ultrasound revealed a 2.65 cm heterogenous capsular bulging mass at the caudal pole of the left kidney, left adrenomegaly (.8 cm), and an enlarged right sublumbar lymph node (.84 cm). A CBC and serum biochemical profile were obtained at that examination, which revealed resolution of the mild alkaline hyperphosphatemia. Other abnormalities detected included a mild hypercholesterolemia (8.6 mmol/L; reference range, 2.4–8.4 mmol/L), mild hypertriglyceridemia (304 mg/dL; reference range, 29–291 mg/dL), mild neutrophilia (10.9 × 109/L; reference range, 2.1–10.6 × 109/L), and a mild monocytosis (0.9 × 109/L; reference range, 0–0.84 × 109/L).
Approximately 1 wk after the third follow-up examination, the patient was reported to have a urinary tract infection. The referring veterinarian prescribed a course of cefpodoxime proxetil, but the dose and duration of therapy were unavailable for review. Approximately 1 mo after the third follow-up examination, a small cyst was noted at the urethrostomy site. A fine-needle aspirate was performed by the referring veterinarian, which revealed blood. No cytologic evaluation was performed on the fluid. The owner reported that a moderate amount of hemorrhage occurred after the aspirate was performed. The cefpodoxime proxetil was discontinued at that time, and the patient was prescribed a course of enrofloxacinj of unknown dose and duration.
The patient was examined again 233 days after surgery. At that time, his appetite was declining and his attitude was changing (he was becoming withdrawn). In addition, it appeared that he was having a hard time sitting, seemed uncomfortable, and had a small amount of hemorrhage noted at the urethrostomy site intermittently. Physical examination at that time revealed a 2 cm ulcerated and hemorrhagic lesion at the urethrostomy site, caudal abdominal pain, and a reluctance to sit. The thoracic radiographs revealed an increase in both number and size of the pulmonary nodules, consistent with progressive metastatic disease (Figure 4). The abdominal ultrasound showed progressive left adrenomegaly (1 cm), a mottled spleen, and a 13 mm nodule associated with the urethrostomy site. The mass previously noted on the left kidney was still present, but equivocally smaller in size (Figure 5). A CBC and serum biochemical profile were obtained at that time and revealed mild alkaline hyperphosphatemia (146 µkat/L; reference range, 5–131 µkat/L), hypoglycemia (1.22 mmol/L; reference range, 3.85–7.7 mmol/L), hyperkalemia (5.7 mmol/L; reference range, 3.6–5.5 mmol/L), hypercholesterolemia (9.4 mmol/L; reference range, 2.4–8.4 mmol/L), mild hypertriglyceridemia (333 mg/dL; reference range, 29–291 mg/dL), elevated amylase (1,204 µkat/L; reference range, 290–1,125 µkat/L), mild thrombocytopenia (162 × 109/L; reference range, 170–400 × 109/L) with an adequate estimation. Pain control was attempted by increasing the tramadol (4.6 mg/kg PO q 8 hr), and metoclopramidek (.34 mg/kg PO q 8 hr) was initiated in the event that nausea was contributing to the hyporexia. Given the patient’s continued discomfort, he was euthanized 3 days later. The patient survived 236 days.
Citation: Journal of the American Animal Hospital Association 50, 2; 10.5326/JAAHA-MS-5984
Citation: Journal of the American Animal Hospital Association 50, 2; 10.5326/JAAHA-MS-5984
Discussion
Previous reports have estimated the overall prevalence of HSA to account for 3–7% of all canine malignancies.2,3,5,8 HSA typically affects middle-aged to older animals, with a mean age of 8–13 yr.1–5,8 Several breeds have been documented to have a predisposition for the development of HSA, including German shepherd dogs, golden retrievers, Labrador retrievers, and schnauzers.1–5,8 It has been shown, however, that animals of all ages and any breed can develop HSA, as an 18 mo old lurcher was diagnosed with HSA of the scapula.16 Clinical signs that are commonly reported with HSA include lethargy, anorexia, weight loss, exercise intolerance, and weakness.1,2,4,5 More specific clinical signs that are commonly reported include abdominal distension with hemoperitoneum, lameness with bone lesions, and seizures with central nervous system involvement.2,4,5 Physical exam findings may include arrhythmias associated with either cardiac or splenic involvement; muffled heart sounds or signs of right-sided heart failure (i.e., jugular distension, peripheral edema, hepatomegaly, ascites, pleural effusion) with cardiac involvement; hematuria or dysuria with bladder or kidney involvement; and dermal lesions with cutaneous involvement.2,4,5 Common clinicopathologic abnormalities include a normocytic normochromic anemia, reticulocytosis, and a neutrophilic leukocytosis.1,2,5 Thrombocytopenia is another common abnormality associated with HSA, the cause of which is believed to be multifactorial.5
Historically, the poor prognosis associated with HSA has justified the recommendation for early surgical intervention with adjunctive chemotherapy. Although one retrospective study did not document a statistical significance in survival times between patients that were treated with surgery alone; surgery and immunotherapy; or surgery, immunotherapy, and a combination of chemotherapy, the chemotherapy protocols did not use doxorubicin.1 A variety of chemotherapy protocols have been documented, including doxorubicin as a single agent, doxorubicin in combination with cyclophosphamide, and doxorubicin in combination with cyclophospamide and vincristine.3,8,15,17 One report documented a significant improvement in survival time in dogs with right atrial HSA that received adjunctive chemotherapy (mean, 164 days; median, 174 days) versus dogs that did not receive adjunctive chemotherapy (mean, 46 days; median, 42 days).17 Given the retrospective design of this study, the chemotherapy protocols varied between patients, but all contained doxorubicin. Hammer et al. (1991) documented a median survival time of 172 days in 15 dogs treated with vincristine, doxorubicin, and cyclophosphamide. Cutaneous HSA, if localized to the dermis, offers a better prognosis because it is associated with a much lower metastatic rate and longer survival times.18 One study that retrospectively compared stage 1, stage 2, and stage 3 cutaneous HSA revealed that stage 1 tumors were associated with significantly longer survival times (780 days) compared with those of stage 2 or 3 (172 and 307 days, respectively).19
Micturition disorders can be classified into neurogenic and nonneurogenic etiologies. Neurogenic causes lead to a functional urethral obstruction and include lower motor neuron disorders, upper motor neuron disorders, detrusor-urethral dyssynergia, and dysautonomia.20 Nonneurogenic causes lead to either partial or complete mechanical obstructions and include urolithiasis, infection, inflammation, and neoplasia of the urinary bladder or urethra.20 In this particular case, because the initial diagnostics yielded no signs of urolithiasis, bladder or urethral neoplasia, infection, or inflammation, a preliminary diagnosis of detrusor-urethral dyssynergia was made. Once lysis of the os penis and penile mass was identified, treatment was discontinued.
The V-BTA test is a rapid latex agglutination test that utilizes bladder tumor analytes that have been isolated from human patients with bladder cancer. Those tumor analytes contain high molecular weight glycoproteins, predominantly in the form of basement membrane proteins, but may also contain immunoglobulin.21 The formation of those protein complexes is the result of destruction of the basal lamina, which is a common finding in patients with lower urinary tract neoplasia. Transitional cell carcinoma is reportedly the most common neoplasia of the lower urinary tract, and that test was adapted from a bladder tumor antigen test used in humans with transitional cell carcinoma.22,23 The V-BTA test uses human IgG, which will react with the protein complexes within the urine and result in an agglutination reaction. With the use of a specially formulated testing strip, if agglutination should occur, a visual color change takes place and indicates a positive test result. Several different studies have been performed to evaluate the efficacy of the V-BTA test as a screening tool for dogs with transitional cell carcinoma.21,24–25 Although they have documented good sensitivity, the specificity and positive predictive values are poor (41% and 2.8%, respectively).21 One study in particular compared the use of the V-BTA test in healthy dogs to dogs diagnosed with lower urinary tract neoplasia and found a sensitivity of 90% and specificity of 94.4%.24 That same study, however, had a third population of dogs with nonmalignant lower urinary tract disease, and when compared with dogs with lower urinary tract neoplasia, the specificity dropped to 35%.24 The V-BTA test has also been associated with significant intraobserver variability due to the subjective nature of interpreting the color change.24 Hematuria and pyuria have also been documented to cause false-positive results, which make it difficult to evaluate because dogs with lower urinary tract neoplasia often have concurrent urinary tract infections.24,25 Therefore, the V-BTA test has been valued as an adequate screening tool to rule out lower urinary tract neoplasia, but not to confirm the presence of transitional cell carcinoma. It is likely the positive V-BTA result in this case was due to concomitant hematuria.
Conclusion
To the author’s knowledge, penile HSA with lysis of the os penis has only been reported in one other case.12 The case reported in this manuscript is unusual in that it is the first documented case in which a penile HSA results in stranguria and pollakiuria with lysis of the proximal os penis, but tumor invasion of the urethral lumen did not occur. In addition, the patient described herein went on to survive 236 days postoperatively, although adjunctive chemotherapy was declined. The study authors concede that limited information can be obtained from one individual and further case studies are required. It is possible that penile HSA may represent an intermediate-grade tumor and prognosis may not be as poor as previously expected. Further research involving this particular location and this tumor type would be required for more statistically significant information.
Right lateral abdominal radiograph showing osteolysis of the proximal one-third of the os penis. R, right.
A positive-contrast urethrogram (via right lateral abdominal radiography) shows an elongated, smoothly marginated filling defect causing severe narrowing of the urethral lumen. The urethral narrowing corresponds to the region of the radiographically observed osteolysis of the os penis in Figure 1.
Photograph of the amputated penis that has been transected longitudinally along the ventral surface. A mass (solid white arrow) is located at the distal end of the os penis (solid black arrow) in close proximity to the spongiosum (broken black arrow). A fracture of the os penis (broken white arrow) is visible due to the infiltrative nature of the mass.
During the fourth recheck (233 days after the penile amputation and scrotal urethrostomy), a left lateral thoracic radiograph revealed progression of the pulmonary nodules in both number and size. The pulmonary nodules were consistent with progressive metastatic disease. L, left.
Abdominal ultrasound at the fourth recheck reveals a persistent mass measuring 2 cm × 1.7 cm (indicated by the measurements labeled A and B) associated with the left kidney. This mass was suspected to be a metastatic lesion as well; however, neither cytologic nor histopathologic evaluation was performed.
Contributor Notes
J. Fry's present affiliation is Nashville Veterinary Specialists and Animal Emergency, Nashville, TN.
D. Burney's present affiliation is Veterinary Specialists of North Texas, Dallas, TX.
C. Feagin's present affiliation is ImageVet Radiology, Dallas, TX.
