Introduction

Urinary bladder cancer has been reported to make up 2% of all naturally occurring cancers in canines.¹ The vast majority of urinary bladder cancers are determined to be urothelial carcinomas (transitional cell carcinomas).¹ Squamous cell carcinoma, adenocarcinoma, undifferentiated carcinoma, various sarcomas (including leiomyosarcoma, rhabdomyosarcoma, osteosarcoma, hemangiosarcoma, fibrosarcoma), and lymphoma have all been reported with much lesser frequency.^2–9 Histiocytic sarcoma of the canine urinary bladder represents another rare diagnosis, as evidenced by only one reported case in both human and veterinary oncology.^10,11 Both of these cases were characterized by relatively short survival times following diagnosis. To the authors’ knowledge, this case report represents only the second report of confirmed histiocytic sarcoma of the canine urinary bladder and the first report of prolonged survival following treatment.

Case Report

A 9 yr old castrated male miniature schnauzer presented to the Toronto Veterinary Emergency and Referral Hospital oncology service 1 mo following surgical cystotomy for radiographically identified urolithiasis. At the time of cystotomy, a reported 1 cm urinary bladder mucosal lesion arising from the ventral bladder wall (apex) was observed; excisional biopsy was performed and submitted for histopathologic evaluation. Hematoxylin and eosin staining of the urinary bladder lesion revealed an incompletely excised anaplastic stromal sarcoma (Figures 1A, B). Immunohistochemistry revealed the following staining pattern: ionized calcium-binding adapter molecule 1 positive (Figure 1C), CD18 positive (Figure 1D), and CD31 negative, smooth muscle actin negative (images not shown), providing a definitive diagnosis of histiocytic sarcoma. The urinary bladder stones were removed and determined to be calcium oxalate. Diagnostic staging was performed 1 mo following cystotomy. Complete blood count was unremarkable. Serum biochemistry revealed elevations in alanine transaminase (ALT; 371 U/L; reference range 10–125 U/L) and alkaline phosphatase (ALP; 1,876 U/L; reference range 23–212 U/L). Urinalysis revealed a marked proteinuria (3+) and mild hematuria (1+). Thoracic radiographs were unremarkable with no evidence of pulmonary metastasis. An ultrasound evaluation of the urinary bladder revealed a nonpedunculated papillary mass at the cranioventral margin of the urinary bladder wall with adjacent poorly demarcated moderate thickening of the urinary bladder wall (Figure 2A). Local recurrence of histiocytic sarcoma was presumed but not confirmed via cytology and/or histopathology (further surgery was not elected). No other substantial abnormalities were noted on ultrasound examination of the remainder of the abdomen. Lomustine^a (70 mg/m²) was administered orally. Hepato-supportant therapy (Denamarin^b) was prescribed concurrently to be administered daily. The patient’s ALT was documented to decrease before the second administration of lomustine (ALT 229 U/L; reference range 12–118 U/L). Prior to the third administration of lomustine, ALT and ALP were markedly elevated (ALT 938 U/L; reference range 10–125 U/L and ALP >2000 U/L; reference range 23–212 U/L). Increased hepatic enzyme activity was attributed to known adverse effects of lomustine. Subsequently, lomustine was discontinued. Ultrasound examination performed 70 days following initial examination revealed a decrease in size of the urinary bladder mass equating to a partial response (1.8–1.0 cm diameter, 45% reduction) based on Response Evaluation Criteria In Solid Tumors criteria (Figure 2B). The patient’s liver continued to be normal on ultrasound evaluation. Further adjuvant chemotherapy with doxorubicin^c (1 mg/kg) was administered. Six doses of doxorubicin were administered over a 15 wk period (total dose 52.64 mg). No significant doxorubicin-associated toxicities were documented. Hepatic enzyme activity continued to decrease following cessation of lomustine. Periodic abdominal ultrasounds (performed 70, 132, 239, and 768 days following diagnosis) revealed continued decrease in the size of the urinary bladder mass until complete remission (CR) following the last dose of doxorubicin (time to CR, 239 days; Figures 2C, D). The last follow-up was 768 days following diagnosis. At this visit, a CR persisted on ultrasound evaluation. No metastatic lesions were evident on abdominal ultrasound or thoracic radiographs from time of diagnosis to last follow-up. Hepatic enzyme activity was also within the normal reference range. The patient remains alive at the time of manuscript preparation.

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Discussion

Several breed predispositions for histiocytic sarcoma have been reported,¹² including more recently the miniature schnauzer.¹³ Only one previous report of histiocytic sarcoma of the canine urinary bladder currently exists in the veterinary literature.¹⁰ In contrast to the previous report, this current case report demonstrates a significantly longer survival period (60 versus 768 days, respectively). In the previously published report, the mass involved the trigone region of the bladder, which may have played a significant role in the short survival. The single case report of histiocytic sarcoma of the urinary bladder in the human literature reported a short survival time (1 mo following diagnosis) because treatment was only characterized as palliative because of a rapidly deteriorating clinical condition.¹¹ Anatomic location of urinary bladder tumors has been demonstrated to be a significant prognostic indicator.¹⁴ Chemotherapy remains the mainstay of treatment of canine urinary bladder tumors, particularly those involving the trigone region. Lomustine remains the most commonly prescribed chemotherapeutic agent in the treatment of canine histiocytic sarcoma.^15,16 Although a response was seemingly evident following two administrations of lomustine, it was discontinued in this particular case because of observed hepatotoxicity. The partial response observed in this patient would contrast the progressive disease after 2 mo observed in the previous case report following lomustine.¹⁰ Subsequently, lomustine would still appear to be a viable treatment option for histiocytic sarcoma of the urinary bladder following this report. Further response was also documented with doxorubicin administration. Doxorubicin has demonstrated efficacy in the treatment of canine histiocytic sarcoma in combination with lomustine.¹⁷ Further study is warranted to determine the efficacy of single-agent doxorubicin in the treatment of histiocytic sarcoma of the urinary bladder (or other anatomic sites). Interestingly, no evidence of metastasis was documented in this patient or in the previously published case report.¹⁰ Certain forms of histiocytic sarcoma are characterized by very high metastatic potential.¹⁸ Although there are too few reported cases to draw any conclusions from, it is possible that histiocytic sarcoma of the urinary bladder may reflect a more localized form of histiocytic sarcoma rather than a rapidly disseminating form.

Conclusion

Only represented by one previous case report, histiocytic sarcoma should continue to be considered a rare differential diagnosis for canine urinary bladder masses. The current case diverges significantly from the previous report by revealing the possibility of long-term survival. Furthermore, this report may also reveal a potential role for doxorubicin in the treatment of histiocytic sarcoma of the canine urinary bladder.