Canine renal cancer: Case report and review of the literature

Riley, a 6 year old spayed female Pembroke Welsh Corgi, presented through the emergency service for an acute onset of stranguria and inability to urinate. On examination, the abdomen was tense with a large and non-expressible bladder. Abdominal radiographs confirmed a large urinary bladder with no obvious evidence of urinary calculi. Subsequent abdominal ultrasound revealed a moderately distended urinary bladder with an echogenic mass-like filling defect within the length of the visible urethra with slight protrusion into the trigone. Within the right kidney was a 6 x 5.5 cm heterogeneously hypoechoic mass destroying the cranial pole (Figure 1).

mullin1Figure 1. Ultrasound image of the right renal mass. Image courtesy of Chris Ryan, VMD, DACVR, Hope Veterinary Specialists.

 

 

 

 

 

 

A urinary catheter was passed and the mass-like filling defect in the urethra was found to be a large blood clot. Continued hematuria was noted after an indwelling urinary catheter was placed and thought related to the right renal mass. Ultrasound-guided fine needle aspirate cytology of the mass was consistent with malignant neoplasia, with suspicion for possible nephroblastoma (Figure 2).

mullin2Figure 2. The four slides from Riley consist of a small to moderate amount of peripheral blood, numerous large free nuclei, and few small aggregates of poorly preserved cells associated with extracellular pink matrix/stroma. These round to irregularly shaped cells cells have a scant amount of lightly basophilic cytoplasm and a large round to oval to slightly irregularly-shaped nucleus with finely stippled chromatin. Anisokaryosis moderate to marked. Image courtesy of Casey LeBlanc, KDL VetPath.

 

 

 

Blood work (CBC/Chemistry) was within normal limits and three-view thoracic radiographs revealed no evidence of pulmonary metastatic disease. Exploratory laparotomy identified an encapsulated 6 cm mass associated with the cranial pole of the right kidney with omental adhesions. A right ureteronephrectomy was performed and histologic evaluation of the right renal mass was consistent with a completely excised grade III fibrosarcoma with highly pleomorphic nuclei, 2-5 mitoses/HPF, and large areas of necrosis. The patient recovered from surgery without complication and an adjuvant doxorubicin-based chemotherapy protocol was recommended and initiated.

Primary renal tumors in dogs are rare, comprising less than 2% of all canine cancers. Secondary renal tumors (i.e. metastasis to the kidneys from other locations or presenting as part of a multicentric process) are more common. Renal cell carcinoma, arising from the renal epithelium, is the most common primary kidney tumor in dogs, accounting for 49 to 65% of primary renal tumors. Other tumor types include sarcomas (arising from the renal mesenchyme), hemangiosarcoma (arising from the vasculature), or much less commonly, nephroblastoma (arising from the embryonal tissue of mixed origin).(1,2) Presenting complaints and clinical signs may be non-specific and include polyuria/polydipsia, weight loss, vomiting, and a palpable abdominal mass. Hematuria is the most common sign, occurring in 32% of patients. Azotemia is the most common laboratory abnormality and can occur with any of the various tumor types. Renal carcinomas and sarcomas are typically found in middle-aged to older dogs. Nephroblastomas have been reported to more commonly affect dogs younger than 2 years of age, although one study that evaluated dogs with primary renal neoplasia included 2 dogs with nephroblastoma over the age of 8 years old.(2) A rare syndrome consisting of bilateral, multifocal renal cystadenocarcinomas and nodular dermatofibrosis has been described in German shepherd dogs and is related to a mutation in the folliculin gene.(1) To the author’s knowledge, no other confirmed etiologic factors have been identified for canine renal cancer.

The biologic behavior and prognosis associated with renal tumors is dependent upon tumor type and therapy pursued. Renal cell carcinoma is similar in both dogs and humans and is characterized by infiltrative primary tumor growth often leading to kidney dysfunction, a moderate metastatic rate (16-34%) at the time of diagnosis, a high metastatic rate (70-75%) in the late-stage of disease, and <5% of patients presenting with bilateral kidney involvement.(2,3)  Metastatic sites commonly include the contralateral kidney, other abdominal organs and omentum/peritoneum, and the lungs. There is a paucity of data available that evaluates the outcome of canine patients with renal tumors, however one fairly large study from 2006 suggested a survival time of approximately 16 months for dogs with renal carcinomas treated with surgical excision.2 A recent pathologic study evaluating the kidneys of 70 dogs undergoing nephrectomy for renal cell carcinoma found that mitotic index (MI), defined as the number of mitotic figures in ten 400x fields, was the sole independent prognostic variable. Specifically, the median survival time for dogs with an MI >30 was 187 days compared to 1184 days for dogs with an MI of <10. Dogs with an intermediate MI (10 to 30) had a median survival time of 452 days (Figure 3).(3) The carcinomas were categorized into four subtypes based on histologic features and histochemical and immunohistochemical staining: (1) clear cell, (2) chromophobe, (3) papillary, and (4) multilocular cystic renal cell carcinomas. Clear cell carcinoma, accounting for 9% of cases, was associated with a significantly decreased survival time (median 87 days).(3)

mullin3Figure 3. Kaplan-Meier survival curve for dogs following nephrectomy for renal cell carcinoma. Dogs are grouped according to mitotic index, which stratifies dogs based on overall survival (log-rank, p<0.0001). Dogs were censored if they were lost to follow-up or alive at the conclusion of the study. (From Edmondson EF, Hess AM, Powers BE. Prognostic significance of histologic features in canine renal cell carcinomas: 70 nephrectomies. Vet Pathol 2015;52(2):260-8).

 

 

A study of 14 dogs with renal hemangiosarcoma reported a median survival time of approximately 9 months with surgical excision +/- chemotherapy. Dogs with hemoabdomen had a significantly shorter median survival time (62 days vs. 286 days) than dogs without hemoabdomen.(4) Interestingly, the rates of hemoabdomen (14%) and metastasis (1/14) at initial diagnosis were lower than those typically seen with other forms of hemangiosarcoma; the median survival time of 9 months is also longer than that seen with other visceral presentations (typically ~6 months with surgery and adjuvant chemotherapy). A group of 28 dogs with multiple subtypes of renal sarcomas (n=12 hemangiosarcoma, n=7 sarcoma, n=4 leiyomyosarcoma, n=3 malignant fibrous histiocytoma, n=1 spindle cell sarcoma, n=1 fibroleiyomyosarcoma) treated with nephrectomy +/- chemotherapy similarly had a median survival time of 9 months. The metastatic rate was 14% at diagnosis and 88% at the time of death for this population of dogs.(3)

A small case series of 5 dogs with nephroblastoma reported a median survival time of just 6 months, however scattered case reports document long-term survival with surgery +/- chemotherapy.(3,5,6)   

Successful management of primary renal neoplasia is dependent upon complete excision of the mass.(1,2)  Because of the high metastatic risk, some form of adjuvant chemotherapy is typically recommended for these tumors following surgery. Specific protocols recommended are dependent upon exact tumor type, and for some there is no standard of care, thus treatment is often empiric and based on clinician experience and studies from the human literature. Specifically, for renal cell carcinoma, several studies in humans with this tumor describe disappointing outcomes in patients treated with conventional chemotherapy, as this cancer appears to possess some innate resistance to conventional cytotoxic agents. However, dramatically improved survival times in human patients have been documented since the advent of novel therapeutic agents such as small molecular inhibitors, anti-angiogenic drugs, and immunotherapies. In fact, interleukin-2 (IL-2) and interferon-alpha comprise the current backbone of therapy for this disease in humans.(7) For canine renal hemangiosarcoma, standard of care adjuvant therapy following surgical tumor removal typically involves a doxorubicin-based chemotherapy, as such protocols have been shown to significantly extend survivals for dogs undergoing surgery for hemangiosarcoma arising from other organs. The efficacy of adjuvant chemotherapy has not yet been prospectively evaluated for a large group of dogs with renal hemangiosarcoma. Nephroblastoma has been anecdotally treated with various different protocols, but there is not yet a protocol that has been defined as superior to others, certainly because of the rarity of this tumor.

Major types of kidney and renal pelvis cancer in humans include renal cell carcinoma, transitional cell carcinoma, and nephroblastoma (Wilms’ tumor), which is most commonly seen in pediatric patients. The estimated number of new cases of renal cancer in the United States in 2015 is over 61,000 and this disease is expected to be responsible for approximately 14,000 deaths this year. About 65% of patients are diagnosed with localized (non-metastatic/confined to the primary site) disease and the 5-year survival for this group of patients is 92%, whereas the 5-year survival rate for patients with regional metastasis is 65.4%, and 11.8% for patients with advanced stage disease (distant metastasis).(7,8)

Submitted by:

Christine Mullin, VMD, Diplomate ACVIM (Oncology)

References

  1. Knapp DW and McMillan SK. Tumors of the urinary system. In: Small Animal Clinical Oncology. 5th edn., SW Withrow and DM Vail Eds., St. Louis, Saunders/Elsevier, 2013:579-580.
  1. Bryan JN, Henry CJ, Turnquist SE, et al. Primary renal neoplasia of dogs. J Vet Intern Med 2006;20:1155-1160 http://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2006.tb00715.x/abstract
  1. Edmondson EF, Hess AM, Powers BE. Prognostic significance of histologic features in canine renal cell carcinomas: 70 nephrectomies. Vet Pathol 2015;52(2):260-8. http://vet.sagepub.com/content/52/2/260.short
  1. Locke JE and Barber LG. Comparative aspects and clinical outcomes of canine renal hemangiosarcoma. J Vet Intern Med 2006;20:962-967. http://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2006.tb01812.x/abstract
  1. Montinaro V, Boston SE, Stevens B. Renal nephroblastoma in a 3-month-old golden retriever. Can Vet J 2013;54(7):683-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3685002/
  1. Seaman RL and Patton CS. Treatment of renal nephroblastoma in an adult dog. J Am Anim Hosp Assoc 2003;39:76-79. http://www.jaaha.org/doi/abs/10.5326/0390076
  1. Parekh H, Rini BI. Emerging therapeutic approaches in renal cell carcinoma. Expert Rev Anticancer Ther 2015;17:1-10. [Epub ahead of print]. http://www.tandfonline.com/doi/abs/10.1586/14737140.2015.1090315 – .Vj3ybYS5eFI

8. SEER Stat Fact Sheets: Kidney and Renal Pelvis Cancer. http://seer.cancer.gov/statfacts/html/kidrp.html

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