Tumors of the Urinary System

Chapter 14 Tumors of the Urinary System



Renal Neoplasia



I. Primary renal tumors are uncommon, comprising approximately 1% of all neoplasms in dogs and 1% to 1.5% of all neoplasms in cats.
A. Occur with equal frequency in the left or right kidney.

B. Approximately 4% are bilateral.

II. Most are of epithelial origin (approximately 85%), metastasize, and are associated with a poor prognosis.

III. Problems at presentation:
A. Renal hematuria (painless).

B. Renal failure if bilateral involvement (e.g., as with lymphosarcoma [LSA]).

C. Mass effect: Based on abdominal palpation or finding on imaging with ultrasound or radiographs (Figure 14-1).

D. Paraneoplastic syndromes: Polycythemia, extreme leukocytosis, cachexia, hypoglycemia, hypertrophic osteopathy.

E. Metastases: Bone, lung, lymph nodes.

IV. Definitive diagnosis requires biopsy in most instances.
A. LSA frequently can be diagnosed by fine-needle aspiration cytology.

B. Aspiration cytology can be highly suggestive for renal adenocarcinoma.

image

FIGURE 14-1 Renal ultrasonography of normal and neoplastic kidney. Note normal left kidney in A (length of 5.2 cm) compared with the very enlarged (length 8.5 cm) and misshapen right kidney, B. The right kidney is also quite hyperechoic. The right kidney was enlarged due to a benign tumor (myxoma).


(Courtesy of Dr. Lisa Zekas and the Radiology Section of The Ohio State University College of Veterinary Medicine, Columbus, Ohio.)



Renal Adenoma



I. Approximately 15% of primary renal epithelial tumors.

II. Usually an incidental finding on necropsy.

III. Typically solitary nodules <2 cm in diameter.

IV. Arise from the epithelium of the proximal convoluted tubule.


Renal Carcinoma



I. Most common primary renal tumor of dogs; occur sporadically in cats.

II. Usually occurs in older dogs (average age, 8 years), but can occur in dogs younger than 2 years of age. Affected cats typically are older than 9 years of age.

III. Male dogs are more commonly affected than female dogs; in cats there is no sex or breed predilections.


image Renal carcinoma is the most common primary renal tumor of dogs.




Clinical Signs




A. Include hematuria, palpable abdominal mass, and weight loss.

B. Polycythemia may be seen due to increased erythropoietin production.

C. Hypertrophic osteopathy may be present with or without pulmonary metastases.

D. Other paraneoplastic syndromes include disseminated intravascular coagulation, neutrophilic leukocytosis, and bone infarcts.

E. Metastases often are present by the time of presentation.


Gross or Ultrasonographic Appearance




A. Spherical or ovoid mass, usually on one pole of the kidney.

B. Typically well demarcated; the remaining renal tissue is atrophic and compressed (Figure 14-2).

C. Usually gray or light yellow in color, with areas of necrosis and hemorrhage.

D. Can invade the renal pelvis, ureter, renal vein, and hilar lymphatics.


image

FIGURE 14-2 Renal adenocarcinoma in an older cat. Note well-demarcated nodular region on the cranial pole of the right kidney of this ultrasound image (1.35 × 1.24 cm). The diagnosis was established by fine-needle aspiration (FNA) and by surgical removal that followed.



Nodular Dermatofibrosis With Renal Cystadenocarcinoma in German Shepherd Dogs



I. Autosomal dominant syndrome; 6 % of German shepherd dogs in Norway are affected with renal tumors.

II. Cystadenocarcinoma is usually bilateral and can metastasize to lymph nodes, peritoneum, liver, spleen, lung, and bone.

III. All breeds are potentially at risk but most commonly reported in German shepherds. No sex predisposition.

IV. Lesions of the skin and subcutis are the main reason for presentation. Some dogs are lame as a consequence of lesions on the paws that frequently are overlooked. Ulceration and inflammation can be associated with the skin lesions.

V. Fibrosis may occur both in skin and kidney. Tubular obstruction and cyst formation occur in the kidneys. The lesion may progress from cyst to cystic adenomatous hyperplasia to cystadenoma and ultimately to cystadenocarcinoma.

VI. Affected kidneys may be enlarged and abnormally shaped on abdominal radiographs. Cysts of varying size are identified on renal ultrasonography, which also confirms changes in renal size and shape.

VII. Computed tomography identifies multiple cysts and tumor masses of varying size bilaterally. The earliest lesions have been detected between 4 and 5 years of age, with the smallest cysts being 2 to 3 mm in diameter. Small amounts of tumor tissue often can be identified inside the cyst wall or renal parenchyma.

VIII. In one study, mean age at first detection of nodular dermatofibrosis was 6.4 years, renal cystadenocarcinoma with nodular dermatofibrosis was 8.2 years, and death occurred at 9.3 years.

IX. Most intact females also have multiple uterine leiomyomas at the time of diagnosis.

X. Euthanasia usually results, as a consequence of extensive renal lesions and metastases.


Nephroblastoma (Wilms Tumor, Embryonal Nephroma)



I. Occurs sporadically in dogs and cats.

II. More common in adult dogs than in young dogs (Figure 14-3).

III. Originate from nephrogenic blastema and may contain epithelial and mesenchymal components.

IV. Extremely large in size, causing abdominal enlargement. There may be multiple tumors in one kidney; occasionally they are bilateral.

V. Widespread metastasis to lung and liver is common in affected dogs.

VI. Prognosis is good if tubular or glomerular differentiation is observed; prognosis is poor if categorized as a sarcoma.

image

FIGURE 14-3 Nephroblastoma. Ultrasonographic image from an 8-year-old dog with renal enlargement. Note irregular renal enlargement with both hyperechoic and hypoechoic regions within the kidney. Only the left kidney was involved.



Other Tumors



I. Transitional cell papilloma and carcinoma of the renal pelvis are very rare.

II. Squamous cell carcinoma of the renal pelvis is uncommon, but has been associated with renal pelvic calculi.

III. Primary mesenchymal tumors have a poor prognosis.
A. Hemangioma is most common; hematuria is the most consistent clinical sign.

B. Hemangiosarcoma has been reported in the cat.

C. Angiomyolipoma has been reported in the cat.

D. Interstitial cell tumors occur in old dogs in the renal cortex and medulla.

E. Benign cortical fibroma.

F. Congenital mesoblastic nephroma.

G. Renal oncocytomas originate from the collecting ducts.

IV. Metastatic tumors are common.
A. Primary pulmonary adenocarcinomas are difficult to distinguish from primary renal adenocarcinoma with pulmonary metastases.

B. LSA is common, and is the most common renal neoplasm in cats.
1. Nodules are poorly defined and fatty in appearance at surgery or necropsy.

2. If there is diffuse involvement, the kidney may appear fatty and enlarged.

3. Hypoechoic nodules frequently are observed in cats with renal LSA during ultrasonography.

4. A recent study showed that hypoechoic subcapsular thickening of the kidney is associated with renal LSA in the cat (Figure 14-4).

5. Can occur in feline leukemia virus (FeLV)-negative or feline immunodeficiency virus (FIV)-negative cats, but retrovirus status still should be checked because these viral infections can be associated with LSA.

6. Renal LSA usually is bilateral in cats. It can be associated with renal failure if infiltration of the kidneys is extensive.

7. We have observed long-term remissions of renal LSA in some cats treated with chemotherapy. In some instances, dramatic improvement in renal function has accompanied chemotherapy.

image

FIGURE 14-4 Subcapsular lymphosarcoma (LSA) in a cat. Note the hypoechoic region outside the kidney parenchyma. This could be confused with a perinephric pseudocyst, but a fine-needle aspiration (FNA) of this region yielded a large population of malignant lymphocytes.



Treatment



I. If renal neoplasia is unilateral with no metastases, nephrectomy is the treatment of choice. Efforts should be made before surgery to ensure adequate function of the contralateral kidney in patients with marginal renal function before surgery. Renal scintigraphy with determination of individual kidney glomerular filtration rate (GFR) is ideal to make this assessment.

II. Renal LSA is treated by chemotherapy.

III. Prognosis is not well defined. Survival time is usually short, but some have survived up to 4 years. Nephroblastoma is less metastatic, and nephrectomy can be curative. Benign tumors may also be cured with surgery.


Bladder Neoplasia



I. Bladder neoplasia accounts for approximately 2% of all reported malignancies in dogs.


image Bladder neoplasia accounts for approximately 2% of all malignancies in dogs.


II. Primary malignant bladder tumors.
A. Epithelial.
1. Transitional cell carcinoma (TCC) is the most common tumor of the bladder in dogs.

2. Squamous cell carcinoma (SCC).

3. Adenocarcinoma (ACA).

4. Undifferentiated carcinoma.


image Transitional cell carcinoma (TCC) is the most common bladder tumor of dogs and cats.




B. Mesenchymal.
1. Fibrosarcoma.

2. Leiomyosarcoma.

3. Rhabdomyosarcoma.

III. Primary benign tumors.
A. Fibroma.

B. Leiomyoma.

C. Papilloma.

IV. Secondary metastatic tumors of the bladder.
A. Hemangiosarcoma.

B. Lymphoma.

C. Adenocarcinoma.

V. Canine bladder neoplasia.
A. TCC is most common.

B. Papilloma.

C. Benign mesenchymal.

D. Unclassified carcinoma.

E. SCC.

F. ACA.

G. Rhabdomyosarcoma.
1. Young dogs.

2. Often large breed.

3. Sometimes associated with hypertrophic osteopathy (HO).

4. Usually located at trigone and not usually surgically resectable.

5. Often botryoid (grape-like cluster) in appearance (Figure 14-5).

6. Special immunohistochemical staining may be needed to confirm the skeletal muscle origin of the tumor. Desmin, sarcomeric actin, and vimentin are likely to be positive, whereas cytokeratin and smooth muscle actin should be negative on immunohistochemistry. Cross-striations of skeletal muscle are sometimes seen on routine hematoxylin and eosin–stained specimens.

VI. Feline bladder neoplasia.
A. TCC is most common, but much less common than in dogs.

B. SCC.

C. Benign mesenchymal.

D. ACA.

E. Lymphoma.

F. Leiomyosarcoma.

G. Hemangiosarcoma.

H. Rhabdomyosarcoma.

image

FIGURE 14-5 Botryoid rhabdomyosarcoma. Note the ultrasonographic appearance of this tumor in a young Great Dane with significant obstruction to urinary outflow in A. Note the classic grape-like clusters of malignant tissue in the everted bladder following cystotomy in a young Bassett hound, B.



Etiology and Risks



I. Etiology is multifactorial. Risk factors are related to chemical carcinogen exposure. The bladder is the storage site for eliminated waste products, and chronic exposure of bladder tissue to carcinogenic compounds appears to play a role.

II. Obesity. Fat tissue acts as a storage site for lipophilic chemicals and pesticides allowing for prolonged exposure in the body.

III. Previous treatment with the chemotherapeutic agent, cyclophosphamide. Cyclophosphamide frequently causes sterile hemorrhagic cystitis. Chronic irritation of the bladder by this drug may play a role in development of neoplasia.

IV. Bladder tumors are more common in industrialized parts of the world.
A. A direct correlation was found between level of industrialization and manufacturing in the United States and parts of Canada and the occurrence of bladder cancer in dogs.

B. Bladder neoplasms have been induced experimentally by administration of industrial chemicals containing aromatic amines (e.g., tryptophan, benzene, beta-naphthylamine) to dogs.

V. Chemical Exposure.
A. Topical flea and tick dips, shampoos, powders, sprays and collars, and the dose applied were directly correlated with disease in one study.

B. The use of spot-on flea and tick control products containing fipronil and imidacloprid did not cause increased risk of TCC in Scottish terriers.

C. Scottish terriers exposed to phenoxy herbicide lawn treatments had increased risk of developing TCC. Dogs with seasonal or year-round exposure had higher risk than those with only sporadic exposure.

D. Dogs living near areas that are frequently sprayed with insecticides to control mosquito populations are more likely to develop TCC.

VI The incidence of bladder neoplasia is unrelated to second-hand cigarette smoke exposure or to chronic drinking of chlorinated water (known risk factors in humans).

VII. Neutered female dogs are at higher risk for TCC than males, whereas neutered male cats are at increased risk as compared with females. Potential reasons for this association have been proposed.
A. Females void less frequently than male dogs. Marking behavior in male dogs leads to more frequent urination. Prolonged urinary retention in female dogs increases contact time for toxins with the bladder epithelium.


image Female dogs and male cats are at a higher risk for development of bladder neoplasia.



B. Females have a higher percentage of body fat than males.

VIII. Bladder neoplasia is more common in dogs than cats.
A. Tryptophan metabolism differs between cats and dogs. Dogs metabolize this amino acid by forming ortho-amino-phenol, which is similar in structure to chemicals known to induce bladder tumors in dogs.

B. Cats do not form the same metabolite from tryptophan and thus have less ortho-amino-phenol in their urine.

IX. Vegetable Consumption.
A. A study of TCC in Scottish terriers found a significant correlation between vegetable ingestion and risk of TCC.
1. Consumption of any type of vegetable at least three times per week decreased the risk of developing TCC by 70%.

2. Green, leafy vegetables and yellow-orange vegetables consumed at least three times weekly decreased risk of TCC by 70% to 90%.

3. Consumption of cruciferous vegetables did not decrease the risk of TCC.

4. A dose response relationship was identified: The higher the frequency of vegetable consumption, the greater the reduction in risk of TCC.

B. Green, leafy vegetables and yellow-orange vegetables have antitumor activity.
1. Plants contain phytochemicals or other bioactive compound that detoxify carcinogenic chemicals and remove oxidizing agents.

2. These vegetables contain carotenoid and retinol that are hypothesized to control cell proliferation and differentiation and stabilize cell membranes, making them less susceptible to carcinogens.


Canine Transitional Cell Carcinoma (TCC)



I. TCC is a primary malignant neoplasm arising from the transitional cells of the bladder and is the most common bladder tumor in dogs and cats.
A. Epithelial neoplasms account for 90% of canine bladder cancer.

B. Of the epithelial tumors, 75% to 90% are TCC.

C. The prevalence of TCC in dogs increased more than 600% between 1975 and 1995.


Signalment




A. Older dogs (average age, 11 years at the time of diagnosis).

B. Females more commonly affected than males with a female to male ratio of 1.7:1.

C. Breed predispositions have been identified (Table 14-1). The reason for these associations is unknown but, genetic predisposition is suspected. Differences in metabolic activation and detoxification pathways could account for increased risk in selected breeds.
1. Scottish terriers have the highest prevalence of TCC and are 18 times more likely to develop TCC than mixed breed dogs.

TABLE 14-1 Breed Risk for Diagnosis of Transitional Cell Carcinoma in Dogs



























































Breed Odds Ratio 95% Confidence Interval
Mixed breed 1.0 —
All purebreds 0.74 0.62-0.88
Scottish terrier 18.09 7.30-44.86
Shetland sheepdog 4.46 2.48-8.03
Beagle 4.15 2.14-8.05
Wirehaired fox terrier 3.20 1.19-8.63
West Highland white terrier 3.02 1.43-6.40
Miniature Schnauzer 0.92 0.54-1.57
Miniature poodle 0.86 0.55-1.35
Doberman pinscher 0.51 0.30-0.87
Labrador retriever 0.46 0.30-0.69
Golden retriever 0.46 0.30-0.69
German shepherd 0.40 0.26-0.63

Modified from Knapp DW, Glickman WN, DeNicola DB, et al: Naturally-occurring canine transitional cell carcinoma of the urinary bladder: A relevant model of human invasive bladder cancer. Urol Oncol 5:47-59, 2000. Data in this table provides a summary from 1290 dogs with transitional cell carcinoma (TCC) and 1290 institution and age-matched control dogs without TCC in the Veterinary Medical Data Base.



image Scottish terriers have the highest prevalence of transitional cell carcinoma.


2. West Highland white terrier.

3. Airedale terrier.

4. Beagle.

5. Dachshund.

6. Shetland sheepdog.

7. Collie.

8. German shepherd dogs are underrepresented.


Clinical Signs




A. Lower urinary tract signs are most common.
1. Dysuria (84%).

2. Hematuria (50%).

3. Pollakiuria (37%).

4. Stranguria.

5. Urinary incontinence.

B. Polyuria and polydipsia may be associated with partial obstruction.

C. Oliguria or anuria, vomiting, and anorexia may be associated with azotemia if acute or chronic obstruction is present.

D. Lameness may be caused by bone metastasis or HO secondary to metastatic lung lesions.
1. Bone metastases often are lytic on radiographs.

2. Metastases from prostate neoplasia, mammary tumors, and bladder TCC are most commonly associated with lytic bone lesions.

E. Respiratory difficulty caused by pulmonary metastasis.

F. Lethargy.

G. Weight loss.


History




A. The history of treatment with antibiotics for chronic recurrent lower urinary tract infections (UTIs) is often reported by owners. Minimal long-term clinical improvement is observed in response to this therapy.



image Many dogs with transitional cell carcinoma have been treated for repeated urinary tract infections prior to diagnosis.



Physical Examination




A. Rectal examination may reveal a thickened urethra and enlarged sublumbar lymph nodes if the tumor has spread to the urethra and metastasis has already occurred.

B. A mass in the caudal abdomen may be palpated in smaller dogs and cats.

C. Spinal hyperpathia caused by metastasis to lumbar vertebral bodies.

D. Physical examination can be normal in up to 30% of dogs with bladder tumors.


Differential Diagnoses



Benign Tumors





1. Fibroma.

2. Papilloma.

3. Leiomyoma.


Non-Neoplastic Lower Urinary Tract Disease





1. Chronic cystitis.

2. Polypoid cystitis.

3. Eosinophilic granuloma.

4. Proliferative (granulomatous) urethritis.

5. Prostatitis.

6. Benign prostatic hyperplasia.


Diagnostic Tests



Laboratory Evaluation





1. A complete blood count (CBC) and biochemical profile should be performed to rule out other systemic diseases. The most common abnormalities recognized are azotemia and anemia of chronic disease.

2. Do not obtain urine samples by cystocentesis. TCC tumors are exfoliative and tumor cells can be seeded anywhere along the needle tract, including the skin (Figure 14-6).

image

FIGURE 14-6 Needle tract seeding of transitional cell carcinoma (TCC) from a cat that underwent multiple episodes of cystocentesis. Note multiple nodules of carcinoma along the peritoneum at necropsy.



image If urinary bladder neoplasia is suspected, do not obtain urine samples by cystocentesis because of the risk of tumor seeding.




3. Urinalysis.
a. Proteinuria.

b. Pyuria.

c. Hematuria.

d. Bacteriuria.

e. Neoplastic transitional cells are identified in 30% of cases.
(1) Rafts of epithelial cells.

(2) Neoplastic cells are difficult to distinguish from reactive epithelial cells that result from chronic inflammation.

(3) Results may be highly suggestive for TCC (e.g., anisocytosis, anisokaryosis, binucleate cells, mitotic figures, clumps or rafts of epithelial cells) (Figure 14-7).

(4) Clumps of epithelial cells may be clinically suggestive of TCC if they occur alone or with red blood cells especially in the absence of white blood cells or bacteria (Figure 14-8).

image

FIGURE 14-7 Wet mount microscopy of urine sediment from a dog with transitional cell carcinoma (TCC). Note cellular atypia. Multinucleated epithelial cell is in the center of the field. The other large cells are also epithelial cells (Sedi-Stain, ×600).


image

FIGURE 14-8 Rafts of epithelial cells from a dog with transitional cell carcinoma (TCC)–wetmount urinary sediment microscopy. In panel A, only red blood cells and clumps of large epithelial cells are seen. This is very suggestive for TCC in the absence of pyuria. Panel B shows more detail of cellular atypia in clumps of epithelial cells (Sedi-Stain, ×400).



image Clumps of epithelial cells (rafts) in the urine sediment should raise suspicion for TCC.

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Related posts:

  1. Familial Renal Diseases of Dogs and Cats
  2. Diseases of the Glomerulus
  3. Acute Renal Failure
  4. Disorders of Micturition and Urinary Incontinence

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Jul 10, 2016 | Posted by in INTERNAL MEDICINE | Comments Off on Tumors of the Urinary System

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