GENERAL CONSIDERATIONS


General Considerations

•primary renal tumors account for 0.3%-1.7% of all tumors in dogs

•etiologic factors have not been identified in domestic animals, but causes in humans include smoking, polycyclic hydrocarbons, cadmium, coffee, and animal fat and protein

•renal LSA is very rare in dogs and epithelial tumors account for > 75%-85% of canine renal tumors

•renal carcinoma is the most common renal tumor in dogs, but other epithelial tumors include ADC, TCC, and SCC

•sex predisposition for renal epithelial tumors: male

•mesenchymal tumors are rare (11% in dogs) but are aggressive and highly metastatic

•mesenchymal renal tumors include HSA, FSA, CSA, and leiomyosarcoma

•nephroblastoma is a congenital renal tumor with both epithelial and mesenchymal components

•benign tumors have been reported but, except for hemangioma, are usually asymptomatic and incidental findings

•benign tumors include hamartoma (= hemangioma, fibroma and intrarenal lesions such as myxoma, lipoma and mixed tumors), leiomyoma, fibroma, adenoma, papilloma, lipoma, and perithelioma

•metastatic tumors are common in the kidney because of the large blood supply and abundant capillaries


Renal Carcinoma


General Considerations

•renal carcinoma is predominantly seen in older, male, medium-to-large breed dogs

•renal carcinoma is usually unilateral and large with left and right kidneys are equally affected

•renal carcinomas are classified as solid, tubular, and papillary on the basis of histologic patterns, however, most exhibit a mixed pattern


Biologic Behaviour

•invasion of caudal vena cava and tributary veins with the development of a tumor thrombus has been reported and can complicate surgical treatment

•paraneoplastic syndromes: polycythemia and neutrophilic leukocytosis

•metastatic disease is common:

•60% metastatic rate in cats

•54% metastatic rate to the lungs in dogs, 54% to abdominal organs, and 27% to the regional lymph nodes

•metastatic sites include the lungs, liver, ipsilateral adrenal gland, regional lymph node, contralateral kidney, omentum, peritoneum, diaphragm, skin, heart, brain, and appendicular and axial skeleton


Cystadenocarcinoma


General Considerations

•renal cystadenocarcinoma is an autosomal dominant condition in GSD with a genetic linkage to chromosome 5

•renal cystadenocarcinoma represent 6% of all renal tumors in GSD

•renal cystadenocarcinoma has also been described in a GSD-cross dog and Golden Retriever

•renal cystadenocarcinoma is a bilateral disease with slowly progressive deterioration of renal function

•renal cystadenocarcinoma is associated with nodular dermatofibrosis and uterine leiomyoma

•nodular dermatofibrosis is present in all cases and appear as small, firm, and mobile subcutaneous masses


Biologic Behaviour

•clinical signs are worse with bilateral disease and the size of skin and uterine tumors increase with advancing age

•metastasis reported in up to 47% of cases:

•metastatic sites including sternal and abdominal lymph nodes, liver, lungs, pleura, and peritoneum

•metastasis is more common with large, solid, and poorly differentiated tumors

•main causes of death are renal failure, metastatic disease and secondary skin infections


Renal Pelvis Tumors

•renal pelvis TCC are pedunculated, multilobulated, and locally aggressive

•metastatic rate of renal pelvic TCC is lower than renal carcinoma in dogs, but higher in cats

•renal pelvic tumors may be associated with struvite calculi because of urothelial irritation by renal calculi resulting in squamous metaplasia and malignant transformation of the urothelium

•prognostic factors in humans include multifocality, tumor grade and stage, DNA ploidy, and history of bladder TCC


Nephroblastoma


General Considerations

•nephroblastoma is an uncommon congenital tumor originating from the metanephric blastema and resulting from abnormal differentiation of the kidney during embryogenesis

•mixed tumor consisting of blastema, epithelial, and mesenchymal components in various stages of differentiation


Biologic Behaviour

•nephroblastoma is a highly malignant tumor

•nephroblastoma destroys the renal parenchyma by invasion and compression

•local invasion of adjacent structures occurs if the tumor penetrates the renal capsule

•65% metastatic rate

•metastatic sites include the lungs and liver (common), with other sites such as regional and distant lymph nodes, adrenal glands, thyroid gland, pleura, contralateral kidney, and appendicular skeleton

•caudal vena cava and renal vein thrombosis has been reported in dogs with nephroblastoma


Clinical Features

•nephroblastoma is usually diagnosed in animals < 12 months

•nephroblastoma is graded as either favorable or unfavorable on the basis of histologic findings

•staging system, based on the extent of tumor involvement and surgical findings, for nephroblastoma has been developed by the National Wilms' Tumor Study Group






















DIAGNOSIS


Clinical Signs

•clinical signs are non-specific such as abdominal enlargement and abdominal pain

•urinary signs are uncommon

•skin lesions (i.e., dermatofibrosis) are associated with renal cystadenocarcinomas in GSD

•lameness caused by either skeletal metastases or hypertrophic osteopathy

•paraneoplastic polycythemia may be more common with renal tumors as majority of renal carcinomas involve the proximal convoluted tubule which is the main site of erythropoietin production


Urinalysis and Urine Sediment Cytology

•proteinuria is a common finding with renal tumors

•hematuria is uncommon with renal carcinoma, but can be seen with HSA, hemangioma, and renal pelvis TCC

•urine sediment cytology is rarely diagnostic for renal tumors


Blood Tests

•hematology and serum biochemistry findings are usually normal or non-specific

•mild-to-moderate normochromic, normocytic anemia can be caused by either hematuria or bone marrow suppression secondary to chronic disease

•polycythemia is a reported paraneoplastic syndrome with renal tumors

•uremia may result from obstruction of urinary outflow, bilateral renal tumors, or age-related renal failure


Imaging


General Considerations

•survey abdominal and thoracic radiographs, contrast radiography, ultrasonography, CT, and MRI are imaging modalities used to identify the presence and extent of renal tumors


Survey Abdominal Radiography

•survey abdominal radiographic findings: sublumbar lymph node enlargement, renomegaly, and skeletal metastases, especially lumbar vertebrae and pelvis

•abdominal mass is identified in 81% and localized to the kidney in 54% of dogs with primary renal tumors

•focal mineralization can be observed but difficult to differentiate tumor from renal calculi and GI opacities


Excretory Urography

•excretory urographic findings: space occupying renal mass, variable opacification of the renal parenchyma, and distortion of the renal pelvis

•excretory urography successfully identifies a renal mass in 96% dogs with primary renal tumors


Ultrasonography

•ultrasonography results in earlier diagnosis and more successful treatment of renal neoplasia in humans

•renal tumors, except for LSA, produce a mixed echogenicity with disruption of the normal renal architecture

•renal LSA is usually hypoechoic

•ultrasonography is also useful in detecting neoplastic involvement of regional lymph nodes and adjacent structures such as the adrenal glands ± caudal vena cava


Advanced Imaging

•CT scans are used for the diagnosis and local staging of renal neoplasia with a high correlation between CT findings and gross pathology

•MRI is preferred for identifying adjacent vascular and visceral invasion, especially if renal-sparing surgery is planned

•other imaging techniques include caval venography and nuclear scintigraphy


Biopsy

•biopsy is required for definitive diagnosis of renal tumors

•biopsy techniques: FNA, needle biopsy, and wedge biopsy

•FNA and needle-core biopsy can be performed using a blind, ultrasound-guided, laparoscopic, or open technique

•ultrasound-guided biopsy is a rapid, safe, and accurate technique for diagnosing focal and diffuse renal disease

•blind percutaneous needle biopsy can be performed in cats where the kidney can be immobilized by palpation

•percutaneous biopsy should be performed with bilateral renal lesions or suspected renal LSA

•single procedure surgical biopsy, staging, and definitive treatment preferred for unilateral lesions

•complications of needle biopsy: minor localized hemorrhage, microscopic hematuria, and tumor seeding


Clinical Staging































SURGICAL MANAGEMENT


General Considerations

•surgical management depends on behaviour of the tumor, presence of metastases and bilateral renal involvement, and invasion of the caudal vena cava and adjacent structures

•nephroureterectomy is recommended for:

•malignant renal and ureteral tumors except LSA

•grading and staging of nephroblastoma

•nephron sparing techniques should be used for benign tumors and bilateral disease to reduce the risk of renal failure



ADJUNCTIVE MANAGEMENT


Chemotherapy and Immunotherapy for Renal Cell Carcinoma

•renal carcinoma is considered resistant chemotherapy, hormonal therapy, and radiation therapy

•response rates to chemotherapy are < 10% and chemoresistance is most likely caused by the presence of the multidrug resistance p170 glycoprotein on the surface of tumor cells

•multiple chemotherapeutic agents do not improve response rates but increases toxicity

•current investigations in humans include combining vinblastine with immunotherapy or multidrug resistant antagonists such as cyclosporine analogues, tamoxifen, or verapamil

•immunotherapy using agents such as recombinant IL-2 and IFN-λ have provided encouraging results

•immunotherapy was investigated as nephroureterectomy resulted in regression of metastatic lesions in humans with renal carcinoma due to an enhanced immune response, however, this effect has not been observed in animals

•immunotherapy and chemotherapy have not been investigated in cats or dogs with renal carcinoma


Chemotherapy and Radiation Therapy for Nephroblastoma

•surgical resection and chemotherapy is recommended for all stages of nephroblastoma in children

•vincristine and actinomycin D are recommended for all stages

•doxorubicin is added for stage II tumors with unfavorable histology and stage III tumors with favorable histology

•actinomycin D has been used in canine nephroblastoma with partial responses and prolonged survival times

•neoadjuvant chemotherapy is recommended for large inoperable tumors, bilateral disease, and neoplastic involvement of the caudal vena cava

•radiation therapy is recommended for stages III and IV tumors with favorable histology and stage II-IV tumors with unfavorable histology

•principal concerns in children are the effects of chemotherapy and radiation therapy on developing organs as children are more sensitive to the cardiotoxic effects of doxorubicin and radiation therapy can affect development of the lungs and spine



PROGNOSIS


Renal Carcinoma

•MST 8-16 months for dogs with renal carcinoma

•however, surgical resection has resulted in prolonged survival times of up to 4 years

•paraneoplastic polycythemia is a poor prognostic sign in humans, but not animals

•poor survival time in animals reflects the advanced stage of disease at diagnosis, difficulty in completely excising the tumor, and high metastatic rate


Nephroblastoma

•effective diagnosis, staging, and multimodality therapy has dramatically reduced the morbidity and mortality in children with nephroblastoma

•poor prognostic factors in children include the presence of bone metastases and tumor spillage during surgery

•survival times following nephroureterectomy ± chemotherapy ranges from 8 to > 25 months in 4 dogs


Mesenchymal Renal Tumors

•prognosis for non-lymphatic mesenchymal tumors is grave with a MST 8 months following surgical excision

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Stage

Description

I

Tumor limited to the kidney and the renal capsule intact

Tumor completely excised

II

Extension of the tumor into adjacent structures

Tumor thrombi or vascular extension of the tumor evident

Local spillage of tumor contents, but tumor completely excised and no evidence of residual tumor

III

Evidence of tumor extension into hilar or peri-aortic lymph nodes

Diffuse spillage of tumor into the peritoneal cavity during excision

Evidence of tumor in the peritoneal cavity

Local infiltration of vital structures precluding complete resection

IV

Evidence of hematogenous spread of the tumor

V

Bilateral renal involvement

T0

No evidence of neoplasia

T1

Small tumor without deformation of the kidney

Primary Tumor

T2

Single tumor with deformation ± enlargement of the kidney

T3

Tumor invading perinephric structures ± pelvis or ureter ± renal blood vessels

N0

No evidence of regional lymph node involvement

N1

Ipsilateral regional lymph node involvement

Node

M0

No evidence of metastasis

M1

Evidence of distant metastasis with site specified with (a) single metastasis, (b) multiple metastasis in 1 organ, and (c) multiple metastasis in ≥ 2 organs

Metastasis

T4

Tumor invading adjacent organs

N2

Bilateral regional lymph node involvement

N3

Distant lymph node involvement