Sarah M. Lambert, MD
Pasquale Casale, MD, FACS
BASICS
DESCRIPTION
Renal cell carcinoma (RCC) is a very rare tumor in childhood arising from the renal tubular epithelium
EPIDEMIOLOGY
Incidence
• 2–6% of all pediatric renal tumors
• Only ∼4 cases of pediatric RCC per year
• Estimated at <0.3% of all pediatric tumors
• Just over 350 cases reported in the literature
• Mean age of presentation between 8 and 10 yr vs. <3 yr for Wilms tumor
• Equal male:female
Prevalence
N/A
RISK FACTORS
• Von Hippel–Lindau syndrome
• Tuberous sclerosis
Genetics
• Translocation type of RCC, which forms a distinct category has recently emerged as the predominant type of RCC in children and adolescents, whereas it is rarely diagnosed in adults.
• Chromosomal translocations in Xp11.3 region involving TFE3 gene (1).
• Less frequently, 6p21 translocation.
• If seen with Von Hippel–Lindau, more likely to be bilateral.
PATHOPHYSIOLOGY
• Thought to arise from renal tubular epithelium
• Most frequently papillary subtype with Xp11 translocation
– Role of translocation at Xp11.2 region involving TFE3 gene unknown (1)
• Lung and bone are the most common distant metastases.
ASSOCIATED CONDITIONS
• Tuberous sclerosis, chronic renal failure, neuroblastoma, and teratoma with chemotherapy
• Rarely associated with adult familial RCC
GENERAL PREVENTION
N/A
DIAGNOSIS
HISTORY
• Gross hematuria (∼40%), flank pain, abdominal distension (2)
• Nausea, vomiting, malaise common
• Pain in up to 50%
• 30% found incidentally (2)
PHYSICAL EXAM
• Palpable abdominal mass (∼40%) (2)
• Triad of hematuria, flank pain, and palpable mass found in <6% of children (3)
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Urinalysis: Hematuria found in >40% of patients (3)
• CBC: Polycythemia is rare
• Liver and renal function tests: Baseline prior to treatment
Imaging
• Abdominal x-ray may show tumor calcifications (∼25%) vs. Wilms tumor (∼5%) (3)
• US demonstrates solid or cystic renal mass.
• CT or MRI with and without contrast reveal enhancing renal mass.
• Pediatric RCCs typically present as large, heterogeneous masses, commonly hemorrhage and contain internal calcifications.
• IVP can demonstrate renal mass by displacement of the collecting system.
• Chest x-ray or chest CT scan for workup of metastatic disease.
• Radionuclide bone scan is indicated based on concern for mets.
Diagnostic Procedures/Surgery
Biopsy is not indicated
Pathologic Findings
• Predominately papillary histologic features in children vs. clear cell features in adults
• Pathologic staging based on modified Robson staging system
• Up to 25% pediatric RCC cannot be clearly classified due to atypical features
• Pathologic parameters typically associated with poor outcome in adults (metastasis/high tumor stage, high Fuhrman nuclear grade, angiolymphatic invasion, tumor necrosis), do not appear to have similar implications in pediatric patients
DIFFERENTIAL DIAGNOSIS
• Benign renal mass in children:
– Choledochal cyst, intestinal duplication cyst
– Congenital mesoblastic nephroma
– Hydronephrosis
– Mesenteric cyst
– Multicystic dysplastic kidney
– Polycystic kidney
– Renal abscess
– Splenomegaly
• Malignant renal masses in children:
– Hepatoblastoma
– Lymphoma
– Lymphosarcoma
– Neuroblastoma
– RCC
– Rhabdomyosarcoma
– Wilms tumor
TREATMENT
GENERAL MEASURES
Management is primarily surgical excision by either radical nephrectomy or partial nephrectomy
MEDICATION
First Line
• The use of chemotherapy, immunotherapy, or tyrosine kinase inhibitors is not adequately described in pediatric population.
• The use of tyrosine kinase inhibitors should be considered in the pediatric patient with unresectable, metastatic, or advanced-stage RCC.
• Small series of patients treated with neoadjuvant chemotherapy according to Wilms tumor protocol.
Second Line
N/A
SURGERY/OTHER PROCEDURES
• Radical nephrectomy (4)
– Removal of entire kidney and portion of the ureter
– Common approaches in children include flank and abdominal incisions
• Partial nephrectomy (5)
• Laparoscopic and robotic-assisted radical or partial nephrectomy for RCC in children are described in select cases (6,7)
ADDITIONAL TREATMENT
Radiation Therapy
Has been used for both initial treatment and recurrence but not well studied in pediatric populations
Additional Therapies
• Adjuvant chemotherapy for metastatic disease has been tried in the pediatric population but not well characterized.
• Tyrosine inhibitors have been used in children with metastatic disease but data are limited (9).
Complementary & Alternative Therapies
N/A
ONGOING CARE
PROGNOSIS
• Overall survival similar to adult RCC and depends on (Robson) stage:
– Rest prognosis stage with stage I (>90%) and II (>80%)
– Stage III ∼75%, stage IV ∼15% (2)
COMPLICATIONS
• Surgical complications (bleeding, infection, diathesis, bowel injury)
• Metastasis to lung and bone, multiple other sites
FOLLOW-UP
Patient Monitoring
• Adult protocols followed as there are no pediatric protocols
• No long-term follow-up guidelines:
– Physical exam, chest x-ray, chemistry panel, CBC, and urinalysis every 6 mo for 5 yr
– CT on yearly basis for 5 yr
• Risk of chronic kidney disease likely attributed to reduced renal reserve capacity should be recognized and treated with nephrologic evaluation (8)
Patient Resources
National Cancer Institute http://www.cancer.gov/cancertopics/pdq/treatment/wilms/patient
REFERENCES
1. Ramphal R, Pappo A, Zielenska M, et al. Pediatric renal cell carcinoma: Clinical, pathologic, and molecular abnormalities associated with the members of the MiT transcription factor family. Am J Clin Pathol. 2006;126:349–364.
2. Estrada CR, Suthar AM, Eaton SH, et al. Renal cell carcinoma: Children’s Hospital Boston experience. Urology. 2005;66:1296–1300.
3. Undolfi P, Terenziani M, Casale F, et al. Renal cell carcinoma in children: A clinicopathologic study. J Clin Oncol. 2003;21:530–535.
4. Caran A, Akyuz C, Sari N, et al. Renal cell carcinoma in children: Experience of a single center. Nephron Clin Pract. 2007;105:c58–c61.
5. Cook A, Lorenzo AJ, Salle JL, et al. Pediatric renal cell carcinoma: Single institution 25 year case series and initial experience with partial nephrectomy. J Urol. 2006;175:1456–1460.
6. Perlman EJ. Pediatric renal cell carcinoma. Surg Pathol Clin. 2010;3(3):641–651.
7. Cost NG, Geller JI, DeFoor WR Jr, et al. A robotic-assisted laparoscopic approach for pediatric renal cell carcinoma allows for both nephron-sparing surgery and extended lymph node dissection. J Pediatr Surg. 2012;47(10):1946–1950.
8. Cozzi DA, Ceccanti S, Frediani S, et al. Chronic kidney disease in children with unilateral renal tumor. J Urol. 2012;187(5):1800–1805.
9. Chowdhury T, Prichard-Jones K, Sebire NJ, et al. Persistent complete response after single-agent sunitinib treatment in a case of TFE translocation positive relapsed metastatic pediatric renal cell carcinoma. J Pediatr Hematol Oncol. 2013;35(1):e1–e3.
ADDITIONAL READING
• Dome JS, Fernandez CV, Mullen EA, et al. Children’s Oncology Group’s 2013 blueprint for research: Renal tumors. Pediatr Blood Cancer. 2013;60(6):994–1000.
• Spreafico F, Collini P, Terenziani M, et al. Renal cell carcinoma in children and adolescents. Expert Rev Anticancer Ther. 2010;10(12):1967–1978.
See Also (Topic, Algorithm, Media)
• Neuroblastoma
• Reference Tables: TNM: Kidney Cancer
• Reference Tables: TNM: Kidney Cancer
• RCC, General
• RCC, Localized (T1, T2)
• RCC, Locally Advanced (T3–T4)
• RCC, Metastatic (N+, M+)
• Renal Mass
• Robson Staging System
• Translocation Renal Cell Carcinoma; Translocation Xp11.2
• Von Hippel–Lindau Disease/Syndrome
• Wilms Tumor
CODES
ICD9
• 189.0 Malignant neoplasm of kidney, except pelvis
• 197.0 Secondary malignant neoplasm of lung
• 198.5 Secondary malignant neoplasm of bone and bone marrow
ICD10
• C64.9 Malignant neoplasm of unsp kidney, except renal pelvis
• C78.00 Secondary malignant neoplasm of unspecified lung
• C79.51 Secondary malignant neoplasm of bone
CLINICAL/SURGICAL PEARLS
The most common subtypes of RCC in children are the translocation-associated tumors, papillary RCC, renal medullary carcinoma, and oncocytic RCC.