Adam O. Kadlec, MD
Robert C. Flanigan, MD, FACS
BASICS
DESCRIPTION
• Sarcomas of the kidney are rare solid tumors that arise from the embryonic mesoderm
– Sarcomas of the renal parenchyma itself are very rare. More commonly, “renal sarcomas” represent a soft tissue sarcoma that either invades or abuts the kidney.
– In large case series of adult patients, leiomyosarcoma and liposarcoma are the most common histologic subtypes
• Renal sarcomas are more likely to be seen in childhood than adulthood
• Childhood sarcomas
– Represented almost exclusively (approximately 95%) by Wilms tumor (historically called nephroblastoma) (1)[A]
– Other sarcomas of childhood include clear cell sarcoma, rhabdomyosarcoma, congenital mesoblastic nephroma, and fibrosarcoma
EPIDEMIOLOGY
Incidence
• Adults: 1–2% of genitourinary cancer with peak incidence in 5th decade
• Children: 6–7% of childhood cancers represented mainly by Wilms tumor
• Wilms tumor occurs equally in boys and girls, with a median age of onset of 3.5 yr
Prevalence
N/A
RISK FACTORS
• Specific etiologies are not known
• HIV is associated with Kaposi sarcoma of the kidney
• Wilms tumor does have a small component of family history
Genetics
• Adult renal sarcomas unknown; suggestion of familial tendency with angiosarcoma
– Possible role of DNA mismatch repair pathway
• 1–2% of Wilms tumor patients have an inherited genetic predisposition
– Most common loss or inactivation of a tumor suppressor gene called WT1 on chromosome 11
– WT1 located at 11p13 and is associated with renal and gonadal development
– WT2 located at 11p15 and is associated with Beckwith–Wiedemann syndrome
– 90% of Wilms tumors arise from somatic mutations with overall genetic paradigm remaining unknown
PATHOPHYSIOLOGY
• Most common adult renal sarcomas are leiomyosarcomas, representing as many as 50–60% of such tumors. A wide variety of other types, such as liposarcoma and fibrosarcoma, are also found (2)[B].
• Sarcomas exhibit aggressive local growth with high rate of local recurrence, even in the event of negative surgical margins, due to a tendency for “skip lesions.”
• RCC with sarcomatoid features is an increasingly recognized variant of RCC (<5% of all cases) that contains regions of mesenchymal-appearing malignant cells adjacent to or within another typical RCC histology
• Later metastasis to the lung and liver can occur
• Wilms tumor is categorized into favorable or unfavorable histology; this has important implications regarding treatment (1)[A]
ASSOCIATED CONDITIONS
Wilms tumor is associated with aniridia, hemihypertrophy, Beckwith–Wiedemann syndrome, Denys–Drash, and GU abnormalities (hypospadias and cryptorchidism)
GENERAL PREVENTION
N/A
DIAGNOSIS
HISTORY
• Age and sex of patient
• Family history
• History of mental retardation or GU anomalies
• Noticeable abdominal mass (esp. Wilms)
• Shortness of breath, lethargy, abd pain, weight loss, and other systemic symptoms may be present
PHYSICAL EXAM
• Abdominal exam for mass
– In children, a palpable mass will be seen with Wilms tumor in >80% of cases
• Assess for associated lymphadenopathy
• GU exam to assess for GU anomalies such as hypospadias or undescended testis, which may alert to syndromes such as Denys–Drash
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Comprehensive metabolic panel to include liver function tests
• CBC
• UA (microhematuria, pyuria)
• No reliable tumor markers for sarcoma
Imaging
• CXR or CT to evaluate for metastatic disease in the chest or abdomen
• CT/MRI to assess local extent of tumor may aid surgical planning
• On MRA, sarcomas tend to be avascular
• Renal US may be helpful in evaluation of cystic renal mass
Diagnostic Procedures/Surgery
Biopsy of limited utility
Pathologic Findings
• Morphologically, renal sarcomas are similar to their extrarenal counterparts
• In adults they can arise from both the parenchyma and the renal capsule
• Wilms tumor
– Generally soft and friable with hemorrhage and necrosis
– Classic: Coexistence of blastemal, epithelial, and stromal cells
– Unfavorable histology is associated with nuclear enlargement, hyperchromasia, and abnormal mitotic figures
• Leiomyosarcoma (most common)
– Cell origin is smooth muscle of capsule or the perinephric structures
– Displaces rather than invade parenchyma
• Fibrosarcoma, malignant fibrous histiocytomas, anaplastic sarcoma of the kidney are other histologic types
DIFFERENTIAL DIAGNOSIS
• Adults: A solid primary renal mass in adult is most likely to be a RCC, although urothelial carcinoma or metastatic diseases are other considerations
– AML: Fat in a renal mass strongly suggests AML; fat-poor AML may resemble RCC
– Carcinoid tumors
– Collecting duct tumor (Bellini)
– Cystic nephromas
– Cysts (simple, hemorrhagic, infected)
– Focal pyelonephritis
– Hemangioma
– Inflammatory masses (xanthogranulomatous pyelonephritis, abscess)
– Leiomyoma: Usually in renal capsule
– Metanephric adenoma
– Metastasis: Lung, gastric, breast cancers most common; melanoma and others
– Oncocytoma: Benign; cannot be reliably differentiated from RCC on imaging studies
– Pseudotumors (column of Bertin, others)
– Renal capsule neoplasm
– Renal cell carcinoma (RCC)
– Renal cortical adenoma: Controversial; cannot be distinguished from RCC on imaging: <2 cm
– Renal lymphoma
– Renal medullary carcinoma
– Renal sarcomas
Angiosarcoma
Chondrosarcoma
Clear cell sarcoma
Ewing sarcoma/primitive neuroectodermal tumor
Fibrosarcoma
Kaposi sarcoma
Leiomyosarcoma (including the myxoid types)
Liposarcoma
Malignant fibrous histiocytoma
Malignant hemangiopericytoma
Malignant mesenchymoma
Malignant schwannoma
Osteogenic sarcoma
Rhabdomyosarcoma
Sarcomatoid renal cell carcinoma
Synovial sarcoma
Wilms tumor
– Reninoma (JG apparatus tumors)
– Urothelial carcinoma upper tract (UTUC)
• Benign renal mass in children:
– Choledochal cyst, intestinal duplication cyst
– Congenital mesoblastic nephroma
– Crossed-fused ectopia
– Cystic nephroma (multiloculated cystic nephroma)
– Hydronephrosis
– Mesenteric cyst
– Multicystic dysplastic kidney (MCDK): involuted nonfunctional kidney
– Polycystic kidney disease
– Renal abscess
– Splenomegaly
• Malignant renal masses in children:
– Lymphoma, lymphosarcoma
– Neuroblastoma (actually adrenal origin)
– Ossifying renal tumor of infancy
– RCC (rare in children)
– Sarcomas (clear cell, rhabdomyosarcoma)
– Wilms tumor (nephroblastoma): A renal mass in childhood is Wilms until proven otherwise
ALERT
Primary renal sarcoma is extremely rare. Primary retroperitoneal soft tissue sarcoma (such as leiomyosarcoma or liposarcoma) with secondary renal invasion is the more common clinical presentation.
TREATMENT
GENERAL MEASURES
• In adults, the lesions are usually approached as for RCC, with surgical excision being 1st-line therapy, as the histology of lesion is rarely known preoperatively (3)[B]
• Masses tend to be quite large, presumably due to rapid growth pattern
• The primary treatment of renal sarcomas is surgical excision. Local recurrences should be resected when feasible.
• The role of adjuvant and neoadjuvant therapy in the adult population is poorly understood
MEDICATION
First Line
• Dactinomycin and vincristine are used for more favorable stages of Wilms, with the addition of doxorubicin and abdominal radiation for more advanced stages
• Doxorubicin for clear cell sarcoma in children
• Doxorubicin, dacarbazine, and ifosfamide have been used with adult sarcomas; however, response rates at best are poor
Second Line
N/A
SURGERY/OTHER PROCEDURES
• Mainstay of treatment for all sarcomas involving the kidney is radical nephrectomy with excision of entire tumor mass, which may require resection of adjacent organs. In some cases, partial nephrectomy may be possible (2)[B].
• Wide excision is the preferred approach due to sarcomas’ tendencies toward skip lesions
• Sarcomas tend to surround the renal vasculature as well as surrounding vascular structures
• No defined role for lymphadenectomy
• Preoperative chemotherapy is given in advanced cases of Wilms to downstage prior to surgery, usually with external radiation therapy. In bilateral disease, nephron sparing is indicated.
ADDITIONAL TREATMENT
Radiation Therapy
• Sometimes employed in management of Wilms tumor postoperatively. Radiation of the tumor bed is indicated if the tumor extended beyond the renal capsule to involve adjacent organs or lymph nodes or with intraoperative tumor spillage.
• Radiation therapy after surgery in adult sarcomas may reduce local recurrence.
Additional Therapies
N/A
Complementary & Alternative Therapies
N/A
ONGOING CARE
PROGNOSIS
• Adult sarcomas, especially high grade, have a generally poor prognosis, with 5-yr survival rates of approximately 50%
– Poor prognostic variables include high-grade histology, metastases at presentation, large tumor size, and incomplete resection/margin positivity
• Local recurrence alone is associated with a better survival rate than local recurrence with concomitant metastasis
• Pediatric patients with Wilms tumors can expect a >90% cure rate, but prognosis for clear cell sarcoma and especially rhabdoid tumors is much worse
COMPLICATIONS
Children should be monitored for long-term effects of radiation and/or chemotherapy (such as cardiac dysfunction, HTN, secondary malignancies, endocrinologic abnormalities, and ovarian or testicular failure)
FOLLOW-UP
• Careful patient monitoring is essential due to the high recurrence rate
– Adults: Close follow-up for 2–5 yr
CXR every 3–6 months
Abd MRI or CT screening every 3–6 min
No specific tumor markers to follow
– Children: Same as adults. Try to limit studies such as CT due to long-term ionizing radiation risks.
Patient Resources
Kidney Cancer Association www.kidneycancer.org/
REFERENCES
1. Davidoff AM. Wilms tumor. Adv Pediatr. 2012;59(1):247–267.
2. Wang X, Xu R, Yan L, et al. Adult renal sarcoma: Clinical features and survival in a series of patients treated at a high-volume institution. Urology. 2011;77(4):836–841.
3. Dotan ZA, Tal R, Golijanin D, et al. Adult genitourinary sarcoma: The 25-year Memorial Sloan-Kettering experience. J Urol. 2006;176(5):2033–2038.
ADDITIONAL READING
• Buckley K. Pediatric genitourinary tumors. Curr Opin Oncol. 2012;24(3):291–296.
• Russo P, Brady MS, Conlon K, et al. Adult urological sarcoma. J Urol. 1992;147(4):1032–1036.
See Also (Topic, Algorithm, Media)
• Ossifying Renal Tumor of Infancy
• Renal Capsular Neoplasms
• Renal Cell Carcinoma, General Considerations
• Renal Cell Carcinoma, Sarcomatoid
• Renal Leiomyosarcoma
• Renal Mass
• Renal Sarcoma, Adult and Pediatric Image 
• Wilms Tumor
CODES
ICD9
• 171.5 Malignant neoplasm of connective and other soft tissue of abdomen
• 236.91 Neoplasm of uncertain behavior of kidney and ureter
ICD10
• C49.4 Malignant neoplasm of connective and soft tissue of abdomen
• D41.00 Neoplasm of uncertain behavior of unspecified kidney
• D41.01 Neoplasm of uncertain behavior of right kidney
CLINICAL/SURGICAL PEARLS
• Primary renal sarcomas are very rare. Soft tissue sarcomas that involve the kidney are the more common presentation.
• Renal sarcomas are more likely to be seen in childhood than adulthood. Wilms tumor is the most common pediatric renal sarcoma and has a distinct treatment algorithm.
• The primary treatment of renal sarcomas is surgical excision. Wide excision is the preferred approach due to sarcomas’ tendencies toward skip lesions. Local recurrences should be resected when feasible.
• It is important to differentiate renal or soft tissue sarcomas from RCC with sarcomatoid features, which is an aggressive variant of RCC, not a primary sarcoma.