PEDIATRIC UROLOGIC ONCOLOGY 0094-0143/00 $15.00 + .OO NON-WILMS’ RENAL TUMORS IN CHILDREN Bruce Broecker, MD Renal tumors other than Wilms’ tumor are tastases occur in 40% to 60% of patients with infrequent in childhood. Wilms’ tumors ac- clear cell sarcoma of the kidney, whereas they count for 6% to 7% of childhood cancer, are found in less than 2% of patients with whereas the remaining renal tumors account Wilms’ tumor.**,26 This distinct clinical behav- for less than l%.27The most common non- ior is one of the features that has led to its Wilms‘ tumors are clear cell sarcoma of the designation as a separate tumor. Other clini- kidney, rhabdoid tumor of the kidney (both cal features include a lack of association with formerly considered unfavorable Wilms’ tu- sporadic aniridia or hemihypertrophy. mor variants but now considered separate tu- Clear cell sarcoma of the kidney has not mors), renal cell carcinoma, mesoblastic been reported to occur bilaterally and is not nephroma, and multilocular cystic nephroma. associated with nephroblastomatosis. It has Collectively, these tumors account for less been reported in infancy and adulthood, but than 10% of the primary renal neoplasms in the peak incidence is between 3 and 5 years childhood. of age. It has an aggressive behavior that responds poorly to treatment with vincristine and actinomycin alone, leading to its original CLEAR CELL SARCOMA designation by Beckwith as an unfavorable histology pattern. The addition of doxorubi- Clear cell sarcoma of the kidney is cur- cin in aggressive chemotherapy regimens has rently considered a separate tumor distinct improved outcome. Current 4year survival is from Wilms’ tumor, although in early Na- 75% in a group of 50 patients in NWTS-III.17 tional Wilms’ Tumor Studies (NWTS) and In- In the ongoing NWTS-V protocols, clear cell ternational Society of Pediatric Oncology sarcoma of the kidney at all stages is treated (SIOP) studies, it was considered an unfavor- with the same regimen used for Wilms’ tumor able histology pattern of Wilms’ tumor (Table with diffuse anaplasia (excluding stage I), 1): In these early NWTS series, 4% of regis- that is, radical nephrectomy followed by che- tered renal tumors were designated clear cell motherapy with cyclophosphamide, etopo- sarcoma.S,’8 The tumor was first described as side, vincristine, and doxorubicin for 24 a distinct entity in 1978 by three independent weeks and radiotherapy. groups, Beckwith and Palmer,5 Morgan and Kidd,“ and Marsden and co-worker~,~~who RHABDOID TUMOR OF THE KIDNEY labeled it “bone metastasizing renal tumor of childhood” in recognition of its well-known As is true for clear cell sarcoma, rhabdoid propensity for skeletal metastasis. Bone me- tumor of the kidney was formerly categorized From the Section of Pediatric Urology, Children’s Hospital of Atlanta and the Department of Urology, Emory University School of Medicine, Atlanta, Georgia UROLOGIC CLINICS OF NORTH AMERICA ’ VOLUME 27 NUMBER 3 * AUGUST 2000 463 ! 464 BROECKER Table 1. SUMMARY OF CHARACTERISTICS OF NON-WILMS’ RENAL TUMORS OF CHILDREN Renal Cell Congenital Myoblastic Characteristic Clear Cell Sarcoma Rhabdoid Tumor Carcinoma Nephroma CNICPDN Median age 4 Years 11 Months 12 Years <3 Months 1-2 Years Malignant potential Yes Yes Yes Cellular variant Risk of local potentially malignant recurrence if (rare) tumor spill Follow-up/ Aggressive Aggressive ? Immunotherapy Usually none Usually none adjuvant therapy chemotherapy and chemotherapy for metastatic Consider chemo- Obtain follow- radiotherapy and radiotherapy disease therapy for cellular up imaging variant if intra- operative tumor spill Unique Bone metastases in Associated with Infiltrates renal characteristics 50% medulloblastoma parenchyma Propensity for brain metastases Prognosis 75% Survival 20% Survival Good for localized Excellent Excellent disease Poor for metastatic disease CN = cystic nephroma; CPDN = cystic partially differentiated nephroblastoma. as an unfavorable histologic pattern of Wilms’ ity is 80%.61 Even patients with completely tumor but is now considered a separate tu- resected tumors with negative lymph nodes mor? It is rare, accounting for 2% of the renal have a 50% mortality rate. The current treat- tumors registered with NWTS. It may arise ment protocol in NWTS-V is radical ne- in extrarenal locations, although controversy phrectomy followed by chemotherapy with remains regarding the exact identity of these carboplatinum, etoposide, and cyclophospha- extrarenal rhabdoid tumors.& Haas and co- mide for 24 weeks and radiothyapy. workers2Rgave the tumor its present name and suggested its separate identity in 1981, but it was first described by Beckwith and RENAL CELL CARCINOMA Palmer in 1978 and referred to as a rhabdo- myosarcomatoid neoplasm, reflecting the Renal cell carcinoma is the most common presence of cells with a rhabdomyoblast ap- renal neoplasm in adults and occurs rarely in pearan~e.~On immunohistochemical staining, the pediatric patient. Approximately 1% to this resemblance appears to be deceiving, and 2% of renal cell carcinomas occur in patients evidence of a myogenic lineage is generally aged less than 21 years, and these lesions not found.62A diversity of phenotypic mark- account for 2% to 5% of primary renal tumors ers are expressed, but the most common and in this age group. The earliest well-docu- consistent are vimentin and cytokeratin. mented cases in the English language were Current thought is that rhabdoid tumor of reported by Boyd and Lisa12 and McCurdy41 the kidney is probably neurogenic in origin. in 1934. By 1960, more than 50 occurrences The tumor is typically large and central/ hilar had been published as case reports. The first in origin, often replacing the entire kidney. It series of patients with renal cell carcinoma presents early in life, with more than 50% of was reported by Dehner and co-workersZ1 patients aged less than 1 year. The median from the Armed Forces Institute of Pathology age is 11 months.6’ Metastases may be found (15 patients) in 1970. The two largest series in not only in the lungs and liver (as is true for the literature are 20 patients collected from Wilms’ tumor) but also in the brain (unlike four institutions reported on by Raney and Wilms’ tumor). In addition to brain metasta- co-~orkers~~in 1983 and 22 patients from the ses, primary brain tumors have been reported Memorial Sloan-Kettering Cancer Center re- to occur in 10% to 15% of patients, the most ported on by Aronson and co-workers2 in common being medulloblastoma.ll,61 1996. Rhabdoid tumor of the kidney is an aggres- Renal cell carcinoma has been reported in sive lesion with a poor prognosis. Most pa- infancy, but most .patients are older, with a tients present with advanced stage disease, mean age of 9 to 15 years. During the second the tumor responds poorly to current chemo- decade of life (age 10 to 20 years), patients therapy and radiotherapy, and overall mortal- presenting with a primary intrarenal tumor QON-WILMS’ RENAL TUMORS IN CHILDREN 465 are equally likely to have a Wilms’ tumor or of 48 patients was reported in 1973. Clinico- renal cell carcinoma.29Although one of the pathologic features included its occurrence in patients with renal cell carcinoma reported on the neonatal period as an unencapsulated and in the series by Hartman and ~olleagues~~hadlocally invasive fibrous lesion that could be bilateral tumors, that feature is uncommon cured by nephrectomy alone (“no cases of for this tumor. tumor recurrence by metastasis having been It has been debated whether pediatric renal documented”).l0Local recurrence as a result cell carcinoma is a different tumor than its of incomplete resection could occur. In subse- adult counterpart. Caraco and co-~orkers’~ quent cases, patients with documented metas- studied 16 pediatric patients from three chil- tasis and a malignant course have been re- dren‘s hospitals in Canada and reported a ported, and the histology of the tumors in higher incidence of papillary histology than these patients has been shown to contain seen in adult renal cell carcinoma and, per- atypical cellular features and a high mitotic haps more persuasively, cytogenetic translo- index.- cations involving the X chromosome, which The relationship of congenital mesoblastic are rarely seem in adult tumors, in two of nephroma to Wilms’ tumor continues to be four patients with tumor karyotyping. The debated. It has been reported in a patient clinical behavior of pediatric renal cell carci- with Beckwith-Wiedemann syndrome who noma and adult tumor is similar; neverthe- was noted to have cytogenetic rearrange- less, that is, the most significant prognostic ments at chromosome 11~15,and adjacent variable for survival is complete resection and normal renal tissue that may contain subcap- low-stage disease.2,49 Survival for patients sular tumorlets, supporting the association presenting with stage I disease is greater than with Wilms’ tumor.5oOther investigators have 90%, for patients with stage I1 and 111 disease noted that the cellular variant of congenital approximately 50%, and for patients with mesoblastic nephroma may metastasize to stage IV disease almost 0%. The tumor is not bone and brain and has histologic features responsive to radiotherapy, and there is no more reminiscent of clear cell sarcoma of the effective chemotherapy for nonlocalized or kidney, stressing the latter tumor as a more relapsed disease, although MacArthur and probable association.54 co-worker~~~reported a complete response to Hypertension