Hyperplastic perilobar nephroblastomatosis: long-term survival of 52 patients.

BACKGROUND: This study provides insight into the clinical behavior, diagnostic complexities, and long-term management of patients with hyperplastic perilobar nephroblastomatosis (HPLN). PROCEDURE: Fifty-two patients with HPLN with available long-term follow-up were retrospectively analyzed for pathologic, radiologic, and clinical features. RESULTS: The mean age at diagnosis was 16 months; the lesions were bilateral in 49 patients. Of 33 patients who initially underwent diagnostic biopsy and adjuvant chemotherapy, 18 (55%) developed Wilms tumor (WT) at a mean of 35 months from diagnosis. Of 16 patients whose initial therapy included nephrectomy and adjuvant therapy, three (19%) developed WT at a mean of 36 months from diagnosis. All three patients who underwent initial diagnostic biopsy and received no adjuvant therapy during their initial course developed WT 4, 4, and 10 months following diagnosis. 24/52 patients developed either a single (13 patients) or multiple (11 patients) WT throughout their course; 8/24 (33%) of WT were anaplastic. The time from initial diagnosis to the development of the last WT ranged from 13 to 116 months (mean 42 months). Three children with HPLN died of WT at 3, 5, and 6 years of age; 2/3 were anaplastic. CONCLUSIONS: HPLN is a self-limited, pre-neoplastic proliferative process associated with a high risk of developing WT. The accurate diagnosis and the choices of therapy during the often-complex course of HPLN depend on the availability and accurate interpretation of a combination of pathologic, radiologic, and clinical information. When such information is appropriately obtained, the long-term survival of patients with HPLN is excellent.

Treatment with nephrectomy only for small, stage I/favorable histology Wilms' tumor: a report from the National Wilms' Tumor Study Group.

PURPOSE: Children younger than 24 months with small (< 550 g), favorable histology (FH) Wilms tumors (WTs) were shown in a pilot study to have an excellent prognosis when treated with nephrectomy only. PATIENTS AND METHODS: A study of nephrectomy only for the treatment of selected children with FH WT was undertaken. Stringent stopping rules were designed to insure closure of the study if the true 2-year relapse-free survival rate was 90% or lower. RESULTS: Seventy-five previously untreated children younger than 24 months with stage I/FH WTs for which the surgical specimen weighed less than 550 g were treated with nephrectomy only. Three patients developed metachronous, contralateral WT 1.1, 1.4, and 2.3 years after nephrectomy, and eight patients relapsed 0.3 to 1.05 years after diagnosis (median, 0.4 years; mean, 0.51 years). The sites of relapse were lung (n = 5) and operative bed (n = 3). The 2-year disease-free (relapse and metachronous contralateral WT) survival rate was 86.5%. The 2-year survival rate is 100% with a median follow-up of 2.84 years. The 2-year disease-free survival rate (excluding metachronous contralateral WT) was 89.2%, and the 2-year cumulative risk of metachronous contralateral WT was 3.1%. CONCLUSION: Children younger than 24 months treated with nephrectomy only for a stage I/FH WT that weighed less than 550 g had a risk of relapse, including the development of metachronous contralateral WT, of 13.5% 2 years after diagnosis. All patients who experienced relapse on this trial are alive at this time. This approach will be re-evaluated in a clinical trial using a less conservative stopping rule.

Primary renal neoplasms with the ASPL-TFE3 gene fusion of alveolar soft part sarcoma: a distinctive tumor entity previously included among renal cell carcinomas of children and adolescents.

The unbalanced translocation, der(17)t(X;17)(p11.2;q25), is characteristic of alveolar soft part sarcoma (ASPS). We have recently shown that this translocation fuses the TFE3 transcription factor gene at Xp11.2 to ASPL, a novel gene at 17q25. We describe herein eight morphologically distinctive renal tumors occurring in young people that bear the identical ASPL-TFE3 fusion transcript as ASPS, with the distinction that the t(X;17) translocation is cytogenetically balanced in these renal tumors. A relationship between these renal tumors and ASPS was initially suggested by the cytogenetic finding of a balanced t(X;17)(p11.2;q25) in two of the cases, and the ASPL-TFE3 fusion transcripts were then confirmed by reverse transcriptase-polymerase chain reaction. The morphology of these eight ASPL-TFE3 fusion-positive renal tumors, although overlapping in some aspects that of classic ASPS, more closely resembles renal cell carcinoma (RCC), which was the a priori diagnosis in all cases. These tumors demonstrate nested and pseudopapillary patterns of growth, psammomatous calcifications, and epithelioid cells with abundant clear cytoplasm and well-defined cell borders. By immunohistochemistry, four tumors were negative for all epithelial markers tested, whereas four were focally positive for cytokeratin and two were reactive for epithelial membrane antigen (EMA) (one diffusely, one focally). Electron microscopy of six tumors demonstrated a combination of ASPS-like features (dense granules in four cases, rhomboid crystals in two cases) and epithelial features (cell junctions in six cases, microvilli and true glandular lumens in three cases). Overall, although seven of eight tumors demonstrated at least focal epithelial features by electron microscopy or immunohistochemistry, the degree and extent of epithelial differentiation was notably less than expected for typical RCC. We confirmed the balanced nature of the t(X;17) translocation by fluorescence in situ hybridization in all seven renal tumors thus analyzed, which contrasts sharply with the unbalanced nature of the translocation in ASPS. In summary, a subset of tumors previously considered to be RCC in young people are in fact genetically related to ASPS, although their distinctive morphological and genetic features justify their classification as a distinctive neoplastic entity. Finally, the finding of distinctive tumors being associated with balanced and unbalanced forms of the same translocation is to our knowledge, unprecedented.

Human anotocephaly (aprosopus, acrania-synotia) in the Vilnius anatomical collection.

A genetic theory of "multifactorial" malformations, i.e., anomalies of blastogenesis or organogenesis, involving polygenic predisposition with morphogenetic threshold effect, was developed by Sewall Wright in the 1920s and remains an essential basis of birth defects biology. Because of the phenomenon of universality, i.e., the deployment of identical inductive, or pattern-forming, upstream molecular mechanisms during the earliest stages of mammalian morphogenesis, Wright's work on guinea pig otocephaly is highly pertinent to "corresponding," i.e., homologous malformations in humans. This concept is illustrated on the hand of a human fetus in the Vilnius (Lithuania) Pathological Museum with anotocephaly, i.e., anencephaly and otocephaly so severe as to correspond to Wright's guinea pig otocephaly grade 11 or 12. The observation also supports our apology for old museums and old books as repositories for anomalies, no less important for their rarity.

A distinctive pediatric renal neoplasm characterized by epithelioid morphology, basement membrane production, focal HMB45 immunoreactivity, and t(6;11)(p21.1;q12) chromosome translocation.

We report two cases of a hitherto undescribed pediatric renal neoplasm that is distinctive at the morphological, immunohistochemical, ultrastructural, and cytogenetic levels. On light microscopy, the tumors are composed of nests of polygonal, clear to eosinophilic cells associated with a subpopulation of smaller cells that surround hyaline material. Despite their epithelioid morphology, these tumors do not label immunohistochemically for epithelial markers but instead label focally for melanocytic markers HMB45 and Melan A. The hyaline material is positive with periodic acid-Schiff and methenamine-silver histochemical stains, and labels immunohistochemically for type 4 collagen. Ultrastructural examination confirms that it represents basement membrane material. Cytogenetic analysis reveals the identical t(6;11)(p21.1;q12) chromosome translocation as the sole abnormality in these two tumors, confirming their identity and distinctive nature.

Low-grade myxoid renal epithelial neoplasms with distal nephron differentiation.

We report 4 distinctive renal epithelial neoplasms that are essentially identical at the morphologic and immunohistochemical levels and do not fit an accepted category in the existing classification of these lesions. The patients were all females, with ages ranging from 32 to 79 years (mean, 50 years). The tumors were well circumscribed and were composed of uniform, predominantly low cuboidal cells with eosinophilic, focally vacuolated cytoplasm. Tumor cells generally formed interconnecting tubules, with smaller areas of cordlike growth and spindling in a bubbly, myxoid stroma. All tumors were confined to the kidney, and all were immunoreactive for high-molecular-weight cytokeratin 34betaE12, cytokeratin 7, epithelial membrane antigen, and cytokeratin cocktail AE1/3. Only 1 tumor was focally immunoreactive for Ulex europaeus agglutinin. Ultrastructural study showed tumor cells forming tubular structures reminiscent of the loop of Henle or distal convoluted tubule. Follow-up in all 4 cases was benign. These distinctive tumors may be confused with aggressive sarcomatoid renal cell carcinomas because of their spindled morphology. The morphologic, immunohistochemical, and ultrastructural features of these lesions indicate differentiation toward distal nephron segments. Similar tumors probably have been reported among low-grade collecting duct carcinomas or tumors "possibly related to the loop of Henle."

The spectrum of metanephric adenofibroma and related lesions: clinicopathologic study of 25 cases from the National Wilms Tumor Study Group Pathology Center.

The authors report nine new metanephric adenofibroma (MAFs; previously termed nephrogenic adenofibroma) and 16 related tumors from the files of the National Wilms Tumor Study Group Pathology Center (NWTSGPC). All tumors contained a variable amount of a bland spindle cell stroma, which is essentially identical to the recently described metanephric stromal tumor (MST). Features that distinguish this stroma from congenital mesoblastic nephroma (CMN) include intratumoral angiodysplasia, concentric cuffing of entrapped tubules ("onion skinning"), and heterologous differentiation. The epithelial components of these lesions spanned a wide range of appearances. All tumors contained at least focally an inactive embryonal epithelium identical morphologically to metanephric adenoma (MA), and hence each case could be classified as containing MAF. The epithelium of nine tumors had this appearance throughout, and hence these were considered usual MAFs. The epithelium of four tumors demonstrated increased mitotic activity but was otherwise similar to MA. The epithelial component of seven tumors spanned a morphologic spectrum from inactive MA to malignant epithelial predominant Wilms tumor (WT), with gradual transitions noted in several cases. Five other tumors contained a carcinomatous component distinct from these lesions but identical morphologically to papillary renal cell carcinoma (PRCC). In one of these cases, this component had metastasized to the regional lymph nodes at the time of diagnosis. No tumor recurred during follow-up, although almost all patients received adjuvant therapy for WT regardless of their tumor's histology and NWTSGPC diagnosis. In conclusion, MAF is a biphasic tumor that spans the morphologic spectrum between benign pure stromal (MST) and pure epithelial (MA) lesions, and can merge with the morphology of WT, supporting the concept that these are all related lesions. A relationship to PRCC is also evident.

Primary malignant neuroepithelial tumors of the kidney: a clinicopathologic analysis of 146 adult and pediatric cases from the National Wilms' Tumor Study Group Pathology Center.

Primary malignant neuroepithelial tumors of the kidney (NETKs) comprise a group of primitive, highly malignant neoplasms that histologically and clinically are not well characterized. A large cohort of 146 of these tumors, occurring in adults and children, has been collected at a single depository site, the National Wilms' Tumor Study Group (NWTSG) Pathology Center. The authors undertook a systematic retrospective review of the histologic, ultrastructural, and clinical features of these tumors, based on materials collected by the NWTSG and the consultation files of one of the authors (J.B.B.). Histologic features were generally those of primitive neural tumors with varying amounts of rosettes and neuropil; however, a large proportion of cases displayed unusual features such as spindle cells, ganglion cells, clear cell sarcoma-like foci, rhabdoid cells, epithelioid cells, and organoid foci. CD99 staining had been performed on 69 cases and showed membranous staining in 65. The NETKs were present in patients with a wide age spectrum, ranging from 1 month to 72 years (median, 18 years). EWS/FLI1 fusion analysis using reverse transcriptase-polymerase chain reaction and immunohistochemical stains for cytokeratin, chromogranin, and epithelial membrane antigen were performed successfully on a subset of 45 cases with available paraffin blocks. Only 13 of the 45 were fusion-positive, and there was no correlation between fusion status and histology, presence of rosettes, ultrastructural features, or cytokeratin positivity. CD99-negative cases were usually fusion-negative (six of seven cases), and all three chromogranin-positive cases were fusion-negative. Tumor staging, performed on 72 clearly defined and quantifiable cases by using NWTSG criteria, indicated that these are aggressive tumors, because only six were Stage 1, compared with 16 Stage 2, 31 Stage 3, and 19 Stage 4 lesions. The authors conclude that NETKs are a somewhat diverse group of generally aggressive, high-grade lesions that may present in a wide age range and are difficult to characterize without immunohistochemistry and cytogenetics/molecular biology.

Secondary acute myelogenous leukemia in patients previously treated for childhood renal tumors: a report from the National Wilms Tumor Study Group.

PURPOSE: This review characterized cases of secondary acute myelogenous leukemia (AML) occurring after treatment of renal neoplasms on protocols of the National Wilms Tumor Study Group (NWTSG) between October 1969 and December 1991. PATIENTS AND METHODS: The NWTSG database was reviewed for cases of secondary AML and for WT1 status of the affected patients. Referring institutions were contacted by a confidential letter requesting pathology reports, results of immunophenotyping, cytogenetic, and molecular analyses, and details concerning treatment of AML. RESULTS: Of the 5,278 patients treated during the study period, 43 had second malignant neoplasms, and 7 of these 43 had AML. At the time of diagnosis of Wilms tumor, the median age of the seven patients (4 boys) was 3.2 years. Five of the seven renal neoplasms had favorable histologic characteristics. The most common French-American-British morphology was M5. One patient had bilateral tumors, and two were treated for recurrent Wilms tumor. All patients received chemotherapy regimens that included doxorubicin (6) or etoposide (1), and six were treated with infradiaphragmatic irradiation. The median latency period from initial diagnosis of the renal neoplasm to development of secondary AML was 3 years (range, 1.2-4 yrs). One patient had the translocation t(9:11)(p22;q23); WT1 status was not noted for any of the seven patients. CONCLUSIONS: The development of secondary AML in this subset of patients after treatment of renal neoplasms may reflect the interaction of the effects of treatment and possible genetic predisposition toward cancer.

Familial Wilms' tumor with neural elements: characterization by histology, immunohistochemistry, and genetic analysis.

Wilms' tumor (WT) is the most common renal malignancy of children. While most occur sporadically, a small percentage are familial or occur as part of a developmental syndrome. Classic WTs exhibit a triphasic histologic pattern composed of blastema, epithelium, and stroma. Occasionally, heterologous elements may also be observed. In this study we investigated a series of four WTs that occurred within a single familial aggregate and contained focal areas of neural differentiation. The tumors were evaluated histologically for the presence of neural elements and immunohistochemically for expression of neural-related markers. Genetic linkage analysis was performed on 3 of the 4 WTs. In addition to the classic triphasic histology, the WTs contained tumor rosettes (4/4), ganglion cells (2/4), foci of ganglioneuromatous differentiation (2/4), and anaplasia (1/4). Staining for chromogranin, S-100, synaptophysin, vimentin, and neuron-specific enolase was positive in all 4 tumors within the areas of neural differentiation whereas staining for CD99 (013) and glial fibrillary acidic protein was negative. Linkage analysis studies suggest that the familial predisposition gene segregating in this family is at 19q13.4. To our knowledge, this is the first reported series of WTs with neural differentiation that occurred within a single family aggregate. Genetic linkage analysis of this family is consistent with linkage to the FWT2 WT predisposition gene at 19q13.4. We propose that these tumors may represent a unique manifestation of tumor susceptibility in this family.

Primary renal synovial sarcoma: molecular and morphologic delineation of an entity previously included among embryonal sarcomas of the kidney.

We report 15 primary renal neoplasms with morphologic, immunohistochemical, and molecular features identical to those of synovial sarcoma. These tumors form a distinct subset of the entity previously designated as embryonal sarcoma of the kidney. Most were diagnosed between the ages of 20 and 50 years. On gross examination, tumors are large, partially necrotic, and usually contain smooth-walled cysts. Microscopically, tumors are characterized by mitotically active, monomorphic plump spindle cells with indistinct cell borders growing in short, intersecting fascicles. Grossly identified cysts are lined by mitotically inactive polygonal eosinophilic cells with apically oriented nuclei ("hobnailed epithelium"). The spindle cells are immunoreactive for vimentin, often immunoreactive for EMA, but typically non-immunoreactive for desmin, actin, S100, or cytokeratins, whereas the cyst epithelium is cytokeratin-positive. These findings are consistent with monophasic, spindled synovial sarcoma encircling dilated native renal collecting ducts. The presence of an SYT-SSX gene fusion resulting from the t(X;18) characteristic of synovial sarcoma was demonstrated by reverse transcriptase polymerase chain reaction in three of three tumors in which adequate RNA could be obtained from paraffin blocks. An additional case demonstrated the characteristic t(X; 18) translocation on cytogenetic analysis, but adequate material to perform molecular studies was not available in this case or the remaining 11 cases. Primary renal synovial sarcoma is a distinctive clinicopathologic entity confirmed by molecular detection of SYT-SSX fusion transcripts.

Metanephric stromal tumor: report of 31 cases of a distinctive pediatric renal neoplasm.

We report 31 cases of a novel pediatric renal neoplasm, metanephric stromal tumor (MST). Mean patient age was 2 years, and the most common presentation was that of an abdominal mass. Gross examination typically revealed a fibrous lesion centered in the renal medulla containing smooth-walled cysts (mean tumor size, 5.5 cm). MST is histologically identical to the stromal component of metanephric adenofibroma (MAF, previously termed nephrogenic adenofibroma) and is an unencapsulated spindle cell lesion that entraps native kidney. Characteristic histologic features of MST include alternating cellularity that imparts a nodular low-power appearance, onion-skin cuffing around entrapped renal tubules, heterologous differentiation (glia or cartilage), and vascular alterations (angiodysplasia of entrapped arterioles, juxtaglomerular cell hyperplasia in entrapped glomeruli). Three tumors in which the vascular alterations were particularly florid were associated with extrarenal vasculopathy and attendant morbidity. A majority of cases stained for CD34, although the degree of staining was variable. Most patients were treated with surgical excision alone, and none experienced recurrence or metastasis. Recognition of this entity can spare a child potentially toxic adjuvant chemotherapy that might be used for lesions in its differential diagnosis, specifically clear cell sarcoma of the kidney.

Detection of the ETV6-NTRK3 chimeric RNA of infantile fibrosarcoma/cellular congenital mesoblastic nephroma in paraffin-embedded tissue: application to challenging pediatric renal stromal tumors.

We report the development of a reverse transcriptase polymerase chain reaction assay that reliably detects the ETV6-NTRK3 chimeric RNA characteristic of infantile fibrosarcoma and the cellular variant of congenital mesoblastic nephroma (CMN) in formalin-fixed, paraffin-embedded tissue blocks. The 188 base pair polymerase chain reaction fusion product was detected in 11 of 12 cases of cellular CMN from which a larger sized control RNA band could be amplified, and even in 7 of 8 cases in which the control band was not detectable. A variety of other tumors that are in the histologic differential diagnosis of cellular CMN yielded negative results, including four classic CMNs, four rhabdoid tumors of the kidney, and four clear cell sarcomas of the kidney, confirming the assay's specificity. We further demonstrate the assay's utility by illustrating two cases of molecularly confirmed cellular CMN that mimicked rhabdoid tumor and clear cell sarcoma of the kidney. In contrast to previous reports, five mixed CMNs that had both classic and cellular areas all lacked the ETV6-NTRK3 fusion transcript. These results suggest that cases morphologically defined as mixed CMN may represent a mixed group of genetically distinct entities.

Clear cell sarcoma of the kidney: a review of 351 cases from the National Wilms Tumor Study Group Pathology Center.

We reviewed 351 cases of clear cell sarcoma of the kidney (CCSK), including 182 cases entered on National Wilms Tumor Study Group (NWTSG) trials 1-4 for which clinical follow-up information was available. Tumors were restaged using NWTS 5 criteria. Mean age at diagnosis in the NWTS group was 36 months with a range of 2 months to 14 years. The male to female ratio was 2:1. Typical gross features included large size (mean diameter 11.3 cm), a mucoid texture, foci of necrosis, and prominent cyst formation. Nine major histologic patterns were identified (classic, myxoid, sclerosing, cellular, epithelioid, palisading, spindle, storiform, and anaplastic); virtually all tumors contained multiple patterns that blended with one another. Immunohistochemical stains were performed on 45 cases; only vimentin was consistently immunoreactive. Consistently negative results with other antibodies helped exclude other tumors in the differential diagnosis; all CCSKs were cytokeratin-negative, including epithelioid tumors that mimicked Wilms tumor, and MIC2-negative, including cellular tumors that mimicked primitive neuroectodermal tumor. The p53 gene product was rarely overexpressed in non-anaplastic CCSKs, but strikingly overexpressed in two of three anaplastic CCSKs. Overall survival was 69%. Multivariate analysis revealed four independent prognostic factors for survival: treatment with doxorubicin, stage, age at diagnosis, and tumor necrosis. Of note, stage 1 patients had a remarkable 98% survival rate. No other histologic or clinical variable independently correlated with survival.

Hemizygous deletions of chromosome band 16q24 in Wilms tumor: detection by fluorescence in situ hybridization.

Loss of heterozygosity (LOH) for markers on chromosome arm 16q in Wilms tumor has been linked to an increased risk of treatment failure. We therefore postulated that fluorescence in situ hybridization (FISH) with probes from this region might enhance current strategies for identifying high-risk patients at diagnosis. In a blinded comparative pilot study of 19 Wilms tumor samples from 18 patients with favorable histology, FISH and DNA polymorphism analysis yielded concordant results in 14 cases, either retention (n = 6) or loss (n = 8) of chromosome arm 16q markers. Discordant findings in 4 of the 5 remaining cases resulted from detection of LOH, but no loss by FISH. Two of these cases, directly comparable at marker D16S422, appeared to have tumor-specific uniparental disomy, in that 2 copies of D16S422 and the 16 centromere were evident, despite LOH. In 2 other cases, the discrepancies could be explained by LOH confined to loci distal to the D16S422 locus. In the fifth case, FISH detected 2 distinct populations of tumor cells, one characterized by normal diploidy and the other by monosomy 16, whereas DNA polymorphism analysis failed to indicate LOH altogether. Thus, FISH confirmed the presence of allelic loss (hence, the possible location of biologically important tumor suppressor genes) on the distal long arm of chromosome 16 in cases of favorable-histology Wilms tumor, with the advantages of technical simplicity, successful analysis of samples that were otherwise uninformative by analysis of DNA polymorphisms, and the addition of internal controls for chromosomal aneusomy. We suggest that combined analysis of the chromosome 16q region in Wilms tumor by FISH and DNA polymorphism analysis would improve evaluations to identify high-risk patients who might benefit from alternative therapy.

Nuclear morphometry and prognosis in favorable histology Wilms' tumor: A prospective reevaluation.

PURPOSE: This study was designed to evaluate the ability of a previously published nuclear morphometry discriminant function to predict disease-free survival in patients with Wilms' tumor. PATIENTS AND METHODS: We identified 218 patients with stage I-IV Wilms' tumor of favorable histology who were entered onto the National Wilms' Tumor Study (NWTS) between January 1, 1990 and April 15, 1994. The nuclear morphometry score was calculated for each patient as follows: MV(f) = (0.02 x AGE) + (1.17 x SNRF) + (90.6 x LEFD) - 94, with AGE denoting age at diagnosis in months, SNRF the skewness of the nuclear roundness factor, and LEFD the lowest value of nuclear ellipticity as measured by the feret diameter method. Relative risks of relapse were estimated for the total score and for each of its components. Sensitivity and specificity were determined for the criterion of "MV(f) is greater than -0.35" as a predictor of relapse. RESULTS: By contrast with previously published results, neither the SNRF nor the LEFD made any contribution to the prediction of disease-free survival. Sensitivity and specificity of the criterion of "MV(f) is greater than -0.35" were 71% and 56%, respectively. CONCLUSION: Re-evaluation of a published nuclear morphometry score showed that it did not predict disease-free survival in patients with Wilms' tumor. The earlier study very likely overestimated the predictive power of nuclear morphometry by using the same data set both to develop the score and to evaluate its properties. Because of the huge number of combinations of nuclear morphometry measurements that may enter into the multivariate discriminant function, use of appropriate statistical methods is essential to estimate accurately the sensitivity and specificity.

Oncocytoid renal cell carcinoma after neuroblastoma: a report of four cases of a distinct clinicopathologic entity.

Four children who developed oncocytoid renal cell carcinoma (RCC) after neuroblastoma are reported. One patient had multiple, bilateral RCCs. The mean age at time of diagnosis of RCC was 8.8 years (range, 5-13 years). The mean interval between neuroblastoma and RCC was 7.15 years (range, 3.1-11.5 years). The histologic findings of these RCCs did not fit within the spectrum of known renal epithelial neoplasms. Most of the neoplastic cells in all cases had eosinophilic, oncocytoid cytoplasm and were arranged in solid and papillary growth patterns. A subset of cells with reticular cytoplasm was also present. Immunohistochemical studies demonstrated keratins 8 and 18 in all neoplasms and keratin 20 in two cases. DNA ploidy analysis revealed that two of three neoplasms assessed were aneuploid. Cytogenetic studies revealed 45, XX, add or dup (7)(q32q36) in one neoplasm, and 83-89, XXXX, -1 ,-3, del (3)(q11.1q2?1), der(4)t(4;?22) (q32;q11.2), -14, -22 in a second tumor. Microsatellite polymerase chain reaction analysis detected no abnormalities in one neoplasm and allelic imbalance of chromosomes 2p31-32.2, 8p22, 9p22-24, 13q22, 20q13, and 22q11 in a second tumor. In case 4, two different RCCs excised 6 months apart were analyzed. The initial neoplasm showed allelic imbalance of chromosomes 2q31-32.2, 5q22, 5q31, 10p13-14, 13q22, 14q31, and 20q13. The subsequent neoplasm showed allelic imbalance of chromosomes 3p21.3, 14q31, and 20q13. The common presence of 14q31 and 20q13 abnormalities suggests that these two neoplasms were genetically related. In aggregate, these findings are distinctive, are not found in known types of RCC, and support the morphologic impression that oncocytoid RCC after neuroblastoma is a distinct clinicopathologic entity.