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J B Beckwith

Publications and source records attributed to J B Beckwith.

At least 37 records · Page 2Linked to original sources
PubMed1999

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.

Adenoma, Oxyphilic↗
PubMed1999

Surgery-related factors and local recurrence of Wilms tumor in National Wilms Tumor Study 4.

OBJECTIVE: To assess the prognostic factors for local recurrence in Wilms tumor. SUMMARY BACKGROUND DATA: Current therapy for Wilms tumor has evolved through four studies of the National Wilms Tumor Study Group. As adverse prognostic factors were identified, treatment of children with Wilms tumor has been tailored based on these factors. Two-year relapse-free survival of children in the fourth study (NWTS-4) exceeded 91%. Factors once of prognostic import for local recurrence may lose their significance as more effective therapeutic regimens are devised. METHODS: Children evaluated were drawn from the records of NWTS-4. A total of 2482 randomized or followed patients were identified. Local recurrence, defined as recurrence in the original tumor bed, retroperitoneum, or within the abdominal cavity or pelvis, occurred in 100 children. Using a nested case-control study design, 182 matched controls were selected. Factors were analyzed for their association with local failure. Relative risks and 95% confidence intervals were calculated, taking into account the matching. RESULTS: The largest relative risks for local recurrence were observed in patients with stage III disease, those with unfavorable histology (especially diffuse anaplasia), and those reported to have tumor spillage during surgery. Multiple regression analysis adjusting for the combined effects of histology, lymph node involvement, and age revealed that tumor spillage remained significant. The relative risk of local recurrence from spill was largest in children with stage II disease. The absence of lymph node biopsy was also associated with an increased relative risk of recurrence, which was largest in children with stage I disease. The survival of children after local recurrence is poor, with an average survival rate at 2 years after relapse of 43%. Survival was dependent on initial stage: those who received more therapy before relapse had a worse prognosis. CONCLUSIONS: This study has demonstrated that surgical rupture of the tumor must be prevented by the surgeon, because spills produce an increased risk of local relapse. Both local and diffuse spills produce this risk. Stage II children with local spill appear to require more aggressive therapy than that used in NWTS-4. The continued critical importance of lymph node sampling in conjunction with nephrectomy for Wilms tumor is also established. Absence of lymph node biopsy may result in understaging and inadequate treatment of the child and may produce an increased risk of local recurrence.

Child, Preschool↗
PubMed1999

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.

Child↗
PubMed1998

ETV6-NTRK3 gene fusions and trisomy 11 establish a histogenetic link between mesoblastic nephroma and congenital fibrosarcoma.

Congenital mesoblastic nephroma (CMN) is an infantile spindle cell tumor of the kidney that is subdivided into "classical" and "cellular" forms based on the degree of cellularity and mitotic activity. The histogenesis of CMN remains obscure, but relationships to other pediatric renal neoplasms have been proposed. However, cellular CMN is virtually identical histologically to congenital fibrosarcoma (CFS), a malignant tumor of fibroblasts in children of the same age group. Moreover, cytogenetic studies have reported common trisomies in CFS and cellular CMN, particularly of chromosome 11. We show here that t(12;15)(p13;q25)-associated ETV6-NTRK3 gene fusions described in CFS are also present in cellular CMN. ETV6-NTRK3 chimeric transcripts were detected in 8 of 9 cellular CMNs and 2 of 2 mixed CMNs. In contrast, all of the four classical CMNs tested were negative, as were cases of Wilms' tumor and clear cell sarcoma of the kidney. Moreover, we found trisomy 11 only in cellular or mixed CMNs with the ETV6-NTRK3 gene fusion. Our studies indicate that classical and cellular CMN have different genetic features and support the concept that cellular CMN is histogenetically related to CFS. They also provide insight into potential mechanisms involved in the transformation of the classical into the cellular form of CMN.

Child, Preschool↗
PubMed1998

Nephrogenic rests and the pathogenesis of Wilms tumor: developmental and clinical considerations.

Nephrogenic rests (NR) are abnormally persistent clusters of embryonal cells, representing microscopic malformations (dysplasias) of the developing kidney. Though NR are best known as precursors of Wilms tumor (WT), many alternative fates are observed, and most rests are destined for eventual atresia. Biological and clinical distinctions between the two major NR categories, perilobar and intralobar rests (PLNR and ILNR) are emphasized. PLNR occur in fetal overgrowth and with certain overgrowth syndromes. ILNR are frequently associated with deletions or mutations of WT1. Data are presented concerning the prevalence of NR in general pediatric autopsy populations, and in selected syndromes. The age at diagnosis of WT was determined for the largest series of patients with WT-associated syndromes reported to date. These data provide a basis for determining how long patients with these conditions are at risk for WT development.

Humans↗
PubMed1998

Vignettes from the history of overgrowth and related syndromes.

Vignettes of several stages in the evolution of present concepts of overgrowth and related syndromes are presented. The scientific study of this topic did not begin until the 18th century because of its delayed emergence from superstition and fallacy. Examples of early superstitions concerning gigantism are presented, with some historical comments on infant giants. The pioneering contributions of Isodore Geoffroy Saint-Hilaire to the scientific analysis of overgrowth are emphasized. Details concerning the early history of the growth syndrome associated with the names of Wiedemann and Beckwith is presented, with emphasis on cases reported prior to ours.

Growth Disorders↗
PubMed1998

Cystic embryonal sarcoma of kidney: a case report.

BACKGROUND: Morphologic analysis of malignant renal tumors of childhood and adolescence has resulted in the identification of a variety of tumor types with characteristic histology and clinical behavior. The authors report a case of renal sarcoma in a 19-year-old male that differs in morphology from the various established categories of primitive renal tumors. METHODS: Sections taken from the nephrectomy specimen were stained by routine methods and by immunohistochemistry for stromal and epithelial markers, and for proliferation markers. In addition, ultrastructural studies were undertaken. RESULTS: The tumor, which the authors termed cystic embryonal sarcoma, was comprised of poorly differentiated malignant mesenchyme in a myxoid stroma. Numerous epithelial-lined cysts were present. The distribution of the cysts and proliferation kinetics of cyst-lining epithelial cells suggested that they were derived from entrapped renal tubules. The tumor showed early recurrence postoperatively and after aggressive chemotherapy. The pathologic features and clinical behavior of the tumor resemble those of 2 previously reported cases and an additional 25 cases from the files of the National Wilms' Tumor Study Pathology Center. CONCLUSIONS: The clinical and histologic features of cystic embryonal sarcoma differ from those of other renal tumors of childhood and adolescence, and the tumor appears to be a novel form of renal malignancy.

Adult↗
PubMed1998

Misleading leads: Wilms tumor with a metachronous lesion appearing in the remaining kidney.

Medullary dysplasia may be present in the kidneys of children with the Beckwith-Wiedemann Syndrome (BWS). This is usually visible only at the microscopic level, but superimposed pyelonephritis in a child with the BWS led to gross changes that produced a filling defect on CT scanning of the remaining kidney. The finding could have been misinterpreted as a metachronous wilms tumor.

Beckwith-Wiedemann Syndrome↗
PubMed1998

Comparison between single-dose and divided-dose administration of dactinomycin and doxorubicin for patients with Wilms' tumor: a report from the National Wilms' Tumor Study Group.

PURPOSE: The National Wilms' Tumor Study (NWTS)-4 was designed to evaluate the efficacy, toxicity, and cost of administration of different regimens for the treatment of Wilms' tumor (WT). PATIENTS AND METHODS: Between August 6, 1986 and September 1, 1994, 1,687 previously untreated children less than 16 years of age with stages I to II/favorable histology (FH) or stage I/anaplastic histology WT (low-risk [LR] group) or stages III to IV/FH WT or stages I to IV/clear cell sarcoma of the kidney (high-risk [HR] group) were randomized to treatment that included vincristine and either divided-dose (standard [STD]) courses (5 days) or single-dose (pulse-intensive [PI]) treatment with dactinomycin. HR patients also received either STD courses (3 days) or PI treatment with doxorubicin. RESULTS: The 2-year relapse-free survival (RFS) rates for LR patients were 91.3% for 544 randomized to treatment with PI and 91.4% for 556 randomized to treatment with STD chemotherapy (P = .988). The 2-year RFS rates for HR patients were 87.3% for 299 randomized to treatment with PI and 90.0% for 288 randomized to treatment with STD chemotherapy (P = .865). CONCLUSION: We conclude that patients treated with PI combination chemotherapy for LR or HR WT or clear cell sarcoma of the kidney have equivalent 2-year RFS to those treated with STD regimens. PI drug administration is recommended as the new standard based on demonstrated efficacy, greater administered dose-intensity, less severe hematologic toxicity, and the requirement for fewer physician and hospital encounters.

Adolescent↗
PubMed1998

Effect of duration of treatment on treatment outcome and cost of treatment for Wilms' tumor: a report from the National Wilms' Tumor Study Group.

PURPOSE: National Wilms' Tumor Study (NWTS)-4 was designed to evaluate the efficacy, toxicity, and cost of the administration of different regimens for the treatment of Wilms' tumor (WT). PATIENTS AND METHODS: Between August 6, 1986 and September 1, 1994, 905 previously untreated children aged younger than 16 years with stage II favorable histology (FH) WT (low-risk [LR]), stages III to IV FH WT, or stages I to IV clear-cell sarcoma of the kidney (high-risk[HR]) were randomized after the completion of 6 months of chemotherapy to discontinue (short) or continue for 9 additional months (long) treatment with chemotherapy regimens that included vincristine and either divided-dose (standard [STD]) courses (5 days) or single-dose (pulse-intensive [PI]) treatment with dactinomycin. HR patients also received either divided-dose (STD) courses (3 days) or single-dose (PI) treatment with doxorubicin. RESULTS: The 4-year relapse-free survival (RFS) rates after the second randomization for LR patients were 83.7% for the 190 patients treated with short and 88.2% for the 187 patients treated with long chemotherapy (P = .11). The 4-year RFS rates after the second randomization for HR FH patients were 89.7% for the 256 patients treated with short and 88.8% for the 246 patients treated with long chemotherapy (P = .87). The charge for treatment with the short PI treatment regimens for all children with stages I through IV FH WT was approximately one half of that with the long STD treatment regimens. CONCLUSION: The short administration schedule for the treatment of children with WT is no less effective than the long administration schedule and can be administered at a substantially lower total treatment cost.

Adolescent↗
PubMed1997

New developments in the pathology of Wilms tumor.

Wilms tumor (WT) is an embryonal renal neoplasm that has proven to be an exceptionally productive model for the study of tumor pathogenesis and therapy. It also provides a striking demonstration of what can be achieved through the collaborative study of rare tumors, as well as the importance of incorporating formal pathological review into the design of therapeutic cancer trials. As a result of the National Wilms Tumor Study, a majority of children are now cured of their WT with less intense and prolonged therapy than was customary at the middle of the 20th century. The presence of extreme polyploidy (anaplasia) identifies a small subset of WT which have a grim prognosis in the context of present therapy, and which will require innovative therapeutic intensification. Recent evidence suggests that anaplasia is a marker of resistance to adjuvant therapy, rather than increased aggressiveness. Stage I anaplastic WT and advanced-stage WT with anaplasia limited to a portion of the primary tumor seem to fare as well as nonanaplastic WT and do not require therapeutic intensification. New neoplastic entities formerly confused with WT have been identified, and refinements of staging criteria have been achieved. New insight into the pathogenesis has significant implications for clinical management. Despite these achievements, much remains to be learned from this tumor model, before we have achieved the ultimate goal of curing every child with WT, while exposing that child to the minimum possible adverse sequelae of therapy. Adverse effects of therapy are far more significant for the young child cured of cancer than for the elderly patient, and their avoidance is therefore the most important goal beyond the cure itself.

Humans↗
PubMed1996

Familial Wilms' tumor: a descriptive study.

Among 6,209 patients with Wilms' tumor entered on the National Wilms' Tumor Study (NWTS), 93 patients (1.5%) from 63 families had a positive family history. In 30 of these 63 families a (half) sibling or parent of the NWTS patient was confirmed to have had Wilms' tumor. Fifteen (16.1%) of the familial, but only 7.1% of sporadic cases, had bilateral disease. Mean ages at diagnosis were 15.8 vs. 35.2 months (P = 0.012) for bilateral vs. unilateral familial cases and 32.0 vs. 44.7 months for sporadic cases. Intralobar nephrogenic rests were found twice as frequently in association with the tumors of familial as with those of sporadic cases. Cases of bilateral and metastatic disease tended to cluster within specific families, suggesting heterogeneity in the genetic etiology. The number and age distribution of familial cases transmitted through the father were about the same as those of cases transmitted through the mother. This finding is inconsistent with models of genomic imprinting that involve familial transmission of a tumor-suppressor gene and it casts further doubt on the hypothesis that all bilateral cases are hereditary.

Adolescent↗
PubMed1996

Histological analysis of aggressiveness and responsiveness in Wilms' tumor.

The clinical behavior and outcome for any neoplasm are determined originally by its aggressiveness. As adjuvant therapy becomes increasingly effective for that neoplasm, responsiveness to therapy assumes a larger role in determining outcome. Wilms' tumor (WT) provides instructive examples of the dissociation of aggressiveness from responsiveness. The presence of gigantic nuclei with multipolar mitotic figures (anaplasia) appears to be a marker of resistance to therapy, but not of increased aggressiveness. For this reason, anaplasia in a stage 1 WT and anaplasia confined to discrete foci within the primary tumor have no adverse prognostic significance following surgical resection. The prognostic significance of anaplasia is apparently limited to those patients in whom anaplastic cells remain following attempted surgical resection. WT with predominantly epithelial differentiation usually have a low degree of aggressiveness. In this study, 81.3% of WT with this pattern were stage 1. This feature accounts for the high cure rate associated with this pattern prior to the advent of effective adjuvant therapy. However, epithelial predominant WT that present with advanced stage disease may be quite resistant to therapy, with relapse and death rates higher than for more aggressive WT patterns. In contrast, the diffuse blastemal pattern is associated with marked aggressiveness, but with high survival rates suggesting it is usually responsive to current therapy. These features illustrate the independence of aggressiveness and responsiveness in determining outcome for some patients with cancer. Grading systems must be reevaluated with each significant change in therapy. In order to formulate rational therapy, it is important to determine whether prognostic markers are associated with aggressiveness or responsiveness.

Anaplasia↗
PubMed1996

Loss of heterozygosity at chromosome regions 22q11-12 and 11p15.5 in renal rhabdoid tumors.

Rhabdoid tumors of the kidney are highly malignant neoplasms that occur primarily within the first 3 years of life. Although they are regarded as distinct from Wilms' tumors, their pathogenesis remains unclear. Whereas most cytogenetic studies of these tumors have revealed normal karyotypes, a few reports have indicated abnormalities at chromosome regions 22q and 11p15.5. We analyzed 30 primary renal rhabdoid tumors for loss of heterozygosity (LOH) at both regions and found that 24 of 30 tumors (80%) had LOH at chromosome arm 22q and that 5 of 30 (17%) had LOH at chromosome band 11p15.5. All of the five tumors with LOH at chromosome arm 11p also had LOH at chromosome arm 22q. The data suggest that there is a gene in chromosome 22, probably a tumor suppressor, inactivation of which may be involved in the genesis of renal rhabdoid tumors. A second gene in chromosome segment 11p15.5, in the region of the putative WT2 gene, may also be involved, in at least a subset of rhabdoid tumors. In addition, five tumors were characterized by microsatellite instability at three or more of 21 loci examined, suggesting a possible role for a replicative error in tumorigenesis or progression in some cases of renal rhabdoid tumors. Genes Chromosom Cancer 15:10-17 (1996).

Chromosome Deletion↗
PubMed1996

Renal salvage procedures in patients with synchronous bilateral Wilms' tumors: a report from the National Wilms' Tumor Study Group.

Synchronous bilateral Wilms' tumor accounts for 4% to 6% of all Wilms' tumors. Renal salvage procedures (partial nephrectomy and enucleation) have been recommended to conserve renal parenchyma. The objective of this study was to review the results of renal salvage operations performed in children who had bilateral neoplasms. The authors reviewed the records of 98 children enrolled in the Fourth National Wilms' Tumor Study who had synchronous bilateral tumors and underwent renal salvage procedures. One hundred thirty-four kidneys were managed with renal salvage procedures. Complete excision of gross disease was accomplished in 118 (88%) of the 134 kidneys. Local tumor recurrence in the remnant kidney or tumor bed occurred in 11 cases (8.2%). Overall, 72% of the kidneys were preserved, and the 4-year survival rate was 81.7%. The surgical morbidity after a salvage procedure was comparable to that of a complete nephrectomy in patients with unilateral Wilms' tumor. Although the incidence of positive surgical margins is worrisome, it did not invariably lead to local recurrence in the remnant kidney or the tumor bed.

Biopsy↗