Tumor Study Pathology Center Research Articles

Anaplastic Sarcoma of the Kidney

We report 20 cases of a distinct, previously unrecognized renal neoplasm, anaplastic sarcoma of the kidney with polyphenotypic features. The tumors were identified by re-reviewing tumors with unusual anaplastic features from the National Wilms Tumor Study Pathology Center, the International Society of Pediatric Oncology and the United Kingdom Children's Cancer Study Group trials. Patients ranged in age from 10 months to 41 years (median age 5 y, mean age 12 y) and females predominated (1.5:1). Twelve tumors presented in the right kidney, and 5 in the left (laterality was unknown in 3 cases). The most common presentation was a renal mass. Grossly, most tumors were large, measured 4 to 21 cm (mean 12.7 cm) and weighed 115 to 1820 g (mean 835 g). Seven out of 12 tumors suitable for assessment had a distinct cystic component. The tumors involved the pelvi-calyceal system in 5 of the cases. Histologically, all tumors showed a spindle cell component which contained either multiple foci or diffuse, widespread anaplastic changes with bizarre pleomorphic cells and very atypical mitotic figures. Chondroid differentiation was seen in 16 cases, usually in the form of islands of hyaline cartilage (13 cases) or chondroid matrix (3 cases). The nodules of cartilage showed both benign and malignant features, often within the same tumor. In 2 cases small foci of osteoid were found whereas osteoclast-like giant cells were seen in 4 cases. Only 3 of the tumors exhibited a primitive blastema-like area. No neoplastic epithelial structures were identified. No nephrogenic rests were found. Limited immunohistochemical studies showed vimentin positivity in 5/5 cases, desmin was positive in 4/6 cases, MYF4 showed focal weak nuclear positivity in 1/4 cases, but MyoD1 was negative in all cases (0/5). PGP9.5 was focally, strongly positive in 4/5 cases and p53 was strongly positive in 3/6 cases. Cytokeratin, using the antibody CAM5.2, was uniformly negative within the tumor cells. Finally, CD56 was focally positive in 1/6 tumors, whereas all other markers were negative including NB84a (4/4), CD34 (5/6), CD99 (5/5), and WT1 (6/6 cases). In 4 tumors reverse transcriptase-polymerase chain reaction was performed to detect the SYT-SSX fusion transcript produced by the t(x;18), and the ETV6-NTRK3 fusion transcript using RNA extracted from archived paraffin blocks-results were negative in all 4 specimens. Tumor stage was known in 15 patients including 7 stage I, 4 stage II, 3 stage III, and 1 stage IV tumors. They were usually diagnosed as anaplastic Wilms tumors and treated accordingly. Of the 13 patients with a minimum of 2 years follow-up, 4 patients developed distant metastases and 1 had local recurrence including 1 patient with stage IV, 2 with stage III, and 2 with stage I at presentation. Three of them died and 2 were lost to follow-up. One patient with stage I tumor developed widespread metastases and died. Another stage I patient developed local recurrence after 3 months of diagnosis, but was lost to follow-up. Five stage I patients were alive and free of tumor at last follow-up. The most common sites of metastases were lung (3 cases), and liver and bones (2 cases each). These tumors showed pathologic features similar to the pleuropulmonary blastoma of childhood and undifferentiated (embryonal) sarcoma of the liver. In the differential diagnosis, anaplastic Wilms tumor, primary renal synovial sarcoma, malignant mesenchymoma, ectomesenchymoma, and mesenchymal chondrosarcomas have been considered but none of these tumors shared the same features as the 20 cases described here which represent a distinct clinicopathologic entity with morphologic features of a polyphenotypic anaplastic sarcoma of the kidney. Further molecular studies are needed to better understand its nature and more accurate classification.

Immunohistochemistry of primary malignant neuroepithelial tumors of the kidney: a potential source of confusion?: A study of 30 cases from the National Wilms Tumor Study Pathology Center

Ewing sarcoma/peripheral primitive neuroectodermal tumor (pPNET) is a rare primary tumor of the kidney with morphologic features similar to those of other primitive tumors. Previous studies have shown that these tumors frequently stain positively with immunostains against CD99 and FLI-1 and negatively with stains against WT-1, suggesting that these markers may be used for the distinction between Wilms tumor and pPNET. We present 30 cases of primary malignant neuroepithelial tumor with immunohistochemical profiles and reverse transcriptase polymerase chain reaction (RT-PCR) analysis and show that immunophenotypic overlap exists between Wilms tumor and pPNET. A subset of 30 neuroepithelial tumors from the National Wilms Tumor Study originally categorized as putative pPNETs of the kidney was stained with FLI-1, WT-1, and thyroid transcription factor-1. Bicolor fluorescence in situ hybridization studies were performed on 19 of the cases. Other data on these tumors were available from a previous study (Am J Surg Pathol 2001;25:133). Of 7 primary tumors that had the EWS/FLI-1 fusion transcript by RT-PCR, 6 exhibited strong immunopositivity for FLI-1. Nine that were negative by RT-PCR stained positively with the FLI-1 stain. Five fusion-negative cases stained with both FLI-1 and WT-1. Three fusion-negative cases were negative for FLI-1 but positive for WT-1. Five fusion-negative cases were negative for both FLI-1 and WT-1. Of the 30 cases, 29 were positive for CD99. Seven cases that were negative for the EWS-FLI-1 fusion by RT-PCR were positive by fluorescence in situ hybridization. All cases were negative for thyroid transcription factor-1. Reliance upon immunohistochemistry as the sole means of ancillary diagnosis in renal pPNET can lead to confusing results. We recommend molecular fusion studies for clarification of primitive renal tumors with unexpected immunophenotypic results.

Cystic Embryonal Sarcoma of the Kidney

Recently the WHO classification of renal neoplasms in children and adults has been revised but various rare and unclassifiable renal tumors remain. A novel type of malignancy, cystic embryonal sarcoma of the kidney, was reported in 1998 by Delahunt et al, 1 who found 25 similar cases in the files of the National Wilms Tumor Study Pathology Center. 2 This series of 25 cases was designated as embryonal sarcoma of adult and pediatric kidneys at the 1995 meeting of the United States and Canadian Academy of Pathology. 2 The case reported by Delahunt et al and most of the National Wilms Tumor Study cases had a poor prognosis despite surgical resection and adjuvant chemotherapy. We report a case of cystic embryonal sarcoma of the kidney and review the relevant literature.

The National Wilms Tumor Study Pathology Center Relocates to Hopkins.

The National Wilms Tumor Study Pathology Center Relocates to Hopkins.

The Importance of Accurate Diagnosis and Early Close Followup in Patients With Suspected Multicystic Dysplastic Kidney

Purpose Conservative management of children who have unequivocal multicystic dysplastic kidney with a stable or regressive pattern of disease during close followup is well established. However, a clear diagnosis may prove difficult. We report 3 cases in which the diagnosis was particularly difficult to increase awareness of the importance of applying strict criteria for the diagnosis of multicystic dysplastic kidney. Materials and Methods Three children in whom a diagnosis of multicystic dysplastic kidney was suspected underwent surgical exploration. One patient who did not comply with followup presented with a large retroperitoneal mass suspicious for neuroblastoma 8 months later. In another patient a growing renal cystic mass was suspicious for a multilocular cyst at 3 months of followup. At 2 months of followup a cystic nephroma was suspected in the remaining patient. Results All patients underwent surgical exploration. The patient with suspected neuroblastoma had extensive stage 3 Wilms tumor. In the child with a suspected multilocular cyst segmental multicystic dysplastic kidney of the lower pole of an ipsilateral duplicated system was found. In the patient in whom cystic nephroma was suspected mesoblastic nephroma was confirmed by the National Wilms Tumor Study Pathology Center. Conclusions An unequivocal diagnosis of multicystic dysplastic kidney should be made early in life. The urologist should have an active role in making the initial radiological diagnosis and close followup with renal ultrasound every 3 to 4 months is essential during year 1 of life. Surgical exploration is indicated if the diagnosis becomes equivocal at any point or should concerns exist regarding compliance with followup.

Nephrogenic Adenofibroma: An Unusual Renal Tumor

Nephrogenic adenofibroma is a recently described subset of tumors from the National Wilms Tumor Study pathology center.' We report a case of this lesion found at partial nephrectomy for an indeterminate renal mass. CASE REPORT A 36-year-old man presented with left flank discomfort and microscopic hematuria. Physical examination was normal, blood pressure was 152/68 mm. Hg and hemoglobin was 15.3 gm./dl. (normal 14 to 18). Excretory urography showed no obstruction but it suggested a left lower pole mass. Ultrasonography and computerized tomography (CT) showed a 2 cm. right lower pole mass that was hyperechoic on ultrasound and hyperdense on noncontrast CT (fig. 1). Ultrasound confirmed the cystic nature of the left lower pole mass seen on excretory urography and CT. Cystoscopy was normal. Right lower pole partial nephrectomy was performed. Intraoperatively frozen sections suggested a neoplasm of uncertain type with a positive resection margin after wedge excision. Completion of lower pole nephrectomy yielded a negative margin. Followup CT at 6 and 12 months showed no evidence of disease. Microscopic hematuria has resolved. The specimen consisted of a tan nodular 2 X 1.7 X 1.2 cm. mass. Microscopically the tumor was nonencapsulated but circumscribed. It comprised multifocal nests of tubulopapillary and papillary configurations of benign appearing embryonal epithelium surrounded by stroma composed of benign appearing fibroblast-like cells (fig. 2). Numerous psammoma bodies were noted. Immature cells were cuboidal or columnar with round to oval nuclei containing peppery chromatin and inconspicuous nucleoli surrounded by scant amphophilic cytoplasm. Cell borders were indistinct, no mitotic figures were identified and nuclei overlapped. The tumor was markedly vascularized and many vascular spaces were lined with endothelial cells. Some larger blood vessels had thick walls and lacked muscular organization. Neither necrosis nor inflammatory exudate was noted. There was no evidence of collecting duct carcinoma or cysts in the tumor. Immunohistochemistv study was not performed.

Benign adenomatous kidney neoplasms in children with polycythemia: imaging findings.

To correlate pathologic, computed tomographic (CT), and ultrasound (US) characteristics of nephrogenic adenofibromas and embryonal adenomas (uncommon pediatric renal tumors) in children. Medical records and imaging and pathologic findings were reviewed in three children (aged 6 1/2, 7, and 11 years) with adenomatous renal tumors and polycythemia. Specimens were reviewed at the National Wilms Tumor Study Pathology Center (Loma Linda, Calif). All tumors were smaller than 3 cm in greatest dimension. They were hyperechoic on US scans and had high attenuation on unenhanced CT scans. Two patients underwent nephrectomy for initial diagnosis of Wilms tumor. The third underwent local excision. At pathologic examination, embryonal-appearing adenomatous epithelial cells were found to form tubules and papillae with abundant psammomatous calcifications. Two masses were classified as embryonal adenomas and one as nephrogenic adenofibroma. Increased attenuation on CT scans and increased echogenicity on US scans of renal adenomatous tumors are distinctive findings that may reflect the presence of tubulopapillary structures and psammomatous calcifications.

Renal neoplasms mimicking rhabdoid tumor of kidney. A report from the National Wilms' Tumor Study Pathology Center.

Fifty-six renal neoplasms reviewed by the National Wilms' Tumor Study Pathology Center presented with histologic features that resulted in confusion with rhabdoid tumor of kidney, a usually lethal childhood renal tumor; all were eventually diagnosed as other entities. Conspicuous filamentous cytoplasmic inclusions or large nucleoli, typical findings in rhabdoid renal tumors, were the usual source of diagnostic difficulty. Most, but not all, tumors occurred in pediatric patients. Sixteen were examples of Favorable Histology Wilms' tumor, which invited confusion with rhabdoid tumors either on the basis of filamentous cytoplasmic inclusions (15 cases) or macronucleoli (one case). In most cases, foci of typical Wilms' tumor blastemal aggregation or evidence of definitive nephrogenic differentiation facilitated the correct diagnosis. All 10 patients for whom information about outcome was available were alive at last follow-up. The other 40 renal lesions mimicking rhabdoid tumor of kidney consisted of a clinically and histogenetically diverse group of neoplasms, including anaplastic Wilms' tumor, congenital mesoblastic nephroma, renal cell carcinoma, transitional cell carcinoma, collecting-duct carcinoma, oncocytoma, rhabdomyosarcoma, malignant neuroepithelial tumors, and lymphoma. Most of these lesions could be separated from renal rhabdoid tumors and correctly classified on the basis of careful attention to light microscopic details, but in several cases electron microscopy or immunocytochemical studies were helpful or essential.

Benign nodal lesions mimicking metastases from pediatric renal neoplasms: A report of the National Wilms' Tumor Study Pathology Center

Regional lymph node status is a key factor in the staging of pediatric renal tumors on the National Wilms' Tumor Study (NWTS). A review of cases entered on the NWTS has uncovered a number of cases where benign lymph node findings were mistaken for metastases. Most frequently, this was due to the presence of complexes of epithelial cells and Tamm-Horsfall protein within nodal sinuses. The epithelial cells were derived from damaged nephrons, usually resulting from obstruction by tumor. Another epithelial pseudometastic lesion, intranodal squamous epithelial cells, was found to originate from metaplastic calyceal urothelium. Benign mesothelial or coelomic inclusions similar to those previously described in pelvic and periaortic lymph nodes of adult females were found in nodes of four patients, including two boys, who are, to our knowledge, the first to be described with this finding. Other sources of confusion included protrusion of lymphoid follicles or germinal centers into nodal sinuses, thick endothelial cells of postcapillary venules mimicking epithelial tubules, nodal megakaryocytes resembling anaplastic nuclear changes, and histiocytic granulomas. Immunocytochemical methods were useful in evaluating some of these phenomena. Recognition of these pseudometastatic lesions is essential in order to avoid unnecessary and potentially hazardous therapeutic intensification.

Multilocular cyst of the kidney (cystic nephroma) and cystic, partially differentiated nephroblastoma. Terminology and criteria for diagnosis

The entities commonly known as multi-locular cyst of the kidney (MLC) and cystic partially differentiated nephroblastoma (CPDN) were reviewed, based on material in the National Wilms' Tumor Study Pathology Center. The authors recommend several modifications of existing terminology and definitional criteria for these lesions. Because MLC probably represents a neoplastic lesion, the designation "cystic nephroma" (CN) is preferred. This term should be used only for predominantly cystic tumors composed entirely of differentiated tissues, without blastema or other embryonal elements. The designation CPDN should be applied to predominantly cystic lesions, lacking nodular solid regions, in which blastemal or other embryonal cells are present in the septa of the cysts. Solid Wilms' tumor with multifocal cystic change should be distinguished from CPDN. Five cases of CN and 18 cases of CPDN were reviewed. No CN, for which follow-up data was available, showed aggressive behavior. Only one case of CPDN underwent local recurrence, and there were no metastases. In general, nephrectomy alone appears to be adequate therapy for CPDN, but regular monitoring by noninvasive techniques would seem advisable.

Anaplasia in unilateral Wilms' tumor: a report from the National Wilms' Tumor Study Pathology Center.

Fifty-eight unilateral anaplastic Wilms' tumors entered on the Third National Wilms' Tumor Study (NWTS-3) were reviewed. The favorable outcome of stage I anaplastic tumors was confirmed. In stage II-IV tumors, the extent and severity of anaplasia were not of prognostic importance. However, two histologic features were correlated with extremely poor outcome; anaplasia in extrarenal tumor sites (P = .016) and predominantly blastemal tumor pattern (P = .020). The importance of these features in predicting relapse and death for children with anaplastic Wilms' tumor was supported by the study of 47 additional anaplastic Wilms' tumor cases from NWTS-2. These results emphasize the importance of examining sites of extrarenal spread in anaplastic Wilms' tumors. Cytologic criteria for anaplasia and clues to its recognition are reviewed, and the potential clinical and biological implications of our findings are discussed.

Annotated Bibliography: Renal Pathology

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Wilms' tumor and other renal tumors of childhood: A selective review from the National Wilms' Tumor Study Pathology Center

Selected studies of Wilms' tumor and related renal neoplasms in children, which have been based on the National Wilms' Tumor Study Pathology Center collection of more than 2,600 renal tumors of childhood, are reviewed. The purpose of the review is to illustrate the value of the collaborative approach to uncommon pathologic specimens and to distinguish several tumors often confused with Wilms' tumor, including renal adenocarcinoma, renal teratoma, and renal neurogenic tumors. The unfavorable prognostic significance of anaplastic cells in Wilms' tumor is emphasized. Two recently described clinicopathologic entities--clear cell sarcoma of kidney and malignant rhabdoid tumor of kidney--and morphologic variants often confused with Wilms' tumor or congenital mesoblastic nephroma of infancy are discussed. Clear cell sarcoma of kidney and malignant rhabdoid tumor of kidney are, apparently, distinctive neoplasms, not Wilms' tumor variants.