Cytodifferentiated renal tumors occurring with Wilms' tumors of the opposite kidneys: report of two cases.

The most common differentiated renal tumor of early childhood is the congenital mesoblastic neophroma. Well-differentiated forms of Wilms' tumor may present a difficult differential diagnosis from these benign neoplasms. The cases of two patients found to have well-differentiated renal neoplasms after being treated for Wilms' tumor of the opposite kidneys are reported. The second neoplasms were composed of a benign-appearing stroma with mature skeletal muscle and completely lacked any embryonal, nephroblastic tissue. These benign-appearing neoplasms may be cytodifferentiated variants of Wilms' tumor. Though tumors of this type may have a malignant potential, there is evidence to indicate that they may be approached more conservatively than the usual nephroblastoma. In cases of bilateral Wilms' tumor, well-differentiated tumors might be treated by partial nephrectomy alone, with careful preservation of functional renal tissue.     

Wilms' tumor in adults: aspiration cytology and cytogenetics

The fine-needle aspiration cytologic findings of Wilms' tumor occurring in a 20-yr-old female patient and a 35-yr-old male patient showing blastemal, spindled sarcomatous and rare epithelial components are reported. The male patient had the typical presentation of renal mass with metastasis to lung and pleura, whereas the female patient had an unusual presentation with the tumor originated from the subcapsular nephrogenic zone of the kidney, extending into the liver without invasion into the renal cortex. Cytogenetic analysis of this case identified: 90, XXXX, +2x3-4, -5, -15, -16, -17, -17, i (17)(q10) x2. This finding may represent a genetic change associated with Wilms' tumor of older pediatric and young adult patients. To the best of our knowledge, this case is the sixth case with cytogenetic study and the first case revealing isochromosome 17q of an adult Wilms' tumor.     

A human adult Wilms' tumor. Histologic, ultrastructural, and cytogenetic analysis

The cytogenetic, histologic, and electron microscopic studies of an adult patient with Wilms' tumor are presented. Wilms' tumor (nephroblastoma) is a common renal tumor of childhood but is extremely rare in people over 15 years old. The histologic analysis of the patient's tumor, including both light and electron microscopic analysis, indicated that this tumor satisfies the histologic criteria for an adult Wilms' tumor, namely, blastemic cells that are immature renal parenchymal cells, embryonic tubular structures, and a scanty stromal component consisting of loosely arranged spindle cells. The tumor showed several ultrastructural features characteristic of adult Wilms' tumor, namely, markedly elongated mitochondria, autophagic vacuoles, and intracytoplasmic filaments. Karyotypic analysis was performed on the patient's peripheral leukocytes and tumor cells. The leukocytes showed no significant increase in gaps and breaks, and the patient appears to have a normal male karyotype. Some interesting chromosomal anomalies were observed in the cultured tumor cells: at least one chromosome 13, both chromosomes 22, and the X chromosome are missing, three markers are present, and there is a possible deletion of 12p.     

Hyperdiploidy including trisomy 8 in a cystic partially differentiated nephroblastoma

Cystic partially differentiated nephroblastoma (CPDN), a rare, cystic, renal lesion of childhood, has not been previously karyotyped. It is distinguished histologically from multilocular renal cyst by the presence of blastemal cells, and from Wilms' tumor by lack of expansile, solid growth and by indolent clinical behavior. In the present case, ten of 20 analyzed cells from a 3-week culture obtained from the tumor had a clonal, hyperdiploid karyotype. The modal chromosome number was 51, with chromosomes 8, 12, 17, 19, and 20 usually being present in three copies. Trisomy 8 was present in every hyperdiploid cell examined. A normal 46,XY constitutional karyotype was also observed. In degree and significance, the hyperdiploidy of CPDN is thus distinct from that reported in the prognostically unfavorable, anaplastic Wilms' tumor, where the DNA index is typically near-tetraploid. Trisomy 8, as a constitutional mosaicism, has been previously reported in children with bilateral CPDN and/or undifferentiated sarcomas, although none of their tumors were karyotyped. The present findings support a neoplastic nature for CPDN, while emphasizing its pathogenetic distinctiveness from Wilms' tumor, and provide further evidence for significance of trisomy 8 in the pathobiology of this tumor.     

Cytopathology of uncommon malignant renal neoplasms in the pediatric age group

Malignant renal neoplasms are common solid tumors in pediatric oncology practice. These include the common Wilms' tumor/nephroblastoma and the uncommon neoplasms such as clear-cell sarcoma of the kidney (CCSK), rhabdoid tumor, renal-cell carcinoma, and others. The aim of this study was to describe in detail the cytopathological features of the histopathologically proven uncommon pediatric renal tumors. Aspirates from Wilms' tumor, which are mesenchyme predominant, show clusters of spindle cells associated with the matrix material. Evidence of rhabdomyoblastic differentiation may be present. CCSK, classic subtype, is characterized by round to oval cells arranged perivascularly and also in sheets and clusters intimately associated with a metachromatic matrix mucopolysaccharide material better appreciated in May-Grunwald-Giemsa (MGG)-stained smears. The cells also have more abundant cytoplasm and may show nuclear grooves. Spindle-cell pattern of CCSK is difficult to diagnose on aspiration cytology. Renal-cell carcinoma of childhood shows similar cytological features as its adult counterpart. Rhabdoid tumor of the kidney is characterized by a monomorphic population of cells with abundant cytoplasm, eccentric nuclei with prominent nucleoli. Intrarenal yolk sac tumor is a rare neoplasm and shows severely pleomorphic cells on aspiration.Awareness of these entities is important for the practicing cytopathologist. Further, non-Wilms' renal malignant neoplasms must be distinguished from the common Wilms' tumor so that appropriate chemotherapy protocols may be instituted in cases where the tumor is in an advanced stage of malignancy.     

Rezidiv eines Wilms' Tumors nach 9jährigem krankheitsfreien Intervall

Summary We report the case of a 25-year old female patient, who presented with intrapulmonary metastases of a Wilms' tumor nine and a half year after initial therapy of a stage I tumor with surgery, local radiation and combined chemotherapy. In general, relapses of Wilms' tumor occur within two year after nephrectomy. Reccurences after more than 7 years are very rare. A relapse of a Wilms' tumor in an adult patient after more than 9 years is not yet published. We treated our patient according to the therapeutic procedure, which is recommended by the National Wilms' Tumor Study as curative treatment of relapses in childhood: complete resection of pulmonary metastases, irradiation of the whole lunge and repeatingly combined chemotherapy with actinomycin D and vincristin. The patient is doing well without evidence of tumor 13 months after thoractomy. A short review of the literature is given.

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Rezidiv eines Wilms' Tumors nach 9jährigem krankheitsfreien Intervall

Abkürzungsverzeichnis Gy Gray = 100 rad - NWTS National Wilms' Tumor Study     

Adult variant of congenital mesoblastic nephroma

Congenital mesoblastic nephroma is a relatively rare tumor predominantly of childhood. Occurrence in adults is exceedingly rare and, to my knowledge, only two cases have been reported to date. This article pertains to a mesoblastic nephroma in a 41-year-old woman. The tumor was composed mainly of compact fibrocollagenous elements interspersed with areas containing immature tubules and occasionally glomeruloid structures. There was no evidence of capsular or renal invasion or cytological malignant features. It has been postulated that this neoplasm may represent a form of mature Wilms' tumor with a benign clinical course.     

Genomic changes in the WT-gene (WT1) in Wilms' tumors and their correlation with histology.

The authors studied genomic changes in unilateral Wilms' tumors by using WT33, a candidate cDNA for the tumor, and their correlation with histology. By Southern blot analysis, three cases of genomic deletions of both alleles were found in 25 tumors. The three tumors that showed genomic deletions were histologically classified as triphasic nephroblastic Wilms' tumor and one of them was associated with intralobar nephroblastomatosis and a rhabdomyomatous component. In one case, the WT1 gene was totally deleted, in another case, the 3' region of the gene was partially deleted, and in the last one, the deletion of DNA was intragenic. This is the first report of a comparison of genomic alteration with histopathology. These findings show new aspects of the role of the WT1 gene in the development of Wilms' tumor.     

Unique insertional translocation in a childhood Wilms' tumor survivor detected when his daughter developed bilateral retinoblastoma

Retinoblastoma and Wilms' tumor are rare childhood embryonic tumors associated with loss or inactivation of tumor suppressor genes, RB1 located within 13q14, and WT1 located within 11p13. Interchromosomal insertional translocations occur rarely, and such rearrangements within RB1 or WT1, even rarer. We report a unique family in which an insertional translocation of a chromosomal segment that included band 13q14 inserted into 11p13 caused childhood Wilms' tumor in the father, and whose child developed bilateral retinoblastoma. This is the first case of an insertional translocation that caused both tumors. This insertional translocation had significant consequences for genetic counseling and in utero diagnosis. The estimated risk for an offspring of this father to develop Wilms' tumor is up to 50%, to develop retinoblastoma up to 25%, to have neither tumor 25%, and to have both tumors 0%.     

Genomic imprinting of human p57KIP2 and its reduced expression in Wilms' tumors

p57KIP2 is a potent tight-binding inhibitor of several G1 cyclin complexes, and is a negative regulator of cell proliferation. The gene encoding human p57KIP2 is located on chromosome 11p15.5, a region implicated in both sporadic cancers and Beckwith-Wiedemann syndrome (BWS), a cancer syndrome, making it a tumor suppressor candidate. Several types of childhood tumors including Wilms' tumor, adrenocortical carcinoma and rhabdomyosarcoma display a specific loss of maternal 11p15 alleles, suggesting that genomic imprinting plays an important part. Genetic analysis of the familial BWS has indicated maternal carriers and suggested a role in genomic imprinting. Previously, we demonstrated that p57KIP2 is imprinted in the mouse. Here we describe the genomic imprinting of human p57KIP2 and the reduction of its expression in Wilms' tumors. High resolution mapping locates p57KIP2 in the region responsible for both tumor suppressivity and BWS.      

On the nature and significance of nodular renal blastoma (author's transl)]

In nephrectomy specimens from a series of 24 Wilms' tumors three different types of neoplastic lesion were found in the uninvolved kidney parenchyma: nodular renal blastema, Wilms' tumorlet and metanephric hamartomas. The histologic features of the first two abnormalities are presented. They show the following characteristics: Being found in patients of younger age they occur mostly bilateral. In older children they are associated to Wilms' tumor. They are related, as this is the case with Wilms' tumors, to certain congenital malformation syndromes. Nodular blastema has been also observed in association with Wilms' tumor in siblings. These findings suggest a genetic relationship between nodular renal blastema-nephroblastomatosis complex and Wilms' tumor. Furthermore, such lesions may represent potential progenitor stages of most nephroblastomas. The clinical implications hereof are discussed.     

Cytological identification of metastatic epithelial nephroblastoma in pleural fluid: report of a case and review of literature

Nephroblastoma (Wilms' tumor) is the most common childhood renal tumor and usually presents with a histology and cytology consisting of blastemal, epithelial, and stromal cells. Effusions are not uncommon and may suggest an unfavorable prognosis when containing anaplastic tumor cells. In the present case, we report the cytological appearance of a Wilms' tumor metastatic to the pleura. The effusion consisted primarily of tumor cells demonstrating epithelial differentiation. The tumor cells mostly presented as three-dimensional aggregates in an inflammatory background. Many cystic and tubular structures were identified. The tumor cells demonstrated strong CD56 and WT1 immunoreactivity. The histology of a subsequent surgical specimen reflected the features seen in cytology.     

Aniridia and Wilms' tumor in a child constitutionally mosaic for 11p-;12q+: a new chromosomal change also present in Wilms' tumor cells of the blastema type

A child with congenital aniridia was assessed closely, by repeated abdominal ultrasound examinations, beginning at birth. The Wilms' tumor subsequently discovered and removed was analyzed karyotypically and found to have some cells with a terminal deletion of chromosome 11; in other cells this deletion was associated with a duplication in the long arm of chromosome 12. These findings were identical to those observed in the patient's peripheral blood mononuclear cells. This case further substantiates the association between changes in chromosome 11 and Wilms' tumor and demonstrates how chromosomal abnormalities in early infancy may lead to the development of Wilms' tumor.     

Blastemal cells of nephroblastomatosis complex share an onco-developmental antigen with embryonic kidney and Wilms'' tumor. An immunohistochemical study on polysialic acid distribution.

Previous investigations on polysialic acid of the neural cell adhesion molecule NCAM in human kidney have demonstrated its presence during nephrogenesis in embryonic kidney, absence in normal adult kidney, and reexpression in Wilms' tumor. These data showed that polysialic acid of NCAM is an onco-developmental antigen in human kidney and provided more direct evidence for the metanephric origin of Wilms' tumor. In the present study, five cases of Wilms' tumor associated with nephroblastomatosis complexes were immunohistochemically investigated with a monoclonal antibody for the presence of polysialic acid. Regardless of the type of nephroblastomatosis complex, ie, renal nodular blastema, simple tubular metanephric hamartoma, sclerosing metanephric hamartoma with adenoma, or incipient Wilms' tumor, immunoreactivity for polysialic acid was found in the blastemal cells, but was undetectable in all other structural elements. Because only blastemal cells exhibited a characteristic feature of embryonal differentiating metanephric derivatives, it appears that Wilms' tumor has its origin not exclusively in nodular renal blastema but rather in blastemal cells present in the various forms of nephroblastomatosis complex. The presence of polysialic acid of NCAM in blastemal cells in such lesions indicates that further events in addition to the expression of the embryonic form of this cell adhesion molecule may be involved in the pathogenesis of Wilms' tumor.     

Immunohistochemical localization of transport mediators in Wilms' tumor: comparison with fetal and mature human kidney

Immunostaining for Na+, K+-ATPase, carbonic anhydrase (CA) II, and band 3 anion channel glycoprotein was compared in developing and mature human kidneys and in Wilms' tumors. In fetal kidneys, ATPase first appeared in proximal and distal tubules. At birth an adult pattern was present with abundant enzyme in all segments of the distal tubule and lesser amounts in proximal and collecting tubules. CA II was detected in fetal kidneys first in proximal and then in distal tubules and eventually, as in the adult, throughout the nephron. Band 3 glycoprotein was not detected in fetal kidneys and only weak staining was present in the basolateral plasmalemma of intercalated cells in newborn and infant kidneys. The number of cells reactive for band 3 and the intensity of staining in a given cell increased to near adult levels at about 2 years. This finding may provide a partial explanation for the 'physiological acidosis' characterized by a low systemic pH in newborn and young infants. ATPase was present in basolateral membranes of most epithelial cells in nonanaplastic Wilms' tumors but was absent in the epithelial component of two anaplastic Wilms' tumors. CA II was detected only in a few epithelial cells in four tumors. Neoplastic epithelial cells reactive for CA II also stained for ATPase but not vice versa. Band 3 glycoprotein was not detected in any Wilms' tumor. These findings show that the immunohistochemical assessment of protein involved in electrolyte transport provides a further means for determining the relative level of differentiation of tumor cells of epithelial origin and suggest that these methods may be a valuable aid in determining the prognosis of some carcinomas.     

Loss of alleles at polymorphic loci on chromosome 2 in uveal melanoma

The loss of alleles at loci on specific chromosomes in some malignant tumors, such as retinoblastoma and Wilms' tumor, suggests that recessive mutations are important in their oncogenesis. We postulate that similar mechanisms may be involved in the formation of uveal melanomas. We studied alleles at autosomal loci in uveal melanoma cells and in the constitutional cells from 19 patients who developed the tumors. We observed loss of alleles only at loci on chromosome #2. This suggests that recessive alleles at some chromosome #2 locus may be important in the oncogenesis of uveal melanomas.     

Molecular mechanisms of oncogenesis

Cellular oncogenes (c-oncs) have been highly conserved throughout evolution and subserve important roles in growth and development. Both in development and the neoplastic state, c-oncs appear to collaborate rather than function independently. Cellular oncogenes are activated in the neoplastic process by four (nonviral) mechanisms; (a) chromosomal translocations; (b) gene amplifications; (c) point mutations; and (d) DNA rearrangements. The timing of c-onc gene product expression may be as important in oncogenesis as the level of expression. At this writing, mutant oncogenes have not been shown to be inherited. Oncogene amplification, if important in oncogenesis, is more likely to be involved with tumor progression rather than initiation. Chromosomal/molecular aberrations tend to be characteristic for a given type of cancer. These genetic alterations are often situated near heritable fragile sites, tumor-suppressor gene loci and/or oncogene loci. Similar molecular mechanisms involving translocations and inversions may underly the common T and B cell neoplasms. The loss/inactivation of both normal alleles at a locus thought to encode for tumor-suppressing activities (antioncogenes) may represent an event common to many childhood and adult neoplasms. The consistency and cell specificity with which this has been identified is consistent with a role for such genes in cellular differentiation. At this writing, the paradigm for such a controlling locus is 13q14, the site of the retinoblastoma gene. Based on recent studies in familial and sporadic Wilms' tumor which suggest etiological heterogeneity, theoretical modifications of the carcinogenesis model which has been central to understanding retinoblastoma may soon be forthcoming to explain molecular mechanisms operative in other cancer. The role of genomic imprinting in carcinogenesis is only recently being explored. Further study of this process may prove to be a fruitful area of future research.     

JUXTAGLOMERULAR CELL TUMOR

A left kidney tumor was found in a 33 years old female with diastolic hypertension and hyperreninemia. A yellowish white 6 × 4 cm tumor with capsule was located in the upper pole. Polygonal mesenchymal cells with Bowie-positive and rhomboid-shaped granules and occasional tubular component were identified. The diagnosis of J-G cell tumor was made. The first electron microscopic observation of the tubular epithelium showed immature features.50–100 A microfilaments in the epithelium were identical to those reported in epithelium of Wilms' tumor. The results support that the tubular component is a tumor constituent and that the case is a biphasic tumor. Biphasic pattern and clinical characteristics of reported J-G cell tumor with tubular component are those of mesoblastic nephroma and adult multllocular cystic nephroma. Therefore, J-G cell tumor with tubular component would have to be classified as a metanephric blastema origin tumor as like Wilms' tumor, mesoblastic nephroma, and multllocular cystic nephroma.     

Extrarenal Wilms' tumor in the adult patient. A case report and review of the world literature

A case of an extrarenal Wilms' tumor arising in the retroperitoneal region of a 49-year-old male is reported. A review of the world literature indicates that the incidence of the tumor arising in the extrarenal region is extremely rare. A total of 14 cases have previously been reported, but the number of cases that occurred in adult patients is only 2. The clinical and pathologic features are briefly discussed.