Bone metastasis of Wilms' tumor with monophasic epithelial histology in a young adult

A unique case of Wilms' tumor with monophasic epithelial histology in the bone metastasis at initial presentation in an 18-year-old Taiwanese girl is presented. Histologically, a purely differentiated epithelial component in the L1-3 vertebrae was noted, which is consistent with the epithelial component in primary Wilms' tumor of the kidney by both microscopy and immunohistochemistry. Hence, Wilms' tumor should be included in the differential diagnosis of a metastatic lesion presenting a purely epithelial histology in a young adult or a child.     

Aspiration cytology of Wilms' tumor: correlation of cytologic and histologic features

We examined the cytomorphologic features of fine-needle aspiration biopsy (FNAB) specimens from 23 Wilms' tumor patients. The findings were correlated with histopathologic patterns from these tumors. The study revealed a close resemblance between the cytologic and histopathologic appearance of various cellular elements in Wilms' tumors. The major cellular patterns seen in Wilms' tumor include blastemal cells, blastemal cells with epithelial differentiation, blastemal cells with tubular differentiation, and stromal elements. It is hoped that recognition of these cellular components in aspiration smears will be helpful in establishing an FNAB diagnosis of Wilms' tumor.     

Expression of insulin-like growth factor-II mRNA in fetal kidney and Wilms' tumor. An in situ hybridization study

The pattern of insulin-like growth factor II (IGF-II) mRNA expression in developing kidney and Wilms' tumor was examined with in situ hybridization. In developing kidney, IGF-II was primarily expressed in blastemal cells and lost with their differentiation. In triphasic Wilms' tumor, a similar relationship was found. But in a monomorphous Wilms', tumor cells with epithelial differentiation expressed IGF-II mRNA. These data suggest that IGF-II may be involved in fetal nephrogenesis, that its expression is inversely coupled to normal epithelial differentiation, and that this differentiation may be aberrantly regulated in Wilms' tumor.     

Biphasic intraabdominal desmoplastic small round cell tumor: Fine-needle aspiration cytology findings

The present report describes the case of a 9-yr-old boy with an abdominal desmoplastic small round cell tumor (DSRCT) which on fine-needle aspiration cytology and histology revealed a biphasic pattern, making initial diagnosis difficult. Epithelial-like clusters of cells and loosely-arranged poorly-differentiated cells with scant cytoplasm associated with cells having a larger nucleus and multinucleated larger cells represented the smears' counterpart of epithelial clusters and lobules and sarcomatous-like tissue recognized in the histologic sections. Multinucleated cells were common in the sarcomatous-like areas of the tumor. The biphasic pattern was highlighted by immunohistochemistry. Keratin and epithelial membrane antigen stained predominantly or only the epithelial component, while desmin diffusely decorated the sarcomatous areas and the epithelial cells as a paranuclear cytoplasmic dot. Immunosera 013 mainly stained the sarcomatous component. © 1995 Wiley-Liss, Inc.     

Wilms' tumor in the adult--report of a case and review of the literature

Wilms' tumor is rare in adults. Its histology, grading and staging are identical to those in children. Investigators agree on a combined modality approach in the treatment of adult Wilms' tumor (AWT), but differ on how aggressive it should be. Some advocate adopting the current pediatric protocols which take into account tumor stage and grade. Others recommend using advanced disease regimens for all stages and grades. We report on an 18 year-old male with stage IV favorable histology Wilms' tumor. The patient underwent radical nephrectomy and received postoperative radiotherapy with intensive four-drug chemotherapy. He had one relapse after 12 months which was successfully treated with chemotherapy and radiotherapy. He remains in remission without relapses 36 months after the initial diagnosis. The genetics of Wilms' tumor has been well studied in children but is practically unknown in adults; karyotype and molecular genetic studies in this case were normal.     

Clear cell sarcoma of the kidney. An immunohistochemical study

Three cases of clear cell sarcoma of the kidney (CCSK) and 5 cases of Wilms' tumor were investigated immunohistochemically to examine the expression of tissue-specific intermediate filaments (cytokeratin, vimentin, and desmin) and myoglobin. In CCSK, tumor cells were negative for cytokeratin, except for occasional tubular structures, and vimentin was demonstrated in only one case. In Wilms' tumor, epithelial components were positive for cytokeratin and stromal cells were positive for vimentin, while no staining was found in blastemal cells for either. Both desmin and myoglobin were negative in all tumor cells except for skeletal muscle cells in Wilms' tumor. In the current study, some neoplastic cells in CCSK were revealed to be of mesenchymal nature, but blastemal cells in Wilms' tumor were not.     

Cytomorphology and morphometry of small round-cell tumors in the region of the kidney

Small round-cell tumors (SRCTs), with malignant cell components measuring 10 m or less in diameter with scanty cytoplasm in alcohol-fixed smears, pose a diagnostic challenge at fine-needle aspiration cytology (FNAC), especially when they are situated in and around the kidney and need facilities such as electron microscopy, immunohistochemistry, tissue culture, and cytogenetics for their subtyping. A precise cytodiagnosis of SRCTs is important because a definite diagnosis is mandatory in preoperative diagnostic workup for presurgical chemotherapy in these cases. With this view in mind, an attempt has been made to diagnose SRCTs in the region of the kidney based on cytomorphology and morphometry alone so as to facilitate its diagnosis in a simple cytology laboratory of a developing country where facilities for auxiliary techniques are not easily available. Of 2,028 abdominal aspirates in a 12-yr period, 36 SRCTs were diagnosed in the region of the kidney by correlating with histology, radiology, and clinical features. The smears were studied for cellularity, morphology, pattern of cell arrangement, and smear background and morphometrically analyzed using an ocular micrometer. An aspirate with preponderant malignant round cells that were larger or double the size of red blood cells in air-dried smears or measured less than 10 micro in diameter in alcohol-fixed smears was considered as a small blue-cell tumor. Twenty-one were diagnosed as Wilms' tumor (WT), 10 were diagnosed as neuroblastoma (NB), 3 were ganglioneuroblastoma (GNB), 1 was a cellular congenital mesoblastic nephroma (CMN), and 1 was an adrenocortical carcinoma (ACC). Cell clusters with neuropil and cytoplasmic processes were diagnostic of NB, ganglion cells of GNB, and blastema with tubular differentiation in WT. Aspirates from CMN and ACC were considered as simulators/mimickers of SRCT because they had superficial resemblance to SRCT and their differentiating cytomorphological features observed at histology were too subtle to be noted at cytology. The latter were appreciated only on retrospective analysis after histological confirmation.Thus, morphometry in correlation with cytology, clinical history, physical findings, and radiological data is helpful in guided FNA for a definite diagnosis of SRCT in the region of the kidney. One needs to keep in mind the mimickers of small round-cell lesions at this anatomic site.     

CLEAR CELL SARCOMA OF THE KIDNEY An Immunohistochemical Study

Three cases of clear cell sarcoma of the kidney (CCSK) and 5 cases of Wilms' tumor were investigated immunohistochemically to examine the expression of tissue-specific intermediate filaments (cytokeratin, vimentin, and desmin) and myoglobin. In CCSK, tumor cells were negative for cytokeratin, except for occasional tubular structures, and vimentin was demonstrated in only one case. In Wilms' tumor, epithelial components were positive for cytokeratin and stromal cells were positive for vimentin, while no staining was found in blastemal cells for either. Both desmin and myoglobin were negative in all tumor cells except for skeletal muscle cells in Wilms' tumor. In the current study, some neoplastic cells in CCSK were revealed to be of mesenchymal nature, but blastemal cells in Wilms' tumor were not.     

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.     

Clear cell sarcoma of kidney: report of the first Malaysian case.

Clear cell sarcoma of kidney (CCSK) is a rare but distinct tumor of childhood frequently confused with Wilms' tumor (nephroblastoma). It has a characteristic histology, a marked predilection for metastasis to bone, and an aggressive clinical course with a high relapse rate in spite of surgical excision, chemotherapy and radiotherapy. We report the first histologically proven CCSK in a Malaysian patient. This was an 8-mth-old Malay boy who was clinically diagnosed to have stage I Wilms' tumor. Despite treatment, he developed multiple metastases 10 mths after initial presentation and died soon after. Emphasis is placed on recognizing this entity in view of (1) its naturally aggressive behaviour and (2) the prospect of improving prognosis with currently recommended intensified chemotherapeutic regimes. Its immunohistochemical profile of vimentin-positivity and negativity for epithelial membrane antigen, cytokeratin and Factor-8 related antigen is more in favour of a mesenchymal or glomerular origin than a tubular or vascular origin.     

Extrarenal Wilms' tumor: an analysis of four cases

During a review of Wilms' tumor, four located external to the kidney were identified. Patient age ranged from 7 months to 4 years; three were female. One neoplasm was located in the parametrial connective tissue to the left of the uterus; both kidneys were radiographically normal. Three neoplasms were located in the right retroperitoneum adherent to the surface of the ipsilateral kidney, but separated from the parenchyma by a thick fibrous capsule. Two were attached to the upper pole, while the third was attached to the midportion of the kidney. Radiologic studies showed displacement of all three kidneys, but intravenous pyelogram (IVP) revealed no calyceal distortion. All four neoplasms were favorable histology Wilms' tumor: one was monophasic epithelial type, one was monophasic blastemal type, and two had a mixture of stromal, epithelial, and blastemal tissue. No teratomatous elements were present. Immunoperoxidase staining for cytokeratin (AE-1, AE-3, CAM 5.2), vimentin, and epithelial membrane antigen (EMA) showed the strongest focal positive staining of tubular structures with CAM 5.2, and slight staining with EMA. Staining reaction to vimentin was variable, but negative in most areas. Three tumors extracted from paraffin were diploid by quantitative flow cytometric DNA analysis; in one case, flow cytometry could not be performed. Clinical follow-up from 2 years to 6 years showed all children to be alive without evidence of disease. Based on the similarity to conventional renal Wilms' tumor, these findings support the hypothesis of displaced mesonephric/metanephric rests for the origin of extrarenal Wilms' 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.     

The G401 cell line, utilized for studies of chromosomal changes in Wilms' tumor, is derived from a rhabdoid tumor of the kidney.

The histology, ultrastructure, and messenger RNA expression of heterotransplants derived from the G401 cell line (American Type Culture Collection) have been characterized by comparison with Wilms' and rhabdoid tumors of the kidney. This analysis illustrates that the properties of G401 heterotransplant were consistent with a rhabdoid phenotype rather than that of a Wilms' tumor. The G401 cell line has been utilized in recent experiments to demonstrate the central role of chromosome 11 in Wilms' tumor. However, the present results suggest that these experiments may be more relevant to define the involvement of chromosome 11 in rhabdoid tumor of the kidney, a malignancy distinct from Wilms' tumor. This is clinically relevant since the rhabdoid tumor of the kidney is very aggressive and associated with an extremely poor prognosis.     

Histochemical evidence for tubule segmentation in a case of Wilms' tumor

A lectin histochemical and immunohistochemical approach was used to compare the different histologic elements of an unusual case of Wilms' tumor with normal kidneys. This case was stained with ten lectin-horseradish peroxidase conjugates; immuno-stained for Tamm-Horsfall glycoprotein, epidermal keratin, and vimentin; and compared with 19 control kidneys. The morphologic and cytochemical properties of various tumor elements in this specimen served to identify them as tumor analogs of all segments of the normal kidney tubules except distal tubules. Evidence for Wilms' tumor differentiation is provided by this case, whose epithelium histochemically resembles normal human epithelial cells.     

Gain of 1q is associated with adverse outcome in favorable histology Wilms' tumors

Although several genes/genetic loci involved in the etiology of Wilms' tumor have been identified, little is known of the molecular changes associated with relapse. We therefore undertook an analysis by comparative genomic hybridization (CGH) of 58 tumor samples of favorable histology Wilms' tumor taken at initial diagnosis and/or relapse. Tumors with anaplastic histology were excluded as this is known to be associated with p53 mutation and a poor prognosis. A control group of 21 Wilms' tumors that did not relapse was also analyzed. The overall frequency of gains or losses of genetic material detected by CGH was similar in both groups (77% in relapsing tumors and 70% in the nonrelapse group) as was the median number of changes per tumor (relapse group: n = 4, range, 1 to 19; nonrelapse group: n = 3, range, 1 to 8). However, gain of 1q was significantly more frequent in the relapse series [27 of 46 (59%) versus 5 of 21 (24%), P: = 0.019]. In 12 matched tumor pairs, the CGH profiles, including 1q gain, were similar at diagnosis and relapse, with little evidence for further copy number changes being involved in clonal evolution. The results suggest that 1q gain at diagnosis could be used to identify patients with favorable histology Wilms' tumor at increased risk of relapse who might benefit from early treatment intensification.     

Pure cystic nephroblastoma of the ovary with a review of extrarenal Wilms' tumors

A second case of pure ovarian extrarenal Wilms' tumor (EWT) is presented. A clinical stage Ic tumor occurred in the right ovary of a 21-year-old female and corresponded to a 19-cm multilocular mass which histologically was a cystic, partially differentiated Wilms' tumor, closely resembling the highly differentiated metanephric adenoma. This pattern is reported for the first time in an ectopic location. At the interface between epithelial nests and ovarian tissue, plaques of alpha-inhibin positive cells were detected that corresponded to foci of peripheral stromal luteinization. Differential diagnosis with entities such as retiform Sertoli-Leydig cell tumors and with adenosarcoma should be made. The literature on EWT is also reviewed.     

Fine-needle aspiration cytology of epithelioid angiosarcoma: a diagnostic dilemma

A 28-year-old woman with a 2-yr history of unilateral chronic leg swelling, initially thought to be secondary to deep vein thrombosis, later thought to be due to congenital venous malformation, eventually developed a pelvic mass, which was biopsied by fine-needle aspiration. On the basis of cytologic features on smears, high-grade sarcoma was reported. The patient underwent surgery to resect the pelvic mass, which showed anastomosing vascular channels arising from external iliac vein in histology. However, the tumor cells unexpectedly showed strong and diffuse immunohistochemical expression of cytokeratin and epithelial membrane antigen. The case was sent for expert consultation, and the expert's opinion was epithelioid angiosarcoma. The expert's diagnosis was confirmed 2 yr later by local recurrence. The clinical presentation, cytology, histology, and immunohistochemistry of the current case and 15 other cases of epithelioid angiosarcoma found in the cytology literature are summarized. This case illustrates that morphology with clinicopathologic correlation tends to be a better guide than available special techniques.     

Adenomatoid tumor of the pancreas: a case report with comparison of histology and aspiration cytology.

We present a 58-year-old woman who presented with a 1.5-cm, hypodense lesion in the head of the pancreas. Endoscopic ultrasound-guided fine-needle aspiration yielded bland, monotonous cells with wispy cytoplasm, slightly granular chromatin, and small nucleoli. A presumptive diagnosis of a neuroendocrine lesion was rendered. Whipple procedure yielded a well-circumscribed, encapsulated lesion with dense, hyalinized stroma and a peripheral rim of lymphocytes. Spindled and epithelioid cells formed short tubules, cords, and nests. The neoplasm stained for CK 5/6, calretinin, vimentin, CD 99, pancytokeratin, and EMA, consistent with mesothelial origin. This characteristic histology and immunohistochemistry is consistent with an adenomatoid tumor. We believe we are the first to report this benign neoplasm in such an unusual location. Herein we address the diagnosis of adenomatoid tumor by histology, immunohistochemistry, and aspiration cytology. Our case is particularly unique in that the histology and cytology are compared and correlated.     

Expression and localization of HGF and met in Wilms' tumours.

A number of growth factors and cognate receptors that contribute to normal kidney development have been shown to play roles in the pathogenesis of Wilms' tumours. Expression of both hepatocyte growth factor (HGF) and its tyrosine kinase receptor met has been demonstrated in normal tissues and their neoplastic counterparts, implicating these factors in normal development and tumour progression. HGF and met expression has not been studied in Wilms' tumour. Since HGF and met function in a paracrine fashion by regulating tubulogenesis in normal kidney development, they could be involved in the pathogenesis of Wilms' tumour, in which tubular formation is dysplastic. In the present study, a series of ten homotypic (consisting of blastemal, epithelial, and stromal elements) and ten heterotypic (consisting of triphasic histology and a muscle component) Wilms' tumour cases were examined for expression of HGF and met, using in situ hybridization, immunohistochemistry, and western blot analysis. Relatively high met message and protein expression, compared with normal kidney, were evident in homotypic and heterotypic tumour blastemal, epithelial, and rhabdomyoblastic cells and a 145 kD met polypeptide was found in all tumours, with a few cases also expressing the 170 kD precursor form. No apparent alterations of the met receptor were observed. Similarly, HGF protein was also abundantly expressed in blastemal, epithelial, and rhabdomyoblastic cells of the homotypic and heterotypic Wilms' tumours and a 69 kD HGF polypeptide was demonstrated by western blot analysis. Immunohistochemistry for the Ki-67 proliferation marker indicated that the pattern of Ki-67 expression correlated with the HGF and met pattern of expression in both homotypic and heterotypic tumours. These results reveal, for the first time, significant co-expression of met/HGF in Wilms' tumours, with a correspondingly high proliferative index in the same cell groups.