Renal tumours of childhood are a very interesting group of tumours and recognition of their clinicopathological features and appropriate treatment represents a success story of paediatric oncology. However, apart from Wilms' tumour, they are very rare and an average paediatric pathologist is likely to see very few in his/her professional career, making the correct diagnosis difficult. Therefore, it is critical that these tumours are studied by a panel of pathologists who developed their expertise by studying a large number of cases in multicentre trials.

Renal tumours other than Wilms' tumours are infrequent in childhood. Wilms' tumours account for 6% to 7% of childhood cancer, whereas the remaining renal tumors account for less than 1%.

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The most common non-Wilms' tumors are clear cell sarcoma of the kidney, rhabdoid tumor of the kidney, renal cell carcinoma, mesoblastic nephroma, and multilocular cystic nephroma. Collectively, these tumours account for less than 10% of the primary renal neoplasms in childhood.

The survival of Wilms’ tumour has increased from 5% in 1900 to around 90% in 1990s. This has in part been achieved by cooperation between pathologists that has led to the recognition of new benign and malignant childhood renal tumours (mesoblastic nephroma, clear cell sarcoma, malignant rhabdoid tumour, nephrogenic adenofibroma etc).

Renal tumours of childhood have recently been reviewed.

Classification:

Mesoblastic Nephroma - i) classical ii) cellular: click

Wilms’ tumour (nephroblastoma):- i) without anaplasia ii) with anaplasia: click

- Nephrogenic rests: click

- Cystic partially differentiated nephroblastoma: click

Clear cell sarcoma of kidney (CCSK): click

Malignant rhabdoid tumour of kidney: click

Nephrogenic adenofibroma: click

Metanephric adenoma: click

Others:

Ossifying renal tumour of infancy ; Renal medullary cell carcinoma ;Renal cell carcinoma ; Angiomyolipoma ; PNET: click.

Other renal tumours in children:

Many other renal tumours occur less commonly in children.

Renal cell carcinoma-like areas are sometimes seen in Wilms’ tumours, but pure renal cell carcinoma may arise in the context of von Hippel Lindau syndrome or sporadically. (von Hippel Lindau disease ocular manifestation)

Renal medullary cell carcinoma is associated with sickle cell trait, and is an aggressive rumour of young adults.

Angiomyolipoma is easy to diagnose in the context of tuberous sclerosis, but may cause problems in small biopsies when it occurs in isolation. Extrarenal Angiomyolipoma

Some cases are composed exclusively of epithelioid smooth muscle cells and may closely simulate RCC.

Positive reactions for HMB45, desmin and muscle specific actin helps in difficult cases.

PNETof the kidney has only been recognized recently , with only a few cases described in the literature. Extraskeletal Ewing's Sarcoma / PNET.

PNET is rarely an organ based tumour, but presents more often in soft tissue (e.g. paraspinal, chest wall). However, it seems to have a predilection for the kidney where it affects older children than Wilms' tumour as well as adults.

The usual histological appearance is of nodules and sheets of monotonous small round cells and focal formation of rosettes.

Immunohistochemistry is positive for neuron specific enolase and CD99.

Published examples show t(11;22)(q24;q12) as in soft tissue PNETs.

The outlook is often poor with the tumours presenting at an advanced stage and showing a poor response to chemotherapy.

Visit: Immunohistochemistry and Molecular Biology of Wilms' Tumour and related lesions. ; Staging of Paediatric Renal Tumours.

Differential Diagnosis:

Although classical renal tumours of childhood pose few diagnostic difficulties, differential diagnosis may prove difficult in atypical cases.

Useful clues which are helpful in reaching the correct diagnosis include age, and unique histological and clinical features of certain tumours.

Many tumours occur in well defined age groups. Mesoblastic Nephroma is the most common tumour in a neonatal period, but it never occurs after 3 years of age. Similarly, rhabdoid tumour of kidney is usually diagnosed in the first 3 years of life, rarely up to 5 years, and is virtually never seen in older age groups. In contrast, anaplastic Wilms’ tumour has never been diagnosed in the first 6 months of life, is extremely uncommon up to first 2 years of life, but is far more common after the age of 5 years. Clear cell sarcoma of kidney is extremely rare under 6 months of age, its peak incidence is in the second to third year.

A Wilms' tumour is the only typical renal tumor of childhood which may be bilateral (in about 5% of cases) and multicentric. Other unique histological features of Wilms' tumour are the presence of nephrogenic rests , skeletal muscle, and fat. Genuine neoplastic tubules are characteristic, but also seen in metanephric tumours. Also, only Wilms’ tumour may be familial or associated with syndromes such as hemihypertrophy, Beckwith-Wiedemann syndrome (BWS), WAGR (Wilms tumour, Aniridia, Genitourinary abnormalities, mental Retardation) and Denys-Drash (DD) [glomerulopathy, male genital abnormalities] syndrome.

Pediatric renal masses: Wilms tumor and beyond.Radiographics. 2000 Nov-Dec;20(6):1585-603.

A variety of pediatric renal masses may be differentiated from Wilms tumor on the basis of their clinical and imaging features. Wilms tumor is distinguished by vascular invasion and displacement of structures and is bilateral in approximately 10% of cases. Nephroblastomatosis occurs most often in neonates and is characterized by multiple bilateral subcapsular masses, often associated with Wilms tumors. Renal cell carcinoma is unusual in children except in association with von Hippel-Lindau syndrome and typically occurs in the 2nd decade. Mesoblastic nephroma is the primary consideration in a neonate with a solid renal mass. Multilocular cystic renal tumor is suggested by a large mass with multiple cysts and little solid tissue. Clear cell sarcoma is distinguished by frequent skeletal metastases, and rhabdoid tumor is distinguished by its association with brain neoplasms. Angiomyolipoma frequently contains fat and is associated with tuberous sclerosis. Renal medullary carcinoma occurs in patients with sickle cell trait or hemoglobin SC disease and manifests as an infiltrative mass with metastases. Ossifying renal tumor of infancy is differentiated from mesoblastic nephroma by the presence of ossified elements. Metanephric adenoma lacks specific features but is always well defined. Renal lymphoma is characterized by multiple homogeneous masses, often with associated adenopathy.

Renal neoplasms of childhood.Radiol Clin North Am. 1997 Nov;35(6):1391-413.

Wilms' tumor is the most common childhood renal tumor. This article describes the epidemiology, histopathologic features, and clinical manifestations of Wilms' tumor along with the spectrum of imaging findings using different modalities. The distinguishing features of other renal tumors encountered in children, such as clear cell sarcoma, rhabdoid tumor, congenital mesoblastic nephroma, multilocular cystic renal tumor, renal cell carcinoma, and angiomyolipoma are also reviewed.

Pediatric renal tumors.Semin Surg Oncol. 1999 Mar;16(2):105-20.

A broad spectrum of renal tumors occurs in infants and children ranging from the benign cystic nephroma to the extremely aggressive malignant rhabdoid tumor of the kidney. A thorough understanding of these tumors is crucial to the optimal diagnosis and management of children with renal masses. The common renal tumors in infants and children are discussed and an orderly method for their evaluation is presented. Recent developments in the molecular biology of Wilms' tumor are outlined to provide insight into the origin of this tumor.

Drug resistance in renal tumors of childhood.Curr Pharm Biotechnol. 2007 Apr;8(2):99-104.

Renal cancers are as one of the most common drug resistant neoplasms affecting children and multidrug resistance (MDR) happened to be an important reason for the failure of chemotherapy in refractory cancers of childhood. MDR can be intrinsic or acquired, depending on the time of its occurrence, either at diagnosis or during chemotherapy. Renal cancers often have intrinsic form of MDR because of de novo expression of P-glycoprotein (P-gp) in renal cells. Molecular investigations on MDR during the past two decades have led to the isolation and characterization of genes coding for P-gp, multidrug resistance-associated protein (MRP), lung resistance-related protein (LRP), breast cancer resistance protein (BCRP/MXR), drug resistance-associated protein (DRP), and ATP-binding cassette protein (ABCP). Several molecular probes, primer pairs, and monoclonal antibodies have been developed over the years to quantify the regulation and expression of these drug resistance markers in tumor cells. Methodologies have also been standardized to estimate the gene amplification, mRNA and protein expression, and functionality of drug resistance proteins in clinical specimens from cancer patients. Because of the recent developments in microarray technology, DNA and protein arrays against drug resistant genes are available commercially now. This review includes techniques for detection and quantification of the expression and function of these drug resistance genes in childhood renal tumors. Since these markers have clinical significance, currently available technology warrants the application of these markers in clinical oncology. Moreover, the first, second and third generation drug resistance modifiers have been developed over the past several years for overcoming drug resistance problem in tumor cells. Unfortunately, these reversing agents are yet to be proved successful clinically. Since treatment protocols are usually adopted from adult tumor patients into childhood population, clinical trials with modifying agents are yet to be undertaken and/or concluded in pediatric renal cancer patients. More clinical studies may be required to analyze the genes involved in the MDR of childhood renal cancer patients and trials have to be undertaken to evaluate the efficacy of MDR modifying agents in them, at least in parallel with adult patients.

Classification of malignant pediatric renal tumors by gene expression.
Pediatr Blood Cancer. 2006 Jun;46(7):728-38.

BACKGROUND: The most common malignant renal tumors of childhood are Wilms tumor (WT), clear cell sarcoma of the kidney (CCSK), cellular mesoblastic nephroma (CMN), and rhabdoid tumor of the kidney (RTK). Because these tumors present significant diagnostic difficulties, the goal was to define diagnostically useful signatures based on gene expression. PROCEDURES: Gene expression analysis using oligonucleotide arrays was performed on a training set of 47 tumors (10 CCSKs, 9 CMNs, 8 RTKs, and 20 WTs). Classifiers were developed for each tumor type using variations of compound covariate class predictor. The classifiers were applied to an independent test set of 72 tumors (3 CMN, 7 CCSK, 4 RTK, and 58 WT). Central review diagnosis was utilized as the gold standard. Correlation with the institutional diagnosis and qualitative estimation of confidence levels at the time of central review were noted. RESULTS: Within the training set, classifiers resulted in no errors when >10 genes were utilized. Top genes in each classifier were verified using quantitative reverse transcription-polymerase chain reaction (RT-PCR). Applying the classifiers to the test set, 71 of 72 tumors were correctly classified with a confidence level of >99%. The exception was incorrectly classified by the gold standard. In comparison, by histopathology 31% of the non-WT were not accurately classified by the local institution, and 29% were classified with <95% confidence on central review. CONCLUSIONS: Classifiers based on gene expression provide diagnostic confidence and accuracy greater than that of pathologic analysis alone. Tumors that show ambiguous gene expression profiles are those that are also pathologically and molecularly ambiguous and merit further analysis.

Cytopathology of uncommon malignant renal neoplasms in the pediatric age group.Diagn Cytopathol. 2005 May;32(5):281-6.

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.

Fine needle aspiration cytology characteristics of renal tumors in children.Pathology. 1994 Oct;26(4):359-64.

The cytologic findings observed in fine needle aspiration (FNA) biopsy smears from 27 cases of renal tumors in children are reported. The aspirates were from 16 cases of classical Wilms' tumor (WT), one anaplastic WT, 2 clear cell sarcomas of the kidney (CCSK), 2 malignant rhabdoid tumors of the kidney (MRTK) and 6 congenital mesoblastic nephromas (CMNs). The stromal component was present in 16 of the 17 cases (94%) of WT, and the epithelial component in 13 of the cases (76%). Blastema was noted in all 17 cases of WTs. Necrosis was present in 11 (65%) of the smears from WTs. Other features identified include tubular and glomerular differentiation (6 cases), rosette formation (2 cases), striated muscle differentiation (one case) and anaplasia (one case). Smears from malignant rhabdoid tumors of the kidney (MRTK) tended to be very cellular, comprizing cells with prominent esinophilic nucleoli. Cells from clear cell sarcoma of the kidney (CCSK) were usually arranged in smaller discrete groups with fragile cytoplasm. In congenital mesoblastic nephroma (CMN), the cells tend to be spindly and very cohesive. A definite tumor type was able to be made on 25 of the 27 cases (93%) of renal tumors.

October 2007