Paediatric renal tumors: An insight into molecular characteristics, histomorphology and syndromic association

Table 1 Molecular characteristics of paediatric renal tumors

Renal tumor	Molecular feature
Paediatric cystic nephroma	DICER1 mutation[12]
Metanephric adenoma	BRAFV600E mutation[25]; KANK1::NTRK3 gene fusion in BRAF negative cases[26]
Metanephric stromal tumor	BRAFV600E mutation[32]
Metanephric adenofibroma	BRAFV600E mutation[35]
Ossifying renal tumor of infancy	Clonal trisomy 4[39]
MN	(1) Cellular MN: t(12;15)(p13;q25) resulting in fusion of ETV6 and NTRK3 genes[45]; (2) Classic MN: EGFR ITD[47] (3) Mixed MN: Either EGFR ITD or ETV6::NTRK3 gene fusion[47]
Nephroblastoma (Wilms tumor)	Genetic changes in WT1, CTNNB1, IGF2, TP53, MYCN genes and 1q gain[56]
Malignant rhabdoid tumor of the kidney	Biallelic inactivation of SMARCB1/INI1[65]
Clear cell sarcoma of the kidney	(1) BCOR-ITD exon 15[74]; (2) YWHAE: NUTM2 gene fusion[76]; (3) BCOR::CCNB3 gene fusion[75]
Anaplastic sarcoma of the kidney	DICER 1 and RNAase IIIb mutation[82]
Renal Ewing sarcoma	(1) t(11;22)(q24;q12) resulting EWSR1-FLI1 fusion[89]; (2) t(21;22)(q22;q12) resulting in EWSR1-ERG fusion[90]
Renal cell carcinoma with MiT translocations	TFE3 rearranged RCCs-fusion of TFE3 with other genes like ASPL, PRCC, PSF, CLTC[93]; TFEB rearranged RCCs-MALAT1 (Alpha)::TFEB fusion[94]
ALK-rearranged renal cell carcinomas	VCL-ALK fusion[98]; TPM3-ALK fusion [97]; Rarely STRN-ALK, EML4-ALK, HOOK1-ALK fusions[96,99]
Eosinophilic solid and cystic renal cell carcinoma	Biallelic somatic mutations of TSC1 or TSC2 genes[106]
SMARCB1-deficient renal medullary carcinoma	Inactivation of SMARCB1 gene[112]

MN: Mesoblastic nephroma; ITD: Internal tandem duplication.

Table 2 Immunohistochemistry of paediatric renal tumors

Renal tumor	Immunohistochemistry expression
Paediatric cystic nephroma	ER positive[16]
Metanephric adenoma	WT1 and CD57 positive[24]
Metanephric stromal tumor	CD34 positive[29,31]
Metanephric adenofibroma	CD34 positive[33]
Ossifying renal tumor of infancy	EMA and Vimentin positive [38]
Nephroblastoma (Wilms tumor)	The blastemal component is WT1 and PAX8 positive; the epithelial component is cytokeratin and Epithelial Membrane Antigen and positive; stromal component is vimentin positive[2]
Malignant rhabdoid tumor of the kidney	SMARCB1/INI1 loss[64]
Clear cell sarcoma of the kidney	Cyclin D1 and BCOR positive[73]
Renal Ewing sarcoma	CD99 and NKX2-2 positive[87-88]
Renal cell carcinoma with MiT translocations	TFE3 positive[92]
ALK-rearranged renal cell carcinomas	ALK positive, INI1/SMARCB1 retained[97]
Eosinophilic solid and cystic renal cell carcinoma	CK20 and PAX8 positive whereas CK7 and C-kit negative[105]
SMARCB1-deficient renal medullary carcinoma	PAX8, Epithelial Membrane Antigen and vimentin positive [110]; SMARCB1/INI1 loss[111]

Table 3 Genetic syndromes associated with paediatric renal tumors

Genetic syndromes	Renal tumors	Extra renal manifestations	Ref.
DICER 1 syndrome	Wilms tumor, cystic nephroma, anaplastic sarcoma of kidney	Pinealoblastoma, pleuropulmonary blastoma	Caroleo et al[83]
WAGR syndrome	Wilms tumor	Aniridia, genitourinary anomaly, developmental delay	Hol et al[10]
Denys–Drash syndrome	Wilms tumor, rapid progressive nephropathy	Male pseudo-hermaphroditism	Kucinskas et al[9]
Beckwith–Wiedemann syndrome	Wilms tumor	Hepatoblastoma, neuroblastoma, hemihypertrophy, macroglossia, macrosomia, organomegaly, omphalocele	MacFarland et al[11]
Simpson-Golabi-Behmel Syndrome Type I	Wilms tumor	Hepatoblastoma, adrenal neuroblastoma, macrocephaly, cardiovascular and skeletal abnormalities, visceromegaly	Tenorio et al[57]
Rhabdoid tumor predisposition syndrome	Malignant rhabdoid tumor of the kidney	Malignant rhabdoid tumors at various sites like central nervous system, liver, bladder, mediastinum	Nemes et al[66]

Table 4 Modes of presentation of paediatric renal tumors

Renal tumor	Presentation
Paediatric cystic nephroma	Palpable abdominal lump[7]
Metanephric adenoma	Asymptomatic to symptomatic (fever, haematuria, abdominal pain and mass), polycythaemia[20]
Metanephric stromal tumor	Abdominal mass, extrarenal vasculopathy, such as bleeding and hypertension[29]
Metanephric adenofibroma	Haematuria and polycythaemia[34]
Ossifying renal tumor of infancy	Haematuria[37]
Mesoblastic nephroma	Abdominal mass[44]
Nephroblastoma (Wilms tumor)	Abdominal mass[54]
Malignant rhabdoid tumor of the kidney	Abdominal mass[63]
Clear cell sarcoma of the kidney	Abdominal mass[70]
Anaplastic sarcoma of the kidney	Large renal mass[79]
Renal Ewing sarcoma	Abdominal pain, mass, hematuria[85]
Renal cell carcinoma with MiT translocations	Asymptomatic to symptomatic abdominal pain and haematuria[92]
ALK-rearranged renal cell carcinomas	Haematuria, abdominal pain or periumbilical pain[96]
Eosinophilic solid and cystic renal cell carcinoma	Asymptomatic[103]
SMARCB1-deficient renal medullary carcinoma	Haematuria, flank or abdominal pain, dysuria, weight loss[107]