Pediatric renal mesenchymal tumors

2023-02-21   Paola Dal Cin, PhD , Rita Alaggio, MD 

1.Brigham and Women's Hospital , Harvard Medical School, Boston , MA (USA)
2.IRCCS Ospedale Bambino Gesú , Roma (Italy)

Keywords
pediatric renal tumors, mesenchymal renal tumors

Classification

Definition

Mesenchymal tumors represent less than 9% of kidney tumors in children. Malignant tumors that typically arise in soft tissue are also being recognized with increasing frequency in the kidney. However, a few specific distinct entities have been identified only in kidney. 1 The clinical behavior varies from benign or locally aggressive lesions like mesoblastic nephroma to highly aggressive such as rhabdoid tumor and clear cell sarcoma of kidney. 2-4 The widespread use of cytogenetic and molecular techniques, including next generation sequencing (NGS), allows reliable diagnosis of most of these entities even based on small needle biopsy, and contributes to the identification of specifically activated pathways potentially targetable by new therapies. 5-8

Pediatric renal mesenchymal tumorsGenetic event(s)
Ossyfying renal tumor of infancy (ORTI)Trisomy 4 is the only recurrent genetic alteration, so far. 9,10
Congenital mesoblastic nephroma (CMN)Cryptic t(12;15)(p13;q25) /ETV6::NTRK3 fusion, with additional aberrations , almost exclusively in cellular type and in a subset of mixed subtype. 7,11-13 A single EML4::ALK gene fusion. 14
ETV6::NTRK3has been described in a increasing number of neoplasms 15. pan-Trk immunohistochemistry could detect ETV6::NTRK3 fusions as reliably as RT-PCR and FISH.16
Single cases NTRK1-3 and BRAF rearrangements 17-19 Larotrectinib is a highly selective TRK inhibitor with activity in adult and pediatric patients with NTRK 1-3 rearrangement tumors. 20
Recurrent EGFR activation and BRAF-IDT, in CMN negative by canonical ETV6::NTRK3 rearrangement. 18,19,21
Rhabdoid tumor of the kidnery Bi-allelic SMARCB1 inactivation at 22q11.2 results in a complete loss of function via a spectrum of events including,-22/22q- and mutations. 7,22 Rare cases have loss of SMARCA4 function , another SWI/SNF member, rather than SMARCB1. 23
An increasing number of SMARCB1 -deficient neoplasms outside of the rhabdoid tumors have been described. 23-25 
Rhabdoid tumor predisposition syndrome (RTPS): RTPS1 syndrome OMIM:609322 and RTPS2 syndrome OMIM:613325.26
Clear cell sarcoma of the kidney (CCSK)BCOR-internal tandem duplication (ITD) at exon 15 27-29 in the majority of the CCSK cases. BCOR-ITD is a common genetic alteration in a wide range of cancers.30,31
t(10;17)(q22;p13)/YWHAE::NUTM2B fusion in 12% of the cases.32
BCOR::CCNB3 fusion. 33-37
Single cases with t(2;13)(q13;q22), t(3:17) (q29;p11.2) 38 or RX2::TERT fusion.39
EGFR amplification, point mutation (T790M) 40 and EGFR-ITD .41

Article Bibliography

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4363267502023Pediatric renal tumor epidemiology: Global perspectives, progress, and challenges.Libes J et al
5177651932007Part II: Treatment of primary malignant non-Wilms' renal tumours in children.Ahmed HU et al
6318115522019Novel therapy for pediatric and adolescent kidney cancer.Walz AL et al
7331837282020Pediatric Renal Tumors: Updates in the Molecular Era.Treece AL et al
8335914022021Progress Update in Pediatric Renal Tumors.Jain J et al
9276339112016Ossifying renal tumor of infancy (ORIT): The clinicopathological and cytogenetic feature of two cases and literature review.Guan W et al
10229762872013Clonal trisomy 4 cells detected in the ossifying renal tumor of infancy: study of 3 cases.Liu J et al
1198113361998Congenital mesoblastic nephroma t(12;15) is associated with ETV6-NTRK3 gene fusion: cytogenetic and molecular relationship to congenital (infantile) fibrosarcoma.Rubin BP et al
12281244682017Congenital mesoblastic nephroma 50 years after its recognition: A narrative review.Gooskens SL et al
13292865632018ETV6-NTRK3 in congenital mesoblastic nephroma: A report of the SIOP/GPOH nephroblastoma study.Vokuhl C et al
14343782832021An unusual fusion gene EML4-ALK in a patient with congenital mesoblastic nephroma.Misove A et al
15314235582020Pan-Trk immunohistochemistry reliably identifies ETV6-NTRK3 fusion in secretory carcinoma of the salivary gland.Bell D et al
16314981782019Pan-TRK Immunohistochemistry: A Useful Diagnostic Adjunct For Secretory Carcinoma of the Breast.Harrison BT et al
17290995032018Recurrent EML4-NTRK3 fusions in infantile fibrosarcoma and congenital mesoblastic nephroma suggest a revised testing strategy.Church AJ et al
18299152642018Recurrent intragenic rearrangements of EGFR and BRAF in soft tissue tumors of infants.Wegert J et al
19325908842020Congenital mesoblastic nephroma is characterised by kinase mutations including EGFR internal tandem duplications, the ETV6-NTRK3 fusion, and the rare KLHL7-BRAF fusion.Zhao M et al
20298934562018Dramatic bone remodeling following larotrectinib administration for bone metastasis in a patient with TRK fusion congenital mesoblastic nephroma.Halalsheh H et al
21324901232020Recurrent EGFR alterations in NTRK3 fusion negative congenital mesoblastic nephroma.Lei L et al
22251691512014SWI/SNF chromatin remodeling complexes and cancer.Biegel JA et al
23292806802018SMARCB1-deficient Tumors of Childhood: A Practical Guide.Pawel BR et al
24281091762017Oncogenic roles of SMARCB1/INI1 and its deficient tumors.Kohashi K et al
25326466142021SWI/SNF complex-deficient soft tissue neoplasms: An update.Schaefer IM et al
26254944912015Rhabdoid tumor predisposition syndrome.Sredni ST et al
27260988672015Consistent in-frame internal tandem duplications of BCOR characterize clear cell sarcoma of the kidney.Ueno-Yokohata H et al
28265169302015Whole transcriptome sequencing identifies BCOR internal tandem duplication as a common feature of clear cell sarcoma of the kidney.Astolfi A et al
29265733252015Recurrent internal tandem duplications of BCOR in clear cell sarcoma of the kidney.Roy A et al
30311502812019BCOR involvement in cancer.Astolfi A et al
31337182452021Specific and Sensitive Diagnosis of BCOR-ITD in Various Cancers by Digital PCR.Barets D et al
32222943822012Characterization of the chromosomal translocation t(10;17)(q22;p13) in clear cell sarcoma of kidney.O'Meara E et al
33288174042017Primary Renal Sarcomas With BCOR-CCNB3 Gene Fusion: A Report of 2 Cases Showing Histologic Overlap With Clear Cell Sarcoma of Kidney, Suggesting Further Link Between BCOR-related Sarcomas of the Kidney and Soft Tissues.Argani P et al
34288333752018Clear cell sarcomas of the kidney are characterised by BCOR gene abnormalities, including exon 15 internal tandem duplications and BCOR-CCNB3 gene fusion.Wong MK et al
35318763612020BCOR-CCNB3 fusion-positive clear cell sarcoma of the kidney.Han H et al
36339095192021BCOR-CCNB3 Sarcoma with Prominent Rhabdoid Cells Mimicking Rhabdomyoblasts: Expanding the Morphologic spectrum of BCOR-CCNB3 Sarcoma.Cai Z et al
37345152512022Primary Renal BCOR-CCNB3 Fusion Sarcoma: A Case Report and Review of the Literature.Zhao M et al
38257515902015Novel Karyotypes and Cyclin D1 Immunoreactivity in Clear Cell Sarcoma of the Kidney.Jet Aw S et al
3925481751989Nutrient composition and protein quality of minor millets.Geervani P et al
40176462702007Multifaceted dysregulation of the epidermal growth factor receptor pathway in clear cell sarcoma of the kidney.Little SE et al
41284400182017Clear cell sarcoma of kidney involving a horseshoe kidney and harboring EGFR internal tandem duplication.Santiago T et al

Citation

Paola Dal Cin, PhD ; Rita Alaggio, MD

Pediatric renal mesenchymal tumors

Atlas Genet Cytogenet Oncol Haematol. 2023-02-21

Online version: http://atlasgeneticsoncology.org/solid-tumor/209013/pediatric-renal-mesenchymal-tumors