Pediatric molecularly defined renal tumors
2024-10-08 Paola Dal Cin, PhD Affiliation1.Brigham and Women's Hospital , Harvard Medical School, Boston , MA (USA)
Classification
Definition
Pediatric non -nephroblastoma/Wilms renal tumors, are a heterogeneous group of neoplasms, mainly renal cell carcinomas (RCCs). Many of these tumors have been previously misdiagnosed or diagnosed as other RCC subtypes or reported as an unclassified RCC. However, they still represent the second most common renal cancer in children and adolescents, after nephroblastoma/WT. Most cases are fusions involving genes in the MiT family of transcription factors e.g. TFE3 and TFEB. ALK-fusion RCCs have been also reported in children with or without sickle cell trait. 1 Loss of SMARCB1 is driving renal medullary carcinoma, a rare and aggressive renal malignancy that has been associated with sickle hemoglobinopathies with African ancestry. 2 There is appears to be an unusual tendency for patients with a history of childhood cancer (especially neuroblastoma) to develop eosinophilic solid and cystic (ESC) RCCs with TSC1/TSC2 mutations. 3
The expansion of knowledge regarding driver genetic alterations for pediatric renal tumors opens new possibilities for correct diagnosis, to potential targetable therapy and/or genetic testing of patients and family members for familial syndromes in a subset of cases. 4,5 See also details in the WHO 2022 Urinary and Male Genital Tumours.
| Pediatric molecularly defined renal tumors | Genetic marker(s) |
|---|---|
| Renal cell carcinoma with MiT translocations | Translocations including transcription factor E3 TFE3 or transcription factor EB TFEB,members of the microphthalmia transcription factor (MiT) family. TFE3 rearrangement is the most common one , with severall differnt partners genes, been the most frequent frequent ASPSCR1 and PRCC. A less common, but well-characterized fusion is MALAT1::TFEB/t(6;11)(p21;q12), affecting generally young parients. 1,6 Both TFE3 and TFEB morphology features may overlap significantly with other categories of renal cell carcinoma. In practice, breakapart FISH has higher sensitivity and specificity for detecting TFE3 translocations than TFE3 immunohistochemical staining. However, NGS-based fusion analysis may be considered to identify uncommon and technically challenging cryptic TFE3 rearrangement by the standard FISH break-apart probes.7 Translocations involving MiT family genes also are found in other tumor types. 6 |
| ALK-rearranged renal cell carcinoma | Either VCL::ALK fusion in patients all with sickle cell trait or ALK rearrangement with different partner gene in patients without sickle cell trait . 8,9 Initial ALK immunohistochemistry, folllow by ALK rearrangement by FISH /next negeration sequecing analyses, is the quick method to recognize these rare renal tumors , due to the availability of targeted therapy with ALK inhibitors. 10 |
| Eosinophilic solid and cystic renal cell carcinoma | Very rare in chlidren, but NGS sequencing showed TSC2 mutation. 11 There appears to be an unusual tendency for patients with a history of childhood cancer (especially neuroblastoma) and TSC1/TSC2 mutation. 3 |
| SMARCB1-deficient renal medullary carcinoma | It is a rare and agressive renal carcinoma which occurs primarily in adolescents/ young adults with sickle cell trait or sickle cell disease with African ancestry. Biallelic inactivation of SMARCB1 occurs in a large majority of cases either via concurrent hemizygous loss and translocation disrupting SMARCB1 or by homozygous loss.2 |
Article Bibliography
| Reference Number | Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|---|
| 1 | 34704642 | 2022 | Translocation carcinomas of the kidney. | Argani P et al |
| 2 | 35806102 | 2022 | Recent Advances in Renal Medullary Carcinoma. | Su Y et al |
| 3 | 37522346 | 2023 | "Oncocytoid Renal Cell Carcinomas After Neuroblastoma" Represent TSC -mutated Eosinophilic Solid and Cystic Renal Cell Carcinomas : Association With Prior Childhood Malignancy and Multifocality With Therapeutic Implications. | Argani P et al |
| 4 | 35238063 | 2022 | Renal cell carcinoma in children and adolescents: a retrospective study of a French-Italian series of 93 cases. | Denize T et al |
| 5 | 36592003 | 2023 | Tumor biology, biomarkers, and liquid biopsy in pediatric renal tumors. | Walz AL et al |
| 6 | 35107169 | 2022 | A review of neoplasms with MITF/MiT family translocations. | Wei S et al |
| 7 | 33460450 | 2021 | Characteristics and outcome of pediatric renal cell carcinoma patients registered in the International Society of Pediatric Oncology (SIOP) 93-01, 2001 and UK-IMPORT database: A report of the SIOP-Renal Tumor Study Group. | van der Beek JN et al |
| 8 | 26773439 | 2016 | ALK-rearranged renal cell carcinomas in children. | Cajaiba MM et al |
| 9 | 33729862 | 2021 | ALK-rearranged Renal Cell Carcinoma (RCC): A Report of 2 Cases and Review of the Literature Emphasizing the Distinction Between VCL-ALK and Non-VCL-ALK RCC. | Wangsiricharoen S et al |
| 10 | 21213368 | 2011 | ALK rearrangement in sickle cell trait-associated renal medullary carcinoma. | Mariño-Enríquez A et al |
| 11 | 32610380 | 2020 | [Eosinophilic solid and cystic renal cell carcinoma with TSC2 gene mutations in children]. | Yang WP et al |
Citation
Paola Dal Cin, PhD
Pediatric molecularly defined renal tumors
Atlas Genet Cytogenet Oncol Haematol. 2024-10-08
Online version: http://atlasgeneticsoncology.org/solid-tumor/209273/pediatric-molecularly-defined-renal-tumors
