Renal Cell Carcinoma Associated With TSC/MTOR Genomic Alterations: An Update on its Expanding Spectrum and an Approach to Clinicopathologic Work-up.
Adv Anat Pathol
; 31(2): 105-117, 2024 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-37899532
ABSTRACT
Renal cell carcinoma (RCC) with tuberous sclerosis complex (TSC)/mammalian target of rapamycin (MTOR) pathway-related genomic alterations have been classically described in hereditary TSC syndrome setting involving germline mutations, whereby cells with a bi-allelic inactivation of genes originate tumors in a classic tumor-suppressor "two-hit" Knudson paradigm. Initial studies of TSC-associated RCC categorized tumors into 3 broad heterogeneous morphologic groups RCC with smooth muscle stroma, chromophobe-like, and eosinophilic-macrocytic. Recently, a similar morphologic spectrum has been increasingly recognized in novel and emerging entities characterized by somatic mutations in the TSC1/2 and MTOR in patients who do not suffer from the TSC. Correct recognition of RCC with TSC / MTOR mutations is critical for accurate prognostication because such tumors with aggressive behavior have the potential to be tailored to mTOR inhibitors. Whether TSC/MTOR mutated renal epithelial neoplasms represent a distinct molecular class has been confounded by the fact that TSC1/2 , and the gene encoding the downstream protein MTOR, are mutated secondarily in â¼5% of the more common subtypes of RCC, including the commonest subtype of clear cell RCC. This review summarizes the expanding morphologic spectrum of renal tumors with TSC/mTOR pathway alterations, specifically for sporadically occurring tumors where these genomic alterations likely are primary pathologic events. Finally, a practical surgical pathology approach to handling these tumors, and a conceptual framework of renal epithelial tumors with TSC/MTOR mutations as a "family of tumors", is presented.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Esclerose Tuberosa
/
Carcinoma de Células Renais
/
Neoplasias Renais
Limite:
Humans
Idioma:
En
Revista:
Adv Anat Pathol
Assunto da revista:
ANATOMIA
/
PATOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article