Undifferentiated and dedifferentiated urological carcinomas: lessons learned from the recent developments

Area of Science:

• Pathology
• Oncology
• Genitourinary Cancer Research

Background:

• Neoplasms can lose differentiation, leading to dedifferentiated or undifferentiated carcinomas.
• This phenomenon is recognized in various organs but less defined in genitourinary cancers.
• These tumors are often misclassified as poorly differentiated or unclassified carcinomas.

Purpose of the Study:

• To review the morphological and molecular spectrum of dedifferentiated and undifferentiated genitourinary carcinomas.
• To highlight recent developments in understanding these challenging tumors.
• To emphasize the importance of accurate subtyping for patient management.

Main Methods:

• Review of existing literature on genitourinary carcinomas with loss of differentiation.
• Analysis of histological patterns and immunophenotypic features.
• Discussion of molecular genetic alterations associated with dedifferentiation.

Main Results:

• Dedifferentiation occurs in various renal cell carcinoma (RCC) subtypes, particularly those with specific genetic deficiencies (SDH-, FH-, PBRM1-).
• Histological patterns include spindle cells, giant cells, rhabdoid cells, and monomorphic cells, sometimes with mesenchymal components.
• Immunophenotype is often simple, with vimentin and variable keratin or EMA expression.

Conclusions:

• Accurate subtyping of undifferentiated/dedifferentiated genitourinary carcinomas is crucial and relies on comprehensive sampling.
• Immunohistochemistry and molecular studies are essential for distinguishing between urothelial and RCC origins, and for identifying specific RCC subtypes.
• Further research is needed to fully define the diagnostic and therapeutic landscape for these tumors.