[Challenges in the research and diagnosis of rare diseases].

Abstract

Molecular methods have improved the diagnosis of many rare tumors but have also revealed their limitations. Gene fusions that originally appeared specific occur "promiscuously" in biologically distinct mesenchymal and epithelial tumors, underscoring the importance of integrated morphologic-molecular diagnostics. By contrast, similar tumor biology-which is difficult to prove in rare tumors-supports the concept of entity-defining gene fusions for a spectrum of morphologically diverse tumors. Still other rare tumors have no diagnostically or prognostically helpful molecular profile, and their rarity and lack of authentic tumor models are obstacles to the use of, for example, new single-cell-based molecular or AI-assisted morphological methods and preclinical functional analyses. These peculiarities of rare tumors are illustrated by thymic, testicular, salivary gland, and soft tissue neoplasms.