‘I Can’t Keep Up!’: an update on advances in soft tissue pathology occurring after the publication of the 2020 World Health Organization classification of soft tissue and bone tumours

Abstract

Progress in our understanding of the pathogenesis and diagnosis of soft tissue neoplasia is exceptionally rapid. Although the most recent World Health Organization classification of soft tissue tumours contains many new entities and refinements of older ones, even this comprehensive document is by now incomplete or in need of modification. This review will attempt to summarise the developments in soft tissue pathology that have occurred since 2020, emphasising lesions for which morphology and genetics intersect in a complementary fashion. Novel entities discussed include KMT2A-rearranged sarcoma, PRRX::NCOAx fibroblastic tumours, EWSR1::PATZ1 sarcomas, BRAF-altered infantile fibrosarcoma-like lesions, NUTM1-rearranged colorectal sarcomas, and a variety of interesting giant cell-rich and matrix-producing lesions. In addition, recently described mimics of atypical lipomatous tumour/welldifferentiated liposarcoma are covered, as is a wholly new, morphologically defined and genetically confirmed entity, pseudoendocrine sarcoma. Finally, exciting new developments in the use of immunohistochemistry as a surrogate for molecular genetic techniques are discussed.

Loss of Chromosome 3q Is a Prognostic Marker in Fusion-Negative Rhabdomyosarcoma

“…The first molecular tools for substratification of RMS came with the definition of the fusion of FOXO1 with PAX3 or PAX7 , which splits tumors into two major subtypes and roughly correlates with the histologic features: ERMS and alveolar RMS. 15 , 16 More recently, data suggest that some of the previously categorized ERMS tumors have a distinctive morphology composed of elongated spindle cells and often sclerotic stroma. The WHO classification since 2013 16 , 17 has classified these tumors as ssRMS with a subset of them carrying mutations in MYOD1 .…”

“… 15 , 16 More recently, data suggest that some of the previously categorized ERMS tumors have a distinctive morphology composed of elongated spindle cells and often sclerotic stroma. The WHO classification since 2013 16 , 17 has classified these tumors as ssRMS with a subset of them carrying mutations in MYOD1 .…”

New molecular entities of soft tissue and bone tumors

“…The fifth edition of the WHO Classification of Soft Tissue and Bone Tumors includes new entities in which molecular alterations have played an important role in their delineation, either to define or to support their diagnosis. New entities with distinct genetic findings are continuously being described, so it is anticipated that this trend will drive a further refinement in the next edition of the classification [45 ▪ ]. For instance, neoplasms defined by GLI1 alterations [46,47] or ‘pseudoendocrine sarcomas’ with recurrent CTNNB1 mutations [48] have recently been reported and further illustrate the dynamic field of molecular diagnostics and their significant role in the recognition of new entities.…”

Mesenchymal Tumors of the Gastrointestinal Tract—Beyond GIST—A Review

“…Rearrangements of are not limited to NUT carcinomas and have been described in poromas and porocarcinomas [143], embryonal tumors of the central nervous system [144], and undifferentiated sarcomas [145]. Sarcomas with NUTM1 rearrangements often show fusions involving the MAX family genes or CIC [146,147].…”

“…GIST, synovial sarcoma, sarcomatoid carcinomas, sarcomatoid mesothelioma, and rhabdoid tumors should be considered in the differential diagnosis. The expression of NUT or NUTM1 rearrangement is key for the diagnosis [146].…”