Histologic and Genetic Advances in Refining the Diagnosis of “Undifferentiated Pleomorphic Sarcoma”

Abstract

Undifferentiated pleomorphic sarcoma (UPS) is an inclusive term used for sarcomas that defy formal sub-classification. The frequency with which this diagnosis is assigned has decreased in the last twenty years. This is because when implemented, careful histologic assessment, immunohistochemistry, and ultra-structural evaluation can often determine lineage of differentiation. Further attrition in the diagnostic frequency of UPS may arise by using array-comparative genomic hybridization. Gene expression arrays are also of potential use as they permit hierarchical gene clustering. Appraisal of the literature is difficult due to a historical perspective in which specific molecular diagnostic methods were previously unavailable. The American Joint Committee on Cancer (AJCC) classification has changed with different inclusion criteria. Taxonomy challenges also exist with the older term “malignant fibrous histiocytoma” being replaced by “UPS”. In 2010 an analysis of multiple sarcoma expression databases using a 170-gene predictor, re-classified most MFH and “not-otherwise-specified” (NOS) tumors as liposarcomas, leiomyosarcomas or fibrosarcomas. Interestingly, some of the classifier genes are potential molecular therapeutic targets including Insulin-like growth factor 1 (IGF-1), Peroxisome proliferator-activated receptor γ (PPARγ), Nerve growth factor β (NGF β) and Fibroblast growth factor receptor (FGFR).

Deregulation of the Hippo pathway in soft-tissue sarcoma promotes FOXM1 expression and tumorigenesis

“…), which are associated with specific chromosomal translocations (2). A paucity of knowledge regarding the cellular and molecular mechanisms underlying human UPS makes targeted therapeutic intervention difficult (1,3). Metastasis in UPS patients likely occurs downstream of excessive primary tumor growth, resulting in a hypoxic microenvironment that promotes tumor cell dissemination (4).…”

Orbital Rhabdomyosarcoma with a good life prognosis after surgical treatment in a 14-year-old patient

“…Malignant fibrous histiocytoma (MFA) was considered the most soft tissue sarcoma in adults [13]. Nowadays this term has been supplanted by undifferentiated pleiomorphic sarcoma (UPS) [14].…”

“…Further in the diagnosis, frequency of UPS may arise by using array-comparative genomic hybridization [Kelleher]. Rhabdomyosarcomas are categorized in the second molecular subclasses of sarcoma, which have numerous non-reccurent chromosomal alterations leading to complex Karotypes [13].…”

“…In 2010, a different classification for sarcoma was introduced based on clinical, pathological and molecular features [13]. Regarding this classification, rhabdomyosarcoma is included in the pleiomorphic sarcoma category with complex karyotypes and gene expression profiles.…”

“…Regarding this classification, rhabdomyosarcoma is included in the pleiomorphic sarcoma category with complex karyotypes and gene expression profiles. There are studies [13] which showed that the spindle and pleiomorphic sarcomas were found to have a similar gene expression profiles compared to the other tumors (normal cell liposarcoma, etc).…”