Soft tissue sarcomas: introduction to the Virchows Archiv review issue

Abstract

Soft tissue sarcomas constitute a heterogeneous category ofneoplasms composed mostly of uncommon tumours ofdifferent histology, different biology, and different outcome.Thirty years ago, the diagnosis of these neoplasms wasmainly based on morphology coupled with some classicalhistochemical stains such as periodic acid-Schiff, reticulin,and trichrome stains. In the last 15 years, thanks to thesubstantial development of immunohistochemistry, cytoge-netics and molecular genetic analysis significant improve-ments have been made regarding the classification anddiagnosis of these tumors, with direct implications forclinical management and prognosis [1, 2]. Many newentities were recognized of which desmoplastic small roundcell tumor and intimal sarcomas are examples. Othersarcoma entities gradually disappeared or lost in importance(e.g., the so-called malignant fibrous histiocytoma [3],hemangiopericytoma [4], and fibrosarcoma categories).During the same period of time, molecular ancillarytechniques (including a vast array of polymerase chainreaction-based techniques, fluorescence in situ hybridiza-tion (FISH), conventional and array-based comparativegenomic hybridization, expression arrays, direct genomesequencing, and DNA methylation analysis to name a few)allowed detailed analysis of these tumors and the resultingdata facilitated better understanding of their biology(Fig. 1). In addition, thanks to improvements in nucleicacid preservation and isolation, many molecular techniquesprovided new parameters important for diagnostics and/orprognosis and were modified to be applicable on formalin-fixed, paraffin-embedded material (e.g., FISH, polymerasechain reaction-based techniques). This is all condensed in asubstantial revision of the World Health Organizationclassification which combined histology with genetics [2].Methodological advances thus allowed better understandingof biology, within turn novel classifications based uponnew histogenetic concepts and robust diagnostic methods.This review issue focuses on the pathobiology of softtissue sarcomas. In the introductory paper, Bovee andHogendoorn introduced to the reader the most significantmolecular acquisitions that occurred in the domain ofsarcomas and their implications for the patient in terms ofdiagnosis, prognosis, and clinical management [5]. Thegenomic characteristics of soft tissue sarcomas are exposedin an article of Mertens and coworkers [6]. Here, theauthors discuss how the genomic characterization of softtissue sarcomas has not only provided cell biologists withdecisive information on the parts of the genome that mayharbor genes that are essential for tumor development, butalso given the clinicians involved in the management ofthese patients a valuable diagnostic tool. Beck et al. sharewith us the “state of the art” of gene expression profiling insoft tissue sarcomas and how this technique has led toadvancements in the understanding of sarcoma pathobiol-ogy, the identification of clinically useful biomarkers, andthe refinement of sarcoma classification schemes, withhopefully significant benefits to patients [7].There are two intriguing and highly relevant questions insarcoma pathobiology: the first one is “why do some peopledevelop sarcomas?” and the second is “from which cells dosarcomas develop?”. Recent studies in model systems as