Sarcomas, colloquially known as the forgotten cancers, are rare malignancies that account for less than 1% of all adult solid tumours. They provide a diagnostic challenge owing to both their rarity and wide diversity of histological subtypes. The heterogeneity in classification is accompanied by a broad range of diverse biological behaviour, from locally aggressive but non-metastasizing tumours (e.g. desmoid fibromatosis) to highly metastatic tumours (e.g. Ewing sarcoma). While some sarcomas are well-differentiated, up to 25% of tumours are unclassifiable and do not resemble normal tissues. In addition, benign neoplasms are much more common than malignant tumours.
Correct diagnosis is invaluable in distinguishing between benign and malignant tumours, for distinguishing between different histological subtypes, for predicting prognosis, and directing appropriate therapeutic treatment. Diagnoses, however, may prove challenging, and pathologists need access to a complete diagnostic toolbox to aid them in providing an accurate diagnosis.
Diagnostic information may initially be obtained from gross examination of the tumour specimen sent to the laboratory. After sectioning, tissue architecture and cellular features can be viewed using hematoxylin and eosin (H&E) staining, and a differential diagnosis can be made. Ancillary testing is then used to confirm the most likely diagnosis. This includes the use of immunohistochemical stains, as well as molecular testing such as cytogenetics and karyotyping, fluorescence in situ hybridisation (FISH), polymerase chain reaction (PCR) and next-generation sequencing (NGS).
|Next Generation Sequencing||SureSelect hybrid-capture technology (Custom NGS designs)||Agilent|
|SureSelect All-in-One Solid Tumour Assay (Off-the-shelf)||Agilent|
|ArcherDx FusionPlex Sarcoma kit (RNA-based)||ArcherDx|
|Alissa Interpret Software (Clinical Interpretation tool)||Agilent|
|Fluorescence in situ hybridication (FISH)||SureFISH (ROS1 and ALK); custom ISH probes||Agilent|
|Hematoloxylin and Eosin (H&E) Stains||Dako Hematoxylin and Eosin||Agilent|
|Array based techniques||SurePrint G3 Human Gene Expression Microarrays||Agilent|
|Cancer Research CGH +/SNP microarrays||Agilent|
|Immunohistochemistry (IHC)||CD99 (Ewing’s sarcoma)|
Actin (leiomyosarcoma and rhabdomyosarcoma)
CD31 (hemangiosarcoma, Kaposi sarcoma, angiosarcomas)
CD68 (histiocytic sarcoma)
Smooth muscle actin (leiomyosarcoma)
Von Willebrand factor (angiosarcoma)
|Control Tissue||Multi-control block for ROS1, for use in IHC and FISH||HistoCyte|
- Demicco, E.G. & Lazar, A.J. The Current State of Molecular Pathology in Diagnosing Sarcomas. http://sarcomahelp.org/articles/molecular-pathology-sarcoma.html (accessed 23 June 2020)
- Schaefer, I-M., Cote, G.M., Hornick, J.L. (2018). Contemporary Sarcoma Diagnosis, Genetics, and Genomics. J Clin Oncol 36. DOI: 10.1200/JCO.2017.74.9374