Sarcomas are malignant tumors that arise in the bone and soft tissue. With numerous subtypes of sarcoma that can have overlapping histological, immunophenotypic, and clinical features, diagnosis can be extremely challenging. This challenge increases when rare subtypes are encountered for which most pathologists will have little experience. Using only histological and immunophenotypic features can lead to a high rate of inaccurate diagnoses. Published data indicates a substantial number of patients have discordant diagnoses between referring institutions and specialty centers. Supplementing the histologic diagnosis with genetic testing can improve diagnostic accuracy and overall patient management.
By the Numbers
sarcoma types assessed
fusion variants detected
Genetic fusions have been described in an increasing number of sarcoma types, making comprehensive testing a valuable diagnostic tool. In order to aid in the diagnosis for a wide range of tumors, our next-generation sequencing panel includes fusions in 138 individual genes. This analysis covers fusions described in 39 types of soft tissue, bone, and other mesenchymal tumors. Because fusion events can occur between known or novel gene partners, our next-generation sequencing panel (Mayo ID: SARCP) is designed to provide the most comprehensive analysis by including 138 genes, 124 gene fusion pairs, 274 fusion variants, and novel gene partner detection.
In cases where comprehensive NGS analysis cannot be performed or the diagnosis is highly suspect, we also offer a variety of single-gene fluorescence in situ hybridization (FISH) tests to identify common genetic rearrangements in the genes EWSR1, USP6, TFE3, PDGFB, SS18, SYT, FUS, DDIT3, CHOP, FOXO1, FKHR, NR4A3, ETV6, ALK, and others.
In some cases, the genetic abnormality may be something other than a fusion, and testing is available to support these cases. One such abnormality is the ring and giant rod chromosomes derived from amplified sequences of chromosome bands 12q13-15, which include several amplified genes such as MDM2, CPM, CDK4, and TSPAN31. This analysis is specifically useful in diagnosing well-differentiated liposarcomas and may be useful in a small subset of low-grade osteosarcomas.
Point mutations and small insertions and deletions may also arise in some types of sarcomas. Desmoid-type fibromatosis is challenging to diagnosis histologically, but identification of mutations in CTNNB1 (also known as BCAT) can greatly improve the diagnostic accuracy. CTNNB1 mutations are also indicative of a higher recurrence rate, making this an important prognostic marker.
Gastrointestinal stromal tumors (GIST) are one of the few sarcomas characterized by mutations, with 85-90% harboring mutations in the KIT or PDGFRA genes. Next-generation sequencing analysis can simultaneously analyze these genes to aid in the diagnosis and selection of therapy in cases of GIST.
Overall, sarcomas represent a small percentage of surgical pathology cases, with some entities being quite rare. For cases needing an added level of support, our second-opinion pathology consultations are conducted by a team of pathologists who are experts in bone and soft tissue pathology. As a referral practice, our five bone and soft tissue pathologists review more than 3,000 cases every year, including rare subtypes and complex cases. Our pathologists will provide a thorough review of the case information, including a review of radiological images and any other materials sent with the case, determine what ancillary IHC or genetic testing is needed, and provide a comprehensive, integrated report.
PATHC | Pathology Consultation