Modern criteria for assessing the therapeutic pathomorphosis of synovial sarcoma: clinical significance and outcome prediction

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Abstract

Synovial sarcoma is a rare malignant soft tissue tumor characterized by high aggressiveness and a propensity for metastasis. The assessment of therapeutic pathomorphosis plays a crucial role in predicting disease outcomes and selecting the optimal treatment strategy. This article discusses the morphological and molecular characteristics of synovial sarcoma, existing classifications of pathomorphosis, modern assessment methods, and the prognostic significance of pathomorphosis degree. 
Special attention is given to the impact of various factors on treatment efficacy, the prospects of personalized medicine, and the integration of innovative technologies in the diagnosis and management of this tumor.

About the authors

D. R. Makhachev

N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia

Author for correspondence.
Email: dalgat2002@mail.ru
ORCID iD: 0009-0007-0930-5272

1 Ostrovityanova St., Moscow 117513,

Russian Federation

D. V. Bulanov

N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia

ORCID iD: 0009-0005-3772-6643

1 Ostrovityanova St., Moscow 117513,

Russian Federation

D. M. Ametov

N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia

ORCID iD: 0009-0009-4294-8557

1 Ostrovityanova St., Moscow 117513,

Russian Federation

M. O. Abakarov

N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia

ORCID iD: 0009-0002-3305-7903

1 Ostrovityanova St., Moscow 117513,

Russian Federation

A. R. Abacharaeva

N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia

ORCID iD: 0009-0003-9353-5150

1 Ostrovityanova St., Moscow 117513,

Russian Federation

P. A. Bagandova

N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia

ORCID iD: 0009-0000-5790-2062

1 Ostrovityanova St., Moscow 117513,

Russian Federation

R. M. Gabibullaev

N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia

ORCID iD: 0009-0007-4725-8307

1 Ostrovityanova St., Moscow 117513,

Russian Federation

A. D. Dzhanboriev

N.N. Burdenko Voronezh State Medical University, Ministry of Health of Russia

ORCID iD: 0009-0009-6778-0519

10 Studencheskaya St., Voronezh 394036

Russian Federation

References

  1. Gazendam A.M., Popovic S., Munir S. et al. Synovial sarcoma: a clinical review. Curr Oncol 2021;28(3):177. doi: 10.3390/curroncol28030177
  2. Lesovaya E.A., Fetisov T.I., Bokhyan B.Y. et al. Genetic and molecular heterogeneity of synovial sarcoma and associated challenges in therapy. Cells 2024;13(20):1695. doi: 10.3390/cells13201695
  3. Qiu H., Tang Z., Nie D. Primary renal synovial sarcomas diagnosed by a novel fusion gene. Oncologie 2024;26(1):679–85. doi: 10.1515/oncologie-2024-0101
  4. Landuzzi L., Manara M.C., Pazzaglia L. et al. Innovative breakthroughs for the treatment of advanced and metastatic synovial sarcoma. Cancers (Basel) 2023;15(15):3887. doi: 10.3390/cancers15153887
  5. Righi A., Gambarotti M., Benini S. et al. Primary synovial sarcoma of bone: a retrospective analysis of 25 patients. Histopathology 2022; 81(6):912–21. doi: 10.1111/his.14602
  6. Tay T.K.Y., Sukma N.B., Lim T.H. et al. Correlating SS18-SSX immunohistochemistry with SS18 FISH in synovial sarcomas. Virchows Arch 2021;479(4):785–93. doi: 10.1007/s00428-021-03135-0
  7. Fiore M., Sambri A., Spinnato P. et al. The biology of synovial sarcoma: state-of-the-art and future perspectives. Curr Treat Options Oncol 2021;22(12):109. doi: 10.1007/s11864-021-00914-4
  8. Murphey M.D., Gibson M.S., Jennings B.T. et al. From the archives of the AFIP: Imaging of synovial sarcoma with radiologic-pathologic correlation. Radiographics 2006;26(5):1543–65. doi: 10.1148/rg.265065084
  9. Kadam S.S., Kadam T. Primary gastric synovial sarcoma in a young male: a rare case report and review of literature. Indian J Surg Oncol 2023;14(3):690–3. doi: 10.1007/s13193-023-01738-4
  10. Folpe A.L., Schmidt R.A., Chapman D., Gown A.M. Poorly differentiated synovial sarcoma: immunohistochemical distinction from primitive neuroectodermal tumors and high-grade malignant peripheral nerve sheath tumors. Am J Surg Pathol 1998;22(6):673–82. doi: 10.1097/00000478-199806000-00004
  11. Baranov E., McBride M.J., Bellizzi A.M. et al. A novel SS18-SSX fusion-specific antibody for the diagnosis of synovial sarcoma. Am J Surg Pathol 2020;44(7):922–33. doi: 10.1097/PAS.0000000000001447
  12. Henderson D.W., Reid G., Kao S.C. et al. Challenges and controversies in the diagnosis of malignant mesothelioma: part 2. Malignant mesothelioma subtypes, pleural synovial sarcoma, and other tumors. J Clin Pathol 2013;66(10):818–23. doi: 10.1136/jclinpath-2013-201609
  13. Thoenen E., Curl A., Iwakuma T. TP53 in bone and soft tissue sarcomas. Pharmacol Ther 2019;202:149–64. doi: 10.1016/j.pharmthera.2019.06.010
  14. Hirakawa N., Naka T., Yamamoto I. et al. Overexpression of bcl-2 protein in synovial sarcoma: a comparative study of other soft tissue spindle cell sarcomas and an additional analysis by fluorescence in situ hybridization. Hum Pathol 1996;27(10):1060–5. doi: 10.1016/s0046-8177(96)90284-1
  15. Feng Q., Guo P., Wang J. et al. High expression of SDF-1 and VEGF is associated with poor prognosis in patients with synovial sarcomas. Exp Ther Med 2018;15(3):2597–603. doi: 10.3892/etm.2018.5684
  16. El Beaino M., Jupiter D.C., Assi T. et al. Diagnostic value of TLE1 in synovial sarcoma: a systematic review and meta-analysis. Sarcoma 2020;2020:7192347. doi: 10.1155/2020/7192347
  17. Thway K., Fisher C. Synovial sarcoma: defining features and diagnostic evolution. Ann Diagn Pathol 2014;18(6):369–80. doi: 10.1016/j.anndiagpath.2014.09.002
  18. Machen S.C., Gautam P., Tubbs R.R., Goldblum J.R. Utility of cytokeratin subsets for distinguishing poorly differentiated synovial sarcoma from peripheral primitive neuroectodermal tumour. Histopathology 1998;33(6):501–7. doi: 10.1046/j.1365-2559.1998.00562.x
  19. Nassif E.F., Auclin E., Bahleda R. et al. TP53 Mutation as a prognostic and predictive marker in sarcoma: pooled analysis of MOSCATO and ProfiLER precision medicine trials. Cancers 2021;13(13):3362. doi: 10.3390/cancers13133362
  20. Mancarella C., Morrione A., Scotlandi K. Unraveling the IGF system interactome in sarcomas exploits novel therapeutic options. Cells 2021;10(8):2075. doi: 10.3390/cells10082075
  21. Krasny L., Arthur A., Guljar N. et al. Characterisation of a novel cell line (ICR-SS-1) established from a patient-derived xenograft of synovial sarcoma. Cells 2022;11(15):2418. doi: 10.3390/cells11152418
  22. Roy P., Biswal R., Honap S.N., Thambudorai R. et al. A re-look at the modified Ryan regression scoring system in esophageal cancer — validation of prognostic significance and comparison with other less commonly used systems. Indian J Pathol Microbiol 2024;67(4):758–65. doi: 10.4103/ijpm.ijpm_109_23
  23. Drago S.G., Maino C., Giandola T.P. et al. Correlations between apparent diffusion coefficient (ADC) and prognosis in patients with locally advanced rectal cancer. Life 2024;14(10):1282. doi: 10.3390/life14101282
  24. Kiselev N.M., Klimin S.A., Kolesnik Ya.I. et al. Perioperative chemotherapy and morphological response in the treatment of gastric cancer. Modern Oncology = Sovremennaya onkologiya 2024;26(3): 276–83. (In Russ.). doi: 10.26442/18151434.2024.3.202978
  25. Öner İ., Türkel A., İnci B.K. et al. Impact of the CPS-EG score as a new prognostic biomarker in triple-negative breast cancer patients who received neoadjuvant chemotherapy. BMC Cancer 2024;24:420. doi: 10.1186/s12885-024-13100-0
  26. Callegaro D., Miceli R., Mariani L et al. Soft tissue sarcoma nomograms and their incorporation into practice. Cancer 2017;123(17):2802–20. doi: 10.1002/cncr.30721
  27. Pillozzi S., Bernini A., Palchetti I. et al. Soft tissue sarcoma: an insight on biomarkers at molecular, metabolic and cellular level. Cancers 2021;13(12):3044. doi: 10.3390/cancers13123044
  28. Jerby-Arnon L., Neftel C., Shore M.E. et al. Opposing immune and genetic mechanisms shape oncogenic programs in synovial sarcoma. Nat Med 2021;27(6):845–56. doi: 10.1038/s41591-020-01212-6
  29. Peeken J.C., Asadpour R., Specht K. et al. MRI-based delta-radiomics predicts pathologic complete response in high-grade soft-tissue sarcoma patients treated with neoadjuvant therapy. Radiother Oncol 2021;164:73–82. doi: 10.1016/j.radonc.2021.08.023
  30. Trassard M., Le Doussal V., Hacène K. et al. Prognostic factors in localized primary synovial sarcoma: a multicenter study of 128 adult patients. J Clin Oncol 2001;19(2):525–34. doi: 10.1200/JCO.2001.19.2.525
  31. Igarashi K., Kawaguchi K., Li S. et al. Recombinant methioninase combined with doxorubicin (DOX) regresses a DOX-resistant synovial sarcoma in a patient-derived orthotopic xenograft (PDOX) mouse model. Oncotarget 2018;9(27):19263–72. doi: 10.18632/oncotarget.24996
  32. Li X., Hu Y., Xie Y. et al. Soft-tissue sarcoma: modified grading method improves the accuracy of preoperative MRI in predicting patient outcomes. Eur Radiol 2025. doi: 10.1007/s00330-025-11365-y
  33. Guo J., Li Y., Guo H. et al. Parallel CNN-deep learning clinical- imaging signature for assessing pathologic grade and prognosis of soft tissue sarcoma patients. J Magn Reson Imaging 2025;61(2):807–19. doi: 10.1002/jmri.29474
  34. Guo X., Bian X., Li Y. et al. The intricate dance of tumor evolution: exploring immune escape, tumor migration, drug resistance, and treatment strategies. Biochim Biophys Acta Mol Basis Dis 2024;1870(4):167098. doi: 10.1016/j.bbadis.2024.167098
  35. Komdeur R., Plaat B.E.C., Hoekstra H.J. et al. Expression of P-glycoprotein, multidrug resistance-associated protein 1, and lung resistance-related protein in human soft tissue sarcomas before and after chemotherapy. Cancer 2001;91(10):1940–8. doi: 10.1002/1097-0142(20010515)91:10<1940::AID-CNCR1217>3.0.CO;2-3
  36. Pierrevelcin M., Fuchs Q., Lhermitte B.M. et al. Focus on hypoxia- related pathways in pediatric osteosarcomas and their druggability. Cells 2020;9(9):1998. doi: 10.3390/cells909199
  37. Bigos K.J.A., Quiles C.G., Lunj S. et al. Tumour response to hypoxia: understanding the hypoxic tumour microenvironment to improve treatment outcome in solid tumours. Front Oncol 2024;14:1331355. doi: 10.3389/fonc.2024.1331355
  38. Napolitano A., Huang P., Jones R.L. Novel therapeutics in soft tissue sarcoma. Cancers 2024;17(1):10. doi: 10.3390/cancers17010010
  39. Kim S.K., Kim J.H., Kim S.H. et al. PD-L1 tumour expression is predictive of pazopanib response in soft tissue sarcoma. BMC Cancer 2021;21(1):336. doi: 10.1186/s12885-021-08069-z
  40. Panagi M., Pilavaki P., Constantinidou A. et al. Exploring the landscape of immunotherapy approaches in sarcomas. Front Oncol 2023;12:1069963. doi: 10.3389/fonc.2022.1069963
  41. Jones K.B. Synovial Sarcoma. In: Sarcoma oncology: a multidisciplinary approach. New York: Springer, 2019. Pp. 395–412.
  42. Setsu N., Kohashi K., Fushimi F. et al. Prognostic impact of the activation status of the Akt/mTOR pathway in synovial sarcoma. Cancer 2013;119(19):3504–13. doi: 10.1002/cncr.28255
  43. Qin W., Peng C., Yang X. et al. SS18-SSX drives TYK2 expression to activate STAT3/Bcl2 axis, facilitating apoptosis evasion and advancing synovial sarcoma progression. Cell Biol Toxicol 2024;41(1):8. doi: 10.1007/s10565-024-09952-8
  44. Ramteke P., Deb A., Shepal V., Bhat M.K. Hyperglycemia associated metabolic and molecular alterations in cancer risk, progression, treatment, and mortality. Cancers 2019;11(9):1402. doi: 10.3390/cancers1109140
  45. Mao X., Wu S., Huang D., Li C. Complications and comorbidities associated with antineoplastic chemotherapy: rethinking drug design and delivery for anticancer therapy. Acta Pharm Sin B 2024;14(7):2901–26. doi: 10.1016/j.apsb.2024.03.006

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Copyright (c) 2025 Makhachev D.R., Bulanov D.V., Ametov D.M., Abakarov M.O., Abacharaeva A.R., Bagandova P.A., Gabibullaev R.M., Dzhanboriev A.D.

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