Advertisement

WHO Pathology

Highlights of the 2020 Sarcoma Update
      The 2020 WHO Classification of Soft Tissue and Bone Tumors has incorporated a number of changes to reflect recent advances made in the histopathologic and molecular diagnostic workup of soft tissue tumors.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribers receive full online access to your subscription and archive of back issues up to and including 2002.

      Content published before 2002 is available via pay-per-view purchase only.

      Subscribe:

      Subscribe to Surgical Oncology Clinics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • WHO Classification of Tumours Editorial Board
        5th ed. WHO classification of tumours: soft tissue and bone tumours. 3. IARC Press, Lyon2020 (World Health Organization)
        • Fletcher C.
        • Bridge J.A.
        • Hogendoorn P.C.W.
        • et al.
        WHO classification of tumours of soft tissue and bone.
        IARC Press, Lyon2013
        • Kallen M.E.
        • Hornick J.L.
        The 2020 WHO classification: what's new in soft tissue tumor pathology?.
        Am J Surg Pathol. 2021; 45: e1-e23
        • Marino-Enriquez A.
        • Nascimento A.F.
        • Ligon A.H.
        • et al.
        Atypical spindle cell lipomatous tumor: clinicopathologic characterization of 232 cases demonstrating a morphologic spectrum.
        Am J Surg Pathol. 2017; 41: 234-244
        • Creytens D.
        • van Gorp J.
        • Savola S.
        • et al.
        Atypical spindle cell lipoma: a clinicopathologic, immunohistochemical, and molecular study emphasizing its relationship to classical spindle cell lipoma.
        Virchows Arch. 2014; 465: 97-108
        • Mentzel T.
        • Palmedo G.
        • Kuhnen C.
        Well-differentiated spindle cell liposarcoma ('atypical spindle cell lipomatous tumor') does not belong to the spectrum of atypical lipomatous tumor but has a close relationship to spindle cell lipoma: clinicopathologic, immunohistochemical, and molecular analysis of six cases.
        Mod Pathol. 2010; 23: 729-736
        • Bahadir B.
        • Behzatoglu K.
        • Hacihasanoglu E.
        • et al.
        Atypical spindle cell/pleomorphic lipomatous tumor: a clinicopathologic, immunohistochemical, and molecular study of 20 cases.
        Pathol Int. 2018; 68: 550-556
        • Alaggio R.
        • Coffin C.M.
        • Weiss S.W.
        • et al.
        Liposarcomas in young patients: a study of 82 cases occurring in patients younger than 22 years of age.
        Am J Surg Pathol. 2009; 33: 645-658
        • Coffin C.M.
        • Alaggio R.
        Adipose and myxoid tumors of childhood and adolescence.
        Pediatr Dev Pathol. 2012; 15: 239-254
        • Boland J.M.
        • Colby T.V.
        • Folpe A.L.
        Liposarcomas of the mediastinum and thorax: a clinicopathologic and molecular cytogenetic study of 24 cases, emphasizing unusual and diverse histologic features.
        Am J Surg Pathol. 2012; 36: 1395-1403
        • Creytens D.
        • van Gorp J.
        • Ferdinande L.
        • et al.
        Array-based comparative genomic hybridization analysis of a pleomorphic myxoid liposarcoma.
        J Clin Pathol. 2014; 67: 834-835
        • Hofvander J.
        • Jo V.Y.
        • Ghanei I.
        • et al.
        Comprehensive genetic analysis of a paediatric pleomorphic myxoid liposarcoma reveals near-haploidization and loss of the RB1 gene.
        Histopathology. 2016; 69: 141-147
        • Creytens D.
        • Folpe A.L.
        • Koelsche C.
        • et al.
        Myxoid pleomorphic liposarcoma-a clinicopathologic, immunohistochemical, molecular genetic and epigenetic study of 12 cases, suggesting a possible relationship with conventional pleomorphic liposarcoma.
        Mod Pathol. 2021; 34: 2043-2049
        • Kao Y.C.
        • Flucke U.
        • Eijkelenboom A.
        • et al.
        Novel EWSR1-SMAD3 gene fusions in a group of acral fibroblastic spindle cell neoplasms.
        Am J Surg Pathol. 2018; 42: 522-528
        • Michal M.
        • Berry R.S.
        • Rubin B.P.
        • et al.
        EWSR1-SMAD3-rearranged fibroblastic tumor: an emerging entity in an increasingly more complex group of fibroblastic/myofibroblastic neoplasms.
        Am J Surg Pathol. 2018; 42: 1325-1333
        • Habeeb O.
        • Korty K.E.
        • Azzato E.M.
        • et al.
        EWSR1-SMAD3 rearranged fibroblastic tumor: case series and review.
        J Cutan Pathol. 2021; 48: 255-262
        • Foot O.
        • Hallin M.
        • Jones R.L.
        • et al.
        EWSR1-SMAD3-positive fibroblastic tumor.
        Int J Surg Pathol. 2021; 29: 179-181
        • Marino-Enriquez A.
        • Fletcher C.D.
        Angiofibroma of soft tissue: clinicopathologic characterization of a distinctive benign fibrovascular neoplasm in a series of 37 cases.
        Am J Surg Pathol. 2012; 36: 500-508
        • Yamada Y.
        • Yamamoto H.
        • Kohashi K.
        • et al.
        Histological spectrum of angiofibroma of soft tissue: histological and genetic analysis of 13 cases.
        Histopathology. 2016; 69: 459-469
        • Bekers E.M.
        • Groenen P.
        • Verdijk M.A.J.
        • et al.
        Soft tissue angiofibroma: clinicopathologic, immunohistochemical and molecular analysis of 14 cases.
        Genes Chromosomes Cancer. 2017; 56: 750-757
        • Jin Y.
        • Moller E.
        • Nord K.H.
        • et al.
        Fusion of the AHRR and NCOA2 genes through a recurrent translocation t(5;8)(p15;q13) in soft tissue angiofibroma results in upregulation of aryl hydrocarbon receptor target genes.
        Genes Chromosomes Cancer. 2012; 51: 510-520
        • Carter J.M.
        • Weiss S.W.
        • Linos K.
        • et al.
        Superficial CD34-positive fibroblastic tumor: report of 18 cases of a distinctive low-grade mesenchymal neoplasm of intermediate (borderline) malignancy.
        Mod Pathol. 2014; 27: 294-302
        • Lao I.W.
        • Yu L.
        • Wang J.
        Superficial CD34-positive fibroblastic tumour: a clinicopathological and immunohistochemical study of an additional series.
        Histopathology. 2017; 70: 394-401
        • Puls F.
        • Pillay N.
        • Fagman H.
        • et al.
        PRDM10-rearranged Soft tissue tumor: a clinicopathologic study of 9 cases.
        Am J Surg Pathol. 2019; 43: 504-513
        • Merchant W.
        • Calonje E.
        • Fletcher C.D.
        Inflammatory leiomyosarcoma: a morphological subgroup within the heterogeneous family of so-called inflammatory malignant fibrous histiocytoma.
        Histopathology. 1995; 27: 525-532
        • Chang A.
        • Schuetze S.M.
        • Conrad 3rd, E.U.
        • et al.
        So-called "inflammatory leiomyosarcoma'': a series of 3 cases providing additional insights into a rare entity.
        Int J Surg Pathol. 2005; 13: 185-195
        • Arbajian E.
        • Koster J.
        • Vult von Steyern F.
        • et al.
        Inflammatory leiomyosarcoma is a distinct tumor characterized by near-haploidization, few somatic mutations, and a primitive myogenic gene expression signature.
        Mod Pathol. 2018; 31: 93-100
        • Nord K.H.
        • Paulsson K.
        • Veerla S.
        • et al.
        Retained heterodisomy is associated with high gene expression in hyperhaploid inflammatory leiomyosarcoma.
        Neoplasia. 2012; 14: 807-812
        • Michal M.
        • Rubin B.P.
        • Kazakov D.V.
        • et al.
        Inflammatory leiomyosarcoma shows frequent co-expression of smooth and skeletal muscle markers supporting a primitive myogenic phenotype: a report of 9 cases with a proposal for reclassification as low-grade inflammatory myogenic tumor.
        Virchows Arch. 2020; 477: 219-230
        • O'Neill A.C.
        • Craig J.W.
        • Silverman S.G.
        • et al.
        Anastomosing hemangiomas: locations of occurrence, imaging features, and diagnosis with percutaneous biopsy.
        Abdom Radiol (NY). 2016; 41: 1325-1332
        • Brown J.G.
        • Folpe A.L.
        • Rao P.
        • et al.
        Primary vascular tumors and tumor-like lesions of the kidney: a clinicopathologic analysis of 25 cases.
        Am J Surg Pathol. 2010; 34: 942-949
        • Montgomery E.
        • Epstein J.I.
        Anastomosing hemangioma of the genitourinary tract: a lesion mimicking angiosarcoma.
        Am J Surg Pathol. 2009; 33: 1364-1369
        • Caballes A.B.
        • Abelardo A.D.
        • Farolan M.J.
        • et al.
        Pediatric anastomosing hemangioma: case report and review of renal vascular tumors in children.
        Pediatr Dev Pathol. 2019; 22: 269-275
        • Joseph N.M.
        • Brunt E.M.
        • Marginean C.
        • et al.
        Frequent GNAQ and GNA14 mutations in hepatic small vessel neoplasm.
        Am J Surg Pathol. 2018; 42: 1201-1207
        • Bean G.R.
        • Joseph N.M.
        • Gill R.M.
        • et al.
        Recurrent GNAQ mutations in anastomosing hemangiomas.
        Mod Pathol. 2017; 30: 722-727
        • Bean G.R.
        • Joseph N.M.
        • Folpe A.L.
        • et al.
        Recurrent GNA14 mutations in anastomosing haemangiomas.
        Histopathology. 2018; 73: 354-357
        • Suurmeijer A.J.H.
        • Dickson B.C.
        • Swanson D.
        • et al.
        A novel group of spindle cell tumors defined by S100 and CD34 co-expression shows recurrent fusions involving RAF1, BRAF, and NTRK1/2 genes.
        Genes Chromosomes Cancer. 2018; 57: 611-621
        • Kao Y.C.
        • Suurmeijer A.J.H.
        • Argani P.
        • et al.
        Soft tissue tumors characterized by a wide spectrum of kinase fusions share a lipofibromatosis-like neural tumor pattern.
        Genes Chromosomes Cancer. 2020; 59: 575-583
        • Drilon A.
        TRK inhibitors in TRK fusion-positive cancers.
        Ann Oncol. 2019; 30: viii23-viii30
        • Agaram N.P.
        • Zhang L.
        • Sung Y.S.
        • et al.
        Recurrent NTRK1 Gene Fusions Define a Novel Subset of Locally Aggressive Lipofibromatosis-like Neural Tumors.
        Am J Surg Pathol. 2016; 40: 1407-1416
        • Davis J.L.
        • Lockwood C.M.
        • Stohr B.
        • et al.
        Expanding the Spectrum of Pediatric NTRK-rearranged Mesenchymal Tumors.
        Am J Surg Pathol. 2019; 43: 435-445
        • Hung Y.P.
        • Fletcher C.D.M.
        • Hornick J.L.
        Evaluation of pan-TRK immunohistochemistry in infantile fibrosarcoma, lipofibromatosis-like neural tumour and histological mimics.
        Histopathology. 2018; 73: 634-644
        • Diaz-Perez J.A.
        • Nielsen G.P.
        • Antonescu C.
        • et al.
        EWSR1/FUS-NFATc2 rearranged round cell sarcoma: clinicopathological series of 4 cases and literature review.
        Hum Pathol. 2019; 90: 45-53
        • Bode-Lesniewska B.
        • Fritz C.
        • Exner G.U.
        • et al.
        EWSR1-NFATC2 and FUS-NFATC2 Gene Fusion-Associated Mesenchymal Tumors: Clinicopathologic Correlation and Literature Review.
        Sarcoma. 2019; 2019: 9386390
        • Perret R.
        • Escuriol J.
        • Velasco V.
        • et al.
        NFATc2-rearranged sarcomas: clinicopathologic, molecular, and cytogenetic study of 7 cases with evidence of AGGRECAN as a novel diagnostic marker.
        Mod Pathol. 2020; 33: 1930-1944
        • Chougule A.
        • Taylor M.S.
        • Nardi V.
        • et al.
        Spindle and Round Cell Sarcoma With EWSR1-PATZ1 Gene Fusion: a sarcoma with polyphenotypic differentiation.
        Am J Surg Pathol. 2019; 43: 220-228
        • Bridge J.A.
        • Sumegi J.
        • Druta M.
        • et al.
        Clinical, pathological, and genomic features of EWSR1-PATZ1 fusion sarcoma.
        Mod Pathol. 2019; 32: 1593-1604
        • Wang G.Y.
        • Thomas D.G.
        • Davis J.L.
        • et al.
        EWSR1-NFATC2 Translocation-associated Sarcoma Clinicopathologic Findings in a Rare Aggressive Primary Bone or Soft Tissue Tumor.
        Am J Surg Pathol. 2019; 43: 1112-1122
        • Antonescu C.R.
        • Owosho A.A.
        • Zhang L.
        • et al.
        Sarcomas With CIC-rearrangements are a distinct pathologic entity with aggressive outcome: a clinicopathologic and molecular study of 115 cases.
        Am J Surg Pathol. 2017; 41: 941-949
        • Specht K.
        • Sung Y.S.
        • Zhang L.
        • et al.
        Distinct transcriptional signature and immunoprofile of CIC-DUX4 fusion-positive round cell tumors compared to EWSR1-rearranged Ewing sarcomas: further evidence toward distinct pathologic entities.
        Genes Chromosomes Cancer. 2014; 53: 622-633
        • Hung Y.P.
        • Fletcher C.D.
        • Hornick J.L.
        Evaluation of ETV4 and WT1 expression in CIC-rearranged sarcomas and histologic mimics.
        Mod Pathol. 2016; 29: 1324-1334
        • Sugita S.
        • Arai Y.
        • Tonooka A.
        • et al.
        A novel CIC-FOXO4 gene fusion in undifferentiated small round cell sarcoma: a genetically distinct variant of Ewing-like sarcoma.
        Am J Surg Pathol. 2014; 38: 1571-1576
        • Solomon D.A.
        • Brohl A.S.
        • Khan J.
        • et al.
        Clinicopathologic features of a second patient with Ewing-like sarcoma harboring CIC-FOXO4 gene fusion.
        Am J Surg Pathol. 2014; 38: 1724-1725
        • Pierron G.
        • Tirode F.
        • Lucchesi C.
        • et al.
        A new subtype of bone sarcoma defined by BCOR-CCNB3 gene fusion.
        Nat Genet. 2012; 44: 461-466
        • Kao Y.C.
        • Owosho A.A.
        • Sung Y.S.
        • et al.
        BCOR-CCNB3 Fusion Positive Sarcomas: A Clinicopathologic and Molecular Analysis of 36 Cases With Comparison to Morphologic Spectrum and Clinical Behavior of Other Round Cell Sarcomas.
        Am J Surg Pathol. 2018; 42: 604-615
        • Specht K.
        • Zhang L.
        • Sung Y.S.
        • et al.
        Novel BCOR-MAML3 and ZC3H7B-BCOR Gene Fusions in Undifferentiated Small Blue Round Cell Sarcomas.
        Am J Surg Pathol. 2016; 40: 433-442
        • Kao Y.C.
        • Sung Y.S.
        • Zhang L.
        • et al.
        BCOR Overexpression Is a Highly Sensitive Marker in Round Cell Sarcomas With BCOR Genetic Abnormalities.
        Am J Surg Pathol. 2016; 40: 1670-1678
        • Cohen-Gogo S.
        • Cellier C.
        • Coindre J.M.
        • et al.
        Ewing-like sarcomas with BCOR-CCNB3 fusion transcript: a clinical, radiological and pathological retrospective study from the Societe Francaise des Cancers de L'Enfant.
        Pediatr Blood Cancer. 2014; 61: 2191-2198
        • Gronchi A.
        • Lo Vullo S.
        • Fiore M.
        • et al.
        Aggressive surgical policies in a retrospectively reviewed single-institution case series of retroperitoneal soft tissue sarcoma patients.
        J Clin Oncol. 2009; 27: 24-30
        • Evans H.L.
        Liposarcoma: a study of 55 cases with a reassessment of its classification.
        Am J Surg Pathol. 1979; 3: 507-523
        • Elgar F.
        • Goldblum J.R.
        Well-differentiated liposarcoma of the retroperitoneum: a clinicopathologic analysis of 20 cases, with particular attention to the extent of low-grade dedifferentiation.
        Mod Pathol. 1997; 10: 113-120
        • Marino-Enriquez A.
        • Fletcher C.D.
        • Dal Cin P.
        • et al.
        Dedifferentiated liposarcoma with "homologous" lipoblastic (pleomorphic liposarcoma-like) differentiation: clinicopathologic and molecular analysis of a series suggesting revised diagnostic criteria.
        Am J Surg Pathol. 2010; 34: 1122-1131
        • Gronchi A.
        • Collini P.
        • Miceli R.
        • et al.
        Myogenic differentiation and histologic grading are major prognostic determinants in retroperitoneal liposarcoma.
        Am J Surg Pathol. 2015; 39: 383-393
        • Baranov E.
        • Black M.A.
        • Fletcher C.D.M.
        • et al.
        Nuclear expression of DDIT3 distinguishes high-grade myxoid liposarcoma from other round cell sarcomas.
        Mod Pathol. 2021; 34: 1367-1372
        • Mentzel T.
        • Calonje E.
        • Wadden C.
        • et al.
        Myxofibrosarcoma. Clinicopathologic analysis of 75 cases with emphasis on the low-grade variant.
        Am J Surg Pathol. 1996; 20: 391-405
        • Widemann B.C.
        • Italiano A.
        Biology and Management of Undifferentiated Pleomorphic Sarcoma, Myxofibrosarcoma, and Malignant Peripheral Nerve Sheath Tumors: State of the Art and Perspectives.
        J Clin Oncol. 2018; 36: 160-167
        • Fletcher C.D.
        • Gustafson P.
        • Rydholm A.
        • et al.
        Clinicopathologic re-evaluation of 100 malignant fibrous histiocytomas: prognostic relevance of subclassification.
        J Clin Oncol. 2001; 19: 3045-3050