The WHO 2021 thymoma classification: a work in progress

Abstract

The updated, recently published 2021 WHO classification of thymic tumors incorporates the most recent advances in the field of thymic pathology, with particular emphasis on primary thymic epithelial neoplasms. This new edition retains the basic format of previous editions for the classification of primary thymic epithelial neoplasms reaffirming the schema originally proposed in the first edition, which utilized a combination of letters and numbers for the designation of these tumors. Only minimal changes have been incorporated in the new edition compared with the previous ones. A new helpful feature is a summary in each chapter of recommendations for “essential” and “desirable” criteria to facilitate the diagnosis. A few issues in this classification, however, still require clarification. In this review, the changes and advances in the classification of thymoma presented in the latest WHO book on Thoracic Tumors will be reviewed along with some of the areas that may still benefit from the additional investigation.

Keywords

Thymoma / WHO classification / thymic epithelial neoplasms / atypical thymoma

References

[1] Suster S.Thymoma classification: current status and future trends.Am J Clin Pathol2006;125:542-54

[2] Suster S.Histologic classification of thymoma: the World Health Organization and beyond.Hematol Oncol Clin North Am2008;22:381-92

[3] Rosai J.Histological typing of tumors of the thymus, In: Rosai J, editor. World Health Organization International Histological Classification of Tumors. Berlin: Springer-Verlag; 1999.

[4] WHO classification of tumors editorial Board. Thoracic Tumors. WHO Classification of Tumors. Lyon: IARC; 2021.

[5] Travis WD,Burke AP,Nicholson AG.WHO classification of tumors of the lung, pleura, thymus and heart. World Health Classification of Tumors. Lyon: IARC; 2015.

[6] Inoue M,Zettl A.Correlating genetic aberrations with World Health Organization-defined histology and stage across the spectrum of thymomas.Cancer Res2003;63:3708-15

[7] Petrini I,Kim IK.A specific missense mutation in GTF2I occurs at high frequency in thymic epithelial tumors.Nat Genet2014;46:844-9 PMCID:PMC5705185

[8] Radovich M,Felau I.Cancer Genome Atlas NetworkThe integrated genomic landscape of thymic epithelial tumors.Cancer Cell2018;33:244-258.e10 PMCID:PMC5994906

[9] Suster D,Pihan G,Suster S.Expression patterns for Bcl-2, EMA, β-catenin, E-cadherin, PAX8, and MIB1 in thymomas.Mod Pathol2021;34:1831-8

[10] Bernatz PE,Claggett OT.Thymoma: a clinicopathologic study.J Thorac Cardiovasc Surg1961;42:424-44

[11] Lattes R.Pathological and clinical features in 80 cases of thymoma.Bull N Y Acad Med1957;33:145-7

[12] Masaoka A,Nakahara K.Follow-up study of thymomas with special reference to their clinical stages.Cancer1981;48:2485-92

[13] Bernatz PE,Harrison EG.Thymoma: factors influencing prognosis.Surg Clin North Am1973;53:885-92

[14] Chalabreysse L,Cordier JF,Gamondes JP.Correlation of the WHO schema for the classification of thymic epithelial neoplasms with prognosis: a retrospective study of 90 tumors.Am J Surg Pathol2002;26:1605-11

[15] Rieker RJ,Morresi-Hauf A.Histologic classification of thymic epithelial tumors: comparison of established classification schemes.Int J Cancer2002;98:900-6

[16] Pan C,Yang C,Chiang H.The clinicopathological correlation of epithelial subtyping in thymoma: a study of 112 consecutive cases.Hum Pathol1994;25:893-9

[17] Regnard J,Dromer C.Prognostic factors and long-term results after thymoma resection: a series of 307 patients.J Thorac Cardiovasc Surg1996;112:376-84

[18] Marino M.Thymoma and thymic carcinoma. Relation of thymoma epithelial cells to the cortical and medullary differentiation of thymus.Virchows Arch A Pathol Anat Histopathol1985;407:119-49

[19] Travis WD,Muller-Hermelink HK. Tumors of the lung, pleura, thymus and heart. World Health Organization Classification of Tumors. Lyon: IARC Press; 2004.

[20] Ströbel P,Rosenwald A.Corticomedullary differentiation and maturational arrest in thymomas.Histopathology2014;64:557-66

[21] Radovich M,Hancock BA.A large microRNA cluster on chromosome 19 is a transcriptional hallmark of WHO type A and AB thymomas.Br J Cancer2016;114:477-84 PMCID:PMC4815766

[22] Suster D,Pihan G,Suster S.Lymphocyte-rich spindle cell thymoma: clinicopathologic, immunohistochemical, ultrastructural and molecular genetic study of 80 cases.Am J Surg Pathol2022;

[23] Suster S.Thymoma, atypical thymoma, and thymic carcinoma. A novel conceptual approach to the classification of thymic epithelial neoplasms.Am J Clin Pathol1999;111:826-33

[24] Suster S.Primary thymic epithelial neoplasms showing combined features of thymoma and thymic carcinoma. A clinicopathologic study of 22 cases.Am J Surg Pathol1996;20:1469-80

[25] Suster S.Spindle cell thymic carcinoma: clinicopathologic and immunohistochemical study of a distinctive variant of primary thymic epithelial neoplasm.Am J Surg Pathol1999;23:691-700

[26] Quintanilla-martinez L,Ferry JA.Thymoma-morphologic subclassification correlates with invasiveness and immunohistologic features: a study of 122 cases.Hum Pathol1993;24:958-69

[27] Suster DI,DiStasio M,Pihan G.Atypical thymomas with squamoid and spindle cell features: clinicopathologic, immunohistochemical and molecular genetic study of 120 cases with long-term follow-up.Mod Pathol2022;

[28] Gupta R,McKenna RJ.Evidence-based pathology and the pathologic evaluation of thymomas: transcapsular invasion is not a significant prognostic feature.Arch Pathol Lab Med2008;132:926-30

[29] Roden AC,Jenkins SM.Reproducibility of 3 histologic classifications and 3 staging systems for thymic epithelial neoplasms and its effect on prognosis.Am J Surg Pathol2015;39:427-41

[30] Oselin K,Lepik K.Pathological discrepancies in the diagnosis of thymic epithelial tumors: the Tallinn-Lyon experience.J Thorac Dis2019;11:456-64 PMCID:PMC6409262

[31] Verghese ET,Campbell A.Interobserver variation in the classification of thymic tumours--a multicentre study using the WHO classification system.Histopathology2008;53:218-23

[32] Wick MR.Prognostic factors for thymic epithelial neoplasms, with emphasis on tumor staging.Hematol Oncol Clin North Am2008;22:527-42

[33] Kirschner T.In: Cecilia Fenoglio-Preiser M, Wolff M, Rilke F, editors. Progress in surgical pathology. Berlin, Heidelberg: Springer; 1989.

[34] Giraud F,Auger C,Loire R.Human thymic epithelial tumors: heterogeneity in immunostaining of epithelial cell markers and thymic hormones.Thymus1990;15:15-29

[35] Hofmann WJ,Möller P,Kayser K.Expression of cortical and medullary thymic epithelial antigens in thymomas. An immunohistological study of 14 cases including a characterization of the lymphocytic compartment.Histopathology1989;14:447-63

[36] Müller-Hermelink HK,Palestro G,Kirchner T.Immunohistological evidences of cortical and medullary differentiation in thymoma.Virchows Arch A Pathol Anat Histopathol1985;408:143-61

[37] Suster S,Chan JK.Thymoma with pseudosarcomatous stroma: report of an unusual histologic variant of thymic epithelial neoplasm that may simulate carcinosarcoma.Am J Surg Pathol1997;21:1316-23

[38] Yoneda S,Heimann S,Kikuchi M.Low-grade metaplastic carcinoma of the thymus.Histopathology1999;35:19-30

[39] Suster S.Micronodular thymoma with lymphoid B-cell hyperplasia: clinicopathologic and immunohistochemical study of eighteen cases of a distinctive morphologic variant of thymic epithelial neoplasm.Am J Surg Pathol1999;23:955-62