Surgical Pathology Criteria–

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Definition

• Thymoma with a mixture of lymphocyte poor and lymphocyte rich areas

Alternate / Historical Names

• Mixed thymoma
• Small polygonal type

Diagnostic Criteria

• Mixture of variable proportions of lymphocyte-poor and lymphocyte rich areas
  • May be discrete areas or intermixed
  • If lymphocyte pure areas separate small islands of type A thymoma, consider micronodular thymoma with lymphoid stroma
• Lymphocyte poor areas have features of Type A thymoma
  • Bland epithelial cells with few lymphocytes
• Immature T lymphocytes must fulfill at least one of the following criteria
  • 10% of area contains moderate numbers of immature cells ("difficult to count") OR,
  • Any areas of dense immature cells ("impossible to count")
• Lymphocyte rich areas differ from types B1, B2 and B3
  • Epithelial cells are essentially the same as those of Type A
    • Spindled to oval cells
    • Nuclei are bland, small, round to oval
      • Dispersed chromatin
      • Inconspicuous nucleoli
• Type AB thymoma is not simply a mixture of Type A and Type B patterns
  • It is better considered as a Type A thymoma with lymphocyte rich areas
    • A better classification would be A1 (= type A) and A2 (= type AB)

Supplemental Studies

• Epithelial cells (in both components)
  • Keratin AE1, p63, PAX8 positive
  • CK14-19 variable
  • EMA negative to focally positive
  • CD20 focally positive in many cases
  • CD5 negative
• Increased immature T cells (CD1a, CD99, TdT)
  • T cells express most pan-T cell markers (CD3, CD5)
• Few B cells

Clinical

• Associations
  • Myasthenia gravis
  • Pure red cell aplasia
• Very rarely recurs or metastasizes
• 90% long term survival

Differential Diagnosis

Type AB Thymoma	Micronodular Thymoma with Lymphoid Stroma
Lymphocyte rich areas contain scattered epithelial cells	Lymphocyte rich areas lack epithelial cells
Lymphocyte rich areas composed predominantly of T cells	Lymphocyte rich areas contain many B cells, frequently with germinal centers

Type AB Thymoma	Type B2 Thymoma
Epithelial cells have small oval to spindled nuclei with dispersed chromatin and inconspicuous nucleoli	Epithelial cells have vesicular nuclei with prominent nucleoli
Areas of Type A are usually present	Type A areas not present

Both may be composed of an essentially even mixture of epithelial cells and lymphocytes

Type AB Thymoma	Type B3 Thymoma
Predominantly spindle cells	Predominantly polygonal cells
Lacks any epidermoid features	Frequently has epidermoid differentiation (but lacks overt keratinization and bridges)
Frequent glandular structures lined by cuboidal to flat cells	Frequent perivascular spaces surrounded by palisaded epithelial cells
Lacks cytologic atypia	Mild to moderate cytologic atypia
Epithelial cells may be CD20 positive	Epithelial cells CD20 negative
Epithelial cells EMA and CD5 negative	Epithelial cells may be focally positive for EMA or CD5
Prominent reticulin within epithelial areas	Lacks prominent reticulin around epithelial cells

Lymphocyte poor areas of Type AB may be confused with Type B3

Bibliography

• Shimosato Y, Mukai K, Matsuno Y. Tumors of the Mediastinum, Atlas of Tumor Pathology, AFIP Fourth Series, Fascicle 11, 2010
• Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG eds. World Health Organization Classification of Tumors. Pathology and genetics of tumors of the lung, pleura, thymus and heart. IARC Press: Lyon 2015.
• Nonaka D, Henley JD, Chiriboga L, Yee H. Diagnostic utility of thymic epithelial markers CD205 (DEC205) and Foxn1 in thymic epithelial neoplasms. Am J Surg Pathol. 2007 Jul;31(7):1038-44.
• Alexiev BA, Drachenberg CB, Burke AP. Thymomas: a cytological and immunohistochemical study, with emphasis on lymphoid and neuroendocrine markers. Diagn Pathol. 2007 May 11;2:13.
• Tateyama H, Eimoto T, Tada T, Hattori H, Murase T, Takino H. Immunoreactivity of a new CD5 antibody with normal epithelium and malignant tumors including thymic carcinoma. Am J Clin Pathol. 1999 Feb;111(2):235-40.
• Dorfman DM, Shahsafaei A, Chan JK. Thymic carcinomas, but not thymomas and carcinomas of other sites, show CD5 immunoreactivity. Am J Surg Pathol. 1997 Aug;21(8):936-40.
• Okumura M, Ohta M, Tateyama H, Nakagawa K, Matsumura A, Maeda H, Tada H, Eimoto T, Matsuda H, Masaoka A. The World Health Organization histologic classification system reflects the oncologic behavior of thymoma: a clinical study of 273 patients. Cancer. 2002 Feb 1;94(3):624-32.
• Vladislav IT, Gökmen-Polar Y, Kesler KA, Loehrer PJ Sr, Badve S. The prognostic value of architectural patterns in a study of 37 type AB thymomas. Mod Pathol. 2013 Nov 15. doi: 10.1038/modpathol.2013.203. [Epub ahead of print]

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