Surgical Pathology Criteria–

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Definition

• Thymoma composed of bland spindle to oval cells with few to no lymphocytes

Alternate / Historical Names

• Medullary thymoma
• Predominantly epithelial thymoma
• Spindle cell thymoma

Diagnostic Criteria

• Predominantly composed of spindled to oval epithelial cells
• Bland oval, occasionally round nuclei
  • Evenly dispersed chromatin
  • Inconspicuous nucleoli
  • Infrequent mitotic figures
  • No Hassall corpuscles
• Scant to absent lymphoid component
  • Immature T phenotype lymphocytes at most should be easily countable
  • If lymphocytes are numerous in areas, consider Type AB
    • Type AB is basically just a Type A thymoma with lymphocyte rich areas
      • A better classification would be A1 (= type A) and A2 (= type AB)
    • If lymphocyte pure areas separate small islands of type A thymoma, consider micronodular thymoma with lymphoid stroma
      • These commonly overlap
• Occasional features
  • Gland-like structures / cysts
    • May have distinct lining layer but no specific glandular differentiation
    • Microcystic areas are common
  • Papillary and pseudopapillary formation
  • Hemangiopericytoma-like staghorn vessels
    • Perivascular spaces usually not prominent
  • Pseudo-rosettes with or without lumens
  • Glomeruloid bodies projecting into cysts
  • Adenomatoid/reticular pattern
    • Signet ring appearance may be seen in reticular areas
  • Occasional cases may resemble somewhat B3 thymomas
    • Mild to moderate atypia, increased mitotic figures, focal necrosis
    • Nonaka has proposed expanding Type A into multiple subtypes
      • All patients in their series were alive without disease regardless of atypical features
      • As with all thymomas, what really matters is stage, not type
    • I prefer to acknowledge that some Type A thymomas may have atypical features
      • In addition, some just are not reliably classified
• Typically lacks broad fibrous bands
  • Capsule may range from inconspicuous to thick
  • Cases with desmoplastic stroma have been described
• Reticulin fibers individually surround most cells
• May infiltrate into fat but invasion of adjacent structures is infrequent

Supplemental Studies

• Epithelial cells
  • Keratin positive
    • May be variable, especially in background of gland-like areas
      • Gland lining typically strongly stained
    • AE1, p63, PAX8 positive, CK20 negative
      • CK7-19 variable
  • EMA negative to focally positive
  • CD20 focally positive in many cases
  • CD5, CD117 negative
• Lymphocytes
  • Most mature T phenotype
  • Few with immature T phenotype (CD1a, CD99, TdT)
• Few B cells except in micronodular thymoma with lymphoid stroma

Clinical

• Associations
  • Myasthenia gravis
  • Pure red cell aplasia
• Infrequently recurs or metastasizes
• Close to 100% long term survival in some series
  • Moran (2012) finds no difference in survival by type

Differential Diagnosis

Type A 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

Type A Thymoma	Solitary Fibrous Tumor
Plump spindle cells with appreciable cytoplasm	Thin spindle cells without appreciable cytoplasm on H&E stain
Keratin positive, CD34 negative	CD34 positive, keratin negative
Some immature T cells usually present	Any lymphocytes present are mature T cells

Both may have hemangiopericytoma like vasculature

Type A Thymoma	Thymic Spindle Cell Carcinoma
Mild cytologic atypia at worst	Cytologically atypical
Epithelial cell mitotic figures rare	Epithelial cell mitotic figures may be frequent
Some immature T cells usually present	Lymphocytes are mature T and B cells
Usually well circumscribed, with only microscopic invasion	Usually clearly invasive

Type A Thymoma, Adenomatoid/Reticular Variant	Mediastinal Yolk Sac Tumor
Lacks hyaline globules and Schiller-Duval bodies	Frequent hyaline globules and Schiller-Duval bodies
Mitotic figures infrequent or absent	Mitotic figures may be frequent
No necrosis or hemmorhage	Frequent necrosis and hemmorhage
Serum AFP negative	Serum AFP positive (immunohistochemistry is not reliable)
SALL4 and glypican 3 not tested	SALL4 and glypican 3 positive

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.
• Moran CA, Kalhor N, Suster S. Invasive Spindle Cell Thymomas (WHO Type A): A Clinicopathologic Correlation of 41 Cases. Am J Clin Pathol. 2010 Nov;134(5):793-8.
  
• Weissferdt A, Kalhor N, Suster S, Moran CA. Adenomatoid spindle cell thymomas: a clinicopathological and immunohistochemical study of 20 cases. Am J Surg Pathol. 2010 Oct;34(10):1544-9.
• Kalhor N, Suster S, Moran CA. Spindle cell thymomas (WHO Type A) with prominent papillary and pseudopapillary features: a clinicopathologic and immunohistochemical study of 10 cases. Am J Surg Pathol. 2011 Mar;35(3):372-7.
• Moran CA, Weissferdt A, Kalhor N, Solis LM, Behrens C, Wistuba II, Suster S. Thymomas I: a clinicopathologic correlation of 250 cases with emphasis on the World Health Organization schema. Am J Clin Pathol. 2012 Mar;137(3):444-50.
• Nonaka D, Rosai J. Is there a spectrum of cytologic atypia in type A thymomas analogous to that seen in type B thymomas? A pilot study of 13 cases. Am J Surg Pathol. 2012 Jun;36(6):889-94.
• Weissferdt A, Moran CA. The histomorphologic spectrum of spindle cell thymoma. Hum Pathol. 2012 Dec 19. doi:pii: S0046-8177(12)00328-0. 10.1016/j.humpath.2012.08.025. [Epub ahead of print]
• Weissferdt A, Moran CA. Desmoplastic spindle cell thymomas: a clinicopathologic and immunohistochemical study of 14 cases. Hum Pathol. 2013 Apr;44(4):623-7.
• Weissferdt A, Hernandez JC, Kalhor N, Moran CA. Spindle cell thymomas: an immunohistochemical study of 30 cases. Appl Immunohistochem Mol Morphol. 2011 Jul;19(4):329-35.
  

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