Stanford School of Medicine

Surgical Pathology Criteria

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Thymic Carcinoma


  • Epithelial neoplasm of the thymus exhibiting clear malignant cytologic or architectural features

Alternate/Historical Names

  • Type C thymoma
  • Malignant thymoma (an imprecise term also used for usual thymomas exhibiting aggressive behavior)


  • Thymic neuroendocrine neoplasms are covered separately
  • So called "well differentiated thymic carcinoma" is covered as thymoma type B3

Diagnostic Criteria

  • Requires either cytologic or invasive features of carcinoma
    • Unequivocal cytologic atypia is usually present
      • Mitotic figures may be frequent and atypical
    • Aggressive, destructive invasion with stromal response is usually present
  • Lacks dense capsule and fibrous septa typical of thymomas
  • Lacks infiltrate of immature T cells typical of most thymomas
    • May contain variable numbers of mature T cells and some B cells
  • Any type of thymic carcinoma may arise in or form cysts
  • Thymic carcinoma may rarely arise in the setting of a conventional thymoma
  • Metastatic carcinoma must be ruled out
  • A variety of patterns have been described
    • Low grade carcinomas (grading is approximate due to rarity of most of these types)
      • Well differentiated, keratininzing squamous cell carcinoma
        • Most common type reported in Japan, but also relatively common in USA
      • Basaloid carcinoma
        • Rare
        • Papillary/cystic and solid nest patterns
        • Frequently arises in multilocular cysts
        • May have comedonecrosis
        • May form a capsule
      • Papillary adenocarcinoma
        • Rare
      • Adenosquamous carcinoma
        • Mixture of gland formations (may be scant) and squamous carcinoma
      • Low grade mucoepidermoid carcinoma
        • Rare
        • Mixture of glandular, squamous and intermediate cells
        • May be considered a subset of adenosquamous
        • High stage low grade mucoepidermoid carcinoma behaves as high grade carcinoma (Minoka)
      • Micronodular with lymphoid stroma
        • Rare
      • Undifferentiated large cell carcinoma associated with Castleman disease-like reaction
    • High grade carcinomas (grading is approximate due to rarity of most of these types)
      • Lymphoepithelial-like
        • Most common type reported in USA
        • In spite of frequent association with EBV and histologic similarity to nasopharyngeal carcinoma, it does not share the good response to radiation therapy
      • Large cell undifferentiated
        • Rare
      • Clear cell
        • Rare
      • Mucinous or signet ring adenocarcinoma
        • Rare
      • Sarcomatoid
        • Rare
        • May have heterologous elements
      • NUT midline carcinoma with t(15;19)
        • Rare, aggresive neoplasm of young patients
          • 5-34 years old
        • Variety of histologic patterns
          • Poorly to well differentiated squamous carcinoma
          • Usually exhibits foci of abrupt keratinization
  • Associated autoimmune disease is quite unusual in thymic carcinomas

Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting/updates: 9/24/10, 12/1/13

Supplemental studies


Epithelial cell staining (thymocytes and T cells are CD5 positive and B cells are PAX8 positive)
  CD5 CD117 CD57 PAX8
Thymoma (except B3) neg 4% pos 90-100%
B3 Thymoma / Atypical Thymoma 50% <10% pos 90%
Thymic Carcinoma 70-100% >80% rare 77%
  • These markers should be used with caution in the distinction from lung and other carcinomas
  • CD5 stains about 15% of lung squamous carcinomas
  • CD117 stains about 20% of lung squamous carcinomas
  • Only PAX8 appears to be specific vs lung squamous and adenocarcinoma
  • Basaloid carcinoma is p63 positive and negative for synaptophysin and TTF1


Differential Diagnosis

Metastatic Carcinoma must be ruled out before the diagnosis of primary thymic carcinoma is made

  • Clinical findings, history and imaging are most valuable
  • CD5 and/or CD117 positivity are suggestive of thymic primary but not specific
    • 15-20% of lung squamous carcinomas are positive for these markers
  • PAX8 reacts with 77% of thymic carcinomas
    • Lung squamous and adenocarcinomas are negative


Metastatic Small Cell Neuroendocrine Carcinoma of Lung Thymic Basaloid Carcinoma
History and imaging may reveal primary site History and imaging should reveal no other primary site
TTF1and synaptophysin positive in >90% of lung neuroendocrine carcinomas Synaptophysin and TTF1 negative
p63 negative p63 positive


Thymic Well Differentiated Neuroendocrine Carcinoma Thymic Basaloid Carcinoma
Most cases have a moderate amount of cytoplasm Scant cytoplasm
Inconspicuous nucleoli Variable, may have large nucleoli
Synaptophysin positive Synaptophysin negative
p63 negative p63 positive
Both have peripheral palisading and necrosis


Thymoma (general features) Thymic Carcinoma
Cytologically bland, moderate atypia at most Typically cytologically malignant
Lacks desmoplastic response to invasion Aggressive, destructive invasion with desmoplastic response
Lobular growth pattern Irregular growth pattern
Thick fibrous capsule and septa Lacks prominent capsule and septa
Immature T cells present Mature T and B cells may be present, but lacks immature T cells
Epithelial cells CD5 (except for B3) and CD117 <5% Epithelial cells CD5 and CD117 >70%
Micronodular thymoma with lymphoid stroma may lack a capsule while basaloid carcinoma may form a capsule

Special types of thymoma:

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 B2 Thymoma Thymic Lymphoepithelial Carcinoma
Mild cytologic atypia at worst Cytologically atypical
Epithelial cell mitotic figures rare Epithelial cell mitotic figures may be frequent
Lymphocytes are immature T cells Lymphocytes are mature T and B cells


Type B3 Thymoma Thymic Low Grade Squamous Carcinoma
Cytologic atypia usually mild, moderate at worst Cytologically atypical
Epithelial cell mitotic figures usually <2/10hpf Epithelial cell mitotic figures may be frequent
Lymphocytes few, but with immature T phenotype Lymphocytes are mature T and B cells
Overt squamous differentiation usually scant and focal Overtly squamous, with intercellular bridges usually identifiable
Lobular growth pattern Infiltrative growth pattern
Frequent perivascular spaces surrounded by palisaded epithelial cells Lacks perivascular spaces and palisading
Epithelial cells CD117 negative to rare Epithelial cells CD117 65-80% positive
Epithelial cells CD5 negative to at most focally positive Epithelial cells CD5 70% positive


Metaplastic Thymoma Thymic Carcinoma with Sarcomatoid Differentiation
Cytologically bland Usually cytologically atypical
Mitotic figures rare Mitotic figures may be numerous
Metaplastic thymoma may have scattered bizarre nuclei but the general epithelial population is bland


Micronodular Thymoma with Lymphoid Stroma Metastatic Carcinoma in a Lymph Node
Epithelial nodules usually scattered throughout Carcinoma usually subcapsular, sinusoidal or focal
Cytologically very bland Usually cytologically atypical
Mitotic figures very rare Mitotic figures may be numerous
Lacks a subcapsular sinus Subcapsular sinus present
Presence of adjacent nonneoplastic thymus supports a thymic neoplasm Typically no adjacent thymus
Immature T cells may be present Immature T cells absent
Rare micronodular thymic carcinomas have been reported; these show all features of micronodular thymoma but exhibit atypia and mitotic figures


Mediastinal (thymic) Germ Cell Neoplasms are separable morphologically and immunologically

  • Seminoma (germinoma) may lack the classic pattern of sheets of uniform cells
    • Intimate involvement of the thymic epithelium by seminoma cells may give rise to thymic epithelial hyperplasia, which may give concern for carcinoma
      • Keratin weak to negative seminoma cells may be difficult to identify
    • Sheets of clear seminoma cells with sharp cell borders may be confused with clear cell carcinoma
  • Yolk sac tumor may exhibit a variety of patterns including papillary and clear cell that could be confused with thymic carcinoma
    • Identification of areas of reticular pattern may be helpful for recognition of yolk sac tumor
  • Teratoma, embryonal carcinoma and choriocarcinoma have distinctive histologic patterns that should not be confused with thymic carcinoma
  • Keratin is not useful for the distinctions as all are positive
    • Seminoma is usually faint and focal
  • SALL4 (all germ cell tumors) and OCT3/4 (seminoma and embryonal carcinoma) are quite useful
    • They are very sensitive for germ cell tumors based on large numbers tested
    • They are very specific for germ cell tumors based on a wide variety of other neoplasms tested
    • Very few thymic carcinomas have been tested, so some caution is advised

Mediastinal (Thymic) Large B Cell Lymphoma is easily separated immunologically

  • Lymphoma is positive for LCA, CD20 and other B lymphoid markers and negative for keratin

Grading / Staging


  • Low grade
    • Well differentiated squamous carcinoma
    • Basaloid carcinoma
    • Adenosquamous carcinoma
    • Low grade mucoepidermoid carcinoma
    • Adenocarcinoma
  • High grade carcinomas
    • Lymphoepithelial-like
    • Large cell undifferentiated
    • Clear cell
    • Sarcomatoid
    • Midline carcinoma with t(15;19)
  • (modified from Suster and Rosai)


  • The same TNM proposed for thymomas has been proposed for thymic carcinomas:
pT1 Completely encapsulated
pT2 Invades through capsule into fat or normal thymus, but not through pleura or pericardium (may be adherent) or into adjacent organs
pT3 Invades through pleura or pericardium or into adjacent organs (great vessels, lung)
pT4 Pleural or pericardial implants
pN1 Metastasis only to anterior mediastinal nodes
pN2 Metastasis to other intrathoracic nodes
pN3 Metastasis to extrathoracic nodes
pM1 With distant metastases
  • From Tsuchiya et al. Pathol Int 1994; 44:506 and 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
  • An alternative system has been proposed by Moran
    Stage 0 Encapsulated, no invasion of fat
    Stage 1 Invasion of fat only
    Stage 2a

    Invasion of innominate vein, mediastinal pleura or lung

    Stage 2b Invasion of pericardium, aorta, superior vena cava or heart
    Stage 3a Intrathoracic "drop" mets (discontinuous from primary) or nodes
    Stage 3b Extrathoracic spread

Classification / Lists

Intrinsic Tumors of the Thymus

Non-Thymic Neoplasms that May Arise Primarily in the Thymus

  • Hematopoietic
    • Primary mediastinal large B cell lymphoma
    • Extranodal marginal zone lymphoma
    • Precursor T lymphoblastic lymphoma/leukemia
    • Hodgkin lymphoma
  • Germ cell tumors
    • Seminoma (Germinoma)
    • Embryonal carcinoma
    • Yolk sac tumor
    • Teratoma
    • Choriocarcinoma
    • With associated somatic type malignancy
      • Embryonal rhabdomyosarcoma
      • Angiosarcoma
      • Others
    • With associated hematologic malignancy
      • Acute myelogenous leukemia
      • Acute megakaryoblastic leukemia
      • Others


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