Thymic Carcinoma

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

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

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

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

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

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