TABLE 1.

Pathological diagnosis of thymic epithelial tumor (TET).

WHO classification	Diagnostic prerequisites	Other diagnostic criteria
TM
Type A	A thymic epithelial tumor, with bundle, storiform or pericytoma‐like growth, spindle and oval‐shaped, rarely polygonal‐shaped; Lack of immature TdT‐positive T cells; Most tumors lack necrotic areas, mitotic figures are rare, and Ki‐67 index is low; Atypical type A thymoma can have high proliferation index and focal necrosis	Strong expression of epithelial markers
Type AB	A thymic tumor with lobulated growth pattern; Compose of spindle cell components, Type A lacks lymphocytes and type B is lymphocyte‐rich; Thymic epithelial cells were spindle, oval and focal polygonal‐shaped, with a large amount of immature T cells (focal or diffuse); Spindle cell tumor with moderate TdT‐positive T cell infiltration in more than 10% area	TdT immunohistochemistry assessing TdT‐positive cell density can be used for differential diagnosis from type A thymoma
Type B1	A thymic epithelial tumor with organoid (corticomedullary) structure, mainly composed of cortex; Non‐clustered thymic epithelial cells scattered among a large number of lymphocytes	Scattered epithelial cells with positive cytokeratin, p40 and p63; TdT‐positive immature T cells are distributed in TdT‐negative nodules (medulla) area
Type B2	Lobulated structure; Large amount of lymphocytes; More polygonal or oval‐shaped neoplastic epithelial cells than normal thymic cortex, often appearing in clusters	Scattered or clustered epithelial cells with positive cytokeratin, p40 and p63, and the staining was stronger than that of normal thymic cortex
Type B3	Lobulated structure; Slight or moderate heterotypic and polygonal‐shaped tumor cells are distributed in sheet‐like pattern; Scattered around blood vessels; Lack of lymphocytes	A small amount of immature T cells stained with TdT
Micronodular thymoma with lymphoid stroma	Multiple discrete nodules composed of spindle or oval‐shaped epithelial cells; Abundant epithelial lymphoid stroma	CD20‐positive B cells are dominant in the stroma
Metaplastic thymoma	Biphasic thymoma; Heterotypic unequal, polygonal‐shaped epithelial cells forming interconnected island structures; With spindle cells as the background
Lipofibroadenoma	A benign thymic tumor similar to breast fibroadenoma, with fat cells and thin epithelial cell bundles, mainly composed of fibrous tissue
TC (type C)
Squamous cell carcinoma	An invasive thymic carcinoma, often with fibroproliferative or sclerotic stroma; Exclude adjacent lung cancer invasion or metastasis	Positive CD5, KIT (CD117), FOXN1 and CD205 in immunohistochemistry; KIT mutation
Basal cell carcinoma	A basal cell‐like thymic carcinoma with nested shape or cystic spaces, lined with palisade‐shaped basal cell‐like tumor cells	Positive p40 and KIT (CD117); and negative TTF1, neuroendocrine biomarkers and the nuclear protein of the testis (NUT) in immunohistochemistry
Lymphoepithelial carcinoma	Primary thymic carcinoma; Cancer cells are arranged in sheet, nest and strip‐like patterns, with obvious multinuclear, vesicular chromatin and nucleolus; A large number of mixed lymphocytes and plasma cells	Negative Epstein‐Barr Early RNA (EBER) (in situ hybridization) does not affect the diagnosis of typical lymphoepithelial carcinoma morphology; EBER‐negative can support the diagnosis of cases with fewer lymphocytes
NUT carcinoma	NUTM1 rearrangement or immunohistochemical NUT positive detected in poorly differentiated squamous cell carcinoma or other cancer
Clear cell carcinoma	Invasive thymic tumor; The cytoplasm of cancer cells is transparent, forming islands and frames; Abundant vitreous stroma in hyaline clear cell carcinoma	Positive cytokeratin, P40 and P63 in immunohistochemistry; EWSR1 translocation of hyaline clear cell carcinoma
Low grade papillary adenocarcinoma	Low grade, primary thymic adenocarcinoma with tubular papillary growth	Exclusion of thyroid, pleural, lung and extrathoracic papillary tumors by immunohistochemistry
Mucoepidermoid carcinoma	A primary thymic carcinoma characterized by mixing of mucus‐producing cells, intermediate cells and squamous cells in the nested and cystic structures; The diagnosis of high grade mucoepidermoid carcinoma requires at least the presence of focal intracellular mucin	MAML2 rearrangement can help the diagnosis of complicated cases, especially for high grade cases; Patients with negative MAML2 rearrangement cannot be excluded
Adenoid cystic carcinoma‐like thymic carcinoma	A thymic carcinoma with morphology similar to adenoid cystic carcinoma, but usually lacks of true gland in cribriform‐basaloid island; Exclude metastatic carcinoma of salivary gland, lung or breast	Negative KIT (CD117) and myoepithelial biomarkers in immunohistochemistry
Intestinal adenocarcinoma	A primary thymic tumor similar to colorectal adenocarcinoma	Expression of at least one intestinal differentiation marker (CD20, CDX2 and MUC2)
Adenocarcinoma Unspecific (NOS)	Exclude mediastinal metastasis of other cancers and defined thymic adenocarcinoma (low grade papillary and intestinal type)	Exclusion of mediastinal metastasis and defined thymic adenocarcinoma by immunohistochemistry
Adenosquamous carcinoma	A thymic carcinoma with both squamous and adenocarcinoma differentiation; Exclude mucoepidermoid carcinoma
Sarcomatoid carcinoma, Carcinosarcoma	The thymic epithelium, which is partially or completely composed of atypical spindle cells, has at least the characteristics of focal epithelium or heterologous sarcoma‐like components	Immunohistochemistry and molecular detection
Undifferentiated carcinoma	Primary malignant thymic tumor with only epithelium differentiation, and does not conform to other clearly‐defined types; Immunohistochemistry and molecular detection are required
Thymic carcinoma (NOS)	Exclude the above mentioned thymic cancer types; Currently, this type includes hepatoid carcinoma, rhabdoid carcinoma, undifferentiated large cell carcinoma with Castleman's disease‐like reaction and sebaceous adenocarcinoma

Abbreviations: TC, thymic carcinoma; TM, thymoma.