Thymoma Staging 

Updated: Jul 25, 2017
  • Author: Evan C Dannhardt, DO; Chief Editor: Neetu Radhakrishnan, MD  more...
  • Print

Staging and Classification of Thymoma

Establishing a staging system for thymic epithelial tumors (TETs) has been difficult due to the rarity of these tumors. [1, 2] Staging has most commonly been performed using the Masaoka-Koga Staging System. [3] This system, based on a small single-center study, was first developed by Akira Masaoka in 1981, and was later updated by Kenji Koga in 1994. Though several other staging systems were previously proposed, the Masaoka-Koga system has been widely used because it is a prognostic indicator for thymic malignancy and a predictor of tumor recurrence. [4]

The Masaoka-Koga Staging system is based on the local micro- and/or macroscopic invasion of the tumor and the presence of lymphogenous or hematogenous metastasis. See Table 1, below.

Table 1. Modified Masaoka Clinical Staging of Thymoma (Open Table in a new window)

Stage Definition
I Macroscopically and microscopically completely encapsulated
IIA Microscopic transcapsular invasion
IIB Macroscopic invasion into surrounding fatty tissue or grossly adherent to but not through mediastinal pleura or pericardium
III Macroscopic invasion into neighboring organs (ie, pericardium, great vessels, or lung)
IVA Pleural or pericardial dissemination
IVB Lymphogenous or hematogenous metastasis

The World Health Organization (WHO) developed a histologic classification system in 1999, with revisions in 2004, and later 2015. [5] The WHO classification system has produced a standard agreement among pathologists at varying institutions. This system appears to be a prognostic indicator for tumor recurrence both independently and when combined with the Masaoka staging system. However, it may not be suitable as an independent prognostic indicator. [1, 6] The 2004 WHO histologic classification system is shown in Table 2, below.

Table 2. 2004 WHO Histologic Classification System (Open Table in a new window)

Type Histologic description
A Tumor in which foci having features of type A thymoma are admixed with foci rich in lymphocytes
 



B1



Tumor resembles normal functional thymus; combines large expanses having an appearance practically indistinguishable from that of normal thymic cortex with areas resembling thymic medulla
 



B2



Tumor in which neoplastic epithelial component appears as scattered plump cells with vesicular nuclei and distinct nucleoli among a heavy population of lymphocytes; perivascular spaces are common and sometimes very prominent; a perivascular arrangement of tumor cells resulting in a palisading effect may be seen.
 



B3



Thymoma predominantly composed of epithelial cells having a round or polygonal shape and exhibiting no or mild atypia; they are admixed with a mild component of lymphocytes, resulting in a sheetlike growth of the neoplastic epithelial cells
 



C



Thymic tumor exhibiting clear-cut cytologic atypia and a set of cytoarchitectural features no longer specific to the thymus, but rather analogous to those seen in carcinomas of the other organs; type C thymomas lack immature lymphocytes; whatever lymphocytes may be present are mature and usually admixed with plasma cells

The 2015 refinement of the WHO histologic classfication system added obligatory and optional features for clarification of previously ambiguous histologic criteria, including improved staining methods and immunohistochemistry. Thymomas frequently exhibit multiple histologic patterns, and instead of classifying them as "combined" types, the new classfication system lists the differing subtypes separately. The new system also includes immunohistochemical features in the criteria, and includes a new atypical type A variant subtype of thymoma. [5]

While the clinical significance of the WHO classification system is debatable, the system is useful as a tool that provides standardization among pathologists. We recommend using the updated 2015 WHO classification system, shown in Table 3, below.

                         Table 3. 2015 Revised WHO Classification System                                                                                        (Open Table in a new window)

Thymoma Subtype Obligatory Criteria Optional Criteria
Type A Occurrence of bland, spindle-shaped epithelial cells (at least focally); paucitya or absence of immature (TdT+) cells throughout the tumor Polygonal epithelial cells; CD20+ epithelial cells
Atypical type A variant Criteria of type A thymoma; in addition, comedo-type tumor necrosis; increased mitotic count (>4/2 mm2); nuclear crowding Polygonal epithelial cells; CD20+ epithelial cells
Type AB Occurrence of bland, spindle-shaped epithelial cells (at least focally); abundancea of immature (TdT+) T cells focally or thoughout tumor  Polygonal epithelial cells; CD20+ epithelial cells
Type B1 Thymuslike architecture and cytology: abundance of immature T cells, areas of medullary differentiation (medullary islands); paucity of polygonal or dendritic epithelial cells without clustering (ie, <3 contiguous epithelial cells) Hassall's corpuscles; perivascular spaces
Type B2 Increased numbers of single or clustered polygonal or dendritic epithelial cells intermingled with abundant immature T cells Medullary islands; Hassall corpuscles; perivascular spaces
Type B3 Sheets of polygonal slightly to moderately atypical epithelial cells; absent or rare intercellular bridges; paucity or absence of intermingled (TdT+) T cells Hassall corpuscles; perivascular spaces
MNTb Nodules of bland spindle or oval epithelial cells surrounded by an epithelial cell-free lymphoid stroma Lymphoid follicles; monoclonal B cells and/or plasma cells (rare)
Metaplastic thymoma Biphasic tumor composed of solid areas of epithelial cells in a background of bland-looking spindle cells; absence of immature T cells Pleomorphism of epithelial cells; actin, keratin, or EMA-positive spindle cells
Rare othersb    
  a Paucity versus abundance: any area of crowded immature T cells or moderate numbers of immature T cells in more than 10% of the investigated tumor are indicative of "abundance."



b Microscopic thymoma, sclerosing thymoma, lipofibroadenoma.



WHO = World Health Organization; MNT = micronodular thymoma with lymphoid stroma; EMA = epithelial membrane antigen



 

There has been a recent push to develop a traditional tumor, nodes, metastasis (TNM) system for the staging of thymoma and thymic cancer. A TET TNM staging system and node map proposed by the International Thymic Malignancies Interest Group (ITMIG) and the Thymic Domain of the Staging and Prognostic Factors Committee (TD-SPFC) of the International Association for the Study of Lung Cancer (IASLC) have been included in the 8th edition of the American Joint Committee on Cancer's AJCC Cancer Staging Manual. [7, 3, 8] Implementation of the 8th edition staging will begin in January 2018. [9]

This system has similarities to the Masaoka-Koga Staging system, especially the T component, and also includes parts of the WHO histologic classification system. The TNM system contains differences from the Masaoka-Koga system, including the distinction of whether the tumor is encapsulated or not, as encapsulation does not appear to be clinically relevant. The capsule is believed to be a process induced by the tumor rather than a normal anatomic structure. [3] The TNM system is outlined in Tables 4-7, below.

Table 4. T Stage (Open Table in a new window)

Category Definition
T1a Encapsulated or unencapsulated, with or without extension into mediastinal fat
T1b Extension to mediastinal pleura
T2 Extension to/involvement of pericardium
T3 Extension to/involvement of lung, brachiocephalic vein, superior vena cava, chest wall, phrenic nerve, hilar (extrapericardial) pulmonary vessels
T4 Extension to/involvement of aorta, arch vessels, main pulmonary artery, myocardium, trachea, or esophagus

Table 5. N Stage (Open Table in a new window)

Category Definition
N0 No nodal involvement
N1 Anterior (perithymic) nodes
N2 Deep intrathoracic, pericardial, or distant sites

Table 6. M Stage (Open Table in a new window)

Category Definition
M0 No metastatic disease
M1a Separate pleural or pericardial nodule(s)
M1b Pulmonary intraparenchymal nodule or distant organ metastasis

Table 7. Stage Grouping (Open Table in a new window)

Stage T N M
1 T1 N0 M0
2 T2 N0 MO
3a T3 N0 M0
3b T4 N0 M0
4a T any



T any



N1



N0,1



M0



M1a



4b T any



T any



N2



N any



M0,1a



M1b



There is hope that the proposed TNM system will provide a unified clinical and pathologic staging system that maintains the prognostic significance of the Masaoka-Koga staging system. More studies will be needed to establish this conclusion definitively.