Thymoma Staging
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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)
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)
Table 5. N Stage (Open Table in a new window)
Table 6. M Stage (Open Table in a new window)
Table 7. Stage Grouping (Open Table in a new window)
T any
T any
N1
N0,1
M0
M1a
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.
Tseng YC, Tseng YH, Kao HL, Hsieh CC, Chou TY, Goan YG, et al. Long term oncological outcome of thymoma and thymic carcinoma – an analysis of 235 cases from a single institution. PLoS One. 2017. 12 (6):e0179527. [Medline]. [Full Text].
Siesling S, van der Zwan JM, Izarzugaza I, Jaal J, Treasure T, Foschi R, et al. Rare thoracic cancers, including peritoneum mesothelioma. Eur J Cancer. 2012 May. 48 (7):949-60. [Medline]. [Full Text].
Detterbeck FC, Stratton K, Giroux D, Asamura H, Crowley J, Falkson C, et al. The IASLC/ITMIG Thymic Epithelial Tumors Staging Project: proposal for an evidence-based stage classification system for the forthcoming (8th) edition of the TNM classification of malignant tumors. J Thorac Oncol. 2014 Sep. 9 (9 Suppl 2):S65-72. [Medline]. [Full Text].
Kondo K, Yoshizawa K, Tsuyuguchi M, et al. WHO histologic classification is a prognostic indicator in thymoma. Ann Thorac Surg. 2004 Apr. 77(4):1183-8. [Medline].
Marx A, Chan JK, Coindre JM, Detterbeck F, Girard N, Harris NL, et al. The 2015 World Health Organization Classification of Tumors of the Thymus: Continuity and Changes. J Thorac Oncol. 2015 Oct. 10 (10):1383-95. [Medline]. [Full Text].
Guerrera F, Rendina EA, Venuta F, Margaritora S, Ciccone AM, Novellis P, et al. Does the World Health Organization histological classification predict outcomes after thymomectomy? Results of a multicentre study on 750 patients. Eur J Cardiothorac Surg. 2015 Jul. 48 (1):48-54. [Medline].
Kondo K, Van Schil P, Detterbeck FC, Okumura M, Stratton K, Giroux D, et al. The IASLC/ITMIG Thymic Epithelial Tumors Staging Project: proposals for the N and M components for the forthcoming (8th) edition of the TNM classification of malignant tumors. J Thorac Oncol. 2014 Sep. 9 (9 Suppl 2):S81-7. [Medline]. [Full Text].
Bhora FY, Chen DJ, Detterbeck FC, Asamura H, Falkson C, Filosso PL, et al. The ITMIG/IASLC Thymic Epithelial Tumors Staging Project: A Proposed Lymph Node Map for Thymic Epithelial Tumors in the Forthcoming 8th Edition of the TNM Classification of Malignant Tumors. J Thorac Oncol. 2014 Sep. 9 (9 Suppl 2):S88-96. [Medline]. [Full Text].
American Joint Committee on Cancer. Implementation of AJCC 8th Edition Cancer Staging System. AJCC. Available at https://cancerstaging.org/8thEdImplementation/Pages/FAQ.aspx. Accessed: July 25, 2017.
Falkson CB, Bezjak A, Darling G, et al. The management of thymoma: a systematic review and practice guideline. J Thorac Oncol. 2009 Jul. 4(7):911-9. [Medline].
American Society of Clinical Oncology. Thymoma: Stages. Cancer.Net. Available at http://www.cancer.net/cancer-types/thymoma/stages. May 2016; Accessed: July 25, 2017.
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
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
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
T any
T any
N1
N0,1
M0
M1a
T any
T any
N2
N any
M0,1a
M1b
Evan C Dannhardt, DO Resident Physician, Department of General Surgery, Keesler Air Force Base
Disclosure: Nothing to disclose.
Sarah Sauter Woodside, MD General Medical Officer, Flight Surgery Tour, Department of Surgery, Keesler Air Force Base
Sarah Sauter Woodside, MD is a member of the following medical societies: American Chemical Society, American College of Physicians, American College of Surgeons, Catholic Medical Association
Disclosure: Nothing to disclose.
A Letch Kline, MD Chief, Academic Affliations, Gulf Coast Veterans Health Care System; Clinical Assistant Professor, Department of Surgery, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine
A Letch Kline, MD is a member of the following medical societies: American College of Chest Physicians, American College of Surgeons, Southeastern Surgical Congress
Disclosure: Nothing to disclose.
Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Nothing to disclose.
Christopher D Braden, DO Hematologist/Oncologist, Chancellor Center for Oncology at Deaconess Hospital; Medical Director, Deaconess Hospital Outpatient Infusion Centers; Chairman, Deaconess Hospital Cancer Committee
Christopher D Braden, DO is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology
Disclosure: Nothing to disclose.
Neetu Radhakrishnan, MD Associate Professor (Adjunct) of Medicine, Division of Hematology/Oncology, University of Cincinnati Medical Center; Hematology/Oncology Medical Director, West Chester Outpatient Clinics
Neetu Radhakrishnan, MD is a member of the following medical societies: American College of Physicians, American Society of Clinical Oncology, American Society of Hematology
Disclosure: Nothing to disclose.
Quintessa Miller, MD
Quintessa Miller, MD is a member of the following medical societies: American College of Surgeons, National Medical Association
Disclosure: Nothing to disclose.
Thymoma Staging
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