R0 resection is defined as complete resection without macroscopic or microscopic involvement of the margin by the tumour. R1 (incomplete) resection indicates microscopic tumour at the resection margin. R2 (incomplete) resection is defined as macroscopic tumour present at the resection margin. If the specimen is disrupted at the time of gross evaluation and cannot be reconstructed, then the assessment of margins might not be possible.
1 Kondo K and Monden Y (2003). Lymphogenous and hematogenous metastasis of thymic epithelial tumors. Ann Thorac Surg 76(6):1859-1864; discussion 1864-1855.
2 Ruffini E, Detterbeck F, Van Raemdonck D, Rocco G, Thomas P, Weder W, Brunelli A, Evangelista A, Venuta F and European Association of Thoracic Surgeons (ESTS) Thymic Working Group (2014). Tumours of the thymus: a cohort study of prognostic factors from the European Society of Thoracic Surgeons database. Eur J Cardiothorac Surg 46(3):361-368.
3 Moser B, Scharitzer M, Hacker S, Ankersmit J, Matilla JR, Lang G, Aigner C, Taghavi S and Klepetko W (2014). Thymomas and thymic carcinomas: prognostic factors and multimodal management. Thorac Cardiovasc Surg. 62(2):153-160.
Single selection value list:
• No nodes submitted or found
• Not involved
Involvement of lymph nodes by TETs is an adverse prognostic factor.1,2 Lymph node status should be recorded according to the recommended anatomic map in relation to the ITMIG & IASLC TNM system,1,3 namely anterior (perithymic) nodes (N 1) and deep intrathoracic or cervical nodes (N 2), whilst any positive lymph node was viewed as stage IVb within the Masaoka-Koga system. As the location of lymph nodes found during the gross inspection of a thymectomy specimen may be problematic, either the specimen needs to be properly oriented by the surgeon, or labelled specifically within separate pots. Lymph nodes outside N1 and N2 are regarded as distant metastasis (pM1b).1
1 Kondo K, Van Schil P, Detterbeck FC, Okumura M, Stratton K, Giroux D, Asamura H, Crowley J, Falkson C, Filosso PL, Giaccone G, Huang J, Kim J, Lucchi M, Marino M, Marom EM, Nicholson AG and Ruffini E (2014). 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 9(9 Suppl 2):S81-87.
2 Viti A, Bertolaccini L and Terzi A (2014). What is the role of lymph nodal metastases and lymphadenectomy in the surgical treatment and prognosis of thymic carcinomas and carcinoids? Interact Cardiovasc Thorac Surg 19(6):1054-1058.
3 Bhora FY, Chen DJ, Detterbeck FC, Asamura H, Falkson C, Filosso PL, Giaccone G, Huang J, Kim J, Kondo K, Lucchi M, Marino M, Marom EM, Nicholson AG, Okumura M, Ruffini E and Van Schil P (2014). 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 9(9 Suppl 2):S88-96.
if involved, record Number of lymph nodes examined and Number of positive lymph nodes for each location type
Immunohistochemical analysis of thymic resection specimens may be performed for several reasons:
1. To exclude or confirm the presence of a tumour of thymic epithelial origin1
2. To aid in subtyping of thymomas2
3. To establish the origin of a thymic carcinoma as either a primary thymic carcinoma or a metastasis
The differential diagnostic spectrum of thymoma is related to either its epithelial component or to the lymphoid component. The lymphoid component of “B-type” thymoma and of thymic follicular hyperplasia may raise the suspicion of non-Hodgkin lymphoma, especially T-lymphoblastic leukaemia/lymphoma. Immunohistochemistry may be applied to type the lymphoid population [normally composed of immature, CD3/terminal deoxynucleotidyl transferase (TdT/CD1a/CD99+) lymphocytes], or to confirm the presence of an epithelial component, which may be highlighted by pan-cytokeratin and/or p63 stains. The epithelial component in thymic epithelial tumours with a sparse lymphoid component may raise the possibility of either a germ cell tumour or metastatic carcinoma.1,3 Germ cell tumours may be diagnosed by appropriate immunohistochemical stains including SALL4, OCT4, CD117, CD30, D2-40, human chorionic gonadotropin (hCG), placental alkaline phosphatase (PLAP), and α-fetoprotein (AFP).1
Subtyping of thymomas is primarily based on histology; immunohistochemical stains (cytokeratin and/or p63) may be helpful in the evaluation of the density of the epithelial cells in B-type thymoma thus aiding the diagnosis of B1/2/3 thymoma. Similarly, cytokeratin stains may be used to confirm the epithelial nature of the spindle cells in type A, type AB and in metaplastic thymoma. Epithelial expression of CD20 is reported to be more frequent among type A and AB thymomas.4 Neuroendocrine markers may be useful to rule out neuroendocrine tumours.2
Distinguishing thymoma (in particular type B3 thymoma) and thymic carcinoma may occasionally be problematic; there are no immunohistochemical markers that can reliably segregate these entities. However, CD5, CD117 and the recently described markers GLUT1 and MUC1 show a higher incidence of staining in thymic carcinoma (in particular, thymic squamous cell carcinoma) compared to thymoma.5,6 Ki-67 labelling index in epithelial tumour cells of ≥13.5% has been suggestive of thymic carcinoma.7
The diagnosis of thymic carcinoma essentially involves the exclusion of metastasis; immunohistochemical analysis may support a diagnosis of thymic carcinoma but cannot establish the diagnosis with certainty. Expression of CD5, particularly in combination with CD117 positivity, lends some support to a diagnosis of thymic carcinoma. Several new markers (FoxN1 and CD205) may further support a diagnosis of thymic carcinoma. Other markers may be applied to rule out thymic carcinoma by confirming a non-thymic origin, such as TTF-1. However, given the great diversity in histological subtypes of thymic carcinoma, the specificity of markers routinely used to diagnose carcinoma of a particular origin may be considerably lower in this situation.8
1 den Bakker MA and Oosterhuis JW (2009). Tumours and tumour-like conditions of the thymus other than thymoma; a practical approach. Histopathology 54(1):69-89.
2 den Bakker MA, Roden AC, Marx A and Marino M (2014). Histologic classification of thymoma: a practical guide for routine cases. J Thorac Oncol 9(9 Suppl 2):S125-130.
3 Marchevsky A, Marx A, Strobel P, Suster S, Venuta F, Marino M, Yousem S and Zakowski M (2011). Policies and reporting guidelines for small biopsy specimens of mediastinal masses. J Thorac Oncol 6(7 Suppl 3):S1724-1729.
4 Chilosi M, Castelli P, Martignoni G, Pizzolo G, Montresor E, Facchetti F, Truini M, Mombello A, Lestani M, Scarpa A and et al. (1992). Neoplastic epithelial cells in a subset of human thymomas express the B cell-associated CD20 antigen. Am J Surg Pathol 16(10):988-997.
5 Kaira K, Murakami H, Serizawa M, Koh Y, Abe M, Ohde Y, Takahashi T, Kondo H, Nakajima T and Yamamoto N (2011). MUC1 expression in thymic epithelial tumors: MUC1 may be useful marker as differential diagnosis between type B3 thymoma and thymic carcinoma. Virchows Arch 458(5): 615-620.
6 Kojika M, Ishii G, Yoshida J, Nishimura M, Hishida T, Ota SJ, Murata Y, Nagai K and Ochiai A (2009). Immunohistochemical differential diagnosis between thymic carcinoma and type B3 thymoma: diagnostic utility of hypoxic marker, GLUT-1, in thymic epithelial neoplasms. Mod Pathol 22(10):1341-1350.
7 Roden AC, Yi ES, Jenkins SM, Donovan JL, Cassivi SD, Garces YI, Marks RS and Aubry MC (2015). Diagnostic significance of cell kinetic parameters in World Health Organization type A and B3 thymomas and thymic carcinomas. Hum Pathol 46(1):17-25.
8 Marx A, Ströbel P, Badve SS, Chalabreysse L, Chan J, Chen G, de Leval L, Detterbeck F, Girard N, Huang J, Kurrer MO, Lauriola L, Marino M, Matsuno Y, Molina TJ, Mukai K, Nicholson AG, Nonaka D, Rieker R, Rosai J, Ruffini E and Travis WD (2014). ITMIG Consensus Statement on the Use of the WHO Histological Classification of Thymoma and Thymic Carcinoma: Refined Definitions, Histological Criteria and Reporting. J Thor Oncol 9:596-611.
If performed, record positive, negative and equivocal markers and interpretation and conclusions
Interpretation and conclusions
Single selection value list:
• Not performed
Molecular studies have not been applied routinely for the diagnosis of thymic epithelial tumours. A diagnosis of NUT carcinoma needs immunohistochemical and/or molecular genetic confirmation.1,2 The sensitivities of NUT immunohistochemical staining have been reported as 60% and 87%.1,2 There have been a few reports of primary mediastinal synovial sarcoma confirmed by FISH.
1 French CA (2010). Demystified molecular pathology of NUT midline carcinomas. J Clin Pathol 63(6):492-496.
2 Haack H, Johnson LA, Fry CJ, Crosby K, Polakiewicz RD, Stelow EB, Hong SM, Schwartz BE, Cameron MJ, Rubin MA, Chang MC, Aster JC and French CA (2009). Diagnosis of NUT midline carcinoma using a NUT-specific monoclonal antibody. Am J Surg Pathol 33(7):984-991.
At least 15 different stage classification systems have been proposed, beginning as far back as 1978.1 Until 2016, the most widely used was the Masaoka system,2 modified and refined in 1994,3 with refinement of definitions for anatomic staging parameters proposed in 2011.4 This has now been replaced by a TNM-based classification based on data from the ITMIG retrospective database of over 8000 patients.5 In the new TNM 8th editions, both UICC6 and AJCC7, T stage is based on the extent of direct invasion of mediastinal structures (see above section),8 nodal disease is based on involvement of lymph nodes in anterior (perithymic) (N1) and deep/cervical (N2) compartments, and M stage based on the presence of separate pleural and pericardial nodules (M1a) and pulmonary intraparenchymal nodule or distant organ metastasis (M1b).9 The Masaoka-Koga system could still be used if part of ongoing studies but the TNM system should be used henceforth as the method of staging.10
1 Filosso PL, Ruffini E, Lausi PO, Lucchi M, Oliaro A and Detterbeck F (2014). Historical perspectives: The evolution of the thymic epithelial tumors staging system. Lung Cancer 83(2):126-132.
2 Masaoka A, Monden Y, Nakahara K and Tanioka T (1981). Follow-up study of thymomas with special reference to their clinical stages. Cancer 48(11):2485-2492.
3 Koga K, Matsuno Y, Noguchi M, Mukai K, Asamura H, Goya T and Shimosato Y (1994). A review of 79 thymomas: modification of staging system and reappraisal of conventional division into invasive and non-invasive thymoma. Pathol Int 44(5):359-367.
4 Detterbeck FC, Nicholson AG, Kondo K, Van Schil P and Moran C (2011). The Masaoka-Koga stage classification for thymic malignancies: clarification and definition of terms. J Thorac Oncol 6(7 Suppl 3):S1710-1716.
5 Bhora FY, Chen DJ, Detterbeck FC, Asamura H, Falkson C, Filosso PL, Giaccone G, Huang J, Kim J, Kondo K, Lucchi M, Marino M, Marom EM, Nicholson AG, Okumura M, Ruffini E and Van Schil P (2014). 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 9(9 Suppl 2):S88-96.
6 Brierley JD, Gospodarowicz MK and Wittekind C (eds) (2016). UICC TNM Classification of Malignant Tumours, 8th Edition, Wiley-Blackwell.
7 Amin MB, Edge SB and Greene FL et al (eds) (2017). AJCC Cancer Staging Manual. 8th ed., Springer, New York.
8 Nicholson AG, Detterbeck FC, Marino M, Kim J, Stratton K, Giroux D, Asamura H, Crowley J, Falkson C, Filosso PL, Giaccone G, Huang J, Kondo K, Lucchi M, Marom EM, Okumura M, Ruffini E and Van Schil P (2014). The IASLC/ITMIG Thymic Epithelial Tumors Staging Project: proposals for the T Component for the forthcoming (8th) edition of the TNM classification of malignant tumors. J Thorac Oncol 9(9 Suppl 2):S73-80.
9 Kondo K, Van Schil P, Detterbeck FC, Okumura M, Stratton K, Giroux D, Asamura H, Crowley J, Falkson C, Filosso PL, Giaccone G, Huang J, Kim J, Lucchi M, Marino M, Marom EM, Nicholson AG and Ruffini E (2014). 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 9(9 Suppl 2):S81-87.
10 Rami-Porta R (ed) (2016). Staging Manual in Thoracic Oncology, 2nd edition: An International Association for the Study of Lung Cancer Publication, Developed in collaboration with AJCC and UICC, Editorial Rx Press, North Fort Myers, FL, US.
Note that permission to publish cancer staging tables may be needed in your implementation. It is advisable to check.
Record as applicable
• r - recurrent
• m - multiple primary tumours
• y - post treatment