Version 0 Thymic Epithelial Tumours 2nd revision, published September 2017



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In relation to the new TNM-based staging system, the presence of capsular invasion was not prognostically significant in data from the ITMIG retrospective database study and tumours are therefore categorised as pT1a, independent of whether the capsule is breached, if the tumour has not directly infiltrated the mediastinal pleura. Similar data were found in separate meta-analyses.5,6 Invasion through the mediastinal pleura was also not found to be of prognostic significance in the cases from the ITMIG database, although evidence from Japanese patients demonstrated that invasion of the mediastinal pleura was associated with the cumulative incidence of recurrence (CIR)7 so this parameter remains part of the dataset, to be collected for further review and is categorised as pT1b, although it is recognised that this anatomic margin may not be easily identifiable on histology.5 Discussion with the surgeon may facilitate its identification in specimens.8
In order to maintain consistency in data collection, the following definitions, agreed by expert consensus, were proposed by an ITMIG-based group:
• Pericardial invasion - microscopic involvement of the pericardium (either partial in the fibrous layer or penetrating through the serosal layer);
• Visceral pleura/lung - microscopically confirmed direct penetration through the outer elastin layer of the visceral pleura with or without invasion into the lung parenchyma.
In relation to the great vessels, opinions differed between involvement being defined as tumour cells being present within the adventitia, media or lumen. The consensus opinion, in the context of great vessels, was that tumour cells present within the media is the preferred histological compartment through which to define involvement, as it is easily seen compared to the adventitia on an elastic stain, and its involvement is likely relevant to surgical management in terms of need for partial resection and repair. In a similar fashion, involvement of the phrenic nerve is defined as tumour cells being present within the perineurium. ‘Other’ should be used if tumours infiltrate structures such as myocardium, trachea, oesophagus or chest wall. Involvement of muscle layers is viewed as the most reproducible parameter through which to collect data on positive involvement.

References
1 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.
2 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.
3 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.
4 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.
5 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.
6 Gupta R, Marchevsky AM, McKenna RJ, Wick M, Moran C, Zakowski MF and Suster S (2008). Evidence-based pathology and the pathologic evaluation of thymomas: transcapsular invasion is not a significant prognostic feature. Arch Pathol Lab Med 132(6):926-930.
7 Ogawa K, Uno T, Toita T, Onishi H, Yoshida H, Kakinohana Y, Adachi G, Itami J, Ito H and Murayama S (2002). Postoperative radiotherapy for patients with completely resected thymoma: a multi-institutional, retrospective review of 103 patients. Cancer 94(5):1405-1413.
8 Detterbeck FC, Moran C, Huang J, Suster S, Walsh G, Kaiser L and Wick M (2011). Which way is up? Policies and procedures for surgeons and pathologists regarding resection specimens of thymic malignancy. J Thorac Oncol 6:S1730-1738.

Heading

Core

Tumour capsule

Single selection value list:
• No invasion beyond capsule or limit of the thymus
• Invasion beyond the mediastinum

 

 

Core

Mediastinal pleura

Single selection value list:
• Not involved
Involved
Cannot be assessed
Not applicable

 

 

Core

Pericardium

Single selection value list:
• Not involved
• Involved
• Cannot be assessed
• Not applicable

 

 

Core

Lung (pulmonary parenchyma, visceral pleura, or both)

Single selection value list:
• Not involved
• Involved (specify lobe/s of the lung)
• Cannot be assessed
• Not applicable

 

 

Core

Great vessels

 

 

Heading

Core

Brachiocephalic (innominate) vein

Single selection value list:
• Not involved
• Involved
• Cannot be assessed
• Not applicable

 

 

Core

Superior vena cava

Single selection value list:
• Not involved
• Involved
• Cannot be assessed
• Not applicable

 

 

Core

Extrapericardial pulmonary artery or veins

Single selection value list:
• Not involved
• Involved
• Cannot be assessed
• Not applicable

 

 

Core

Aorta (ascending, arch or descending)

Single selection value list:
• Not involved
• Involved
• Cannot be assessed
• Not applicable

 

 

Core

Arch vessels

Single selection value list:
• Not involved
• Involved
• Cannot be assessed
• Not applicable

 

 

Core

Intrapericardial pulmonary artery

Single selection value list:
• Not involved
• Involved
• Cannot be assessed
• Not applicable

 

 

Core

Phrenic nerve

Single selection value list:
• Not involved
• Involved
• Cannot be assessed
• Not applicable

 

 

Core

Other involved organ(s)/site(s) by direct spread

Text

 

 

Core

SEPARATE EXTRATHYMIC TUMOUR NODULES/METASTASES

 

Separate extrathymic tumour nodules must be recorded as they form part of the TNM staging system. These are divided into two groups: first, those nodules that are limited to the pericardium and/or pleura (sometimes referred to as pericardial and pleural seeding), which constitute pM1a in TNM staging: second, nodules that are either within the lung parenchyma or distant organs, which constitute pM1b.1,2 The number of nodules in the pleura/pericardium should be recorded as there is some evidence that greater numbers portend an adverse prognosis.3
These synchronous metastatic foci will usually have the same morphology as the primary thymic neoplasm and need to be distinguished from the far rarer synchronous primary thymic epithelial tumours (see MACROSCOPIC SITE OF PRIMARY TUMOUR).4,5

References


1 Detterbeck FC, Moran C, Huang J, Suster S, Walsh G, Kaiser L and Wick M (2011). Which way is up? Policies and procedures for surgeons and pathologists regarding resection specimens of thymic malignancy. J Thorac Oncol 6:S1730-1738.
2 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.
3 Okuda K, Yano M, Yoshino I, Okumura M, Higashiyama M, Suzuki K, Tsuchida M, Usuda J and Tateyama H (2014). Thymoma patients with pleural dissemination: nationwide retrospective study of 136 cases in Japan. Ann Thorac Surg 97(5):1743-1748.
4 Bernatz PE, Harrison EG and Clagett OT (1961). Thymoma: a clinicopathological study. J Thorac Cardiovasc Surg 42:424-444.
5 Leuzzi G, Marino M, Alessandrini G, Sciuto R, Pescarmona E and Facciolo F (2015). Synchronous triple thymoma and true thymic hyperplasia simultaneously detected by F FDG PET-CT. Rev Esp Med Nucl Imagen Mol 34(4):272-274.

Heading

Core

Pleural and/or pericardial

Single selection value list:
• Not identified
• Present (specify location/s and optionally the number/location)

 

 

Core

Pulmonary intraparenchymal

Single selection value list:
• Not identified
• Present

 

 

Core

Distant organ

Single selection value list:
• Not identified
• Present (specify site(s))

 

 

Non-core

RESPONSE TO NEOADJUVANT THERAPY

Single selection value list:
• Cannot be assessed
• Prior treatment not known
• No prior treatment
• No response
• Positive response
o No or minimal tumour response
o Partial tumour response
o Complete

There is no recommended or agreed system for tumour regression grading (TRG) in TETs. There are sparse reports documenting the effects of neoadjuvant chemotherapy on TETs1 but there are no systematic studies on this subject. In other organ systems including carcinomas of the breast, stomach, oesophagus and colorectum, there is evidence that the response to neoadjuvant therapy provides prognostic information. Schemes for TRG for several of these organ systems have been published.2 Steroid therapy may also affect morphology by eliminating lymphocytes although this is not viewed as part of neoadjuvant therapy.
In TETs, RECIST (Response Evaluation Criteria In Solid Tumours) parameters have been recorded as indicators of TRG. Histological features which have been assessed as TRG factors include decrease in number of viable cells,3,4 fibrosis,5 necrosis6,7 and cystic change. Biological cell cycle markers (e.g. p53) were used in one study combined with viability according lung cancer parameters (25% increments).4 However, few studies have systematically recorded TRG elements in a methodical fashion1 and there are no studies which have correlated TRG with disease outcome. A scoring system for the degree of fibrosis, adapted from lung cancer TRG, has been applied to TETs5 and it has been suggested that macroscopic evaluation with microscopic confirmation of the extent of necrosis should be recorded and that the viable tumour cell proportion should be recorded in 10% increments.8,9 It should be noted that similar changes to those documented in neoadjuvant-treated TETs may be observed in non-treated thymomas (necrosis, cystic change) as degenerative features.1
It is recommended that the response to neoadjuvant treatment in TET be recorded with the following provisos:
1. TRG is performed on resection specimens
2. Resected specimens should be adequately sampled (at least 1 block per centimetre of maximum tumour diameter)
3. The amount of viable tissue should be assessed as a percentage of the tumour
4. TRG should be scored using a 3-tier system – refer to Table 1.

Table 1: Proposed 3-tiered TRG system

Score 1: Criterion: Mainly viable tumour with no or minimal regression-associated fibro-inflammatory and cystic change* limited to a few foci. TRG: No or minimal tumour response
Score 2: Criterion: Multifocal or diffuse regression associated fibro-inflammatory changes and cystic change*, with viable tumour ranging from diffuse sheets, streaks or nodules, to extensive regression with multifocal but easily identifiable residual tumour. TRG: Partial tumour response
Score 3: Criterion: Mainly regression, with few irregularly scattered individual tumour cells or cell groups (all measuring less than 2 mm), or no residual tumour identified. TRG: Complete or near-complete response
* Regression associated fibro-inflammatory changes: fibrosis associated with macrophages, including foam cells, mixed inflammatory cells and calcification.


References


1 Weissferdt A and Moran CA (2013). The impact of neoadjuvant chemotherapy on the histopathological assessment of thymomas: a clinicopathological correlation of 28 cases treated with a similar regimen. Lung 191(4):379-383.
2 McCluggage WG, Judge MJ, Clarke BA, Davidson B, Gilks CB, Hollema H, Ledermann J, Matias-Guiu X, Mikami Y, Stewart CJR, Vang R and Hirschowitz L (2015). Dataset for reporting of ovary, fallopian tube and primary peritoneal carcinoma: Recommendations from the International Collaboration on Cancer Reporting (ICCR). Mod Path 28(8):1101-1122.
3 Korst R.J et al (2014). Neoadjuvant chemoradiotherapy for locally advanced thymic tumors: a phase II, multi-institutional clinical trial. J Thorac Cardiovasc Surg 147(1):36-44, 46 e31.
4 Mineo TC et al (2010). New predictors of response to neoadjuvant chemotherapy and survival for invasive thymoma: a retrospective analysis. Ann Surg Oncol 17(11):3022-3029.
5 Kawasaki H et al (2014). Weekly chemotherapy with cisplatin, vincristine, doxorubicin, and etoposide followed by surgery for thymic carcinoma. Eur J Surg Oncol 40(9):1151-1155.
6 Wright CD et al (2008). Induction chemoradiotherapy followed by resection for locally advanced Masaoka stage III and IVA thymic tumors. Ann Thorac Surg 85(2):385-389.
7 Kim ES et al (2004). Phase II study of a multidisciplinary approach with induction chemotherapy, followed by surgical resection, radiation therapy, and consolidation chemotherapy for unresectable malignant thymomas: final report. Lung Cancer 44(3):369-379.
8 Detterbeck FC, Moran C, Huang J, Suster S, Walsh G, Kaiser L and Wick M (2011). Which way is up? Policies and procedures for surgeons and pathologists regarding resection specimens of thymic malignancy. J Thorac Oncol 6:S1730-1738.
9 Huang J et al (2010). Standard outcome measures for thymic malignancies. J Thorac Oncol 5(12):2017-2023.

 

Non-core

COEXISTENT PATHOLOGY

Multi select value list (choose all that apply):
• Thymic hyperplasia
o Follicular
o Epithelial
o True
• Cystic changes
o In tumour
o In adjacent thymus
• Other (specify)

Thymectomy specimens from myasthenia gravis patients commonly demonstrate pathologic findings in the non-neoplastic thymus and the most common feature is thymic follicular hyperplasia. Thymic hyperplasia can be classified into three types: follicular, epithelial and true hyperplasia. Follicular hyperplasia is defined by the presence of B-cell follicles irrespective of the size or weight of the thymus. The standardised macroscopic and histopathological work-up of thymectomy specimens including the grading of thymic follicular hyperplasia has been reported by MGTX .1,2 Epithelial hyperplasia (nodular epithelial hyperplasia, also called ‘microscopic thymoma’) is a thymic epithelial cell proliferation forming discrete microscopic islands and it is not infrequently observed in thymic tissue from myasthenia gravis patients.3,4 It should be differentiated from ‘microthymoma’ which represents microscopic-sized true thymoma.5 True thymic hyperplasia is an increase in volume of the thymus which maintains normal histology.6 Because of wide variations of sizes and weights of the thymus in the normal population, true thymic hyperplasia is difficult to define except for extreme cases. The presence of thymic hyperplasia adjacent to a thymoma, irrespective of the type, has no known clinical significance.
Cystic changes can involve both thymic epithelial tumours and adjacent thymus.7-11 The description of cystic changes, although not of prognostic significance, may be important for clinicopathological correlation.

a Thymectomy and Myasthenia gravis multicentre, international clinical trial (MGTX)



References
1 Ströbel P, Moritz R, Leite MI, Willcox N, Chuang WY, Gold R, Nix W, Schalke B, Kiefer R, Müller-Hermelink HK, Jaretzki III A, Newsom-Davis J and Marx A (2008). The ageing and myasthenic thymus: A morphometric study validating a standard procedure in the histological workup of thymic specimens. J Neuroimmunol 201-202:64-73.
2 Marx A, Pfister F, Schalke B, Nix W and Ströbel P (2012). Thymus pathology observed in the MGTX trial. Ann NY Acad Sci 1275:92-100
3 Pescarmona E, Rosati S, Pisacane A, Rendina EA, Venuta F and Baroni CD (1992). Microscopic thymoma: histological evidence of multifocal cortical and medullary origin. Histopathology 20:263-266.
4 Puglisi F, Finato N, Mariuzzi L, Marchini C, Floretti G and Beltrami CA (1995). Microscopic thymoma and myasthenia gravis. J Clin Pathol 48:682-683.
5 Cheuk W, Tsang WY and Chan JK (2005). Microthymoma: definition of the entity and distinction from nodular hyperplasia of thymic epithelium (so-called microscopic thymoma). Am J Sur Pathol 29:415-419
6 Hofmann WJ, Möller P and Otto HF (1987). Thymic hyperplasia. I. True thymic hyperplasia. Review of the literature. Klin Wochenschr 65:49-52.
7 Suster S and Rosai J (1991). Multilocular thymic cyst: an acquired reactive process. Study of 18 cases. Am J Surg Pathol 15(4):388-398.
8 Moran CA and Suster S (2001). Thymoma with prominent cystic and hemorrhagic changes and areas of necrosis and infarction: a clinicopathologic study of 25 cases. Am J Surg Pathol 25(8):1086-1090.
9 Weissferdt A and Moran CA (2011). Thymic carcinoma associated with multilocular thymic cyst: a clinicopathologic study of 7 cases. Am J Surg Pathol 35(7):1074-1079.
10 Nakamura S, Tateyama H, Taniguchi T, Ishikawa Y, Kawaguchi K, Fukui T, Mizuno T, Ishiguro F and Yokoi K (2012). Multilocular thymic cyst associated with thymoma. A clinicopathologic study of 20 cases with an emphasison the pathogenesis of cyst formation. Am J Surg Pathol 36:1857-1864.
11 Araki T, Sholl LM, Gerbaudo VH, Hatabu H and Nishino M (2014). Intrathymic cyst: clinical and radiologic features in surgically resected cases. Clin Radiol 69(7):732-738

 

Core

MARGIN STATUS

Single selection value list:
• Cannot be assessed
• Not involved
• Involved
o Macroscopic (specify margin/s, if possible)
o Microscopic (specify margin/s, if possible)

Complete resection has been repeatedly shown to be a prognostic parameter in thymomas and thymic carcinomas.1-3 Therefore, the evaluation and recording of the margin status is important. To be able to assess the margins, orientation of the specimen is crucial. As discussed earlier (see MACROSCOPIC SITE OF PRIMARY TUMOUR), once the tumour is removed from the tumour bed, orientation becomes difficult. Furthermore, the fatty tissue can become easily disrupted. Therefore, orientation of the specimen should ideally be started in situ by the surgeon and areas of concern need to be clearly communicated to the pathologist. Anterior, posterior, right and left surfaces should be clearly distinguished (e.g. inked with different colours or with a detailed block key). Furthermore, the surgeon should mark areas of concern and also representative areas adjacent to the pericardium, the large vessels (or mark these structures if resected) and right/left mediastinal pleural surfaces (if resected). If the resection specimen includes neighbouring organs such as lung, or large vessels, margins need to be evaluated on those organs as well.
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