thymoma diagnosis work up and management final.pptx

This presentation on the presentation, work up, management of thymoma focusing on latest guide lines. It enamurates the clinical suspicious, age of presentation, differential diagnosis and treatment.

1. Thymic Carcinoma Dr Iqra Iftikhar PGR RADIATION ONCOLOGY 3/12/2023 1

2. Presentation layout Introduction Inmol data Anatomy Presentation Types Workup Staging Treatment 3/12/2023 2

3. Introduction Adults aged 40 to 60 . 20% of all mediastinal tumors but 50% anterior mediastinal tumors . Thymic carcinomas represent less than 1% of thymic tumors . No known etiologic factors 3/12/2023 3

4. Inmol Data 2022 1 7210 0.013% 2021 5 7174 0.06% 2020 7 5743 0.12% 2019 1 7365 0.013% 2018 2 5877 0.03% 2017 1 5296 0.018% 2016 1 5481 0.018% 3/12/2023 4

5. Presentation layout Introduction Inmol data Anatomy Presentation Types Workup Staging Treatment 3/12/2023 5

6. ANATOMY Thymus is an anterior mediastinal structure R esponsible for the maturation of T-cells. Lymphatic drainage is to the Lower cervical , I nternal mammary, H ilar nodes. Thymus consists of Capsule C ortex, Medulla . 3/12/2023 6

7. Histologically , it includes Epithelial cells, E pithelioreticular cells (form Hassall’s corpuscles ), Myoid cells, E arly T lymphocytes (“ thymocytes ”), B Lymphocytes 3/12/2023 7

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9. IHC Markers of Thymic carcinoma CD 20+ intratumoral B Lymphocyte CD57+ CD5+ Tdt + T cells CK+ 3/12/2023 9

10. Presentation layout Introduction Inmol data Anatomy Presentation Types Workup Staging Treatment 3/12/2023 10

11. Presentation Often incidental finding on imaging. Local symptoms due to mass effect Chest pain, D yspnea , C ough, P hrenic nerve palsy, SVC syndrome. 3/12/2023 11

12. Para neoplastic syndromes prior to or after diagnosis. Up to 50% of patients will present with Myasthenia Gravis ; I t is less common for MG patients to have associated thymoma. Other less common Para neoplastic syndromes R ed cell aplasia, I mmunodeficiency, M ultiorgan autoimmunity . 3/12/2023 12

13. Differentials Mediastinal mass Non-neoplastic conditions intrathoracic goiter , thymic cysts, lymphangiomas, lymphangiomas Masses in the anterior mediastinum can be Non-neoplastic conditions Non-neoplastic conditions , lymphomas, Non-neoplastic conditions , 3/12/2023 13 Non-neoplastic conditions Neoplastic conditions intrathoracic goiter , Non-neoplastic conditions Neoplastic conditions Intrathoracic goiter Lymphomas Thymic cysts Thymic carcinoids Lymphangiomas Thymolipomas Thymic carcinomas Germ cell tumors Lung mets

14. Thymoma Thymic carcinoma Cells resemble non cancerous thymic cells Myasthenia Gravis 10-80% Cells different from normal thymic cells No association with MG Grows slowly Rarely undergo metastasis Grow rapidly Significant metastasis CD5, CD 70, CD117 Expression epithelial cells not seen CD5, CD 70, CD117 Expression epithelial cells 60% Long survival due to indolent course More common Short survival progressive disease Less common 3/12/2023 14

15. Thymic Carcinoma Subtypes • Squamous carcinomas Squamous cell carcinoma, NOS Basaloid carcinoma Lymphoepithelial carcinoma
• Adenocarcinomas Adenocarcinoma, NOS 3/12/2023 15 Squamous carcinomas Adenocarcinomas Mucoepidermoid carcinoma Squamous cell carcinoma, NOS Adenocarcinoma, NOS Clear cell carcinoma Basaloid carcinoma Low grade papillary adenocarcinoma Sarcomatoid carcinoma Lymphoepithelial carcinoma Thymic carcinoma with adenoid cystic carcinoma-like features Carcinosarcoma Adenocarcinoma, enteric-type Adenosquamous carcinoma

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21. Presentation layout Introduction Inmol data Anatomy Presentation Types Workup Staging Treatment 3/12/2023 21

22. WORK UP H&P. If thymoma suspected and considered resectable , biopsy may be omitted and resection performed. If unresectable /inoperable , core needle biopsy to confirm diagnosis (open biopsy also possible; biopsy should not violate pleural space ); M ultidisciplinary evaluation indicated. 3/12/2023 22

23. Serum b- hCG and AFP (rule out germ cell tumor ), CBC, CMP, serum level of anti-Ach antibodies to assess for MG. Imaging: Chest CT with contrast, PET/CT (optional), PFTs. 3/12/2023 23

24. Presentation layout Introduction Inmol data Anatomy Presentation Types Workup Staging Treatment 3/12/2023 24

25. Masaoka –Koga Staging System for Thymoma Stage Definition I Grossly and microscopically completely encapsulated tumor IIa Microscopic transcapsular invasion IIb Macroscopic invasion into surrounding fatty tissue or grossly adherent to but not breaking through mediastinal pleura or pericardium III Macroscopic invasion into neighboring organ (e.g., pericardium, great vessels, or lung) IVA Pleural or pericardial dissemination IVB Distant metastasis 3/12/2023 25

26. Modified Masaoka clinical staging Thymoma STAGE I Macro + microscopically completely encapsulated STAGE II II A Microscopic transcapsular invasion II B Macroscopic invasion fatty tissue Adherent to but not through mediastinal pleura or pericardium 3/12/2023 26

27. STAGE III Macroscopic invasion adjacent organs ( pericardium , lung) III A Without invasion great vessel III B With invasion great vessel STAGE IV Pleural pericardial dissemination Lymphogenous or hemetogenous mets 3/12/2023 27

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29. Thymic carcinomas TNM Tx Tumor cannot be assessed T0 No tumor T1 Tumor encapsulated Extend mediastinal fat T1a Mediastinal pleura not involved T1b Mediastinal pleura involved 3/12/2023 29

30. T2 Direct invasion pericardium T3 Direct invasion lung , brachiocephalic , phrenic nerve , chest wall, extra pericardial pulmonary artery and vein T4 Invasion, aorta , arch vessel, trachea, oesophagus , myocardium , intrapericardial pul artery 3/12/2023 30

31. N0 No nodes N1 Anterior Perithymic nodes + N2 Deep intrathoracic and cervical nodes + 3/12/2023 31

32. M0 No mets M1 Mets pleura, pericardium , distant mets M1a separate pleural pericardial nodes M1b pulmonary intrapericardial nodes or distant mets 3/12/2023 32

33. Presentation layout Introduction Inmol data Anatomy Presentation Types Workup Staging Treatment 3/12/2023 33

34. TREATMENT Surgery : Total thymectomy with negative margins is mainstay of therapy in resectable cases. This is typically performed with median sternotomy . 3/12/2023 34

35. Resection of both phrenic nerves should be avoided to prevent severe respiratory compromise. Signs and symptoms of MG should be controlled medically with anticholinesterase inhibitors prior to surgery. Thoracic surgeons with experience in managing thymomas and thymic carcinomas. Stage ≥ II cases should be discussed and evaluated by a multidisciplinary team. 3/12/2023 35

36. 3/12/2023 36 Surgical biopsy should be avoided if a resectable thymoma S ubstantial potential of tumor seeding when the tumor capsule is violated . Biopsy of a possible thymoma should avoid a transpleural approach because of the substantial risk of converting a stage I thymoma to a stage IV thymoma by spreading tumor within the pleural space . Prior to surgery, patients should be evaluated for signs and symptoms of myasthenia gravis and should be medically controlled prior to undergoing surgical resection .

37. Complete resection may require the resection of adjacent structures, including the pericardium, phrenic nerve, pleura, lung , and even major vascular structures. Surgical clips should be placed at the time of resection to areas of close margins, residual disease, or tumor adhesion to unresected normal structures to help guide accurate RT when indicated. During thymectomy , the pleural surfaces should be examined for pleural metastases . If feasible, resection of pleural metastases to achieve complete gross resection. 3/12/2023 37

38. CHEMOTHERAPY Platinum-based CHT is indicated for thymic carcinoma , U nresectable disease, medically inoperable with gross disease . D ownstaging and postoperatively based on degree of resection . For diffuse metastases, consider CHT alone . No randomized trials have identified superior regimen . Common regimens include cyclophosphamide/ adriamycin /cisplatin (CAP ), cisplatin/ etoposide (PE), or carboplatin/paclitaxel . 3/12/2023 38

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41. RADIATION Indications : PORT should be offered for positive surgical margins , stage III disease and considered for any thymic carcinoma. Dose: RT dosing is based on degree of resection with 45 to 54 Gy , for R0 55 to 60 Gy , for R1 60 to 70 Gy for R2, Definitive RT indicated for medically inoperable disease, with the addition of CHT and its sequencing empiric. 3/12/2023 41

42. Radiation Dose Unresectable disease . 60 to 70 Gy • For adjuvant treatment, 45 to 50 Gy for clear/close margins 54 Gy for microscopically positive resection margins . 60–70 Gy gross residual disease (similar to patients with unresectable disease ),when conventional fractionation is applied . P alliative setting , 8 Gy in a single fraction , 20 Gy in 5 fractions , 30 GY in 10 fractions 3/12/2023 42

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44. Radiation volume GTV Any grossly visible tumor. Surgical clips indicative of gross residual tumor should be included for postoperative adjuvant RT . CTV for postoperative RT E ntire thymus (for partial resection cases), surgical clips, and any potential sites with residual disease. The CTV should be reviewed with the thoracic surgeon . Extensive elective nodal irradiation (ENI ) (entire mediastinum and bilateral Supraclavicular nodal regions) is not recommended, as thymomas do not commonly metastasize to regional lymph nodes . PTV should consider the target motion and daily setup error . 3/12/2023 44

45. The PTV margin should be based on the individual patient’s motion, simulation techniques used (with and without inclusion motion), reproducibility of daily setup of each clinic 3/12/2023 45

46. OAR Tolerance Dose Heart Thyroid Mean < 26 Gy V45< 100% Lung Esophagus V 20 < 30% MEAN < 34% V50 < 40% Spinal Cord TMJ Parotid Dmax < 50Gy V60 < 60% B/L MEAN < 25 Gy U/L MEAN < 30-32 Gy 3/12/2023 46

47. Toxicity related to CHT Nephrotoxicity Haemorrhagic cystitis Cardiotoxicity Neuropathy Myalgia Secondary malignancy 3/12/2023 47

48. Toxicity related to RT Acute: Fatigue, C ough , S kin erythema. 3/12/2023 48

49. Late : H ypothyroidism , Second malignancy Cardiac morbidity Radiation fibrosis 3/12/2023 49

50. Follow up Thymoma Thymic Carcinoma 6 monthly H & P CT CHEST with contrast for 2 years than annually for 10 years 6 monthly H & P CT CHEST with contrast for 2 years than annually for 5 years 3/12/2023 50

51. Survival rates Thymoma 10 year overall survival Thymic carcinoma 5 year overall survival Stage I 90% Stage I – II 91% Stage II 70% Stage III – IV 90% ( 5 Yr OS with complete resection) Stage III – IV 31% ( even with complete resection) 3/12/2023 51

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55. Case Summary ABC 49y/F known MG patient since 2007, resident Lahore presented with C/O Muscle weakness Slurred speech 2/9/21 CT CAP Large mediastinal mass 8.4 x 5.1 x 5.9cm Encasement left brachiocephalic vein with narrowing 3/12/2023 55

56. Encasement left subclavian and carotid vessel No visceral mets T4 N0 M0 Stage IIIB 16/4/21 Mediastinal mass biopsy THYMOMA Tdt + Tcells CK+ KI67 High PI 3/12/2023 56

57. PLAN 3DCRT 60Gy/30fx to mediastinal mass 3/12/2023 57