Clinical, pathological and prognostic aspects

THYMOMAS

 All thymomas originate from epithelial thymic cells  4% of them consist of a pure population of epithelial cells  Most have mixed populations of lymphoid cells to a varying extent

THYMOMAS

 20% of all mediastinal neoplasms  50% of all primary tumors in the anterior compartment  90% of thymic tumors are thymomas

THYMOMAS

 Slow-growing tumors  Exhibit malignant potential:   Local invasion Systemic metastasis without overt cytological features of malignancy  More common between ages 40 to 60

Clinical presentation

 ~50% - asymptomatic, discovered incidentally on CXR or at autopsy  ~30% local symptoms related with pressure or local invasion: SVC sdr., cough, chest pain, dysphonia, dysphagia  ~20%- 70% associated with an autoimmiune disease:     Myasthenia gravis Pure red cell aplasia Polymyosistis hypogammaglobulnemia

Prognostic factors

Their morphologic heterogeneity has caused much confusion regarding their classification.

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Several classifications have been proposed to correlate histology and clinical course.

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Previous studies have shown that the mediastinal invasion as reflected by the staging system of Masaoka negatively affects survival

Prognostic factors

Stage II tumors can recur after complete resection. indicating that the Masaoka classification might not be sufficient to classify the role of combined treatment modalities in patients with thymoma

Prognostic factors

Tumor extent but also grading the tumor could be required to predict prognosis and recurrence pattern which might help to define more precisely the role of adjuvant and neoadjuvant treatments.

Therefore, not only staging, the several histologic

classifications have been assessed, but they did not help to predict the evolution of thymic tumors after resection

Histologic classifications

 1961- Bernatz et al. –Mayo Clinic  According to the lymphocyte-epithelial cell ratio:    Lymphocytic Epithelial Mixed  Spindle subtypes At that time thymic carcinomas were not segregated but grouped with thymomas

1978 Levine and Rosai

 New classification of high clinical relevance  Benign thymoma- circumscribed  Malignant thymomas-invasive:   Type I- invasive with minimal atypia Type II- moderate to marked atypia (thymic carcinoma)

Wick 1982 Lewis 1987

 Thymomas  Thymic carcinoma Mixed thymomas with islets of thymic carcinoma behave clinically like typical thymoma more than like thymic carcinoma Thymomas carry the potential for malignant transformation into malignant thymic carcinoma

Marino & Muller Hermelink 1985

The origin of the cells, according to their resemblance to the normal epithelial cells in other parts of the thymic lobule Cortical thymoma - epi. cells are large, round, poligonal Medullary thymoma - epi. cells are smaller, spindle-shaped Cortical thymoma more agressive than medullary thymoma

Muller-Hermelink

    This classification was suggested to have independent prognostic implications 1990- Pescarmona- 80-patient cases found that M-H classif. reliably predicted prognosis Medullary thymoma   More encapsulated Clinically act benign Cortical thymoma   More invasive Malignant in nature

Muller-Hermelink

 Wilkins-1995 reported:  Few recurrences in patients with medullary and mixed thymoma  Higher recurrences in pts. with cortical thymomas

WHO classification Rosai, 1999

 Reflects the consensus of the pathologists  The cellular origins are emphasized  Is a successful synthesis of the most widely used classification  Resemble more the M-H classification  Currently –the preferred classification

WHO classification

 Type A- atrophic adult-life cells, spindle or oval in shape  Type B- bioactive thymic cells of fetus or infant with dentritic or epitheloid appearance  Further divided into B1, B2, B3 on the basis of increasing epithelial to lymfoid ratio and the emergence of atypia of the cells  Type AB- display the common features of type A and B  Type C – franckly malignant cells;low-to-high grade

CLASSIFICATIONS

ROSAI-LEVINE Tip WHO MULLER-HERMELINK BENIGN THYMOMA A MEDULLARY THYMOMA BENIGN THYMOMA AB MIXED THYMOMA MALIGNANT TYPE I B1 PREDOMINANT CORTICAL MALIGNANT TYPE I B2 CORTICAL THYMOMA MALIGNANT TYPE I B3 WELL-DIFFERENTIATED CARCINOMA MALIGNANT TYPE II C THYMIC CARCINOMA

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WHO Classification

Type A thymoma.

This type accounts for approximately 4% to 7% of all cases of thymoma, and is also referred to as spindle cell thymoma or medullary thymoma. • The prognosis for people with type A thymoma is good, with a 15-year relative survival rate near 100%.

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WHO Classification

Type AB thymoma.

Type AB thymoma, or mixed thymoma, accounts for approximately 28% to 34% of thymoma cases. Type AB thymoma is similar to type A; however, there are lymphocytes that are mixed in the tumor, and approximately 16% of cases are thought to be associated with myasthenia gravis. The prognosis for people with type AB thymoma is also good, with a 15-year relative survival rate of approximately 90%.

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WHO Classification

Type B1 thymoma.

Type B1 thymoma accounts for approximately 9% to 20% of thymoma cases, and is also known as lymphocyte-rich thymoma, lymphocytic thymoma, predominantly cortical thymoma, and organoid thymoma. This type of thymoma has a high concentration of lymphocytes in the tumor, but the cells of the thymus appear normal. Approximately 57% of type B1 thymoma cases are thought to be associated with myasthenia gravis. The prognosis for people with type B1 thymoma is also good, with a 20-year relative survival rate of approximately 90%.

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WHO Classification

Type B2 thymoma.

Type B2 thymoma has a high concentration of lymphocytes, like type B1 thymoma; however, the thymus cells do not appear normal. Type B2 thymoma is also known as cortical thymoma and polygonal cell thymoma, and accounts for approximately 20% to 36% of all thymoma cases.

About 71% of cases of type B2 thymoma are thought to be associated with myasthenia gravis. The 20-year relative survival rate for people with type B2 thymoma is approximately 60%.

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WHO Classification

Type B3 thymoma.

Type B3 thymoma is also known as epithelial thymoma, atypical thymoma, squamoid thymoma, and well differentiated thymoma. It accounts for approximately 10% to 14% of thymoma cases. This type of thymoma has few lymphocytes, and the thymus cells look close to normal.

About 46% of type B3 thymoma cases are thought to be associated with myasthenia gravis, and the 20-year relative survival rate is approximately 40%.

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WHO Classification

Type C thymoma (or Thymic carcinoma).

Type C thymoma is very aggressive. The cells in thymic carcinoma do not look like normal thymus cells, but like cancers in other organs of the body. • Thymic carcinoma may start from a pre-existing thymoma that has transformed into a more aggressive tumor. • This type of thymoma is often advanced when diagnosed, • Can be divided into two categories: low grade (better prognosis) and high grade (more likely to grow and spread quickly).

WHO Classification

Low-grade thymic carcinoma includes: - basaloid, - mucoepidermoid, - well-differentiated squamous cell types.

High-grade thymic carcinoma includes: - anaplastic/undifferentiated, - clear cell, - poorly differentiated squamous cell, - sarcomatoid, - small cell/neuroendocrine types.

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Thymic carcinoma

People with thymic carcinoma do not have associated myasthenia gravis.

• The five-year relative survival rate of people with thymic carcinoma is 38%. • The 10-year relative survival rate of people with thymic carcinoma is 28%.

Prognosis after histologic type

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WHO Histologic Description

A AB B1 B2 B3 C Medullary thymoma Mixed thymoma Cortical thymoma

Free Survival at 10 years, %

Predominantly cortical thymoma Well-differentiated thymic carcinoma Thymic carcinoma 100 100 83 83 35 28 Series of 100 thymomas resected in Japan between 1973 and 2001 using the WHO classification .

“

Prognostic Relevance of Masaoka and Muller Hermelink Classification in Patients With Thymic Tumors”

Didier Lardinois, MD, Renate Rechsteiner, MD, R. Hubert La¨ ng, MD, Matthias Gugger, MD, Daniel Betticher, MD, Christian von Briel, MD, Thorsten Krueger, MD, and Hans-Beat Ris, MD (Ann Thorac Surg 2000;69:1550 –5) Department of Thoracic and Cardiovascular Surgery, Institute of Pathology, Division of Pulmonary Medicine, Institute of Oncology and Clinic of Radio-oncology, University of Berne, Berne, Switzerland

Results

Masaoka stage found Stage I - 31 patients (44.9%), stage II - 17 (24.6%), stage III - 19 (27.6%), and stage IV - 2 (2.9%). The 10-year overall survival rate was; 83.5% for stage I, 100% for stage IIa, 58% for stage IIb, 44% for stage III, 0% for stage IV.

Results

Histologic classification according to Muller-Hermelink medullary tumors in 7 patients (10.1%),

- mixed in 18 (26.1%),

- organoid in 14 (20.3%), - cortical in 11 (15.9%), - well-differentiated carcinoma in 14 (20.3%), - endocrine carcinoma in 5 (7.3%), 10- year overall survival rates of 100%, 75%, 92%, 87.5%, 30%, and 0%, respectively.

Medullary, mixed, and well-differentiated organoid tumors were correlated with stage I and II, Well-differentiated thymic carcinoma and endocrine carcinoma with stage III and IV (p < 0.001)

Results

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Multivariate analysis showed age, gender, myasthenia gravis, and postoperative adjuvant therapy not to be significant predictors of survival after complete resection, whereas

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the Muller-Hermelink and Masaoka classifications were independent significant predictors for overall (p < 0.05)

Masaoka anatomic classification 1981

 Based on the presence or abscence of gross or microscopic invasion of the tumor capsule as well as the metastatic status  Medullary and mixed thymomas are usually not invasive and correspond to stages I and II  Cortical thymomas are more commonly invasive and more likely to be in stages III and IV

Masaoka Classification-1981

STAGE I Encapsulated tumor with no gross or microscopic invasion TREATMENT Complete surgical excision STAGE II Macroscopic invasion into the mediastinal fat or pleura or microscopic invasion into the capsule TREATMENT Complete surgical excision and postoperative radiotherapy to decrease the incidence of local recurrence STAGE III Macroscopic STAGE IVA STAGE IVB i nvasion of the pericardium, great vessels, or lung TREATMENT Complete surgical excision and postoperative radiotherapy to decrease the incidence of local recurrence Pleural or pericardial metastatic spread TREATMENT Surgical debulking, radiotherapy, and chemotherapy Lymphogenous or hematogenous metastases TREATMENT Surgical debulking, radiotherapy, and chemotherapy

Modified Masaoka Clinical Staging as used by Koga 1994 and Nakagawa 2003 More widely adopted Incorporated microscopic incomplete capsular invasion into stage I, leaving transcapsular invasion in stage II Stage I - fully encapsulated tumor ( a thymoma completely surrounded by a fibrous capsule that is not infiltrated in its full thickness) Stage II- tumor infiltrates beyond the capsule into the thymus or fatty tissue. Adhesion to the mediastinal pleura may be present Stage III- macroscopic invasion into neighboring organs Stage IVA- pleural or pericardial dissemination Stage IVB- lymphogenous or hematogenous metastases

“Observer variation in the histopathological classification of thymoma: correlation with prognosis

.”

A Dawson, N B Ibrahim, and A R Gibbs Department of Histopathology, Llandough Hospital, Cardiff.

AIMS -To assess the ability of three histopathologists, experienced in thoracic surgical reporting, consistently to classify thymomas as cortical, medullary, or mixed pattern tumours METHODS--Three histopathologists classified 74 thymomas (none frank carcinomas) as of either cortical, medullary, or mixed pattern, on two separate occasions. Kappa statistics were used to assess inter- and intra-observer agreement. Tumour type was compared with surgical stage as a predictor of biological behaviour.

RESULTS Inter- and intra-observer agreement were only moderate (kappa 0.48 and 0.52, respectively).

For only 26 of 74 tumours could a categorisation be consistently agreed on. . The prognoses for those 26 of 74 cases appeared to be at variance from previously reported studies, and showed internal inconsistency, with the mixed pattern category showing a worse survival than the cortical category. For the group as a whole, however, stage at presentation was related to survival, with an overall five year survival of 78% 100% for stage I, 84% for stage II, 27% for stage III and 0% for stage IV

CONCLUSIONS

The classification of thymomas into cortical, medullary, or mixed pattern tumours is difficult to apply. Surgical stage remains a better guide to prognosis.

Proposed WHO TNM Classification

 So much controversy during the past 4 decades, no authorized TNM system has been adopted  The proposed WHO TNM scheme remains tentative pending validation of its reliability, reproducibility and predictive power

WHO TNM Classification

 T factor       Tx- primary can not be assessed T0- no evidence of primary tumor T1- macroscopically completely encapsulated and microscopically no capsular invasion T2- macroscopically adhesion or invasion into surrounding fatty tissue or mediastinal pleura or microscopic invasion into the capsule T3-invasion into neighboring organs such as pericardium, great vessels, lung T4- pleural or pericardial dissemination

WHO TNM Classification

 N factor  Nx- regional lymph nodes can not be assessed  N0- no lymph nodes metastasis  N1- metastases to anterior mediastinal lymph nodes  N2- metastases to intrathoracic lymph nodes except anterior mediastinal lymph nodes  N3- metastases to extrathoracic lymph nodes

WHO TNM Classification

 M factor  Mx- distant metastases can not be assessed  M0- no distant metastases  M1- hematogenous metastases

Stage grouping as detailed by Haserjion 2005

 Stage I- T1, N0,M0  Stage II- T2, N0, M0  Stage III- T1, N1, MO; T2, N1, MO, T3, N0-1, MO  Stage IV- T4, any N, M0; any T, N2-3, M0; any T, any N, M1

DIAGNOSIS

• • • Biopsy: If a patient presents with atypical features or is found to have an invasive tumor and is under consideration for induction therapy, obtaining preoperative biopsy is indicated.

The limited anterior mediastinotomy (Chamberlain approach) is the standard approach that typically is performed over the projection of the tumor.

A thoracoscopic approach for biopsy also can be used

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DIAGNOSIS

Chest CT scan is the imaging procedure of choice in patients with MG. – – Thymic enlargement should be determined because most enlarged thymus glands on CT scan represent a thymoma. CT scan with intravenous contrast dye is preferred – – – to show the relationship between the thymoma and surrounding vascular structures, to define the degree of its vascularity, and to guide the surgeon in removal of a large tumor, possibly involving other mediastinal structures

MV, male, 46 years old, 6w. history of MG- Oss. III, CT suspicious for thymoma, Op. 2004, histology- thymic lymphoid hyperplasia + mediastinal ectopies, post.op.- complete remission

GE, 19 years old man, Hashimoto thyroiditis, hemolytic anemia, (Hb-4g/dl), CT- thymoma, op.dec 2005, histology- thymic lymphoid hypertrophy

PF, female, 21 years old, MG- OSS III, CT- thymic hyperplasia, op. 1997- histology- lymphocitic thymoma

DIAGNOSIS

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Magnetic resonance imaging (MRI).

An MRI uses magnetic fields, not x-rays, to produce detailed images of the body.

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Positron emission tomography (PET) scan.

In a PET scan, radioactive sugar molecules are injected into the body. Cancer cells absorb sugar more quickly than normal cells, so they light up on the PET scan.

PET scans are often used to complement information gathered from CT scan, MRI, and physical examination. CT scanning reveals evidence of an anterior mediastinal mass, the PET scan shows a hypermetabolic mass consistent with this location, thereby raising suspicion of malignancy. PET scanning should be added to the armamentarium as an available diagnostic modality to aid in staging and excluding extramediastinal involvement

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PROGNOSIS

The prognosis of a person with a thymoma is based on the tumor's gross characteristics at operation, not the histological appearance.

Benign tumors are noninvasive and encapsulated.

Conversely, malignant tumors are defined by local invasion into the thymic capsule or surrounding tissue. The Masaoka staging system of thymomas is the most commonly accepted system.

Preponderance of evidence indicates that all thymomas, except completely encapsulated stage 1 tumors, benefit from adjuvant radiation therapy

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SURGERY

The preferred approach is a median sternotomy providing adequate exposure of the mediastinal structures and allowing complete removal of the thymus, If the tumor is small and appears readily accessible, perform a total thymectomy with contiguous removal of mediastinal fat.

If the tumor is invasive, perform a total thymectomy in addition to en bloc removal of involved pericardium, pleura, lung, phrenic nerve, innominate vein, or superior vena cava. Resect one phrenic nerve; however, if both phrenics are involved, do not resect either nerve, and debulk the area. Clip areas of close margins or residual disease to assist the radiation oncologist in treatment planning

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Radiotherapy

Adjuvant radiation therapy in completely or incompletely resected stage III or IV thymomas is considered a standard of care. The use of postoperative radiation therapy in stage II thymomas has been more questionable. Thymomas are indolent tumors that may take at least 10 years to recur; therefore, short-term follow-up will not depict relapses accurately.

Furthermore, the gross appearance of tumor invasiveness is subjective, depending on the opinion of the surgeon. In one report at Massachusetts General Hospital, 22% of patients (5 out of 23) with stage II disease developed recurrence, leading to a proposed recommendation that postoperative radiation be instituted in all patients with stage II thymoma

Radiotherapy

• • In a study conducted by Curran and colleagues, of 21 patients with stage II and III disease who did not undergo postoperative radiation therapy, 8 had recurrence in the mediastinum. The 5 patients who received adjuvant radiation did not have recurrences.

A series from Memorial Sloan Kettering Cancer Center, showed that adjuvant radiation therapy did not improve survival or decrease recurrence in stage II and III disease. To reduce the incidence of local relapse, perform postoperative adjuvant radiation therapy in patients without completely encapsulated stage I tumors.

Thymomas operated in the IIIrd. Surgical Unit

 82 thymic lesions operated over a period 1982-2008  23 thymomas- 28%  Out of 23 thymomas- 19 cases were associated with MG 82,6%

Histologic distribution

Clasificarea WHO Type A-2 cases Type AB-7 cases Muller-Hermelink medullary- 2 cases mixt -7 cases Type B1-9 cases Type B2- 0 cases Type B3-3 cases predominant cortical-9 cases cortical 0 cases well differentiated -3 cases Type C- 1case carcinom anaplazic-1case Thymic carcinoid – 1 case

TREATMENT  Stage Masaoka I- 9 cases:  4 no adjuvant therapy,   2 radiochemotherapy, death at 4 months and 6 years due to acute respiratory failure, 1 radiotherapy only  2 chemotherapy only WHO classification of thymomas stage Masaoka I Type A -2 cases Type B1-5 cases,- 2 deaths Type B3-1case

Treatment

 Masaoka II- 5 cases  1 case radiotherapy only  1 case chemotherapy only  3 cases radio+chemotherapy After Who classification: Type AB-2 Type B1-2 Type B3-1

Treatment

 Masaoka III- 8cases: radiochemotherapy in all  3 deaths:   2 deaths at 2(C) and 6(AB) postop. years due to acute resp. failure 1 death at 17(AB) postop. years due to miocardial infarction Who classification: Type AB-5 cases, Type B1-1, Type B3-1, Type C-1 Ovaral mortality 5 out of 28 cases: 1 medical cause 1 unresectable malignant II thymomas- Bx

Complications radiotherapy

Complications :  radiation pericarditis,  radiation pneumonitis,  pulmonary fibrosis Consider carefully the risk versus benefit ratio of adjuvant radiation therapy because deaths from these complications have been reported

Recurrence

 Relapse after primary therapy for a thymoma may occur after 10-20 years.  Therefore, long-term follow-up probably should continue to be performed throughout the patient's life.

Chemotherapy

• • • The most common chemotherapy drugs in the treatment of thymoma are: • • • • • doxorubicin (Adriamycin, Rubex), cisplatin (Platinol), cyclophosphamide (Cytoxan, Neosar), etoposide (VePesid, Etopophos, Toposar), and ifosfamide (Ifex, Holoxan). The common combinations used for the treatment of thymoma include: cyclophosphamide, doxorubicin, and cisplatin, or etoposide and cisplatin.

Chemotherapy

• Chemotherapy combinations are sometimes used to shrink the tumor before surgery if the thymoma is more advanced. • Chemotherapy may also be used for stage IV thymoma or recurrent thymoma that is not surgically removable.

Chemotherapy

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Drug combinations.

The combination of carboplatin (Paraplatin) and paclitaxel (Taxol) is being studied for the treatment of advanced thymoma.

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New agents.

Therapies explored in clinical trials: Premetrexed (Alimta)- antifolate antineoplastic agent for treating advanced thymic cancers.

• Imatinib (Gleevec) is a drug that turns off an enzyme that causes cells to become cancerous and multiply.

It is being studied to treat patients with thymic tumors over expressing the c-kit and/or PDGF genes.

“Asociatia chimioterapie-radioterapie in tratamentul timoamelor maligne” Anda I.Buiuc, Lidia Andriescu, Elena Albulescu Rev. Romana de Oncologie, 36(2),171-175, 1999  11 invasive thymoma patients, treated over a period of 10 years: 1989-1999 • Multimodal treatment: surgery, chemotherapy, radiotherapy.

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Results

7 timoame invasive associate cu MG au fost initial operate, (5 rezectie complete si 2 incomplete) 3 au primit numai radioterapie -2, asociere radio/chimio-2 numai chimioterapie .

Radioterapia a fost adm.la 4-6 sapt postop. Cu o doza totala de 44-50Gy prin 2 campuri opuse AP mediastinale. La 2 cazuri rxT s-a interrupt din cauza insuficientei respiratorii cu intubare consecutive.

1 caz a decedat in timpul radioterapiei dupa adm. De CP iv 200mg/zi si dexa 16mg/zi urmate de plasmafereza.

Cazurile numai cu trat.ChT- CP 200mg/zi perop 10 zile/luna, 4-6 cicluri.

Rezultate: 1 remisie comleta, 5 remisii partiale- mestinon 1/zi, 1 deces.

Radiochemotherapy in locally advanced malignant thymomas 4 cases of locally advanced malignant thymoma proven on biopsy Case I -invasive mixed thymoma, stage III, female, 31years old, 4 sessions of ADOC-ADOC (Adriamicine,Cisplatin,Vincristine,Ciclophosphamide) partial response+ radiotherapy 44GY + 1 session ADOC. At 6 years the tumor size decreased with 75%, no symptoms.

Case 2- female, 27 years old, mixed thymoma stage III, SVC sdr.

4 sessions ADOC with complete remission+ radiotherapy 44 Gy, At 1 year posttherapy- no detectable tumor on CT, and no symptoms

AS, female, 27 years old, CT-1998- TUMOR MASS WITH NECROTIC AREAS IN THE ANTERO-SUPERIOR MEDIASTINUM

CT aspect after chemo/radiotherapy

CT aspect after chemo/radiotherapy

Radiochemotherapy in locally advanced thymomas  Case 3- male, 27 years old, thymic carcinoma stage III- SVC sdr. Chemotherapy- cisplatin, vinblastin, bleomicina, adriamicina- 5 sessions with partial remission after the first 2 cycles, radiotherapy-44Gy , CHTX.- ADOC+CISPLATIN/ETOPOSID, partial response, death at 2 years from diagnosis  Case 4.- male, 38 years old, anaplasic thymic carcinoma invading the ribs, left lung, compressing trachea, SVC.

Chemotherapy + RXT: 2 cycles ADOC, 40GY- reduction 50%, 3 cycles ADOC+ bleomicina- complete remission for 4 months, Bilateral adrenal MTS, cisplatin/etoposid partial response after 3 cycles.

Liver MTS death at 15 months from diagnosis.

Future treatment

• Studies have investigated the molecular changes in thymomas. In one study, 10 out of 12 thymomas exhibited epidermal growth factor receptor (EGFR) expression. This information would be useful in selecting patients that may benefit from EGFR inhibitors as part of their treatment regimen. • • Other areas of investigation include apoptosis-related markers, such as p63, a member of the p53 family. p63 was found to be expressed in virtually all thymomas.

Further research pertaining to the biology of thymomas will allow more adequate approaches to treatment.

CT, 60 years old, thymoma+MG, Oss.IV, op. 2002, Lymphocitic thymoma (type I malignant thymoma)-Masaoka II ( well encapsulated but microscopic capsular invasion), adhesions to left M. pleura which was resected

Radiotherapy 44 Gy, chemotherapy, 1 year CP+PDN Pericarditis and mixedema at 1 year postRxT Remission of MG for 5 years, 2008- AChE

AM, 46 years old, multinodular goitre with hyperthyroidy and myasthenia gravis

Compressive goitre Retrosternal goitre

Normal thymus on CT scan ?, Total thyroidectomy for MNG, myasthenia gravis persisted

Normal Chest Normal thymus

Antero- inferior mediastinal mass

Paramedian low retrosternal mass Well-encapsulated mass

Thymic scintigraphy- hypercaptation of 99m-Tc tetrofosmin consistent with a thymoma Thymectomy 6 months after total thyroidectomy

Timom AB, HE, invazie extracapsulara in grasimea peritimica

Timom AB, focar de invazie extracapsulara, van Gieson

GM, 32 years old, Cushing sdr. , ACTH -292pg/ml.(n<46). CT- anterior mediastinal mass, pericardial adhesion, Op. sept. 2008-thymectomy+pericardectomy+mediastinal pleurectomy. Histology: well-differentiated thymic neuroendocrine carcinoma, transcapsular invasion, pT2NxMx, Immunehistochemistry: NSE, chromogranin, synaptophizin- intense positive, MNF116-moderate positive, Ki 67-10%, post.op. ACTH-37pg/ml. Chushingoid clinical aspect disapeared

GV, 59 years old, MG-Oss.III, CT- anterior mediastinal mass invading left mediastinal pleura, Op. -2004, Histology- predominant cortical thymoma, B1, Masaoka II, Adjuvant radiochemotherapy

GV, B1 type thymoma, R0 extended thymectomy, good recovery after radiochemotherapy

A.Gh. 65 years old, 3 w. of severe myasthenia, Oss.III

CT-calcified thymoma adherent to the left mediastinal pleura, op. 2003, histology- type A, medullary thymoma without capsular invasion, chemotherapy CP+PDN, obvious improvement

TD, 39 years old, MG-Oss.III, intubated for 3 w. 3PF without result, CT –mediastinal mass, op. jan. 2007, after 3 w. of intubation, tracheostomy, histology- thymus with cystic degeneration, after 3 months CR

Conclusions

 No clear histologic distinction between benign and malignant thymomas exists.  The propensity of a thymoma to be malignant is determined by the invasiveness of the thymoma.