Transcript THYMOMAS - UMF Iasi

Clinical, pathological and
prognostic aspects
Lidia Ionescu Andriescu, Cozmin Radulescu,Daniel Guta,
Irina Trifescu, Cristian Dragomir- the IIIrd.Surgical Unit
Dan Ferariu, Doina Butcovan- Pathology Departement
December- 2008
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.
 Several classifications have been proposed to correlate histology
and clinical course.
 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
BENIGN THYMOMA
AB
MIXED THYMOMA
MALIGNANT TYPE I
B1
PREDOMINANT CORTICAL
MALIGNANT TYPE I
B2
MALIGNANT TYPE I
CARCINOMA
MALIGNANT TYPE II
MEDULLARY THYMOMA
CORTICAL THYMOMA
B3
C
WELL-DIFFERENTIATED
THYMIC CARCINOMA
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%.
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%.
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%.
WHO Classification
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•
•
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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%.
WHO Classification
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•
•
•
Type B3 thymoma.
Type B3 thymoma is also known as epithelial thymoma,
atypical thymoma, squamoid thymoma, and welldifferentiated 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%.
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.
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
WHO
Histologic Description
Free Survival at
10 years, %
• A
Medullary thymoma
100
• AB
Mixed thymoma
100
• B1
Predominantly cortical thymoma
83
• B2
Cortical thymoma
83
• B3
Well-differentiated thymic carcinoma 35
• C
Thymic carcinoma
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
 Multivariate analysis showed age, gender, myasthenia
gravis, and postoperative adjuvant therapy not to be
significant predictors of survival after complete
resection, whereas
 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 invasion of the pericardium, great vessels, or lung
TREATMENT Complete surgical excision and postoperative radiotherapy to
decrease the incidence of local recurrence
STAGE IVA
Pleural or pericardial metastatic spread
TREATMENT Surgical debulking, radiotherapy, and chemotherapy
STAGE IVB
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
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
• Magnetic resonance imaging (MRI).
An MRI uses magnetic fields, not x-rays, to produce detailed images of the body.
• 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
PROGNOSIS
• The prognosis of a person with a thymoma is based on the
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•
•
•
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
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
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
Muller-Hermelink
Type A-2 cases
medullary- 2 cases
Type AB-7 cases
mixt
-7 cases
Type B1-9 cases
predominant cortical-9 cases
Type B2- 0 cases
cortical0 cases
Type B3-3 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:
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•
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•
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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
Drug combinations.
• The combination of carboplatin (Paraplatin) and paclitaxel (Taxol) is
being studied for the treatment of advanced thymoma.
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 overexpressing 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.
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-Tctetrofosmin 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,
Immunhistochemistry: NSE, chromogranin, synaptophizin- intense positive,
MNF116-moderate positive, Ki 67-10%,
post.op. ACTH-37pg/ml. Chushingoid clinical aspect disappeared
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.