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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
Malignant thymomas-invasive:
Type I- invasive with minimal atypia
Type II- moderate to marked atypia (thymic carcinoma)
Wick 1982
Lewis 1987
Thymomas
Thymic carcinoma
• 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.
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)
AIMS -To assess the ability of three histopathologists, experienced in thoracic surgical
reporting, consistently to classify thymomas as cortical, medullary, or mixed pattern tumours
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 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.
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
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
23 thymomas- 28%
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
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.