Thymic tumors arise from the thymus gland in the anterior mediastinum. Thymomas are the most common type of thymic tumor and generally have an indolent growth pattern. Complete surgical resection is the primary treatment for thymomas. Adjuvant radiation and chemotherapy may be considered depending on the stage and completeness of resection. Thymic carcinomas are more aggressive and have a poorer prognosis than thymomas. Treatment involves surgical resection when possible along with chemotherapy and radiation.

1. Thymic Tumors
Dr. Kiran Kumar BR

2. Anatomy Of Mediastinum:
Boundaries
– Anterior: sternum
– Posterior: vertebral column
– Superior: thoracic inlet
– Inferior: diaphragm
– Lateral: parietal pleura

3. Superior
Mediastinum
T5
Anterior
Mediastinum
Posterior
Mediastinum
Middle
Mediastinum
Sternal
Angle
T4
divided into superior mediastinum and inferior mediastinum by an imaginary line passing
through sternal angle anteriorly lower border of 4th thoracic vertebra posteriorly
Mediastinum divisions

4. Thymus
Embryology
• 6th week
– Primordia arise from 3rd pharyngeal
pouches
• 14th week to 16th week
– Cortex and medulla complete
– Phenotypic characterization
– X- or H-shaped
– Average
• 15-30 grams.

5. INTRODUCTION
Mediastinal malignancies are quite heterogeneous in scope.
Invasive thymomas and thymic carcinomas are relatively rare
tumors, together representing about 0.2% to 1.5% of all malignancies.
Thymic carcinomas are rare, accounting for only 0.06% of all thymic
neoplasms.
Arising from thymic, neurogenic, lymphatic, germinal, and mesenchymal
tissues, mediastinal tumors are usually located in the anterior mediastinum
but can also appear in the posterior and middle mediastinum or neck.

7. Thymomas:
The thymus gland is an irregular lobulated lymphoepithelial organ in the
anterior mediastinum.
Embryologically, the thymus is derived from the endoderm of the lower
portion of the germ cell tumors can all arise within the thymus, only
thymomas, thymic carcinomas, and thymolipomas arise from true
thymic elements

8. Epidemiology:
Thymomas are exceedingly rare.
The Surveillance, Epidemiology, and End Results (SEER) project
reported the thymoma incidence to be 0.15 per 100,000 person-years.15
For patients with associated myasthenia gravis, the peak age is in the
fourth decade, whereas for patients without myasthenia gravis, the peak
age is in the seventh decade or later.
Thymomas are more common in men than in women.

9. Thymomas are the most common of the anterior mediastinal
masses, accounting for about 30% of all such masses.
Of all mediastinal masses, thymomas represent 20% of the
tumors in adults6,11,24,25 and 15% in pediatric populations.
Associations of thymomas with Epstein-Barr virus,lymphoepitheliomas,
radiation exposure, and cytogenetic abnormalities have been suggested.

10. • Natural History
Thymomas are generally characterized by an indolent growth pattern
that can be locally invasive. Thirty percent to 40% of patients with a
thymoma also have myasthenia gravis.
The vast majority of thymomas are cytologically bland tumors and
approximately half of them are noninvasive.
Roughly one-third of thymomas are asymptomatic and found
incidentally on chest x-rays.

11. Symptomatic thymomas, about 40% of cases present with symptoms relating to
impingement by the intrathoracic mass, ranging from cough, chest pain, dyspnea,
hoarseness, superior vena cava obstruction, and even tumor hemorrhage.
Another 30% present with systemic signs and the remainder present with signs of
myasthenia gravis. Thymomas are associated with several parathymic syndromes,
the most common of which is myasthenia gravis.
Other autoimmune conditions such as benign cytopenia, hypogammaglobulinemia,
and polymyositis have been reported in 2% to 5% of patients.
Myasthenia gravis occurs in approximately 45% of patients with thymomas,
Conversely, only 10% to 15% of patients with myasthenia gravis have a thymoma
Roughly one-fourth of patients with myasthenia gravis will have a normal
thymus.58 Of the 75% who have an abnormal thymus, only 15% to 20% will have a
thymoma and 60% will have thymic lymphoid hyperplasia.

12. Other systemic symptoms occur in 5% to 10% of patients
with thymomas as part of a constellation of autoimmune disorders.
These include erythroid and neutrophil hypoplasia, pancytopenia,
Cushing syndrome, DiGeorge syndrome, carcinoid
syndrome, Lambert-Eaton syndrome, pernicious anemia,
nephrotic syndrome, syndrome of inappropriate antidiuretic
hormone hypersecretion, Whipple’s disease, lupus erythematosus,
pemphigus, myotonic dystrophy, scleroderma, polymyositis,
polyneuritis, myocarditis polyarthropathy, myotonic dystrophy,
Sjogren syndrome, Addison’s disease, panhypopituitarism,
sarcoidosis, hypogammaglobulinemia, ulcerative colitis, rheumatoid
arthritis, Hashimoto’s thyroiditis, hyperthyroidism,
hyperparathyroidism, and thyroid carcinoma.

13. The vast majority of thymomas are indolent, but if the
tumors spread, they most commonly implant on regional pleural
surfaces and can cause pleural plaques, diaphragmatic
masses, and malignant pleural effusions

14. Diagnosis
Thymic tumors account for 50% of all anterior mediastinal
masses, another 25% are lymphomas, and the remainder
are various other tumors.
Biopsy can be performed via a fine-needle aspiration, bronchoscopy,
mediastinoscopy, video-assisted thoracoscopy, or
open biopsy.

15. The diagnostic workup begins with a careful evaluation for
myasthenia gravis. Routine blood work for common associated
syndromes should be done, with serum α-fetoprotein and β-
human chorionic gonadotropin in men to rule out a germ cell
Tumor.
CT SCAN
MRI
PET CT

17. Pathologic Classification

18. Thymic carcinomas can be readily subclassified into well or
poorly differentiated. Well-differentiated thymic carcinomas
have features typical of thymomas but also contain areas of
atypia and mitoses, but usually fewer than 2 per 10 high-power
field.
Poorly differentiated thymic carcinomas are clearly recognized as a
distinct group. The virtual absence of parathymic syndromes and clear-
cut cellular atypia are consistently associated with poor prognosis.
Thymic carcinomas can be subdivided into squamous cell,
mucoepidermoid, basaloid, lymphoepithelioma-like, small cell or
neuroendocrine, sarcomatoid, clear cell, and undifferentiated or
anaplastic subtypes.

19. The WHO classification is similar to the Muller-Hermelink system but recognizes six different types
of thymic tumors A, AB, B1, B2, B3, C.
Type A composed of neoplastic oval or spindle-shaped epithelial cells without atypia or lymphocytes.
Type AB is similar to type A, but with foci of lymphocytes. Type B tumors consist of plump
epithelioid cells that can be subdivided into three subtypes defined by increasing proportions of
epithelial cells and increasing atypia.
Type B1 tumors resemble normal thymic cortex with areas similar to thymic medulla.
Type B2 have scattered neoplastic epithelial cells with vesicular nuclei and distinct nucleoli among a
heavy population of lymphocytes; perivascular spaces are prominent and a palisading effect of tumor
cells along the perivascular spaces may be present.
Type B3 is composed of predominantly round or polygonal epithelial cells exhibiting mild atypia
admixed with a minor component of lymphocytes; thus, this type resembles what others have
described as welldifferentiated thymic carcinoma.
Thymic carcinomas are designated type C tumors and have clear-cut cytologic atypia and a
cytoarchitecture resembling carcinoma that is distinctively unlike normal thymus tissue.

20. Molecular Characterization:
EGFR
VEGF
IGF-1R
KIT
steroid receptor expression

21. Staging
The most commonly used staging system for thymomas was published by Masaoka et al.in
1981.
Staging is based on the extent of either macroscopic or microscopic invasion into mediastinal
structures at the time of surgery.

22. Prognostic Factors
• The two factors that have consistently demonstrated prognostic value in
multivariate analyses in large studies are tumor invasiveness (i.e., disease stage)
and completeness of resection. tumor size (>10 cm) and the presence of
symptoms.

23. General Management
Surgery
Surgical resection is the mainstay of treatment for thymomas.
A complete en-bloc surgical resection (R0) remains the treatment
of choice for all thymomas regardless of invasiveness,
except in rare advanced cases with extensive intrathoracic
or extrathoracic metastasis. Fortunately, the vast majority
(90% to 95%) of thymomas are localized.177 Operative mortality
rates average 2.5% (range, 0.7% to 4.9%).

24. Traditional surgical techniques for patients with stage I thymic
tumors produce 5-year survival rates in excess of 90%,
with survival rates decreasing slightly at 10 years18,21,64 and
with local recurrence rates of <5%. For stage II and III disease,
recurrence rates after surgery alone range from 10% to 47%.

25. Patterns of Failure
The pattern of failure in the overwhelming majority of thymomas is
locoregional: 81% of recurrences are local, 9% are distant, and 11% are both.
Most recurrences arise within 3 to 7 years, but recurrence has been
documented as late as 32 years after the initial resection.
The treatment for recurrence is usually surgery and adjuvant
radiation.
Most recurrences (50% to 75%) are operable,and of those that are operable,
the reported rates of a successful R0 resection range from 45% to 71%.
Patients with a recurrence after an R0 resection generally experience
acceptable short-term and long-term results,with 10-year
actuarial survival rates ranging from 53% to 72%.

27. • Radiation Therapy
Adjuvant Radiation After Complete Resection:
Radiation therapy can be considered as an adjuvant treatment
for patients with resected stage II and III thymomas, although
recurrence rates for stage I thymomas after an R0 resection are
so low that radiation is considered unlikely to offer improvement.
The indications for radiation are controversial, with
some recommending adjuvant radiation for all patients
others recommending adjuvant radiation for stage II and III
Thymomas, and still others recommending radiation
only after an incomplete resection.

28. Adjuvant Radiation after Incomplete Resection
Radiation is often considered when complete resection is not possible.
Two studies have suggested that adjuvant radiation can be beneficial for
patients with subtotally resected thymomas.
Unfortunately both studies were small and, as always,
subject to selection bias.
Another study of 44 patients who had had R0 or R1,2 resections of stage III
thymoma showed that adjuvant radiation produced lower recurrence rates
(40% vs. 24% without radiation) and may have reduced the recurrence rates
among patients with stage IV disease as well.

29. Radiation as Neoadjuvant Therapy
Radiation has been proposed as a neoadjuvant strategy to reduce tumor
burden and improve resectability, especially for cases involving gross
invasion of critical structures.
The rates of R0 resections after neoadjuvant radiation for stage III
thymoma can be as high as 53% to 75%,106,203 which are favorable
compared with the typical 50% rate of R0 resections of stage III
thymomas.

30. Radiation as Definitive Therapy
Radiation therapy alone has been used for patients who cannot undergo
surgery because of medical conditions or those for whom surgical
resection is not possible, with modest results.
Arakawa et al. reported that 7 of 12 patients presenting with
unresectable tumors treated with primary radiation therapy were still
alive at follow-up times ranging from 1 to 5 years.

31. Chemotherapy
Thymomas are quite sensitive to chemotherapy, with approximately
two-thirds of patients showing a clinical response and
one-third experiencing a complete response.
The duration of response ranges from 12 to 93 months. Whether
chemotherapy influences long-term survival is more difficult to assess.
In one retrospective analysis of 90 patients, chemotherapy reduced the
rates of metastases to the lung, pleura, or other sites by half (17% vs.
38%; P <.05).
All of those patients had stage III or IV tumors and were treated with
radiation and partial or no resection.

32. The most promising use of chemotherapy is in the neoadjuvant
setting. Like preoperative radiation, chemotherapy seems
to render tumors more suitable for complete resection. One
study demonstrated that neoadjuvant chemotherapy was associated
with improved survival for patients with stage III or IVa
Thymomas.
Drugs commonly used in combination chemotherapy
include cisplatin, doxorubicin, and cyclophosphamide. Aside from cytotoxic
agents, somatostatin analogs (e.g.,
octreotide) and high-dose corticosteroids have shown promise
in thymomas.

33. Combined Modality Therapy
Some evidence exists to suggest that multimodality treatment can improve
resectability and survival among patients with stage III or IV thymomas.
typical combinations include neoadjuvant chemotherapy followed by surgery and
postoperative radiation, chemotherapy, or both.

34. Radiation Therapy Techniques
Radiation doses given for thymoma have ranged from 30 to
60 Gy, most often given in standard 1.8- to 2.0-Gy fractions.
Typical postoperative doses are 45 to 50 Gy, with higher doses
for positive surgical margins or frank invasion.

35. Radiation Fields
As radiation planning techniques have evolved, the trend in
treating thymic tumors, like non–small cell lung cancer, has
been toward use of involved-field techniques. Because thymomas
do not routinely spread via the lymphatic system, the
draining nodal distributions do not need to be included in the
radiation fields

36. • Hemithoracic radiation could be beneficial in thymic malignancies
because of their tendency for pleural metastases. This technique has
been assessed in several studies.
• In one such study, Sugie et al. reported findings from 60 patients with
stage I to IV invasive thymoma, 48 of whom had been treated with
fields limited to the mediastinum to a dose of 30 to 64 Gy and the
other 12 given hemithoracic radiation therapy to a dose of 11.2 to 16
Gy.
• Although the toxicity of the extended-field (hemithoracic) radiation
was acceptable and seemed to produce modest improvements in
pleural dissemination rates, no differences were found in overall
survival between the two techniques.

38. Thymic Carcinoma
Thymic carcinomas are considerably less common than thymomas.
Like thymomas, thymic carcinomas are thought to arise from thymic
epithelium and typically appear in the anterosuperior
mediastinum.
The clinical behavior of thymic carcinoma is quite different from that of
thymoma, being more aggressive and having a higher propensity for capsular
invasion.
Thymic carcinoma often presents as advanced disease, the 5-year survival
rates for which are much poorer than for thymomas.

39. Clinically, thymic carcinoma can present as cough, dyspnea,
pleuritic chest pain, phrenic nerve palsy, or superior vena cava
syndrome.
Associated paraneoplastic syndromes have been observed occasionally as
well.
CT scans often demonstrate an irregular mass with necrotic, cystic, or
calcified
regions.
In about 80% of cases, thymic carcinoma shows radiographic evidence of
invasion into adjacent structures in the mediastinum, with mediastinal
lymphadenopathy evident at presentation in about 40%.
Distant metastases to regional lymphatics, bone, liver, kidney, and lung
are common clinical features.

40. Historically, thymic carcinomas have been classified as type
C thymic tumors in the WHO classification, and disease staging
is most often done with the Masaoka clinical staging system for
thymomas.
Because histologic grade is one of the most significant indicators of
prognosis, a revised histologic classification has been proposed that
broadly divides thymic carcinomas into high- or low-grade lesions.
Most thymic carcinomas are undifferentiated high-grade lesions with
anaplasia and marked cellular atypia, lacking the histologic features of a
normal thymus; others may be of adenocarcinomatous, sarcomatous,
squamous, basoloid, mucoepidermoid, or lymphoepithelial- like
histology

41. Current management strategies involve an aggressive multimodality
approach including primary surgical resection and adjuvant cisplatin-
based chemotherapy, often coupled with postoperative radiation therapy.
Although incomplete resection does not necessarily preclude long-term
survival if multimodality platinum-based therapy is used,complete
resection is nevertheless the cornerstone of treatment.
Takeda et al.observed a median survival time of 57 months for patients
with completely resected thymic carcinomas versus 13 months for those
with incomplete resection.
Most studies have used adjuvant radiation therapy to a dose of 40 to 70
Gy delivered in standard fractionation (1.8- to 2.0-Gy fractions). In one
series of 26 patients treated with surgery and postoperative radiation
without chemotherapy.

42. Thymic carcinoma generally is less responsive to chemotherapy
than thymoma,292 and outcomes after chemotherapy
alone are dismal. However, the use of adjuvant cisplatin-based
chemotherapy has shown significantly beneficial effects in several
Studies.
The key to longer survival for thymic carcinoma, like thymoma, is the
resectability of the disease. A large multiinstitutional study of patients
with totally resected thymic carcinoma showed 5-year survival rates of
81.5% for those given chemotherapy, 46.6% for those given
chemoradiation, 73.6% for those given radiotherapy alone, and 72.2%
for those given no adjuvant treatment.

43. Thymic Carcinoid
Thymic carcinoid (neuroendocrine) tumors of the thymus are very rare,
accounting for <5% of all neoplasms of the anterior
mediastinum.
They originate from normal thymic Kulchitsky cells, which belong to
the amine-precursor-uptake and decarboxylation group.
Thymic carcinoid tumors are often confused with thymomas because of
similarities in their clinical behavior.
Most patients with thymic carcinoid are men aged 30 to 50 years; the
male-to-female ratio is 3 to 1.
Roughly half of thyroid carcinoids are associated with endocrine
disorders such as multiple endocrine neoplasia type-1 (MEN-1) or
secondary Cushing syndrome

44. Thymic carcinoids
can present with symptoms related to compression of normal
structures (chest pain, dyspnea, cough, hoarseness, superior
vena cava syndrome)300,305 or with no symptoms.
Thymic carcinoids are best evaluated by CT or MRI for visualizing local
invasion of the surrounding structures (pericardium, great vessels,
pleura, sternum) and metastases within or outside the
thorax.
Most thymic carcinoids detected on radiographic studies
are already advanced, commonly metastasizing to regional
lymph nodes.
Metastases are present in up to 70% of patients
within 8 years of the initial diagnosis,306 which may explain the
poor prognosis associated with these tumors

45. Thymic carcinoids
Complete surgical resection is the preferred method of
treatment, although recurrence is common. Incomplete resections
followed by adjuvant radiation, chemotherapy, or both

46. • THANK YOU

47. The specific regional nodal areas are as follows:
• Perigastric along the greater curvature (including
greater curvature, greater omental)
• Perigastric along the lesser curvature (including lesser
curvature, lesser omental)
• Right and left paracardial (cardioesophageal)
• Suprapyloric (including gastroduodenal)
• Infrapyloric (including gastroepiploic)
• Left gastric artery
• Celiac artery
• Common hepatic artery
• Hepatoduodenal (along the proper hepatic artery,
including portal)
• Splenic artery
• Splenic hilum