The document discusses pathology of mediastinal tumors. It begins with anatomy of the mediastinum and its compartments. Common tumor types in each compartment are then described, including thymomas, thymic carcinomas, germ cell tumors, neurogenic tumors, and lymphomas. Key features of thymomas such as classification, staging, and treatment approaches are summarized in depth. The document provides an overview of mediastinal tumor pathology.

1. Pathology of Mediastinal
Tumors
By
Osama El-Zaafarany

2. Anatomy
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The mediastinum is the
space between:
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•
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the thoracic inlet & the diaphragm,
The sternum & vertebral column,
The 2 lungs.
 Compartments:
• Anterior.
• Superior.
• Middle.
• Posterior.

3. 
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The anterior mediastinum:
thymus, lymph nodes, and
small vessels.
The middle mediastinum:
the heart, proximal great
vessels, central airway
structures, and lymph
nodes.
The posterior mediastinum:
sympathetic chain ganglia,
vagus nerve, thoracic
duct, and esophagus

4. DD of Mediastinal Mass
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Antero-superior mediastinum:
 Thymic tumors:
Thymomas, Thymic carcinomas, Thymic cysts.
 Lymphomas:
Hodgkin's disease, Non-Hodgkin's lymphomas.
 Germ cell tumors:
Seminomas, Non-seminomas.
 Endocrine tumors:
Parathyroid adenomas, Thyroid tumors (retrosternal).
 Mesenchymal tumors:
Lipoma, liposarcoma, haemangioma, lymphangioma….

5. DD of Mediastinal Mass
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The middle mediastinum:
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Lymphomas.
Cysts: Bronchogenic,pericardial,thoracic duct.
Mesenchymal tumors.
Tracheal tumors.
Cardiac and pericardial tumors
Vascular tumors: e.g. Aortic aneurysm.
Lymphadenopathy:
Inflammatory, Granulomatous, Sarcoidosis.

6. DD of Mediastinal Mass
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The posterior mediastinum:
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Lymphomas
Neurogenic tumors:
Peripheral nerves: Schwannomas
Sympathetic ganglia: Ganglioneuromas, Neuroblastomas
Paraganglia: Paragangliomas
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Mesenchymal tumors
Esophageal tumors and cysts
Hiatal hernias.
Thoracic duct cyst.
Meningocele.

8. Thymic Tumors
thymus gland
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is an irregular lobulated lympho-epithelial organ in the
anterior mediastinum.
derived from the endoderm of third pharyngeal pouch.
involutes during adulthood, gradually being replaced by
adipose tissue.
(I) Thymoma:

Thymomas are epithelial tumors associated with an
exuberant lymphoid component composed of immature
cortical thymocytes.

Thymomas are exceedingly rare.
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incidence of 0.15 per 100,000 person-years.
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higher in males than females.

10. ‫‪Thymoma‬‬
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11. Thymoma
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characterized by an indolent growth pattern that
can be locally invasive.
Long survival.
myasthenia gravis is present in 30% to 40% of
patients;(The cardinal features are weakness and
fatigability of skeletal muscles)
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81 % of recurrences are local, 9% distant.

12. Thymoma
Pathological Classification: (WHO)
Type A: tumors are 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 and are subdivided into three
subtypes.
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.
Type B3 is composed of predominantly round or polygonal epithelial cells
exhibiting mild atypia admixed with a minor component of lymphocytes; have
described as well-differentiated thymic carcinoma.
Type C: Thymic carcinomas these have clear-cut cytologic atypia and a
cytoarchitecture resembling carcinoma distinctively unlike normal thymus
tissue

13. Thymoma
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Masaoka Staging System
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I : Macroscopically completely encapsulated, with no
microscopic capsular invasion
II :
 IIa: Macroscopic invasion into surrounding mediastinal
fatty tissue or mediastinal pleura.
 IIb: Microscopic invasion into the capsule
III : Macroscopic invasion into surrounding organs
IV :
 IVa: Pleural or pericardial implants/dissemination
 IVb: Lymphogenous or hematogenous metastases

14. Thymoma
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Treatment:
• Surgical resection is the mainstay of treatment
for thymomas, and complete en- bloc surgical
resection (R0) remains the treatment of choice
for all thymomas regardless of invasiveness.
• Radiation therapy is often considered for the
adjuvant setting in patients with resected stage
II and III thymomas. And still others recommend
radiation only in the circumstance of incomplete
resection.

15. Thymoma,
Treatment
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Chemotherapy:
• Thymomas have proven to be very sensitive to
chemotherapy.
• A clinical response is seen in roughly two thirds of
patients.
• The duration of response ranges from 12 to 93 months.
• The most promising use of chemotherapy is in the
neoadjuvant setting; appears to be effective at
rendering tumors more amenable to a complete
resection.
• The commonly employed drugs in combination
chemotherapy are cisplatin, doxorubicin, and
cyclophosphamide.
• May be combined with post-operative radiotherapy for
stages III and IV.

16. (II) Thymic Carcinoma:
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Thymic carcinomas are less common than
thymoma.
arise from thymic epithelium.
more aggressive with a higher propensity
for capsular invasion.
frequently present with advanced disease
and have a poorer 5-year survival than
with thymomas

17. Thymic Carcinoma
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The majority of thymic carcinomas are
undifferentiated high-grade lesions with:
• Anaplasia.
• marked cellular atypia.
• lacking the histologic features of a normal thymus.
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Others: adenocarcinomatous, sarcomatous, squamous,
basaloid, mucoepidermoid, or lymphoepithelial like.
60% expression of CD5, CD70 and CD117 in
epithelial cells.
Current management requires an aggressive
multimodality approach, including primary
surgical resection and the use of adjuvant
cisplatin-based chemotherapy, often coupled with
postoperative radiation therapy.

18. (III) Thymic Carcinoid:
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Thymic carcinoid tumors (neuroendocrine
tumors) of the thymus are very rare.
They originate from the normal thymic Kulchitsky
cells, which belong to the amine precursor uptake
and decarboxylation (APUD) group.
Approximately 50% are associated with
endocrine disorders, such as multiple endocrine
neoplasia (MEN -1), or secondary Cushing's
syndrome.
Complete surgical resection is the preferred
method of treatment, although recurrence is
common.

19. Malignant Mediastinal Germ Cell
Tumors
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The mediastinum is the most common site of
primary extragonadal germ cell tumors in young
adults.
A number of malignant processes are associated
with nonseminomatous germ cell tumors; acute
myeloid leukemia and malignant histiocytosis.
Arise from germ cells that migrate along the
urogenital ridge during embryonic development,
which extends from C6 to L4.
Meticulous work-up must be performed to
prevent overlooking an occult gonadal primary,
including testicular ultrasound.

20. Malignant Mediastinal Germ Cell Tumors
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Primary mediastinal germ cell tumors have the
same morphologic and histologic appearance as
those of the testes.
They are divided into seminomatous and
non-seminomatous tumors.
Have a poor prognosis and aggressive behavior.
Tumor markers can aid in diagnosis:
The Alpha-fetoprotein (AFP) is elevated in 75% of
patients.
• The β-subunit of human chorionic gonadotropin (β-HCG)
is elevated less than half of the time.
• Lactate dehydrogenase (LDH) is elevated in 50% of
patients.
•
 Main line of treatment is chemotherapy.

21. Mediastinal Neurogenic Tumors
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Arise in the posterior mediastinum from
peripheral nerves, sympathetic ganglia, or
mediastinal chemoreceptors.
Neuroblastoma is an aggressive variant of
neurogenic tumors and is a disease of childhood.
In adults, the majority of neurogenic tumors are
benign schwannomas and neurofibromas in the
setting of neurofibromatosis type 1 (NF-1) or von
Recklinghausen's disease.

22. Mediastinal Neurogenic Tumors
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Paragangliomas are rare tumors that arise from
extra-adrenal paraganglia and potentially are
catecholamine secreting. Most tumors are benign
(~10% malignant), and surgical resection is usually
curative.
Malignant peripheral nerve sheath tumors
(MPNSTs) have increased risk in Patients with NF-1.
MPNSTs are difficult to detect, metastasize rapidly,
and thus carry a poor prognosis.

23. Mediastinal Neurogenic Tumors
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Management for patients with malignant
mediastinal neurogenic tumors entails a
multidisciplinary approach similar to the
management of adult soft-tissue sarcomas.
Surgical resection is the mainstay of therapy, and
an R0 resection should be attempted.
Adjuvant radiation has been incorporated into the
management of localized MPNSTs.
Unresectable disease, radiation can be delivered
either alone or with chemotherapy that is used
for soft-tissue sarcomas; doxorubicin, ifosfamide.