Thymic Epithelial Tumors

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Thymic Epithelial Tumors

• Brent A.Orr M.D., Ph.D.4/30/2008

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Disclosures

• No Relevant Financial or Commercial Interests

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Overview

• Review the anatomy and histology of the thymus
• Discuss the Clinical Features of Thymomas and
  Thymic Carcinomas
• Review the Staging and Classification of Thymic
  epithelial tumors
• Review some differential diagnosis and helpful
  IHC panels

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Normal Anatomy of the Thymus
http//en.wikipedia.org/wiki/Thymus
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Cell types of the Thymus

• Epithelial cells
• Thymocytes
• Other    a. interdigitating reticulum cells   
  b. Langerhans cells    c. Mast cells    d.
  Eosinophils (especially in neonates)    e.
  Mesenchymal stromal cells

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Thymic epithelial cells

• Endodermally derived
• Modulates differentiation of T lymphocytes
• Keratin, HLA-DR
• Subtypes of Thymic Epithelial cells
• Cortical medium to large, round or
  polygonal,clear nuclei with nucleoli
• Medullary spindle nuclei
• Epithelium forming Hassalls corpuscle

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Tumors of Thymus (WHO classification)
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Epidemiology of Thymoma and Carcinoma

• Represent 20 of all mediastinal neoplasms in
  adults
• Most common anterior mediastinal neoplasm in
  adults (less common in children)
• incidence of thymoma is 0.15 cases per 100,000
• Age range is generally 40-60
• Slight male predominance
• No known risk factors (/- myasthenia gravis)
• Thymic carcinoma represents less than 1 of
  thymic malignancies (thymomas are considered
  malignant)

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Myasthenia Gravis (MG)

• 30-50 of patients with MG have thymomas
• Males and Females equally affected
• Belief is that the MG occurs in response to the
  thymoma, and not a independent risk factor of
  thymoma (paraneoplastic MG)
• 80-90 of patients with MG and thymoma have
  specific anti-titin antibodies in striated muscle
  as well as anti-acetylcholine receptor antibodies
• MG does cluster in specific histological subtype
  of thymoma

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Clinical Presentation of thymoma and thymic
carcinoma

• Up to one half detected incidentally in
  asymptomatic patients
• Other symptoms include
• SOB
• Chest pain
• Pleural effusion
• Systemic symptoms
• (fever, sweats)
• 3. Thymic Carcinoma presentation
• Cough
• Chest pain
• Phrenic nerve palsey
• Superior vena cava sydrome

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Thymoma Histology

• Tumor of thymic epithelium cytologically bland,
  with associated cortical-type non-neoplastic T
  cells
• Lobular Architecture with fibrous septae
• Appear spindle shape or more often polygonal
• Considered malignant despite paucity of cytologic
  atypia (invasion potential)

Up To Date
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Histology (contd)
Spindle cells
Pseudorossettes

• Thymic Carcinoma
• Anaplasia
• Cellular atypia
• Highly proliferative

Up To Date
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WHO Classification of Thymic Epithelial Tumors
Rosai, J. 1999
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Comparison of new WHO to previous histological
classifications
Note these authors designate the WHO B3 as a
carcinoma whereas others refer to it as a
atypical thymoma
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WHO A Thymoma (spindle cell thymoma)
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WHO B1 Thymoma (lymphocyte predominant)
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WHO B3 Thymoma (Epithelial Thymoma)
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WHO C Thymic Carcinoma
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Key Points of WHO Classification
Okumura et al. 2008

• The cells shift from spindle shaped to polygonal
  in higher grade lesions
• Higher grade lesions have greater cellular atypia
• The proportion of epithelial cells to lymphocytes
  increases with increasing
• grade (generally greater number of lymphocytes
  favorable prognosis).

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WHO Classification System

• Correlates with clinical aggressiveness and
  likelihood of invasion
• Correlates with prognosis
• Risk C gt B3 gt B2 gt B1 gt AB gt A.

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Disease-Free Survival in Thymoma
Kondo et al. 2004
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Clinical Staging of Thymic Epithelial Tumors
Masaoka, A 1981
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Clinical Staging of Thymic Epithelial Tumors

• Big dropoff in survival after extension to other
  organs
• People dont generally survive after metastasis

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TNM staging (Yamakawa)

• This system transforms original Masaoka Staging
  system into more conventional TNM stage system
• May better classify some high grade lesions
• Doesnt add much to the original staging method

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Modified Staging Scheme of Yamakawa (1991)
Yamakawa et al. 1991
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Treatment of Thymoma and Thymic Carcinoma

• Surgical Resection for non-metastatic neoplasms
• Radiation
• Locally advanced disease
• Macroscopic or microscopic residual disease after
  incomplete ressecton
• Following incomplete ressection of invasive
  thymoma or thymic carcinoma
• 3. Chemotherapy

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Specific Chemotherapy Regimens
CR Chemotherapy resistant rate, PR Partial
response rate, RR response rate
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Genetics of B3 Thymomas

• Gain of chromosome 1q and loss of chromosome 6
  (nearly 100 of B3 tumors)
• Epidermal Growth Factor Receptor gene
  amplification (more often in higher grade
  lesions)
• C-Jun upregulation
• Not routine to do genetic testing on thymomas

Reviewed in Okumura et al. 2008
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Differential Diagnosis of WHO A Thymoma

• Solitary Fibrous Tumor
• Ewing Sarcoma

Note All three stain positive for CD99
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Differential Diagnosis of Thymic Carcinoma

• WHO B3 Thymoma
• Metastatic Carcinoma (Squamous Cell Carcinoma of
  Lung)

Stains infiltrating immature lymphocytes
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References

• 1. Yamakawa Y, Masaoka A, et al. A tentative
  Tumor-Node-Metastasis classification of thymoma.
  Cancer. 1991 68 1984-1987.
• 2. Rosai J. Histological Typing of Tumours of the
  Thymus, Springer. 1999.
• 3. Okumura M, Hiroyuki S. et al. Gen Thorac
  Cardiovasc Surg. 2008 561016.
• 4. Masaoka A, Monden Y, et al. Follow-up study of
  thymomas with special reference to their clinical
  stage. Cancer. 1981 48 2485-2492.
• 5. Kondo, K et al. Ann Thorac Surg. 2004 77
  1183-1188.
• 6. www. Immunoqurery.com
• 7. www.uptodate.com