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thymoma

Wednesday 15 September 2004

thymomas

WP WebPathology

Digital cases

- JRC:477 : Thymoma with micronodular features
- JRC:1607 : Thymoma (differential diagnosis. lymphohistiocytoid mesothelioma).
- JRC:3189 : Thymic carcinoma. Thymoma, type C.
- JRC:3190 : Mixed thymoma Thymoma, B1 or B2.
- JRC:3191 : Spindle cell thymoma. Thymoma, type C.

Links

- Thymoma - General (WebPathology)
- Thymoma type A (Webpathology)
- Thymoma type AB (Webpathology)
- Thymoma type B1 (Lymphocyte-rich) (Webpathology)
- Thymoma type B2 (Webpathology)
- Thymoma type B3 (Webpathology)
- Thymic carcinomas (Webpathology)

Definition: Thymoma is the most frequent tumor arising in human thymus (thymic tumors). Thymoma is a tumor originating from the epithelial cells of the thymus.

Thymoma is an uncommon tumor, best known for its association with the neuromuscular disorder myasthenia gravis. Thymoma is found in 15% of patients with myasthenia gravis. Once diagnosed, thymomas may be removed surgically. In the rare case of a malignant tumor, chemotherapy may be used.

Epidemiology

Men and women are equally affected by thymomas. The typical age at diagnosis is 30–40, although cases have been described in every age group, including children.

Types

- thymic epithelial tumors

WHO types Traditional (Bernatz) Kirchner Muller-Hermelink
type A thymoma spindle cell thymoma medullary lypmhoma
type AB thymoma combined thymoma mixed thymoma
type B thymoma - -
type B1 thymoma lymphocyte-rich thymoma predominantly cortical thymoma
type B2 thymoma mixed lymphoepithelioma cortical thymoma
type B3 thymoma epithelial-rich thymoma well-differentiated thymic carcinoma
type C thymoma thymic carcinoma (NOS) other types of thymic carcinoma

- ectopic hamartomatous thymoma

Macroscopy

The tumor is pink-tan, solid, and composed of lobules separated by fibrous septa. About 80% of cases of thymoma are well-encapsulated.

Microscopy

Thymomas have lobulated architecture with fibrous bands separating individual lobules as seen in this low power view. Some lobules may have angulated contours. The lobules are composed of neoplastic epithelial cells and non-neoplastic lymphocytes in varying proportions.

Areas of hemorrhage, necrosis, and cyst formation may be seen in larger thymomas.

Tumors that are entirely cystic may be mistaken for multilocular thymic cyst.

Perivascular spaces in a thymoma contain a loose network of neoplastic epithelial cells, lymphocytes, proteinaceous fluid, red blood cells, and foamy histiocytes. They are more commonly seen in Type B Thymomas.

Thymomas may show glandular structures. This image shows several variably-sized glandular structures in a Type A Thymoma (Spindle cell).

Clinical synopsis

A third of all people with a thymoma have symptoms caused by compression of the surrounding organs by an expansive mass. These problems may take the form of superior vena cava syndrome, dysphagia (difficulty swallowing), cough, or chest pain.

One-third to one-half of all persons with thymoma have no symptoms at all, and the mass is identified on a chest X-ray or CT/CAT scan performed for an unrelated problem.

When a thymoma is suspected, a CT/CAT scan is generally performed to estimate the size and extent of the tumor, and the lesion is sampled with a CT-guided needle biopsy. Increased vascular enhancement on CT scans can be indicative of malignancy, as can be pleural deposits.

Limited biopsies are associated with a very small risk of pneumomediastinum or mediastinitis and an even-lower risk of damaging the heart or large blood vessels.

The diagnosis is made via histologic examination by a pathologist, after obtaining a tissue sample of the mass. Final tumor classification and staging is accomplished pathologically after formal surgical removal of the thymic tumor

Selected laboratory tests can be used to look for associated problems or possible tumor spread. These include: full blood count, protein electrophoresis, antibodies to the acetylcholine receptor (indicative of myasthenia), electrolytes, liver enzymes and renal function.

Autoimmune disorders

One-third of patients have their tumors discovered because they have an associated autoimmune disorder.

As mentioned earlier, the most common of those conditions is myasthenia gravis (MG); 10–15% of patients with MG have a thymoma and, conversely, 30–45% of patients with thymomas have MG.

Additional associated autoimmune conditions include pure red cell aplasia and Good’s syndrome (thymoma with combined immunodeficiency and hypogammaglobulinemia).

Other reported disease associations are with acute pericarditis, Addison’s disease, agranulocytosis, alopecia areata, ulcerative colitis, Cushing’s disease, hemolytic anemia, limbic encephalopathy, myocarditis, nephrotic syndrome, panhypopituitarism, pernicious anemia, polymyositis, rheumatoid arthritis, sarcoidosis, scleroderma, sensorimotor radiculopathy, stiff person syndrome, systemic lupus erythematosus and thyroiditis.

Classification

Thymoma originates from the epithelial cell population in the thymus, and several microscopic subtypes are now recognized.

There are three principal histological types of thymoma, depending on the appearance of the cells by microscopy:

- Type A if the epithelial cells have an oval or fusiform shape (less lymphocyte count);
- Type B if they have an epithelioid shape. Type B has three subtypes:

  • B1 (lymphocyte-rich)
  • B2 (cortical)
  • B3 (epithelial).)
    - Type AB if the tumor contains a combination of both cell types.

Thymic cortical epithelial cells have abundant cytoplasm, vesicular nucleus with finely divided chromatin and small nucleoli and cytoplasmic filaments contact adjacent cells.

Thymic medullary epithelial cells in contrast are spindle shaped with oval dense nucleus and scant cytoplasm thymoma if recapitulates cortical cell features more, is thought to be less benign.

Staging

The Masaoka Staging System is used widely and is based on the anatomic extent of disease at the time of surgery:

- I: Completely encapsulated
- IIA: Microscopic invasion through the capsule into surrounding fatty tissue
- IIB: Macroscopic invasion into capsule
- III: Macroscopic invasion into adjacent organs
- IVA: Pleural or pericardial implants
- IVB: Lymphogenous or hematogenous metastasis to distant (extrathoracic) sites

The WHO classification system

A Tumor in which foci having features of type A thymoma are admixed with foci rich in lymphocytes
B1 Tumor resembles normal functional thymus; combines large expanses having an appearance practically indistinguishable from that of normal thymic cortex with areas resembling thymic medulla
B2 Tumor in which neoplastic epithelial component appears as scattered plump cells with vesicular nuclei and distinct nucleoli among a heavy population of lymphocytes; perivascular spaces are common and sometimes very prominent; a perivascular arrangement of tumor cells resulting in a palisading effect may be seen.
B3 Thymoma predominantly composed of epithelial cells having a round or polygonal shape and exhibiting no or mild atypia; they are admixed with a mild component of lymphocytes, resulting in a sheetlike growth of the neoplastic epithelial cells
C Thymic tumor exhibiting clear-cut cytologic atypia and a set of cytoarchitectural features no longer specific to the thymus, but rather analogous to those seen in carcinomas of the other organs; type C thymomas lack immature lymphocytes; whatever lymphocytes may be present are mature and usually admixed with plasma cells

Treatment

Surgery is the mainstay of treatment for thymoma. If the tumor is apparently invasive and large, preoperative (neoadjuvant) chemotherapy and/or radiotherapy may be used to decrease the size and improve resectability, before surgery is attempted.

When the tumor is an early stage (Masaoka I through IIB), no further therapy is necessary.

Removal of the thymus in adults does not appear to induce immune deficiency.

In children, however, postoperative immunity may be abnormal and vaccinations for several infectious agents are recommended. Invasive thymomas may require additional treatment with radiotherapy and chemotherapy (cyclophosphamide, doxorubicin and cisplatin).

Prognosis

Prognosis is much worse for stage III or IV thymomas as compared with stage I and II tumors.

Invasive thymomas uncommonly can also metastasize, generally to pleura, bones, liver or brain in approximately 7% of cases.

Patients with stage III and IV tumors may nonetheless survive for several years with appropriate oncological management.

Guidelines

- Pathology: Recommendations for the Reporting of Surgically Resected Thymic Epithelial Tumors : http://ajcp.ascpjournals.org/content/132/1/10.full - DOI: 10.1309/AJCPHII8GRIG3JHV
- Pathology : Thymoma checklist : http://www.thymic.org/uploads/mainpdf/thymoma05_pw.pdf (Janvier 2005)
- http://guideline.gov/content.aspx?id=13302
- https://www.cancercare.on.ca/common/pages/UserFile.aspx?serverId=6&path=/File%20Database/CCO%20Files/PEBC/pebc7-11f.pdf
- http://www.ncbi.nlm.nih.gov/pubmed/21070994
- http://www.ncbi.nlm.nih.gov/pubmed/19557895

Cytogenetics

- chromosome 6 anomalies

  • del(6)(p22p25) in type A and type AB thymomas (#14499698#)
  • ring chromosome 6

- chromosomes 12 and 16 anomalies

  • pseudodicentric (16;12)(q11;p11.2) (type AB or mixed thymoma)

Allelotyping (Loss of heterozygosity (LOH) loci)

  • 6q23.3-25.3 (23.5%-45.8%) (#12368223#)
  • 3p14.2 (FHIT gene locus)
  • 5q21 (APC)
  • 6p21
  • 6q21-22.1
  • 7p21-22
  • 8q11.21-23
  • 13q14 (RB)
  • 17p13.1 (p53)

Tumorigenetic pathways

- APC-associated pathway: 5q21 - 3p22-24.2 - 13q14 - 17p13.1 regions.
- type A thymomas: 6q23.3-25.5 only

Microsatellite instability (MSI)

- microsatellite instability (MSI): 2.4%-12.5% (#12368223#) .

  • type B3 thymoma only (?)

See also

- surgpathcriteria.stanford.edu (http://surgpathcriteria.stanford.edu/thymus/thymoma/)

Portfolio

  • Thymoma, type A
  • Thymoma, type A
  • Thymoma, type A
  • Thymoma, type A