Pediatric Thymoma Workup

Updated: Oct 14, 2021
  • Author: Richard A Bickel, MD; Chief Editor: Harumi Jyonouchi, MD  more...
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Workup

Laboratory Studies

A CBC count reveals associated anemia, thrombocytopenia, or granulocytopenia.

Quantitative immunoglobulins (Igs) in patients with thymoma should be routinely drawn to assess Ig levels. Panhypogammaglobulinemia is noted in patients with acquired immunodeficiency and thymoma. Functional antibody responses to immunizations may be impaired in some patients. [11] Therefore, prevaccination and postvaccination antibody levels against protein and polysaccharide vaccines should be measured to assess humoral immune responses.

Immunophenotypic analysis of peripheral blood lymphocytes shows absent or very low B-cell counts and decreased absolute CD4+ T-cell numbers. [23]

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Imaging Studies

Chest radiography

One third of patients with thymoma are diagnosed as the result of an abnormality on a chest radiograph, such as mediastinal widening on posteroanterior (PA) views or retrosternal opacification on lateral views.

Chest CT scanning or MRI

These tests provide more definitive methods to exclude or characterize the thymoma.

CT scan or MRI can reveal the morphology of the mass and detect fat invasion, cysts, or necrosis.

Although uncommon, distant metastases occur with thymoma in 30-40% of patients with advanced disease; other scans may be warranted, depending on clinical symptoms.

Adenopathy in the middle or posterior mediastinum suggests lymphoma or lung carcinoma.

Calcification of cysts suggests germ cell tumor.

Functional imaging with oncotropic tracers and radioligands

These images have also proven useful. [24]

Oncotropic tracers concentrate in thymic tumors and correlate with tumor grades and cellularity; these include thallium TI 201 chloride, technetium Tc 99m sestamibi, and fluorine F 18 fluorodeoxyglucose.

The radioligands bind to specific receptors: [111In-DTPA-D-Phe1]-octreotide binds to the somatostatin receptor subtype 2; [111In-DTPA-Arg1]-substance P binds to receptors that are mainly expressed in the thymuses of patients with autoimmune diseases.

Although [111In-DTPA-D-Phe1]-octreotide concentrates in most thymomas, it does not concentrate in benign lymphofollicular hyperplasia and can assist in distinguishing these 2 pathologies in patients with myasthenia gravis (MG). [25]

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Other Tests

Cell-mediated immune responses are evaluated with delayed-type hypersensitivity (DTH) skin testing and in vitro T-cell responses to mitogens. [23] Patients with decreased cell-mediated immunity have absent DTH responses and decreased T-cell responses to mitogens.

Anti-AChR antibodies are appropriate because they are present in 90% of patients with MG and occasionally in patients with thymoma without muscle weakness. [26]

Perform additional studies to diagnose these and other paraneoplastic syndromes as indicated by history and physical examination findings.

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Procedures

Adequate tissue samples are important for histologic preparation and possible flow cytometry.

Fine-needle aspiration is considered inferior to a larger sample (eg, obtained by core biopsy or a limited anterior mediastinal sternotomy).

Mediastinoscopy does not provide adequate access to the anterior mediastinal compartment.

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Histologic Findings

Thymomas are characterized by a mixture of epithelial and lymphoid tissue and are usually encapsulated. In proposing a new classification system, Muller-Hermelink and Marx describe the traditional classification system as follows: [27]

Traditionally, thymic epithelial tumors (TET) have been classified histologically into four categories: predominantly spindle cell, predominantly lymphocytic, predominantly mixed lymphocytic and epithelial, and predominantly epithelial thymoma on the basis of lymphocyte/epithelial cell ratio and the shape of epithelial cells. To obtain better clinical and prognostic relevance, Levine and Rosai use tumor invasiveness (ie, stage) and cytological atypia to differentiate between benign thymomas and malignant thymomas of categories I and II ('thymic carcinoma'). Malignant thymomas belonging to category II were subsequently classified as squamous cell carcinoma, mucoepidermoid carcinoma, etc, according to the standard rules of extrathymic carcinomas.

Muller-Hermelink and Marx proposed a histogenetic or functional classification of TET based on the morphologic resemblance of neoplastic epithelial cells to subtypes of normal thymic epithelial cells. This method of classification excludes thymic carcinoma as belonging to category II (nonorganotypic) TET.

The World Health Organization (WHO) recently developed terminology based on the following criteria: Thymomas are divided into 2 major types depending on whether the neoplastic epithelial cells have a spindle or oval shape (type A) or whether they have a dendritic or epithelioid appearance (type B). Tumors that combine these features are designated as type AB. Type B thymomas are further divided based on an increasing epithelial lymphocyte ratio and emergence of atypia of the neoplastic epithelial cell into 3 subtypes, respectively designated B1, B2, and B3. Nonorganotypic thymic carcinomas, which generally resemble tumors arising outside the thymus, are regarded as type C thymoma. [27]

Table 1. Comparison of the Different Classifications of Thymic Epithelial Tumors [27] (Open Table in a new window)

Clinicopathologic Classification

WHO Type

Terminology of the Histogenetic Classification for the Histologic Subtypes of Thymic Epithelial Tumors

Benign thymoma

A

AB

Medullary thymoma

Mixed thymoma

Malignant thymomas,

Category I

B1

B2

B3

Predominantly cortical thymoma

Cortical thymoma

Well-differentiated thymic carcinoma

Malignant thymomas,

Category II

C

Epidermoid keratinizing (squamous cell) carcinoma

Epidermoid nonkeratinizing carcinoma

Lymphoepithelioma-like carcinoma

Sarcomatoid carcinoma (carcinosarcoma)

Clear cell carcinoma

Mucoepidermoid carcinoma

Undifferentiated carcinoma

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Staging

Areas of the thymus can become cystic, hemorrhagic, or necrotic, although most thymomas are solid. Although lacking the histologic features of malignancy, approximately one third of thymomas may invade through the capsule extending into the mediastinal fat, pleura, pericardium, great vessels, right atrium, and/or the lung (ie, invasive thymoma). Although rare (3-6%), transdiaphragmatic extension and drop metastases may occur; however, hematologic or lymph node metastases rarely occur. [11, 28, 3, 29]

The Masaoka staging system is the most widely used staging system and is based on the extent of invasion. It has been shown to correlate well with the 5-year and 10-year survival rates, based on WHO schema. [30] Loehrer summarizes the Masaoka staging system for thymomas as follows: [19]

  • Stage I - Macroscopically completely encapsulated with no microscopic capsular invasion

  • Stage II

    • Macroscopic invasion into the surrounding fatty tissue, mediastinal pleura, or both

    • Microscopic invasion into the capsule

  • Stage III - Macroscopic invasion into neighboring organs (eg, pericardium, great vessels, lung)

  • Stage IVa - Pleural or pericardial dissemination

  • Stage IVb - Lymphogenous or hematogenous metastases

Loehrer summarizes the Groupe d'Etudes des Tumeurs Thymiques (GETT) classification, which is based on the extent of surgical resection, as follows: [19]

  • Stage IA - Encapsulated tumor, totally resected

  • Stage IB - Macroscopically encapsulated tumor, totally resected, but with a suspicion of mediastinal adhesions and potential capsular invasion

  • Stage II - Invasive tumor, totally resected

  • Stage IIIA - Invasive tumor, subtotally resected

  • Stage IIIB - Invasive tumor, biopsy

  • Stage IVA - Supraclavicular metastasis or distant pleural implants

  • Stage IVb - Distant metastasis

Lymphofollicular thymitis or follicular thymus hyperplasia is a type of pathology found in approximately 70% of patients with MG. Lymphoid follicles with germinal centers appear in the perivascular spaces with destruction of the basal membrane between the perivascular spaces and thymic medulla. Myoid cells in the medulla form abnormal complexes with antigen-presenting dendritic cells. The concept of an intrathymic pathogenesis of MG in lymphofollicular thymitis is now generally accepted.

According to this postulate, AChRs derived from thymic myoid cells are ingested, processed, and presented by dendritic cells to potentially AChR-reactive T cells that then activate autoantibody-producing B cells and initiate plasma cell differentiation. In these patients, the thymus is the organ with the highest autoantibody production against AChR, at least in the early phase of MG. Dissemination of the autoreactive T cells from the thymus via the blood to peripheral lymphoid organs is an early event. Therefore, thymectomy can initiate complete remission in a large number of patients, provided it is performed early enough to prevent the establishment of a systemic anti-AChR response. [27]

See Thymoma Staging for summarized information.

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