The following cellular classification of thymoma and thymic carcinoma is largely based on the classification scheme presented in a World Health Organization monograph published in 1999.[1] Although the histologic classification of thymomas may have independent prognostic significance, staging is the most important determinant of survival in thymoma patients.[2,3] In contrast, a retrospective study of 40 patients with thymic carcinomas suggests that tumor histology is more important than stage as a prognostic indicator for survival in patients with thymic carcinoma.[4] To date, no specific chromosomal abnormalities have been associated with specific histologic types of thymoma or thymic carcinoma.[5-8]

Thymoma

Thymoma is a thymic epithelial tumor in which the epithelial component exhibits no overt atypia and retains histologic features specific to the normal thymus.[1] Immature non-neoplastic lymphocytes are present in variable numbers depending on the histologic type of thymoma. The histologic types of thymoma are as follows:

• Type A thymoma

  Type A thymoma (also known as spindle cell thymoma and medullary thymoma) accounts for approximately 4% to 7% of all thymomas.[2,3] Approximately 17% of this type may be associated with myasthenia gravis.[2] Morphologically, the tumor is composed of neoplastic thymic epithelial cells that have a spindle/oval shape, lack nuclear atypia, and are accompanied by few, if any, nonneoplastic lymphocytes.[1] The appearance of this tumor can be confused with that of a mesenchymal neoplasm, but the immunohistochemical and ultrastructural features are clearly those of an epithelial neoplasm. Most type A thymomas are encapsulated (see Stage Information). Some, however, may invade the capsule and, on rare occasion, may extend into the lung. Chromosome abnormalities, when present, may correlate with an aggressive clinical course.[8] The prognosis for this tumor type is excellent and have long-term survival rates (15 years or more) that are reported to be close to 100% in retrospective studies.[2,3]




• Type AB thymoma

  Type AB thymoma (also known as mixed thymoma) accounts for approximately 28% to 34% of all thymomas.[2,3] Approximately 16% of this type may be associated with myasthenia gravis.[2] Morphologically, type AB thymoma is a thymic tumor in which foci having the features of type A thymoma are admixed with foci rich in nonneoplastic lymphocytes.[1] The segregation of the different foci can be sharp or indistinct, and a wide range exists in the relative amount of the two components. The prognosis for this tumor type is good and have long-term survival rates (15 years or more) that are recently reported to be approximately 90% or better in two large retrospective studies.[2,3]




• Type B1 thymoma

  Type B1 thymoma (also known as lymphocyte-rich thymoma, lymphocytic thymoma, predominantly cortical thymoma, and organoid thymoma) accounts for approximately 9% to 20% of all thymomas and depends on the study cited.[2,3] Approximately 57% of cases may be associated with myasthenia gravis.[2] Morphologically, this tumor resembles the normal functional thymus because it contains large numbers of cells that have an appearance almost indistinguishable from normal thymic cortex with areas resembling thymic medulla.[1] The similarities between this tumor type and the normal active thymus are such that distinction between the two may be impossible on microscopic examination. The prognosis for this tumor type is good and has a long-term survival rate (20 years or more) of approximately 90%.[2,3]




• Type B2 thymoma

  Type B2 thymoma (also known as cortical thymoma and polygonal cell thymoma) accounts for approximately 20% to 36% of all thymomas and depends on the study cited.[2,3] Approximately 71% of cases may be associated with myasthenia gravis.[2] Morphologically, the neoplastic epithelial component of this tumor type appears as scattered plump cells with vesicular nuclei and distinct nucleoli among a heavy population of nonneoplastic lymphocytes.[1] Perivascular spaces are common and on occasion very prominent. A perivascular arrangement of tumor cells that results in a palisading effect may be seen. This type of thymoma resembles type B1 thymoma in its predominance of lymphocytes, but foci of medullary differentiation are less conspicuous or absent. Long-term survival is decidedly worse than for thymoma types A, AB, and B1. The 20-year survival rate (as defined by freedom from tumor death) for this thymoma type is approximately 60%.[2]




• Type B3 thymoma

  Type B3 thymoma (also known as epithelial thymoma, atypical thymoma, squamoid thymoma, and well-differentiated thymic carcinoma) accounts for approximately 10% to 14% of all thymomas. Approximately 46% of this type of tumor may be associated with myasthenia gravis.[2] Morphologically, this tumor type is predominantly composed of epithelial cells that have a round or polygonal shape and that exhibit no atypia or mild atypia.[1] The epithelial cells are admixed with a minor component of nonneoplastic lymphocytes, which results in a sheet-like growth of neoplastic epithelial cells. The 20-year survival rate (as defined by freedom from tumor death) for this thymoma type is approximately 40%.[2]

Thymic Carcinoma

Thymic carcinoma (also known as type C thymoma) is a thymic epithelial tumor that exhibits a definite cytologic atypia and a set of histologic features no longer specific to the thymus but rather similar to those histologic features observed in carcinomas of other organs.[1] In contrast to type A and B thymomas, thymic carcinomas lack immature lymphocytes. Any lymphocytes that are present are mature and usually admixed with plasma cells. Hypothetically, thymic carcinoma may arise from malignant transformation of a pre-existing thymoma.[9] This hypothetical evolution could account for the existence of thymic epithelial lesions that exhibit combined features of thymoma and thymic carcinoma within the same tumor.[10]

Thymic carcinomas are usually advanced when diagnosed and have a higher recurrence rate and worse survival compared with thymoma.[4,11] In a retrospective study of 40 patients with thymic carcinoma, the 5-year and 10-year actuarial overall survival rates were 38% and 28%, respectively.[4] In contrast to the thymomas, the association of thymic carcinoma and autoimmune disease is rare.[12]

Histologic subtypes of thymic carcinoma include the following:

• Squamous cell (epidermoid) thymic carcinoma

  This type of thymic carcinoma exhibits clear-cut cytologic atypia. In routinely stained sections, the keratinizing form exhibits equally clear-cut evidence of squamous differentiation in the form of intercellular bridges and/or squamous pearls, while the nonkeratinizing form lacks obvious signs of keratinization. Another subtype, basaloid carcinoma, is composed of compact lobules of tumor cells that exhibit peripheral palisading and an overall basophilic staining pattern caused by the high nucleocytoplasmic ratio and the absence of keratinization.




• Lymphoepithelioma-like thymic carcinoma

  This type of thymic carcinoma has morphologic features indistinguishable from those of lymphoepithelial carcinoma of the respiratory tract. The differential diagnosis with germ cell tumors, particularly seminomas, can be difficult but important for treatment.




• Sarcomatoid thymic carcinoma (carcinosarcoma)

  This is a type of thymic carcinoma in which part or all of the tumor resembles one of the types of soft tissue sarcoma.




• Clear cell thymic carcinoma

  This is a type of thymic carcinoma composed predominantly or exclusively of cells with optically clear cytoplasm.




• Mucoepidermoid thymic carcinoma

  This type of thymic carcinoma has an appearance similar to that of mucoepidermoid carcinoma of the major and minor salivary glands.




• Papillary thymic adenocarcinoma

  This type of thymic carcinoma grows in a papillary fashion. This histology may be accompanied by psammoma body formation, which may result in a marked similarity with papillary carcinoma of the thyroid gland.




• Undifferentiated thymic carcinoma

  This is a rare type of thymic carcinoma that grows in a solid undifferentiated fashion but without exhibiting sarcomatoid (spindle cell or pleomorphic) features.

Combined Thymoma

Combinations of the above histologic types can occur within the same tumor. For these cases, the term combined thymoma can be used, followed by a listing of the components and the relative amount of each component.[1]

References

1. Rosai J: Histological Typing of Tumours of the Thymus. New York, NY: Springer-Verlag, 2nd ed., 1999. 
   
   
2. Okumura M, Ohta M, Tateyama H, et al.: The World Health Organization histologic classification system reflects the oncologic behavior of thymoma: a clinical study of 273 patients. Cancer 94 (3): 624-32, 2002.  [PUBMED Abstract]
   
   
3. Chen G, Marx A, Wen-Hu C, et al.: New WHO histologic classification predicts prognosis of thymic epithelial tumors: a clinicopathologic study of 200 thymoma cases from China. Cancer 95 (2): 420-9, 2002.  [PUBMED Abstract]
   
   
4. Ogawa K, Toita T, Uno T, et al.: Treatment and prognosis of thymic carcinoma: a retrospective analysis of 40 cases. Cancer 94 (12): 3115-9, 2002.  [PUBMED Abstract]
   
   
5. Zettl A, Ströbel P, Wagner K, et al.: Recurrent genetic aberrations in thymoma and thymic carcinoma. Am J Pathol 157 (1): 257-66, 2000.  [PUBMED Abstract]
   
   
6. Zhou R, Zettl A, Ströbel P, et al.: Thymic epithelial tumors can develop along two different pathogenetic pathways. Am J Pathol 159 (5): 1853-60, 2001.  [PUBMED Abstract]
   
   
7. Inoue M, Marx A, Zettl A, et al.: Chromosome 6 suffers frequent and multiple aberrations in thymoma. Am J Pathol 161 (4): 1507-13, 2002.  [PUBMED Abstract]
   
   
8. Penzel R, Hoegel J, Schmitz W, et al.: Clusters of chromosomal imbalances in thymic epithelial tumours are associated with the WHO classification and the staging system according to Masaoka. Int J Cancer 105 (4): 494-8, 2003.  [PUBMED Abstract]
   
   
9. Suster S, Moran CA: Thymic carcinoma: spectrum of differentiation and histologic types. Pathology 30 (2): 111-22, 1998.  [PUBMED Abstract]
   
   
10. Suster S, Moran CA: Primary thymic epithelial neoplasms showing combined features of thymoma and thymic carcinoma. A clinicopathologic study of 22 cases. Am J Surg Pathol 20 (12): 1469-80, 1996.  [PUBMED Abstract]
    
    
11. Blumberg D, Burt ME, Bains MS, et al.: Thymic carcinoma: current staging does not predict prognosis. J Thorac Cardiovasc Surg 115 (2): 303-8; discussion 308-9, 1998.  [PUBMED Abstract]
    
    
12. Levy Y, Afek A, Sherer Y, et al.: Malignant thymoma associated with autoimmune diseases: a retrospective study and review of the literature. Semin Arthritis Rheum 28 (2): 73-9, 1998.  [PUBMED Abstract]
    
    

Back to Top

< Previous Section  |  Next Section >