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Thymoma
- 1. R A W A M U H S I N Thymoma
- 2. Definition Thymic epithelial neoplasm exhibiting some organotypic features, accompanied by variable numbers of reactive lymphoid cells Organotypic features lobulation medullary differentiation perivascular spaces presence of immature T lymphocytes
- 4. Clinical Age and gender 5th to 6th decades Equal sex incidence Symptoms Chest pain, dyspnea, paraneoplastic (myasthenia, red cell aplasia, hypogammaglobulinemia, thyroiditis, SLE) Asymptomatic in 30% Low-grade and indolent Distant metastases are rare Surgical excision Radiation therapy for invasive or incompletely excised tumors
- 5. Macroscopic Well-circumscribed, encapsulated Homogeneous tan-white, rubbery, lobulated Solid, but may be cystic and multilocular Additionally Calcifications in capsule or within tumor Multifocal Ectopic in posterior mediastinum, lung, neck, or pleura Necrosis and hemorrhage Invasive tumors compromise adjacent structures
- 9. Grossing Ink outer surface If other structures attached also ink the true margins 1 section per 1 cm of greatest tumor dimension Minimum of five representative blocks regardless Additional sections if variegated to detect mixed types Solid areas in cystic tumors Include inked surface in sections
- 10. Classification Suster & Moran WHO Well-differentiated thymic epithelial neoplasm (thymoma) Type A (spindle cell) Type AB (spindle cell with abundant lymphocytes) Type B1 (lymphocyte predominant) Type B2 (lymphoepithelial) Moderately differentiated thymic epithelial neoplasm (atypical thymoma) Type B3 (epithelial rich) Poorly differentiated thymic epithelial neoplasm (thymic carcinoma) Thymic carcinoma
- 11. Classification
- 12. Cell types Oval/spindle cells (types A, AB) Round/epithelioid cells (types B1-3)
- 13. Type A Oval or spindle cells, scattered nuclear chromatin, absent nucleoli, no mitotic activity Few lymphocytes Majority are low grade and encapsulated
- 16. Type AB Oval or spindle cells similar to those in type A Abundant small T lymphocytes
- 19. Type B1 Round/epithelioid cells with single small eosinophilic nucleoli and abundant cytoplasm Numerous small T lymphocytes predominate Dilated perivascular spaces and areas of medullary differentiation
- 25. Type B2 Equal admixture of round epithelial cells and small lymphocytes Admixtures with B1 or B3 areas in ~30% of cases Report by providing percentage of various types present
- 30. Type B3 Sheets of large epithelioid cells with nuclear enlargement, dense chromatin, prominent nucleoli Scant lymphocytes Additionally Rare mitoses Raisin-like nuclei Abundant, eosinophilic cytoplasm with sharp borders Palisading around perivascular spaces
- 33. Unusual types Hemangiopericytic Micronodular Metaplastic Adenoid Sclerosing Rosette-forming
- 34. Immunohistochemistry Antibody Pattern Positive Cases p63 Nucleus 100% 122 CK5/6 Cytoplasm 99% 94 CD99 Membrane 94% 101 FOXN1 (99% in 76), CD205 (97% in 76), SDHB (100% in 62).
- 35. Immunohistochemistry Antibody Thymoma Thymic carcinoma CD5 3% (422) 62% (230) Mesothelin 2% (130) 64% (90) CD117 0% (90) 67% (82)
- 41. Prognostic factors Tumor stage (most important) Tumor size Invasion of capsule A < AB < B1 < B2 < B3 Completeness of excision
- 47. Modified Masaoka staging Stages I (44%): 5-year survival of 90% Stage II (23%): 5-year survival of 88% Stage III (27%): 5-year survival of 67% Stage IV (6%): 5-year survival of 50%
- 48. Differential diagnosis Lymphoblastic lymphoma No keratin-positive cells, rapid growth, younger age Thymic carcinoma Overt cytologic features of malignancy with loss of organotypical features of thymic differentiation Neuroendocrine carcinoma Nested pattern, stippled chromatin, neuroendocrine markers Acquired multilocular thymic cyst Cuboidal or squamous lining, severe inflammation, cholesterol cleft granulomas Solitary fibrous tumor IHC profile, ropy collagen, lack of immature T cells
- 49. Bonus
Editor's Notes
- The usual location of thymoma is the anterosuperior mediastinum.
- Thymoma type AB (WHO). Beige lobulated tumor with thin connective tissue septae. Intact tumor capsule.
- Gross appearance of bisected thymoma shows a well-circumscribed, fleshy, lobulated mass composed of tan-white, homogeneous rubbery tissue with focal areas of congestion and hemorrhage.
- Solid cystic tumor with macroscopically intact capsule. Thymoma Type B2 and B3. Microscopic invasion of the capsule.
- Spindle cell thymoma (WHO type A) is composed of spindle cells with elongated nuclei, dispersed chromatin, and absence of nucleoli. The spindle cells usually predominate, and stromal lymphocytes are very scant.
- Spindle cell thymoma (WHO type A) shows fascicles of bland-appearing spindle cells admixed with a few scattered small lymphocytes.
- Lymphocyte-rich spindle cell thymoma (type AB thymoma) is composed of small spindle cells admixed with numerous small lymphocytes; the tumor can closely resemble a B1 thymoma on scanning magnification because of the abundance of lymphocytes.
- Lymphocyte-rich spindle cell thymoma (WHO type AB) shows storiform fascicle of spindle cells (center) with few lymphocytes surrounded by areas containing scattered spindle cells admixed with numerous lymphocytes.
- Higher magnification of round cellular lobule in lymphocyte-rich thymoma (WHO type B1) shows a predominantly lymphoid cell population. The lobules are separated by thin bands of fibrocollagenous tissue. These tumors can be easily mistaken for lymphocytic lymphomas.
- WHO type B1 thymoma is composed of large, round epithelioid cells with large, vesicular nuclei containing single prominent eosinophilic nucleoli and surrounded by an indistinct rim of amphophilic cytoplasm.
- Lymphocyte-rich thymoma (WHO type B1) shows a dilated perivascular space (center of the field) filled with scattered small lymphocytes. Notice the small vessel lumen floating inside the empty perivascular space.
- Lymphocyte-rich thymoma (WHO type B1) shows an area of medullary differentiation (center). This area is sparsely cellular and contains fewer lymphocytes than the surrounding parenchyma, as well as areas of hyalinization with abortive Hassall corpuscles.
- Area of necrosis and infarction is seen in lymphocyte-rich (WHO type B1) thymoma. This is caused by vasoocclusive phenomena in the vicinity of the infarcted areas of tumors with cystic changes. This should not be confused for a sign of malignancy or more aggressive behavior.
- Mixed lymphoepithelial (WHO type B2) thymoma shows approximately equal admixture of lymphocytes with neoplastic epithelial cells.
- Lymphoepithelial thymoma (WHO type B2) is composed of similar cells to WHO type B1, except they are more numerous & easily spotted on intermediate magnification. The nuclei are large with vesicular chromatin and eosinophilic nucleoli and have a rim of lightly eosinophilic to amphophilic cytoplasm.
- Combinations of thymoma WHO type B2 and B3 are seen in ~ 30% of cases. The nodule on the right corresponds to a focus of atypical thymoma (WHO type B3). The areas on the left show lymphoepithelial thymoma (WHO type B2) and contain a higher density of small lymphocytes.
- Focus of vascular invasion in lymphocyte-rich thymoma (WHO type B2) is shown. The significance of this finding is unknown, but it is believed to be associated with more aggressive behavior.
- Higher magnification shows a nodule with atypical thymoma (WHO type B3) in a combined thymoma, type B2 + B3. Notice the large size of the epithelial cells.
- WHO type B3 thymoma shows sheets of large epithelioid to polygonal cells with enlarged nuclei, marked increase in nuclear chromatin, prominent nucleoli, and abundant eosinophilic cytoplasm with sharp cell borders.
- Positive staining of the tumor cells for CD99 is seen in this lymphocyte-rich thymoma (WHO type B1). CD99 is a marker of T lymphoblasts and can be used in lieu of CD1a or TdT for the demonstration of immature T-lymphoblastic cells in lymphocyte-rich thymomas.
- Strong membrane positivity for CD3 is observed in this lymphocyte-rich thymoma (WHO type B1). A similar pattern of staining should also be expected for CD1a, a marker of immature T cells.
- Lymphocyte-rich thymoma with starry-sky appearance simulating lymphoblastic lymphoma shows striking nuclear positivity in small lymphocytes for TdT, not to be confused with lymphoblastic lymphoma.
- Immunoperoxidase stain for cytokeratin AE1/AE3 in lymphocyte-rich thymoma simulating lymphoblastic lymphoma shows scattered, isolated, keratin-positive tumor cells. Identification of keratin-positive cell population is critical for making the correct diagnosis.
- Immunohistochemical staining of lymphocyte-rich spindle cell thymoma (WHO type AB) with p63 antibody shows strong nuclear positivity in the spindle thymic epithelial cells. Notice how the stain highlights the elongated, oval to spindle shape of the nuclei in the tumor cells.
- Spindle cell thymoma (WHO type A) shows capsular invasion by tumor . Notice the solid nodule traversing the fibrous capsule of the thymus that is still attached to the underlying main tumor mass by a short pedicle.
- Invasive thymoma. The main tumor is enclosed in a fibrous capsule. An invasive tumor bud has penetrated the capsule, and it lacks a fibrous clothing.
- Metastasis of spindle cell thymoma to a mediastinal lymph node is seen. Notice the gland-like structures in the lymph node sinus percolating into the node adjacent to a follicle with a germinal center.
- The tumor is composed of 2 cell types: Small cells with scant cytoplasm and hyperchromatic nuclei, and larger cells with oval vesicular nuclei . Scattered lymphocytes are also present throughout the tumor .
- The stroma in this case is edematous and highlights the associated capillary vasculature .
- Low magnification of a spiradenoma shows a dermal-based tumor characterized by irregularly-shaped nodules and smaller lobules in the dermis.