CD117, BAP1, MTAP, and TdT Is a Useful Immunohistochemical Panel to Distinguish Thymoma from Thymic Carcinoma

SIMPLE SUMMARY: Thymic epithelial tumors, including thymomas and thymic carcinomas are malignant neoplasms that occur in the prevascular (anterior) mediastinum. Thymic carcinomas have a worse outcome than thymomas, and, therefore, management and treatment may differ. However, the morphologic distinction between thymomas and thymic carcinomas can be challenging, as has also been shown in reproducibility studies. We aimed to identify immunohistochemical markers that aid in the distinction between thymomas and thymic carcinomas. We found that a panel of CD117 with a cut-off of 10% tumor cell expression, BAP1, mTAP, and TdT was able to predict 88.9% of thymic carcinomas and 77.8% of thymomas (among the studied types A and B3 thymomas and micronodular thymomas with lymphoid stroma). Only a small subset of thymic carcinomas (11.1%) and thymomas (22.2%) could not be predicted with that model. ABSTRACT: Background: The morphologic distinction between thymic carcinomas and thymomas, specifically types B3, A, and occasionally micronodular thymomas with lymphoid stroma (MNTLS) can be challenging, as has also been shown in interobserver reproducibility studies. Since thymic carcinomas have a worse prognosis than thymomas, the diagnosis is important for patient management and treatment. This study aimed to identify a panel of immunohistochemical (IHC) markers that aid in the distinction between thymomas and thymic carcinomas in routine practice. Materials and Method: Thymic carcinomas, type A and B3 thymomas, and MNTLS were identified in an institutional database of thymic epithelial tumors (TET) (1963–2021). IHC was performed using antibodies against TdT, Glut-1, CD5, CD117, BAP1, and mTAP. Percent tumor cell staining was recorded (Glut-1, CD5, CD117); loss of expression (BAP1, mTAP) was considered if essentially all tumor cells were negative; TdT was recorded as thymocytes present or absent (including rare thymocytes). Results: 81 specimens included 44 thymomas (25 type A, 11 type B3, 8 MNTLS) and 37 thymic carcinomas (including 24 squamous cell carcinomas). Using BAP1, mTAP, CD117 (cut-off, 10%), and TdT, 88.9% of thymic carcinomas (95.7% of squamous cell carcinomas) and 77.8% of thymomas could be predicted. Glut-1 expression was not found to be useful in that distinction. All tumors that expressed CD5 in ≥50% of tumor cells also expressed CD117 in ≥10% of tumor cells. In four carcinomas with homozygous deletion of CDKN2A, mTAP expression was lost in two squamous cell carcinomas and in a subset of tumor cells of an adenocarcinoma and was preserved in a lymphoepithelial carcinoma. Conclusion: A panel of immunostains including BAP1, mTAP, CD117 (using a cut-off of 10% tumor cell expression), and TdT can be useful in the distinction between thymomas and thymic carcinomas, with only a minority of cases being inconclusive.