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  • Title: PAX1 expression in thymic epithelial neoplasms and morphologic mimics.
    Author: Parrack PH, Hornick JL, Sholl LM.
    Journal: Hum Pathol; 2023 Dec; 142():7-14. PubMed ID: 37776957.
    Abstract:
    Thymic epithelial neoplasms are morphologically diverse and can pose a diagnostic challenge that is complicated by a lack of immunohistochemistry (IHC) markers that are entirely sensitive and specific for thymic epithelium. Polyclonal PAX8 is often used in this context, but it is not a specific marker. The PAX1 transcription factor shares significant homology with PAX8 and plays an integral role in thymic development in humans and murine models. This study evaluated the role of PAX1 IHC in differentiating thymic epithelial neoplasms from morphologic mimics on whole slide tissue sections. The PAX1 antibody stained all 74 thymoma cases; however, there was wide variability in staining intensity within each subtype. The antibody was less sensitive in thymic carcinomas and thymic neuroendocrine tumors compared to thymomas and demonstrated weak staining in a subset of morphologic mimics (21 squamous cell carcinomas, 6 pulmonary neuroendocrine tumors, 1 mesothelioma, 1 lymphoblastic lymphoma, and 1 granulosa cell tumor). With a H-score positive threshold of 75, the antibody had 100% specificity, and sensitivities of 92%, 56%, and 47% in thymomas, thymic neuroendocrine tumors, and thymic carcinomas respectively. The PAX1 antibody showed frequent geographic reduction in staining consistent with compromised antigenicity from variable formalin fixation. PAX1 IHC has a moderate-to-high sensitivity for thymic epithelial neoplasms; however, the wide staining variability and fixation effects may lead to difficulty with consistent interpretation. This marker is unlikely to supplant the role of PAX8 in diagnostic practice, but it may be a useful addition to immunohistochemistry panels when evaluating for thymic primary tumors.
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