Inhibin immunohistochemical staining: A practical approach for the surgical pathologist in the diagnoses of ovarian sex cord-stromal tumors

Through a brief introduction of inhibin history, characteristics of the antibody against inhibin, and normal tissue distribution of α-inhibin expression, this comprehensive review focuses on a practical approach to using α-inhibin in the differential diagnosis of ovarian sex cord-stromal tumors (SCSTs). Alpha-inhibin has become a most useful immunohistochemical marker of gonadal SCST, regardless if the tumors are primary, recurrent, or metastatic. However, pathologic diagnosis of individual SCST is still based largely on morphologic criteria. Alpha-inhibin immunohistochemical (IHC) staining should be used only when a difficult morphologic diagnosis is encountered. In this perspective, α-inhibin and other properly selected markers should be ordered at the same time. This is simply because α-inhibin is not specific for SCSTs. Caution should be exercised in the interpretation of α-inhibin-positive cells, because a wide variety of primary and metastatic ovarian tumors may contain significant numbers of α-inhibin-positive stromal cells. As with other immunohistochemical stains, a panel of stains and comparison with the corresponding hematoxylin and eosin (H&E) slides is necessary, especially when staining patterns and cellular localization are in question. The antibody will not help to differentiate tumors within the category of SCST. The pattern or the intensity of staining in SCSTs does not predict tumor behavior, although there is a tendency of loss of α-inhibin expression in poorly differentiated Sertoli or Sertoli-Leydig cell tumors. In cases where metastatic granulosa or Sertoli-Leydig cell tumors are a concern, positive α-inhibin staining is diagnostic, but a negative result does not rule out metastatic disease. Calretinin has been recently recognized as a more sensitive, but less specific marker for SCSTs and it may be used to recognize an inhibin-negative SCST. In this review, we have listed nine of the most commonly encountered clinical scenarios where α-inhibin and other markers could be used in diagnostic surgical pathology of ovarian tumors.