Cytoplasmic Staining of OCT4 in Pheochromocytoma Is Highly Sensitive and Specific: A Novel Immunohistochemical Finding
Riley E Alexander, David J Grignon, Muhammad T Idrees. Indiana University School of Medicine, Indianapolis, IN
Background: OCT4 immunostaining has become an essential resource in the diagnosis of germ cell neoplasia. OCT4 is a transcription factor and has a characteristic nuclear staining specific to germ cell neoplasms. The diagnosis of adrenal malignancy is sometimes challenging and it is often difficult to establish a diagnosis on morphology alone, especially in metastatic cases. In our institute, it has been observed that paraganglionic tissue consistently displayed intense cytoplasmic staining and we intended to determine if OCT4 can provide additional diagnostic utility in adrenal tumors. To our knowledge, the cytoplasmic expression of OCT4 in pheochromocytoma has not been specifically studied. The goal of this study is to analyze the immunoreactivity of adrenal cortical carcinoma (ACC) and pheochromocytoma, especially in metastatic settings.
Design: Thirty cases of primary pheochromocytoma, 24 cases of ACC (two metastatic), and 8 cases of metastatic pheochromocytoma were selected from our database. Hematoxylin and eosin (H&E) stained slides were reviewed and OCT4 (MRQ-10, Mouse monoclonal, Cell Marque Corp.; Rocklin CA, ready to use) immunostaining was performed. OCT4 staining was scored on a four-tier system (0-3), judging two separate criteria: intensity and extent of staining.
Results: In 30 of 30 (100%) cases of primary pheochromocytoma, strong and diffuse (3+3) immunoexpression was observed. In metastatic pheochromocytoma, all cases showed diffuse staining. Six of 8 (75%) metastatic pheochromocytomas showed strong expression (3+3), the remaining two (25%) showed moderate intensity (2+3). In 24 of 24 (100%) cases of ACC, including metastatic cases, OCT4 was completely negative. In all positive staining pheochromocytoma cases, the staining pattern was uniformly cytoplasmic. Nuclei were overshadowed by cytoplasmic staining in most cases. Controls, using seminoma, stained in an appropriate nuclear fashion.
Conclusions: The results describe a novel staining pattern for OCT4 in pheochromocytoma. This staining pattern has not been demonstrated elsewhere and appears to be highly specific and sensitive to paraganglionic tissue. These findings suggest that OCT4 is an immunostain with diagnostic implications in adrenal neoplasms. The difference in staining pattern may be reactivity to an unknown cross-reacting cytoplasmic antigen and needs further analysis. Additional immunoelectron microscopic and comparative studies using different commercially available OCT4 antibodies may be helpful in determining the cytoplasmic antigen.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 46, Tuesday Afternoon