Utility of Automated Immunohistochemical Stain for MYC in the Identification of B-Cell Lymphoproliferative Disorders with MYC Translocation
Brenda Ly, Claudiu V Cotta. Cleveland Clinic, Cleveland, OH
Background: An immunohistochemical (IHC) stain using a new antibody for MYC has been reported to be useful in the diagnosis of B-cell lymphomas with MYC translocations (BL-MYC). The initial study used a manual IHC staining technique. Our study is the first to investigate an automated MYC IHC staining technique in the identification of cases with MYC translocations and reports staining patterns different than those initially described.
Design: 38 cases of B-lymphoproliferative disorders with intermediate and large cell morphology were analyzed by fluorescence in-situ hybridization (FISH) for MYC-translocations. These cases were stained for MYC using an automated IHC staining system. Then they were examined by two observers, in an independent and blinded fashion. 100 neoplastic cells were counted in each case. Cells with strong nuclear staining were counted as positive, while cells with very dim or negative nuclear staining were counted as negative.
Results: Suboptimal fixation leads to stains that are difficult to interpret, with most cells demonstrating intermediate or dim nuclear staining. The previously reported cytoplasmic staining pattern is completely absent. When adequately processed, FISH positive cases show most neoplastic cells to be strongly positive by IHC. In FISH negative cases only a few cells are positive. Statistical analysis shows that the difference in IHC staining between the FISH positive and negative cases is significant (p<0.05). Using a cutoff value of 30% of positive neoplastic cells, 15 of 19 MYC FISH positive case are positive by IHC (true positives-TP), with 1 of 19 negative cases being false positive (FP). If cases with suboptimal fixation are excluded, 12 of 14 cases are TP (no FP cases). If all cases are accepted, 18 of 19 FISH MYC negative cases are true negative (TN) by IHC, with 4 cases being false negative (FN). 14 of 15 well-fixed cases are TN, with 2 FN. This leads to a sensitivity of 79% (86% for well-fixed cases) and a specificity of 95% (100%).
Conclusions: The automated IHC stain for MYC is a useful tool in the diagnosis of BL-MYC. The specificity of this test is excellent even in poorly-fixed specimens. Its sensitivity is satisfactory, at 79% (86% in well fixed specimens), when a cutoff of 30% is employed. Including this stain in the workup of lymphomas could result in an economical use of MYC FISH and a shorter sign-out turnaround time.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 179, Tuesday Afternoon