Annexin A1 (ANXA1), Key Confirmatory Marker Discriminating Hairy Cell Leukemia from Variant Hairy Cell Leukemia and Other Morphologically Similar B-Cell Neoplasms
Shannon Gabriel-Griggs, Michelle Bleile, Adam Bell, Nancy Rosenthal, Sergei Syrbu. University of Iowa, Iowa City, IA
Background: Differentiating hairy cell leukemia (HCL) from variant hairy cell leukemia (vHCL), splenic marginal zone lymphoma (MZL), mantle cell lymphoma (MCL) or chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) can be problematic especially when evaluating core biopsy material. Distinguishing HCL is of clinical importance as treatment differs markedly. As morphology and immunophenotype can overlap, a marker specific for HCL would be advantageous. Annexin A1 (ANXA1), a gene upregulated in HCL, has been reported in a single study to provide highly sensitive and specific immunocytochemical detection of HCL. We evaluated ANAX1 and TRAP, a classic stain for HCL, to determine their usefulness in distinguishing HCL from morphologically similar entities.
Design: Tissue microarrays were constructed with duplicate paraffin-embedded tissue cores from 11 HCLs, 2 vHCLs, 22 MZLs, 14 MCLs, and 23 CLL/SLLs. Immunostaining was performed on all specimens using antibodies against ANXA1 and TRAP. Each core was evaluated for the percentage of tumor cells staining and recorded for Proportion [P(0): 0%, P(1): 1-25%, P(2): 25-50%, and P(3): >50%] and Intensity [I (0-3+)]. A score was then calculated P+I=total. Scores of 0 were considered negative and >0 positive.
Results: Our study showed 11/11 (100%) of classical HCL cases strongly positive for ANXA1 while both (100%) of the vHCL cases were negative (P+I=0). All of the other B-cell neoplasms tested were also negative for staining with ANXA1; taking into account that ANXA1 can stain myeloid cells and T-lymphocytes. TRAP staining showed 11/11 (100%) HCL cases were strongly positive (P+I=6) while 2/2 (100%) of vHCL cases were negative (P+I=0). 22/22 (100%) of MZL cases were positive for TRAP with P+I scores ranging from 3-5. 13/14 (93%) of MCL cases were positive for TRAP with P+I scores ranging from 2-3. 18/23 (78%) of CLL/SLL cases were positive for TRAP with P+I scores ranging from 2-6 with most cases P+I=2-3.
Conclusions: ANXA1 paraffin immunomorphologic detection of hairy cell leukemia demonstrates 100% specificity and sensitivity, with no staining seen in vHCL. While TRAP staining is highly sensitive, it is non-specific with significant staining seen in other B-cell neoplasms, though it is negative in vHCL. Thus TRAP is a supportive but not diagnostic stain in the diagnosis of hairy cell leukemia. Due to its high sensitivity and specificity, ANXA1 should be used as the key confirmatory marker in discriminating hairy cell leukemia from vHCL and morphologically similar B-cell neoplasms.
Monday, March 19, 2012 1:00 PM
Poster Session II # 227, Monday Afternoon