The "CLL" FISH Panel Is Not Specific for a Diagnosis of CLL; Only Prognostic.
Ana Hettinga, Kaaren K Reichard. TriCore, Albuquerque, NM; Univ. of New Mexico, Albuqerque
Background: Dohner et al. showed in 2000 that certain FISH findings predict disease outcomes in chronic lymphocytic leukemia (CLL). Since that publication, we have noticed that some individuals equate the prognostic power of the CLL FISH panel in CLL with diagnostic power. This could potentially result in a misdiagnosis with downstream outcome effects. Therefore, we sought to demonstrate that FISH abnormalities seen in typical cases of CLL could also be seen in mantle cell lymphoma (MCL) (which is the main immunophenotypic differential diagnostic consideration).
Design: We evaluated 50 cases of CD5+ mantle cell lymphoma (MCL) with our "CLL" FISH panel. The panel detects deletions of 13q14, 13q34, 17p13 (TP53), 11q22 (ATM), and trisomy 12. We compared the findings to 162 consecutive cases of CLL. FISH for the CCND1-IGH@ fusion confirmed and excluded all cases of MCL and CLL, respectively.
Results: FISH abnormalities (abns) were seen in 31/50 MCL (62%) and 129/162 CLL (80%). Of the abnormal MCL, 10/31 had a single abn (80% were an ATM or TP53 deletion), 7/31 had two abns, and 14/31 had >3 abns. Of the abnormal CLL, 81% had a single abn (61% del13q14, 24% +12, 9% ATM deletion, 6% TP53 deletion), 19% had two abns and no cases had >3 abns (0%). 9/14 MCL with >3 abns had a triple deletion pattern involving ATM/13q14/13q34. Of cases with two FISH abns, the dual deletion patterns of ATM/13q14 or TP53/13q14 were reasonably similar between CLL cases 16/25 (64%) and MCL cases 3/7 (42%).
Conclusions: The "CLL" FISH panel is not specific for a diagnosis of CLL, only prognostic. In our study, the CLL FISH panel revealed a "CLL-like" abnormality in 62% of mantle cell lymphoma cases (main differential diagnosis). This could potentially result in a misdiagnosis and/or inappropriate management if FISH for CCND1-IGH@ or cyclin D1 immunohistochemistry is not performed. We report several key findings. First, single deletions occur in 30% of MCL; mostly TP53 or ATM deletions. While such deletions correlate with a worse prognosis in CLL, similar to that expected in MCL, disease management could be adversely affected by an incorrect diagnosis. Second, a "triple hit" deletion of ATM/13q14/13q34 is recurrent in MCL whereas three FISH abns in CLL is exceedingly rare. If >3 abns is seen in a case of newly suspected CLL, consider MCL. Three, the finding of two abnormalities by FISH is similar between MCL (23%) and CLL (19%) and is often a combination of deletion 13q14 with ATM or TP53. One should use caution when interpreting the results of a "CLL" FISH panel as diagnostic of CLL.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 163, Wednesday Morning