Chronic lymphocytic leukemia with t(14;18) and trisomy 12: Report of 2 cases and review of the literature

Archives of Pathology & Laboratory Medicine,  Dec 2002  by Sen, Filiz,  Lai, Raymond,  Albitar, Maher

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* The chromosomal abnormality t(14;18) is most commonly associated with neoplasms of follicular center cell origin. However, t(14;18) also has been reported in rare cases of chronic lymphocytic leukemia (CLL). In 2215 cases of CLL studied by conventional cytogenetics in our institution, we identified 2 cases of CLL carrying t(14;18). Both patients were men, aged 52 and 71 years at the time of diagnosis. One patient presented with leukemia and the other primarily with nodal disease. In addition to t(14;18), trisomy 12 (+12) was identified in the same clone in both cases. Atypical morphologic features were identified: case 1 contained more than 15% lymphoid cells with cleaved nuclei, whereas case 2 contained more than 15% plasmacytoid lymphoid cells. The immunophenotype of case 2 was also unusual for CLL, showing weak CD23 expression and FMC7 positivity. We identified 6 other t(14;18)-carrying CLL cases in the literature; 2 had t(14;18) as the sole abnormality and 2 contained +12 as the additional abnormality. To conclude, cases of CLL carrying t(14;18) are exceedingly rare, and +12 appears to be the most common cytogenetic abnormality coexisting with t(14;18) in CLL. (Arch Pathol Lab Med. 2002;126:1543-1546)

Various cytogenetic abnormalities have been described in B-cell chronic lymphocytic leukemia (CLL).1,2 Trisomy 12 (+12) is the most frequent numeric chromosomal abnormality. t(14;18), which is highly characteristic of neoplasms of follicular center cell origin, is exceedingly rare in CLL. It has been reported that rare cases of CLL carry t(14;18). We identified 6 cases of CLL with t(14;18) in the literature, 2 of which also had +12 in the same clone. In this report, we describe the clinical and pathologic features of 2 additional cases of CLL with coexisting t(14;18) and +12 and review the literature.

COMMENT

In this report, we describe 2 rare cases of CLL characterized by the coexistence of t(14;18)(q32;q21) and +12. Both of these 2 cases also demonstrated atypical morphologic features that meet the criteria of "atypical CLL" as previously proposed.5 Case 1 had more than 15% lymphoid cells with cleaved nuclei. Case 2 had more than 15% plasmacytoid cells. The second case also showed an immunophenotypic pattern that is unusual for CLL: positive for FMC7 and weakly positive for CD23.

Trisomy 12 is the most frequent numeric chromosomal abnormality in CLL, with 10% to 20% of cases containing + 12 by conventional cytogenetic studies.2,6 Roughly half of these cases also have other coexisting cytogenetic abnormalities. Trisomy 12 has been found to be associated with atypical morphologic features in CLL; increased prolymphocytes and increased lymphoid cells with irregular nuclear contours or plasmacytoid features are more common in CLL carrying +12.5,7 Immunophenotypic features that are unusual for CLL, such as bright surface immunoglobulin and FMC7 expression, are also found to be associated with +12 in CLL.7 Thus, the presence of atypical morphologic and/or immunophenotypic features in the current 2 cases is not surprising, since these 2 cases carry +12. Nevertheless, 1 CLL case reported by Geisler and colleagues8 had bright expression of surface immunoglobulin but no +12. This finding raises the possibility that t(14;18) by itself also may be associated with atypical immunophenotype.

The t(14;18) translocation has been identified in up to 90% of follicular lymphomas9 and 20% to 30% of diffuse large B-cell lymphomas, the latter presumably of follicle center cell origin. In lymphomas of nonfollicular origin, t(14;18) is extremely rare. In one study,10 none of the 25 cases of hairy cell leukemia and 22 cases of splenic lymphoma with villous lymphocytes showed t(14;18)(q32; q21). In other studies,11,12 no t(14;18) was identified in any of the studied nonfollicular lymphomas, including mantle cell lymphomas and lymphomas of mucosa-associated lymphoid tissue.

The presence of t(14;18)(q32;q21) is highly unusual in CLL. Of 640 cases of B-cell CLL studied by the International Working Party on Chromosomes in CLL, only 3 cases were found to have t(14;18). We identified only 3 additional cases in the literature.13,14 The current 2 cases were identified in our file, which contains 2215 cases of CLL. The Table summarizes the available pathologic features of these 6 cases found in the literature and those of the current 2 cases. As a group, the mean patient age for t(14;18)positive CLL is 68 years (range, 52-82 years), with a maleto-female ratio of 7:1. Most patients (n = 5) present as having Rai stage I disease. Interestingly, 6 of these 8 cases had cytogenetic abnormalities other than t(14;18) in the same clone, most commonly +12 (4 cases). The other 2 cases showed t(2;8) and t(1;5), respectively. Only 2 of 8 cases of t(14;18)-positive CLL had t(14;18) as the sole cytogenetic abnormality. The frequency (ie, 4 of 8 cases, 50%) of +12 in the t(14;18)-positive CLL appears to be higher than that seen in CLL as a group, which has been reported as 10% to 20%.2 This apparent association between t(14; 18) and + 12 is interesting but needs to be confirmed.