p27(Kip1) immunostaining for the differential diagnosis of small B-cell neoplasms in trephine bone marrow biopsies

The distinction between mantle cell lymphoma (MCL) and other small B-cell n on-Hodgkin lymphomas (NHL) is important because MCL has a more aggressive c linical course. In bone marrow (BM) biopsy specimens, this distinction can be particularly difficult. Although cyclin D1 immunostaining and molecular detection of the t(11;14) translocation are highly specific markers for MCL , they fail to detect a proportion of cases. We have recently described tha t MCL typically lacks detectable expression of the cyclin-dependent kinase inhibitor p27(kip1) protein by immunostaining, which is expressed at high l evels in most small B-cell NHL inversely correlated to the proliferation ra te. We therefore examined whether p27(kip1) immunostaining could be a usefu l adjunct for the differential diagnosis of small B-cell NHL infiltrates in the BM. Trephine BM biopsy specimens of 96 patients, including well-charac terized MCL (19 cases), B-cell. chronic lymphocytic leukemia (27 cases), fo llicular lymphoma (18 cases), hairy cell leukemia (22 cases), and marginal zone lymphoma (10 cases) as well as 10 reactive BM, including five with ben ign lymphoid aggregates were investigated. In addition, the presence of a t (11; 14) translocation involving the major translocation cluster was studie d by PCR in all MCL Ali cases of B-cell chronic lymphocytic leukemia, folli cular lymphoma, and marginal zone lymphoma revealed a strong p27(kip1) nucl ear staining in the majority of neoplastic cells. Fourteen (76%) cases of M CL were p27(kip1)-negative in the tumor cells, whereas four cases revealed a weak nuclear positivity. Seventeen (77%) cases of hairy cell leukemia wer e also either completely negative for p27(kip1) or showed a faint positive staining in a minority of the neoplastic cells. Nine of 19 cases (47%) of M CL showed a bcll rearrangement involving the major translocation cluster re gion. These findings demonstrate that P27(kip1) immunostaining is a valuabl e additional marker for the differential diagnosis of small B-cell NHL infi ltrates in BM biopsies. The reduction or lack of p27(kip1) protein expressi on in MCL, as well as in hairy cell leukemia, might be an important event i n the pathogenesis of these disorders.