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New prognostic relevant factors in primary cutaneous diffuse large B-cell lymphomas

https://doi.org/10.1016/j.jaad.2006.12.026Get rights and content

Background

There is a growing body of literature that has enhanced our understanding of the biology of primary cutaneous diffuse large B-cell lymphoma (PCDLBCL) including in the context of gene profiling studies. Recent studies have demonstrated an activated proliferation profile associated with leg type lymphoma including overexpression of proto-oncogenes PIM1, PIM2, and cMYC, and the transcription factors MUM1 and OCT2. Although gene profiling is very useful in understanding the molecular basis of diffuse large B-cell lymphoma (LBCL), it is not practical from a routine diagnostic perspective. In this regard, the purpose of the study was to further define an armamentarium of easily applied immunohistochemical stains to accurately prognosticate PCDLBCL.

Methods

In all, 35 patients with PCDLBCL, 14 of follicle center and 21 of leg type, were analyzed using antibodies against CD5, CD138, BCL2, BCL6, OCT2, MUM1, FOXP1, and cMYC. Findings were correlated with clinical data.

Results

All cases stained negative for CD5 and CD138. Both subtypes differed in distinct staining patterns for BCL6, BCL2, OCT2, MUM1, and FOXP1. Staining for BCL2, OCT2, and/or MUM1 was associated with poor, and BCL6 with a favorable prognosis. Expression of cMYC was irrespective of prognosis or subtype, whereas ulceration or primary manifestation on the leg or multiple lesions was indicative for worse prognosis.

Limitations

Case number was a limitation.

Conclusion

Discriminating PCDLBCL supports the validity of the World Health Organization/European Organization for Research and Treatment of Cancer classification. To identify risk factors in patients with PCDLBCL we recommend thorough evaluation of clinical presentation and exploratory staining pattern for BCL2, BCL6, MUM1 and OCT2.

Section snippets

Patients and samples

For examination we used formalin-fixed skin biopsy specimens from patients with LBCL-L and LFCL. An informed consent was obtained from each patient before biopsy. All biopsy specimens were taken for diagnostic reasons. For inclusion into our study the lymphoma had to be restricted to the skin at the time of diagnosis. This was confirmed by appropriate staging procedures. Patients with immunosuppression have been excluded from the study. We only included cases composed of diffuse arranged

Clinical parameters

In all, 35 patients with primary cutaneous LBCL were included into the study; 16 of them were male and 19 were female. The lymphomas were classified as LFCL in 14 cases and as LBCL-L in 21 cases.

The mean age was 64.6 years (SD 14.8, median 68 years, range 23-90 years) at the time of diagnosis and the mean follow-up was 60.2 months (median 59.5 months, range 4-156 months).

The distribution of the lesions included legs (14 cases with exclusive location on the leg: 6 right, 6 left, 2 bilateral),

Discussion

In this study we investigated clinical and immunophenotypic characteristics in a large number of PCDLBCLs including cases with LBCL-L and LFCL.

Both groups show significant differences in clinical presentation and prognosis. In LBCL-L the patients are usually older and present more often with multiple lesions. Pooling all lymphomas together we identified diagnosis, location on the leg, ulceration, and multiple lesions at presentation as significant prognostic factors. In our study all 5 patients

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    Funding sources: None.

    Conflicts of interest: None identified.

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