Bcl-2 protein expression is the strongest independent prognostic factor of survival in primary cutaneous large B-cell lymphomas

Abstract

Bcl-2 protein expression has been associated with poor prognosis in patients with noncutaneous diffuse large B-cell lymphomas. In primary cutaneous large B-cell lymphomas, the location on the leg, the round-cell morphology defined as the predominance of centroblasts and immunoblasts over large centrocytes, and multiple skin lesions were identified as adverse prognostic factors. The prognostic value of bcl-2 protein expression has not been studied in large series of patients. We evaluated 80 primary cutaneous large B-cell lymphomas collected by the French Study Group on Cutaneous Lymphomas. The prognostic value of age, sex, number of lesions, cutaneous extent, location, serum lactate dehydrogenase (LDH) level, B symptoms, morphology, and bcl-2 protein expression was studied. The overall 5-year specific survival rate was 65%. In univariate analysis, advanced age, multiple skin lesions (n ‫؍‬ 48), location on the leg (n ‫؍‬ 25), round-cell morphology (n ‫؍‬ 32), and bcl-2 expression (n ‫؍‬ 39) were significantly related to death from lymphoma. In multivariate analysis, bcl-2 expression (P ‫؍‬ .0003), multiple skin lesions (P ‫؍‬ .004), and age remained independent prognostic factors. The 5-year specific survival rates in bcl-2-positive and bcl-2-negative patients were 41% and 89%, respectively (P < .0001). A new prognostic classification of primary cutaneous B-cell lymphoma should be based primarily on bcl-2 protein expression rather than the location of skin lesions. (Blood. 2004;103: 3662-3668)

WHO-EORTC classification for cutaneous lymphomas

“…In contrast to the group of PCFCLs, PCLBCL, leg type, shows strong bcl-2 expression, also in cases not located on the legs ( Figure 10C). 41,43,142,158 Bcl-6 is expressed by most cases, whereas CD10 staining is generally absent. 142 Unlike PCFCL, most PCLBCL, leg types, express MUM-1/IRF4 protein ( Figure 10D).…”

“…2,4,5,[33][34][35]38,42,150,151 A recent study suggests that strong expression of bcl-2 in PCFCLs with a diffuse large-cell histology is associated with a more unfavorable prognosis. 158 Therapy. In patients with localized or few scattered skin lesions, radiotherapy is the preferred mode of treatment, even in cases with a predominance of large "cleaved" cells.…”

“…36,152,[165][166][167] In contrast, recent studies suggest that expression of bcl-2 protein by more than 50% of the neoplastic B cells in PCFCLs with a diffuse proliferation of large centrocytes, observed in approximately 15% of cases, is associated with a more unfavorable prognosis. 158 Further studies are warranted to define the clinical and biological significance of bcl-2 expression and/or the presence of t(14;18) observed in some cases of PCFCL. Notwithstanding, demonstration of bcl-2 expression and/or t(14; 18) should always raise suspicion of a systemic lymphoma involving the skin secondarily.…”

Cutaneous B‐cell lymphomas: 2013 update on diagnosis, risk‐stratification, and management

“…Differences in growth pattern, the density of centroblasts, and cytogenetic findings do not appear to provide meaningful prognostic information. Bcl-2 expression among PCFCL with a diffuse large B-cell histology may be a notable exception [16]. In contrast, PCLBCL, LT is associated with a 5-year diseasespecific survival of approximately 50% and with cytogenetic changes, including translocations involving c-myc, that confer a poor prognosis among systemic DLBCLs [1,17].…”

Primary Cutaneous B-Cell Lymphoma: Management and Patterns of Recurrence at the Multimodality Cutaneous Lymphoma Clinic of The Ohio State University

“…The consensus recommendations from the ISCL-EORTC, based on stage and subtype of PCBCL, suggest that multiple treatment options are reasonable [14]. After treatment, the recurrence rates for PCBCL have ranged from 25% to 68% [15][16][17][18][19][20]. The effect of the treatment modality on the patterns of disease recurrence is not well known.…”