Defining the borders of splenic marginal zone lymphoma: a multiparameter study

Abstract

Classic splenic marginal zone lymphomas are CD5-, CD10-, CD23-, CD43-, and usually IgD+ with biphasic white pulp nodules. However, the 2008 World Health Organization classification accepts splenic marginal zone lymphomas with monophasic marginal zone-like white pulp nodules and recognizes a group of unclassifiable splenic small B-cell lymphomas. To explore the relationship of classic splenic marginal zone lymphomas to these other less well-defined splenic lymphomas, a multiparameter study of 47 splenic marginal zone lymphomas and unclassifiable splenic small B-cell lymphomas was performed. Seventeen of 31 splenic marginal zone lymphomas were biphasic, and 14 were monophasic (90%-100% marginal zone-like white pulp nodules). Sixteen cases were unclassifiable splenic small B-cell lymphomas, most lacking a marginal zone-type component. There were many clinical similarities between the 3 groups, including similar survivals. Monophasic and unclassifiable cases were less likely to have a typical splenic marginal zone lymphoma phenotype (28.6%, 23.1%) compared with biphasic cases (86.7%), usually because of IgD negativity (P < .003). Thirty-four of 42 (81%) cases had cytogenetic abnormalities by fluorescence in situ hybridization; and 17 of 20 (85%), by classical cytogenetics. The most frequent fluorescence in situ hybridization abnormalities among the splenic marginal zone lymphomas were del(7)(q31) (26%), +12 (25%), and +3q27 (27%); and among the unclassifiable cases, +12 (50%) and +3q27 (36%). Five of 6 unclassifiable cases with exclusively small non-marginal zone-like lymphocytes involving both white and red pulp had +12 compared with 9 of 34 other cases (P < .02). CDK6 (2 cases) and BCL3 (1 case) rearrangements were only seen in the unclassifiable group. These results support including both biphasic and monophasic cases as splenic marginal zone lymphomas, but suggest that the lack of a non-marginal zone-like population in the monophasic group is associated with some biologic differences. They also demonstrate a relatively large proportion of unclassifiable cases, including a group with frequent +12.

Figure 1

A. Biphasic SMZL with expanded WP nodules consisting of a central core of small lymphocytes surrounded by an outer zone of marginal zone-like cells The lower nodule may demonstrate remnants of a follicular center. B. In contrast to the small lymphocytes in the central core of the WP nodules (top), the cells in the marginal zone are larger, have more dispersed chromatin including some with nucleoli and have more abundant pale cytoplasm. (A&B, case 39) C. Monophasic SMZL with large WP nodule consisting entirely of marginal zone-like cells with no inner core of small lymphocytes. D. The relatively monotonous neoplastic cells resemble a normal splenic marginal zone. (C&D, case 9). E. Unclassifiable splenic small B-cell lymphoma with small lymphocytes diffusely infiltrating the RP. Some WP nodules composed of small lymphocytes were also present. F. The numerous small lymphocytes appear somewhat plasmacytoid. (E&F, case 43). (H&E, A, C, E, 10×; B, D, F, 100×)

Figure 2

Kappa (A) and lambda (B) staining in a SMZL with plasmacytic differentiation demonstrates kappa light chain restricted plasma cells predominantly within the white pulp nodules (case 2, 100×). CD43 (C) and CD3 (D) from the same biphasic SMZL showing CD43 negativity in the lymphoma (case 39, 40×). Note the ring of T cells surrounding the neoplastic white pulp nodules. E. Biphasic SMZL showing IRF4/MUM1 negativity. The inset demonstrates few scattered positive lymphocytes, including some that were large (case 47, 40×, inset 500×). F. Biphasic SMZL showing diffuse IgD positivity (case 39, 40×). (immunohistochemical stains with hematoxylin counterstain)

Figure 3

FISH analysis for del(7)(q31.2) A. Representative case without del(7)(q31.2) showing two signals for CEP7 (green) and two signals for D7S486 (red). B. Representative case with del(7)(q31.2) showing two signals for CEP7 (green), but only one signal for D7S486 (red).

Figure 4

Overall survival curves for biphasic, monophasic and unclassifiable groups (p=not significant).