Nodular lymphocyte-predominant hodgkin lymphoma with atypical T cells: a morphologic variant mimicking peripheral T-cell lymphoma

Abstract

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a distinct Hodgkin lymphoma subtype composed of few neoplastic lymphocyte-predominant (LP) cells in a background of reactive small B and T cells. We have seen occasional NLPHL cases that contain background T cells with prominent cytologic atypia, raising the differential diagnosis of peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) or a composite lymphoma. We sought to characterize the clinicopathologic features of such cases. Eleven NLPHL cases with atypical T cells diagnosed from 1977 to 2010 were identified at 2 institutions and compared with 24 control NLPHL cases lacking atypical T cells. All 9 male patients and 2 female patients presented with localized peripheral lymphadenopathy. In comparison with control patients, they were younger (median age, 13.8 vs. 36.1 y; P=0.015), with more frequent cervical lymph node involvement (54.5% vs. 8.3%, P=0.015). In all 11 cases, areas of NLPHL with typical B-cell-rich nodules containing LP cells were present. Nine cases contained sheets of atypical T cells surrounding primary and secondary follicles in a pattern mimicking the T-zone pattern of PTCL-NOS; the remaining 2 cases contained atypical T cells presented as large clusters at the periphery of B-cell-rich nodules. In all cases, the atypical T-cell-rich areas contained rare scattered LP cells, which were IgD in 5 of 7 cases (71.4%). The atypical T cells showed no pan-T-cell antigen loss or aberrant T-cell antigen expression in any case, and polymerase chain reaction or Southern blot analysis showed no evidence of T-cell clonality in 6 cases tested. The atypical T cells exhibited a variable immunophenotype with respect to germinal center, follicular T-helper, T-regulatory, and cytotoxic T-cell markers. Among 8 patients with clinical follow-up (median follow-up: 6.4 y), 5 patients had recurrent NLPHL at 6 months to 12 years after diagnosis and 6 patients are alive without disease at 9 months to 18 years after diagnosis. In comparison with control patients, NLPHL patients with atypical T cells were more likely to develop recurrent NLPHL (71.4% vs. 13.6%, P=0.008) and to have a shorter time to relapse (P=0.04). Our findings suggest that some cases of NLPHL, occurring predominantly in younger patients, contain prominent populations of morphologically atypical T cells that may raise the possibility of concurrent nodal involvement by PTCL-NOS, a rare diagnosis in children. The clinical behavior of these cases appears similar to that of NLPHL with T-cell-rich diffuse areas, with a higher risk of disease recurrence and no difference in overall survival; however, this finding warrants confirmation in studies of larger numbers of patients.

FIGURE 1.

Kaplan-Meier analysis of time to first relapse following the initial diagnosis of NLPHL. Patients with morphologically atypical T cells had a shorter time to relapse compared with control patients lacking morphologically atypical T cells (P = 0.04). Broken line indicates NLPHL patients with morphologically atypical T cells and solid line indicates control patients. Vertical lines represent censored patients.

FIGURE 2.

Cytologic features of NLPHL with atypical T cells. Atypical T cells demonstrated a morphologic spectrum but were typically larger than the small lymphocytes within primary follicles (A, case 1; B, case 5; C, case 7; D, case 4; E, case 6; F, case 11), with vesicular (A) or dispersed (B-E) chromatin, irregular nuclei (B-D), occasional prominent nucleoli (B, F), moderately abundant pale eosinophilic cytoplasm (B-C, F), and increased mitotic activity (B-F). Rare scattered LP cells with multilobated nuclei, pale chromatin, and prominent nucleoli were visible within the T-cell-rich areas, both interspersed among the atypical T cells and at the periphery of primary follicles (A inset; B-C, arrows). In case 4, the T cells were associated with fine compartmentalizing background fibrosis (D).

FIGURE 3.

Architectural features of NLPHL with atypical T cells. A, All cases contained at least focal areas of NLPHL with typical B-cell-rich nodules (inset: CD20 stain), as illustrated in this representative image from case 1. B, In some cases, such as case 4, conspicuous fibrotic bands surrounded expanded B-cell-rich nodules. C, Case 1 also contained areas with a distinct interfollicular growth pattern, seen in the majority of cases, in which sheets of atypical T cells were present around mostly primary follicles and some secondary follicles. D, Case 6 with interfollicular atypical T cells, surrounding primary and secondary follicles; secondary follicles were prominent in this case. E, In a minority of cases, the atypical T cells formed large aggregates at the periphery of and in between expanded B-cell-rich nodules of NLPHL, as shown in this representative image from case 10. F, Case 11 also showed the less common parafollicular growth pattern, with atypical T cells surrounding an enlarged B-cell-rich NLPHL nodule. Note the narrow band of fibrosis partially encircling the atypical T-cell-rich area on the left.

FIGURE 4.

Immunohistochemical features of NLPHL with atypical T cells. A, Low-power view of case 3 showing the T-cell-rich area with an interfollicular growth pattern. B, On higher magnification, the T cells were relatively small and only slightly atypical with dispersed chromatin and occasional apoptotic cells; scattered LP cells were present in these areas (arrows and inset). C, A CD3 stain highlights T-cell-rich areas. D, A CD20 stain highlights scattered large cells within T-cell-rich areas, consistent with LP cells. Small primary follicles at the left-hand and right-hand sides of the image also stain for CD20. E, LP cells were positive for IgD in this case. F, The T-cell-rich areas demonstrated an elevated proliferation index by Ki67 staining (approximately 30% in this case). Note the contrast with the much lower proliferation index in the B cells of the adjacent primary follicles.