Characterization of Variant Patterns of Nodular Lymphocyte Predominant Hodgkin Lymphoma with Immunohistologic and Clinical Correlation

Abstract

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) has traditionally been recognized as having two morphologic patterns, nodular and diffuse, and the current WHO definition of NLPHL requires at least a partial nodular pattern. Variant patterns have not been well documented. We analyzed retrospectively the morphologic and immunophenotypic patterns of NLPHL from 118 patients (total of 137 biopsy samples). Histology plus antibodies directed against CD20, CD3, and CD21 were used to evaluate the immunoarchitecture. We identified six distinct immunoarchitectural patterns in our cases of NLPHL: "classic" (B-cell-rich) nodular, serpiginous/interconnected nodular, nodular with prominent extranodular L&H cells, T-cell-rich nodular, diffuse with a T-cell-rich background (T-cell-rich B-cell lymphoma [TCRBCL]-like), and a (diffuse) B-cell-rich pattern. Small germinal centers within neoplastic nodules were found in approximately 15% of cases, a finding not previously emphasized in NLPHL. Prominent sclerosis was identified in approximately 20% of cases and was frequently seen in recurrent disease. Clinical follow-up was obtained on 56 patients, including 26 patients who had not had recurrence of disease and 30 patients who had recurrence. The follow-up period was 5 months to 16 years (median 2.5 years). The presence of a diffuse (TCRBCL-like) pattern was significantly more common in patients with recurrent disease than those without recurrence. Furthermore, the presence of a diffuse pattern (TCRBCL-like) was shown to be an independent predictor of recurrent disease (P = 0.00324). In addition, there is a tendency for progression to an increasingly more diffuse pattern over time. Analysis of sequential biopsies from patients with recurrent disease suggests that the presence of prominent extranodular L&H cells might represent early evolution to a diffuse (TCRBCL-like) pattern. We also report three patients who presented initially with diffuse large B-cell lymphoma and later developed NLPHL.

Follicular dendritic cells: origin, function, and different disease-associated patterns

“…In patterns 1 and 2, scattered popcorn cells ringed by T cells are present within a nodular reactive background although the nodules may be serpiginous and connected in pattern 2. The FDC processes highlighted by CD21 stain usually sharply delineate the unstained popcorn cells and their T-cell rosettes [61,62] (Fig. 7).…”

“…Most T cells within the nodules of NLPHL are germinal center-derived CD4, CD57, and PD-1 positive T cells that form rings or rosettes surrounding the popcorn cells. Fan et al subclassified NLPHL into 6 distinct immunoarchitectural patterns: (1) classical nodular pattern, (2) serpiginous/interconnected pattern, (3) nodular with prominent extranodular popcorn cells, (4) nodular with Tcell-rich background, (5) diffuse pattern "T-cell-rich B-cell lymphoma like," and (6) diffuse pattern "moth-eaten with Bcell rich background [61]. In patterns 1 and 2, scattered popcorn cells ringed by T cells are present within a nodular reactive background although the nodules may be serpiginous and connected in pattern 2.…”

Small intestinal presentation of nodular lymphocyte-predominant Hodgkin lymphoma with T cell/histiocyte-rich B cell lymphoma-like areas—with review of literature on extranodal presentation of this disease

“…A pure diffuse pattern and a nodular pattern with many extranodular LP cells have potential clinical significance, and diffuse pattern is an independent predictor of recurrence. Presence of extranodular LP cells is thought to represent early evolution to diffuse pattern [1].…”

“…Recurrences of cHL usually show features of cHL, whereas recurrences of NLPHL can show either NLPHL or transformation to a large B cell lymphoma. In approximately 3-7% patients with NLPHL, concurrent or subsequent transformation to a diffuse large B cell lymphoma (DLBCL) is observed [1][2][3][4]. A clonal relationship has been demonstrated between the LP cells of NLPHL and the neoplastic large B cells of the associated DLBCL by molecular genetics [1,[6][7][8].…”

“…Involvement of spleen (8%), liver (3%), bones (2%), and lung (1%) during the course of the disease has been reported [12]. On the other hand, nearly one half of patients with THRLBCL present with liver, bone marrow, and/or spleen involvement [1]. In addition, primary cutaneous, ethmoidal sinus, and meningeal presentations of THRLBCL are documented [13][14][15].…”