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Lymphocyte Predominant Hodgkin's Lymphoma

Synonyms: L and H Nodular Type Hodgkin Disease, Lukes and Collins , Nodular Lymphocyte Predominance Hodgkin's Lymphoma, Nodular Paragranuloma

Definition

A subtype of Hodgkin lymphoma mostly composed of small lymphoid cells with a vague large nodular pattern. Interspersed in this cellular infiltrate are usually variant large cells with multilobulated nuclei, smaller nuclei and indistinct nucleoli (L and H or popcorn cells). Classic Reed Sternberg cells are absent.

Clinical Features

Gross Pathology

Involved Lymph Nodes

Histopathology

L&H or ‘Popcorn’ Cells (Fig. 4)

Lymphocyte predominance Hodgkin's lymphoma. High-power view showing the lymphocytic and/or histiocytic (L&H) type of cell (‘popcorn’ cell) that is characteristic of this condition.

Fig. 4: Lymphocyte predominance Hodgkin's lymphoma. High-power view showing the lymphocytic and/or histiocytic (L&H) type of cell (‘popcorn’ cell) that is characteristic of this condition.

  • Variable but usually large number
  • Type of Reed–Sternberg cell:
    • nucleus:
    • folded
    • multilobed
    • smaller nucleoli than Reed–Sternberg cells
  • Occasionally:
    • predominate at margins of nodules, creating a ‘wreath’ around them
    • cluster in large confluent sheets resembling diffuse large cell lymphoma

Special Stains and Immunohistochemistry

L&H Cells

Differential Diagnosis

Classic Hodgkin's Lymphoma

T-cell-rich B-cell Lymphoma

  • Differential diagnosis fraught with practical and conceptual difficulties

Follicular Lymphoma

  • May be simulated on low power
  • Nodules of NLPHL:
    • more irregular in size and staining quality
    • mottled appearance (see Fig. 3)

Staging/Grading

  • Most cases are stages I and II

Staging

  • Established by Ann Arbor Workshop in 1971 and modified at Cotswolds in 198933–35

Ann Arbor Staging Classification For Hodgkin's lymphoma (As Modified At Cotswolds)36

Stage I
  • Involvement of a single lymph node region (I) or single extralymphatic organ or site (Ig)
Stage II
  • Involvement of two or more lymph node regions on same side of diaphragm (II) or localized involvement of an extralymphatic organ or site (IIg)
Stage III
  • Involvement of lymph node regions on both sides of the diaphragm (III) or localized involvement of an extralymphatic organ or site (IIIg) or spleen (IIIg) or both (IIIse)
Stage IV
  • Diffuse or disseminated involvement of one or more extralymphatic organs with or without associated lymph node involvement. The organ(s) involved should be identified by a symbol:
    • A, asymptomatic
    • B, fever >38° previous month, sweats previous month, weight loss >10% of body weight previous 6 months
  • X, bulk (>10 cm for lymph node, >1/3 of internal transverse diameter of thorax at >5/6 on a posteroanterior chest radiograph)

Management

  • Two pillars of therapy:
    • radiation therapy
    • chemotherapy
  • Choice largely dependent on:
    • stage
    • bias of individual centers37–39

References

1 Bodis S, Kraus MD, Pinkus G, Silver B, Kadin ME, Canellos GP, et al. Clinical presentation and outcome in lymphocyte-predominant Hodgkin's disease. J Clin Oncol. 1997;15:3060–3066.

2 Neiman RS. Current problems in the histopathologic diagnosis and classification of Hodgkin's disease. Pathol Annu. 1978;13(Pt 2):289–328.

3 Siebert JD, Stuckey JH, Kurtin PJ, Banks PM. Extranodal lymphocyte predominance Hodgkin's disease. Clinical and pathologic features. Am J Clin Pathol. 1995;103:485–491.

4 Delabie J, Greiner TC, Chan WC, Weisenberger DD. Concurrent lymphocyte predominance Hodgkin's disease and T-cell lymphoma: a report of three cases. Am J Surg Pathol. 1997;20:355–362.

5 Ohno T, Huang JZ, Wu G, Park KH, Weisenburger DD, Chan WC. The tumor cells in nodular lymphocyte-predominant Hodgkin's disease are clonally related to the large cell lymphoma occurring in the same individual. Direct demonstration by single cell analysis. Am J Clin Pathol. 2001;116:506–511.

6 Brauninger A, Hansmann ML, Strickler JG, Dummer R, Burg G, Rajewsky K, et al. Identification of common germinal-center B-cell precursors in two patients with both Hodgkin's disease and non-Hodgkin's lymphoma. New Engl J Med. 1999;340:1239–1247.

7 Marafioti T, Hummel M, Anagnostopoulos I, Foss HD, Falini B, Delsol G, et al. Origin of nodular lymphocyte-predominant Hodgkin's disease from a clonal expansion of highly mutated germinal-center B-cells. N Engl J Med. 1997;337:453–458.

8 Stoler MH, Nichols GE, Symbula M, Weiss LM. Lymphocyte predominance Hodgkin's disease. Evidence for a k light chain-restricted monotypic B-cell neoplasm. Am J Pathol. 1995;146:810–818.

9 Brauninger A, Küppers R, Strickler JG, Wacker HH, Rajewsky K, Hansmann ML. Hodgkin's and Reed–Sternberg cells in lymphocyte predominant Hodgkin's disease represent clonal populations of germinal center-derived tumor B-cells. Proc Natl Acad Sci U S A. 1997;94:9337–9342.

10 Poppema S. Lymphocyte-predominance Hodgkin's disease. Semin Diagn Pathol. 1992;9:257–264.

11 Poppema S, Kaiserling E, Lennert K. Epidemiology of nodular paragranuloma (Hodgkin's disease with lymphocytic predominance, nodular). J Cancer Res Clin Oncol. 1979;95:57–63.

12 Poppema S, Kaiserling E, Lennert K. Hodgkin's disease with lymphocytic pre-dominance, nodular type (nodular paragranuloma) and progressively transformed germinal centers. A cytohistological study. Histopathology. 1979;3:295–308.

13 Lukes RJ, Butler JJ, Hicks EB. Natural history of Hodgkin's disease as related to its pathologic picture. Cancer. 1966;19:317–344.

14 Chittal SM, Alard C, Rossi JF, al Saati T, Le Tourneau A, Diebold J, et al. Further phenotypic evidence that nodular, lymphocyte-predominant Hodgkin's disease is a large B-cell lymphoma in evolution. Am J Surg Pathol. 1990;14:1024–1035.

15 Cibull ML, Stein H, Gatter KC, Mason DY. The expression of the CD3 antigen in Hodgkin's disease. Histopathology. 1989;15:599–605.

16 Coles FB, Cartun RW, Pastuszak WT. Hodgkin's disease, lymphocyte-predominant type. Immunoreactivity with B-cell antibodies. Mod Pathol. 1988;1:274–278.

17 Kamel OW, Gelb AB, Shibuya RB, Warnke RA. Leu 7 (CD57) reactivity distinguishes nodular lymphocyte predominance Hodgkin's disease from nodular sclerosing Hodgkin's disease, T-cell-rich B-cell lymphoma and follicular lymphoma. Am J Pathol. 1993;142:541–546.

18 Momose H, Chen YY, Ben-Ezra J, Weiss LM. Nodular lymphocyte-predominant Hodgkin's disease. Study of immunoglobulin light chain protein and mRNA expression. Hum Pathol. 1992;23:1115–1119.

19 Nicholas DS, Harris S, Wright DH. Lymphocyte predominance Hodgkin's disease – an immunohistochemical study. Histopathology. 1990;16:157–165.

20 Ruprai AK, Pringle JH, Angel CA, Kind CN, Lauder I. Localization of immunoglobulin light chain mRNA expression in Hodgkin's disease by in situ hybridization. J Pathol. 1991;164:37–40.

21 Von Wasielewski R, Werner M, Fischer R, Hansmann ML, Hubner K, Hasenclever D, et al. Lymphocyte-predominant Hodgkin's disease. An Immunohistochemical analysis of 208 reviewed Hodgkin's disease cases from the German Hodgkin's Study Group. Am J Pathol. 1997;150:793–803.

22 Regula DP, Weiss LM, Warnke RA, Dorfman RS. Lymphocyte predominance Hodgkin's disease. A reappraisal based upon histological and immunophenotypical findings in relapsing cases. Histopathology. 1987;11:1107–1120.

23 Trudel MA, Krikorian JG, Neiman RS. Lymphocyte predominance Hodgkin's disease. A clinicopathologic reassessment. Cancer. 1987;59:99–106.

24 Möller P, Lennert K. On the angiostructure of lymph nodes in Hodgkin's disease. An immunohistochemical study using the lectin I of Ulex europaeus as endothelial marker. Virchows Arch [A]. 1984;403:257–270.

25 Soderstrom N, Norberg B. Observations regarding the specific postcapillary venules of lymph nodes in malignant lymphomas. Acta Pathol Microbiol Scand (A). 1974;82:71–79.

26 Regula DP, Hoppe RT, Weiss LM. Nodular and diffuse types of lymphocyte predominance Hodgkin's disease. N Engl J Med. 1988;318:214–219.

27 Ferry JA, Zukerberg LR, Harris NL. Florid progressive transformation of germinal centers. A syndrome affecting young men, without early progression to nodular lymphocyte predominance Hodgkin's disease. Am J Surg Pathol. 1992;16:252–258.

28 Said JW, Sassoon AF, Shintaku IP, Kurtin PJ, Pinkus GS. Absence of bcl-2 major breakpoint region and JH gene rearrangement in lymphocyte predominance Hodgkin's disease. Results of Southern blot analysis and polymerase chain reaction. Am J Pathol. 1991;138:261–264.

29 Schmid C, Sargent C, Isaacson PG. L and H cells of nodular lymphocyte predominant Hodgkin's disease show immunoglobulin light-chain restriction. Am J Pathol. 1991;139:1281–1289.

30 Gelb AB, Dorfman RF, Warnke RA. Coexistence of nodular lymphocyte predominance Hodgkin's disease and Hodgkin's disease of the usual type. Am J Surg Pathol. 1993;17:364–374.

31 Mason DY, Banks PM, Chan J, Cleary ML, Delsol G, de Wolf Peeters C, et al. Nodular lymphocyte predominance Hodgkin's disease. A distinct clinicopathological entity (editorial). Am J Surg Pathol. 1994;18:526–530.

32 Khalidi HS, Lones MA, Zhou Y, Weiss LM, Medeiros LJ. Detection of Epstein–Barr virus in the L & H cells of nodular lymphocyte predominance Hodgkin's disease. Report of a case documented by immunohistochemical, in situ hybridization, and polymerase chain reaction methods. Am J Clin Pathol. 1997;108:687–692.

33 Carbone PP, Kaplan HS, Musshoff K, Smithers DW, Tubiana M. Report of the committee on Hodgkin's disease staging classification. Cancer Res. 1971;31:1860–1861.

34 Lacher MJ. Routine staging laparotomy for patients with Hodgkin's disease is no longer necessary. Cancer Invest. 1983;1:93–99.

35 Lister TA, Crowther D, Sutcliffe SB, Glatstein E, Canellos GP, Young RC, et al. Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin's disease. Cotswolds meeting. J Clin Oncol. 1989;7:1630–1636.

36 Warnke RA, Weiss LM, Chan JKC, Cleary ML, Dorfman RF. Tumors of the lymph nodes and spleen. Atlas of tumor pathology, series 3, fascicle 14. Washington, D.C.: Armed Forces Institute of Pathology; 1995;.

37 Rosenberg SA, Kaplan HS. The evolution and summary results of the Stanford randomized clinical trials of the management of Hodgkin's disease. 1962–1984. Int J Radiat Oncol Biol Phys. 1985;11:5–22.

38 Straus DJ. Strategies in the treatment of Hodgkin's disease. Semin Oncol. 1985;13:26–34.

39 Urba WJ, Longo DL. Hodgkin's disease. N Engl J Med. 1992;326:678–687.

40 Wright CJE. Prospects of cure in lymphocyte-predominant Hodgkin's disease. Am J Clin Pathol. 1977;67:507–511.

Last updated: 9 Apr 2006

Lymphocyte Predominant Hodgkin's Lymphoma

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