Home Diseases and Health Information  

Home Home Translating Report News Physicians Diseases Body Sites Diseases and Health Information Search


Hodgkin's disease has been divided into classic and non-classic types. This non-classic type also known as Nodular Lymphocyte Predominance has been separated from classic cases of Hodgkin's disease because of its distinct morphologic and clinical behavior. These patients usually present with isolated lymphadenopathy of several months duration. These patients have a clincal course resembling B cell Non-Hodgkin's lymphoma with a very indolent growth pattern with single and multiple relapses which may become generalized.


Disease Associations  
Laboratory/Radiologic/Other Diagnostic Testing  
Gross Appearance and Clinical Variants  
Histopathological Features and Variants  
Special Stains/Immunohistochemistry/Electron Microscopy  
Differential Diagnosis  
Commonly Used Terms  
Internet Links  

SYNONYMS Nodular lymphocyte predominance
Lymphocytic and histiocytic
L and H type
Nodular paragranuloma
INCIDENCE 2-6% of cases of Hodgkin's disease
AGE-RANGE AND MEDIAN Peak in 4th decade


B cell lymphoma Although it behaves like a low grade B cell lymphoma but lacks clonal immunoglobulin gene rearrangement or bcl-2 rearrangement

The Tumor Cells in Nodular Lymphocyte-Predominant Hodgkin Disease Are Clonally Related to the Large Cell Lymphoma Occurring in the Same Individual Direct Demonstration by Single Cell Analysis

Toshiyuki Ohno, MD, James Z. Huang, MD, Grant Wu, MD, Kwang Hwa Park, MD, Dennis D. Weisenburger, and Wing C. Chan, MD

Am J Clin Pathol 2001;116:506-511 Abstract quote

Large cell lymphoma (LCL) sometimes occurs concurrently or subsequently in patients with nodular lymphocyte-predominant Hodgkin disease (NLPHD). Although there is evidence of a clonal relationship between LCL and NLPHD, there has been no direct demonstration that the lymphocytic and histiocytic (L&H) cells in NLPHD are related to the tumor cells in LCL.

We identified 2 cases of NLPHD with an associated LCL. Single L&H cells, the Reed-Sternberg cell variants in NLPHD, were isolated from immunostained tissue sections by micromanipulation, and the immunoglobulin heavy chain gene (IgH) complementarity determining region (CDR) III of the cells was amplified by the polymerase chain reaction (PCR). The products were compared with those obtained from microdissected LCL cells using polyacrylamide gel electrophoresis and nucleotide sequencing. The IgH CDRIII sequences from the L&H cells were related to each other, but also showed nucleotide substitutions, consistent with a germinal center origin. The sequences from the L&H cells also were related to those from the corresponding LCL cells.

We have provided direct evidence through sequence analysis of the IgH CDRIII that the L&H cells are clonally related to the corresponding LCL arising in 2 cases of NLPHD.



Most commonly involves the cervical, axillary, and inguinal nodes

B symptoms uncommon


Bone marrow involvement in patients with nodular lymphocyte predominant Hodgkin lymphoma.

Khoury JD, Jones D, Yared MA, Manning JT Jr, Abruzzo LV, Hagemeister FB, Medeiros LJ.

Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.

Am J Surg Pathol. 2004 Apr;28(4):489-95. Abstract quote  

The significance of bone marrow involvement in patients with nodular lymphocyte predominant Hodgkin lymphoma is unknown. Of 275 patients diagnosed as lymphocyte predominant Hodgkin lymphoma at our institution (1983-2003), we identified 7 patients with purely nodular disease in the diagnostic lymph node biopsy specimen who also had bone marrow involvement. The latter was detected at the time of initial diagnosis in four patients, after one cycle of chemotherapy in one patient, and at relapse in two patients.

There were six men and one woman with a median age of 37 years (range, 25-47 years). In all cases, the bone marrow was involved by large B cells, representing <10% of all cells, associated with a prominent T-cell and histiocytic background. All patients had laboratory, radiologic, and/or morphologic evidence of aggressive disease at the time of detection of bone marrow involvement. At last follow-up, four patients had died of their disease and three were alive following therapy.

In conclusion, a small subset of patients in whom lymph node biopsy shows nodular lymphocyte predominant Hodgkin lymphoma with a purely nodular pattern also may have lymphoma in the bone marrow. Bone marrow involvement is associated with laboratory, radiologic, or morphologic evidence of aggressive disease and poor prognosis. Although the best terminology for these bone marrow lymphomas is uncertain, the aggressive clinical behavior of these neoplasms supports the need for intensive therapy.


GENERAL Diagnostic Reed-Sternberg cells are not required for diagnosis
L and H cells Large cells with large nuclei and scant cytoplasm
Multilobated nuclear appearance resembling popcorn
Lymph node

Architecture focal obliterated with areas of uninvolved or hyperplastic lymphoid tissue-may have adjacent progressive transformation of germinal centers

Large nodules composed of the L and H cells are present imparting a mottled appearance to the node

Diffuse Lymphocyte Predominance (Diffuse paragranuloma) Cases which show minimal or absent nodularity but L and H cells present

Reactive follicular hyperplasia with enlargement of secondary follicles blurring the distinction between germinal centers and the mantle zone

Results in large nodules of small lymphocytes scattered among reactive follicles

Lacks L and H cells


Dark staining transformed follicles are 2-4x the size of surrounding follicles, lack well defined germinal centers or have irregular "broken-up" germinal centers

Formed mostly by small B lymphocytes, which are intermingled with isolated or small clusters of follicular center B cells

No polylobated L and H cells

May co-exist with Nodular lymphocyte predominant HD or precede its development

Risk of developing Nodular lymphocyte predominant HD in a patient with a lymph node that shows a pure PTGC is low (0-5%)


Characterization of variant patterns of nodular lymphocyte predominant hodgkin lymphoma with immunohistologic and clinical correlation.

Fan Z, Natkunam Y, Bair E, Tibshirani R, Warnke RA.
Am J Surg Pathol. 2003 Oct;27(10):1346-56. Abstract quote  

SUMMARY: 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.


Classic immunophenotype for the L and H cells Show features consistent with B cell lineage:

Nodular lymphocyte predominant Hodgkin lymphoma. An immunophenotypic reappraisal based on a single-institution experience.

Uherova P, Valdez R, Ross CW, Schnitzer B, Finn WG.

Department of Pathology, University of Michigan Medical School, Ann Arbor, USA.

Am J Clin Pathol 2003 Feb;119(2):192-8 Abstract quote

In our experience, certain commonly cited immunophenotypic features of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) are not encountered in day-to-day practice.

We reviewed 60 cases of NLPHL (18 women, 42 men; median age, 34 years) to discern immunophenotypic features from a large, single-institution cohort. All cases contained lymphocytic and histiocytic (L&H) cells. These cells expressed CD20 in 98% (59/60), CD79a (usually faint) in 87% (27/31), CD30 in 7% (4/59), epithelial membrane antigen in 21% (12/56), bcl-2 in 5% (2/41), and bcl-6 in 83% (30/36) of cases. CD10 was negative in all 36 cases studied; 100% of cases (55/55) demonstrated CD3+ rosettes. Although CD57+ T cells were common within the background infiltrate, CD57+ rosettes were seen in only 48% of cases (15/31) and were rare when encountered.

Based on these patterns, we conclude that bcl-2 and bcl-6 may be useful additions to the immunophenotypic analysis of NLPHL, but that the diagnostic usefulness of epithelial membrane antigen and CD57 rosettes may have been overemphasized in previous reports.

Small lymphocytes Mostly B cells

Lymphocyte Predominance Hodgkin's Disease The Use of bcl-6 and CD57 in Diagnosis and Differential Diagnosis

Madeleine D. Kraus, M.D.; Jane Haley, HT, QIHC

From The Lauren V. Ackerman Laboratory of Pathology, Washington University School of Medicine, St. Louis, Missouri

Am J Surg Pathol 2000;24:1068-1078 Abstract quote

Distinction of lymphocyte predominance Hodgkin's disease (LPHD) from other forms of lymphoma often requires immunohistochemistry (IHC). Most previously published recommended panels include markers to define the large neoplastic cells (for example, CD20, J chain, CD45) as well as the non-neoplastic background cells (CD21, CD45RO, CD57, TiA1).

In the present study we examine the practical use of a double IHC method designed to look simultaneously at two germinal center specific cell types: bcl6+ cells and [bcl6+, CD57+] co-positive cells.

All 10 nodular LPHD had bcl6+ large cells and numerous CD57+ small background cells, including [bcl6+CD57+] cells in rosettes. One case of LPHD with large cell transformation contained numerous bcl6+ large cells both singly (in areas of typical LPHD) and in sheets (in foci of large cell transformation), many CD57+ small cells but few [bcl6+CD57+] co-positive cells and no rosettes. In none of the five cases of florid progressive transformation of germinal centers were true rosettes seen, although all contained variable numbers of bcl6+ large cells and CD57+ cells. Lymphocyte-rich classic Hodgkin's disease LRCHD cases were notable for bcl6 reactivity in Reed-Sternberg cells in all cases, numerous background small bcl6+ lymphocytes, and rare CD57+ cells. Two phenotypic profiles were associated with the 10 cases of T cell-rich B cell large cell lymphoma (TCRBCL). In the first, group ``A,'' six of six cases had bcl6 large cells and few CD57+ small cells, and none had significant numbers of [bcl6+, CD57+] co-positive cells. In the second, group ``B,'' four of four cases had bcl6+ large cells with numerous CD57+ and [bcl6+, CD57+] co-positive cells.

These findings not only show that LPHD can be distinguished from its morphologic mimics through identification of specific germinal center cell types, but also identifies a second group of TCRBCL (group ``B'') whose phenotype suggests it might be an architectural variant of nodular LPHD.

TARC, a CC Chemokine, Is Frequently Expressed in Classic Hodgkin's Lymphoma But Not in NLP Hodgkin's Lymphoma, T-Cell-Rich B-Cell Lymphoma, and Most Cases of Anaplastic Large Cell Lymphoma

S. C. Peh, M.B.B.S., F.R.C.Path.; L. H. Kim, B.BMed.Sc.; S. Poppema, M.D., Ph.D., F.R.C.P.

From the Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur and Department of Pathology and Laboratory Medicine, University Hospital Groningen, The Netherlands.

Am J Surg Pathol 2001;25:925-929 Abstract quote

Thymus and activation-regulated chemokine (TARC) has been identified as a lymphocyte-directed CC chemokine that attracts activated T-helper type 2 (Th2) cells in humans. Recent studies showed that the T cells surrounding Reed-Sternberg cells in Hodgkin's lymphomas (HL) are Th2 type. Anaplastic large cell lymphomas (ALCL), T-cell-rich B-cell lymphoma (TCRBCL) can mimic HL in some instances.

This study aimed to establish the pattern of TARC expression in these diseases. Immunohistochemical stain using a polyclonal goat anti-human antibody to TARC was performed on 119 cases of confirmed HL; 99 were classical type (43 mixed cellularity, 43 nodular sclerosis, 5 lymphocyte depleted, 4 lymphocyte rich, 4 unclassifiable) and 20 lymphocyte predominant HL. Additional 27 ALCL (9 T-, 18 null-cell phenotype), 16 T-cell and 8 B-cell non-Hodgkin's lymphoma (NHL) were studied.

A total of 85.8% of the classical HL, one case of ALCL, and one case of large cell B-cell lymphoma with anaplastic morphology showed positive TARC expression in the tumor cells. The expression was paranuclear and/or diffuse in the cell cytoplasm. The tumor cells in all cases of lymphocyte predominant HL, TCRBCL, null ALCL, and T-NHL did not express TARC.

The high frequency of TARC expression in the Reed-Sternberg cells of classical HL may explain the characteristic T-cell infiltrate in this disease. The absence in other types that may be morphologically similar indicates that staining for TARC may aid in differential diagnosis.


Sex M>F Same
Mediastinal involvement Rare Same
Stage Most commonly stage I/II (70-80%) Same
B symptoms Rare Same
Morphologic pattern Usually fairly closely packed large lymphoid nodules containing neoplastic large cells Same
Immunophenotype of background cells Nodules composed of small B cells, punctuated by small cavities populated by the large neoplastic cells which are rosetted by T cells Same
Age Slightly older (mean 43 years) Mean age 35 years
Relapse pattern Relapses are usually single Repeated relapses, often delayed
Treatment response at relapse Not good Good
Clinical outcome Good (5 YRS 80%) but slightly worse than N-LPHL Very good (5YRS 98%)
Morphological pattern of nodules Germinal centers commonly found in the nodules, and the neoplastic cells are concentrated in the expanded mantle zones Nodules do not have germinal centers
Neoplastic cells are concentrated within the nodules, but can also be found in the internodular areas
Cytology of neoplastic cells Reed-Sternberg cells and variants Popcorn (L and H) cells
Immunophenotype of neoplastic cells CD20-/+, CD30+, CD15+/-, bcl-6- CD20+, CD30-, CD15-, bcl-6+
EBV association ~40% (but varies according to population) None


Prognostic Factors

Stage is the most important factor

See Hodgkin's disease staging

5 Year Survival

60% survival for stage IV disease

Transformation to a B or T cell Non-Hodgkin's lymphoma has been reported in 1-10% of cases

TREATMENT Dependent upon the clinical stage

Atlas of Tumor Pathology-Tumors of the Lymph Nodes and Spleen. Volume 14, Third Series. AFIP Press. 1995.
Taken from Chan JKC. Practical Lymphoma Diagnosis: A Simplified Approach. Presented at the 111th Semi-Annual California Tumor Tissue Registry. December 2001.

Commonly Used Terms

Hodgkin's Disease


Learn the basic disease classifications of cancers, infections, and inflammation

Commonly Used Terms
This is a glossary of terms often found in a pathology report.

Diagnostic Process
Learn how a pathologist makes a diagnosis using a microscope

Surgical Pathology Report
Examine an actual biopsy report to understand what each section means

Special Stains
Understand the tools the pathologist utilizes to aid in the diagnosis

How Accurate is My Report?
Pathologists actively oversee every area of the laboratory to ensure your report is accurate

Got Path?
Recent teaching cases and lectures presented in conferences

Internet Links
Last Updated 4/29/2004

Send mail to The Doctor's Doctor with questions or comments about this web site.
Copyright © 2004 The Doctor's Doctor