Nodular lymphocyte predominant Hodgkin lymphoma, NLPHL



NLPHL accounts for approximately 5% of all Hodgkin lymphomas. There is a unimodal age distribution; patients are predominantly male and 30-50 years old.

Clinical features

Usually involves cervical, axillary or inguinal nodes, most cases presenting as stage I or II disease. Some cases are preceded by biopsies progressive transformation of germinal centres, but most cases of PTGC do not progress to NLPHL. Thymic involvement is rare2.


The nodal architecture is replaced by a nodular or nodular and diffuse infiltrate composed of small lymphocytes and scattered L&H cells. L&H cells have a single large nucleus, often folded or multilobated to form a "popcorn" cell. Nucleoli are usually small, multiple, peripheral and basophilic. Cytoplasm is scanty. Histiocytes and plasma cells may be seen but neutrophils and eosinophils are absent.



















rare / weak


most cases



most cases


~50% cases

The L&H cells are rosetted by CD3+/CD57+/bcl-6+ T cells. These help to distinguish from PTGC, LR-CHL and (most) THRLBCL, which lack these rosetting T cells2.

Oct-2 and BOB.1 are co-activators of immunoglobulin synthesis and may prove useful in differentiated NLPHL (positive for both) from classical HL (never positive for both). The transcription factor PU.1 is also regularly expressed in NLPHL but not in CHL or THRLBCL2.

CD20 and CD21 are useful in demonstrating nodularity when it is subtle.

Differential diagnosis

One nodule showing the features of NLPHL is sufficient to establish the diagnosis. It is uncertain whether purely diffuse lymphocyte predominant Hodgkin lymphoma exists; most cases should be reclassified as;


NLPHL is usually very indolent, with prolonged disease-free intervals, albeit with frequent late relapses. Stage I & II; 10 year survival >80%. Advanced stage has a poor prognosis. 3-5% of case progress to large B cell lymphoma, although if localised this retains a good prognosis.


World Health Organization Classification of Tumours, Tumours of the haematopoietic and lymphoid tissues, IARC Press 2001.

1Jones D. Dismantling the germinal center: comparing the processes of transformation, regression and fragmentation of the lymphoid follicle. Advances in Anatomic Pathology 2002;9:129-138.

2Pileri, S. A., Ascani, S., Leoncini, L., Sabattini, E., Zinzani, P. L., Piccaluga, P. P., Pileri, A., Jr., Giunti, M., Falini, B., Bolis, G. B., Stein, H. Hodgkin's lymphoma: the pathologist's viewpoint. J Clin Pathol 2002;55:162-176.

This page last revised 3.12.2002.

©SMUHT/PW Bishop