Pearls and Pitfalls in Lymph Node Diagnosis
Case 5 -
Nodular Lymphocyte Predominant Hodgkin's Lymphoma (NLPHL)
Massachusetts General Hospital
20-year-old male with a 3 cm
left neck mass. Within the large, ill-defined nodules filling the node are numerous small B cells
(CD20+) and scattered large atypical B cells (CD20+, CD15-, CD30-, bcl6+). Also present are many T cells
(CD3+), including many co-expressing CD57. T cells cluster around the large B cells. CD21 highlights
expanded dendritic networks of follicular dendritic cells.
Case 5 - Slide 1
Nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL).
NLPHL comprises 5% of all cases of Hodgkin's lymphoma. There is a male:female ratio of 3:1. Patients
are affected over a wide age range with a median in the thirties and a unimodal age distribution, in
contrast to classical Hodgkin's lymphoma. The typical presentation is with localized disease involving
peripheral lymph nodes, most often cervical, followed by axillary and then by inguinal nodes. Typically
there are long disease-free intervals but relapses are common. NLPHL is indolent, with excellent
survival in most cases . Those patients who present with high-stage disease may not have a favorable
outcome . In approximately 3% of all cases there is an associated diffuse large B-cell lymphoma that
may represent outgrowth of the neoplastic cells of the original Hodgkin's lymphoma .
Lymph nodes are replaced by an infiltrate that is entirely or partially nodular. The nodules are
large, poorly circumscribed and expansile and they contain scattered neoplastic cells (L&H cells or
popcorn cells). The large, pale lobated popcorn cells are CD20+ bcl-6+, CD15-, CD30-, CD45+ and
Epstein-Barr virus-negative. Single L&H cells that have been extracted and analyzed by PCR are
clonal with ongoing mutation of the Ig variable region genes, analogous to normal follicle center cells.
The normal counterpart of the L&H cell is believed to be the follicle center centroblast.
Reactive cells include lymphocytes, histiocytes and follicular dendritic cells. The lymphocytes in
most cases are mostly B-cells with an admixture of T-cells. T-cells tend to cluster around the popcorn
cells and in some cases T cells co-express CD57. Nodules are delimited by expanded, motheaten networks
of follicular dendritic cells. In addition to this classic pattern, some cases have variant patterns:
1. The nodules may contain small cells that are predominantly T cells (T-cell rich nodular pattern), 2.
L&H cells may be found around but outside the nodules (nodular with prominent extranodular L&H
cell pattern), 3. Nodules may be serpiginous and interconnected (serpiginous/interconnected nodular
pattern), 4. Nodularity can be vague and difficult to appreciate but with a B-cell rich background
(diffuse B-cell rich pattern), or 5. There may be diffuse areas with small cells that are mostly T cells,
resembling T-cell rich large B-cell lymphoma (T-cell rich large B-cell-like pattern). The presence of a
TCR-BCL-like component may indicate a higher risk for recurrence .
The differential diagnosis of NLPHL includes classical Hodgkin's lymphoma, especially nodular
lymphocyte-rich classical Hodgkin's lymphoma which has a background similar to that of NLPHL ,
T-cell/histiocyte rich large B-cell lymphoma, follicular lymphoma and reactive hyperplasia with prominent
progressive transformation of germinal centers .
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- Hansmann M, Stein H, Fellbaum C, Hui P, Parwaresch M, Lennert K. Nodular paragranuloma can transform into high-grade malignant lymphoma of B type. Hum Pathol 1989;20:1169-1175.
- Fan Z, Natkunam Y, Bair E, Tibshirani R, Warnke R. Characterization of variant patterns of nodular lymphocyte predominant Hodgkin lymphoma with immunohistologic and clinical correlation. Am J Surg Pathol 2003;27:1346-1356.
- 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.