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Nodular Lymphocyte Predominant

Hodgkin Lymphoma

Definition
A monoclonal B-cell neoplasm
characterized by a nodular pattern,
with or without diffuse areas, in
which large neoplastic lymphocytic
and/or histiocytic (L&H) cells are
present against a background of
numerous lymphocytes and
histiocytes, and follicular dendritic
cells in nodular areas

Epidemiology
5% of all cases of Hodgkin
Male > Female
Can occur at all age; peak at 30-50
years old

Pathogenesis
Traditionally has been included in the
classification of HL
L&H cells
B-cell origin; functional B-cell differentiation
program
immunophenotype are dissimilar from H/R-S cells
strongly express a variety of panB-cell antigens
and transcription factors or cofactors, as well as
germinal center B-cellassociated antigens and
leukocyte common antigen (LCA; CD45).
almost always negative for CD15 and CD30

Pathogenesis
L&H cells
Progressive transformation of germinal
centers (PTGC) as precursor lesion

Clinical features
Localized; lymph node enlargement
frequently perpheral (cervical, axillary,
inguinal)
Clinically indolent; may be treated with
involved-field radiotherapy without
chemotherapy
Unfavorable prognostic features or
advanced stage treated as cHL (ABVD)
Excellent overall survival, but relapses
frequent

Histologic features
large, expansile nodules;
partially/totally replace the lymph
node architecture; displace and
compress uninvolved lymphoid
tissue.

Histologic features
Nodules vary in size; larger, vaguer
outlines than reactive lymphoid
follicles

a single large tumor nodule is present composed of dark small


lymphocytes, pale histiocytes

Histologic features
nodules are typically arranged
closely, often in back-to-back fashion
composed of:
numerous, small, round lympho-cytes;
typical and epithelioid histiocytes;
follicular dendritic cells; and
neoplastic L&H cells

Histologic features
L&H cells:
1% of all cells in the nodules
Large cells, scant pale cytoplasm
Nuclei: multilobated or folded, has
vesicular nucleoplasm, inconspicuous
nucleolus, thin nuclear membrane
popcorn cells
Mitoses are uncommon

Large multilobated L&H cells can be seen in this


field. Most of the L&H cells in this case had
distinct or prominent eosinophilic nucleoli, unlike
classic popcorn cells.

Touch imprint showing L&H cells against a background of


numerous small lymphocytes and few histiocytes. The L&H
cells in this case fit the classic description of popcorn
cells.

Histologic features
Reactive germinal centers are
unusual
Epithelioid histiocytes are present
(single or in small clusters)
Fibrosis is usually absent
Eosinophils, neutrophils, and plasma
cells are not a part of NLPHL.

In this case, small reactive germinal centers


(arrowheads) can be identified within tumor nodules.
L&H cells (arrows) also are present.

Histologic variants
Classic nodular
Serpiginous/interconnected nodular
Irregular outlines, fuse with other nodules

Nodular with extranodular L&H cells


a subset or most of the L&H cells occur
are the periphery of the tumor nodules

Nodular with T-cellrich background


reactive small B cells are markedly
decreased

Histologic variants
The T-cellrich B-cell lymphoma-like
diffuse pattern
composed of scattered large L&H cells
against a background of numerous T cells
and histiocytes

The diffuse moth-eaten pattern with


a B-cellrich background
except for its diffuse pattern, otherwise
resembles the classic nodular NLPHL cases

Immunophenotypic findings
Positive for panB-cell markers
CD20, CD22, CD75, and CD79a

Positive for the transcription factors


and cofactors PAX5/B-cellspecific
activating protein (BSAP),
Positive B-cell octamer-binding protein
1 (BOB.1)
Positive germinal center B-cell
associated antigens (including BCL-6)

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