Diagnostic Cytology
Fig. 24.37 Hodgkin's lymphoma, classic Hodgkin and Reed-
Sternberg cells. Bilobed nuclei with prominent nucleoli and abundant
cytoplasm. (A) Papanicolaou x OI. (B) Diff-Quik x OI.
stains may be performed on sections of the cell block includ-
ing epithelial, lymphoid, germ cell, and melanocytic markers to
differentiate these entities.
Hodgkin and Reed-Sternberg cells are characteristically CD45-,
EMA-negative, CD30+, and CD15+ (Fig. 24.38). Usually they are
negative for T- and B-cell markers, although in about a quarter of
the cases they stain for CD20, but usually of varied intensity and
presenting only on a minority of the neoplastic cells. Cases of
EBV-associated HL will be positive for Epstein-Barr virus LMP.187
Peripheral T-cell lymphomas and ALCLs may be mistaken
for HL.188 These may overlap in immunophenotypic patterns,
although the presence of T-cell antigens in the atypical cells favors
T-cell lymphoma. CD45, EMA, and T-cell antigen positivity
favors ALCL, while CD15+ favors HL. In difficult cases molecu-
lar studies may be helpful in detecting monoclonal beta T-cell
receptor gene rearrangements in PTCL and t(2:5) in ALCL.
Key features of classic Hodgkin's lymphoma
• HRS cells;
• Polymorphous background inflammation;
• CD15+, CD30+, CD45-, ALK-1-negative HRS cells;
• FCM often nondiagnostic; and
• Important differential diagnosis with nodular
lymphocyte-predominant Hodgkin's lymphoma
(NLPHL), ALCL, reactive hyperplasia, and nonlymphoid
Nodular Lym phocyte-Predom inant Hodgkin's
Lym phom a
Nodular lymphocyte-predominant Hodgkin's lymphoma is
relatively uncommon and most patients present with localized
peripheral adenopathy with slow progression. In some patients,
it may progress to diffuse large B-cell or other aggressive
of lymphocytic
and/or histiocytic
Sternberg cell variants is a typical feature of NLPHL. L&H cells
are also known as "popcorn" cells since they usually have one
multilobated or extremely folded (like popcorn) nucleus with
vesicular chromatin, a thin nuclear membrane, and scant cyto-
plasm. The nucleoli of L&H cells are usually multiple, basophilic,
and smaller than those seen in classic HRS cells. The "popcorn-
like" artifact is not as well appreciated in cytologic prepara-
tions and can even be overlooked in histologic preparations
(Fig. 24.39).182 The background cells are characterized by an
abundance of small lymphocytes and an absence of the neu-
trophils and eosinophils often seen in classic HL.
D ifferential Diagnosis
There are important immunophenotypic differences between
classic HL and lymphocyte-predominant Hodgkin's lymphoma
(LPHL). The L&H cells of NLPHL are CD20+ and CD45+, whereas
classic HRS cells are usually CD20- and CD45-. L&H cells, in
contrast to classic HRS cells, lack CD15 and only sometimes
express CD30.189,190
The differential diagnostic list of LPHL is identical to that of
classic HL and includes reactive lymphoid hyperplasia, nonlym-
phoid malignancies, and NHL (see
Differential Diagnosis
for HL). Having adequate material in the cell block is critical
for immunohistochemistry studies since FCM is often nondi-
agnostic. The CD20+ neoplastic cells and surrounding reactive
T cells can make it difficult to differentiate NLPHL from LBL,
particularly T cell-rich LBL, or a reactive condition. An exci-
sional biopsy is usually necessary to confirm the diagnosis.
Key features of nodular lymphocyte-predominant
Hodgkin's lymphoma
• CD20+, CD45+ L&H cells;
• CD15-, CD30+/-;
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