PART TWO
Diagnostic Cytology
Fig. 24.4 Tingible body macrophages. phagocytized fragments of
degenerated cells in cytoplasm (Papanicolaou x OI).
small lymphocytes. Their nuclei are vesicular with fine evenly
dispersed chromatin, and multiple nucleoli are usually found
near the nuclear membrane. The cytoplasm is easily discernible
as a basophilic narrow rim.
Cytomorphology can be excellent in well-prepared Diff-
Quik-stained material, and it is complementary to Papanico-
laou-stained material. However, differentiation of centroblasts
from centrocytes may be more difficult in Diff-Quik- than in
Papanicolaou-stained material due to the variability in size and
nuclear detail associated with air drying.62,63 In Diff-Quik prepa-
rations, centroblasts are the largest of the cells, with open blast-
like chromatin, prominent nucleoli, and basophilic cytoplasm
(Fig. 24.6). One should also distinguish centroblasts from large
cleaved cells. Although there is an overlap in size, the nuclei of
large centrocytes are more irregular in shape and lack the promi-
nent nucleoli and chromatin pattern of centroblasts.
It is important not to confuse centroblasts with the follicular
dendritic reticulum cells that tend to aggregate within the center
of the neoplastic follicles (Fig. 24.5). Although dendritic cells
have nuclei that are similar in size to centroblasts, the nuclei
of dendritic cells are somewhat coffee bean-shaped, with one
side typically flattened and fine smooth nuclear membranes.
The cytoplasm is indistinct, not basophilic, in contrast to that
of centroblasts. In Papanicolaou-stained preparations the chro-
matin is pale gray and finely granular with small central eosi-
nophilic nucleoli. The cytoplasm of the antigen-presenting
dendritic reticulum cells form long dendritic processes that can
be appreciated in cell blocks by immunohistochemistry staining
for CD21.20
Immunoblasts, in contrast to centroblasts, have a single
centrally located nucleolus, often with surrounding chromatin
clearing, and an appreciative amount of basophilic cytoplasm
(Figs 24.3 and 24.7). These are large cells and are three to four
times the size of a small lymphocyte. Immunoblasts may have
plasmacytoid differentiation.1
Plasma cells (Fig. 24.3) have eccentric nuclei with densely
packed coarse chromatin often arranged in a cartwheel-like pat-
tern. The cytoplasm is deeply basophilic with a paranuclear clear
area (Golgi apparatus).
Non-neoplastic Lymphadenopathy
Enlarged and generally asymptomatic lymph nodes often occur
in the head and neck or inguinal areas and are common in clini-
cal practice. FNA is a rapid and relatively noninvasive method
for investigating persistent lymphadenopathy and may distin-
guish a benign from a malignant process, thus dictating the next
step for management. On-site evaluations can lead to the appro-
priate triage for FCM, microbiologic culture, and other ancil-
lary studies. For example, cytomorphologic features of reactive
follicular hyperplasia can overlap with malignant lymphoma,
making confirmatory immunophenotyping essential in avoid-
ing delay and establishing a diagnosis. Polyclonality by FCM in
conjunction with the appropriate cytomorphology and clinical
presentation supports the reactive nature of an aspirate (Fig.
24.8). Evidence of suppurative or granulomatous lymphadeni-
tis can establish the presence of an infection or other specific
etiology and guide triage for appropriate confirmatory studies
such as culture. Organisms obtained from lymph nodes appear
morphologically identical to those found in material from other
body sites.
Follicular Hyperplasia
Follicular or reactive hyperplasia is characterized by a polymor-
phous population of cells including lymphocytes without obvi-
ous malignant features but of variable size and shape due to a
sampling of cells in different stages of transformation from both
inside and outside the germinal centers. Usually the predominant
cells in follicular hyperplasia are small lymphocytes accompanied
by a variable number of follicle center cells including centrocytes,
centroblasts, and immunoblasts (Figs 24.3, 24.6, and 24.7). Cells
at various stages of plasmacytic differentiation, including plas-
macytoid lymphocytes, mature plasma cells, and plasmablasts,
which can occasionally be binucleated, are also characteristic of
reactive hyperplasia. Mitotic activity is often apparent.64
The presence of an increased number of tingible body macro-
phages (Fig. 24.4) is a distinctive although nonspecific feature of
pronounced follicular hyperplasia. They may also be observed in
malignant lymphomas with rapid cell turnover, such as Burkitt's
lymphoma (BL) and precursor B- or T-cell lymphomas. These
high-grade lymphomas, however, often accompany a mono-
morphic population of atypical lymphoid cells as compared
with the polymorphic pattern of small "normal" lymphocytes in
reactive conditions. Other types of histiocyte-type cells includ-
ing epithelioid histiocytes and interdigitating reticulum cells are
also seen in follicular hyperplasia. Occasionally neutrophils,
eosinophils, and mast cells can also be identified, although mast
cells are best recognized in Romanowsky-stained slides by their
blue-purple cytoplasmic granules.64
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