PART TWO
Diagnostic Cytology
Table 14.5 Cytomorphologic Differential Diagnosis of Gastric Lymphoid
Lesions
Feature
Malignant
lymphoma
Follicular
hyperplasia
Lymphoid cell
population
Homogeneous
polymorphic, with
small to large cells
(predominance of
small)
Nuclear contou rs
Variable, may be highly
Most are round
irregular
and smooth
Tingible body
present in higher grades of
present
macrophages
malignant lymphomas
plasma cells
Infrequent, but when
Often present in
present, usually numerous
low numbers
Key features of malignant lymphoma, large-cell type
• Cellular smears with a background of inflammatory
cells, epithelial cells, and necrotic debris;
• "Pools" of monomorphic noncohesive cells with high
N/C ratios (cells may be entrapped in mucus); and
• Nuclei: distinct membranes often with obvious irregu-
larities (indentations), rather vesicular, finely to mod-
erately granular chromatin, and prominent nucleoli.
The
differential
diagnosis
includes
both
benign
and
malignant entities (Table 14.5). Both peptic ulcers and focal
lymphoid hyperplasia may yield heterogeneous lymphoid ele-
ments in smears. In addition, if lymphoid follicles (typical of
Helicobacter
gastritis) are present in the tissue, tingible-body
macrophages may also be evident. This polymorphism favors
a benign lymphoproliferative lesion and should preclude
the cytologic diagnosis of malignant lymphoma. The diffuse
form of gastric adenocarcinoma may also mimic lymphoma.
However, these cells usually possess greater volumes of cyto-
plasm, eccentrically positioned nuclei, and possibly obvious
cytoplasmic mucin. In addition, most cases manifest at least
some intercellular cohesion. An epithelioid stromal neoplasm
(epithelioid GI stromal tumor) also should be considered as
these unusual neoplasms may present as isolated round or
polygonal tumor cells. The irregular nuclear contours and well-
developed nucleoli of lymphomatous elements and the greater
volumes of cytoplasm in the mesenchymal tumor cells should
aid in this distinction.
The advantage of multiple biopsies over brushings for the diag-
nosis of gastric adenocarcinoma is even greater for lymphoma.
However, the two techniques remain complementary. For exam-
ple, in the sizable series by Sherman et al., negative gastric biopsies
were accompanied by smears suspicious for malignancy in 15% of
the specimen pairs.146 The diagnostic sensitivity of cytology in their
series was 48%; a larger proportion of patients with primary gastric
lymphomas were identified in brushings as compared with patients
with a previous diagnosis of lymphoma elsewhere in the body.
Cabre-Fiol and Vilardell reported two temporally sequential series
of gastric lymphomas.144 In the first, which included blind washings,
neoplastic cells were identified in 41% of the specimens, whereas
87% of the direct brushing smears showed malignant elements;
85% of this latter series were specifically identified as lymphomas.
Only 21 % of the primary gastric lymphomas reported by Lozowski
and Hajdu were diagnosed as such in brushings.145 Sherman et al.
found the reported accuracies of gastric brushings for the diagnosis
of lymphoma to range from 15 to 83%.146 Transmucosal FNAB
may be used to obtain tissue for immunophenotyping to demon-
strate monoclonality.
Stromal Neoplasms
Thought to be derived from cells which are the precursors to the
cells of Cajal, stromal tumors constitute only a small proportion
of all gastric neoplasms.147,148 They arise in the walls of the GI
tract, with the stomach being the most common site followed
by the small intestine. Formerly, many were considered to be
tumors of smooth muscle derivation, namely leiomyomas and
leiomyosarcomas. Recently a majority subgroup has been des-
ignated as GI stromal tumors (GISTs) based on their immuno-
reactivity for C-Kit.149 It is the immunoreactivity for C-Kit and, to
lesser degree, CD34 that distinguishes GISTs from true smooth
muscle tumors positive for desmin and smooth muscle actin
but negative for C-Kit.
Patients with gastric stromal tumors typically present with
upper GI bleeding and/or pain. Approximately half of the gas-
tric tumors occur in the body, where they reside within the wall
and often appear centered in the submucosa. Although they
may present endoscopically as a fungating mass, the character-
istic appearance is that of a dome-shaped submucosal elevation
with at least one centrally positioned ulcer. Histologically, these
are characteristically composed of spindle-shaped mesenchymal
cells arranged in interlacing bundles.147 Each cell possesses a sin-
gle elongated nucleus with squared-off ends. Their eosinophilic
cytoplasm, at times with a perinuclear vacuole, shows no evidence
of specific differentiation. Less often, tumors may be composed
completely of polygonal neoplastic cells with better defined bor-
ders and centrally positioned ovoid nuclei. The latter thus have
an epithelioid configuration. Not infrequently, neoplasms con-
sist of admixtures of both spindled and epithelioid cells. In many
instances, it is difficult to predict accurately the biologic potential
of a given stromal tumor. If at operation the neoplasm is seen to
invade adjacent structures and organs or metastases are identi-
fied, then the tumor may be considered fully malignant. Factors
that favor an aggressive biologic course include a large diameter,
tumoral necrosis, and a brisk mitotic activity.147,150,151
The cytomorphologic features of gastric stromal neoplasms
have only rarely been described in brushings.133,134,136,152,153 In
general, specimens contain only few to moderate numbers of
neoplastic cells. They may be dispersed as isolated elements
or present in small to large clumps (Fig. 14.21). The latter may
be associated with extracellular matrix material. Each cell has
a spindle to ovoid epithelioid contour and a high N/C ratio.
For the most part, cells possess solitary elongated nuclei with
variably blunt ends. The staining intensity of chromatin varies
from specimen to specimen and even within a given brushing.
The chromatin is granular and evenly distributed. Nucleoli are
generally not prominent. Cytoplasm is cyanophilic and cell bor-
ders are indistinct; the latter appear to blend with those of their
neighbors and the adjacent stromal matrix.
Key features of stromal tumors
• Moderate to low cellularity;
• Mostly individual tumor cells; some in small
aggregates;
• Ovoid to spindled cellular and nuclear contours;
• Variably stained, finely granular chromatin; and
• Generally inconspicuous nucleoli.
392
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