PART TWO
Diagnostic Cytology
Table 26.3 Cytologic Differential Diagnosis of Small Cell-rich Mediastinal Lesions
Reactive lym-
phoid hyper-
plasia (thymic
hyperplasia)
Thymoma with
predominance
of cortical
component
precursor
T-lymphoblastic
lymphoma
Hodgkin's
lymphoma
Neuroblastoma
Small cell
carcinoma
Age of patients
Adulthood
Adulthood
Late childhood
and adolescence
Third decade and
late adulthood
Childhood
Elderly
Sex of patients
Female predilec-
tion
No sex predilection
Male predilection
Female predilec-
tion
Slight male predi-
lection
Male predilection
Clinical
symptoms and
associations
Myasthenia gravis
and autoimmune
diseases
Local symptoms,
myasthenia gravis,
hypogammaglob-
ulinemia, and pure
red cell aplasia
Local symptoms
and effusions
Local symptoms
Local symptoms
and elevated
serum/urinary
catecholamines
Local and
paraneoplastic
symptoms
Localization
Anterior mediasti-
num
Superior or anterior
mediastinum
Superior, anterior
or middle medi-
astinum
Superior, anterior
or middle medi-
astinum
Posterior mediasti-
num
Anterior or mid-
dle mediastinum
Cytologic
findings
Mixture of lym-
phocytes, plasma
cells, follicular
center cells, and
some tingible-
body macro-
phages
Loose aggregates
of large bland-
looking polygonal
cells in a sea of
small lymphoid
cells
Monotonous
population of
mitotically active
small lymphoid
cells
Mixture of lym-
phocytes, plasma
cells, eosinophils,
histiocytes, and
small number of
Reed-Sternberg
cells
Loose aggregates
of bland-looking
small round cells in
fibrillary matrix
Loose aggre-
gates of small
to medium-
sized cells with
squashing arti-
facts, apoptotic
bodies, and focal
nuclear molding
Immuno-
phenotype
B- (e.g. CD20) and
T-cell markers (e.g.
CD3) positive
Cytokeratin-
positive and CD57
focally positive
in epithelial cells;
T-cell markers (e.g.
CD3) often positive
and TdT-positive
in background
lymphoid cells
T-cell markers
(e.g. CD3) variably
postive and TdT-
positive
CD30-positive,
CD15-positive,
and B-cell markers
(e.g. CD20) fo-
cally positive in
Reed-Sternberg
cells
Neuronal markers
(e.g. neuro-
filament) positive,
S-100 protein-
positive, and
CD99-negative
Cytokeratin-
positive and
neuroendocrine
markers (e.g.
synaptophysin)
positive
TdT, terminal deoxynucleotidyl transferase.
reactive stromal tissue containing fibroblasts. The samples
are usually of limited cellularity and nondiagnostic. On
the other hand, epithelioid histiocytes are identified in
fine-needle aspirates of granulomatous inflammation sec-
ondary to infections (such as tuberculosis) or sarcoidosis.
In general, these bland-looking fibroblasts and/or histio-
cytes are reactive in nature and may represent a compo-
nent of a more significant lesion.
• Bland-looking spindle tumor cells: Bland-looking spin-
dle tumor cells are characteristically seen in fine-needle
aspirates of type A thymoma, spindle cell carcinoid,
neurilemmoma, neurofibroma, ganglioneuroma, and
a number of benign soft tissue tumors (such as solitary
fibrous tumor). Detailed cytologic examination and
ancillary studies are important in making the
distinction.
• Malignant-looking spindle tumor cells: Spindle tumor
cells with nuclear pleomorphism are identified in fine-
needle aspirates of spindle cell carcinoma (a subtype of
squamous cell carcinoma, either thymic or nonthymic
origin), metastatic malignant melanoma, diffuse large
B-cell lymphoma with sclerosis, and a number of
sarcomas (such as synovial sarcoma). The spindle
appearance of high-grade lymphoma cells is mainly
due to artifactual cellular distortion secondary to
stromal sclerosis.
Concluding Remarks
Fine-needle asp iration cytology is regarded as a useful diagnos-
tic to o l in the assessment o f m ed iastinal lesions. T he procedure
is rapid, h ig h ly reliable, and w ell-tolerated , w ith o n ly m in o r
com p lications o n record. It can help in establishing a p rim a ry
pathologic diagnosis o r at least in separating nonsurgical fro m
surgical cases, thus g uiding the clinicians in p lan ning the subse-
q u en t m anagem ent approach. Fine-needle asp iration cytology
is also c o m m o n ly applied in lym p h node staging o f p rim ary
lu n g cancer, in assessing operability, as w e ll as in detecting resid-
ual disease o r recurrent m ed iastinal tu m o r after therapy. E nd o-
scopic ultrasound-guided fine-needle asp iration is becom ing
increasingly p opular. T he presence o f a p atholog ist o n site also
helps to assess specim en adequacy and op tim izes the selection
o f tissue samples fo r possible ancillary investigations such as
im m unocytochem istry,
electron m icroscopy,
and m olecular
analysis. M ole c u la r techniques, inc lu d in g in s itu h yb rid iza tio n ,
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