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Fine-needle aspiration cytology in tumors and tumor-like conditions of the oral and maxillofacial region Diagnostic reliability and limitations

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220
CANCER
CYTOPATHOLOGY
Cytology of Germ Cell Tumors
Extragonadal, Extracranial Masses and Intraoperative Problems
Michael W. Stanley, M.D.1
Celeste N. Powers, M.D., Ph.D.2
Martha B. Pitman, M.D.3
Soheila Korourian, M.D.1
Ricardo H. Bardales, M.D.1
Kamal Khurana, M.D.2
BACKGROUND. Germ cell tumors (GCTs) and their metastases may be found in
numerous sites that are accessible to cytologic sampling, and many are responsive
to chemotherapy.
METHODS. The authors reviewed 20 examples of GCT cytology from 16 males and
3 females ranging in age from 1.5 to 61 years (median, 34 years). With two excep-
1
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
2
Department of Pathology, State University of
New York, Syracuse, New York.
3
Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.
tions, one benign cystic ovarian teratoma in which intraoperative cytology was
used to diagnose an associated adult-type carcinoma and one undescended testis
in which seminoma presented as an abdominal mass, the material reviewed included no examples of primary gonadal GCT.
RESULTS. The authors studied 7 primary and 13 metastatic GCTs; these studies
were based on 13 in vivo aspirations, 4 intraoperative preparations, and 3 samples
of body cavity fluids. All samples were correctly interpreted as malignant, and only
one was incorrectly classified as a non-GCT malignancy.
CONCLUSIONS. Clinical and cytologic findings are useful in the diagnosis of GCTs
and their metastases. Incorrect interpretation of these neoplasms as poorly differentiated malignancies of other types may deprive the patient of effective chemotherapy. Air-dried, Romanowsky-stained smear material and cell block sections
may contribute to the resolution of diagnostic dilemmas. Cancer (Cancer Cytopathol) 1997;81:220–7. q 1997 American Cancer Society.
KEYWORDS: germ cell tumor, seminoma, dysgerminoma, yolk sac tumor, endodermal sinus tumor, teratoma, cytology, fine-needle aspiration.
G
Presented in part at the 44th Annual Scientific
Meeting of the American Society of Cytopathology, Denver, Colorado, November 6, 1996.
Address for reprints: Celeste N. Powers, State
University of New York Health Science Center,
Department of Pathology, 750 East Adams St.,
Syracuse, NY 13210.
Received February 20, 1997; revision received
March 31, 1997; accepted April 7, 1997.
erm cell tumors (GCTs) may arise in the testis, the ovary, or a
variety of midline extragonadal sites. The latter include the central
nervous system, mediastinum, retroperitoneum, and sacral region.
The current nosology of GCT divides this family of neoplasms into
seminoma/dysgerminoma (SD) and nonseminomatous types, the latter comprising teratomas (mature and immature), embryonal carcinoma (EC), yolk sac tumor (YST) (endodermal sinus tumor), and choriocarcinoma. Each tumor type presents consistent histologic and
cytologic findings regardless of its site of origin and irrespective of
whether one studies a primary tumor or a metastatic deposit. Histologic and cytologic complexities derive from combinations of SD with
nonseminomatous elements, mixtures of various nonseminomatous
components, and therapy-induced alterations.
When exfoliative cytologic samples are considered, GCTs are most
often identified in pleural, peritoneal, or pericardial fluids, with less
common examples in cerebrospinal samples and tracheobronchial
material (including sputum).1 – 11 Urine is rarely positive, and evidence
of GCT in hydrocele fluids as well as gastrointestinal or vaginal material is extremely unusual.1,5,10 Touch preparations (TPs) of intraopera-
q 1997 American Cancer Society
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Cytology of Germ Cell Tumors/Stanley et al.
tive tissue have been used for cytologic diagnosis.11 – 14
Fine-needle aspiration (FNA) is not commonly used to
study primary malignancies in the testis or ovary.15–21
However, this method is well suited to the evaluation of
GCT metastases and is a useful diagnostic method when
applied to extragonadal primary lesions.15,16,18,19,22–30
In this study, we reviewed a multi-institutional experience with the cytologic diagnosis of GCT. The focus of our study was extracranial, extragonadal tumors, whether primary or metastatic. Only two primary gonadal lesions were included in our analysis.
The first arose in an undescended testis, where it presented as an abdominal mass. The second was diagnosed by intraoperative TP. Differential diagnostic
considerations for primary extragonadal GCT and
problems related to mixed tumor types are discussed.
MATERIALS AND METHODS
All available cytologic samples and histologic preparations from primary or metastatic, extragonadal, extracranial GCT in the cytology files of the University of
Arkansas for Medical Sciences (Little Rock, Arkansas),
the State University of New York (Syracuse, New York),
and the Massachusetts General Hospital (Boston, Massachusetts) were reviewed. Clinical information, serum tumor marker data, selected radiographic findings, and follow-up status were obtained by review of
the patients’ medical records.
All FNAs of palpable masses were performed by
one of the authors using 25- or 23-gauge (0.25 or 0.23
mm) needles. Computed tomography (CT) or ultrasound guided FNA of deep-seated masses by radiologists was performed with 20- to 22-gauge needles. In
all cases, the material obtained was smeared onto uncoated glass slides and either air-dried or fixed in 95%
ethanol for a Diff-Quik, Papanicolaou, or rapid hematoxylin and eosin (H & E) stain. When appropriate,
material for a cell block was recovered by FNA, fixed in
10% neutral buffered formalin, embedded in paraffin,
sectioned at 4 mm, and stained with H & E. The latter
methods were also applied to histologic samples. Intraoperative TPs of surgically excised tissues were fixed
in 95% ethanol and stained with a rapid H & E method
used for frozen sections. Exfoliative cytologic samples
were processed and stained by routine methods.
RESULTS
Twenty GCT samples from 19 patients with adequate
cytologic, histologic, and clinical information were
available for this study. Eight were primary and 13
were metastatic at the time of cytologic evaluation.
Table 1 summarizes the clinical, cytologic, and histologic findings in each case.
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221
Metastatic GCTs were studied with in vivo lymph
node aspirations (n Å 8, various sites as summarized
in Table 1), 3 body cavity fluid samples (Case 5, pleural; Cases 7 and 12, peritoneal), a pulmonary FNA, and
a single intraoperative cytologic preparation (Case 6).
Tumor types represented in this group included SD (n
Å 7) and EC (n Å 3) as well as single examples of YST,
metastatic mixed GCT, and a peripheral neuroectodermal tumor that arose in a teratoma. Three patients
(Cases 4, 5, and 11) with a history of GCT and a cytologic diagnosis of recurrence underwent chemotherapy without histologic study of their secondary lesions.
All others received histologic confirmation. In seven of
the remaining cases, histology confirmed the cytologic
diagnosis, whereas in Case 1 it resulted in a more definitive reclassification, from GCT to YST.
Typical examples of SD show a reticulated, glycogen-rich (‘‘tigroid’’) smear background of cytoplasmic
debris through which may be scattered lymphocytes
and granulomatous tissue fragments (Figs. 1 and 2).
However, these features were absent from smears that
were sparsely cellular or diluted with blood (Fig. 3).
The large, fragile cells of GCT are often damaged in
the smearing process, so that large, naked nuclei may
appear as single cells, especially if obscured by blood.
In this setting, one of our seminoma cases was misinterpreted as a high grade malignant neoplasm consistent with malignant lymphoma; only fixed, Papanicolaou-stained smears were available (Case 8, Fig. 4).
In Case 13, rare seminoma cells were aspirated with
lymphoid tissue. Abundant, finely vacuolated cytoplasm facilitated their recognition on air-dried smears,
whereas in the Papanicolaou-stained material they resembled reactive cells of germinal center origin.
As discussed more fully later in this article, cytologic samples from YST (Fig. 5) and EC (Fig. 6) are
difficult to distinguish from adenocarcinoma without
supporting clinical or marker-study data. Conversely,
a metastatic deposit or an appropriately situated primary lesion in a young adult should always suggest
the possibility of a GCT.
Our series includes three teratomatous lesions.
Case 15 showed a typical mature, cystic ovarian teratoma. At the time of intraoperative evaluation of the
macroscopic specimen, a mural nodule distinct from
Rokitansky’s protuberance was noted, and a scrapping
showed adult-type squamous cell carcinoma. This diagnosis was confirmed by histologic analysis, and the
cytologic diagnosis was used to select the optimal samples to be embedded. A mediastinal cystic teratoma
in a myeloma patient (Case 16) was aspirated with
CT guidance. Intraoperative smears from a peripheral
neuroectodermal tumor (PNET) arising in a teratoma
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CANCER (CANCER CYTOPATHOLOGY) August 25, 1997 / Volume 81 / Number 4
TABLE 1
Clinical Findings, Cytologic Diagnoses, and Histologic Diagnoses
Age/Gender
Metastatic GCT
Case 1
27/M
Specimen type/Site
History
Cytologic diagnosis
Histologic diagnosis
Tumor markers
Follow-up
FNA/Left supraclavicular
lymph node
FNA/Right
supraclavicular
lymph node
Cough; sternal pain; 7 cm
mediastinal mass
1 mo. H/O testicular pain and mass;
retroperitoneal and mediastinal
lymphadenopathy by CT scan
Malignant neoplasm consistent
with a germ cell tumor
Seminoma
Yolk sac tumor
AFP Å 3711
AWNED at 27 months
Pure seminoma
Relapse after chemotherapy,
treated with autologous
bone marrow transplant;
currently AWD
2 mo. H/O neck mass; mediastinal
mass by CT scan; S/P
oophorectomy performed in
Mexico, results not available
Testicular seminoma excised 3 yrs
previously
Dysgerminoma
Dysgerminoma
Not done
initially; AFP
and b-HCG
negative at
relapse
ND
Metastatic seminoma
Metastasis treated
chemically
without resection
Metastasis treated
chemically
without resection
Metastatic embryonal
carcinoma
Case 2
24/M
Case 3
24/F
FNA/Left supraclavicular
lymph node
Case 4
37/M
FNA/Lung mass
Case 5
39/M
Pleural fluid
Case 6
21/M
Case 7
Case 8
16/F
61/M
Case 9
61/M
Case 10
35/M
Case 11
29/M
Intraoperative FNA/
Retroperitoneal
lymph node
Ascitic fluid
FNA/Inguinal lymph
node
FNA/Iliac fossa lymph
node
FNA/Iliac fossa lymph
node
FNA/Cervical lymph
node
Case 12
7/M
Case 13
42/M
Primary GCT
Case 14
Dissemination of previously
diagnosed mediastinal embryonal
carcinoma
Previously excised testicular mixed
GCT with teratocarcinoma and
seminoma
Ascites and pelvic mass
Testicular mass and adenopathy
Recurrent embryonal
carcinoma
Metastatic embryonal
carcinoma
Negative initially
and at
recurrance
b-HCG Å 29.2
Alive on chemotherapy at 8
mos
AWNED at 4 yrs
DOD shortly after positive
pleural fluid cytology
Elevated b-HCG
Lost to follow-up
Dysgerminoma
Seminoma
ND
ND
AWNED at 4 yrs
AWNED at 1 yr
Metastatic mixed
GCT
Seminoma
ND
AWD
ND
AWD
Metastasis treated
chemically
without resection
Same patient as Case
18 below
Metastatic
seminoma;
intraparotic lymph
node
ND
Alive at õ1 yr, after
diagnosis
ND
Current case
H/O Malignant mixed GCT of testis
Dysgerminoma
Large cell malignant
lymphoma
Metastatic mixed GCT
H/O testicular seminoma
Metastatic seminoma
Previously resected testicular
embryonal carcinoma
Metastatic embryonal
carcinoma
FNA/Parotid
Remote H/O a testicular mass of
unknown type
Metastatic seminoma
1.5/M
FNA/Liver mass
Abdominal mass
Yolk sac tumor
Yolk sac tumor
Case 15
47/F
Intraoperative scrapping
of a mural nodule in
a mature cystic
teratoma
Adenexal mass
Mature cystic teratoma with a
mural nodule of adult-type
invasive squamous cell
carcinoma
ND
Case 16
37/M
33/M
Multiple myeloma; S/P bone
marrow transplant
Painful testicular mass
Benign cells; rule out teratoma
Case 17
Seminoma
Pure seminoma
ND
Alive with no evidence of
germ cell tumor
AWNED at 6 yrs
Case 18
7/M
Small blue cell malignant
neoplasm
Seminoma
ND
AWNED at 1 yr
36/M
Large pelvic mass and urinary
retension
HIV/: clinically thought to have
lymphoma
Teratoma with PNET
Case 19
FNA of an 8 cm
mediastinal mass
Intraoperative FNA/
Testis
Intraoperative cytology
(imprints)
FNA/Mediastinal mass
Mature cystic
teratoma with a
mural nodule of
adult-type
invasive
squamous cell
carcinoma
Mature teratoma
Seminoma
ND
Case 20
47/M
FNA/Left lower
quadrant abdominal
mass
Undescended testis corresponding
to the mass
Seminoma
Seminoma
ND
Lost to follow-up after
retroperitoneal
recurrence
No follow-up available
Peritoneal fluid
AFP Å 20,800
ND
AWNED at 3 yrs after
chemotherapy
AWNED at 4 mos
M: male; F: female; AFP: serum a-fetoprotein level; b-HCG: serum b-human chorionic gonadotropin level; AWNED: alive with no evidence of disease; AWD: alive with disease; H/O: history of; ND: test not done;
NED: no evidence of disease; DOD: died of the disease; FNA: fine-needle aspiration; GCT: germ cell tumor; CT: computed tomography; PNET: peripheral neuroectodermal tumor.
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223
FIGURE 1. Aspirate smears from a typical case of metastatic seminoma
FIGURE 2. In this smear from a metastatic seminoma (Case 2), granulo-
(Case 2) show cohesive clusters and sheets of large, clearly malignant
cells. These cells feature moderate amounts of variably vacuolated cyto-
matous tissue fragments are set in the same tigroid background that can
be observed in Figure 1 (Diff-Quik, original magnification 1600).
plasm, large nuclei, and occasional prominent nucleoli. A tigroid background of glycogen-rich cytoplasm is formed from the cytoplasm of cells
that have been damaged in the smearing process (Diff-Quik, original magnification 1600).
FIGURE 4. This seminoma aspirate was studied only by the method of
Papanicolaou (Case 8), so that a tigroid background would not be available
in this preparation, despite the high cellularity. Many cells are damaged
FIGURE 3.
This aspirate of metastatic seminoma (Case 10) shows
marked dilution of the tumor cell clusters by blood. Preparations of this
type do not show the expected tigroid background observed in more
cellular smears. These cells illustrate clearly the large, lakelike cytoplasmic
vacuoles of this neoplasm (Diff-Quik, original magnification 1600).
(Case 18) showed only the small blue cell component,
without evidence of teratomatous elements. A subsequently obtained peritoneal fluid contained the same
malignant elements (Case 12).
DISCUSSION
Most exfoliative or FNA cytologic samples from GCT
are readily recognized as representing a malignant
neoplasm. SD is reported more frequently than other
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in the smearing process and, having lost their cytoplasm, are not able to
form cohesive tissue fragments. These damaged cells appear as free-lying
nuclei with lobulations and nucleoli. Such smears can be mistaken for
malignant lymphoma unless a careful search for cohesive tissue fragments
is successful (Papanicolaou stain, original magnification 1400).
GCTs, and it has been suggested that it is more readily
diagnosed in cytologic material than other types of
GCT.29 Akhtar et al described three cell types in SD,
ranging from small Type I cells with scanty cytoplasm
to larger Type II cells with more abundant cyanophilic
cytoplasm. Type III cells are similar to Type II cells,
but they feature large vacuoles with a ‘‘punched-out’’
appearance.16 Others have noted cell damage with numerous naked nuclei.11 The degree to which these cells
either lie singly or form clusters varies among several
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CANCER (CANCER CYTOPATHOLOGY) August 25, 1997 / Volume 81 / Number 4
FIGURE 5.
(A and B) This smear from a metastatic yolk sac tumor (Case 1) shows cohesive three-dimensional aggregates of large, malignant
cells with a high nucleocytoplasmic ratio. Cytoplasmic vacuoles are smaller and more bubbly in appearance than the lakelike clearings in many
seminomas (Fig. 3). Nucleoli are prominent, and the Papanicolaou stain shows finely divided chromatin, slight nuclear pallor, and delicate folds in
the nuclear membranes. Lacking historical, tumor marker, or clinical information suggesting a germ cell tumor or its metastasis, such a case is
most likely to be designated as adenocarcinoma when encountered in cytologic samples (A: Diff-Quik, original magnification 1600; B: Papanicolaou
stain, original magnification 1600).
FIGURE 6. This metastatic embryonal carcinoma (Case 6) shares many
adenocarcinoma-like cytologic features with the yolk sac tumor illustrated
in Figure 5. Background necrosis may be prominent, as shown here (Papanicolaou stain, original magnification 1600).
reports.11,15,16 Individual cells feature round-to-oval
nuclei with chromatin that is finely divided but unevenly distributed. A single prominent nucleolus is often present, but some cells may show several smaller
nucleoli. Granulomatous elements and lymphocytes
may be present,11,22 but they are not specific to SD,
even when the diagnosis of GCT is secure.21 The latter
have been associated with lymphoglandular bodies of
the type most commonly associated with lymphoproliferative processes.15,22
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Much has been made of the ‘‘tigroid’’ background
of dispersed, glycogen-rich cytoplasm that is presumably stripped from the large, fragile SD cells during
cytopreparatory processes.11,15,21 This reproducible artifact can be of considerable diagnostic utility but is
only discernable on air-dried, Romanowsky-stained
preparations. Caraway et al described aspirates from
16 SDs (2 testicular, 2 mediastinal, and 12 metastatic)
and noted this background in only 3 cases; 3 others
showed a granular smear background.15 These investigators also noted that the tigroid background is only
found on highly cellular smear preparations, and they
suggested that its absence from some aspirates might
be due to low cell recovery. A similar background
might be expected in smears from other glycogen-rich
neoplasms; Balslev et al report a tigroid background
in one example each of renal cell carcinoma, squamous cell carcinoma, and synovial sarcoma.21 We have
observed a similar appearance in a single aspirate of
metastatic malignant melanoma (M.W.S., unpublished observation). When fixed smears are examined,
cell damage leaves naked nuclei that can be mistaken
for single cells, as in our Case 8. Difficulties can be
compounded by the fact that a tigroid background is
not seen on fixed slides, and an incorrect diagnosis of
malignant lymphoma may result. Careful searching
can reveal a few cohesive true tissue fragments formed
by intact cells that reflect the epithelial nature of the
neoplasm in question. Such particles were identified
during a retrospective examination of our Case 8.
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‘‘Pseudoclusters’’ of lymphoid cells are most often
formed by damaged cells or are held together by histiocytes to form a lymphohistiocytic aggregate.
Spermatocytic seminoma is a unique testicular
GCT in that it occurs in older patients, has no association with intratubular germ cell neoplasia, rarely metastasizes, is often bilateral, and has no known ovarian
counterpart.31 Immunohistochemically, it is likely to
be cytokeratin positive and lack staining for placental
alkaline phosphatase, a pattern opposite to that of
classic SD. A single example has been described in the
FNA literature.17 The expected variation in tumor cell
size was noted. Both lymphocytes and a tigroid smear
background were absent. The latter is not surprising,
as this tumor lacks abundant glycogen by electron microscopy. However, the smears showed low overall cellularity, making it difficult to evaluate the background’s significance.
In body fluid samples, YST shows clusters of highly
vacuolated cells with prominent nucleoli that closely
simulate adenocarcinoma and may even suggest origin in an ovarian mucinous neoplasm.5 – 8 FNA material
can show papillary clusters of similar cells that are
set in a mucoid background, with necrosis and foamy
macrophages suggestive of either adenocarcinoma or
EC.18,19,24 The cytoplasmic vacuoles of YST are typically
bubbly in appearance and do not resemble the larger,
‘‘punched-out’’ vacuoles of SD.16,19,24 Schiller-Duval
bodies are a frequent feature of YST histology, but they
are generally not appreciated in cytologic samples, including cell blocks prepared from body fluids.5,7,8,19,24
Intracellular and extracellular hyaline globules that are
PAS positive and diastase resistant and correspond to
a-fetoprotein production are a common histopathologic finding in YST and are often noted in cytologic
material as well.4 – 8,18,19,24 They can appear to be either
intracellular or extracellular.
The histology of YST is highly variable and includes reticular, solid, festooning (pseudopapillary),
and polyvesicular vitelline patterns. In addition, these
tumors may show differentiation toward hepatic or
enteric tissue or may grow in a parietal yolk sac pattern.32 In the latter case, tumor cells are separated by
variable amounts of extracellular hyaline material with
immunohistochemical features of basal lamina (Type
IV collagen and laminin positive). Thus, the cytologic
finding of metachromatic extracellular material that
differs from the previously discussed hyaline globules
and resembles basement membrane might be useful
in suggesting a YST component in aspirates from some
complex GCT, as previously suggested by Mizrak and
Ekinci.19 This possibility remains to be more fully explored. However, consideration of this possibility, in
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225
concert with the striking histopathologic variability in
YST, prompts us to suggest that this tumor’s cytologic
spectrum is probably much more broad than has been
described to date. The gland-forming endometrioid
variant of YST has been described in only one cytologic
report.23
The previously described cytology of SD is consistent with the most commonly reported differential diagnostic problems: malignant melanoma, adenocarcinoma, and immunoblastic malignant
lymphoma.4,15,27,28 In many instances, historical
considerations will help greatly in resolving diagnostic difficulties. Additional information can be
obtained from well-known immunohistochemical
panels or evaluation serum a-fetoprotein and b human chorionic gonadotropin levels.15 Diagnostic
utility of these ‘‘tumor markers’’ may be limited by
the fact that a growing list of neoplasms derived
from somatic cells can be associated with measurable elaboration of these substances. In our experience, one is often called on to evaluate cytologic
samples before tumor marker studies are complete.
Thus, although the resulting information may ultimately be useful, it is seldom to be relied on during
initial cytologic diagnosis.
Among non-GCT malignancies, the most serious
differential diagnostic difficulty with YST is adenocarcinoma, which it resembles strongly.4,27 Although immunohistochemical and historical findings may be exploited in this regard, study of histologic material may
be required for final diagnosis.7 When GCTs are considered, YST most closely resembles EC but is said to
have somewhat less advanced degrees of cell clustering and nuclear abnormality.18,19,24,27 Although based
on a limited number of cases, our experience underscores the difficulty of this differential diagnostic distinction.
Our experience with the cytology of teratomatous
lesions is limited. Wojcik and Selvaggi described squamous cells, sheets of columnar cells, and vacuolated
cells of ‘‘presumed sebaceous origin’’ recovered from
cystic ovarian teratomas.20 The presence of mature tissue elements in a mediastinal mass allowed us to suggest this diagnosis for a patient being treated for multiple myeloma (Case 15). Identification of mature elements requires distinction from normal tissues and
developmental cysts or other abnormalities. Immature
elements could suggest a wide range of diagnoses;
neural elements could easily be mistaken for small cell
anaplastic carcinoma. In the intraoperative setting, a
mural nodule found in an otherwise typical mature
cystic teratoma was rapidly shown to be adult-type
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CANCER (CANCER CYTOPATHOLOGY) August 25, 1997 / Volume 81 / Number 4
squamous cell carcinoma by preparation and review
of TP.
No examples of choriocarcinoma were included
in our series. Others have indicated that the large cells
of this neoplasm show bizarre, hyperchromatic nuclei
and variable amounts of intensely eosinophilic cytoplasm in a pattern sometimes mistaken for squamous
cell carcinoma.2,27,30 This neoplasm is notorious for
presenting with widespread hemorrhagic metastases
in the face of an occult primary lesion; a typical presentation may feature dramatic hemoptysis. The finding of multiple masses, often in a young patient, suggests the diagnosis, and b-human chorionic gonadotropin determinations are confirmatory.
The frequent mixture of elements in GCT creates
a special problem for cytologic diagnosis, as relatively
limited sampling may lead to an incomplete picture.14,16,17,21,30 In the study of Balslev et al, 4 of 10
mixed GCTs had a histologic component that was not
detected by cytology.21 Thorough sampling is important, and discordant marker studies may provide
important guides to further evaluation (elevated afetoprotein levels in a patient with an FNA diagnosis
of seminoma, for example).
In addition to our limited experience, others have
commented on the utility of intraoperative cytology
for evaluation of GCT.12,14 TP can be prepared more
rapidly than frozen sections and may provide wider
tumor sampling that can be guided by subtle variations in the macroscopic appearance. In this way, TP
may either replace frozen section or alert the pathologist to nonseminomatous components not identified
in initial sections.14
A final warning is sounded by Oliver et al, who
remind us that masses that persist after chemical treatment of a GCT may contain only microscopic foci of
malignancy.25 Thus, a negative FNA in this setting may
not be reassuring. The utility of this finding may be
increased in selected cases by consideration of clinical,
imaging, and tumor marker data.
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3.
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Hajdu SI, Nolan MA. Exfoliative cytology of malignant germ
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Hudson EA. Sputum cytology of metastatic choriocarcinoma: a case report. Acta Cytol 1981;25:29–32.
Pillai KR, Kannan S, Gangadharan VP, Abraham EK, Chandralekha B, Pillai GR, et al. Role of sputum cytology in the
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reliability, regions, diagnostika, like, aspirations, needle, maxillofacial, oral, limitations, conditions, fine, tumors, cytology
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