PART TWO
Diagnostic Cytology
Fig. 12.13 Granulosa cell tumor. Granulosa cells arranged in rosettes and
cords (H&E x LP).
of granulosa cells that may assume a variety of histologic
patterns and show a spectrum of cytologic differentiation. The
Call-Exner body, a small cavitary space surrounded by granulosa
cells, is seen in many but not all tumors. Likewise, aspirations
of adult GCT may or may not yield cells assuming these rosette-
type formations (Fig. 12.13). The cellular material is generally
abundant, composed of numerous granulosa cells occurring
singly, in trabeculae, or in rosettes,53 with a clean background.
Cytologically, the granulosa cells may or may not exhibit nuclear
grooves.64 The cells have ovoid nuclei, occasional small nucleoli,
and scant wispy cytoplasm (Fig. 12.14). The major differential
diagnosis to consider is the Sertoli cell tumor.
Key features of adult granulosa cell tumor
• Highly cellular;
• Granulosa cells arranged in cords and rosette
formation;
• Many single cells; and
• Prominent nucleoli and nuclear grooves.
Juvenile Granulosa Cell Tumors
The
juvenile GCT
is solid and cystic and composed of a mixture
of granulosa and theca cells. The granulosa cells lack grooves
and may be arranged in follicles. Pleomorphism and mitotic
activity are hallmarks of this neoplasm. The theca cells resem-
ble granulosa cells, but have elongated, blunt-ended nuclei, are
more hyperchromatic, and have less distinct nucleoli.65
Key features of juvenile granulosa cell tumor
• Theca and granulosa cells;
• Often arranged in a follicular pattern; and
• Striking pleomorphism and mitotic activity.
Rare Tumors
Rare tumors that have been identified by aspiration cytology
include extraovarian primaries such as granulocytic
sarcoma
66
and
metastatic breast carcinoma.67
Their cytologic appearance
in ovarian cyst fluid recapitulates that seen in the primary site.
Dimorphic populations of tumor cells are present in
malignant
mixed mullerian tumors
of the ovary,68 which show epithelial and
Fig. 12.14 Granulosa cell tumor. Mild nuclear pleomorphism, nuclear
grooves, and wispy cytoplasm are seen. Direct smear (H&E x MP).
stromal neoplasia, and in
small-cell carcinoma of the ovary with
hypercalcemia,
which commonly shows small- and large-cell
malignant components.69 An unusual periovarian echinococcal
cyst, mistaken for an ovarian cyst, has been reported.70
Ancillary Techniques
The E2 content, measured by radioimmunoassay in fresh cyst
fluid, can distinguish follicular from non-follicular cysts.52,71
Cysts may be considered to be of follicular origin if the E2 level
is more than 4 nmol/L.71
The concentration of carcinoembryonic antigen and CA125
can be extremely high in fluid from ovarian neoplasms, and
malignant tumors, on average, have the highest values.72,73
However, low levels can be measured in both physiologic and
neoplastic cysts.74 Thus, these values are of limited usefulness to
distinguish these processes. Other studies have examined levels
of other biomarkers, such as Activin A,74 inhibin A,75 glycodelin
A,76 calgranulins,77 and claudins 1, 4, 5, and 7,78 in cyst fluids,
and have not yet found adequate sensitivity or specificity to
make such testing diagnostically useful.
Immunocytochemical staining for CD10 may aid in the
detection of endometrial stromal cells in endometrioma aspi-
rates, and in distinguishing them from ovarian fibroblasts.79 In
malignant lesions, the tumor cells in the cyst fluid stain for p53
and overexpress Her-2, which is not seen in benign lesions.80
DNA ploidy analysis has shown that cells from frankly malig-
nant cyst fluids are nondiploid, but benign and functional cysts
may also be nondiploid.81,82 Thus, ploidy analysis cannot be
used routinely as a reliable diagnostic aid.
Diagnostic Accuracy
The single most important factor that determines the accuracy
of ovarian FNA is the ability to retrieve diagnostic cells. An accu-
rate diagnostic classification cannot be rendered for a paucicel-
lular aspirate containing only scattered inflammatory cells. The
percentage of ovarian cyst aspirates that are unsatisfactory varies
from 18%54 to 70%.61,71 In these series, most of the cysts were
benign. However, even aspirates from malignant cysts may yield
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