Ovarian Sex Cord Stromal Tumors:

Uncommon Tumors That May Mimic A Variety of More Common Tumors

An Overview of Helpful Morphology and Immunomarkers

Joseph Rabban MD MPH

Associate Professor
UCSF Pathology Department
joseph.rabban@ucsf.edu
June 2010

Introduction: Sex cord-stromal tumors are uncommon ovarian neoplasms, accounting for 5% to
12% of ovarian tumors, yet many of these tumors may mimic a range of more common epithelial
and germ cell tumors, both benign and malignant. Two growth patterns in ovarian tumors that
are problematic in terms of overlap between sex cord-stromal, epithelial and germ cell tumors are
1.) tubuloglandular growth and 2.) sex cord-like growth. A third but much less common pattern is
that of single infiltrative clusters or cells with signet ring features or vacuoles. This lecture will
focus on differential diagnosis of these three growth patterns, with emphasis on granulosa cell
tumors.

Outline of Lecture:

¾ Immunohistochemistry of Sex Cord-Stromal Ovarian Tumors

¾ Pattern 1: Tubuloglandular:
Granulosa Cell Tumor
Sertoli Cell Tumor / Sertoli Leydig Cell Tumor
Sex Cord Tumor with Annular Tubules
Endometrioid Adenocarcinoma
Carcinoid Tumor
Struma Ovarii
Strumal Carcinoid Tumor
Yolk Sac Tumor, glandular variant

¾ Pattern 2: Sex cord-like:

Granulosa cell Tumor
Fibroma with sex cord elements
Endometrioid Adenocarcinoma (sex cord variant)
Adenofibroma/Adenosarcoma with sex cord-like elements

¾ Pattern 3: Single infiltrating cells/clusters +/- signet ring/mucin/vacuoles

Sclerosing Stromal Tumor
Metastatic Gastric / Breast Cancer
Mucinous Carcinoid (primary or metastatic)

Clinical Context, Gross Findings and Differential Diagnosis:

Patient age, clinical setting and gross findings are useful since many patients with ovarian sex
cord stromal tumors are young, have hormonal alterations (estrogenic or androgenic
manifestations, elevated serum markers (e.g. AFP) or syndromic associations (e.g. Peutz
Jeghers syndrome); the tumors are often unilateral, yellow/orange, and multicystic. In contrast,
many of the mimics, particularly adenocarcinoma, would be unusual in a young patient and would
not likely present with such clinical or gross features. Thus, discordance between the clinical
context and the pathologic impression should prompt for further confirmation of the pathologic
diagnosis. Generally, we prefer to confirm the morphologic diagnosis of granulosa cell tumor,
Sertoli cell tumor or Sertoli Leydig cell tumor with immunohistochemistry given the potential for
overlap with so many other tumor types.
 Immunohistochemistry

Inhibin and calretinin are the traditional markers of ovarian sex cord-stromal differentiation.
Expression tends to be stronger and more diffuse in granulosa cell tumors, Sertoli and Sertoli-
Leydig cell tumors than in fibroma or thecoma. Ovarian steroid cell tumors will also mark with
inhibin and calretinin, as will ovarian hilus cells and cells of stromal hyperthecosis. Nuclear
expression of WT1 and membrane expression of CD99 also characterize many sex cord-stromal
tumors, but in our practice, we don’t use these markers since they are not as reliable as others in
our laboratory. ER and PR may be expressed in many granulosa cell tumors. When trying to
distinguish sex cord-stromal tumors from epithelial tumors, care must be exercised in selection of
epithelial markers: pan-keratin may mark granulosa cell tumors and Sertoli cell tumors to variable
degrees and this may cause confusion with adenocarcinoma. EMA (epithelial membrane
antigen) is a better choice since it is negative in sex cord-stromal tumors. Conversely, some
endometrioid adenocarcinomas may express inhibin, calretinin or WT-1, albeit in a weak, patchy
pattern.

Steroidenic factor 1 (SF 1) is a recently studied nuclear protein that appears to be a useful marker
of ovarian sex cord differentiation. It marks lesions of sex cord-stromal differentiation in a nuclear
pattern and is negative in epithelial tumors.56, 57 SF 1, also known as Adrenal Binding Protein 1,
is found in many of the same tissues that mark with inhibin. SF 1 is a transcription factor
regulating steroidogenesis of the adrenal and pituitary glands. Immunoexpression is observed in
adrenal cortical tumors and pituitary adenoma. It is also thought that SF 1 is involved in gonadal
development. In the testis, SF 1 marks Sertoli cells and Leydig cells. Recently it was
demonstrated that SF 1 marks ovarian sex cord tumors (granulosa cell tumor, Sertoli cell tumor,
Sertoli Leydig cell tumor, and fibroma/thecoma) but not endometrioid adenocarcinoma or
carcinoid tumor. 56, 57 The nuclear expression pattern makes it a preferred marker.

Recommended panel:

To confirm a diagnosis of granulosa cell tumor, we prefer the quartet of SF-1, inhibin, calretinin
and EMA and we avoid cytokeratin stains. The following table lists the results expected in most
tumors, keeping in mind that exceptions do occur.

Marker Granulosa Cell Sertoli Cell Endometrioid Carcinoid Struma

Tumor Tumor Adenocarcinoma Tumor Ovarii

SF-1 Positive Positive Negative Negative Negative

Calretinin Positive Positive Negative Negative Negative
Inhibin Positive Positive Negative Negative Negative
WT-1 Positive Positive Rarely Negative Negative
EMA Negative Negative Positive Rarely Positive

Keratin Variable Positive Positive Positive Positive

Chromogranin Negative Negative Negative Positive Negative
TTF-1 Negative Negative Negative Negative Positive
 Differential Diagnosis by Patterns

PATTERN 1: TUBULOGLANDULAR GROWTH:

Granulosa Cell Tumor versus Endometrioid Adenocarcinoma

The microfollicular and solid pattern of granulosa cell tumor may resemble endometrioid
adenocarcinoma. Morphologic features favoring granulosa cell tumor include nuclear grooves,
Call-Exner bodies, a mixture of growth patterns including trabecular growth, and an absence of
squamous differentiation.

Potential Pitfall: Nuclear grooves are not pathognomonic of granulosa cell tumor.
Nuclear grooves may be seen endometrioid adenocarcinoma.

Endometrioid adenocarcinoma is favored by the presence of endometrioid appearing cells and

squamous differentiation. In questionable cases, immunostains may be helpful (positive EMA,
negative SF-1, calretinin, inhibin).

Granulosa Cell Tumor versus Sertoli Cell Tumor

Microfollicular growth in granulosa cell tumor may resemble the hollow packed tubules of Sertoli
cell tumor, however the latter usually does not exhibit the mixed array of other growth patterns
seen in granulosa cell tumor. In difficult cases, cytokeratin expression can be used to confirm a
diagnosis of Sertoli cell tumor.

Granulosa Cell Tumor versus Carcinoid Tumor

Microfollicular and trabecular growth can be seen in both these tumors but the typical cytologic
features of granulosa cell tumor (nuclear grooves, Call-Exner bodies) will not be seen in carcinoid
tumor. Teratomatous elements favor a diagnosis of carcinoid tumor, as does the presence of
nuclei with neuroendocrine type chromatin texture (stippled or so-called salt and pepper texture).
Neuroendocrine markers such as chromogranin and synaptophysin can be useful to identifiy
carcinoid tumor.

Granulosa Cell Tumor versus Struma Ovarii

Microfollicular growth of granulosa cell tumor may sometimes resemble the follicles of struma
ovarii but otherwise, each entity should show other morphology that clearly leads to the correct
diagnosis. Struma ovarii may be accompanied by other teratomatous elements, something not
expected in granulosa cell tumor. Generally the mixture of other growth patterns in the latter is
not seen in struma ovarii. The nuclear shape may also helpful. Struma ovarii usually exhibits a
uniform, monotonous round/oval nuclear shape without nuclear contour irregularities whereas
most granulosa cell tumors show more nuclear atypia, folds, and grooves.

Granulosa Cell Tumor versus glandular variant Yolk Sac Tumor

Microfollicular and trabecular growth of granulosa cell tumor can resemble the glandular variant of
yolk sac tumor but, again, there are usually other morphologic findings that allow for a
straightforward diagnosis. Yolk sac tumor often shows a mixture of growth patterns (i.e. reticular,
papillary, solid, microcystic) and may be mixed with other germ cell tumor components that are
not expected in granulosa cell tumor. Immunostaining for SALL-4, Glypican 3, AFP

PATTERN 2: SEX CORD LIKE GROWTH

Fibroma with sex cord elements versus Granulosa Cell Tumor

Some fibromas may contain foci of sex cord elements. Typically these are microscopic foci and
only a few foci are present; this does not alter the behavior.
Conversely, some granulosa cell tumors may show a fascicular, spindled growth pattern that
resembles thecoma or cellular fibroma. Though it is unusual for such a tumor to lack other
distinctive patterns of granulosa cell tumor growth (such as microfollicular or trabecular), rare
cases may be difficult to resolve based on morphology alone. Immunohistochemistry is not of
great value since calretinin, inhibin, WT-1, and SF 1 can be seen in both tumor groups. Reticulin
staining, however, is useful. In granulosa cell tumor, the reticulin fibers will highlight bundles,
fascicles and nests of tumor cells but the fibers will not surround individual cells. In contrast, the
reticulin fibers will surround individual spindle cells.

Adenofibroma/Adenosarcoma with sex cord elements versus Granulosa Cell Tumor

Similar to fibroma with sex cord elements, both adenofibroma and adenosarcoma may contain
these elements, typically in a microscopic amount. There usually is sufficient morphology present
to easily make the diagnosis of adenofibroma or adenosarcoma and these tumors are not
typically confused with granulosa cell tumor. Behavior is not affected by sex cord elements.

Endometrioid Adenocarcinoma, Corded and Hyalinized Variant, versus Granulosa Cell

Tumor
A rare variant of endometrioid adenocarcinoma of the ovary or uterus may contain a sex cord-like
or sertoliform growth pattern that resembles granulosa cell tumor.34 The unusual growth zones
may be embedded in hyalinized stroma, thus giving the name “corded and hyalinized
endometrioid adenocarcinoma”. Such tumors generally exhibit clear cut areas of typical
endometrioid adenocarcinoma that allow for the correct diagnosis. However, we have
encountered some cases that lack such areas and truly resemble granulosa cell tumor.
Identification of squamous differentiation is a key clue to correctly diagnosis adenocarcinoma.
Immunostaining can be helpful in difficult cases.

PATTERN 3: INFILTRATING CLUSTERS/CELLS with SIGNET RING/MUCIN/VACUOLES

Sclerosing stromal tumor versus metastatic carcinoma

Lobular breast cancer and metastatic gastric carcinoma involving the ovary may grow as single
infiltrating polygonal tumor cells embedded within fibrotic stroma, resembling a sclerosing stromal
tumor. Such metastases generally lack the distinctive blood vessels and the pseudolobular growth
pattern of sclerosing stromal tumor. In addition, clinical history of a primary gastrointestinal or breast
cancer should be informative in the differential diagnosis. Because sclerosing stromal tumor affects
young women, the likelihood of a metastatic cancer to the ovaries is comparatively low. EMA
immunostaining should highlight metastatic carcinoma cells and confirm that diagnosis.

Sclerosing stromal tumor versus mucinous carcinoid tumor

A rare variant of carcinoid tumor is the mucinous carcinoid tumor, which may be primary to the ovary
or metastatic. A range of growth patterns can be seen. Infiltrative dispersed clusters or single tumor
cells with a mucin droplet or signet ring appearance may raise consideration of either sclerosing
stromal tumor or metastatic mucinous/signet ring adenocarcinoma. Generally, however, there will be
clear cut areas of carcinoid morphology in the tumor. Distinguishing primary versus metastatic origin
of mucinous carcinoid is important; appendiceal origin or other intestinal origin should be considered.
CK7 and CK20 may be helpful for that purpose. Keratin or EMA positivity will separate carcinoid
from sclerosing stromal tumor, as will calretinin and inhibin.
 SUMMARY OF TUMOR TYPES

Granulosa Cell Tumor

Granulosa cell tumors range from small incidentally discovered nodules only a few millimeter in
diameter to large tumors more than 30 cm in diameter. Some are totally solid, but most are partly
cystic. The solid portions are pink, tan, brown, or light yellow and vary from soft to firm in
consistency. Rare granulosa cell tumors grow as large cysts with a wall only a few mm thick.
These are supposedly more likely than other granulosa cell tumors to be androgenic. 27, 36

Microscopically, the tumor cells resemble normal granulosa cells. They are small and round,
cuboidal, or fusiform with pale cytoplasm and ill-defined cell borders. The nuclei are round or
oval with fine chromatin and a single small nucleolus. Longitudinal folds or grooves are present
in many nuclei and are a characteristic feature of the adult type of granulosa cell tumor. Mitotic
figures are usually infrequent and pleomorphic or atypical nuclei are uncommon. Rare granulosa
cell tumors contain foci of cells with bizarre nuclei, but this does not appear to imply an adverse
prognosis. 13, 51 Extensive tumor cell luteinization is seen in about 1% of adult granulosa cell
tumors. Luteinized granulosa cells have abundant eosinophilic cytoplasm, well-defined cell
borders, and central nuclei, and resemble the luteinized granulosa cells of the corpus luteum.
Some luteinized granulosa cell tumors occur in pregnant women, 47 but they are also seen in
patients with androgenic granulosa cell tumors, 35 and as idiopathic findings. 48

A diverse range of growth patterns are exhibited by adult granulosa cell tumors, often mixed
together. The patterns do not have any prognostic significance, but because they may mimic
other tumor types, awareness of them is critical. The microfollicular pattern is the most typical
one and consists of nests and sheets of granulosa cells that contain small spaces filled with
eosinophilic secretions and cellular debris. The spaces resemble the Call-Exner bodies of
developing follicles. In the macrofollicular pattern, large, often irregularly shaped follicles are
lined by stratified granulosa cells. Granulosa cells grow in anastomosing bands, ribbons, and
cords in the trabecular pattern; and in irregular undulating ribbons in the gyriform or watered-silk
pattern. Nests and islands of tumor cells are surrounded by fibrous stroma in the insular pattern.
The cells grow in large irregular sheets with no organized substructure in the solid or diffuse
pattern. Many granulosa cell tumors contain large cysts lined by granulosa cells. The cysts may
contain blood and hemosiderin-laden macrophages are often present in the walls. Rare cystic
granulosa cell tumors grow as large unilocular cysts lined by stratified granulosa cells among
which are microfollicles or areas of trabecular growth.

Granulosa cell tumors have a variable amount of fibrous or thecomatous stroma. Tumors with a
prominent fibrothecomatous stroma have been called granulosa-theca cell tumors but when
granulosa cells comprise > 5-10% of the a tumor it can be classified as a granulosa cell tumor.
Tumors with only a minor granulosa cell component are best classified as a thecoma or fibroma
with minor sex cord elements (<5%). 52 Rarely, a granulosa cell tumor contains heterologous
mucinous epithelium. 4, 9, 37 Equally rare is the finding of foci of hepatic cell differentiation in a
granulosa cell tumor. 1

It is difficult to predict the prognosis of a granulosa cell tumor, 27 but some pathologic findings
correlate to a degree with the clinical outcome. 2, 12, 43 Unfavorable findings include a tumor
diameter > 15 cm, bilateral tumors, rupture, and spread beyond the ovary (FIGO stage > IA).
Diffuse moderate or marked nuclear atypia or a high mitotic rate (variably defined as greater than
2 or 4 mitotic figures per 10 high power fields) appears to predict a higher risk of recurrence. 24, 28,
30
The stage is the single most powerful predictor of prognosis. There is no correlation between
the microscopic pattern and the clinical outcome. More than 80% of granulosa cell tumors are
DNA diploid. Some authors have found ploidy or s-phase fraction to provide significant
prognostic information, 21, 25, 38 but others have not. 10, 20, 44
 Fibroma / Thecoma

Ovarian fibroma is a benign stromal tumor in which spindle shaped stromal cells grow in abundant
collagenous stroma. Immunohistochemistry is rarely performed on fibromas because their
appearance on H&E stained slides is usually distinctive. Fibromas and related tumors such as
cellular fibromas and fibrosarcomas stain only infrequently for inhibin but most are calretinin
positive.8, 26, 33 They show patchy and weak to moderate staining for WT-1.17 SF-1 is positive,
though may have variable intensity/distribution.

Thecoma is a benign spindle cell stromal tumor that differs from fibroma in that it is often hormonally
active, usually secreting estrogen. There are morphologic differences as well, as the tumor cells in a
thecoma tend to be plump, with clear or vacuolated cytoplasm, and there is less collagen in the
background stroma than is present in a fibroma. Thecoma is usually positive for both inhibin and
calretinin.5, 7, 19, 26, 33 Strong positive staining for inhibin favors classifying a stromal tumor as a
thecoma rather than as a fibroma. Stains for myoid markers, such as smooth muscle actin, are often
positive as well.18, 45

The diagnosis of fibroma and thecoma is generally straightforward, however, in addition to distinction
from granulosa cell tumor, there is one problem that may occasionally present difficulty: presence of
mitoses and/or presence of cellularity. The differential diagnosis that is raised is fibrosarcoma, an
exceedingly rare tumor in the ovary.

Mitotically active cellular fibroma

A recent outcome study suggests that mitotic activity in cellular fibroma (that lacks nuclear atypia) is
not associated with recurrence or spread. The study had an average follow up period of 4.7 years.
Isolated case reports of similar tumors that did spread do exist, therefore the authors recommend
that mitotically active cellular fibromas be considered low malignant potential tumors and that careful
surveillance should be offered.22 Ovarian fibrosarcoma should be reserved for the rare case in which
hypercellularity and unequivocal nuclear atypia are present.

Sertoli-Leydig Cell Tumor

Sertoli-Leydig cell tumors (SLCT) are tumors of young women and girls and are notable for virilizing
effects.46 They may be of well, intermediate, or poor differentiation and any of these may be
accompanied by heterologous elements or by retiform growth. In well differentiated variants Sertoli
cells line well formed tubules that grow in a fibrous stroma that contains clusters of polygonal Leydig
cells.53, 55 Immature stromal and Sertoli cells are not present. The more common intermediate and
poorly differentiated Sertoli-Leydig cell tumors contain variably mature Sertoli cells growing in
trabeculae or nests or lining round or retiform tubules.31, 50, 54, 55 The stroma is cellular and immature,
and Leydig cells, present either singly or in clusters, are present in most tumors. Most patients
present with tumors confined to the ovary and have a favorable prognosis.

SLCT versus sertoliform variant of endometrioid adenocarcinoma

Rare ovarian endometrioid adenocarcinomas may exhibit areas of growth that mimic Sertoli cell
proliferation. Because pan-keratin can be expressed in the Sertoli cells of SLCT, it is important to
use EMA in this particular differential diagnosis since Sertoli cells will be negative while
adenocarcinoma will be positive.6, 15, 16, 29 Because some SLCT will express estrogen and/or
progesterone receptors, these markers are less helpful in this setting.11

Heterologous elements in SLCT

Two types of heterologous elements can create diagnostic problems. These are present in about
20% of cases, mostly consisting of gastrointestinal type epithelium. ;49 If prominent, this component
can be confused for a mucinous tumor. Less commonly, hepatoid differentiation can be found.14, 32
These cells can secrete alpha fetoprotein and this may lead to elevated serum AFP. Awareness of
this can prevent confusion with yolk sac tumor, which also results in elevated serum AFP.
 Sclerosing Stromal Tumor

Sclerosing stromal tumor is a rare though benign, hormonally inactive ovarian tumor with a distinct
low magnification growth pattern that arises almost exclusively in young women.3, 23 The tumor
shows a pseudolobular pattern of cellular, spindle cell zones alternating with paucicellular fibrous
zones. Scattered throughout are branched dilated blood vessels having a “hemangiopericytoma-
like” appearance. The tumor cells adjacent to the vessels are often polygonal, vacuolated (lipid, not
mucin) or vaguely myoid in appearance. In rare cases these cells may exhibit signet ring features.
The tumor cells are vimentin positive and they often stain for smooth muscle actin.40-42
Immunostains for inhibin and calretinin are positive in more than 50% of sclerosing stromal tumors.26,
33, 39

References

1. Ahmed E, Young RH, Scully RE. Adult granulosa cell tumor of the ovary with foci of hepatic cell differentiation: a report of four cases and comparison with two
cases of granulosa cell tumor with Leydig cells. Am J Surg Pathol. 1999;23:1089-93.

2. Bjorkholm E, Silfversward C. Prognostic factors in granulosa-cell tumors. Gynecol Oncol. 1981;11:261-74.

3. Chalvardjian A, Scully RE. Sclerosing stromal tumors of the ovary. Cancer. 1973;31:664-70.

4. Chandran R, Rahman H, Gebbie D. Composite mucinous and granulosa-theca-cell tumour of the ovary: an unusual neoplasm. Aust N Z J Obstet Gynaecol.
1993;33:437-9.

5. Costa MJ, Ames PF, Walls J, et al. Inhibin immunohistochemistry applied to ovarian neoplasms: A novel, effective, diagnostic tool. Hum Pathol.
1997;28:1247-54.

6. Deavers MT, Malpica A, Liu J, et al. Ovarian sex cord-stromal tumors: an immunohistochemical study including a comparison of calretinin and inhibin. Mod
Pathol. 2003;16:584-90.

7. Deavers MT, Malpica A, Liu J, et al. Ovarian sex cord-stromal tumors: an immunohistochemical study including a comparison of calretinin and inhibin. Mod
Pathol. 2003;16:584-90.

8. Deavers MT, Malpica A, Liu J, et al. Ovarian sex cord-stromal tumors: an immunohistochemical study including a comparison of calretinin and inhibin. Mod
Pathol. 2003;16:584-90.

9. Doussis-Anagnostopoulou IA, Remadi S, Czernobilsky B. Mucinous elements in Sertoli-Leydig and granulosa cell tumours: A revaluation. Histopathology.
1996;28:372-5.

10. Evans MP, Webb MJ, Gaffey TA, et al. DNA ploidy of ovarian granulosa cell tumors: Lack of correlation between DNA index or proliferative index and
outcome in 40 patients. Cancer. 1995;75:2295-8.

11. Farinola MA, Gown AM, Judson K, et al. Estrogen Receptor alpha and Progesterone Receptor Expression in Ovarian Adult Granulosa Cell Tumors and
Sertoli-Leydig Cell Tumors. Int J Gynecol Pathol. 2007;26:375-82.

12. Fox H, Agrawal K, Langley FA. A clinicopathologic study of 92 cases of granulosa cell tumor of the ovary with special reference to the factors influencing
prognosis. Cancer. 1975;35:231-41.

13. Gaffey MJ, Frierson HFJ, Iezzoni JC, et al. Ovarian granulosa cell tumors with bizarre nuclei: an immunohistochemical analysis. Mod Pathol. 1996;9:308-15.

14. Gagnon S, Tëtu B, Silva EG, et al. Frequency of alpha-fetoprotein production by Sertoli-Leydig cell tumors of the ovary: an immunohistochemical study of
eight cases. Mod Pathol. 1989;2:63-7.

15. Glenn MW, Young RH. Ovarian sertoli-leydig cell tumors with pseudoendometrioid tubules (pseudoendometrioid sertoli-leydig cell tumors). Am J Surg Pathol.
2007;31:592-7.

16. Guerrieri C, Franlund B, Malmstrom H, et al. Ovarian endometrioid carcinomas simulating sex cord-stromal tumors: a study using inhibin and cytokeratin 7. Int
J Gynecol Pathol. 1998;17:266-71.

17. He H, Luthringer DJ, Hui P, et al. Expression of CD56 and WT1 in ovarian stroma and ovarian stromal tumors. Am J Surg Pathol. 2008;32:884-90.

18. He H, Luthringer DJ, Hui P, et al. Expression of CD56 and WT1 in ovarian stroma and ovarian stromal tumors. Am J Surg Pathol. 2008;32:884-90.

19. Hildebrandt RH, Rouse RV, Longacre TA. Value of inhibin in the identification of granulosa cell tumors of the ovary. Hum Pathol. 1997;28:1387-95.
20. Hitchcock CL, Norris HJ, Khalifa MA, et al. Flow cytometric analysis of granulosa tumors. Cancer. 1989;64:2127-32.

21. Holland DR, Le Riche J, Swenerton KD, et al. Flow cytometric assessment of DNA ploidy is a useful prognostic factor for patients with granulosa cell ovarian
tumors. Int J Gynecol Cancer. 1991;1:227-32.

22. Irving JA, Alkushi A, Young RH, et al. Cellular fibromas of the ovary: a study of 75 cases including 40 mitotically active tumors emphasizing their distinction
from fibrosarcoma. Am J Surg Pathol. 2006;30:929-38.

23. Kawauchi S, Tsuji T, Kaku T, et al. Sclerosing stromal tumor of the ovary. A clinicopathologic, immunohistochemical, ultrastructural, and cytogenetic analysis
with special reference to its vasculature. Am J Surg Pathol. 1998;22:83-92.

24. King LA, Okagaki T, Gallup DG, et al. Mitotic count, nuclear atypia, and immunohistochemical determination of Ki-67, c-myc, p21-ras, c-erbB2, and p53
expression in granulosa cell tumors of the ovary: mitotic count and Ki-67 are indicators of poor prognosis. Gynecol Oncol. 1996;61:227-32.

25. Klemi PJ, Joensuu H, Salmi T. Prognostic value of flow cytometric DNA content analysis in granulosa cell tumor of the ovary. Cancer. 1990;65:1189-93.

26. Kommoss F, Oliva E, Bhan AK, et al. Inhibin expression in ovarian tumors and tumor-like lesions: an immunohistochemical study. Mod Pathol. 1998;11:656-
64.

27. Lauszus FF, Petersen AC, Greisen J, et al. Granulosa cell tumor of the ovary: a population-based study of 37 women with stage I disease. Gynecol Oncol.
2001;81:456-60.

28. Malmstrom H, Hogberg T, Risberg B, et al. Granulosa cell tumors of the ovary: prognostic factors and outcome. Gynecol Oncol. 1994;52:50-5.

29. Matias-Guiu X, Pons C, Prat J. Mullerian inhibiting substance, alpha-inhibin, and CD99 expression in sex cord-stromal tumors and endometrioid ovarian
carcinomas resembling sex cord-stromal tumors. Hum Pathol. 1998;29:840-5.

30. Miller BE, Barron BA, Wan JY, et al. Prognostic factors in adult granulosa cell tumor of the ovary. Cancer. 1997;79:1951-5.

31. Mooney EE, Nogales FF, Bergeron C, et al. Retiform Sertoli-Leydig cell tumours: clinical, morphological and immunohistochemical findings. Histopathology.
2002;41:110-7.

32. Mooney EE, Nogales FF, Tavassoli FA. Hepatocytic differentiation in retiform Sertoli-Leydig cell tumors: distinguishing a heterologous element from Leydig
cells. Hum Pathol. 1999;30:611-7.

33. Movahedi-Lankarani S, Kurman RJ. Calretinin, a more sensitive but less specific marker than alpha-inhibin for ovarian sex cord-stromal neoplasms - An
immunohistochemical study of 215 cases. Am J Surg Pathol. 2002;26:1477-83.

34. Murray SK, Clement PB, Young RH. Endometrioid carcinomas of the uterine corpus with sex cord-like formations, hyalinization, and other unusual
morphologic features: a report of 31 cases of a neoplasm that may be confused with carcinosarcoma and other uterine neoplasms. Am J Surg Pathol.
2005;29:157-66.

35. Nakashima N, Young RH, Scully RE. Androgenic granulosa cell tumors of the ovary. A clinicopathologic analysis of 17 cases and review of the literature.
Arch Pathol Lab Med. 1984;108:786-91.

36. Norris HJ, Taylor HB. Virilization associated with cystic granulosa tumors. Obstet Gynecol. 1969;34:629-35.

37. Price A, Russell P, Elliott P, et al. Composite mucinous and granulosa-cell tumor of ovary: case report of a unique neoplasm. Int J Gynecol Pathol.
1990;9:372-8.

38. Roush GR, el-Naggar AK, Abdul-Karim FW. Granulosa cell tumor of ovary: a clinicopathologic and flow cytometric DNA analysis. Gynecol Oncol.
1995;56:430-4.

39. Sabah M, Leader M, Kay E. The Problem With KIT: Clinical Implications and Practical Difficulties With CD117 Immunostaining. Appl Immunohistochem Mol
Morphol. 2003;11:56-61.

40. Sabah M, Leader M, Kay E. The Problem With KIT: Clinical Implications and Practical Difficulties With CD117 Immunostaining. Appl Immunohistochem Mol
Morphol. 2003;11:56-61.

41. Saitoh A, Tsutsumi Y, Osamura RY, et al. Sclerosing stromal tumor of the ovary. Immunohistochemical and electron microscopic demonstration of smooth-
muscle differentiation. Arch Pathol Lab Med. 1989;113:372-6.

42. Shaw JA, Dabbs DJ, Geisinger KR. Sclerosing stromal tumor of the ovary: An ultrastructural and immunohistochemical analysis with histogenetic
considerations. Ultrastruct Pathol. 1992;16:363-77.

43. Stenwig JT, Hazekamp JT, Beecham JB. Granulosa cell tumors of the ovary. A clinicopathological study of 118 cases with long-term follow-up. Gynecol
Oncol. 1979;7:136-52.

44. Suh KS, Silverberg SG, Rhame JG, et al. Granulosa cell tumor of the ovary. Histopathologic and flow cytometric analysis with clinical correlation. Arch Pathol
Lab Med. 1990;114:496-501.

45. Tiltman AJ, Haffajee Z. Sclerosing stromal tumors, thecomas, and fibromas of the ovary: an immunohistochemical profile. Int J Gynecol Pathol. 1999;18:254-
8.
46. Young RH. Sertoli-Leydig cell tumors of the ovary: review with emphasis on historical aspects and unusual forms. Int J Gynecol Pathol. 1993;12:141-7.

47. Young RH, Dudley AG, Scully RE. Granulosa cell, Sertoli-Leydig cell, and unclassified sex cord-stromal tumors associated with pregnancy: a
clinicopathological analysis of thirty-six cases. Gynecol Oncol. 1984;18:181-205.

48. Young RH, Oliva E, Scully RE. Luteinized adult granulosa cell tumors of the ovary: a report of four cases. Int J Gynecol Pathol. 1994;13:302-10.

49. Young RH, Prat J, Scully RE. Ovarian Sertoli-Leydig cell tumors with heterologous elements. I. Gastrointestinal epithelium and carcinoid: A clinicopathologic
analysis of 36 cases. Cancer. 1982;50:2448-56.

50. Young RH, Scully RE. Ovarian Sertoli-Leydig cell tumors with a retiform pattern--A problem in diagnosis: a report of 25 cases. Am J Surg Pathol. 1983;7:755-
71.

51. Young RH, Scully RE. Ovarian sex cord-stromal tumors with bizarre nuclei: A clinicopathologic analysis of 17 cases. Int J Gynecol Pathol. 1983;1:325-35.

52. Young RH, Scully RE. Ovarian stromal tumors with minor sex cord elements: a report of seven cases. Int J Gynecol Pathol. 1983;2:227-34.

53. Young RH, Scully RE. Well-differentiated ovarian Sertoli-Leydig cell tumors: a clinicopathological analysis of 23 tumors. Int J Gynecol Pathol. 1984;3:277-90.

54. Young RH, Scully RE. Ovarian Sertoli-Leydig cell tumors. A clinicopathological analysis of 207 cases. Am J Surg Pathol. 1985;9:543-69.

55. Zaloudek C, Norris HJ. Sertoli-Leydig tumors of the ovary. A clinicopatholgic study of 64 intermediate and poorly differentiated neoplasms. Am J Surg Pathol.
1984;8:405-18.

56. Zhao C, Barner R, Vinh TN, et al. SF-1 is a diagnostically useful immunohistochemical marker and comparable to other sex cord-stromal tumor markers for
the differential diagnosis of ovarian sertoli cell tumor. Int J Gynecol Pathol. 2008;27:507-14.

57. Zhao C, Vinh TN, McManus K, et al. Identification of the most sensitive and robust immunohistochemical markers in different categories of ovarian sex cord-
stromal tumors. Am J Surg Pathol. 2009;33:354-66.