Value of Immunohistochemistry in Gynecological Pathology
Moderator: Dr. W. Glenn McCluggage
Case 2 -
Ovarian Serous Cystadenofibroma With Stromal Sex Cord Elements
Dr. W. Glenn McCluggage
F 61, 40 cm mainly cystic ovarian tumour
Case 2 - Figure 1
Diagnosis: Ovarian Serous Cystadenofibroma with Stromal Sex Cord Elements
Serous cystadenofibromas are common benign ovarian neoplasms composed of an admixture of glands or
cysts lined by benign ciliated serous type epithelium embedded in a fibrous stroma. This case represents
an unusual ovarian serous cystadenofibroma characterised by the widespread presence throughout the stroma
of solid and hollow tubules which morphologically resembled Sertoli cell elements. Immunohistochemical
studies demonstrated that the tubules exhibited true sex cord differentiation. As far as I am aware, sex
cord elements have not been previously described in an ovarian serous cystadenofibroma.
A 61 year old woman presented with recent onset of abdominal distension. There were no signs or
symptoms of hyperoestrogenism or hyperandrogenism. Clinically she was found to have ascites. Serum
CA125 was markedly elevated at 892 U/ml (normal <35). Ultrasound and CT scans of the abdomen
confirmed the presence of ascites and showed a large multicystic mass occupying the whole of the pelvis
and thought to be ovarian in origin. Laparotomy was performed and this revealed a 40cm maximum dimension
right sided cystic ovarian mass. Hysterectomy, bilateral salpingo-oophorectomy and omentectomy was
The surgical specimen comprised a collapsed multicystic right ovarian tumour, with areas of capsular
rupture, measuring 41 x 24 x 10cm. The whole of the lesion was multicystic with little or no solid
component. The cysts were thin walled with no solid or papillary elements.
Multiple sections from the right ovarian mass showed glands and cysts lined by benign ciliated serous
epithelium with a surrounding fibrous stroma. The serous epithelial elements showed no evidence of
borderline change or malignancy. There was focal condensation of the stroma with increased cellularity
around the epithelium but no nuclear atypia or mitotic activity within the stromal elements. Within the
stroma just beneath the epithelium, throughout much but not all of the lesion, there was widespread
formation of solid and hollow tubules which morphologically resembled Sertoli cell tubules. The nuclear
features of these tubules were bland and nuclear grooves were not identified. Stromal Leydig or
luteinised cells were not present. There was no evidence of endometriosis.
Immunohistochemistry showed the tubules to exhibit diffuse positivity with calretinin and to be
focally positive with α inhibin. They were negative with epithelial membrane antigen (EMA),
Ber-EP4, AE1/3 and cytokeratin (CK) 7. Conversely the serous epithelial elements were positive with EMA,
Ber-EP4, AE1/3 and CK7 but calretinin and α inhibin negative.
The multicystic lesion in the right ovary represented a serous cystadenofibroma. A highly unusual
feature was the widespread presence in the stroma of many solid and hollow tubules which morphologically
resembled sex cord structures, specifically Sertoli cell elements. Immunohistochemistry was supportive
of true sex cord differentiation in that the tubules were positive with both calretinin and α
inhibin, the two most commonly utilised markers of sex cord elements within the ovary.
The presence of sex cord elements within an ovarian serous cystadenofibroma has hitherto not been described
in the literature.
Sex cord elements, as well as obviously being present in sex cord tumours, may rarely occur as a
component of several other ovarian neoplasms. Ovarian Müllerian adenosarcomas, similar to their uterine
counterparts, may contain cellular arrangements which are referred to as sex cord-like elements within
the stroma.  The histogenesis of these elements is discussed below. In many adenosarcomas the
stromal component is low grade and the features of malignancy are subtle. However, I consider the
lesion described to represent an adenofibroma rather than an adenosarcoma since although there was focal
condensation of stroma around the epithelium, there was no evidence of nuclear atypia or mitotic
activity. Moreover, adenosarcomas often have a polypoid architecture with the formation of leaf-like
structures resembling a phyllodes tumour of the breast and stromal cores that project into glandular
spaces, features that were absent in the case we describe. Minor sex cord elements have also been
described in ovarian stromal tumours, especially fibromas (ovarian stromal tumours with minor sex cord
elements).  Since the stromal element in a serous cystadenofibroma can be regarded as
analogous to a fibroma, it is perhaps not surprising that sex cord elements might occur rarely in the
stromal component of the former neoplasm.
A case of Sertoli-Leydig cell tumour arising as a circumscribed mural nodule within an ovarian serous
cystadenoma has been reported, this phenomenon being regarded as representing a collision of two
independent neoplasms.  In the current case, the widespread distribution of sex cord elements
throughout much of the stroma and the intimate admixture with the glands and cysts excludes a collision
tumour. I feel it is highly likely that the sex cord elements represent an unusual non-neoplastic
stromal alteration rather than being in themselves neoplastic. Heterologous epithelial elements, usually
mucinous in type, may occur in some ovarian sex cord-stromal tumours, usually of Sertoli-Leydig but
rarely of granulosa cell type.
When these mucinous elements are prominent, they may result
in misdiagnosis as a pure mucinous neoplasm. However, I consider the underlying lesion in this case to
represent a serous cystadenofibroma and do not feel that the serous epithelial elements represent
heterologous differentiation within a Sertoli cell tumour.
As far as I am aware, it has not been established whether the sex cord-like arrangements within
ovarian adenosarcomas represent areas of true sex cord differentiation or simply a sex cord-like
arrangement of the stromal cells. In the case I describe, the tubular elements exhibited
immunohistochemical evidence of true sex cord differentiation in the form of α inhibin and
calretinin positivity. Stromal elements with a sex cord-like arrangement also occur in uterine
adenosarcomas  and endometrial stromal neoplasms and in endometrial stromal neoplasms these
have been shown in some, but not all, cases to exhibit immunohistochemical evidence of true sex cord
It is likely that the sex cord-like arrangements in both ovarian and
uterine adenosarcomas exhibit true sex cord differentiation in at least a proportion of cases.
The clinical significance of the sex cord elements in this case is unknown, although I feel they are
unlikely to be of any clinical import. Five year follow-up in three ovarian fibromas with minor sex cord
elements revealed no evidence of tumour recurrence or metastasis.
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