Ovarian Serous Cystadenofibroma With Stromal Sex Cord Elements Dr. W. Glenn McCluggage Belfast

History F 61, 40 cm mainly cystic ovarian tumour Figure 1 Click to view with ImageScope Click to view with a Web-Based Viewer 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 undertaken. 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. [1, 2, 3] 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. [4] 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). [5] 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. [6] 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. [7, 8, 9] 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 [10] 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 differentiation. [11, 12, 13, 14] 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. References McCluggage WG. Value of inhibin staining in gynecological pathology. Int J Gynecol Pathol 2001;20:79-85 McCluggage WG, Maxwell P. Immunohistochemical staining for calretinin is useful in the diagnosis of ovarian sex cord stromal tumours. Histopathology 2001;38:403-408 McCluggage WG, Maxwell P, Sloan JM. Immunohistochemical staining of ovarian granulosa cell tumors with monoclonal antibody against inhibin. Hum Pathol 1997;28:1034-1038 Eichhorn JH, Young RH, Clement PB, Scully RE. Mesodermal (Müllerian) adenosarcoma of the ovary: a clinicopathologic analysis of 40 cases and a review of the literature. Am J Surg Pathol 2002;26:1243-1258 Young RH, Scully RE. Ovarian stromal tumors with minor sex cord elements: a report of seven cases. Int J Gynecol Pathol 1983;2:227-234 Seo EJ, Kwon HJ, Shim SI. Ovarian serous cystadenoma associated with Sertoli-Leydig cell tumor: a case report. J Korean Med Sci 1996;11:84-87 Aguirre P, Scully RE, DeLellis RA. Ovarian heterologous Sertoli-Leydig cell tumors with gastrointestinal-type epithelium. An immunohistochemical analysis. Arch Pathol Lab Med 1986;110:528-533 McKenna M, Kenny B, Dorman G, McCluggage WG. Combined granulosa cell tumor and mucinous cystadenoma of the ovary: granulosa cell tumor with heterologous mucinous elements. Int J Gynecol Pathol 2005;24:224-247 Young RH, Prat J, Scully RE. Ovarian Sertoli-Leydig cell tumors with heterologous elements. I. Gastrointestinal epithelium and carcinoid: a clinicopathologic analysis of thirty-six cases. Cancer 1982;50:2448-2456 Clement PB, Scully RE. Mullerian adenosarcomas of the uterus with sex cord-like elements. A clinicopathologic analysis of eight cases. Am J Surg Pathol 1989;91:664-672 Baker RJ, Hildebrant RH, Rouse RV et al. Inhibin and CD99 (MIC2) expression in uterine stromal neoplasms with sex cord-like elements. Hum Pathol 1999;30:671-679 Krishnamurthy S, Jungbloth AA, Busam KJ et al. Uterine tumors resembling ovarian sex cord tumors have an immunophenotype consistent with true sex cord differentiation. Am J Surg Pathol 1998;22:1078-1082 McCluggage WG. Uterine tumours resembling ovarian sex cord tumours: immunohistochemical evidence for true sex cord differentiation. Histopathology 1999;34:373-380 Irving JA, Carinelli S, Prat J. Uterine tumors resembling ovarian sex cord tumors are polyphenotypic neoplasms with true sex cord differentiation. Mod Pathol 2006;19:17-24.