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• W2789726314 abstract "The internationally accepted World Health Organization classification of ovarian tumours1Kurman R.J. Carcangui M.L. Herrington C.S. Young R.H. Tumours of the ovaryWHO Classification of Tumours of Female Reproductive Organs.4th ed. International Agency for Research on Cancer, Lyon2014Google Scholar is predicated on histological criteria, but the majority of neoplasms are more fundamentally grouped into three major and seemingly discrete subsets based on their presumed cells of origin. These are firstly the surface epithelial-stromal tumours, secondly the sex cord-stromal and steroid cell tumours and, thirdly the germ cell tumours. On the one hand, it is not unusual for tumours from the first (epithelial) and third (germ cell) groups and, rarely, even miscellaneous tumours such as haemangiomas,2Muronda M. Russell P. Griffith J. Chan F. Bell P. Mahmoud I. Ovarian haemangiomas with peripheral hilus cell proliferation.Pathology. 2017; 49: 438-441Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar to induce a reactive hyperplasia in the adjacent constituent or native ovarian stroma. On the other hand, it is exceptional and quite controversial for individual ovarian tumours to harbour true neoplastic elements derived from more than one of the above subsets. That apparent exception is the combination of mature cystic teratoma and mucinous tumour, most typically of intestinal type. Even in this latter example it has been proposed that the mucinous neoplasm is derived from the teratoma (i.e., is also of germ cell origin) and, therefore, not an exception. Within this paradigm, co-existence of neoplastic Müllerian epithelial and sex cord-stromal elements within a single tumour is vanishingly rare. Those few cases described in the English literature are mainly mucinous epithelial tumours presenting with included elements indistinguishable from adult granulosa cell tumour.3Chandran R. Rahman H. Gebbie D. Composite mucinous and granulosa-theca-cell tumour of the ovary: an unusual neoplasm.Aust NZ J Obstet Gynaecol. 1993; 33: 437-439Crossref PubMed Scopus (15) Google Scholar, 4Kushida Y. Haba R. Kadota K. et al.Composite mucinous and granulosa cell tumor of the ovary.Pathol Int. 2005; 55: 797-801Crossref PubMed Scopus (12) Google Scholar, 5Price A. Russell P. Elliott P. Bannatyne P. Composite mucinous and granulosa-cell tumor of ovary: case report of a unique neoplasm.Int J Gynecol Pathol. 1990; 9: 372-378Crossref PubMed Scopus (22) Google Scholar, 6Singh N. Gilks C.B. Huntsman D.G. et al.Adult granulosa cell tumour-like areas occurring in ovarian epithelial neoplasms: report of a case series with investigation of FOXL2 mutation status.Histopathology. 2014; 64: 626-632Crossref PubMed Scopus (16) Google Scholar We recently encountered a peculiar variation on this theme: a combined benign serous cystadenoma and thecoma occurring within the right ovary of a 68-year-old post-menopausal patient. The patient presented with worsening urinary incontinence over an 8-month period. A pelvic ultrasound demonstrated a large, hypoechoic right adnexal mass. The contralateral ovary was not visualised and the endometrium appeared thickened and showed cystic spaces. The patient had no clinical symptoms of hyperoestrogenism and underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy. Post-operatively, the patient experienced persistent urinary incontinence but remains otherwise well. Grossly, the excised 85 × 80 × 35 mm right ovary had both solid and cystic areas with cyst wall thicknesses of up to 10 mm (Fig. 1A). The cut surface of the solid areas was pale yellow and lobulated. The left ovary, measuring 22 mm in maximum dimension, included a 15 mm complex cystic lesion. Both fallopian tubes were unremarkable. The myometrium contained multiple leiomyomas and the endometrium was up to 2.5 mm thick and focally cystic. Microscopic examination of the right ovarian mass showed a parvilocular cyst lined by typical, benign, ciliated, serous epithelium (Fig. 1B), diffusely reactive for CK7 and for PAX8 in the non-ciliated cells (Fig. 1C). The solid nodules of theca-like cells contained occasional aggregates of hyaline collagen, were separated by bands of paucicellular fibrocollagenous connective tissue and were mostly separated from the lining epithelium of the cyst by a lamina of wavy collagenous stroma characteristic of benign ovarian serous tumours. Only focally was it closely apposed to the cyst lining (Fig. 1D). This solid part of the tumour comprised numerous, variably circumscribed nodules (Fig. 2A) and ill-defined sheets of plump spindle cells, each with a central polygonal nucleus, small nucleolus and abundant pale to amphophilic cytoplasm, consistent with thecal differentiation (Fig. 2B) and diffusely reactive for α-inhibin (Fig. 2C) and FOXL2 (Fig. 2D). The focal juxtaposition between the two discrete tumour elements is demonstrated clearly in these images. The contralateral ovary included a benign mixed mucinous and serous adenofibroma without any theca-like component. The endometrium was mildly oestrogenised and the cystic areas were due to benign sessile basal endometrial polyps. Pure thecomas are extremely uncommon, accounting for less than 1% of primary ovarian neoplasms and are defined as stromal tumours with abundant lipid rich cytoplasm reminiscent of theca interna cells,1Kurman R.J. Carcangui M.L. Herrington C.S. Young R.H. Tumours of the ovaryWHO Classification of Tumours of Female Reproductive Organs.4th ed. International Agency for Research on Cancer, Lyon2014Google Scholar typically occurring in post-menopausal women and macroscopically present with a lobulated yellow to orange cut surface. More commonly, they are admixed with fibromatous elements and referred to as fibrothecomas.7Russell P. Robboy S.J. Prat J. Ovarian sex cord-stromal and steroid cell tumors.in: Robboy S.J. Mutter G.L. Prat J. Robboy's Pathology of the Female Reproductive Tract. 2nd ed. Churchill Livingstone, Edinburgh2009: 693-727Crossref Google Scholar Serous tumours, by contrast, are the most common subtype of epithelial-stromal neoplasms and constitute up to 40% of all primary ovarian tumours in Western populations, with a tendency to occur in patients in the 4th to 6th decade of life.1Kurman R.J. Carcangui M.L. Herrington C.S. Young R.H. Tumours of the ovaryWHO Classification of Tumours of Female Reproductive Organs.4th ed. International Agency for Research on Cancer, Lyon2014Google Scholar Only two cases of combined serous and thecal tumours have been reported in the English literature to date.8Chandanwale S.S. Pal S.S. Kumar H.B. Sammi A.B. Serous cystadenoma and fibrothecoma: a rare combination in collision tumor of ovary with pseudo-Meigs syndrome.J Pathol Transl Med. 2015; 49: 163-166Crossref PubMed Scopus (7) Google Scholar, 9Mishra A. Shamsunder S. Malik S. Zaheer S. Collision tumour of ovary: a rare combination of fibrothecoma with serous cystadenoma.Int J Reprod Contracept Obstet Gynecol. 2017; 6: 1643-1645Crossref Google Scholar Both cases were said to involve a benign serous cystadenoma and a fibrothecoma, and the two components were purported to be sharply demarcated and separated by intervening ovarian stroma, but the second case9Mishra A. Shamsunder S. Malik S. Zaheer S. Collision tumour of ovary: a rare combination of fibrothecoma with serous cystadenoma.Int J Reprod Contracept Obstet Gynecol. 2017; 6: 1643-1645Crossref Google Scholar illustrates a benign transitional cell adenofibroma (Brenner tumour) rather than a serous neoplasm in the cystic component, and its authenticity is questionable. In our current case, the serous epithelial tumour and the thecoma were present both in close juxtaposition in some areas (Fig. 1D) and separated in others. Explaining the intimate coexistence of two histologically distinct tumour types within one ovarian mass is more challenging than simply describing them. Gracing them with a name (‘collision’, ‘composite’, ‘combined’) may be somewhat presumptuous. Some authors have suggested that two such tumours have arisen autonomously and refer to them as collision tumours.3Chandran R. Rahman H. Gebbie D. Composite mucinous and granulosa-theca-cell tumour of the ovary: an unusual neoplasm.Aust NZ J Obstet Gynaecol. 1993; 33: 437-439Crossref PubMed Scopus (15) Google Scholar, 8Chandanwale S.S. Pal S.S. Kumar H.B. Sammi A.B. Serous cystadenoma and fibrothecoma: a rare combination in collision tumor of ovary with pseudo-Meigs syndrome.J Pathol Transl Med. 2015; 49: 163-166Crossref PubMed Scopus (7) Google Scholar, 9Mishra A. Shamsunder S. Malik S. Zaheer S. Collision tumour of ovary: a rare combination of fibrothecoma with serous cystadenoma.Int J Reprod Contracept Obstet Gynecol. 2017; 6: 1643-1645Crossref Google Scholar, 10Bige O. Demir A. Koyuncuoglu M. Secil M. Ulukus C. Saygili U. Collision tumor: serous cystadenocarcinoma and dermoid cyst in the same ovary.Arch Gynecol Obstet. 2009; 279: 767-770Crossref PubMed Scopus (21) Google Scholar Collision tumours are well published entities in a range of organs, but within the ovary not exceeding double figures. Multiple ‘composite’ tumours with a mucinous epithelial component ranging from benign to malignant have been described, wherein the mucinous tumours have presented in combination with teratomas or with sex cord-stromal tumours, such as Sertoli–Leydig cell tumours or granulosa cell tumours.3Chandran R. Rahman H. Gebbie D. Composite mucinous and granulosa-theca-cell tumour of the ovary: an unusual neoplasm.Aust NZ J Obstet Gynaecol. 1993; 33: 437-439Crossref PubMed Scopus (15) Google Scholar, 4Kushida Y. Haba R. Kadota K. et al.Composite mucinous and granulosa cell tumor of the ovary.Pathol Int. 2005; 55: 797-801Crossref PubMed Scopus (12) Google Scholar, 5Price A. Russell P. Elliott P. Bannatyne P. Composite mucinous and granulosa-cell tumor of ovary: case report of a unique neoplasm.Int J Gynecol Pathol. 1990; 9: 372-378Crossref PubMed Scopus (22) Google Scholar, 8Chandanwale S.S. Pal S.S. Kumar H.B. Sammi A.B. Serous cystadenoma and fibrothecoma: a rare combination in collision tumor of ovary with pseudo-Meigs syndrome.J Pathol Transl Med. 2015; 49: 163-166Crossref PubMed Scopus (7) Google Scholar, 11Moid F.Y. Jones R.V. Granulosa cell tumor and mucinous cystadenoma arising in a mature cystic teratoma of the ovary: a unique case report and review of literature.Ann Diagn Pathol. 2004; 8: 96-101Crossref PubMed Scopus (28) Google Scholar, 12Staats P.N. Coutts M.A. Young R.H. Primary ovarian mucinous cystic tumor with prominent theca cell proliferation and focal granulosa cell tumor in its stroma: case report, literature review, and comparison with Sertoli-Leydig cell tumor with heterologous elements.Int J Gynecol Pathol. 2010; 29: 228-233Crossref PubMed Scopus (14) Google Scholar Some authors hypothesise that composite tumours arise incidentally, are induced by oncogenic growth factors, or are the by-product of a change to the microenvironment of the primary tumour facilitating the growth of the second neoplasm.3Chandran R. Rahman H. Gebbie D. Composite mucinous and granulosa-theca-cell tumour of the ovary: an unusual neoplasm.Aust NZ J Obstet Gynaecol. 1993; 33: 437-439Crossref PubMed Scopus (15) Google Scholar, 8Chandanwale S.S. Pal S.S. Kumar H.B. Sammi A.B. Serous cystadenoma and fibrothecoma: a rare combination in collision tumor of ovary with pseudo-Meigs syndrome.J Pathol Transl Med. 2015; 49: 163-166Crossref PubMed Scopus (7) Google Scholar, 10Bige O. Demir A. Koyuncuoglu M. Secil M. Ulukus C. Saygili U. Collision tumor: serous cystadenocarcinoma and dermoid cyst in the same ovary.Arch Gynecol Obstet. 2009; 279: 767-770Crossref PubMed Scopus (21) Google Scholar An alternative explanation for such unusual combinations of tumours within the ovary is that they are ‘biphasic’ with one inducing the formation of the other. In the case of Sertoli–Leydig cell tumours, the mucinous component is considered to be heterologous differentiation.7Russell P. Robboy S.J. Prat J. Ovarian sex cord-stromal and steroid cell tumors.in: Robboy S.J. Mutter G.L. Prat J. Robboy's Pathology of the Female Reproductive Tract. 2nd ed. Churchill Livingstone, Edinburgh2009: 693-727Crossref Google Scholar Singh et al.6Singh N. Gilks C.B. Huntsman D.G. et al.Adult granulosa cell tumour-like areas occurring in ovarian epithelial neoplasms: report of a case series with investigation of FOXL2 mutation status.Histopathology. 2014; 64: 626-632Crossref PubMed Scopus (16) Google Scholar conducted a study on five ovarian epithelial neoplasms which showed stromal components resembling adult granulosa cell tumours (AGCT). FOXL2 mutations (402C→G), characteristic for AGCT, were identified using polymerase chain reaction on paraffin embedded tissues, in two of the five cases. They argued that the absence of this mutation in three cases proved that the AGCT-like stromal elements were proliferative in nature rather than a separate second neoplasm, with the converse applying to the tumours with the FOXL2 mutation. Unless we can intuit the difference between induced hyperplasia and independent neoplasia in each instance, the close spatial relationship described in this case, of and by itself, counsels us to couch its diagnosis in somewhat non-committal terms. One component seems ineluctably derived from the native ovarian mesenchyme and is sufficiently characteristic to be classified as a sex cord-stromal neoplasm. The other is postulated to derive from the ovarian surface epithelium or cortical inclusions and the latter, perhaps, ultimately from the fimbrial mucosa of the fallopian tubes.13Vang R. Shih Ie M. Kurman R.J. Fallopian tube precursors of ovarian low- and high-grade serous neoplasms.Histopathology. 2013; 62: 44-58Crossref PubMed Scopus (206) Google Scholar Given the extreme rarity of this combination, and in the absence of molecular evidence of clonality, who is to say it is due to other than serendipity? The authors state that there are no conflicts of interest to disclose." @default.
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• W2789726314 title "Combined ovarian serous cystadenoma and thecoma" @default.
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