{"paper_id":"77b69627-c10a-4b5f-9baf-1f326502019a","body_text":"Submit Manuscript | http://medcraveonline.com\nIntroduction\nMucinous elements are a common accompaniment in several \nmixed ovarian tumors, frequently so in mixed epithelial tumors. The \nassociation of mucinous elements has also been noted along with \nsex cord stromal tumors, a sizeable proportion admixed with Sertoli \nLeydig cell elements. The combination of mucinous elements with an \nadult granulosa cell tumor has been reported till date in four previous \ncases, one of which was a mucinous cystadenocarcinoma.1–4 We report \na similar case along with a review of the previously reported cases and \ndiscuss the existing theories regarding their histogenesis. \nCase report\nA seventy five year old post menopausal female presented with \nvaginal bleeding for six months. She was menopausal for the past \ntwenty five years. No other relevant family or personal history \nwas elicited. She had never been on hormone replacement therapy. \nGeneral examination revealed mild pallor. No mass was palpable per \nabdomen. On examination per vaginum a 4x4cm mass was palpated \nin the left pouch of Douglas. \nTransvaginal ultrasonography was suggestive of a multi-\ncystic left adnexal mass measuring 5.5x5.3cm. Transabdominal \nultrasound revealed a heterogenous predominantly cystic left ovarian \nmass measuring 5.5x4.5cm. There was no ascites. Serum CA125 \nwas 41.58u/ml and Inhibin was raised at 83.3pg/ml. A clinical \ndiagnosis of benign cystic tumor in the ovary was considered with \nunexplained elevation of inhibin levels. Staging laprotomy with total \nabdominal hysterectomy, bilateral salpingo-oophorectomy, infracolic \nomentectomy and pelvic lymph node sampling was performed. \nPostoperative course was uneventful. The patient is currently on \nfollow up and well five months after surgery. \nPathological features\nThe left ovary measured 5.5cm in diameter and had a smooth \nencapsulated surface. The cut surface revealed multiple tiny cysts \nwith intervening solid yellowish areas. The cysts were filled with \nmucoid fluid. No hemorrhagic or necrotic areas were identified. \nUterus, cervix and bilateral fallopian tubes were unremarkable. The \nendometrial cavity was slit like, endometrial thickness being 0.7cm. \nThe right ovary was enlarged by a serous fluid filled cyst measuring \n1cm in diameter.\nMicroscopic sections from left ovary revealed variable sized cysts \nlined by single layered tall columnar mucin secreting epithelium \nof endocervical type. The epithelial cells stained positive with \nmucicarmine. Goblet cells were not identified. The epithelium did not \ndivulge any evidence of atypia, increased mitosis or multilayering. \nIntimately admixed with the benign mucinous component were diffuse \nsheets of plump to ovoid cells with uniform round to oval pale nuclei, \nmany with longitudinal nuclear grooves and indistinct cytoplasm \nreminiscent of granulosa cells. (Figure 1) Focal thecomatous areas \nand Call Exner bodies were seen.\nFigure 1 Granulosa cells with ovoid nuclei and occasional nuclear grooves \n(arrows). Columnar mucinous epithelium in left upper corner.\nObstet Gynecol Int J. 2021;12(3):190‒193. 190\n©2021 Malhotra et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which \npermits unrestricted use, distribution, and build upon your work non-commercially.\nAdult granulosa cell tumor with Mucinous \ncystadenoma of ovary: a unique case with insight \ninto histogenesis\nVolume 12 Issue 3 - 2021\nKiran Preet Malhotra,1 Ruquiya Afrose,2 Sarla \nAgarwal,3 Mrinalini Kotru4\n1Associate Professor, Department of Pathology, Dr. Ram \nManohar Lohia Institute of Medical Sciences, India \n2Assistant Professor JNMC AMU Aligarh, India\n3Retired Professort, Department of Pathology, University \nCollege of Medical Sciences and Guru T eg Bahadur Hospital, \nIndia\n4Professort, Department of Pathology, University College of \nMedical Sciences and Guru T eg Bahadur Hospital, India\nCorrespondence: Dr. Ruquiya Afrose, MD, Assistant Professor, \nDepartment of Pathology, JNMC, AMU, Aligarh, India, \nT el 9219716166, Email  \nReceived: June 01, 2021 | Published: June 21, 2021\nAbstract\nMixed ovarian tumors are of common occurrence. In this category are placed rare novelties \ndisplaying composite granulosa cell and mucinous tumor elements. Such a combination \nof stromal and epithelial elements may be a chance association of two discrete tumors. \nIntriguing still is the intimate admixture of these two elements which has been reported only \nin two cases till date. (1,2) We report the third such case and review the previous cases with \nan effort to elucidate their enigmatic histogenesis.\nKeywords: concurrent tumors, granulosa cell tumor, histogenesis, mucinous \ncystadenoma, ovary\nObstetrics & Gynecology International Journal\nCase Report\n Open Access\n\n\nAdult granulosa cell tumor with Mucinous cystadenoma of ovary: a unique case with insight into \nhistogenesis\n191\nCopyright:\n©2021 Malhotra et al. \nCitation: Malhotra KP , Afrose R, Agarwal S, et al. Adult granulosa cell tumor with Mucinous cystadenoma of ovary: a unique case with insight into histogenesis. \nObstet Gynecol Int J. 2021;12(3):190‒193. DOI: 10.15406/ogij.2021.12.00574\n Immunohistochemical staining showed pan cytokeratin and \nepithelial membrane antigen positivity in the mucinous epithelium. \nThe granulosa cells were positive for Vimentin, Inhibin and Calretinin. \n(Figure 2) The endometrium revealed simple hyperplasia and right \novary showed a follicular cyst. Cervix and tubes were unremarkable. \nThe pelvic lymph node showed reactive hyperplasia. \nFigure 2 Immunohistochemical profile of the tumor. A- Epithelial Membrane Antigen positivity in mucinous epithelium and B-Vimentin, C- Inhibin and D- \nCalretinin positivity in granulosa cells.\nA diagnosis of adult granulosa cell tumor with heterologous \nmucinous cystadenoma elements was rendered based on morphology \nand immunohistochemical findings. Hyperestrogenic features \nincluding postmenopausal bleeding, endometrial hyperplasia and \nsimple cyst in opposite ovary and raised Inhibin were supportive of an \nestrogen secreting granulosa cell tumor element.\nDiscussion\nMixed ovarian tumors with both elements of Mullerian derivation \none of which is an endocervical type of mucinous cystadenoma is \nof common occurrence and explained by the fact that tumor cells \ndifferentiate towards two closely related epithelial structures. 1,5 \nMucinous tumors found in association with teratomas are usually \nintestinal in type, of germ cell derivation and probably represent \novergrowth of the mucinous epithelium. A report of a concurrent \ngranulosa cell tumor, mucinous cystadenoma and cystic teratoma in \nthe same ovary exists.6 These were considered to represent secondary \ntumors arising from foci of sex cord stromal and epithelial cell \ndifferentiation in a cystic teratoma. \nThe histogenesis is difficult to explain when an epithelial tumor \ncoexists with another tumor of sex cord stromal origin outside the \nsetting of a teratoma. Upto 18% of cases of sertoli leydig cell tumors \nhave been found to contain mucinous cystadenomatous elements. 7 A \nstromal tumor with minor sex cord elements has also been reported in \nassociation with a mucinous cystadenoma. 8 It has been hypothesized \nthat the mucinous elements are of heterologous metaplastic origin, \nsupported by the fact that the two elements were closely intermingled \nand showed zones of transition from one cell type to another.3 \nFrom the literature available to us, four cases of mucinous \ncystadenoma and two of mucinous cystadenocarcinoma concurrent \nwith adult granulosa cell tumors could be identified. Their salient \nfeatures are presented in Table 1. The clinical features were akin to \ngranulosa cell tumors rather than mucinous cystadenomas including \npresentation at postmenopausal age groups with vaginal bleeding. \nSimilarly endometrial hyperplasia and polyp could be explained on \nthe basis of hyperestrogenic effect of the granulosa cell element. Two \nof the cases reported showed separate areas of mucinous epithelium \nand granulosa cell component without intermingling of the two. It is \nlikely that these resulted from the concurrent occurrence of two varied \ntumors which is not unexpected by chance.\nOur case similar to three earlier cases describes intimate \nassociation of the two elements with endocervical type epithelium.1,9,10 \nSuch intermingling cannot be explained by chance occurrence of \nthe two neoplasms together. Two theories can be considered for \nthis association- a likelihood that the mucinous elements represent \nheterologous metaplasia in a granulosa cell tumor and another of \nan origin of the granulosa cell tumor within the reactive stroma of a \nmucinous neoplasm. A heterologous metaplasia akin to sertoli leydig \ncell tumors concurrent with mucinous elements is unlikely since both \nintestinal and endocervical types of mucinous metaplasias have been \nreported. A point in favour is their association with endocervical type \nof epithelium which is of Mullerian derivation and likely to occur in \nan ovarian metaplasia, as opposed to intestinal epithelium which is \nforeign to the ovary.\n\nAdult granulosa cell tumor with Mucinous cystadenoma of ovary: a unique case with insight into \nhistogenesis\n192\nCopyright:\n©2021 Malhotra et al. \nCitation: Malhotra KP , Afrose R, Agarwal S, et al. Adult granulosa cell tumor with Mucinous cystadenoma of ovary: a unique case with insight into histogenesis. \nObstet Gynecol Int J. 2021;12(3):190‒193. DOI: 10.15406/ogij.2021.12.00574\nT able 1 Comparison of features of concurrent mucinous and granulosa cell tumors reported previously and the present case\nCase report Price et al Chandran \net al\nDoussia A \net al\nMcKenna \net al\nKushida Y \net al\nStaats PN \net al\nSubrahmanya \nNB et al Present case\nAge (years) 63 83 49 57 76 73 50 75\nPresentation\nLower \nabdominal \ndiscomfort, \ndistension\nPost \nmenopausal \nbleeding\nMenorrhagia\nAbd \ndistension, \nvomiting, wt \nloss\nLumbago\nPost \nmenopausal \nbleeding\nLower \nabdominal pain\nPost \nmenopausal \nbleeding\nParity 3 10 1 N/A N/A N/A 3 3\nInhibin level N/A N/A N/A N/A N/A N/A N/A 83.3pg/ml\nCA 125 level WNR N/A N/A 90 U/ml 120 U/ml 30 U/ml 19.44 41.6 U/ml\nU/mL\nOvary gross\nMultiple cysts \nwith thickened \nwalls\nSolid-cystic Cyst + nodule Cyst + \nnodule Solid-cystic Multilocular \ncysts\nMultilocular \ncysts\nMultilocular \ncysts; \nintervening solid \nareas\nOvarian size 20x16x11cm 10x10x7 4x2.5x1 30x28x20 10x7x7 22x14x14 8.5x5.5x4cm 6x6x5\nMucinous \nepithelium Endocervical Not \ndescribed Endocervical Intestinal Endocervical Intestinal Intestinal Endocervical\nMucinous \nNeoplasm Benign Malignant Benign Benign Benign Borderline \nmalignant Benign Benign\nMitoses Nil ++ Nil Upto 3/10hpf N/A N/A N/A Nil\nLeutinization Nil Scattered \nclumps Nil N/A N/A N/A Nil Nil\nThecomatous \nstroma Nil Present Nil Nil Prominent Prominent Nil Nil\nIHC \nmucinous \nelements\nAE1/AE3,CAM \n5.2, EMA,CEA\nCK,EMA, \nCEA N/A CK7, focal \nCK20\nCK (pan, \n7,18,19), \nCA125, \nS-100, focal \nCEA & EMA\nN/A CK 20,7 CK, EMA\nIHC \ngranulosa \ncomponent\nVimentin Vimentin N/A Inhibin, \ncalretinin\nVimentin, \nCK \n(18,19,focal \npan), focal \nCarletinin. \nInhibin α \nnegative\nN/A\nFocal Inhibin \nCD99; \nCalretinin\nVimentin, \nInhibin,calretinin\nOpposite \novary U/R Small, \natrophic U/R U/R N/A Cystic N/A Cystic follicle\nUterus\nNo e/o \nhyperplasia in \nhysterectomy \ndone 13 \nyears prior to \ndevelopment \nof ovarian \ntumor\nBenign \ncystic \nhyperplasia\nLeiomyomata; \nendometrium \nU/R\nEndometrial \npolyp U/R\nLeiomyomata, \nadenomyosis, \nweakly \nproliferative\nLeiomyomata Simple \nhyperplasia\nT ubes,cervix U/R U/R U/R U/R U/R U/R U/R U/R\nProposed \nhistogenesis Heterologous Composite Composite Heterologous\nreactive \nstromal \nhyperplasia \nin a pre-\nexisting \nmucinous \nneoplasm\nThecomatous \nstroma of \na mucinous \nneoplasm\nHeterologous Heterologous\nN/A, data not available; WNR, within normal range; U/R, unremarkable; CK, Cytokeratin; EMA, epithelial membrane antigen; CEA, carcino embryonic antigen \n\nAdult granulosa cell tumor with Mucinous cystadenoma of ovary: a unique case with insight into \nhistogenesis\n193\nCopyright:\n©2021 Malhotra et al. \nCitation: Malhotra KP , Afrose R, Agarwal S, et al. Adult granulosa cell tumor with Mucinous cystadenoma of ovary: a unique case with insight into histogenesis. \nObstet Gynecol Int J. 2021;12(3):190‒193. DOI: 10.15406/ogij.2021.12.00574\nMc kenna et al reported close intermingling of granulosa cell \nelements with intestinal type of mucinous epithelium.4 This is similar \nto the cases of sertoli leydig cell tumors with intestinal mucinous \nepithelium.5 Further studies are warranted to explain the origin of \nsuch mixed tumors. The possibility of a teratomatous origin cannot be \ndisregarded in such cases.\nConclusion\nWe report this rare case of heterologous benign mucinous \nmetaplasia in a granulosa cell tumor. The recognition of such an \nentity aids in understanding its histogenesis and is a teaching point \nfor Gynecologists and Pathologists whereby the hyperestrogenic \nfeatures of a cystic tumor likely to be denoted a benign cystadenoma \non radiology can be explained. The prognostic implications of this \nassociation are yet to be seen.\nAcknowledgments\nNone.\nFunding \nNone.\nConflicts of interest \nThe authors declare no conflicts of interest in preparing this article.\nReferences\n1. Price A, Russell P, Elliott P, et al. Composite mucinous and granulosa-cell \ntumor of ovary: case report of a unique neoplasm. Int J Gynecol Pathol . \n1990;9:372–378.\n2. Chandran R, Rahman H, Gebbie D. Composite mucinous and granulosa-\ntheca-cell tumour of the ovary: an unusual neoplasm. Aust NZ J Obstet \nGynaecol. 1993;33(4):43743–43749.\n3. Doussis-Anagnostopoulou IA, Remadi S, Czernobilsky B. Mucinous \nelements in Sertoli-Leydig and granulosa cell tumours: a reevaluation. \nHistopathology. 1996;28:372–375.\n4. McKenna M, Kenny B, Dorman G, et al. Combined adult granulosa cell \ntumor and mucinous cystadenoma of the ovary: granulosa cell tumor with \nheterologous mucinous elements. Int J Gynecol Pathol. 2005;24:224–227.\n5. Kurman RJ. Blaustein’s Pathology of the female genital tract. 5th edn. \nNew York: Springer; 2004.\n6. Moid FY , Jones RV . Granulosa cell tumor and mucinous cystadenoma \narising in a mature cystic teratoma of the ovary: a unique case report and \nreview of literature. Ann Diag Pathol. 2004;8:96–101.\n7. Young RH, Prat J, Scully RE. Ovarian Sertoli-Leydig cell tumors with \nheterologous elements. I. Gastrointestinal epithelium and carcinoid: \na clinicopathologic analysis of thirty-six cases. Cancer (Phila) . \n1982;50:2448–2456.\n8. Yang SW, Cho MY , Jung SH, et al. Mucinous cystadenoma coexisting \nwith stromal tumor with minor sex-cord elements of the ovary: a case \nreport. J Korean Med Sci. 2001;16:237–240.\n9. Staats Paul N, Coutts Michael A, Young Robert H. Primary ovarian \nmucinous cystic tumor with prominent theca cell proliferation and focal \ngranulosa cell tumor in its stroma: case report, literature review, and \ncomparison with sertoli-leydig cell tumor with heterologous elements. Int \nJ Gynecol Pathol. 2010;29(3):228–233.\n10. Yoshio kushida reifi haba path international 2005;55(12):797–801.","source_license":"CC0","license_restricted":false}