{"paper_id":"2d2dd042-76b2-40b6-9b27-8372bb908df1","body_text":"BioMed Central\nPage 1 of 4\n(page number not for citation purposes)\nDiagnostic Pathology\nOpen AccessCase Report\nImmunohistochemical localization patterns for vimentin and other \nintermediate filaments in calcified ovarian fibrothecoma\nEric Scott Sills*1,6, Terrence B Doan2, R James Mock3, George R Dixson4 and \nMichael B Rohlfing5\nAddress: 1Department of Obstetrics, Gynecology & Reproductive Research, Murphy Medical Center, Murphy, NC, USA, 2Department of Surgery, \nMurphy Medical Center, Murphy, NC, USA, 3Gastroenterology Division, Department of Medicine, Murphy Medical Center, Murphy, NC, USA, \n4Department of Radiology, Murphy Medical Center, Murphy, NC, USA, 5Department of Pathology, Murphy Medical Center, Murphy, NC, USA \nand 675 Medical Park, Suite D, Murphy, NC 28906, USA\nEmail: Eric Scott Sills* - drsills@murphywomenscenter.com; Terrence B Doan - tbdoanmd@hotmail.com; R \nJames Mock - jmockmd@brmemc.net; George R Dixson - drdixson@hotmail.com; Michael B Rohlfing - mrohlfing@myway.com\n* Corresponding author    \nAbstract\nProblem: To describe immunohistochemical features encountered in ovarian fibrothecoma with\ncorrelation to clinical presentation and surgical management.\nMethod of study: A female age 75 presented for evaluation of melena. The patient reported total\nabdominal hysterectomy and removal of both ovaries 40 years earlier.\nResults: CA-125 was normal and there was no eviden ce of hyperestrogen effect. Pelvic CT\nrevealed a partially calcified 7 cm pelvic mass without adenopathy or ascites; ultrasound was\nconfirmatory. Endoscopy identified three beni gn intestinal tubular adenomas. Following\nlaparoscopic excision of the pelvic tumor imm unohistochemichal analys is of the mass showed\nnegative staining for keratin, S100 protein, inhibin, calretinin, melan A, smooth muscle actin, CD34,\nCD117, and desmin. The tissue was positive for vimentin, however.\nConclusion: Ovarian fibrothecomas represent an ovarian stromal neoplasm developing in a wide\nspectrum of clinical settings. Particularly if oophorectomy is stated to have been performed remote\nfrom the time of index presentation, the status of the ovaries must be considered whenever pelvic\npathology is encountered. We de scribe a calcified ovarian fi brothecoma identified during\ngastroenterology investigation and confirmed immunohistochemically via high amplitude vimentin\nsignal.\nBackground\nStromal tumors of the ovary include thecoma and\nfibroma, yet as differentiation between these two types\nmay be difficult the term fibrothecoma has emerged in\nrecognition of the similar immunohistochemical features\npresent in both. The exact incidence of fibrothecoma is\nunknown, although they have been described as rare ovar-\nian neoplasms [1]. Here we present an unusual clinical\nmanifestation of calcified ovarian fibrothecoma in the\nabsence of ascites, arising from a residual ovary intention-\nally conserved at laparotomy 40 years earlier.\nPublished: 11 September 2006\nDiagnostic Pathology 2006, 1:28 doi:10.1186/1746-1596-1-28\nReceived: 29 August 2006\nAccepted: 11 September 2006\nThis article is available from: http://www.diagnosticpathology.org/content/1/1/28\n© 2006 Sills et al; licensee BioMed Central Ltd.\nThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), \nwhich permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.\n\nDiagnostic Pathology 2006, 1:28 http://www.diagnosticpathology.org/content/1/1/28\nPage 2 of 4\n(page number not for citation purposes)\nCase report\nA non-smoking 75 year old Caucasian female presented\nfor gastroenterology evaluation due to rectal bleeding. She\nhad mild essential hypertension well controlled on\ndiltiazem, did not smoke, and had no other medical com-\nplaint. She reported intermittent oral use of aspirin, 81\nmg/d. In 1966, she underwent total abdominal hysterec-\ntomy \"when both ovaries were removed\". At the time of\nour evaluation, the patient used supplemental estrogen\noccasionally but was uncertain when this commenced.\nHer only other surgery was an uncomplicated laparo-\nscopic cholecystectomy performed in 1996.\nThe patient's BMI was 26. Vital signs and physical exam\nwere normal although a heme positive stool was noted.\nAbdominal CT showed no significant abnormality,\nalthough pelvic CT revealed a 7 cm partially calcified mass\nat the upper pelvic inlet, indistinguishable from bowel\n[Figure 1]. Ultrasound of this lesion confirmed a 74 × 45\n× 49 mm heterogeneous (partially echogenic) mass in the\nupper right pelvis.\nSerum electrolytes were unremarkable except for BUN and\nCr at 20 mg/dl and 1.1 mg/dl, respectively. Hemoglobin\nwas 11.8 g/dl. Serum hCG, CEA, and CA-125 were all nor-\nmal.\nSurgical management\nA 12 mm umbilical port was placed along with two acces-\nsory ports (both 5 mm caliber), one each at the left upper\nand lower quadrants. Extensive abdominal adhesions\nwere encountered and lysed with blunt dissection and\nharmonic scalpel. Eventually an approximately 7 cm\nsmooth, white glistening mass could be seen in the right\naspect of the pelvis [Figure 2]. The mass was attached lat-\nerally to the right pelvic sidewall; these connections were\nsecured with 10 mm endosurgical clips and then divided\nto free the tumor. Survey of abdomen and pelvis revealed\nno other gross abnormality. Estimated blood loss was ~50\nml and the patient was discharged home the same after-\nnoon in excellent condition.\nImmunohistochemistry protocol\nFormalin-fixed tumor sections embedded in paraffin were\nexposed to 10 mmol/L citrate buffer (pH 6.0), followed by\nincubation with 1:50 dilution of monoclonal mouse anti-\nvimentin (M0725, DakoCytomation, Carpinteria, CA,\nUSA) using 20 min heat-induced epitope retrieval in\nDakoCytomation Target Retrieval solution (S3308) × 30\nmin incubation at room temperature with primary anti-\nbody. Negative control was 1:50 dilution mouse IgG1\n(X0931) which was run simultaneously. Complexes were\nvisualized via DAKO LSAB+/HRP kit (K0679) and auto-\nmated stainer platform. The specimen demonstrated pos-\nitive vimentin staining for mesenchymal spindle and\nround cells, consistent with benign ovarian stromal neo-\nplasm [Figure 3]. The full panel consisted of antibodies to\nkeratin, S100, inhibin, calretinin, melanoma associated\nmarker \"Melan A\", smooth muscle actin, CD34, CD117\nand desmin, but none returned a positive result [Table 1].\nDiscussion\nWe report an unusual case of partially calcified ovarian\nfibrothecoma without ascites in an elderly female report-\ning previous oophorectomy and complaining of melena.\nFor this patient, her gastrointestinal bleeding was deter-\nRight ovarian fibrothecoma (F) and pedicle (P) at laparoscopyFigure 2\nRight ovarian fibrothecoma (F) and pedicle (P) at laparos-\ncopy. Calcified nodule is shown superiorly (arrow).\nF\nP\nPelvic CT demonstrating 7 cm fibrothecoma (F) in the upper right pelvis and associated calcification (arrow)Figure 1\nPelvic CT demonstrating 7 cm fibrothecoma (F) in the upper \nright pelvis and associated calcification (arrow). No ascites or \nbowel dilation is present. Uterus and left ovary are surgically \nabsent in this 75 year-old patient.\nF\n\nDiagnostic Pathology 2006, 1:28 http://www.diagnosticpathology.org/content/1/1/28\nPage 3 of 4\n(page number not for citation purposes)\nmined to be secondary to benign polyps, although it was\nduring the work-up associated with this lesion that suspi-\ncion was raised regarding a 7 cm calcified right pelvic\nmass. While this mass did appear benign intraoperatively,\nmetal endosurgical clips were deployed to assist subse-\nquent radiographic localization of tumor site in the event\nadjuvant radiotherapy was indicated. Excision of the\ntumor at laparoscopy confirmed its ovarian origin, and\nimmunohistochemical labeling was performed to charac-\nterize it more fully as a benign fibrothecoma.\nOther investigators have commented on the protean\nnature of ovarian tumors in this group that may occur in\nthe setting of edema [2], elevated CA-125 [3,4], and preg-\nnancy [5]. While immunohistochemical features of this\nneoplasm have been described previously [6-8], the the-\ncoma-fibroma group of ovarian stromal tumors repre-\nsents a spectrum of lesions in which clear distinctions\nbetween various entities are difficult to define6. However,\ntumor calcification and low serum CA-125 are infrequent\nfindings.\nOne finding that proved useful in finalizing the diagnosis\nfor our patient was the high affinity for vimentin staining,\ncharacteristic of ovarian fibrothecoma [2]. Vimentin is a\n57 kD intermediate filament protein forming the cytoskel-\neton of vertebrate cells. The protein was initially thought\nto be preferentially retained in malignant mesenchymal\ntissues, although coexpression of intermediate filaments\n(particularly cytokeratin and vimentin) was subsequently\nshown to exist in many benign lesions. Accordingly,\napplication of multiple antibodies is recommended to\nformulate a diagnosis with sufficient precision, as demon-\nstrated in our case. Indeed for this calcified ovarian\nfibrothecoma, vimentin was the only positive immuno-\nhistochemical marker registered from a panel of ten anti-\nbodies.\nThe impact of patient recall error while obtaining the sur-\ngical history also warrants comment. A variant of residual\novary syndrome, the problem begins when the patient is\nunaware of an ovary intentionally conserved at surgery.\nThe ovary subsequently develops a pathologic process or\ncauses symptoms necessitating its removal in a second\noperation [9]. Not surprisingly, this is more likely among\nsubjects of advanced age who may have never known (or\nforgotten) important details of an operation performed\nlong ago and for which no written record can be obtained.\nOur patient had believed that she had no ovaries for 40\nyears, a \"fact\" dutifully reported to multiple physicians\nover time. Could awareness of her retained single ovary\nhave alerted this patient's caregivers to the presence of\novarian fibrothecoma sooner? Certainly when hysterec-\ntomy-oophorectomy is stated to have been performed\nremote from the time of index presentation, an in situ\novary should still be considered whenever pelvic pathol-\nogy is encountered.\nTable 1: Immunohistochemical characteristics observed in calcified ovarian fibrothecoma without ascites.\nAssay/antibody Tissue marker for Result\nVimentin Vimentin, intermediate  filaments, mesenchymal cells +\nCAM 5.2 Keratin: 39, 43, 48, 50, 50.6 kD -\nS100 S100 Protein, nerve sheath tumor, melanoma, chondrocyte -\nInhibin Sex cord stromal tumo rs, adrenal (cortical) tumors -\nCalretinin Ca ++ binding protein, mesothelial cells, sex cord stromal tumors -\nMelan A Melanoma asso ciated marker, adrenal (cortical) tumors -\nSMA Smooth muscle actin, myof ibroblasts, myoepithelial cells -\nCD34 Endothelial and stem  cells, GI stromal tumor -\nCD117 Myeloid and mast cells , GI stromal tumor (c-kit) -\nDesmin Muscle, desmoplast ic small round cell tumor -\nMicroscopic features of ovarian fibrothecoma include round and spindle shaped nuclei without atypia or myxoid changeFigure 3\nMicroscopic features of ovarian fibrothecoma include round \nand spindle shaped nuclei without atypia or myxoid change. \nNo mitotic figures were observed. Standard H&E (H) and \nvimentin stain (V), 40× magnification.\nH V\n\nPublish with BioMed Central   and  every \nscientist can read your work free of charge\n\"BioMed Central will be the most significant development for \ndisseminating the results of biomedical research in our lifetime.\"\nSir Paul Nurse, Cancer Research UK\nYour research papers will be:\navailable free of charge to the entire biomedical community\npeer reviewed and published immediately upon acceptance\ncited in PubMed and archived on PubMed Central \nyours — you keep the copyright\nSubmit your manuscript here:\nhttp://www.biomedcentral.com/info/publishing_adv.asp\nBioMedcentral\nDiagnostic Pathology 2006, 1:28 http://www.diagnosticpathology.org/content/1/1/28\nPage 4 of 4\n(page number not for citation purposes)\nReferences\n1. Conte M, Guariglia L, Benedetti Panici P, Scambia G, Rabitti C, Capelli\nA, Mancuso S: Ovarian fibrothecoma: sonographic and histo-\nlogic findings.  Gynecol Obstet Invest 1991, 32:51-54.\n2. 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