{"paper_id":"b7b8c7e8-88f3-488d-bf12-b314b6c8061e","body_text":"C A S E R E P O R T Open Access\nEndometriosis-associated clear cell\ncarcinoma arising in caesarean section scar:\na case report and review of the literature\nGabriella Ferrandina 1,2*, Eleonora Palluzzi 2, Francesco Fanfani 3, Stefano Gentileschi 4, Anna Lia Valentini 5,\nMaria Vittoria Mattoli 6, Ilaria Pennacchia 7, Giovanni Scambia 2 and Gianfranco Zannoni 7\nAbstract\nBackground: Malignant transformation has been reported in approximately 1% of the endometriosis cases; herein,\nwe report a case of clear cell endometrial carcinoma arising from endometriosis foci located within a caesarean\nsection scar.\nCase presentation: In November 2014, a Caucasian, 44-year-old woman was transferred to our institution because\nof severe respiratory failure due to massive lung embolism and rapid enlargement of a subcutaneous suprapubic\nmass. Abdomino-pelvic magnetic resonance showed a 10.5 × 5.0 × 5.0 cm subcutaneous solid mass involving the\nrectus abdominis muscle. Pelvic organs appeared normal, while right external iliac lymph nodes appeared enlarged\n(maximum diameter = 16 mm). A whole-body positron emission tomography/computed tomography scan showed\nirregular uptake of the radiotracer in the 22 cm mass of the abdominal wall, and in enlarged external iliac and inguinal\nlymph nodes. In December 2014, the patient underwent exploratory laparoscopy showing normal adnexae and pelvic\norgans; peritoneal as well as cervical, endometrial and vesical biopsies were negative. The patient was administered\nneo-adjuvant chemotherapy with carboplatin and paclitaxel, weekly, without benefit and then underwent wide\nresection of the abdominal mass, partial removal of rectus abdominis muscle and fascia, radical hysterectomy,\nbilateral salpingo-oophorectomy, and inguinal and p elvic lymphadenectomy. The muscular gap was repaired\nemploying a gore-tex mesh while the external covering was made by a pedicled perforator fasciocutaneous\nanterolateral thigh flap. Final diagnosis was clear cell endometrial adenocarcinoma arising from endometriosis\nfoci within the caesarean section scar. Pelvic and inguinal lymph nodes were metastatic. Tumor cells were positive for\nCK7 EMA, CKAE1/AE3, CD15, CA-125, while immunoreaction for Calretinin, WT1, estrogen, and progesterone receptors,\ncytokeratin 20, CD10, alpha fetoprotein, CDX2, TTF1, and thyroglobulin were all negative. Liver relapse occurred after\n2 months; despite 3 cycles of pegylated liposomal doxorubicin (20 mg/m 2, biweekly administration), the death of the\npatient disease occurred 1 month later.\nConclusions: Attention should be focused on careful evaluation of patient history in terms of pelvic surgery, and\nsymptoms suggestive of endometriosis such as repeated occurrence of endometriosis nodules at CS scar, or cyclic\npain, or volume changes of the nodules.\n* Correspondence: gabriella.ferrandina@gmail.com\n1Department Medicine and Health Sciences, University of Molise,\nCampobasso/Gynecologic Oncology Unit, Campobasso, Italy\n2Gynecologic Oncology Unit, Fondazione “Policlinico Universitario A.\nGemelli”, Rome, Italy\nFull list of author information is available at the end of the article\n© The Author(s). 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0\nInternational License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and\nreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to\nthe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver\n(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.\nFerrandina et al. World Journal of Surgical Oncology  (2016) 14:300 \nDOI 10.1186/s12957-016-1054-7\n\nBackground\nMalignant transformation has been reported in approxi-\nmately 1% of the endometriosis cases, and most fre-\nquently this transformation takes place at the ovary,\naccounting for about 80% of the endometriosis-associated\nmalignancies [1].\nEndometriosis occurring in surgical abdominal scar\nhas been mainly documented after caesarean section\n(CS) or hysterectomy (0.03 up to 0.4%), and its malig-\nnant transformation is very rare [2]: clear cell histology\naccounts for only 4.5% of extragonadal endometriosis-\nassociated malignancies, while representing the most\ncommon histotype in case of parietal localization [1].\nGiven the rarity of malignant transformation of abdomi-\nnal scar endometriosis to clear cell histology, pathogenesis\nand risk factors of this disease are hardly assessable [3].\nNonetheless, due to the increased rate of CS registered in\nthe last years, we can expect a parallel increase of endo-\nmetriosis implants in the CS scar and occurrence of clear\ncell carcinoma (CCC) of the abdominal wall.\nHerein, we report a new case of CCC arising from\nendometriosis foci located within a CS scar; a systematic\nreview of the available literature relative to this issue is\nalso presented.\nCase presentation\nIn November 2014, a Caucasian, 44-year-old woman was\ntransferred to our institution from the emergency unit\nof another hospital where she had been successfully\ntreated for a severe respiratory failure due to massive\nlung embolism and cardiogenic shock.\nHer familial history was uneventful; she had under-\ngone one caesarean section 9 years before without com-\nplications and had assumed oral contraceptives until the\nappearance of symptoms. She had never suffered from\nsigns or symptoms of endometriosis.\nThe patient referred to have documented, since the\nlast 5 months, the slow enlargement of a suprapubic\nmass at the CS scar (lower abdominal incision) and ab-\ndominal swelling.\nIn July 2014, she had already performed abdomino-\npelvic magnetic resonance imaging (MRI) showing a\n10.5×5.0×5.0 cm subcutaneous solid mass with cystic\nareas and internal septa involving the rectus abdominis\nmuscle. The mass appeared strictly adherent to the\nuterus and recto-sigma. Pelvic organs appeared normal,\nwhile right external iliac lymph nodes appeared enlarged\n(short axis maximum diameter = 16 mm).\nThe patient had been already triaged to fine needle\naspiration (FNA) of the mass which was suggestive of\nendometrial tubule-papillary carcinoma.\nAt physical examination, a suprapubic mass of almost\n20 cm maximum diameter was documented close to the\nmidpoint of the CS scar (Fig. 1a –c). Laboratory tests\nrevealed normal levels of CEA, CA125, and squamous\ncell carcinoma antigen.\nOnce the patient recovered from the acute phase of\nlung embolism and achieved haemodynamic compen-\nsation, a whole-body positron emission tomography/\ncomputed tomography (PET/CT) scan was performed\nabout 60 min after the intrav enous administration of\n18F-FDG (148 MBq), showing irregular/non-homoge-\nneous uptake of the radiotracer in the 22 cm mass of\nthe abdominal wall. Increased 18F-FDG uptake was\nalso seen in enlarged external iliac and inguinal lymph\nnodes bilaterally (Fig. 2b, c, e, f ). Abdomino-pelvic\nMRI performed in our institution documented normal\nuterus and adnexae, and confirmed the presence of the\nanterior abdominal wall mass composed of solid as\nwell as locular areas; the mass completely infiltrated\nthe rectus muscle of abdomen and extended up to the\nskin surface, while displacing intestinal loops. The\ncleavage planes neighboring the uterus and bladder\nappeared preserved as well as the inguinal, external\niliac, and obturator lymph nodes (Fig. 2a, d).\nIn December 2014, the patient underwent exploratory\nlaparoscopy showing normal adnexae and pelvic organs;\nFig. 1 Clinical appearance of the patient at time of presentation (a–c): a\nlarge mass (a, b) extended from the pubic symphysis to the umbilicus\nwas evident; the mass appeared mainly solid with some cystic lesions\non the surface. The caesarean section scar is evident ( white arrow ).\nAppearance of the abdominal reconstruction after 2 months from\nsurgery ( d)\nFerrandina et al. World Journal of Surgical Oncology  (2016) 14:300 Page 2 of 8\n\nperitoneal as well as cervical, endometrial, and vesical\nbiopsies were negative.\nConsidering the results of FNA suggesting primary\nMüllerian-derived carcinoma and the extent of disease\nwhose radical resection would require widely demolitive\nsurgical procedures, the patient was triaged to neo-\nadjuvant chemotherapy with carboplatin (AUC = 2), and\npaclitaxel (80 mg/m 2), every week. After 3 cycles (9 ad-\nministrations) MRI documented only a slight reduction\nof the mass and lymphadenopathies, thus leading to\nconsider the need of a multidisciplinary approach with\ngynecologic and medical oncologists, surgeons, and plas-\ntic surgeons in order to plan the most adequate patient\ntreatment. After a thorough evaluation, radical surgery\nwith reconstruction was planned, and an extensive coun-\nseling was carried out with the patient and her relatives.\nAt the beginning of March 2015, the patient under-\nwent wide resection of the abdominal mass, partial re-\nmoval of rectus abdominis muscle and fascia; moreover,\nradical hysterectomy, bilateral salpingo-oophorectomy\n(BSO) as well as inguinal and pelvic lymphadenectomy\nwere performed.\nAt the end of surgery, the abdominal wall defect ap-\npeared as a round hole of 14 × 14 cm which involved the\nabdominal wall thickness completely. The muscular gap\nwas repaired employing a gore-tex mesh anchored directly\non the residual rectus muscles and sheets. The external\ncovering had been planned by a pedicled perforator fascio-\ncutaneous anterolateral thigh flap. The perforator vessels\nfrom the descending branch of the lateral circumflex\nfemoral artery had been preoperatively located, with ultra-\nsound doppler sonography, at the level of the intermuscu-\nlar lateral septum of the thigh. The right thigh was chosen\nas donor site because the perforators were more distal,\nthus allowing to lengthen the pedicle. The donor site, on\nthe right thigh, was repaired both by direct closure, and a\nskin graft harvested from the contralateral thigh. Postope-\nrative course of the wounds was uneventful and stitches\nwere removed at 2 weeks. The patient was discharged\nafter 18 days in good clinical conditions, and the cosmetic\nresult was acceptable (Fig. 1d).\nMacroscopically, the surgical specimen consisted of\ncutis and subcutaneous tissue which contained a capsu-\nlated tumor mass measuring 18 cm in maximum diame-\nter, infiltrating the rectus abdominis muscle. The cut\nsurface was whitish and showed areas of necrosis and\nhemorrhage. Histological examination of tissue samples\nrevealed neoplastic proliferation of large-sized, epithelio-\nmorphous cells with abundant clear or occasionally eosino-\nphilic cytoplasm and prominent nucleoli. A remarkable\ndegree of nuclear atypia with diffuse hyperchromasia and\nirregular nuclear contours, and cellular pleomorphism was\nevident throughout the whole lesion. Architecturally, the\ntumor featured a mixed pattern of growth, both solid and\ntubulocystic, occasionally including distinctive papillary\nareas with hyalinized stromal cores. The clear cells lining\nthe papillae and the cystic spac es showed the characteristic\nhobnail appearance. A few eosinophilic hyaline globules\nwere observed as well (Fig. 3a –c). Interestingly, sparse foci\nof endometriosis were present in the fibrous adipose tissue\nall around. Surgical margins were free of disease.\nImmunohistochemical investigation showed positive\ntumor cell reaction for CK7 (Fig. 3d), EMA, CKAE1/\nAE3, CD15, CA-125. On the contrary, immunoreaction\nfor Calretinin, WT1, estrogen, and progesterone recep-\ntors, cytokeratin 20, CD10, alpha fetoprotein, CDX2,\nTTF1, and thyroglobulin were all negative. Hence, the\nmorphologic findings and the immunohistochemical re-\nsults were consistent with a diagnosis of clear cell\nadenocarcinoma most likely arising in the setting of an\na b c\nde f\nFig. 2 Pre-surgical T2-weighted FSE sagittal MRI ( a) documenting a\nsupra-vesical pelvic mass extending into the anterior pelvic wall and\nshowing non-homogeneous signal intensity and solid components.\nSagittal CT ( b)a n df u s e d18F-FDG PET/CT ( c) images showed non-\nhomogeneous uptake in the 22 cm abdominal mass: in particular,\nintense abnormal 18F-FDG uptake was present in the caudal solid\ncomponent of the mass, whereas an absent area of tracer uptake\nwas evident in its cranial fluid component. Corresponding T2-weighted\nFSE axial MRI (d) confirmed the presence of a solid and partially fluid\npelvic mass, and enlarged loco-regional lymph nodes (arrow). Axial CT\n(e) and fused 18F-FDG PET/CT images (f) showed intense tracer uptake\nin the solid component of the mass, extended up to the skin surface\nof pelvis, and enlarged left external iliac lymph-node, characterized by\nincreased tracer uptake (arrows)\nFerrandina et al. World Journal of Surgical Oncology  (2016) 14:300 Page 3 of 8\n\nabdominal wall endometriosis. Lymph node involvement\nwas documented in 7 out of 14 pelvic lymph nodes, and\nin 8 out of 11 inguinal lymph nodes.\nAfter 2 months from surgery, the patient was submit-\nted to total body CT scan in order to plan subsequent\nadjuvant treatment. Despite the absence of disease in the\npelvis, CT scan documented the appearance of six neo-\nplastic lesions (from 2.7 to 5.5 cm maximum diameter)\nin the liver. Treatment with pegylated liposomal doxo-\nrubicin (20 mg/m 2, biweekly administration) was started,\nand CT scan evaluation after 3 cycles showed the pro-\ngression of hepatic involvement and appearance of asci-\ntes. The death of the patient disease occurred 1 month\nlater.\nDiscussion\nWe have provided an additional patient to the series of\n22 cases of endometriosis-associated CCC arising within\nCS scar, as reported in the literature [4 –24]. Only 2 re-\nports were not available from the requested authors.\nDespite the rarity of this condition, the number of re-\nported cases has increased over time (see Table 1) likely\ndue to a higher attention focused on this disease, but\nalso to the increased rate of CS and uterine surgeries\ndocumented over time. Therefore, more diffuse aware-\nness of this condition and better understanding of its\npathogenesis could be important to provide early diag-\nnosis and more effective treatment.\nEven though the criteria for the diagnosis of\nendometriosis-associated malignancies include also the\ncoexistence of neoplastic endometrial tissue and endo-\nmetriosis, almost one third of CCC arising within CS\nscars were not associated with endometriosis foci (T able 1).\nHowever, it has to be considered that four patients had re-\nferred cyclic pain in the CS scar during menses, or the\ncyclic increase/decrease of the mass volume, which could\nbe highly suggestive of the presence of endometriosis\nimplants [14, 17, 19, 23]. Moreover, previous history of the\nexcision of benign endometriosis foci at the CS scar was\nreported in five cases [9, 11, 13, 15, 16]. Therefore, the ab-\nsence of pathologically assessed endometriosis foci could\nbe interpreted as either a sampling problem or a conse-\nquence of the complete replacement of normal tissue due\nto massive neoplastic proliferation. In this context,\ncareful collection and evaluation of patient history\nwould be important to have a high index of suspicion\nfor endometriosis-associated malignancy.\nIndeed, these masses usually reach very large dimen-\nsions (median diameter: 9 cm, range 2.5 up to 22 cm)\n(Table 1) before the diagnosis is made, thus highlighting\nthe difficulties to suspect this condition and obtain an\nearly diagnosis. This is clinically relevant since primary\nsurgical treatment very frequently requires wide surgical\nexcision of the mass together with partial removal of\npart of the abdominal muscles and reconstructive sur-\ngeries with a mesh or even pedicle-skin-muscle flap.\nDemolitive surgery was also necessary in the 3 cases ini-\ntially triaged to neo-adjuvant chemotherapy ([13, 18]\ncurrent case), since only 1 of them achieved partial re-\nsponse after 8 cycles of carboplatin/paclitaxel chemo-\ntherapy [18]; in addition, wide excision was necessary in\nthe 2 cases who had undergone excision of endometriosis\nnodules at the CS scar in the past, and had been unsuc-\ncessfully treated with GnRh and progestins, respectively,\nbefore being triaged to radical surgery which led to defini-\ntive diagnosis of malignancy. Besides wide resection of the\nmass, other surgical procedures were often carried out\nincluding BSO (82.6%), as well as hysterectomy (71.4%),\nor endometrial biopsy (9.5%, and omentectomy or omen-\ntal biopsy (30.4%), in order to exclude other primary\ntumors sites.\nDespite the aggressiveness of surgery and the multi-\nmodal treatment approach, of 18 cases with available\nfollow up data, 10 experienced relapse of disease, mostly\nat distant sites, and 8 patients died of disease.\nApart from the long time interval to diagnosis and\nthe wide extension of disease in the abdominal wall,\nFig. 3 The tumor displayed a mixed pattern of both tubulocystic\nand papillary growth, HE x5 ( a), and HEx10 ( b); cells were large with\nabundant clear or occasionally eosinophilic cytoplasm. Note the\nhigh-grade nuclear atypia, HEx20 ( c); neoplastic cells showed positive\ncell membrane immunostaining for CK7 (x20) (d)\nFerrandina et al. World Journal of Surgical Oncology  (2016) 14:300 Page 4 of 8\n\nTable 1 Clear cell carcinoma arising from endometriosis of the scar caesarean section\nAge Previous uterine\nsurgeries\nMonths since\nsymptoms\nSize cm FNA or biopsy Primary treatment Pathology Adjuvant\ntreatment\nRelapse Death\nSchnieber Agner-Kolb\n1986 [ 4]\n40 1 CS 15 years before –– – WE, BSO, Hys Mass: CCC + endometriosis\nOvaries and uterus:\nnegative\nRT, progestins – Yes after\n18 months\nHitti, 1996 [ 5] 46 1 CS 14 years before\n1 CS 12 years before\n– 6 – WE, BSO, Hys CCC + endometriosis RT No after\n30 months\nNo after\n30 months\nMiller 1998 [ 6] 38 1 hysterotomy 9 years\nbefore\n1 abortion 3 years\nbefore\n1 CS 2 years before\n8 4 CCC + endometriosis WE, BSO, Hys\nomentectomy\nScar: CCC\nOvaries, uterus,\nomentum: negative\nMargins: close\nCIS-based\nCT\nRT\nNo after\n60 months d\nNo after\n60 months d\nPark 1999 [ 7] 56 1 CS 24 years\n1 CS 20 years\n– 5 – WE Mass: CCC + endometriosis RT ––\nIshida 2003 [ 8] 56 1 CS 24 years\n1 CS 20 years\n7 10 Endometrial carcinoma WE, Hys, BSO Mass: CCC\nOvaries and uterus:\nnegative\nCIS-based\nCT\n– Yes after\n24 months b\nSergent 2006 [ 9] 45 1 CS 25 years\n1 CS 23 years\n2 excisions of benign\nendometriosis nodules\nat the scar\n17 20 – WE, BSO,\nlater on: endometrial\ncurettage\nMass: CCC + endometriosis\nRight ovary: benign\nendometriosis; left ovary\nand uterus: negative\nMargins: 1 cm free\nNot done Yes early after\nsurgerya\nYes after\n6 months\nAlberto 2006 [ 10] 38 1 CS 11 years\nBSO, Hys for\nendometriosis\n66 – WE CCC Carbo/PTX\nRT\n––\nRazzouk 2007 [ 11] 46 1 CS 26 years before\n1 CS 24 years before\n2 excisions of\nendometriosis nodules\nat the scar\n– >20 – GnRh analogue without\nbenefit WE, BSO\nMass: CCC + endometriosis\nOvaries: negative\nLN: 1 positive\nCarbo/PTX Yes during CT Yes after\n6 monthsb\nRust 2008 [ 12]4 2 3 C S\nHys 5 years before\n24 5 Carcinoma WE Mass: CCC + endometriosis\nMargins: 1 mm free\nNot done ––\nBats 2008 [ 13] 38 1 CS 13 years before\n1 excision of\nendometriosic nodule\nat the scar\n– 10 Atypical cells NACT (carbo/PTX)\nNo benefit WE, BSO,\nHys, omentectomy\nMass: CCC + endometriosis\nUterus: adenomyosis\nOther specimens:\nnegative\nMargins: 2 mm free\nNot done Yes after 4 months a –\nWilliams 2009 [ 14] 53 1 CS 17 years before 24 2.5 CCC (excisional\nbiopsy)\nWE of the scar, BSO,\nHys, omentectomy\nInguinal/Pelvic LNctomy\nMass: CCC\nUterus, right ovary,\nomentum: negative,\nleft ovary: teratoma\nInguinal LN: 7 positive/11\nPelvic LN: 8 positive/14\nCarbo/PTX\n(4 cycles)\nYes after 3 monthsa Yes after\n11 months b\nBourdel 2010 [ 15] 43 1 CS 20 years before\n1 CS 15 years before\n1 excision of\nendometriosic nodule\nat the scar\n99 – WE, partial resection of\npubic symphysis, umbilicus,\nright rectus abdomen,\npelvic LN sampling\nLater on: BSO, Hys\nMass: CCC + endometriosis\nPelvic LN: multiple positive\nOvaries, uterus: negative\nCarbo/PTX\n(6 cycles)\nRT\nYes after 6 monthsd Yes after\n22 months b\nFerrandinaet al. World Journal of Surgical Oncology (2016) 14:300 Page 5 of 8\n\nTable 1 Clear cell carcinoma arising from endometriosis of the scar caesarean section (Continued)\nYan 2011 [ 16] 41 2 CS 5 years before\n2 excisions of benign\nendometriosic nodule\nat the scar 1 year and\n4 months before\n4 9 Not done Progestins without\nbenefit WE\nMass: CCC CT No after\n24 months d\nNo after\n24 months d\nLi 2012 [ 17] 49 1 CS 26 years before 25 years 9 Not done WE, Hys, BSO Mass: CCC\nUterus, ovaries: negative\nCarbo/PTX\n(6 cycles)\nNoc after 8 months No c after\n8 months\nMert 2012 [ 19] 42 Tubal ligation, right\novariectomy\n– 15 Tumor cells\nMullerian origin\nNACT (carbo/PTX)\nWE, left SO Hys,\nleft Pelvic LNctomy\nOmentectomy\nMass: CCC + endometriosis\nOther organs: negative\nMargins: free\nNot done No after 1 month a No After\n1 month a\n51 2 CS\nHys for myomas\n12 6 Excisional biopsy\nCCC + endometriosis\nBSO, Omental biopsy Negative\nMargins: free\nRT No after\n31 months b\nNo after\n31 months b\nShalin 2012 [ 18] 47 1 CS 10 3 CCC WE, left ovary\ncystectomy,\nendometrial biopsy,\npelvic LN sampling\nMass: CCC + endometriosis\nOvarian cyst: endometriosis\nEndometrium: negative\nPelvic LN: 2 positive/4\nMargins: positive\nCIS-based\nCT (6 cycles)\nRT\nYes after 5 monthsb No after\n7 months b\nIjichi 2014 [ 20] 60 1 CS 37 years before\n1 CS 35 years before\n48 4 Atypical cells WE Mass: CCC + endometriosis\nMargins: free\nNot done Yes after 8 months a No after\n23 months a\nAust 2015 [ 21] 47 1 CS 16 years before\nvaginal Hys 10 years\nbefore\n61 0 – WE Later on: BSO,\npelvic, aortic LNctomy\nomentectomy\nMass: CCC\nOvaries and omentum:\nnegative\nLN:2 positive/48\nMargins: free\nCarbo/PTX\n(6 cycles)\nNo after\n10 months c\nNo after\n10 months c\nHeller 2014 [ 22]3 7 1 C S\n1C S\n1 CS 8 years before\n96* 18 CCC WE, left SO, pelvic\nLNctomy\nMass: CCC\nOvary: negative\nLFN: multiple LN positive\nRefused\ntreatment\nYes after 5 monthsa –\nLiu 2014 [ 23]3 9 1 C S\n1 excision of\nendometriosic nodule\nat the scar\n60 6 – WE, partial cystectomy,\nBSO, Hys, omentectomy,\ninguinal,pelvic, aortic\nLNctomy\nMass: CCC + endometriosis\nOvaries, uterus, omentum:\nnegative\nBladder: positive\nPelvic LN: 18 positive/21\nAortic LN: 6 positive /6\nInguinal LN: 8 positive/8\nCarbo/PTX\n(3 cycles)\nYES after\n10 months c\nYes after\n12 months c\nSosa-Duràn 2015 [ 24]4 5 1 C S\n1C S\n1C S\n69 – WE, margins: 2 cm free Mass: CCC + endometriosis Not done No after\n16 months a\nNo after\n16 months a\nCurrent case 44 1 CS 9 years before 8 22 Endometrial carcinoma NACT (carbo/PTX)\nWE, BSO, Hys, inguinal,\nand pelvic LNctomy\nMass: CCC + endometriosis\nOvaries, uterus: negative\nPelvic LN: 7 positive/14\nInguinal LN: 8 positive/11\nMargins: free\nNot done Yes after 2 months\nfrom surgery\nYes after\n6 months\nCCC clear cell carcinoma, CS caesarean section, WE wide mass excision, BSO bilateral salpingo-oophorectomy,SO salpingo-oophorectomy,Hys hysterectomy, LNctomy lymphadenectomy,LN lymph node, Carbo carboplatin,\nCIS cisplatin, PTX paclitaxel, RT radiotherapy\n*The mass was reported to have come and gone over the last 8 years since the last CS\naFrom surgical resection\nbFrom initial diagnosis\ncSince completion of chemotherapy\ndNot specified\nFerrandinaet al. World Journal of Surgical Oncology (2016) 14:300 Page 6 of 8\n\nclinical aggressiveness is also sustained by the intrinsic\nbiologic aggressiveness of CCC, which differs from\nother endometrial cancer hi stotypes. In this context,\nproper diagnosis should take advantage of immunohis-\ntochemical panels with several markers in order to ex-\nclude serous histotype as well as mesothelial tumors\nsuch as malignant mesothelioma and papillary meso-\nthelioma which are usually positive for Calretinin,\nWT1, and keratin 5/6, contrary to what is observed in\nCCC. In addition, WT1 is the most important immuno-\nhistochemical marker to distinguish serous carcinoma\nfrom CCC.\nIt has to be acknowledged that of 9 cases undergoing\nlymphadenectomy or sampling, 8 showed diffuse meta-\nstatic involvement of inguinal, and/or pelvic, and/or aor-\ntic lymph nodes ([11, 14, 15, 19, 22, 23] current case).\nOn the other hand, some cases were reported to ex-\nperience relatively longer disease-free and overall sur-\nvival ( ≥30 months) [5, 6, 16, 18]; while recognizing that\na more thorough molecular characterization could hope-\nfully help define prognosis of this very rare condition, it\nhas to be acknowledged that cases with better outcome\npresented with masses ranging between 4 and 9 cm, thus\nsuggesting that a prompt recognition and treatment\ncould make the difference.\nObviously, also prevention of endometriosis implant-\nation at time of CS is of utmost importance: as recently\nemphasized, the uterus should not be exteriorized, ex-\nposure of endometrial mucosa during uterus suturing\nshould be limited, and peritonization may be advised, al-\nthough there is no definitive data about these issues [15].\nConclusions\nAttention should be focused on careful evaluation of pa-\ntient history in terms of pelvic surgery, and symptoms\nsuggestive of endometriosis such as repeated occurrence\nof endometriosis nodules at CS scar, or cyclic pain, or\nvolume changes of the nodules.\nAbbreviations\nAUC: Area under curve; BSO: Bilateral salpingo-oophorectomy;\nCB: Carboplatin; CCC: Clear cell carcinoma; CIS: Cisplatin; CS: Caesarean\nsection; FNA: Fine needle aspiration; HYS: Hysterectomy; LN: Lymph node;\nLNCTOMY: Lymphadenectomy; MRI: Magnetic resonance imaging; PET/\nCT: Positron emission tomography/computed tomography; PTX: Paclitaxel;\nRT: Radiotherapy; WE: Wide mass excision\nAcknowledgements\nNone.\nFunding\nNo funding source to be declared.\nAvailability of data and materials\nAll data (imaging, pathology, immunohistochemistry, and procedures) are\navailable.\nAuthors’ contributions\nGF participated in the management of the patient and wrote the case\nreport. EP participated in the medical management of the patient. FF was\ninvolved in the surgical management of the patient. SG carried out plastic\nsurgery. ALV contributed to imaging characterization. MVM carried out\nimaging characterization. IP performed immunohistochemistry and\ncontributed to pathological characterization. GS participated in the\nmanagement of the patient and contributed to manuscript writing. GZ\nwas in charge of immunohistochemistry and pathological diagnosis. All\nauthors read and approved the final manuscript.\nCompeting interests\nThe authors declare that they have no competing interests.\nConsent for publication\nWe have obtained consent to publish from the legal relative (husband) of\nthe patient, since she passed away before the manuscript planning and writing.\nEthics approval and consent to participate\nAccording to our institutional ethical committee, no specific protocol is\nrequired for retrospective collection of data.\nAuthor details\n1Department Medicine and Health Sciences, University of Molise,\nCampobasso/Gynecologic Oncology Unit, Campobasso, Italy. 2Gynecologic\nOncology Unit, Fondazione “Policlinico Universitario A. Gemelli ”, Rome, Italy.\n3Department Medicine and Aging Sciences, University “GD ’Annunzio”,\nChieti-Pescara, Italy. 4Department Plastic and Reconstructive Surgery,\nFondazione “Policlinico Universitario A. Gemelli ”, Rome, Italy. 5Department\nRadiological Sciences, Institute of Radiology, Catholic University, Rome, Italy.\n6Institute of Nuclear Medicine, Fondazione “Policlinico Universitario A.\nGemelli”, Rome, Italy. 7Department Pathology, Catholic University, Rome, Italy.\nReceived: 14 October 2016 Accepted: 22 November 2016\nReferences\n1. Van Gorp T, Amant F, Neven P, Vergote I, Moerman P. Endometriosis and\nthe development of malignant tumors of the pelvis. A review of the\nliterature. Best Pract Res Clin Obstet Gynaecol. 2004;18:349 –71.\n2. Stevens EE, Pradhan TS, Chak Y, Lee YC. Malignant transformation of\nendometriosis in a cesarean section abdominal wall scar: a case report.\nJ Reprod Med. 2013;58(5-6):264 –6.\n3. Taburiaux L, Pluchino N, Petignat P, Wenger JM. Endometriosis-associated\nabdominal wall cancer. Int J Gynecol Cancer. 2015;25:1633 –8.\n4. Schnieber D, Wagner-Koib D. Malignant transformation of extragenital\nendometriosis. 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Clear cell\nadenocarcinoma arising from abdominal wall endometriosis. Cir Cir. 2016;\n84(3):245–9.\n•  We accept pre-submission inquiries \n  Our selector tool helps you to find the most relevant journal\n  We provide round the clock customer support \n  Convenient online submission\n  Thorough peer review\n  Inclusion in PubMed and all major indexing services \n  Maximum visibility for your research\nSubmit your manuscript at\nwww.biomedcentral.com/submit\nSubmit your next manuscript to BioMed Central \nand we will help you at every step:\nFerrandina et al. World Journal of Surgical Oncology  (2016) 14:300 Page 8 of 8","source_license":"CC0","license_restricted":false}