Endometriosis-associated clear cell carcinoma arising in caesarean section scar: a case report and review of the literature

Background: Malignant transformation has been reported in approximately 1% of the endometriosis cases; herein, we report a case of clear cell endometrial carcinoma arising from endometriosis foci located within a caesarean section scar. Case presentation: In November 2014, a Caucasian, 44-year-old woman was transferred to our institution because of severe respiratory failure due to massive lung embolism and rapid enlargement of a subcutaneous suprapubic mass. Abdomino-pelvic magnetic resonance showed a 10.5 × 5.0 × 5.0 cm subcutaneous solid mass involving the rectus abdominis muscle. Pelvic organs appeared normal, while right external iliac lymph nodes appeared enlarged (maximum diameter = 16 mm). A whole-body positron emission tomography/computed tomography scan showed irregular uptake of the radiotracer in the 22 cm mass of the abdominal wall, and in enlarged external iliac and inguinal lymph nodes. In December 2014, the patient underwent exploratory laparoscopy showing normal adnexae and pelvic organs; peritoneal as well as cervical, endometrial and vesical biopsies were negative. The patient was administered neo-adjuvant chemotherapy with carboplatin and paclitaxel, weekly, without benefit and then underwent wide resection of the abdominal mass, partial removal of rectus abdominis muscle and fascia, radical hysterectomy, bilateral salpingo-oophorectomy, and inguinal and p elvic lymphadenectomy. The muscular gap was repaired employing a gore-tex mesh while the external covering was made by a pedicled perforator fasciocutaneous anterolateral thigh flap. Final diagnosis was clear cell endometrial adenocarcinoma arising from endometriosis foci within the caesarean section scar. Pelvic and inguinal lymph nodes were metastatic. Tumor cells were positive for CK7 EMA, CKAE1/AE3, CD15, CA-125, while immunoreaction for Calretinin, WT1, estrogen, and progesterone receptors, cytokeratin 20, CD10, alpha fetoprotein, CDX2, TTF1, and thyroglobulin were all negative. Liver relapse occurred after 2 months; despite 3 cycles of pegylated liposomal doxorubicin (20 mg/m 2, biweekly administration), the death of the patient disease occurred 1 month later.

Attention should be focused on careful evaluation of patient history in terms of pelvic surgery, and symptoms suggestive of endometriosis such as repeated occurrence of endometriosis nodules at CS scar, or cyclic pain, or volume changes of the nodules. * Correspondence: [email protected] 1Department Medicine and Health Sciences, University of Molise, Campobasso/Gynecologic Oncology Unit, Campobasso, Italy 2Gynecologic Oncology Unit, Fondazione “Policlinico Universitario A. Gemelli”, Rome, Italy Full list of author information is available at the end of the article © The Author(s). 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Ferrandina et al. World Journal of Surgical Oncology (2016) 14:300 DOI 10.1186/s12957-016-1054-7

Malignant transformation has been reported in approxi- mately 1% of the endometriosis cases, and most fre- quently this transformation takes place at the ovary, accounting for about 80% of the endometriosis-associated malignancies [1]. Endometriosis occurring in surgical abdominal scar has been mainly documented after caesarean section (CS) or hysterectomy (0.03 up to 0.4%), and its malig- nant transformation is very rare [2]: clear cell histology accounts for only 4.5% of extragonadal endometriosis- associated malignancies, while representing the most common histotype in case of parietal localization [1]. Given the rarity of malignant transformation of abdomi- nal scar endometriosis to clear cell histology, pathogenesis and risk factors of this disease are hardly assessable [3]. Nonetheless, due to the increased rate of CS registered in the last years, we can expect a parallel increase of endo- metriosis implants in the CS scar and occurrence of clear cell carcinoma (CCC) of the abdominal wall. Herein, we report a new case of CCC arising from endometriosis foci located within a CS scar; a systematic review of the available literature relative to this issue is also presented. Case presentation In November 2014, a Caucasian, 44-year-old woman was transferred to our institution from the emergency unit of another hospital where she had been successfully treated for a severe respiratory failure due to massive lung embolism and cardiogenic shock. Her familial history was uneventful; she had under- gone one caesarean section 9 years before without com- plications and had assumed oral contraceptives until the appearance of symptoms. She had never suffered from signs or symptoms of endometriosis. The patient referred to have documented, since the last 5 months, the slow enlargement of a suprapubic mass at the CS scar (lower abdominal incision) and ab- dominal swelling. In July 2014, she had already performed abdomino- pelvic magnetic resonance imaging (MRI) showing a 10.5×5.0×5.0 cm subcutaneous solid mass with cystic areas and internal septa involving the rectus abdominis muscle. The mass appeared strictly adherent to the uterus and recto-sigma. Pelvic organs appeared normal, while right external iliac lymph nodes appeared enlarged (short axis maximum diameter = 16 mm). The patient had been already triaged to fine needle aspiration (FNA) of the mass which was suggestive of endometrial tubule-papillary carcinoma. At physical examination, a suprapubic mass of almost 20 cm maximum diameter was documented close to the midpoint of the CS scar (Fig. 1a –c). Laboratory tests revealed normal levels of CEA, CA125, and squamous cell carcinoma antigen. Once the patient recovered from the acute phase of lung embolism and achieved haemodynamic compen- sation, a whole-body positron emission tomography/ computed tomography (PET/CT) scan was performed about 60 min after the intrav enous administration of 18F-FDG (148 MBq), showing irregular/non-homoge- neous uptake of the radiotracer in the 22 cm mass of the abdominal wall. Increased 18F-FDG uptake was also seen in enlarged external iliac and inguinal lymph nodes bilaterally (Fig. 2b, c, e, f ). Abdomino-pelvic MRI performed in our institution documented normal uterus and adnexae, and confirmed the presence of the anterior abdominal wall mass composed of solid as well as locular areas; the mass completely infiltrated the rectus muscle of abdomen and extended up to the skin surface, while displacing intestinal loops. The cleavage planes neighboring the uterus and bladder appeared preserved as well as the inguinal, external iliac, and obturator lymph nodes (Fig. 2a, d). In December 2014, the patient underwent exploratory laparoscopy showing normal adnexae and pelvic organs; Fig. 1 Clinical appearance of the patient at time of presentation (a–c): a large mass (a, b) extended from the pubic symphysis to the umbilicus was evident; the mass appeared mainly solid with some cystic lesions on the surface. The caesarean section scar is evident ( white arrow ). Appearance of the abdominal reconstruction after 2 months from surgery ( d) Ferrandina et al. World Journal of Surgical Oncology (2016) 14:300 Page 2 of 8 peritoneal as well as cervical, endometrial, and vesical biopsies were negative. Considering the results of FNA suggesting primary Müllerian-derived carcinoma and the extent of disease whose radical resection would require widely demolitive surgical procedures, the patient was triaged to neo- adjuvant chemotherapy with carboplatin (AUC = 2), and paclitaxel (80 mg/m 2), every week. After 3 cycles (9 ad- ministrations) MRI documented only a slight reduction of the mass and lymphadenopathies, thus leading to consider the need of a multidisciplinary approach with gynecologic and medical oncologists, surgeons, and plas- tic surgeons in order to plan the most adequate patient treatment. After a thorough evaluation, radical surgery with reconstruction was planned, and an extensive coun- seling was carried out with the patient and her relatives. At the beginning of March 2015, the patient under- went wide resection of the abdominal mass, partial re- moval of rectus abdominis muscle and fascia; moreover, radical hysterectomy, bilateral salpingo-oophorectomy (BSO) as well as inguinal and pelvic lymphadenectomy were performed. At the end of surgery, the abdominal wall defect ap- peared as a round hole of 14 × 14 cm which involved the abdominal wall thickness completely. The muscular gap was repaired employing a gore-tex mesh anchored directly on the residual rectus muscles and sheets. The external covering had been planned by a pedicled perforator fascio- cutaneous anterolateral thigh flap. The perforator vessels from the descending branch of the lateral circumflex femoral artery had been preoperatively located, with ultra- sound doppler sonography, at the level of the intermuscu- lar lateral septum of the thigh. The right thigh was chosen as donor site because the perforators were more distal, thus allowing to lengthen the pedicle. The donor site, on the right thigh, was repaired both by direct closure, and a skin graft harvested from the contralateral thigh. Postope- rative course of the wounds was uneventful and stitches were removed at 2 weeks. The patient was discharged after 18 days in good clinical conditions, and the cosmetic

was acceptable (Fig. 1d). Macroscopically, the surgical specimen consisted of cutis and subcutaneous tissue which contained a capsu- lated tumor mass measuring 18 cm in maximum diame- ter, infiltrating the rectus abdominis muscle. The cut surface was whitish and showed areas of necrosis and hemorrhage. Histological examination of tissue samples revealed neoplastic proliferation of large-sized, epithelio- morphous cells with abundant clear or occasionally eosino- philic cytoplasm and prominent nucleoli. A remarkable degree of nuclear atypia with diffuse hyperchromasia and irregular nuclear contours, and cellular pleomorphism was evident throughout the whole lesion. Architecturally, the tumor featured a mixed pattern of growth, both solid and tubulocystic, occasionally including distinctive papillary areas with hyalinized stromal cores. The clear cells lining the papillae and the cystic spac es showed the characteristic hobnail appearance. A few eosinophilic hyaline globules were observed as well (Fig. 3a –c). Interestingly, sparse foci of endometriosis were present in the fibrous adipose tissue all around. Surgical margins were free of disease. Immunohistochemical investigation showed positive tumor cell reaction for CK7 (Fig. 3d), EMA, CKAE1/ AE3, CD15, CA-125. On the contrary, immunoreaction for Calretinin, WT1, estrogen, and progesterone recep- tors, cytokeratin 20, CD10, alpha fetoprotein, CDX2, TTF1, and thyroglobulin were all negative. Hence, the morphologic findings and the immunohistochemical re- sults were consistent with a diagnosis of clear cell adenocarcinoma most likely arising in the setting of an a b c de f Fig. 2 Pre-surgical T2-weighted FSE sagittal MRI ( a) documenting a supra-vesical pelvic mass extending into the anterior pelvic wall and showing non-homogeneous signal intensity and solid components. Sagittal CT ( b)a n df u s e d18F-FDG PET/CT ( c) images showed non- homogeneous uptake in the 22 cm abdominal mass: in particular, intense abnormal 18F-FDG uptake was present in the caudal solid component of the mass, whereas an absent area of tracer uptake was evident in its cranial fluid component. Corresponding T2-weighted FSE axial MRI (d) confirmed the presence of a solid and partially fluid pelvic mass, and enlarged loco-regional lymph nodes (arrow). Axial CT (e) and fused 18F-FDG PET/CT images (f) showed intense tracer uptake in the solid component of the mass, extended up to the skin surface of pelvis, and enlarged left external iliac lymph-node, characterized by increased tracer uptake (arrows) Ferrandina et al. World Journal of Surgical Oncology (2016) 14:300 Page 3 of 8 abdominal wall endometriosis. Lymph node involvement was documented in 7 out of 14 pelvic lymph nodes, and in 8 out of 11 inguinal lymph nodes. After 2 months from surgery, the patient was submit- ted to total body CT scan in order to plan subsequent adjuvant treatment. Despite the absence of disease in the pelvis, CT scan documented the appearance of six neo- plastic lesions (from 2.7 to 5.5 cm maximum diameter) in the liver. Treatment with pegylated liposomal doxo- rubicin (20 mg/m 2, biweekly administration) was started, and CT scan evaluation after 3 cycles showed the pro- gression of hepatic involvement and appearance of asci- tes. The death of the patient disease occurred 1 month later.

We have provided an additional patient to the series of 22 cases of endometriosis-associated CCC arising within CS scar, as reported in the literature [4 –24]. Only 2 re- ports were not available from the requested authors. Despite the rarity of this condition, the number of re- ported cases has increased over time (see Table 1) likely due to a higher attention focused on this disease, but also to the increased rate of CS and uterine surgeries documented over time. Therefore, more diffuse aware- ness of this condition and better understanding of its pathogenesis could be important to provide early diag- nosis and more effective treatment. Even though the criteria for the diagnosis of endometriosis-associated malignancies include also the coexistence of neoplastic endometrial tissue and endo- metriosis, almost one third of CCC arising within CS scars were not associated with endometriosis foci (T able 1). However, it has to be considered that four patients had re- ferred cyclic pain in the CS scar during menses, or the cyclic increase/decrease of the mass volume, which could be highly suggestive of the presence of endometriosis implants [14, 17, 19, 23]. Moreover, previous history of the excision of benign endometriosis foci at the CS scar was reported in five cases [9, 11, 13, 15, 16]. Therefore, the ab- sence of pathologically assessed endometriosis foci could be interpreted as either a sampling problem or a conse- quence of the complete replacement of normal tissue due to massive neoplastic proliferation. In this context, careful collection and evaluation of patient history would be important to have a high index of suspicion for endometriosis-associated malignancy. Indeed, these masses usually reach very large dimen- sions (median diameter: 9 cm, range 2.5 up to 22 cm) (Table 1) before the diagnosis is made, thus highlighting the difficulties to suspect this condition and obtain an early diagnosis. This is clinically relevant since primary surgical treatment very frequently requires wide surgical excision of the mass together with partial removal of part of the abdominal muscles and reconstructive sur- geries with a mesh or even pedicle-skin-muscle flap. Demolitive surgery was also necessary in the 3 cases ini- tially triaged to neo-adjuvant chemotherapy ([13, 18] current case), since only 1 of them achieved partial re- sponse after 8 cycles of carboplatin/paclitaxel chemo- therapy [18]; in addition, wide excision was necessary in the 2 cases who had undergone excision of endometriosis nodules at the CS scar in the past, and had been unsuc- cessfully treated with GnRh and progestins, respectively, before being triaged to radical surgery which led to defini- tive diagnosis of malignancy. Besides wide resection of the mass, other surgical procedures were often carried out including BSO (82.6%), as well as hysterectomy (71.4%), or endometrial biopsy (9.5%, and omentectomy or omen- tal biopsy (30.4%), in order to exclude other primary tumors sites. Despite the aggressiveness of surgery and the multi- modal treatment approach, of 18 cases with available follow up data, 10 experienced relapse of disease, mostly at distant sites, and 8 patients died of disease. Apart from the long time interval to diagnosis and the wide extension of disease in the abdominal wall, Fig. 3 The tumor displayed a mixed pattern of both tubulocystic and papillary growth, HE x5 ( a), and HEx10 ( b); cells were large with abundant clear or occasionally eosinophilic cytoplasm. Note the high-grade nuclear atypia, HEx20 ( c); neoplastic cells showed positive cell membrane immunostaining for CK7 (x20) (d) Ferrandina et al. World Journal of Surgical Oncology (2016) 14:300 Page 4 of 8 Table 1 Clear cell carcinoma arising from endometriosis of the scar caesarean section Age Previous uterine surgeries Months since symptoms Size cm FNA or biopsy Primary treatment Pathology Adjuvant treatment Relapse Death Schnieber Agner-Kolb 1986 [ 4] 40 1 CS 15 years before –– – WE, BSO, Hys Mass: CCC + endometriosis Ovaries and uterus: negative RT, progestins – Yes after 18 months Hitti, 1996 [ 5] 46 1 CS 14 years before 1 CS 12 years before – 6 – WE, BSO, Hys CCC + endometriosis RT No after 30 months No after 30 months Miller 1998 [ 6] 38 1 hysterotomy 9 years before 1 abortion 3 years before 1 CS 2 years before 8 4 CCC + endometriosis WE, BSO, Hys omentectomy Scar: CCC Ovaries, uterus, omentum: negative Margins: close CIS-based CT RT No after 60 months d No after 60 months d Park 1999 [ 7] 56 1 CS 24 years 1 CS 20 years – 5 – WE Mass: CCC + endometriosis RT –– Ishida 2003 [ 8] 56 1 CS 24 years 1 CS 20 years 7 10 Endometrial carcinoma WE, Hys, BSO Mass: CCC Ovaries and uterus: negative CIS-based CT – Yes after 24 months b Sergent 2006 [ 9] 45 1 CS 25 years 1 CS 23 years 2 excisions of benign endometriosis nodules at the scar 17 20 – WE, BSO, later on: endometrial curettage Mass: CCC + endometriosis Right ovary: benign endometriosis; left ovary and uterus: negative Margins: 1 cm free Not done Yes early after surgerya Yes after 6 months Alberto 2006 [ 10] 38 1 CS 11 years BSO, Hys for endometriosis 66 – WE CCC Carbo/PTX RT –– Razzouk 2007 [ 11] 46 1 CS 26 years before 1 CS 24 years before 2 excisions of endometriosis nodules at the scar – >20 – GnRh analogue without benefit WE, BSO Mass: CCC + endometriosis Ovaries: negative LN: 1 positive Carbo/PTX Yes during CT Yes after 6 monthsb Rust 2008 [ 12]4 2 3 C S Hys 5 years before 24 5 Carcinoma WE Mass: CCC + endometriosis Margins: 1 mm free Not done –– Bats 2008 [ 13] 38 1 CS 13 years before 1 excision of endometriosic nodule at the scar – 10 Atypical cells NACT (carbo/PTX) No benefit WE, BSO, Hys, omentectomy Mass: CCC + endometriosis Uterus: adenomyosis Other specimens: negative Margins: 2 mm free Not done Yes after 4 months a – Williams 2009 [ 14] 53 1 CS 17 years before 24 2.5 CCC (excisional biopsy) WE of the scar, BSO, Hys, omentectomy Inguinal/Pelvic LNctomy Mass: CCC Uterus, right ovary, omentum: negative, left ovary: teratoma Inguinal LN: 7 positive/11 Pelvic LN: 8 positive/14 Carbo/PTX (4 cycles) Yes after 3 monthsa Yes after 11 months b Bourdel 2010 [ 15] 43 1 CS 20 years before 1 CS 15 years before 1 excision of endometriosic nodule at the scar 99 – WE, partial resection of pubic symphysis, umbilicus, right rectus abdomen, pelvic LN sampling Later on: BSO, Hys Mass: CCC + endometriosis Pelvic LN: multiple positive Ovaries, uterus: negative Carbo/PTX (6 cycles) RT Yes after 6 monthsd Yes after 22 months b Ferrandinaet al. World Journal of Surgical Oncology (2016) 14:300 Page 5 of 8 Table 1 Clear cell carcinoma arising from endometriosis of the scar caesarean section (Continued) Yan 2011 [ 16] 41 2 CS 5 years before 2 excisions of benign endometriosic nodule at the scar 1 year and 4 months before 4 9 Not done Progestins without benefit WE Mass: CCC CT No after 24 months d No after 24 months d Li 2012 [ 17] 49 1 CS 26 years before 25 years 9 Not done WE, Hys, BSO Mass: CCC Uterus, ovaries: negative Carbo/PTX (6 cycles) Noc after 8 months No c after 8 months Mert 2012 [ 19] 42 Tubal ligation, right ovariectomy – 15 Tumor cells Mullerian origin NACT (carbo/PTX) WE, left SO Hys, left Pelvic LNctomy Omentectomy Mass: CCC + endometriosis Other organs: negative Margins: free Not done No after 1 month a No After 1 month a 51 2 CS Hys for myomas 12 6 Excisional biopsy CCC + endometriosis BSO, Omental biopsy Negative Margins: free RT No after 31 months b No after 31 months b Shalin 2012 [ 18] 47 1 CS 10 3 CCC WE, left ovary cystectomy, endometrial biopsy, pelvic LN sampling Mass: CCC + endometriosis Ovarian cyst: endometriosis Endometrium: negative Pelvic LN: 2 positive/4 Margins: positive CIS-based CT (6 cycles) RT Yes after 5 monthsb No after 7 months b Ijichi 2014 [ 20] 60 1 CS 37 years before 1 CS 35 years before 48 4 Atypical cells WE Mass: CCC + endometriosis Margins: free Not done Yes after 8 months a No after 23 months a Aust 2015 [ 21] 47 1 CS 16 years before vaginal Hys 10 years before 61 0 – WE Later on: BSO, pelvic, aortic LNctomy omentectomy Mass: CCC Ovaries and omentum: negative LN:2 positive/48 Margins: free Carbo/PTX (6 cycles) No after 10 months c No after 10 months c Heller 2014 [ 22]3 7 1 C S 1C S 1 CS 8 years before 96* 18 CCC WE, left SO, pelvic LNctomy Mass: CCC Ovary: negative LFN: multiple LN positive Refused treatment Yes after 5 monthsa – Liu 2014 [ 23]3 9 1 C S 1 excision of endometriosic nodule at the scar 60 6 – WE, partial cystectomy, BSO, Hys, omentectomy, inguinal,pelvic, aortic LNctomy Mass: CCC + endometriosis Ovaries, uterus, omentum: negative Bladder: positive Pelvic LN: 18 positive/21 Aortic LN: 6 positive /6 Inguinal LN: 8 positive/8 Carbo/PTX (3 cycles) YES after 10 months c Yes after 12 months c Sosa-Duràn 2015 [ 24]4 5 1 C S 1C S 1C S 69 – WE, margins: 2 cm free Mass: CCC + endometriosis Not done No after 16 months a No after 16 months a Current case 44 1 CS 9 years before 8 22 Endometrial carcinoma NACT (carbo/PTX) WE, BSO, Hys, inguinal, and pelvic LNctomy Mass: CCC + endometriosis Ovaries, uterus: negative Pelvic LN: 7 positive/14 Inguinal LN: 8 positive/11 Margins: free Not done Yes after 2 months from surgery Yes after 6 months CCC 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, CIS cisplatin, PTX paclitaxel, RT radiotherapy *The mass was reported to have come and gone over the last 8 years since the last CS aFrom surgical resection bFrom initial diagnosis cSince completion of chemotherapy dNot specified Ferrandinaet al. World Journal of Surgical Oncology (2016) 14:300 Page 6 of 8 clinical aggressiveness is also sustained by the intrinsic biologic aggressiveness of CCC, which differs from other endometrial cancer hi stotypes. In this context, proper diagnosis should take advantage of immunohis- tochemical panels with several markers in order to ex- clude serous histotype as well as mesothelial tumors such as malignant mesothelioma and papillary meso- thelioma which are usually positive for Calretinin, WT1, and keratin 5/6, contrary to what is observed in CCC. In addition, WT1 is the most important immuno- histochemical marker to distinguish serous carcinoma from CCC. It has to be acknowledged that of 9 cases undergoing lymphadenectomy or sampling, 8 showed diffuse meta- static involvement of inguinal, and/or pelvic, and/or aor- tic lymph nodes ([11, 14, 15, 19, 22, 23] current case). On the other hand, some cases were reported to ex- perience relatively longer disease-free and overall sur- vival ( ≥30 months) [5, 6, 16, 18]; while recognizing that a more thorough molecular characterization could hope- fully help define prognosis of this very rare condition, it has to be acknowledged that cases with better outcome presented with masses ranging between 4 and 9 cm, thus suggesting that a prompt recognition and treatment could make the difference. Obviously, also prevention of endometriosis implant- ation at time of CS is of utmost importance: as recently emphasized, the uterus should not be exteriorized, ex- posure of endometrial mucosa during uterus suturing should be limited, and peritonization may be advised, al- though there is no definitive data about these issues [15].

Attention should be focused on careful evaluation of pa- tient history in terms of pelvic surgery, and symptoms suggestive of endometriosis such as repeated occurrence of endometriosis nodules at CS scar, or cyclic pain, or volume changes of the nodules. Abbreviations AUC: Area under curve; BSO: Bilateral salpingo-oophorectomy; CB: Carboplatin; CCC: Clear cell carcinoma; CIS: Cisplatin; CS: Caesarean section; FNA: Fine needle aspiration; HYS: Hysterectomy; LN: Lymph node; LNCTOMY: Lymphadenectomy; MRI: Magnetic resonance imaging; PET/ CT: Positron emission tomography/computed tomography; PTX: Paclitaxel; RT: Radiotherapy; WE: Wide mass excision

None. Funding No funding source to be declared. Availability of data and materials All data (imaging, pathology, immunohistochemistry, and procedures) are available. Authors’ contributions GF participated in the management of the patient and wrote the case report. EP participated in the medical management of the patient. FF was involved in the surgical management of the patient. SG carried out plastic surgery. ALV contributed to imaging characterization. MVM carried out imaging characterization. IP performed immunohistochemistry and contributed to pathological characterization. GS participated in the management of the patient and contributed to manuscript writing. GZ was in charge of immunohistochemistry and pathological diagnosis. All authors read and approved the final manuscript. Competing interests The authors declare that they have no competing interests. Consent for publication We have obtained consent to publish from the legal relative (husband) of the patient, since she passed away before the manuscript planning and writing. Ethics approval and consent to participate According to our institutional ethical committee, no specific protocol is required for retrospective collection of data. Author details 1Department Medicine and Health Sciences, University of Molise, Campobasso/Gynecologic Oncology Unit, Campobasso, Italy. 2Gynecologic Oncology Unit, Fondazione “Policlinico Universitario A. Gemelli ”, Rome, Italy. 3Department Medicine and Aging Sciences, University “GD ’Annunzio”, Chieti-Pescara, Italy. 4Department Plastic and Reconstructive Surgery, Fondazione “Policlinico Universitario A. Gemelli ”, Rome, Italy. 5Department Radiological Sciences, Institute of Radiology, Catholic University, Rome, Italy. 6Institute of Nuclear Medicine, Fondazione “Policlinico Universitario A. Gemelli”, Rome, Italy. 7Department Pathology, Catholic University, Rome, Italy. Received: 14 October 2016 Accepted: 22 November 2016

1. Van Gorp T, Amant F, Neven P, Vergote I, Moerman P. Endometriosis and the development of malignant tumors of the pelvis. A review of the literature. Best Pract Res Clin Obstet Gynaecol. 2004;18:349 –71. 2. Stevens EE, Pradhan TS, Chak Y, Lee YC. Malignant transformation of endometriosis in a cesarean section abdominal wall scar: a case report. J Reprod Med. 2013;58(5-6):264 –6. 3. Taburiaux L, Pluchino N, Petignat P, Wenger JM. Endometriosis-associated abdominal wall cancer. Int J Gynecol Cancer. 2015;25:1633 –8. 4. Schnieber D, Wagner-Koib D. Malignant transformation of extragenital endometriosis. Geburtshilfe Frauenheilkd. 1986;46:658 –9. 5. Hitti IF, Glasberg SS, Lubicz S. Clear cell carcinoma arising in extraovarian endometriosis; report of three cases and review of the literature. Gynecol Oncol. 1996;17:520–1. 6. Miller DM, Schouls JJ, Ehelen TG. Clear cell carcinoma arising in extragonadal endometriosis in a cesarean section scar during pregnancy. Gynecol Oncol. 1998;70:127 –30. 7. Park SW, Hong SM, Wu HG, Ha SW. Clear cell carcinoma arising in a cesarean section scar endometriosis: a case report. J Korean Med Sci. 1999; 14(2):217–9. 8. Ishida GM, Motoyama T, Watanabe T, Emura I. Clear cell carcinoma arising in a cesarean section scar. Report of a case with fine needle aspiration cytology. Acta Cytol. 2003;47(6):1095 –8. 9. Sergent F, Baron M, Le Cornee JB, Scotte M, Mace P, Marpeau L. Malignant transformation of abdominal wall endometriosis: a new case report. J Gynecol Obstet Biol Reprod. 2006;35:186 –90. 10. Alberto VO, Lynch M, Labbei FN, Jeffers M. Primary abdominal wall clear cell carcinoma arising in a Caesarean section scar endometriosis. Ir J Med Sci. 2006;175(1):69–71. 11. Razzouk K, Roman H, Chanavaz-Lacheray I, Scotté M, Verspyck E, Marpeau L. Mixed clear cell and endometrioid carcinoma arising in parietal endometriosis. Gynecol Obstet Invest. 2007;63(3):140–2. 12. Rust MM, Susa J, Naylor R, Cavuoti D. Clear cell carcinoma in a background of endometriosis. Case report of a finding in a midline abdominal scar 5 years after a total abdominal hysterectomy. Acta Cytol. 2008;52(4):475 –80. Ferrandina et al. World Journal of Surgical Oncology (2016) 14:300 Page 7 of 8 13. Bats AS, Zafrani Y, Pautier P, Duvillard P, Morice P. Malignant transformation of abdominal wall endometriosis to clear cell carcinoma: case report and review of the literature. Fertil Steril. 2008;90(4):1197. 14. Williams C, Petignat P, Belisle A, Drouin P. Primary abdominal wall clear cell carcinoma: case report and review of literature. Anticancer Res. 2009; 29(5):1591 –3. 15. Bourdel N, Durand M, Gimbergues P, Dauplat J, Canis M. Exclusive nodal recurrence after treatment of degenerated parietal endometriosis. Fertil Steril. 2010;93(6):2074. e1-6. 16. Yan Y, Li L, Guo J, Zheng Y, Liu Q. Malignant transformation of an endometriotic lesion derived from an abdominal wall scar. Int J Gynaecol Obstet. 2011;115(2):202–3. 17. Li X, Yang J, Cao D, Lang J, Chen J, Shen K. Clear-cell carcinoma of the abdominal wall after cesarean delivery. Obstet Gynecol. 2012;120(2 Pt 2):445–8. 18. Shalin SC, Haws AL, Carter DG, Zarrin-Khamel N. Clear cell adenocarcinoma arising from endometriosis in abdominal wall cesarean section scar: a case report and review of the literature. J Cutan Pathol. 2012;39(11):1035 –41. 19. Mert I, Semaan A, Kim S, Ali-Fehmi R, Morris RT. Clear cell carcinoma arising in the abdominal wall: two case reports and literature review. J AJOG. 2012; 207(2):e7–9. 20. Ijichi S, Mori T, Suganuma I, Yamamoto T, Matsushima H, Ito F, Akiyama M, Kusuki I, Kitawaki J. Clear cell carcinoma arising from cesarean section scar endometriosis: case report and review of the literature. Case Rep Obstet Gynecol. 2014;2014:642483. 21. Aust S, Tiringer D, Grimm C, Stani J, Langer M. Therapy of a clear cell adenocarcinoma of unknown primary arising in the abdominal wall after caesarean section and after hysterectomy. Wien Klin Wochenschr. 2015; 127(1-2):62–4. 22. Heller DS, Houck K, Lee ES, Granick MS. Clear cell adenocarcinoma of the abdominal wall: a case report. J Reprod Med. 2014;59(5-6):330 –2. 23. Liu H, Leng J, Lang J, Cui Q. Clear cell carcinoma arising from abdominal wall endometriosis: a unique case with bladder and lymph node metastasis. World J Surg Oncol. 2014;12:51. 24. Sosa-Durán EE, Aboharp-Hasan Z, Mendoza-Morales RC, García-Rodríguez FM, Jiménez-Villanueva X, Peñavera-Hernández JR. Clear cell adenocarcinoma arising from abdominal wall endometriosis. Cir Cir. 2016; 84(3):245–9. • We accept pre-submission inquiries  Our selector tool helps you to find the most relevant journal  We provide round the clock customer support  Convenient online submission  Thorough peer review  Inclusion in PubMed and all major indexing services  Maximum visibility for your research Submit your manuscript at www.biomedcentral.com/submit Submit your next manuscript to BioMed Central and we will help you at every step: Ferrandina et al. World Journal of Surgical Oncology (2016) 14:300 Page 8 of 8