Clear Cell Adenocarcinoma Arising from Endometriosis in Abdominal Wall Cesarean Section Scar: A Case Report and Literature Review

A 48-year-old gravida 2 para 1 female presented with progressively growing mass of cesarean scar, regular pain with menstruation for 15 years. She had a caesarean delivery 22 years ago. Seven years after the operation, she noticed a 2cm × 2cm nodule beside the abdominal scar, red, with slight pain during menstruation. The nodule grew rapidly, and the pain became more serious in the previous 2 years. She complained her troubles of severe dysmenorrhea on the first day of the menstrual period, accompanied by abdominal pain and deep pain in the site of uterine scar, with an intensity of six on the pain scale (6/10). There were no gynecological malignancies in her family history, and she had never received hormone therapy. Physical examination indicated a 13cm mass with multilocular originating from the previous surgical scar without tenderness, red, ulcer with bloody secretions, surrounded by erythema. Abdomino-pelvic CT scan and MRI confirmed a lobular, peripherally enhancing lesion in the rectus muscle sheath, extending to the skin surface within the abdominal wall, with images suggestive of internal septation. It measured around 12.8cm × 7.7cm along the major transverse, anteroposterior and longitudinal axes, respectively ( Figures 1 and 2 ), without any abnormalities in the abdominal cavity. Figure 1 CT image of the abdominal mass shows a heterogeneous tumor associated with cesarean section scar: plain scan ( A ) and contrast enhancement ( B ). ( A ) Plain scan showed a lobulated cystic mass at the previous cesarean section scar. ( B ) The solid components showed mild enhancement after contrast. Figure 2 The MRI show the extensive lobulated cystic components of the mass with low signal on T1WI ( A ) and high signal intensity on T2WI ( B – D ). Axial post-contrast image showed the solid septal component was significantly enhanced. CT image of the abdominal mass shows a heterogeneous tumor associated with cesarean section scar: plain scan ( A ) and contrast enhancement ( B ). ( A ) Plain scan showed a lobulated cystic mass at the previous cesarean section scar. ( B ) The solid components showed mild enhancement after contrast. The MRI show the extensive lobulated cystic components of the mass with low signal on T1WI ( A ) and high signal intensity on T2WI ( B – D ). Axial post-contrast image showed the solid septal component was significantly enhanced. Laboratory findings: tumor marker CA 125 was 164.7 U/mL (the reference range: 0–35 U/mL); her cancer antigen 19–9, α-fetoprotein, and carcinoembryonic antigen were within the reference range. A punch biopsy of the mass showed CCC, without benign endometriosis presented ( Figure 3 ) (Immunophenotype: CK+, CK7+, CK20-, CD99-, HNF1b+, Napsin A (+)). Suggesting, CCC arising from endometriosis of the abdominal wall. Figure 3 Histologically, Hematoxylin and eosin stain, magnification×200 shows typical clear-cell carcinoma with typical tubulocystic and papillary architectures. Histologically, Hematoxylin and eosin stain, magnification×200 shows typical clear-cell carcinoma with typical tubulocystic and papillary architectures. The patient underwent exploratory laparotomy, and found an irregular, cystic and solid mass deep in the rectus muscle of the midline. Extensive resection of the abdominal wall mass was performed with mesh reconstruction of the abdominal wall. The resected specimen was a lobulated mass with a maximum size of 13cm, accompanied by focal hemorrhage and necrosis. It was composed of microcystic spaces, involving the dermis, subcutaneous and skeletal muscle. The pathologic results of the uterus and bilateral accessories (ovary and fallopian tube) were negative. Microscopic examination of the tumor showed similar histopathology to the biopsy. The patient underwent six cycles of cisplatinum-based chemotherapy and adjuvant radiotherapy to the abdomen. Twelve months of follow-up, there was no further evidence of disease by imaging or clinical examination.

Endometriosis is an inflammatory disorder featured by the existence of normal endometrial glands and extrauterine matrix. 1 These pathological changes usually involve the ovaries and, more rarely, ureter, intestine, lung, and abdominal wall. 1 , 2 AWE patients usually have a history of gynecological operation with open uterine cavity. The incidence rate of abdominal surgical scar endometriosis ranges from 0.03% to 1.08% of women undergoing pelvic surgery. 2–4 Women usually account of a periodic menstrual pain, which refers to abdominal wall. Endometriosis is supposed to a benign disease, and malignant transformation is rare. About 80% of endometriosis-related malignant tumors occur in the ovary, while 20% are limited to extragonadal sites. 5 CCC arising from malignant transformation of endometriosis in the abdominal wall after CS is a very rare clinical condition, and the published literature about this subject is frail. Here, we report a case of CCC arising from the abdominal wall at the previous CS scar. In addition, we reviewed the literature on this unusual event.

Malignant transformation to CCC on the abdominal wall from a focus of endometriosis is a very rare case. For middle-aged women with a history of gynecologic or obstetric surgery, developing an abdominal wall mass, the possibility of a primary malignancy arising from endometriosis should be considered. Due to its rarity, there is no published treatment guideline at present. From the perspective of prevention, it must be stressed that every gynecological operation should be carried out with great care not to leave visible tissue residues on the abdominal wall.

Malignancy arising in association with endometriosis is quite rare. The incidence of abdominal surgical scar endometriosis in women undergoing pelvic surgery ranges between 0.3% and 1% (5), and these cases include endometrioid carcinoma (70%), sarcoma (25%) and CCC (5%), of which abdominal wall CCC due to endometriosis is a rare disease reported in the literature (6). CCC caused by malignant transformation of AWE after CS is a rare clinical condition. Although rare, the number of reported cases has increased in recent years (7), possibly owing to the increased rates of CS and conservative uterine surgery worldwide (7). Sampson and John 6 proposed three diagnostic criteria for the malignant tumors arising in endometriosis as follows: (i) demonstration of benign and malignant endometrial tissues in the tumor, (ii) the histological type consistent with the origin of endometrium, and (iii) no other primary tumor sites were found. Moreover, Mostoufizadeh et al 7 stated that the plain coexistence of tumor and endometriotic tissue is enough to prove the derivation of the endometriosis. According to the literature, even if the presence of endometriosis is the pathological diagnosis of the disease, only 36–42% of cases detected in the transition zone. 8 To the best of our knowledge, to date, there are limited literature studies on CCC caused by abdominal wall scarring, and we retrospectively listed and analyzed 12 typical ones (including the present case) ( Table 1 ). In these studies, the average reported age at diagnosis was 45.7 years old, while the mean size of the lesion was 10.9 cm. The literature review showed that 91.7% of cases had a history of CS. The average follow-up time was around 15 months, and about 25% of women died within 15 months of diagnosis. The great majority (our case was included) of cases arose from CS scars, with some exceptions: one case followed myomectomy, 9 one case followed hysterotomy, 10 and one followed open sterilization. 11 All of these procedures would allow endometrium to implant at the surgical incision site. Histological examination showed that more than 66.7% of cases revealed endometriotic tissue. But in our tissue sampling, there was no histological evidence of coexisting endometriosis, either in the peritoneal cavity or in the previous surgical-scar tissue. There are two explanations: 1) all endometrial lesions or ectopic endometrial tissues have been transformed into CCC; 2) primary CCC originated from the abdominal wall scar. In our case, the mass localized to the area of the cesarean scar, which was accompanied by regular pain with menstruation for 15 years, suggesting endometriosis. Therefore, we presumed that CCC was transformed by the pre-existing abdominal-wall endometriosis. Table 1 Cases of CCC Arising from Abdominal Wall Scar (N = 39) No. Reference Year Reported Patient Age (y) Size (cm) Previous Surgery Delay(y)* Coexisting Endometriosis Treatment Follow-Up(mo) Prognosis 1 Schnieb &Wagner-Kolb 12 1986 40 - 1 CS 15 Yes RT, TAH+BSO, RT progesterone 18 DOD 2 Hitti et al 13 1990 46 6 1 CS 14 Yes RT, TAH+BSO 30 NED 3 Miller et al 10 1998 38 4 1 CS 9 Yes Radical resection, TAH+BSO, RT 60 NED 4 Park et al 9 1999 54 5 1 CS 26 Yes Radical resection, RT 1.5 NED 5 Ishida et al 14 2003 56 10 1 CS 24 No Radical resection, RT 24 DOD 6 Sergent et al 15 2006 45 20 2 CS 28 No Radical resection, TAH+BSO, RT, CT 6 DOD 7 Alberto et al 16 2006 38 6 1 CS 11 No Radical resection, CT, RT NA NA 8 Razzouk et al 17 2007 46 >20 2 CS 20 Yes Radical resection, CT 6 DOD 9 Harry et al 11 2007 55 4 Open tubal sterilization 30 Yes Radical resection, RT 18 NED 10 Bats et al 18 2008 38 10 1 CS 13 Yes Radical resection, TAH+BSO CT 2 NED 11 Rust et al 19 2008 42 5 TAH 5 Yes Radical resection NA NA 12 Achach et al 20 2008 49 9 Laparotomy myomectomy 20 Yes Radical resection, CT NA NA 13 Matsuo et al 21 2009 37 14 Laparotomy endometrioma 10 No Radical resection, TAH+BSO pelvic lymph nodes dissection, omentectomy, CT 18 Recurrence 14 Williams et al 22 2009 53 25 1 CS 17 No Radical resection, TAH+BSO CT, RT 11 DOD 15 Bourdel et al 23 2010 43 9 2 CS; scar endometriotic nodule excisions 5 Yes Radical resection, CT, RT 22 DOD 16 Yan et al 24 2011 41 9 2 CS; hysterectomy; scar endometriotic nodules excisions 1 No Radical resection, Q-Ad 24 NED 17 Shalin et al 25 2012 47 3 1 CS NA Yes Radical resection, CT, RT 7 NED 18 Mert et al 26 2012 42 15 2 CS +Tubal ligation; oophorectomy NA Yes CT + Radical resection 1 NED 19 Mert et al 26 2012 51 6 2 CS; TAH NA Yes Radical resection + RT 31 NED 20 Sawazaki et al 27 2012 41 4.8 2 CS 15 Yes Radical resection +CT NA NA 21 Li et al 28 2012 49 9 1 CS 25 No CT 8 NED 22 Dobrosz et al 29 2014 42 8 1 CS 17 Yes Radical resection / NED 23 Ijichi et al 30 2014 60 4 2 CS 35 Yes Radical resection 15 NED 24 Heller et al 31 2014 37 18 3 CS 8 NA Radical resection 5 Recurrence 25 Liu et al 32 2014 39 6 1 CS; scar endometriotic nodule excision 10 Yes Radical resection +CT 12 DOD 26 Aust et al 33 2015 47 10 1 CS; hysterectomy 10 No Radical resection +CT 10 NED 27 Ruiz et al 34 2015 41 15 1 CS 20 Yes Radical resection+ CT+ RT 6 Recurrence 28 Ruiz et al 34 2015 57 19 3 CS 30 Yes Radical resection+ CT + RT NA NED 29 Sosa-Duran et al 35 2015 45 9 3 CS 6 Yes Radical resection 16 NED 30 Ferrandina et al 36 2016 44 22 1 CS 8 Yes Radical resection+ CT 6 DOD 31 Graur et al 37 2017 43 5.9 1 CS 22 No Radical resection+ CT NA NED 32 Wei & Huang 38 2017 46 5.3/6.3 1 CS 18 Yes Radical resection + RT 3 NED 33 Marques et al 39 2017 47 11 3 CS, Tubal ligation 17 Yes Radical resection+ CT 45 NED 34 Gentile et al 40 2017 42 10 1 CS 7 Yes Radical resection+ CT 8 NED 35 Lopes et al 41 2019 48 12 1 CS 30 Yes Radical resection+ CT 4 NED 36 Behbehani et al 42 2019 48 7 1 CS + cervical hysterectomy 5 Yes Radical resection+ CT 2 NED 37 Rolon M et al 43 2019 48 7 3 CS + scar endometriotic nodule excision + hysterectomy, BSO 4 No Radical resection+ CT NA NA 38 Giannella et al 44 2020 45 20 2 CS 13 No CT + RT 7 DOD 39 Dong Liu et al (the present case) 2022 48 12.8 1 CS 22 No Radical resection +TAH-BSO+ CT 12 NED Note : *Delay between the latest Previous Surgery. Abbreviations : CCC, clear cell carcinoma; CS, cesarean section; CT, chemotherapy; RT, radiotherapy; NA, no data in; NED, no evidence of disease; TAH, total abdominal hysterectomy; BSO, bilateral salpingo-oophorectomy; LH, laparoscopic hysterectomy; DOD, died of disease. Cases of CCC Arising from Abdominal Wall Scar (N = 39) Note : *Delay between the latest Previous Surgery. Abbreviations : CCC, clear cell carcinoma; CS, cesarean section; CT, chemotherapy; RT, radiotherapy; NA, no data in; NED, no evidence of disease; TAH, total abdominal hysterectomy; BSO, bilateral salpingo-oophorectomy; LH, laparoscopic hysterectomy; DOD, died of disease. The available case reports in the literature differ in terms of disease-free survival and mortality, which may be related to the timing of diagnosis, the extent of tumor burden and its resectability at the time of diagnosis, as well as different therapeutic effects. Reported cases have been treated with radical resection of the tumor with or without the addition of variable chemotherapeutic and radiotherapy regimens. Due to the low incidence rate, it is difficult to generalize the outcomes or to conduct randomized controlled trials to standardize treatment protocols.