**12. Malignancy**

78 Endometriosis - Basic Concepts and Current Research Trends

theses cases mimic malignant ovarian neoplasms. In these cases the endometriosis involves mainly the peritoneum, with multiple adhesions and ovarian endometriomas. Ascites is

Ectopic endometrial tissue is influenced by hormonal levels of the uterine cycle, so it flakes off with the drop of the hormonal peak as normal endometrium. This mechanism causes an inflammatory reaction in the site of interest and possible ascites in the case of peritoneal endometriosis. The rapid production of fluid by inflamed tissue and the obstruction of subdiaphragmatic lymph vessels, which impair its reabsorption, may be responsible for the

Fine-needle cytology has been successfully used to diagnose endometriosis by demonstrating the presence of epithelial and stromal cells in the smears, but usually their cytological features are not specific enough to allow a definite cytological diagnosis of endometriosis, nor to exclude even a neoplastic process (Zeppa *et al.*, 2004). Endometriosisassociated ascites is commonly mistaken for ascites caused by ovarian neoplasms, especially when associated with an elevated CA-125 level (Sait, 2008), and laparoscopy and microscopic examination of tissue are generally required for diagnosis. Nonetheless, the cytological diagnosis of endometriosis in effusions, avoid more invasive diagnostic

Although there is no established treatment is usually performed conservative surgical

Spontaneous hemoperitoneum in pregnancy is an uncommon yet dramatic cause of hemoperitoneum, associated with high perinatal mortality (31%) and 44% of these deaths attributable to maternal shock. No maternal deaths have been reported in the last 20 years. The condition is most common during the third trimester of pregnancy. Endometriosis is

The cause of this condition is not fully clarified. Inoue *et al.* (1992) have suggested two possible explanations for the involvement of endometriosis: (i) chronic inflammation due to endometriosis may make utero-ovarian vessels more friable; (ii) the resultants adhesions may give further tension to these vessels when the uterus is enlarged during pregnancy. Invasiveness of severe endometriosis has been suggested as a reason for this entity, but Brosens *et al.* (2009) found no apparent correlation between spontaneous hemoperitoneum

The typical presentation of spontaneous utero-ovarian vessel rupture consists of a sudden onset of abdominal pain without vaginal bleeding, associated with signs of acute abdomen and hypovolemia. Fetal distress is an uncommon finding unless there is severe hemodynamic instability. Abdominal ultrasound examination does not reveal signs of placental abruption and fail to diagnose intraperitoneal bleeding as cause of acute pain. Transvaginal ultrasound and computerized tomography scans sometimes indicate the presence of intraperitoneal free fluid, but in most cases the diagnosis is only established at laparotomy (Brosens *et al.*, 2009). Preoperatively other potential diagnoses are placental abruption, uterine rupture, HELLP syndrome, abdominal pregnancy or rupture of the liver

resection and suppression of ovulation with a GnRH agonist (Sait, 2008).

**11. Spontaneous hemoperitoneum in pregnancy and endometriosis** 

detected in large volumes (4254 mL on average) and is bloody or brown (Sait, 2008).

large volumes detected (Zeppa *et al.*, 2004).

considered a major risk factor (Brosens *et al.*, 2009).

in pregnancy and stage of endometriosis.

or spleen (Grunewald & Jördens, 2010).

procedures (Zeppa *et al.*, 2004).

Malignant transformation is an infrequent complication of endometriosis and has been reported in 0.7-1% of patients and 62%-78.7% of the cases occur in the ovary, whereas extragonadal sites represent 21.3%-38% of tumors. The rectovaginal septum, rectosigmoid colon, vagina, and pelvic peritoneum represented the majority of extragonadal sites. Other locations include: bowel, umbilicus, lymph node, urinary tract, pleura, diaphragm, lung, etc (Slavin *et al.*, 2000; Van Gorp *et al.*, 2004; Yantiss *et al.*, 2001). Two possible explanations for the relation-ship between endometriosis and intraperitoneal cancer have been proposed: (i) endometriotic implants undergo malignant transformation secondary to genetic defects (p53 mutations) (Akahane *et al.*, 2007) that also serve to enable the endometriosis to thrive, or (ii) women with endometriosis have a defect in their immune system that enables the endometriosis to flourish, and this baseline defect leaves them more susceptible to subsequent malignant transformation (Modesitt *et al.*, 2002). It has been seen a direct transition from clearly benign epithelium through atypical endometriosis to carcinoma. This association suggest that atypical endometriosis can act as a precancerous lesion, as seen in atypical hyperplasia of the endometrium (Van Gorp *et al.*, 2004).

Among malignancies arising from endometriosis of the ovaries, endometrioid adenocarcinoma is the most common histologic type (23%-69.1%), followed by clear-cell carcinomas (13.5%-23%), sarcomas (11.6%), and rare cell types (6%) (Modesitt *et al.*, 2002). Extragonadal lesions are mostly endometrioid tumors (66%) and sarcomas (25%); clear cell histology is seen in only 4.5% of extragonadal malignancies. Tumors arising in endometriosis are predominantly low grade and confined to the site of origin (Slavin *et al.*, 2000; Van Gorp *et al.*, 2004). The histopathological criteria to classify a malignancy as arising from endometriosis include the demonstration of cancer arising in the tissue and not invading it from another source, and the presence of tissue resembling endometrial stroma surrounding the epithelial glands (Slavin *et al.*, 2000).

The risk factors for malignant transformation in endometriosis are poorly defined. An association has been noted between unopposed estrogen therapy and the development of endometrioid or clear cell epithelial ovarian tumors (Modesitt *et al.*, 2002). Increasing parity, and hormonal contraceptive use for ≥ 5 years, decreases the risks of both subtypes. Breast feeding and tubal ligation are inversely associated, but significantly so only for the endometrioid tumor (Nagle *et al.*, 2008; Van Gorp *et al.*, 2004). Obesity is associated only with clear cell cancers, with a two-fold increased risk. Also a significant trend of decreasing risk with increasing intensity (not duration) of smoking and education beyond high school

Abdominopelvic Complications of Endometriosis 81

Abrao MS, Dias JA, Bellelis P, Podgaec S, Bautzer CR, Gromatsky C. (2009). Endometriosis of the ureter and bladder are not associated diseases. *Fertil Steril*; 91: 1662-1667. Akahane T, Sekizawa A, Purwosunu Y, Nagatsuka M, Okai T. (2007). The role of p53

Anaf V, El Nakadi I, Simon P, Van de Stadt J, Fayt I, Simonart T, Noel JC. (2004). Preferential

Bektas H, Bilsel Y, Sari YS, Ersöz F, Koç O, Deniz M, Boran B, Huq GE. (2010). Abdominal

Berlanda N, Vercelllini P, Fedele L. (2010). The outcomes of repeat surgery for recurrent

Bianchi A, Pulido L, Espin F, Hidalgo LA, Heredia A, Fantova MJ, Muns R, Suñol J. (2007).

Brosens IA, Fusi L, Brosens JJ. (2009). Endometriosis is a risk factor for spontaneous

Brouwer R, Woods RJ. (2007). Rectal endometriosis: results of radical escisión and review of

Busacca M, Fedele L, Bianchi S, Candiani M, Agnoli B, Raffaelli R, Vignali M. (1998).

Camanni M, Delpiano EM, Bonino L, Deltetto F. (2010). Laparoscopic conservative management of ureteral endometriosis. *Curr Opin Obstet Gynecol*; 22: 309-314. Chapron C, Fauconnier A, Vieira M, Barakat H, Dousset B, Pansini V, Vacher-Lavenu MC,

Chapron C, Pietin-Vialle C, Borghese B, Davy C, Foulot H, Chopin N. (2009). Associated

Chapron C, Bourret A, Chopin N, Bousset B, Leconte M, Amsellem-Ouazana D, de Ziegler

De Cicco C, Corona R, Schonman R, Mailova K, Ussia A, Koninckx PR. (2011). Bowel resection for deep endometriosis: a systematic review. *BJOG*; 118: 285-291. Del Rey Moreno A, Jiménez Martín JJ, Moreno Ruiz FJ, Hierro Martín I. (2008). Asociación

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Fauconier A, Foulot H, Dousset B. (2004). Accuracy of rectal endoscopic ultrasonography and magnetic resonance imaging in the diagnosis of rectal involvement for patients presenting with deeply infiltrating endometriosis.

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is associated with decreased development of clear cell cancers only (Nagle *et al.*, 2008). The decreased risk of clear cell ovarian cancer amongst users of combined oestrogen and progestin hormone replacement therapy is interesting given the role of progestin as a potential chemopreventive agent in ovarian cancer (Nagle *et al.*, 2008). 86% of the patients with an extraovarian cancer had undergone a prior hysterectomy and bilateral salpingooophorectomy (Modessit *et al.*, 2002).

Pelvic pain or pelvic mass in a postmenopausal woman with a previous history of endometriosis should raise suspicions of reactivation or malignant transformation of endometriosis. Vaginal bleeding may signify the presence of a vaginal or rectovaginal septum lesion. Malignant transformation of colorrectal endometriosis may produce gastrointestinal dysfunction and/or bleeding. Urinary symptoms may herald urinary tract involvement with this disease (Slavin *et al.*, 2000; Van Gorp *et al.*, 2004).

The differential histological diagnosis of endometrioid and colonic adenocarcinoma is difficult because colonic adenocarcinoma has a significant mucosal component, while endometrioid adenocarcinoma usually involves the outer layers of the colon (30% are intramural) and endoscopic biopsies usually yield insufficient tissue for a definitive pathologic diagnosis (Slavin *et al.*, 2000; Yantiss *et al.*, 2001). Immunohistochemical staining seems to be useful in differentiating colonic endometrioid adenocarcinoma. The endometrioid tumor expresses cytokeratin 7 and CA-125, whereas cytokeratin 20 and carcinoembryonic antigen decorate colonic adenocarcinoma (Slavin *et al.*, 2000).

Primary surgical treatment with complete resection of pelvic tumors should be performed when feasible. Appropriate staging biopsies of lymph nodes and tissues in the upper abdomen should be performed when macroscopic disease is confined to pelvis. After surgical resection, is recommended the progestin therapy. Although postoperative treatment has not been clearly defined, 70% of these patients have been reported to receive chemotherapy or radiotherapy (Modesitt *et al.*, 2002).

Malignant transformation within endometriomas or within extragonadal endometriosis confined to the genital tract carries a much better prognosis, with a 67% 5-year survival for those with disease confined to the ovary and 100% 5-year survival for those with extragonadal disease confined to the site of the origin. Disseminated intraperitoneal disease had a poor prognosis, with a 12% 5-year survival (Van Gorp *et al.*, 2004).
