Extragonadal Endometriosis Research Articles

A case report of bladder and intestinal endometriosis, and the relationship between sex hormone receptor expression and PIK3CA mutation analysis

BackgroundExtragonadal endometriosis is a rare condition, and its disease manifestation and long-term prognosis have not been elucidated. We report an extragonadal endometriosis case controlled by drug therapy for 14 years with analysis of the sex hormone receptor expression and PIK3CA mutation.Case presentationThe patient was diagnosed with bladder endometriosis at age of 30 years, and underwent bilateral nephrostomy and GnRHa therapy with add-back therapy. The patient was switched to dienogest therapy at age 35 and had hematuria and bloody stools at age 38. PET-CT revealed a 6-cm mass in the bladder with fluorodeoxyglucose accumulation and the diagnosis of endometriosis in the bladder, sigmoid colon, and cecum was confirmed after the biopsy result. The lesion’s tubular structures were positive for the estrogen receptor, but only 30% positive for the progesterone receptor, and the H1047R mutation in PIK3CA was found in tubular structures of the bladder lesion. GnRHa therapy caused the tumors to shrink.ConclusionDecreased progesterone receptor expression and oncogenic mutations may influence the course of less common and rare site endometriosis. Rare site endometriosis often requires long-term hormone therapy, and management should be tailored to the patient's life stage, keeping in mind complications, such as decreased bone density.

Endometriosis as a risk factor for colorectal cancer

Endometriosis is a common benign disease in women of reproductive age, it has been associated with an increased risk of various malignancies that is defined by certain histological criteria mainly 80% in ovary and 20% in extragonadal sites such as intestine, rectovaginal septum, abdominal wall, pleura and others; the greatest risk for colorectal cancer is women with adenomyosis or endometriosis; Several genetic alterations have been found in the risk of endometriosis associated with cancer; The symptomatology, imaging and endoscopic characteristics simulate other inflammatory and malignant lesions that make the preoperative diagnosis of extragonadal endometriosis difficult. This is a review of the knowledge about endometriosis and its potential risk of malignancy, particularly with colorectal cancer.

Endometriosis as a Risk Factor for Colorectal Cancer

Endometriosis is a common benign disease in women of reproductive age, it has been associated with an increased risk of various malignancies that is defined by certain histological criteria mainly 80% in ovary and 20% in extragonadal sites such as intestine, rectovaginal septum, abdominal wall , pleura and others; the greatest risk for colorectal cancer is women with adenomyosis or endometriosis; Several genetic alterations have been found in the risk of endometriosis associated with cancer; The symptomatology, imaging and endoscopic characteristics simulate other inflammatory and malignant lesions that make the preoperative diagnosis of extragonadal endometriosis difficult. This is a review of the knowledge about endometriosis and its potential risk of malignancy, particularly with colorectal cancer.

Long‐term survival of a patient with malignant transformation of extragonadal endometriosis treated solely with chemotherapy: A case report

A 52-year-old woman presented to our hospital complaining of genital bleeding and was found to have a 50-mm vaginal tumor that involved the bladder, rectum, and small bowel and extended to the left pelvic side wall. Her history included a bilateral salpingo-oophorectomy and a total abdominal hysterectomy for fibroids and endometriosis. She had been prescribed estrogen replacement therapy (1.25 mg/day) following the second surgery and continued it for 8 years. The pathology of the vaginal biopsy showed endometrioid adenocarcinoma. Total pelvic exenteration was recommended for complete resection, but she chose chemotherapy (paclitaxel 175 mg/m2 and carboplatin AUC:6). Clinical complete remission was obtained for 11 years. She had a recurrence 11 years later. She was again found to have a 5-cm vaginal tumor. Surgical excision with upper vaginectomy was performed. The tumor was resected without invasion of the bladder, rectum and small bowel. Histologic examination of the specimen confirmed clear cell carcinoma with endometriosis. Chemotherapy may be the first-line treatment that can preclude aggressive surgery for malignant transformation of extragonadal endometriosis. However, combined chemotherapy and surgery is necessary for this disease.

Endometriosis of the Appendix

Endometriosis is a well-recognized gynecological condition in the reproductive age group. Endometriosis of the appendix is an entity of extragonadal endometriosis. The incidence of appendiceal endometriosis is lower than 1% among pathologies of pelvic endometriosis. Women can present with symptoms mimicking acute appendicitis or chronic pelvic pain. Diagnosis can be made only after a histopathological examination following the operation. We report here a case of appendiceal endometriosis, which were operated on for a prediagnosis of acute appendicitis, but postoperatively diagnosed as appendiceal endometriosis.

Endometrioid Adenocarcinoma of Caecum Causing Intussusception

Malignant transformation of endometriosis is rare and is usually seen in ovarian endometriosis. The colon and rectum are the most common sites for extragonadal endometriosis, and although serosal involvement is commonly seen, mucosal involvement is rare. Malignant transformation of endometriosis is a rare but a well-known complication of endometriosis. We report an unusual presentation of endometrioid adenocarcinoma with lymph node metastasis, arising from endometriosis in the caecal wall and causing ileocaecal intussusception. The patient presented with sudden onset of abdominal pain with features suggestive of acute appendicitis. Diagnostic laparoscopy revealed an ileocaecal intussusception. Conversion to open surgery confirmed a caecal mass causing ileocaecal intussusception, and a radical right hemicolectomy was performed. Histology revealed endometrioid adenocarcinoma arising in a focus of endometriosis in the muscularis propria and involving the mucosa, with one regional metastatic lymph node.

Intrahepatic endometriosis as differential diagnosis: Case report and literature review

Intrahepatic endometriosis is one of the rarest forms of atypical endometriosis; only eighteen cases have been reported in the English literature. We describe the case of a 32-year-old woman, who presented with persistent, non-cyclical upper right quadrant abdominal pain, a central liver cyst, and no history of endometriosis. Three years previous, she was diagnosed with an intrahepatic cyst. The lesion progressed and two laparoscopic deroofing-operations were performed, yet the diagnosis of intrahepatic endometriosis was never reached. She presented in our clinic with further progress of the cyst as well as obstruction of the intrahepatic biliary system. The magnetic resonance imaging showed a 9.5 cm × 12 cm, lobulated intrahepatic cyst. We performed an ultrasonic pericystectomy. Immunostaining confirmed intrahepatic endometriosis. Only one of the previously described eighteen patients with intrahepatic endometriosis presented with cyclical pain in the upper right abdominal quadrant accompanying menstruation. This lack of a "typical" clinic makes it challenging to diagnose extragonadal endometriosis without histopathology. A previous history of endometriosis was described in only twelve cases, thus the diagnosis of this condition should not be limited to patients with a known history of endometriosis. Six of 18 patients were postmenopausal, demonstrating this condition is not limited to women of reproductive age. A preoperative diagnosis was only reached in seven of the previously described cases, highlighting the importance of preoperative biopsies. Yet due to the potential adverse effects, a transhepatic biopsy must be discussed individually. Although rare, intrahepatic endometriosis should always be considered as a differential diagnosis in women with recurrent hepatic cysts, regardless of age or previous medical history. In such cases, histology is essential and a pericystectomy should be performed as standard of care.

Clear cell carcinoma arising in the abdominal wall: two case reports and literature review

Clear cell carcinoma originating in the abdominal wall is rare and usually develops within endometriotic implants in the scar. We describe 2 patients: a 42 year old with a 15 cm mass on the abdominal wall treated with neoadjuvant chemotherapy and excision and a 51 year old with a 6 cm abdominal mass treated with excision and adjuvant radiotherapy.

Endometriosis of the appendix: Report of three cases

Endometriosis of the appendix is an entity of extragonadal endometriosis. It commonly affects women in the childbearing age with a wide spectrum of clinical manifestations. Women can present with symptoms mimicking acute appendicitis or chronic pelvic pain. The surgical management varies from simple appendectomy to right hemicolectomy depending on the clinical findings. We report 3 cases of endometriosis of the appendix presenting with appendiceal intussusception. The surgical literature is reviewed and current surgical management is discussed.

Malignant transformation of vaginal endometriosis treated with neoadjuvant chemotherapy and surgery

Malignant transformation of extragonadal endometriosis is a described. A 40-year-old multiparous woman presented with dyspareunia and dysmenorrhea. Physical examination revealed a 3 x 3.5 cm vaginal nodule. The histological examination of a bioptic sample revealed a moderately differentiated endometrioid adenocarcinoma. The patient was treated with neoadjuvant chemotherapy followed by surgery and is free from disease after 24 months. The frequency of malignant transformation of vaginal endometriosis is unknown. Obesity, hyperestrogenism, and exposure to unopposed estrogen are known risk factors, but were not present in the medical history of the present patient. In our case, preoperative chemotherapy allowed a complete resection without a vaginal demolitive surgery. This therapeutic option may be considered in order to reduce surgical resection and to preserve sexual function. However, because of the rarity of this disease, it is difficult to establish a standard treatment.

Clear Cell Adenocarcinoma Arising in Endometriosis of a Previous Episiotomy Site

Malignant transformation of endometriosis in an episiotomy site is rare. A 42-year-old woman presented with a palpable mass, 2.5 cm in size, just inside the posterior commissure of the vagina, at the site of a previous episiotomy for a vaginal delivery. Three years previously, an endometriotic cyst had been excised at the same site, and the patient had been treated with a gonadotropin-releasing hormone analogue for 6 months. Biopsy revealed a clear cell adenocarcinoma arising in endometriosis. The patient underwent radical surgery alone without adjuvant therapy. At 10-month follow-up, there was no evidence of recurrence. Patients who experience a recurrence of extragonadal endometriosis after prior therapy should be monitored carefully for malignant degeneration.

Higher frequency of chromosomal aberrations in ovarian endometriosis compared to extragonadal endometriosis: a possible link to endometrioid adenocarcinoma

Endometriosis may progress to invasive endometrioid adenocarcinoma, particularly in the ovary. Up to now, little is known of the molecular mechanisms possibly involved in the malignant transformation of endometriosis. Therefore, in this study, extragonadal endometriosis (n=10), ovarian endometriosis without malignancy (n=10), ovarian endometriosis with direct transition into endometrioid adenocarcinoma (n=8), and normal endometrium (n=12) were investigated for numerical chromosomal aberrations by fluorescence in situ hybridization using centromere enumeration probes. The proportions of cells with aneusomies were semiquantitatively assessed. Trisomies 1 and 7, and monosomies 9 and 17 were found in endometriosis, ovarian endometrioid adenocarcinoma, and normal endometrium. The proportions of aneusomic cells were significantly higher in ovarian endometrioid carcinoma compared with ovarian endometriosis (P<0.001), and in ovarian endometriosis compared with extragonadal endometriosis and normal endometrium (P<0.001). The data provide new evidence of a common lineage of endometriosis and ovarian endometrioid carcinoma. The higher frequency of chromosomal aberrations in endometrioid carcinoma than in endometriosis may reflect an expansion of aberrant cell clones already present in endometriosis during the progression to cancer. The higher frequency of chromosomal aberrations in ovarian endometriosis than in extragonadal endometriosis suggests a role of the ovarian stromal milieu in the induction of genetic changes, which may eventually lead to invasive cancer.

Endometrial Stromal Sarcoma of the Rectosigmoid Colon Arising in Extragonadal Endometriosis and Revealed by Portal Vein Thrombosis

Malignant transformation is an infrequent complication of endometriosis. The ovary is the primary site in 76% of cases, and extragonadal sites are identified in 24%. Endometrioid carcinoma is the most common histologic type; sarcoma is very rare. We report a case of low-grade endometrial stromal sarcoma of the rectosigmoid colon presenting with epigastric pain due to portal vein thrombosis. This tumor arose from extragonadal endometriosis in a 61-year-old woman and was treated by surgical resection. The main differential diagnosis of this unusual colonic neoplasm includes primary mesenchymal tumors, such as gastrointestinal stromal tumors.

A case of clear cell carcinoma arising in extragonadal endometriosis.

Malignancy developing in extragonadal endometriosis is rare with the majority of cases being endometrioid adenocarcinomas. We present a 54-year-old woman who developed a clear cell carcinoma in her perineum, 25 years after excision of a perineal endometrioma in an episiotomy scar. Treatment involved radiotherapy and surgery, with a view to preserving vaginal function. Where benign extragonadal endometriosis occurs, the potential for malignant transformation persists even years after primary treatment.

Adenocarcinoma arising in extragonadal endometriosis

BACKGROUND Malignant transformation is an infrequent but reported complication of endometriosis. Previous reports of these cases have been limited to clinicopathologic studies based on routine histologic examination of these tumors, whereas, to the authors' knowledge, characterization of these lesions based on immunophenotype and hormone receptor and oncoprotein expression has not been described. METHODS Using commercially available monoclonal antibodies, the authors studied three recent cases of adenocarcinoma arising in extragonadal endometriosis using paraffin immunohistochemistry. Proteins examined included different cytokeratin (CK) subtypes, as well as hormone receptor status, proliferation rate, and oncoprotein expression. RESULTS All three cases presented clinically and macroscopically as colonic masses, and the tumors expressed an endometrial CK phenotype (CK7+, CK20-). In contrast, the adjacent benign colonic epithelium expressed the expected opposite phenotype (CK7-, CK20+). Estrogen receptor (ER) and progesterone receptor (PR) were expressed in one of the three tumors. Interestingly, in the ER/PR negative tumors, receptor expression was present in areas of benign endometriosis adjacent to malignancy, suggesting a loss of receptor expression with malignant transformation. The tumors also were examined for proliferation by Ki-67, and the expression of oncoproteins c-erb B-2, p53, cyclin D1, and bcl-2. All cases of malignancy had a high proliferation rate as measured by Ki-67, which was in contrast to areas of benign endometriosis which had a low proliferation rate. Of the other oncoproteins only p53 protein was detected at a significant level in all three cases. Cyclin D1 was overexpressed in two of the three cases. c-erb B2 and bcl-2 overexpression was not detected. CONCLUSIONS The results of the current study 1) show the utility of CK subtypes in confirming endometrioid phenotype in tumors arising in extragonadal endometriosis with colonic involvement and 2) suggest that loss of hormone receptor expression and p53 oncoprotein abnormalities may be involved as mechanisms in malignant transformation in extragonadal endometriosis. Cancer 1998;83:1163-1169. © 1998 American Cancer Society.

Adenocarcinoma arising in extragonadal endometriosis

Malignant transformation is an infrequent but reported complication of endometriosis. Previous reports of these cases have been limited to clinicopathologic studies based on routine histologic examination of these tumors, whereas, to the authors' knowledge, characterization of these lesions based on immunophenotype and hormone receptor and oncoprotein expression has not been described. Using commercially available monoclonal antibodies, the authors studied three recent cases of adenocarcinoma arising in extragonadal endometriosis using paraffin immunohistochemistry. Proteins examined included different cytokeratin (CK) subtypes, as well as hormone receptor status, proliferation rate, and oncoprotein expression. All three cases presented clinically and macroscopically as colonic masses, and the tumors expressed an endometrial CK phenotype (CK7+, CK20-). In contrast, the adjacent benign colonic epithelium expressed the expected opposite phenotype (CK7-, CK20+). Estrogen receptor (ER) and progesterone receptor (PR) were expressed in one of the three tumors. Interestingly, in the ER/PR negative tumors, receptor expression was present in areas of benign endometriosis adjacent to malignancy, suggesting a loss of receptor expression with malignant transformation. The tumors also were examined for proliferation by Ki-67, and the expression of oncoproteins c-erb B-2, p53, cyclin D1, and bcl-2. All cases of malignancy had a high proliferation rate as measured by Ki-67, which was in contrast to areas of benign endometriosis which had a low proliferation rate. Of the other oncoproteins only p53 protein was detected at a significant level in all three cases. Cyclin D1 was overexpressed in two of the three cases. c-erb B2 and bcl-2 overexpression was not detected. The results of the current study 1) show the utility of CK subtypes in confirming endometrioid phenotype in tumors arising in extragonadal endometriosis with colonic involvement and 2) suggest that loss of hormone receptor expression and p53 oncoprotein abnormalities may be involved as mechanisms in malignant transformation in extragonadal endometriosis.

Clear Cell Carcinoma Arising in Extragonadal Endometriosis in a Caesarean Section Scar during Pregnancy

Malignancy arising in ectopic endometriosis is a rare event. This paper documents a case of clear cell carcinoma arising in a focus of ectopic endometrium in a low abdominal transverse scar.

Malignant neoplasms arising in endometriosis

Ten cases of malignant tumors arising in foci of gonadal and extragonadal endometriosis are reported and added to 195 previously reported cases from the English literature. The ovary was the primary site in 165 (78.7%) of the cases, whereas extragonadal sites represented 44 (21.3%). Endometrioid adenocarcinomas accounted for 69% of the lesions, clear-cell carcinomas 13.5%, sarcomas 11.6%, and rare cell types 6%. Extragonadal lesions were mostly endometrioid tumors (66%) and sarcomas (25%). Tumors arising in endometriosis were predominantly low grade and confined to the site of origin. Radiation therapy was often able to control completely tumors limited to the pelvis, but was not beneficial in metastatic disease. Only one patient had a response to chemotherapy. Fourteen patients received postoperative progestin therapy, with a 77% 5-year survival. Follow-up has been reported in 86 patients. The tumor was either confined to the ovary (57), confined to the extragonadal site of origin (11), or spread throughout the peritoneal cavity (18). With each of these situations, the 5-year survival was 65, 100, and 10%, respectively. Fourteen patients had malignant transformation in endometriosis associated with presumed estrogenic stimulation; most lesions (69%) were well differentiated and the 5-year survival was 82%. After surgical resection, we recommend that progestin therapy be included in the treatment of cancer arising in endometriosis. The actual frequency of malignancy arising in endometriosis may be higher than reported.

Unusual and rapid amniotic fluid cell growth

The majority of malignant neoplasms arising in endometriosis have been adenocarcinomas.’ In their recent review, Mostoufizadeh and Scully’ recalled five cases of malignant mixed miillerian tumor and 19 cases of stromal sarcoma originating in gonadal and extragonadal endometriosis. Even rarer is the phenomenon of massive polypoid endometriosis in which the histologic features of conventional endometriosis persist despite the gross appearance which simulates a malignant neoplasm.’ The present case is particularly unique in that a sarcoma developed within extensive endometriosis and that it did so despite apparent obliteration of ovarian function by irradiation. In view of the course of events, the question arises whether the original lesion was indeed histologically benign endometriosis and not adenosarcoma. The original sections contained normal-appearing proliferative-type endometrial glands with focal cystic hyperplasia. The endometrial stroma was unremarkable in most areas with the exception of focal hypercellular and mitotically active regions. This illdefined phenomenon of “stromal hyperplasia” has previously been reported in endometrial curettings from a patient who subsequently developed miillerian adenosarcoma of the uterus.3 Whether the stromal proliferation observed in this case placed the patient at greater risk for subsequent stromal sarcoma is a matter of conjecture inasmuch as the degree of mitotic activity and cellular pleomorphism was much less than in the sarcoma and was consistent with that found in proliferative endometrium. In addition, a classic pattern of neoplastic stromal growth such as stromal nodules or endolymphatic stromal myosis was not present. Irradiation of the ovaries as primary therapy for endometriosis is not generally recommended and was performed in this case only when surgical castration could not be carried out and hormonal therapy was Fig. 3. The sarcoma was composed of oval to spindle-shaped neoplastic mesenchymal cells. They were arranged randomly and in a plexiform pattern in a collagen matrix.

Adenocarcinoma arising from extragonadal endometriosis 14 years after total hysterectomy and bilateral salpingo-oophorectomy for endometriosis: Report of a case with ultrastructural studies

Adenocarcinoma arising from extragonadal endometriosis 14 years after total hysterectomy and bilateral salpingo-oophorectomy for endometriosis: Report of a case with ultrastructural studies