Clear cell adenocarcinoma of the vulva arising in endometriosis. A case report

A clear cell carcinoma, originating from a focus of endometriosis in the vulva, in a 52-year-old woman, operated on eight years before for ovarian endometriosis is reported. Malignant transformation of extraovarian endometriosis is rare. To date only three cases that originated in the vulva have been reported.     

Endometrial adenocarcinoma arising from endometriosis of the rectosigmoid colon

BACKGROUND: Only 21.3% of cases of malignant transformation of endometriosis occur at extragonadal pelvic sites. Forty cases of endometriosis-associated intestinal tumors are reported in the literature. Of these, 17 cases are primary adenocarcinomas arising in the rectosigmoid colon. In 8 of the 17 case reports the patients were using unopposed estrogen replacement therapy. CASE: The patient had previously undergone a total abdominal hysterectomy and bilateral salpingo-oophorectomy for deeply infiltrating rectovaginal endometriosis, and was using estrogen replacement therapy. She presented with rectal bleeding 12 years later, and a polyp was detected arising from the sigmoid colon. A biopsy detected malignant transformation of endometriosis to adenocarcinoma. CONCLUSION: This is the ninth case of a patient with this condition reported in the literature.     

The occurrence of adenocarcinoma in endometriosis of the rectovaginal septum during progestational therapy.

A patient is presented who developed adenocarcinoma in endometriosis of the rectovaginal septum during a second course of hormonal therapy. Malignant transformation in an area of endometriosis during sex steroid therapy has not been previously reported. The rectovaginal septum is recognized as probably the most common site of malignant transformation in extraovarian foci of endometriosis.     

Postmenopausal malignant transformation of extragenital endometriosis. A case report

Malignant transformation of endometriosis is a rare event. The ovaries are the most common sites reported in the literature. Postmenopausal cancer arising in extragenital endometriosis is still more exceptional. Hormone replacement therapy and perhaps, to a lesser extent, Tamoxifen could be risk factors for the malignant transformation of endometriosis. We herein report the case of a patient who has developed, after 11 years of hormone replacement therapy, an extragenital endometrioid carcinoma in the vesico-uterine pouch.     

Adenocarcinoma arising from endometriosis in scar from a cesarean section treated with the use of plastic mesh

OBJECTIVES: Abdominal wall endometriosis is usually a secondary process in scars after a cesarean section or appendectomy. Malignant transformation is an infrequent complication of endometriosis. The great majority of cases belong to adenocarcinoma. Only 21.3% of cases of malignant transformation of endometriosis occur at extragonadal pelvic sites, 4% of cases in scars after laparotomy. STUDY DESIGN: This is a case report of malignant transformation of endometriosis to adenocarcinoma in scar after cesarean section in 45-year old woman. CONCLUSIONS: In cases of abdominal wall endometriosis in scars after cesarean section surgical treatment is a method of choice. Treatment consisted in wide surgical resection followed by prosthetic abdominal wall repair. Using a plastic mesh is a method of choice for abdominal wall reconstruction after surgery.     

Malignant degeneration of perineal endometriosis in episiotomy scar, case report and review of the literature

Although malignant degeneration of cutaneous endometriosis is rare at only 0.3-1% in endometriosis surgical scars, diagnosis and management need to be defined. A case of malignant degeneration of perineal endometriosis is reported, with a review of literature. Physiopathology, epidemiological data, diagnostic and therapeutic methods are discussed for malignant degeneration of cutaneous endometriosis. Any scar lesion that evolves in response to the menstrual cycle should be considered endometriosis until proven otherwise, and thus could require surgical resection, with histological analysis. A history of cutaneous endometriosis with frequent recurrences can indicate malignant degeneration. All cases require long-term clinical follow-up because, despite the rarity of this diagnosis, the delay between benign endometriosis and malignant transformation can vary from a few months to over 40 years.     

Novel insights on the malignant transformation of endometriosis into ovarian carcinoma

The malignant transformation of endometriosis is an uncommon event, which happens in 0.7–2.5% of the cases, and, when occurs, it usually involves the ovary. A 2 to 3-fold higher risk of ovarian endometrioid and clear cell carcinoma has been reported in women with endometriosis. Pathological studies have detected a morphological continuum of sequential steps from normal endometriotic cyst epithelium to atypical endometriosis and finally to invasive carcinoma. Ovarian endometrioid carcinoma harbors mutations of CTNNB1 in 16–53.3%, of PTEN in 14–20% and of ARID1A in 30–55% of the cases. Ovarian clear cell carcinoma harbors mutations of PIK3CA in 20–40% and of ARID1 in 15–75% of the cases. Whereas estrogen receptors and progesterone receptors are quite always absent, HNF-1b is often over-expressed in this histotype. Atypical endometriosis and endometriosis-related ovarian neoplasms share molecular alterations, such as PTEN mutations, ARID1A mutations and up-regulation of HNF-1b. Moreover, ARID1A mutations have been noted in clear cell tumors and contiguous atypical endometriosis, but not in distant endometriotic lesions. The loss of BAF250a protein expression is suggestive for the presence of ARID1A mutations, and represents an useful marker of malignant transformation of endometriosis.     

The role of p53 mutation in the carcinomas arising from endometriosis.

To probe the mechanism of the development of ovarian cancer from endometriosis, which is a multistep process that involves the activation of oncogenes and inactivation of tumor suppressor genes, we evaluated p53 mutations in solitary endometriosis and endometriosis coexisting with ovarian clear cell carcinoma (OCCA) and ovarian endometrioid carcinoma (OEC). We examined 7 cases of solitary ovarian endometriosis, 13 cases of OCCA, and 9 cases of OEC. Cancer tissue specimens that also contained endometriosis without atypia were chosen. Using a laser microdissection system, epithelial cells from the areas of endometriosis were isolated, and DNA was extracted. We amplified exons 5, 6, 7, and 8 of the p53 gene, and direct sequencing was performed. p53 mutation was observed in 4 (30.8%) of 13 specimens of endometriosis coexisting with OCCA, whereas no mutations were detected in solitary endometriosis or endometriosis coexisting with OEC. We thought that some genetic alterations, which induce p53 mutations in endometriosis, may affect malignant transformation of endometriosis into OCCA.     

Malignant transformation of endometriosis and genetic alterations of K-ras and microsatellite instability.

OBJECTIVES: To clarify the role of specific genetic alterations in the multi-step process of malignant transformation of endometriosis. METHODS: In cases of ovarian endometrioid carcinoma, we separated regions of normal endometriosis, atypical endometriosis and ovarian endometrioid carcinoma by laser microdissection, and examined K-ras mutation and microsatellite instability in each separated tissue sample. RESULTS: We detected K-ras mutation and microsatellite instability in endometrioid carcinoma tissue, but not in normal or atypical endometriosis bordering the cancerous region. CONCLUSIONS: The present findings suggest that K-ras mutation and microsatellite instability are associated with malignant transformation from atypical endometriosis to ovarian endometrioid carcinoma.     

Clear cell adenocarcinoma of the vagina in a patient with vaginal endometriosis

BACKGROUND: Malignant transformation of endometriosis is an infrequent complication of endometriosis. Extragonadal disease is uncommon. CASE: 55-year-old female presented with postmenopausal bleeding. Physical examination revealed a 2-cm polypoid lesion at the posterior vaginal apex, which was found to be a moderately differentiated invasive adenocarcinoma. Final pathology at the time of definitive surgery demonstrated a clear cell adenocarcinoma of the vagina arising in vaginal endometriosis. CONCLUSION: Vaginal endometriosis may lead to the development of cancer. Malignancy arising in endometriotic foci is rare, but most commonly occurs in the ovary. We report a case of clear cell malignancy arising in vaginal endometriosis, adding to only seven cases previously reported. Risk factors include unopposed estrogen and obesity, but it may occur in the absence of either.     

Evidence that endometriosis behaves in a malignant manner

It is well known that certain aspects of endometriosis are similar to those of malignant disease. For example, like cancer, endometriosis can be both locally and distantly metastatic; it attaches to other tissues, invades, and damages them. Endometriosis is a common disease that does not create a cachectic or catabolic state, and is rarely fatal. There are, however, numerous reported cases of malignancy arising from endometriotic deposits and substantial histologic evidence that endometriosis is associated with endometrioid carcinoma and clear cell carcinoma of the ovary. A large review article by Mostoufizadeh and Scully investigated the association between endometriosis and endometrioid carcinoma, noting that women who had both diseases tended to be younger [1]. They found no association between endometriosis and serous or mucinous carcinoma of the ovary, and reported that malignant transformation of endometriosis was rare and associated with the use of exogenous estrogens. An epidemiological study of Swedish women reported a higher incidence of breast and ovarian cancer and non-Hodgkin's lymphoma in women with endometriosis compared with controls [2]. Vercellini and colleagues also reported a higher incidence of endometrioid and clear cell carcinoma in women with endometriosis compared with controls [3]. Mutations in genes associated with galactose metabolism have been identified as one possible mechanism for this association. These mutations are more common in ovarian cancer and have been reported to be more common in women with endometriosis. We compared 78 women with endometriosis with 248 controls and were unable to demonstrate an increased frequency of these mutations in any of these groups.     

Malignancy in endometriosis: frequency and comparison of ovarian and extraovarian types.

One thousand consecutive cases of surgically proven endometriosis were reviewed to evaluate the frequency and types of pelvic cancers that were associated with ovarian and extraovarian endometriosis. The frequency and types of histologic abnormalities present in the eutopic endometrium when cancers were noted in endometriosis were also evaluated. In the large subset of cases for which the authors were the primary pathologists and all foci of endometriosis were recorded, the frequency of malignancy was 10.8%. In contrast, the frequency was only 3.2% in cases diagnosed by others previously in our institution. Cancers were more commonly found in ovaries when endometriosis was present in that ovary (5%) compared to when endometriosis was present at other sites (1%). Clear cell and endometrioid carcinomas were the malignancies most commonly seen in ovaries containing endometriosis, while clear cell adenocarcinoma and adenosarcoma were most commonly seen in conjunction with extraovarian endometriosis. The association of endometriosis with endometrioid and clear cell carcinoma was much stronger than that of serous and mucinous tumors (p < .01). Concurrent endometrial pathology was commonly seen in cases of malignant transformation of endometriosis (32% of cases).     

Endometrioid carcinoma of the ovary and endometriosis: the association in postmenopausal women.

Histologic material from 42 patients with endometrioid carcinomas of the ovary was reviewed. Ovarian endometriosis was present in 11 cases (26%) and 8 of these patients were postmenopausal. The exact site of transition from benign to malignant epithelium was observed in 4 cases. The clinical characteristics of patients with associated endometriosis were not significantly different from those without this finding except that endometriosis was present only in patients with Grade 1 or Grade 2 carcinomas. These data suggest that ovarian endometriosis in the postmenopausal patient has the potential to undergo malignant transformation and, when detected, should be removed surgically.     

Epithelial abnormalities in cystic ovarian endometriosis.

OBJECTIVE: To evaluate the prevalence of epithelial abnormalities in cystic ovarian endometriosis. METHODS: In this observational study, the specimens of 388 consecutive patients undergoing a surgical procedure whose final diagnosis included cystic ovarian endometriosis were histopathologically reviewed. The prevalence and patient characteristics of cases featuring epithelial metaplasia, hyperplasia, atypia, and endometrioid carcinoma arising in endometriosis were analyzed. RESULTS: The epithelial lining was evaluable in 339 cases. Left-sided cysts were significantly more common than right-sided ones (P < 0.0001). The observed prevalence was 12.1% for metaplasia, 9.4% for hyperplasia, 5.9% for atypia, and 4.1% for endometrioid carcinoma arising in endometriosis. Complex hyperplasia, but not simple hyperplasia or metaplasia, was significantly more common in cases with associated endometrioid carcinoma than in all other cases (P < 0.00001). A statistically significant trend for increasing age from normal epithelium to carcinoma was observed (P < 0.001). CONCLUSIONS: Epithelial abnormalities are a common finding in cystic ovarian endometriosis. Despite their clinical significance being still debated, complex hyperplasia and atypia can be associated with malignant transformation of endometriosis. Their observation in a surgical specimen, particularly in older patients, should indicate a careful examination of the entire lining of the cyst and a strict follow-up of the patient.     

Inguinal endometriosis: A systematic review

Inguinal endometriosis is a very rare entity with uncertain pathophysiology, that poses several diagnostic and therapeutic challenges. This study aimed to summarize published literature on the diagnosis and treatment of this condition. Thus, a systematic literature search was conducted in PubMed/MEDLINE, Scopus and the Cochrane Library. An effort was made to numerically analyze all parameters included in case reports and retrospective analyses, as well. The typical and atypical features of this condition, investigations used, type of treatment and histopathology were recorded. More specifications about the surgical treatment, such as operations previously performed, type of surgery and treatment after surgery have been acknowledged. Other sites of endometriosis, the presence of pelvic endometriosis and the follow-up and recurrence have been also documented. Overall, the search yielded 61 eligible studies including 133 cases of inguinal endometriosis. The typical clinical presentation includes a unilateral inguinal mass, with or without catamenial pain. Transabdominal or transvaginal ultrasound was typically used as the first line method of diagnosis. Groin incision and exploratory surgery was the treatment indicated by the majority of the authors, while excision of part of the round ligament was reported in about half of the cases. Chemotherapy and radiotherapy were initiated in cases of coexisting endometriosis-related neoplasia. Inguinal recurrence or malignant transformation was rarely reported. The treatment of inguinal endometriosis is surgical and a long-term follow-up is needed. More research is needed on the effectiveness of suppressive hormonal therapy, recurrence rate and its relationship with endometriosis-associated malignancies.     

Endometriosis of the small bowel. Case reports and review of the literature

Endometriosis has been reported with increasing frequency in the literature in recent years, particularly endometriosis in nongynecological sites. Primary endometriosis of the ileum is of particular concern due to the high incidence of small bowel obstruction. The treatment in the past has been castration and resection of the affected bowel, with no guarantee of cure. Two cases are presented which indicate that the hormonal therapy with Danocrine and laser vaporization of endometriotic lesions involving the ileum may alter the natural history of progressive ileal obstruction. A comprehensive review of the literature was undertaken which revealed 204 reported cases of endometriosis of the ileum. New recommendations regarding management of small intestinal endometriosis are proposed.     

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.     

Malignant transformation of ovarian endometriosis

One hundred forty-seven cases of ovarian endometriosis, encountered from 1976 to 1999 at Tsukuba University Hospital, were studied to clarify the incidence of malignant transformation. There were 18 cases (12.2%) of atypical endometriosis, among which we found a case (5.6%) of ovarian cancer arising from endometriosis not diagnosed before surgery. This is accounted for 0.7% of all ovarian endometriosis cases. Because the incidence was equal to that of the previous reports, it is most likely that the malignant change in ovarian endometriosis occurred in 0.7% of this disease.     

Endometriosis of the perineum; report of two new cases and a review of literature.

The incidence of endometriosis at the episiotomy site is quite rare. We have experienced two cases of perineal endometriosis over a 9 year period. The typical clinical history and local findings enable us to make the correct diagnosis of both cases. The treatment of choice is complete surgical excision of endometrial tissue and usually obtains permanent cure. A review of the English literature showed there were 66 cases reported previously. The possible pathogensis of endometriosis and various modality of treatment were also discussed.     

Ovarian carcinomas in endometriosis: an immunohistochemical and comparative genomic hybridization study.

Malignant transformation of endometriosis, an uncommon phenomenon, can occur in gonadal and extragonadal sites and results in a wide histological range of tumors. Published series reporting malignant transformation of endometriosis have largely been confined to clinical and histopathological discussions with no studies reporting oncoprotein expression and genetic alterations. We report three cases of carcinomas arising in ovarian endometriosis: a serous cystadenocarcinoma, an endometrioid carcinoma with squamous differentiation, and a pure squamous cell carcinoma. Each tumor was analyzed immunohistochemically to compare oncoprotein expression (p53, bcl2, cyclin D1, and c-erb B2) between the tumors and the endometriotic tissue as well as with comparative genomic hybridization (CGH) to compare genetic alterations. All three tumors expressed nuclear p53, in contrast to the endometriotic tissue in which no p53 expression was found. Both endometrial and tumor tissue expressed bcl-2. No expression of cyclin D1 or c-erb B2 was detected in endometriotic or tumoral tissues. The CGH analysis revealed one or two chromosomal aberrations in each of the three tumors with gains on chromosomes 1q, 8q, and 13q, and losses on chromosome 10p. The endometriotic tissue, as expected, showed a normal genetic profile. These results suggest that p53 protein abnormalities and chromosomal aberrations may be involved in malignant transformation of endometriosis in the ovary. However, our results are limited by the number of cases examined and a definite conclusion on the pathogenesis of this process should be followed by future studies with a larger number of cases.