Malignant tumors arising in endometriosis: clinical-pathological study and flow cytometry analysis

doi:10.1016/S0301-2115(96)02563-8

European Journal of Obstetrics & Gynecology and Reproductive Biology

Volume 70, Issue 1, December 1996, Pages 69-74

https://doi.org/10.1016/S0301-2115(96)02563-8 Get rights and content

Abstract

Background: Malignant transformation to endometriosis is a well documented phenomenon that occurs most commonly in the ovaries with cancer arising in extra-ovarian endometriosis being a rare event. Methods: A retrospective clinical-pathological evaluation of eleven cases with malignant tumors arising in endometriosis was performed to evaluate the prognostic impact of various factors. Nuclear DNA content (ploidy) was assessed through flow cytometric study. Results: Ovarian origin was identified in eight cases and three were associated with extra-ovarian endometriosis. Histologic type was endometrioid carcinoma in ten patients. The eleventh case had high grade endometrial stromal sarcoma. All tumors were diploid with no relation to stage, grade, or clinical outcome. The S-phase fraction (SPF) was analyzed in nine patients and no correlation could be demonstrated with any histologic parameters or clinical outcome. Conclusions: The DNA content seems to have no association with the classical prognostic parameters in these cases.

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Cited by (25)

The relationship of endometriosis and ovarian malignancy: a review
2008, Fertility and Sterility
Citation Excerpt :
Genomic instability is a known characteristic of cancer cells. Endometriosis demonstrates somatically acquired genetic alterations similar to those found in cancer, leading to clonal expansion of genetically abnormal cells, as demonstrated in several studies (22, 23). Endometriotic cysts are monoclonal and characterized by the loss of heterozygosity in 75% of endometriotic cyst cases with associated adenocarcimona, and even in 28% of cases without accompanying carcinoma.
To review the malignant potential of endometriosis based on epidemiologic, histopathologic, and molecular data.
Literature review.
The pathogenesis of endometriosis remains unclear. The histopathologic development of endometriosis has undergone long-term investigation. Studies have confirmed histologic transition from benign endometriosis to ovarian malignancy, including malignant transformation of extraovarian endometriosis. The prevalence of endometriosis in patients with epithelial ovarian cancer, especially in endometrioid and clear cell types, has been confirmed to be higher than in the general population. Ovarian cancers and adjacent endometriotic lesions have shown common genetic alterations, such as PTEN, p53, and bcl gene mutations, suggesting a possible malignant genetic transition spectrum. Furthermore, endometriosis has been associated with a chronic inflammatory state leading to cytokine release. These cytokines act in a complex system in which they induce or repress their own synthesis and can cause unregulated mitotic division, growth and differentiation, and migration or apoptosis similar to malignant mechanisms.
The malignant potential of endometriosis holds serious implications for management, such as the need for earlier and more meticulous surgical intervention for complete disease treatment.
Ureteral endometriosis: clinicopathological and immunohistochemical study of 7 cases
2008, Human Pathology
Citation Excerpt :
In most cases of premalignant and malignant changes in ureteral endometriosis, there is a history of prolonged unopposed estrogen treatment. However, the role of hormonal therapy in the pathogenesis of cancer is still unclear, and malignant changes in endometriosis have also been seen in patients without any replacement therapy, even after menopause [16,19]. Although a few studies have addressed the immunohistochemical findings in nonureteric endometriosis [20-22], the immunoprofile of ureteral endometriosis has not been well documented.
Ureteral endometriosis is a rare yet important entity that can lead to renal failure due to silent obstruction of the ureter. Awareness of clinical and morphologic features can help in early detection and treatment. We analyzed the clinical, pathologic, and immunohistochemical findings of 7 cases of ureteral endometriosis. Mean age of patients was 51 years. All patients presented with hydroureter, accompanied in the most cases by hydronephrosis. Superimposed pyelonephritis was experienced by 2 of 7 patients. Most patients (4 of 7) had previously undergone total abdominal hysterectomy with bilateral salpingo-oophorectomy. In 6 of 7 cases, endometriosis involved the left ureter. The distal one third of the ureter was involved in 6 cases, whereas the middle third was involved in 1 case. In 4 cases, endometriosis was located extrinsic to the ureter, whereas in 3 cases, the ureter showed intrinsic involvement by endometriosis. One case showed simple endometrial hyperplasia. Surgical management included nephrectomy in 2 cases, distal ureterectomy with reimplantation in 3 cases, ureteral stent placement followed by ureteroureterostomy in 1 case, and relief of ureteral obstruction by resection of pelvic endometrioma in 1 case. Immunostains for cytokeratin-7 (CK7) and progesterone receptor (PR) were positive in all of the cases, whereas immunostains for estrogen receptor (ER) were positive in 83% of cases and immunostains for CK20 were negative in all cases. CA125 immunostains were positive in 67% of cases. The stromal cells were positive for CD10, ER, and PR immunostaining. Our findings suggest that the diagnosis of ureteral endometriosis is preceded in most cases by hysterectomy and bilateral salpingo-oophorectomy, possibly because of prior symptoms related to adenomyosis or pelvic endometriosis and that ureteral endometriosis has a strong predilection for involvement of the lower third of the left ureter. Ureteral endometriosis should be included in the differential diagnosis of obstructive ureteral lesions in women, particularly those involving the lower third of the left ureter, even in postmenopausal patients. Immunostains for ER, PR, CK7, CA125, and CD10 can be helpful in challenging cases.
Malignant extraovarian endometriosis: A review
2006, European Journal of Surgical Oncology
Malignant transformation in extra-ovarian endometriosis is a rare but known complication. This distinct pathological entity is reviewed with a specific focus on aetiology and treatment.
Studies were identified by searching the English language literature in the MEDLINE database and by an extensive review of bibliographies from articles found through that search.
Up to 1% of women with endometriosis will develop endometriosis-associated neoplasm. Almost a quarter of the reported cases of malignancy in endometriosis have involved extra-ovarian tissues. In many cases, hormonal factors may play a role in its pathogenesis. Estrogen monotherapy in obese patients significantly increase the risk of malignant extra-gonadal endometric transformation. Genetic anomalies have also been reported such as loss of heterozygosity on chromosome 5q.
For patients with disease confined to the site of origin, a 82–100% 5-year survival has been noted for endometrioid cell type; disseminated intraperitoneal disease, however, has a very poor associated prognosis, with a 0–12% 5-year survival overall.
Women with endometriosis-associated cancers most likely represent a different class of patients than traditional ovarian cancer patients and may require different therapeutic options.
Malignant tumors arising in extra-ovarian endometriosis: A case report
2005, Journal de Gynecologie Obstetrique et Biologie de la Reproduction
Nous rapportons un cas d’endométriose extra-ovarienne dégénérée. Il s’agit d’une évolution rare de la maladie endométriosique dont la fréquence est estimée à 0,9 %.
Le diagnostic est, dans plus de 50 % des cas, évoqué après un bilan de douleurs abdominales. La dégénérescence est établie quand coexistent un contingent endométriosique et un contingent néoplasique dont le type histologique est compatible avec une origine endométriale. La prise en charge thérapeutique nécessite le plus souvent un premier temps chirurgical aussi maximaliste que possible pour effectuer le stagging de la maladie. Dans un second temps, un traitement complémentaire est envisageable, au cas par cas, associant ou non, de la radiothérapie, de la chimiothérapie, voire même de l’hormonothérapie.
Le pronostic de ce type de tumeur est très variable, allant de 10 à 100 % de survie à 5 ans, dépendant notamment du type histologique et de la localisation de la maladie.
We report a case of degenerative extra-ovarian endometriosis. This is a rare complication of endometriosis, the frequency of which is estimated at 0.9%.
In more than 50% of the cases, the diagnosis is made following investigation for abdominal pain. If the degeneration is of the same histological type as the endometriosis, it can be said to have arisen from the endometriosis. First-line treatment is surgery, removing as much endometriosis as possible, staging at this point is also necessary. Second-line treatment, with chemotherapy, radiotherapy and even hormonotherapy may be needed.
Prognosis for this tumor is variable, from 10 to 100% five-year survival, depending on histological type and localization of the disease.
Malignant tumours arising in extraovarian endometriosis: Three cases reports and review of the literature
2004, Annales de Chirurgie
Dans les formes extraovariennes, la coexistence de tissu endométriosique et d'un néoplasme suffit à établir l'origine endométriosique de la dégénérescence. Les estrogènes et la perte d'hétérozygosie du chromosome 5q seraient impliqués dans leur carcinogenèse. Le plus souvent il s'agit de tumeurs de type endométrioïde révélées par des douleurs abdominales. La fréquence des transformations malignes des foyers d'endométriose extraovarien est estimée à 0,8 % et la survie des formes endométrioïdes confinées au pelvis avoisinerait les 100 % à cinq ans après chirurgie et radiothérapie.
In its extraovarian form, co-existence of carcinoma and endometriosis is a sufficient argument used in favour of the malignant transformation of endometric lesions. Estrogen as well as the loss of 5q chromosome heterozygosity are considerate as initiators of that type of carcinogenesis. Endometrioid histological type is the most frequent and is revealed usually by abdominal pain. The incidence of carcinoma arising in endometriosis is about 0.8% and 5-year survival rate of pelvic endometrioid form is about a 100% after surgery and radiotherapy.
Endometriosis and the development of malignant tumours of the pelvis. A review of literature
2004, Best Practice and Research: Clinical Obstetrics and Gynaecology
For several decades, endometriosis has been suspected of playing a role in the aetiology of ovarian cancer. The literature concerning a possible histogenesis of ovarian cancer from benign endometriosis is reviewed in this chapter. Epidemiological evidence from large-cohort studies confirms endometriosis as an independent risk factor for ovarian cancer. Further circumstantial evidence for this link was found in the common risk factors for ovarian cancer and endometriosis. These risk factors influence retrograde menstruation and endometriosis in the same positive or negative way. Based on data in the literature, the prevalence of endometriosis in epithelial ovarian cancer has been calculated to be 4.5, 1.4, 35.9, and 19.0% for serous, mucinous, clear-cell and endometrioid ovarian carcinoma, respectively. The risk of malignant transformation in ovarian endometriosis was calculated at 2.5% but this might be an underestimate. In addition, some authors described atypical endometriosis in a spatial and chronological association with ovarian cancer. Finally, molecular studies have detected common alterations in endometriosis and ovarian cancer.
These data suggest that some tumours, especially endometrioid and clear-cell carcinomas, can arise from endometriosis. Moreover, endometriosis-associated ovarian cancer represents a distinct clinical entity, with a more favourable biological behaviour, given a lower stage distribution and better survival than non-endometriosis-associated ovarian cancer.

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Regular articleMalignant tumors arising in endometriosis: clinical-pathological study and flow cytometry analysis

Abstract

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