Endometriumkarzinom unter GnRH-Analoga-Therapie bei Endometriose

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This case report describes a 35-year-old patient with endometriosis and adenomyosis who unexpectedly developed endometrium carcinoma during GnRH analogue therapy.

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This case report describes a 35-year-old patient with both endometriosis and adenomyosis who developed an unexpected endometrial carcinoma during treatment with the GnRH analogue Enantone. The malignancy arose from complex atypical hyperplasia and was discovered incidentally after the patient requested a hysterectomy due to fear of cancer, before the therapy course was completed. Although the authors note that endometriosis itself does not increase endometrial cancer risk, they highlight that obesity creates peripheral estrogen synthesis unaffected by GnRH therapy, potentially raising risk in overweight patients. Relevance to endometriosis: Centrally about the condition — specifically discussing a case of endometriosis (and adenomyosis) where GnRH analogues were used as therapy, leading to the incidental discovery of endometrial carcinoma.

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Abstract

Endometriosis affects a 10 % of women during their reproductive years. Unequoral statistics concerning the incidence of adenomyosis are not available although a combined occurrence of both diseases is found in a 20 % of cases. The risk that malignancy arises from endometrioid tissue typical for endometriosis is between a 0.3-1 %. 75 % of these malignancies are ovarian cancer in conjunction with pre-existing ovarian endometriosis; less frequently extraovarian malignancies are found. The development of malignancy of adenomyosis is very rarely reported. In this report we present the case of a 35 year old patient who suffered from both, endometriosis and adenomyosis and who underwent a therapy using GnRH analogues. After five months and before the completion of the therapy a hysterectomy with conservation of the ovaries was performed at the request of the patient (carcinophobia). The histology confirmed the diagnosis of adenomyosis and demonstrated the unexpected finding of an endometrium carcinoma. This latter arose from a complex atypical hyperplasia surrounded by hypoplastic endometrium. There is some evidence that suggests a slightly elevated risk of breast and ovarian cancer as well as haematological malignancies amongst patients with endometriosis. However, there does not appear to be an increased risk of endometrial carcinoma. Adipositas leads to an increased risk for the development of endometrial carcinoma due to the increased conversion of testosterone to estrone in fat. The peripheral synthesis of estrone is unaffected by GnRHa-therapy. A progesterone containing HRT should be added to a GnRHa-therapy in overweight patients to prevent the development of endometrial hyperplasia and/or carcinoma. In conclusion a careful indication has to be made for GnRHa-therapy in overweight patients and before and during the therapy high resolution ultrasound scan should be performed to evaluate the endometrium in those patients.
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Subscribe to RSS DOI: 10.1055/s-2002-38912 © Georg Thieme Verlag Stuttgart · New York Endometriumkarzinom unter GnRH-Analoga-Therapie bei Endometriose Endometrial Carcinoma Using GnRH Analogues Therapy in EndometriosisPublication History Publication Date: 24 April 2003 (online) Zusammenfassung Die Endometriose tritt mit einer Inzidenz von 10 % bei Frauen im reproduktiven Alter auf. Eindeutige Zahlen für die Inzidenz der Adenomyosis uteri liegen nicht vor, jedoch wird ein gemeinsames Vorkommen beider Erkrankungen in ca. 20 % der Fälle beschrieben. Das Entartungsrisiko von endometrioiden Geweben, wie es für die Endometriose typisch ist, liegt bei 0,3-1 %. In 75 % der Fälle handelt es sich dabei um Ovarialkarzinome bei vorbestehender Ovarialendometriose, seltener um extraovarielle Malignome. Die maligne Transformation einer bestehenden Adenomyose ist nur sehr selten beschrieben worden. In der vorliegenden Kasuistik wird der Fall einer 35-jährigen Patientin demonstriert, die sowohl an Endometriose als auch an einer Adenomyose erkrankt war und bei der eine Therapie mit dem GnRH-Analogon Enantone® durchgeführt wurde. Noch vor Abschluss der Behandlung wurde nach 5 Monaten auf Drängen der Patientin (Karzinophobie) die einfache Hysterektomie durchgeführt. Im histologischen Präparat zeigte sich als Zufallsbefund, neben den oben genannten Diagnosen, ein Endometriumkarzinom, das auf dem Boden einer komplexen atypischen Hyperplasie, umgeben von hypoplastischem Endometrium, entstanden war. Einige Hinweise deuten auf ein leicht erhöhtes Risiko von Endometriosepatientinnen hin, an Mamma- und Ovarialkarzinom sowie an hämatologischen Malignomen zu erkranken. Ein erhöhtes Risiko der Frauen an einem Endometriumkarzinom zu erkranken besteht jedoch nicht. Adipositas ist aufgrund der erhöhten Konversion von Testosteron zu Östron im Fettgewebe ein Risikofaktor für die Entwicklung eines Endometriumkarzinoms. Die periphere Östronsynthese bleibt unter GnRH-Therapie unbeeinflusst. Eine progesteronbetonte Add-back- Substitution sollte daher bei adipösen Patientinnen durchgeführt werden, um die Entwicklung einer Endometriumhyperplasie bzw. eines Karzinoms zu verhindern. Festzuhalten ist, dass die Indikationsstellung einer Therapie mit GnRH-Analoga bei Frauen mit Adipositas streng zu stellen ist und vor sowie während der Therapie zur Beurteilung des Endometriums ein hochauflösender Ultraschall durchgeführt werden sollte. Abstract Endometriosis affects a 10 % of women during their reproductive years. Unequoral statistics concerning the incidence of adenomyosis are not available although a combined occurrence of both diseases is found in a 20 % of cases. The risk that malignancy arises from endometrioid tissue typical for endometriosis is between a 0.3-1 %. 75 % of these malignancies are ovarian cancer in conjunction with pre-existing ovarian endometriosis; less frequently extraovarian malignancies are found. The development of malignancy of adenomyosis is very rarely reported. In this report we present the case of a 35 year old patient who suffered from both, endometriosis and adenomyosis and who underwent a therapy using GnRH analogues. After five months and before the completion of the therapy a hysterectomy with conservation of the ovaries was performed at the request of the patient (carcinophobia). The histology confirmed the diagnosis of adenomyosis and demonstrated the unexpected finding of an endometrium carcinoma. This latter arose from a complex atypical hyperplasia surrounded by hypoplastic endometrium. There is some evidence that suggests a slightly elevated risk of breast and ovarian cancer as well as haematological malignancies amongst patients with endometriosis. However, there does not appear to be an increased risk of endometrial carcinoma. Adipositas leads to an increased risk for the development of endometrial carcinoma due to the increased conversion of testosterone to estrone in fat. The peripheral synthesis of estrone is unaffected by GnRHa-therapy. A progesterone containing HRT should be added to a GnRHa-therapy in overweight patients to prevent the development of endometrial hyperplasia and/or carcinoma. In conclusion a careful indication has to be made for GnRHa-therapy in overweight patients and before and during the therapy high resolution ultrasound scan should be performed to evaluate the endometrium in those patients. Schlüsselwörter Endometriose - Adenomyose - GnRH-Analoga - Adipositas - atypische komplexe Hyperplasie - Endometriumkarzinom Key words Endometriosis - adenomyosis - GnRH-analoga-treatment - obesity - complex atypical hyperplasia - endometrium carcinom Literatur - 1 Agorastos T, Bontis J, Vakiani T O, Vavilis D, Constantinidis T. Treatment of endometrials hyperplasia with gonadotropin-releasing hormone agonists: pathological, clinical, morphometric and DNA-cytometric data. Gynecol Oncol. 1997; 65 102-114 - 2 Baloglu H, Cannizzaro L A, Jones J, Koss L G. Atypical endometrial hyperplasia shares genomic abnormalities with endometrioid carcinoma by comparative genomic hybridization. Hum Pathol. 2001; 32 (6) 615-22 - 3 Bird C C, Mcelin T W, Manalo-Estrella P. The elusive adenomyosis of the uterus-revisted. Am J Obstet Gynecol. 1972; 112 583-587 - 4 Brinton L A, Gridley G, Persson I, Baron J, Bergqvist A. Cancer risk after a hospital discharge diagnosis of endometriosis. Am J Obstet Gynecol. 1997; 177 (5) 1274-5 - 5 Colman H I, Rosenthal A H. Carcinoma developing in areas of adenomyosis. Obstet Gynecol. 1959; 14 342-348 - 6 Creasman W, Odicino F, Maissonneuve P, Benedet J, Shepherd J, Sideri M and Pecorelli S. Carcinoma of the corpus uteri. J of Epidemiology and Biostatistics. 1998; Vol. 3, No. 1 35-61 - 7 Giammalvo J T, Kaplan K. The incidence of endometriosis interna in 120 cases of carcinoma of the endometrium. Am J Obstet Gynecol. 1958; 75 161-166 - 8 Grimbizis G, Tsalikis T, Tzioufa V, Kasapis M, Mantalenakis S. Regression of endometrial hyperplasia after treatment with the gonadotrophin- releasing hormone analogue triptorelin: a prospective study. Hum Reprod. 1999; 14 (2) 479-484 - 9 Kurman RJ and Norris H J. Endometrial Hyperplasia and related cellular changes. In BlausteinŽs pathology of the female genital tract Spinger Verlag 411-435 - 10 Marcus C C. Relationship of adenomyosis uteri to endometrial hyperplasia and endometrial carcinoma. Am J Obstet Gynecol. 1961; 82 408-416 - 11 Martin D C. Cancer and endometriosis: do we need to be concerned?. Semin Reprod Endocrinol. 1997; 15 319-24 - 12 Olive D L, Silverberg K M. Endometriosis and Adenomyosis. In: Copeland L, Textbook of GynecologySaunders Company, Philadelphia 1993: 481-504 - 13 Olive DL and Pritts E A. Treatment of Endometriosis. N Engl J Med. 2001; Vol. 345, No. 4 266-275 - 14 Perez-Medina T, Bajo J, Folgueira G, Haya J, Ortega P. Atypical endometrial hyperplasia treatment with progestogens and gonadotopin-releasing hormone analogues: long term follow up. Gynecol Oncol. 1999; 73 (2) 299-304 - 15 Reimnitz C, Brand E, Nieberg R K, Hacker N F. Malignancy arising in endometriosis associated with unopposed estrogen replacement. Obstet Gynecol. 1988; 71 444-7 - 16 Sasaki T, Sugiyama T, Nanjo H, Hoshi N, Murakami M, Sugita A, Takahashi M, Kawamura K, Ono I, Masuda H. Endometroid adenocarcinoma arising from adenomyosis: Report and immunohistochemical analysis of an unusual case. Path Intern. 2001; 51 308-313 PD Dr. Dr. A. D. Ebert Universitätsklinikum Benjamin Franklin · Endometriosezentrum Berlin · Frauenklink und Poliklinik Hindenburgdamm 30 12200 Berlin Email: [email protected]

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Condition tags

endometriosisadenomyosis

MeSH descriptors

Endometrial Neoplasms Endometriosis Gonadotropin-Releasing Hormone Gonadotropin-Releasing Hormone Adult Endometrial Neoplasms Endometrial Neoplasms Endometriosis Female Gonadotropin-Releasing Hormone Humans Hysterectomy Treatment Outcome

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