{"paper_id":"d62235c7-9ab4-4e93-9057-66d94c4b0ab3","body_text":"Introduction\n!\nEndometriosis is an oestrogen-dependent, prolif-\nerative disease that affects ca. 4 to 8 % of all wom-\nen in child-bearing age. It is in principle a benign\ndisease; however, it does exhibit the properties of\nprogression, neoangiogenesis, invasion and organ\ndestruction that also characterise malignant pro-\ncesses. Sampson described for the first time the\nmalignant degeneration of peritoneal endome-\ntriosis [1] and ovarian endometriosis [2], and also\nformulated the criteria that are still valid today to\nprove histologically the malignant degeneration\nof endometriosis:\n1. both carcinomatous and benign endometrial\ntissue must be detectable in the same organ,\n2. cancer structures and benign endometrial tis-\nsue must be histologically correlated like ad-\nenocarcinoma of the uterus is to the endome-\ntrium,\nAbstract\n!\nMalignant degeneration of colon endometriosis is\na very rare event. We report here on three cases. A\n48-year-old woman with a 10-year history of en-\ndometriosis was treated for a rectal adenocarci-\nnoma, a 61-year-old G1P1, who was operated at\nthe age of 40 years for ovarian endometriosis and\nagain at the age of 53 years for an endometriosis-\nassociated endometroid ovarian carcinoma, pre-\nsented for therapy for a lymph node recurrence\nof the ovarian cancer and, secondly, due to a ma-\nlignantly degenerated rectum-sigmoid colon en-\ndometriosis; furthermore a 54-year old woman\nwith a 21-year history of endometriosis was oper-\nated for malignant colon endometriosis. The tu-\nmour occurred during an adjuvant anti-oestrogen\ntreatment with an aromatase inhibitor following\nsurgical and radiotherapy for breast cancer. In all\ncases a radical cancer operation was followed by\nadjuvant chemotherapy and in one case with an\nadditional radiotherapy. In the follow-up periods\nof 18 months, 2 and 5 years, respectively, all\nwomen remained free of recurrences. Although\nthis is not a randomised controlled study due to\nthe rare occurrence of such cases, a radical opera-\ntion followed by individualised adjuvant therapy\nappears to be the treatment of choice.\nZusammenfassung\n!\nDie maligne Entartung einer Darmendometriose\nist sehr selten. Wir berichten über 3 Fälle. Eine\n48-jährige Patientin mit 10-jähriger Endometrio-\nseanamnese wurde wegen eines Adenokarzinom\ndes Rektums behandelt; eine 61-jährige G1P1,\ndie erstmals im Alter von 40 Jahren wegen Ova-\nrialendometriose und dann im Alter von 53 Jah-\nren wegen eines Endometriose-assoziierten en-\ndometrioiden Ovrialkarzinoms operiert wurde,\nkam wegen Lymphknotenrezidiv des Ovarialkar-\nzinoms und zweitens wegen einer maligne ent-\narteten Rektum-Sigma-Endometriose zur Thera-\npie; ferner wurde eine 54-jährige Patientin, die\nseit 21 Jahren an Endometriose litt, wegen malig-\nner Darmendometriose operiert. Der Tumor war\nwährend einer adjuvanten Antiöstrogenbehand-\nlung mit einem Aromatasehemmer nach operier-\ntem und bestrahltem Mammakarzinom entstan-\nden. In allen Fällen erfolgte eine radikale Karzi-\nnomoperation gefolgt von adjuvanter Chemo-\ntherapie und in einem Fall zusätzlich adjuvanter\nRadiatio. Im Nachuntersuchungszeitraum von\n18 Monaten, 2 bzw. 5 Jahren sind alle Frauen bis-\nher rezidivfrei. Obwohl es keine randomisierten,\nkontrollierten Studien wegen der Seltenheit der\nFälle gibt, scheint die radikale Operation gefolgt\nvon einer individualisierten adjuvanten Therapie\ndie Behandlung der Wahl.\nDiagnostics and Therapy for Malignant (Degenerate)\nColon Endometriosis – Three Case Reports\nZur Diagnostik und Therapie maligne entarteter Darmendometriose –\n3 Fallberichte\nAuthors R. Schutz 1, J. Woziwodzki 2, K.-W. Schweppe 1\nAffiliations 1 Endometriosezentrum Ammerland, Frauenklinik, Ammerland-Klinik GmbH, Akademisches Lehrkrankenhaus der Medizini-\nschen Hochschule Hannover, Westerstede\n2 Pathologisches Institut Aurich/Westerstede, Westerstede\nKey words\nl\" bowel endometriosis\nl\" malignant degeneration\nl\" endometriosis‑associated\ncarcinoma\nSchlüsselwörter\nl\" Darmendometriose\nl\" maligne Entartung\nl\" Endometriose‑assoziiertes\nKarzinom\nreceived 6. 8. 2015\nrevised 9. 11. 2015\naccepted 17. 11. 2015\nBibliography\nDOI http://dx.doi.org/\n10.1055/s-0041-109769\nGeburtsh Frauenheilk 2016; 76:\n417–422 © Georg Thieme\nVerlag KG Stuttgart · New York ·\nISSN 0016‑5751\nCorrespondence\nProf. Karl-Werner Schweppe\nEndometriosezentrum\nAmmerland\nFrauenklinik\nAmmerland-Klinik GmbH\nAkademisches Lehrkrankenhaus\nder Medizinischen Hochschule\nHannover\nLange Straße 38\n26655 Westerstede\nkwschweppe@ewetel.net\n417\nSchutz R et al. Diagnostics and Therapy … Geburtsh Frauenheilk 2016; 76: 417 –422\nCase Report\nDeutsche Version unter:\nwww.thieme-connect.de/\nejournals/gebfra\n\n\n3. the adenocarcinoma has genuinely arisen in the organ.\nCorner and co-workers [3] additionally required histological evi-\ndence for a gradual transition from benign to malignant struc-\ntures.\nBeside the genital manifestations, an extragenital endometrial at-\ntack is found in up to 30 % of the cases. These are above all colon\nand bladder endometrioses whereas other locations such as\nlungs, lymph nodes, skin etc. are very rare. With a risk of up to\nca. 1 % (see [4]) the malignant degeneration of an extragenital en-\ndometriosis is a rare event.\nWe report on 3 cases of malignant rectum-sigmoid colon endo-\nmetriosis and discuss the clinical problems on the basis of litera-\nture reports.\nCase Reports\n!\nCase 1\nA 48-year-old woman with an external diagnosis of a sigmoid co-\nlon carcinoma was referred to the surgical department for opera-\ntive management. On account of dysmenorrhoea, hypomenor-\nrhoea and uterus myomatosus, surgery involved myoma enuclea-\ntion, adhesiolysis, and right-sided adnexectomy since an ovarian\nendometriosis was diagnosed intraoperatively. A subsequent en-\ndocrine therapy was not initiated.\nIn 2007 her general practitioner prescribed a gastroenterological\nexamination to clarify perimenstrual pain and stool irregularities\nwith slime and blood mixed in the stool. Colonoscopy revealed at\n20 cm from the anus onwards polypoid protruding mucous\nmembranes with a slight restriction of the lumen, tissue samples\ntaken here exhibited a regularly formed colon mucosa. An MRI\nscan of the pelvis revealed a left-sided cystic ovarian lesion to-\ngether with small sigmoid lesions, and an intramural contrast be-\nhaviour suggestive for endometriosis.\nIn 2010 a laparoscopic supracervical hysterectomy with left-\nsided adnexectomy and extensive adhesiolysis was performed.\nNo information is available about the suspicion of endometriosis\nfrom the previously performed MRI scan. Histology revealed\nmultiple leiomyomas, internal adenomyosis, regressing endome-\ntriosis cysts and a haemorrhagic corpus luteum cyst on the left\novary.\nThe patient was 44 years old at this time and received no further\ngynaecological therapy and no hormone substitution after surgi-\ncal castration. With adipositas per magna (BMI 35) there were\nhardly any complaints about menopausal symptoms.\nIn June 2013 diagnostic work-up initiated by her general practi-\ntioner due to bloody diarrhoea led to the histological diagnosis of\nsigmoid colon cancer. Sonographic and radiological staging ex-\naminations did not provide any indications for metastasis. The\ntumour markers CEA and CA 19-9 were elevated at 27 ng/mL\nand 600 U/mL, respectively. On the gynaecological examination\na cystic, partly echo-poor, partly echo-rich, poorly delineated\n65 × 37 × 40 mm resistance with internal structures was found\nbehind and above the cervical stump, giving rise to the sono-\ngraphic and palpatory suspicion of recurring endometriosis of\nthe posterior compartment including the rectovaginal septum.\nAn interdisciplinary re-re-laparotomy revealed after extensive\nadhesiolysis the tumour at the level of the retrosigmoid junction\nas well as further parietal tumour elements attached to the rec-\ntum. Since the frozen section analysis showed evidence for an ad-\nenocarcinoma, a rectum resection with end-to-end anastomosis\nwas performed with the tumour being removed in toto together\nwith the in conglomerate clogged cervix uteri. This was followed\nby lymphadenectomy. In the final histology, which was con-\nfirmed by an independent pathologist, pronounced endometrio-\nsis was found in the intestinal wall reaching through to the mus-\ncularis propria and submucosa. 18 of 46 regional lymph nodes\nhad been attached by metastases, oral and aboral anastomosis\nrings were tumour-free, as was the cervix uteri.\nOn consideration of the immunohistochemical characteristics\n(l\n\" Fig. 1 and Table 1) of the adenocarcinoma, it was classified as\nan endometrial carcinoma on the basis of colorectal endometrio-\nsis in the region of the left and right adnexa in the condition after\novarian endometriosis (pT2 L1 V0 pNx pM1 [LYM] R0 G2).\nThere were no complications in the postoperative course; the in-\ndication for adjuvant chemotherapy with carboplatin and Taxol\nwas given. The patient received 6 cycles in the appropriate doses\nand intervals. In the follow-up period of to date 18 months there\nhas been no evidence for a recurrence.\nCase 2\nA 61-year-old woman was admitted to hospital in 2008 due to\npersisting lower abdominal and back pain with the suspicion of\na lower abdominal tumour. In 1987 the then 40-year-old patient\nunderwent adhesiolysis, extirpation and management of endo-\nmetriosis because of situation of the adhesions, lower abdominal\npain and a 7-cm long endometrioma in the vicinity of the left\novary; subsequent endocrine therapy was not initiated. In 1993\nhysterectomy, left-sided adnexectomy as well as extensive adhe-\nsiolysis were necessary due to recurrent endometriosis of the left\nadnexa with therapy-refractory lower abdominal pain as well as\nhyper- and dysmenorrhoea. Histology confirmed the deep infil-\ntrating ovarian endometriosis together with adenomyosis uteri\ninterna.\nTable 1 Immunohistochemical findings in the 3 cases.\nIHC Tissue CK7 CK20 ER PR PAX8 WT1 CD10 P53\nCase 1 benign endometriosis\nmalignant endometriosis\n+\n+\n–\n–\n+\n+\n+\n–\n+\n+\n–\n–\n+\n+\n–\n–\nCase 2 benign endometriosis\nmalignant endometriosis\n+\n+\n–\n(+)\n+\n(+)\n+\n–\n+\n+\n–\n–\n+\n+\n–\n–\nCase 3 benign endometriosis\nborderline components\nmalignant endometriosis\n+\n+\n+\n–\n–\n(+)\n+\n+\n–\n+\n–\n–\n+\n+\n+\n–\n+\n+\n+\n+\n–\n–\n–\n+\n+ = positive, (+) = weakly positive, – = negative, IHC = immunohistochemistry, ER = oestrogen receptor, PR = progesterone receptor, CK7 = immunohistochemical marker for epi-\nthelial tumours, CK20 = immunohistochemical marker for intestinal tumours, PAX-8 = immunohistochemical marker for Müller ʼs epithelium, WT1 = immunohistochemial marker\nfor serous tumours, CD10 = immunohistochemical marker for endometrial stroma, P53 = immunohistochemical marker for high-grade endometrial cancer\n418\nSchutz R et al. Diagnostics and Therapy … Geburtsh Frauenheilk 2016; 76: 417 –422\nGebFra Science\n\n\nDuring 1997 the patient complained of moderate menopausal\nsymptoms which, however, did not require hormone substitution\ntherapy. In 2000 the patient underwent a renewed re-laparoto-\nmy due to right-sided lower abdominal pain and a sonograph-\nically as well as palpably unclear, right-sided, adnexa process of\n10 × 8 × 7 cm in size. Histology revealed a moderately differenti-\nated endometroid adenocarcinoma (pT1c G1 –2), which was op-\nerated appropriately for its stage. The staging procedure did not\nreveal any lymph node metastases, or any pulmonary, bone or\nliver metastases. CA 12-5 with 13 U/mL was in the normal range;\nthe tumour cells were hormone receptor positive (PR 90 %, ER\n20 %). Adjuvant gestagen therapy with megestrol acetate 40 mg\ndaily was indicated. After about 5 years the patient terminated\nthis therapy due to unacceptable side effects (weight gain, de-\npressive moods).\nIn 2008 the patient complained again about increasing lower ab-\ndominal pain. During the diagnostic work-up a large cherry-\nsized, poorly moveable resistance was found just above the stub\nof the vagina, which was not well delineated in the cranial direc-\ntion, on sonography a 19 × 18 × 25 mm cystic, partly solid tumour\nwas visualised that could not exactly be delineated from the pos-\nterior bladder wall and the anterior wall of the rectum.\nA re-re-relaparatomy was performed due to the suspicion of a re-\ncurrence. After adhesiolysis palpable tumour formations were\ndetected pararectally deep behind the stub of the vagina and in\nthe region of the sigmoid colon. In the mesosigmoid enlarged\nlymph nodes were conspicuous, an intraoperative frozen section\nanalysis revealed metastatic infiltration by an adenoid, partly pa-\npillary structured tumour that is in accord with a primary meta-\nstatic endometrial carcinoma. A deep anterior rectum resection\nwith lymphadenectomy was performed. The final histological\nanalysis demonstrated two types of tumour formations:\n1. a poorly differentiated ER-negative, PR-negative adenocarcino-\nma in the vicinity of the regional lymph nodes, the mesocolon\nand mesorectum as well as paraaortically,\n2. cystic dilated endometriosis structures with atypically trans-\nformed epithelial formations in the form of a papillary-serous\ncarcinoma in situ with tumour propagation in the region of the\nintramural neural plexus of the intestinal wall and invasive tu-\nmour elements in the region of the intestinal wall endometrio-\nsis. In addition, focal dilated endometriosis cysts without atyp-\nical cell formations.\nThe resection margins were free of tumour. Eight of the total of\n14 removed lymph nodes had been attacked by metastases.\nIn conclusion, the findings were classified on the one hand as en-\ndometriosis of the rectum-sigmoid colon with progressive dys-\nplasia, carcinoma in situ and perineural invasion and, on the oth-\ner hand, as lymph node recurrence of the endometrial ovarian\nFig. 1 a to d Cross-section through the tumorous thickened intestinal wall\nwith a slice of the lumen (case 1). One can see the normal colon mucosa\n(on the right of the picture) and the cancerous pockets in the intestinal wall.\na Haematoxylin and eosin staining, magnification 10 ×. b CK7 immunohis-\ntochemical staining with positive tumour cells and negative intestinal muco-\nsa that excludes a primary adenocarcinoma of the intestine. c Staining of the\noestrogen receptors shows a weakly positive reaction of the malignant cells.\nd CK20 immunohistochemical staining shows negative tumour cells and\npositive reaction of the intestinal mucosa, in accord with the CK7 findings.\n419\nSchutz R et al. Diagnostics and Therapy … Geburtsh Frauenheilk 2016; 76: 417 –422\nCase Report\n\n\ncarcinoma treated surgical and with adjuvant therapy 8 years\npreviously. The patient received an adjuvant chemotherapy with\ncarboplatin AUC5 and Taxol (175 mg/m\n2) in the appropriate\ndoses and intervals. All follow-up examinations of the abdomen\nwere unremarkable. A second recurrent disease had not occurred\nat five years after surgery.\nIt should be mentioned that two years ago the patient underwent\nbreast-conserving surgery and received adjuvant therapy for a\npoorly differentiated invasive ductal breast cancer (pT1c pTIS L0\nV0 pN0 [SN 0 –1] R0). The patient has also not suffered from a re-\ncurrence of the breast disease.\nCase 3\nA 54-year-old woman was admitted to hospital in 2009 because\nof recurring abdominal pain, constipation, loss of appetite and\nloss of energy with an unclarified tumour in the lesser pelvis. 21\nyears before, the then 33-year-old woman underwent a hysterec-\ntomy and resection of a deeply infiltrating parametric and retro-\nvaginal septum endometriosis by laparotomy on account of re-\ncurrent, therapy-resistant hypermenorrhoea and dysmenor-\nrhoea. A postoperative endocrine therapy was not indicated. In\n1993 a continuous gestagen therapy with medrogestone 5 mg\ndaily was started because of a suspected recurrent endometriosis\n(cystic ovarian endometriosis). This was stopped after 14 months\nwhen the patient was diagnosed with a left-sided invasive ductal\nbreast cancer (pT2 pN0 [SN] M0 G3, ER 40 %, PR 30 % Her2/neu-\npositive). In 1995 a breast-conserving operation with radiothera-\npy and adjuvant chemotherapy was carried out (4 cycles of EC\nscheme followed by an antioestrogen therapy with anastrozole\n1 mg/d). Furthermore an adjuvant bilateral laparoscopic adnex-\nectomy was performed (histology of the ovaries did not show\nany evidence of endometriosis, merely functional cysts and se-\nrous membrane inclusion cysts).\nOn clinical examination and vaginal sonography, a good table-\ntennis ball-sized, firm elastic, immobile tumour was conspicuous\nabove and dorsal from the vaginal stub, the rectal mucous mem-\nFig. 2 a and b Intestinal wall with benign endometriosis (case 3). Hyperplas-\ntic thickened intestinal wall with cystic dilated endometriosis glands ( a), filled\nwith secretions with flattened, inactive epithelium. In addition, islands with\nproliferating endometriosis surrounded by fibrosis and muscle cells (b). stain-\ning HE; magn. a = 10× and b = 100×.\nFig. 3 a and b Varying differentiation of the malignancy. The dedifferentia-\ntion spectrum of the tumour in case 3, classified as G2, ranges from border-\nline parts ( a) with epithelial high-grade atypical cell conglomerates without\ndetectable invasion through to little differentiated carcinoma cells in the\nlymph node metastases ( b).\n420\nSchutz R et al. Diagnostics and Therapy … Geburtsh Frauenheilk 2016; 76: 417 –422\nGebFra Science\n\n\nbranes could be moved. A colonoscopy performed 7 months ear-\nlier because of constipation and lower abdominal pain did not re-\nveal any abnormal findings. An MRI scan demonstrated a 3-cm,\nsolid tumorous structure above the vaginal stub that could not\nbe exactly delineated from the rectal wall.\nWith the suspicion of recurrent endometriosis a re-laparotomy\nwas performed and, after difficult adhesiolysis of the frozen pel-\nvis, a mandarin-sized tumour reaching from above and dorsolat-\neral of the vaginal stub to the paraproctium was detected. The\nfrozen section analysis confirmed the clinical suspicion of malig-\nnancy so that after total mesorectal mobilisation a deep anterior\nrectum resection with end-to-end anastomosis was performed.\nThe histological analysis revealed a moderately differentiated en-\ndometrial adenocarcinoma (32 mm in size) on the bed of a previ-\nously existing endometriosis (l\n\" Fig. 2) in the vicinity of the rectal\nwall with infiltration into all layers of the wall through to the\nsubmucosa. In the vicinity of one tumour part changes were seen\nthat corresponded to a borderline tumour. Of 26 regional lymph\nnodes only one had been attacked ( l\n\" Fig. 3). The fibrolipomatous\npelvic connective tissue (residual parametria) was tumour-free,\nas was also the resected vaginal stub. The patient received an ad-\njuvant therapy comprised of 6 cycles of cisplatin/doxorubicin and\nin sequence radiotherapy of the lesser pelvis and pelvic lymph\ndrainage pathways until January 2010. Tumour follow-up find-\nings including imaging procedures (sonography and MRI of the\nlesser pelvis) have remained unremarkable up to date.\nDiscussion\n!\nMalignant degeneration of endometriosis is a rare event and ma-\nlignant degeneration of intestinal endometriosis is extremely\nrare. During the 5-year period reported here (2008 –2012) we\nhave operated on 3416 patients for endometriosis; 263 of them\nfor rectum-sigmoid colon endometriosis (7.7 %). We observed 13\nendometriosis-associated malignancies (0.38 % of all operated\nendometriosis cases); among them were the 3 cases described\nhere. This corresponds to an incidence for malignant degenera-\ntion of extragenital cases of 23 % of all endometriosis-associated\nmalignancies or, respectively, 0.88 per thousand of all endome-\ntriosis cases and 1.14 % of all intestinal endometrioses. Thus, our\nfigures are lower than those given in the literature over the past\nfew years where a risk of 2.5 % for the malignant degeneration of\novarian endometriosis was calculated (6 × higher than in our col-\nlective) [5]. These differences can be explained by considering\nthat the in part low case numbers, the nature of the publishing\nfacility (gynaecology, surgery, pathology) and specialisation of\nthe hospital all have a strong influence on the investigated collec-\ntives. An interdisciplinary, multicentre trial is needed to provide\nvalid incidence data and clinically relevant risk estimations; such\na trial is currently being carried out by Ulrich and co-workers [6].\nAccording to a recent literature review [7] 80 % of all extragonadal\nendometriosis-associated malignancies have their origins in the\nrectum-sigmoid colon and on histology two thirds of the cases\nprove to be adenocarcinomas, 10 % each endometroid stromal\nsarcomas and adenosarcomas as well as malignant Müller ʼs\nmixed tumours in 5 % of the cases. Thus, our three cases corre-\nspond to the most frequent location and the most frequent histo-\nlogical type.\nThe differential diagnosis between endometroid adenocarcino-\nma and primary adenocarcinoma of the colon is difficult, not only\nfor the clinician but also for the pathologist. The symptomatics\nare identical, but clinically the lack of attack on the intestinal mu-\ncous membranes points to an endometroid process, ultimately,\nhowever, immunohistochemical examinations are necessary to\nmake an exact diagnosis. A primary colon carcinoma is CK-20\npositive and CK-7 negative whereas, in contrast, an endometroid\ncarcinoma is CK-7 positive and CK-20 negative (for details of the\ncases, see l\n\" Tab. 1). However, since individual tumour parts can\nexhibit different receptor expressions and immunohistochemical\nreactions (case 1), the differential diagnosis can be problematic.\nThis is also apparent for case 3 where the negative response for\noestrogen receptors can be considered as a sign of dedifferentia-\ntion, whereas the CD 10 negative with positive P53 result sug-\ngests for these differently differentiated carcinomas there are al-\nso areas that correspond to a highly differentiated endometroid\ncarcinoma.\nFurthermore, it is a matter of discussion if the TNM classification\nis meaningful for extragenital malignant endometriosis and\nwhether it should be classified as an ovarian or an intestinal can-\ncer. Thus, for example, this question can be posed in case 3 in\nwhich a hysterectomy had been performed in 1988, a bilateral\nadnexectomy in 1995 and in whom in the absence of internal\ngenital organs a malignant colon endometriosis was operated in\n2009. As a colon carcinoma the classification pT3L0V0pN1 (1/26)\npMx R0 G2 would have been correct because the malignancy had\noriginated from tissue of the genital organs while pT3 pNx pM1\n(LYM + intestine) G2 would have been logical. Similarly in case 1,\nin whom in 2003 a myoma enucleation with right-sided adnexec-\ntomy and in 2010 a supracervical hysterectomy with left-sided\nadnexectomy were performed, both because of endometriosis\nand myomas. In 2013 a sigmoid colon resection and lymphade-\nnectomy with resection of the cervix uteri were carried out. For\nan intestinal carcinoma the classification pT2L1V0pN2 (18/46)\npMx R0 G2 would be correct whereas for an ovarian carcinoma\npT2L1V0pNxpM1 (LYM) R0 G2 would be correct. For the surgical\nprocedure the assignment as intestinal carcinoma is helpful\nwhereas for the adjuvant therapy the phenotype of the carcino-\nma is rather more relevant. Accordingly, the locoregional lymph\nnodes of the colon are removed surgically, the adjuvant chemo-\ntherapy with carboplatin and Taxol then takes the metastatic\n(pM1 LYM) endometroid carcinoma into consideration. Since no\ntumour formula is appropriate for the situation of extragonadal\nmalignant endometriosis, it is recommended to disregard the or-\ngan classification according to the TNM system and to descrip-\ntively report the pathological findings phenotype, tumour size\nand resection margins, lymph node attack and metastasis.\nAt the time of diagnosis the average age was 55.4 years with a\nstandard deviation of 12.8 years, whereby at this time the youn-\ngest patient was 33 years old and the oldest 80 years [7]. Our\ncases were also peri- or, respectively, post-menopausal women\nand Ulrich and co-workers [6] pointed out that in cases of recur-\nrence of endometriosis symptoms in peri- and post-menopausal\npatients the clinician should always consider the possibility of a\nmalignant degeneration of the already known and documented\nendometriosis.\nIn many of the previously published cases the patients had re-\nceived long-term oestrogen monotherapies, but endometriosis-\nassociated carcinomas have also been described under Taxol or\nin one case, respectively, under gestagen therapy [8]. We ob-\nserved carcinomas without any influence of endocrine therapy\n(case 1) or, respectively, after terminated gestagen therapy (case\n2) and during an antioestrogen therapy with an aromatase inhib-\n421\nSchutz R et al. Diagnostics and Therapy … Geburtsh Frauenheilk 2016; 76: 417 –422\nCase Report\n\n\nitor (case 3). The latter situation had not been reported previ-\nously.\nIndividual case reports and small series do not allow for any clear\nrecommendations about endocrine therapy for postmenopausal\nsymptoms in patients with endometriosis; however, an indicated\noestrogen administration should always be combined with a ges-\ntagen [9]. The pathophysiological background for this recom-\nmendation is that oestrogens not only stimulate the proliferation\nof oestrogen receptor-positive cells but also influence the prosta-\nglandin metabolism by means of an increased cyclooxygenase ac-\ntivity. This favours a resistance to apoptosis and in relation with\nthe hyperoestrogenism (favoured locally by aromatase activity)\nleads to a higher risk for malignant transformation. Various other\nmolecular biological mechanisms for endometriosis-associated\nmalignancies of the ovary have been discussed. Thus an Fe\n++-\noverload in the endometriosis lesion can lead to protein changes\nand DNA damage through an elevation of oxygen radicals [10]\nand inactivation of the PTEN tumour suppressor gene as the first\nstep for a malignant transformation [11]. It has not yet been ex-\namined if this mechanism is also applicable for the malignant de-\ngeneration of extragonadal endometriosis.\nThe clinical picture of extragonadal endometriosis frequently re-\nflects its localisation [12]. Vaginal bleeding following a hysterec-\ntomy, rectal bleeding from the posterior compartment in a pa-\ntient with a history of unspecific lower abdominal pain have also\nbeen reported along with stool irregularities, constipation and\nintestinal cramps. Thus, in the diagnostic work-up an interdisci-\nplinary procedure has proved valuable since colonoscopy is often\nunremarkable, as pointed out by Yantiss and co-workers [4] in\ntheir series of 17 cases. Rectovaginal palpation, sonography and\nradiological imaging procedures point in the right direction but\nonly histology is decisive.\nSurgical treatment follows the principles of cancer surgery in the\nlesser pelvis with the target of R0 resection and regional lym-\nphadenectomy. Chemotherapy with platinum-containing sub-\nstances combined with taxanes is recommended as an adjuvant\ntherapy [13], which was also performed in our case 1 whereas in\ncase 3 a combination of platinum with anthracycline was admin-\nistered.\nOn the other hand, it has been suggested that patients with,\nabove all, extragonadal endometriosis-associated malignancies\nthat are limited in extent to the lower pelvis, will benefit more\nfrom adjuvant pelvic radiotherapy [8]. Furthermore, a high-dose\ngestagen therapy may possibly have a similar effect on gestagen\nreceptor-positive malignancies as is known from the therapy for\nendometroid cancer. This was the reason in our case 2 for the ad-\njuvant high-dose gestagen therapy for the endometroid ovarian\ncancer stage I c.\nThere are also discrepancies in the literature with regard to the\nprognosis. Some authors found no differences between endome-\ntriosis-associated and non-endometriosis-associated malignan-\ncies [14, 15] while others found a better prognosis of EAM [8,\n16]. The relatively favourable prognosis for endometriosis-asso-\nciated malignancies in comparison to primary ovarian cancer is\nexplained, on the one hand, as a result of genetic mutations of en-\ndometriosis cells the former is pathogenetically a unique entity\nor, on the other hand, clinically that many carcinomas are diag-\nnosed and treated in the early stages.\nIn the cases reported here, attack on the locoregional lymph\nnodes had already taken place; however, all 3 cases are still free\nof recurrences, in cases 2 and 3 even after almost 5 years which is\nrather in accord with a more favourable prognosis.\nPractical Conclusions\n!\nIn spite of its rare occurrence, the responsible physician should,\nin cases of peri- or postmenopausal patients with a history of en-\ndometriosis, when there is a clinical suspicion of an intestinal tu-\nmour in the lesser pelvis always take the possibility for a malig-\nnant transformation into consideration. Preoperative imaging\nprocedures and biochemical tests are helpful for the interdiscipli-\nnary surgical planning but ultimately the suspected clinical and\nalso intraoperative diagnosis can only be confirmed and man-\naged on the basis of histological examinations. The objective is\nto encourage the pathologist to actively search for an atypical en-\ndometriosis and its malignant transformation and, in the case of\nwomen with a history of endometriosis and suspected intestinal\nadenocarcinoma, to employ the appropriate immunohistochem-\nical examinations in the differential diagnosis. Exact knowledge\nof the origin is extremely important since a malignantly degener-\nated intestinal endometriosis requires different adjuvant therapy\nprocedures than a primary intestinal carcinoma and apparently\nhas a better stage-dependent prognosis.\nConflict of Interest\n!\nNone.\nReferences\n1 Sampson JA. 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