{"paper_id":"b0cb9d71-ffd3-4ae0-9b6c-11c52c9a47cd","body_text":"C A S E R E P O R T Open Access\nDysplastic intestinal-type metaplasia of\nappendiceal endometriosis: a mimic of low grade\nappendiceal mucinous neoplasm\nAndrew Mitchell 1*, Pierre Dubé 2 and Lucas Sideris 2\nAbstract\nWe report an example of dysplastic intestinal-type metaplasia involving endometriosis of the appendix in a 45 year\nold woman. One other example of this phenomenon has been reported. As it occurs within the muscular wall of\nthe appendix, confusion with low grade appendiceal mucinous neoplasm (LAMN) may occur. Evidence supporting\nthe metaplastic nature of the intestinal epithelium is offered. As the initial pathological diagnosis was of invasive\ncancer with perforation of the appendix treatment consisted of peritonectomy and hyperthermic intraperitoneal\nchemotherapy (HIPEC).\nVirtual slides: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/\n1068246472111756.\nKeywords: Appendix, Endometriosis, Intestinal, Metaplasia, Dysplasia\nIntroduction\nEndometriosis of the appendix may be an incidental\nfinding or the cause of appendicitis, intussusception or\nperforation [1]. Various types of metaplasia may involve\nthe epithelial component of endometriosis [2] including\nintestinal-type. The latter has been described in two ca-\nses of appendiceal endometriosis to date, one associated\nwith focal dysplasia [3,4]. We describe a case of endo-\nmetriosis of the appendix with dysplastic intestinal-type\nepithelium presenting as a mucocele with acute appendi-\ncitis and perforation. The differential diagnosis is with\nlow grade appendiceal mucinous neoplasm (LAMN). As\nthe initial pathologic diagnosis was of “infiltrating low-\ngrade adenocarcinoma colonizing endometriosis ” the pa-\ntient was treated with peritonectomy and hyperthermic\nintraperitoneal chemotherapy (HIPEC).\nCase details\nA 45 year old woman underwent surgery at another\nhospital following a diagnosis of acute appendicitis. The\nappendix appeared enlarged and perforated. Multiple\n“peritoneal mucinous implants ” were observed in the\nright pelvis. Following a pathologic diagnosis of “inva-\nsive low-grade carcinoma of the appendix colonizing\nappendicial endometriosis ”, the patient was referred to\nour hospital for consideration of second look laparot-\nomy and HIPEC. An extensive evaluation revealed no\nevidence of metastatic disease.\nWithout recourse to pathological review of the append-\nectomy specimen, second look laparotomy was performed\nexactly one year later. There was no macroscopic evidence\nof neoplasia, but mucin was seen localized to the right\nperitoneal surface. Free intrabdominal mucin was absent.\nRight hemicolectomy, resection of two segments of small\nintestine, omentectomy, bilateral ovariectomy, and peri-\ntoneal resections were carried out. HIPEC (Oxaliplatin\n300 mg/m 2) was administered. Pathologic examination\nshowed foci of endometriosis on the ileal surface of the\nright hemicolectomy specimen, the left Fallopian tube\nand in one of the fragments of peritoneum. The mucin\nwas acellular. Both ovaries had functional cysts.\nThe patient ’s clinical course has been uneventful after\neighteen months.\n* Correspondence: plaines@me.com\n1Department of Anatomic Pathology and Cytology, Maisonneuve-Rosemont\nHospital, Montreal, Quebec, Canada\nFull list of author information is available at the end of the article\n© 2014 Mitchell et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative\nCommons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and\nreproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain\nDedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article,\nunless otherwise stated.\nMitchell et al. Diagnostic Pathology 2014, 9:39\nhttp://www.diagnosticpathology.org/content/9/1/39\n\nMaterial and methods\nThe haematoxylin-phloxin-saffron (HPS) stained sec-\ntions of the appendectomy specimen from the referring\nhospital were reviewed. In turn, 4- micron thick recuts\nof all the formalin-fixed, paraffin-embedded tissue blocks\nwere stained with HPS in our laboratory. Unstained sec-\ntions from all blocks were submitted for histochemical\nand immunohistochemical studies: periodic acid-Schiff\nstain with diastase (PAS-D) and without (PAS), and mo-\nnoclonal antibodies directed against pancytokeratin AE/\nAE3, cytokeratin 7, cytokeratin 20, CD10, estrogen (ER)\nand progesterone (PR) receptors, and Ki-67 (MIB-1).\nPathologic findings\nThe pathology report from the referring hospital described\nan appendix 6 cm in length and varying from 1 to 2,5 cm\nin diameter with presence of a mucocele and perforation.\nThe wall varied from 0,5 to 1 cm in thickness with\n“brownish zones”. Microscopic examination showed acute\nappendicitis, acellular mucin dissecting the wall with ex-\ntension to the serosa compatible with perforation\n(Figure 1a) and multiple foci of endometriosis involving\nthe lamina propria and wall (Figures 1b and 1c). Within\ncertain foci of endometriosis direct transition of endome-\ntriotic epithelium into intestinal-type mucinous epithelium\nwas observed (Figures 1c and d). Whereas this epithelium\nrested in large part on stroma of endometriotic-type\n(Figure 1e) in other areas this stroma was absent and the\nepithelium was in direct contact with smooth muscle.\nOccasional Paneth cells and ciliated cells were identified.\nThe metaplastic epithelium had foci of mild to moderate\ncytologic atypia, occasional mitoses and tufting (Figures 1f\nand g). Although endometriosis extended from the lamina\npropria (Figure 1b) to the subserosa, the luminal epithe-\nlium showed no continuity with endometriosis and no\natypia beyond reactive changes due to inflammation. There\nFigure 1 Histologic findings. a) Low power view of rupture site with free mucin and a dysplastic intestinal-type gland (arrow). b) Low power\nview of normal appendix epithelium with underlying endometriosis. c) Low power view of endometriosis of the appendix wall with transition to\nintestinal-type epithelium (arrows). (d and e) Further low power views of endometriosis of the appendix wall with transition to intestinal-type\nepithelium. f) Higher power view of 1e. Note intestinal-type epithelium (arrow). g) High power view of endometriosis, intestinal-type metaplasia,\nand intestinal-type metaplasia with low-grade atypia (arrows left to right). h) High power view of an area of tufting in low grade dysplasia.\nMitchell et al. Diagnostic Pathology 2014, 9:39 Page 2 of 5\nhttp://www.diagnosticpathology.org/content/9/1/39\n\nwas no evidence of an appendicial diverticulum. The\nmucin at the serosal surface was acellular.\nThe foci of endometriosis showed a typical cytokeratin\n7 positive/cytokeratine 20 negative epithelium (Figure 2a)\nwith rare Ki-67 positive cells. The intestinal-type epithe-\nlium showed a cytokeratine 7 negative/cytokeratine 20 po-\nsitive profile (Figure 2b) with Ki-67 positivity of at least\n20%. The endometriotic stroma underlying both epithelia\nFigure 2 Immunohistochemical findings. a) Cytokeratin 7 positivity limited to endometriotic epithelium. b) Cytokeratin 20 positivity limited to\nintestinal-type epithelium. c) CD10 positivity of endometriotic stroma on which both endometriotic and intestinal-type epithelilia rest. d) CD10\npositive endometriotic stroma surrounding intestinal-type glands. (e and f) ER positivity of endometriotic epithelium and stroma, but absence in\nmetaplastic epithelium. g) Rare ER positive “transitional” cells with intestinal-type differentiation (arrows).\nMitchell et al. Diagnostic Pathology 2014, 9:39 Page 3 of 5\nhttp://www.diagnosticpathology.org/content/9/1/39\n\nwas CD10 positive (Figure 2c and d) and ER and PR po-\nsitive (Figures 2e and 2f). The intestinal-type epithelium\nwas ER negative (Figure 2f) although rare mucinous cells\nat the transition between endometriotic and mucinous\nepithelia were focally ER-positive (Figure 2g).\nThe findings were interpreted as acute appendicitis\nwith perforation and background endometriosis, the lat-\nter with foci of metaplastic intestinal-type epithelium with\noccasional low grade dysplasia.\nDiscussion\nEndometriosis has been described in numerous extra-\npelvic sites including the abdominal wall, pleura, peri-\ncardium, muscle, nerve [5] and bronchus [6]. Confusing\nclinical presentations may result. As one example, within\nthe gynecologic tract co-existence of an ovarian leiomyo-\nma with an endometriotic cyst resulted in appendicitis-\nlike symptoms and urgent laparotomy [7].\nEndometriosis may involve the gastrointestinal tract\nfrom the small intestine to the rectosigmoid colon. The\nlatter is the most common site, followed, in order, by the\nproximal colon, small intestine, the appendix and cecum.\nIleocolic intussusception due to cecal endometriosis has\nbeen documented [8].\nMicroscopic foci of endometriosis are encountered in\nappendices removed for appendicitis or those included\nin colectomy specimens, and are clinically silent. Con-\nversely, endometriosis may present as acute or chronic\nappendicitis, with the latter occasionally causing a mu-\ncocele. Other presentations of appendicial endometriosis\ninclude a mass lesion, perforation during pregnancy\n(most commonly in the first two trimesters and when\nthe endometriosis is transmural), and intussusception of\nthe appendix [1].\nEndometriosis can display metaplastic changes. In the\novary 12-68% of endometriosis lesions show metaplasia\nin the form of ciliated, eosinophilic, hobnail, squamous\nor mucinous change, with endocervical-type metaplasia\nencountered more commonly than intestinal-type [2].\nAlthough in a review of 44 cases of endometriosis in-\nvolving the intestinal tract no examples of intestinal-type\nmetaplasia were found [1], a recent report documents\nintestinal epithelium “colonizing ” endometriosis of the\ncecum of a 55 year-old woman who had previously un-\ndergone appendectomy [9].\nOne other case of dysplastic intestinal-type metaplasia\ninvolving appendicial endometriosis has been reported\n[3]. A 39 year-old woman with severe endometriosis un-\nderwent uterine myomectomy as well as appendectomy\nfor an incidental 1.6 cm nodule of the distal appendix.\nMicroscopic examination showed endometriosis extend-\ning from the serosa to the mucosa of the appendix. Foci\nof intestinal-type metaplasia, including Paneth cells, were\nfound within the endometriosis with one area showing\ncytologic atypia consistant with dysplasia. Regarding histo-\ngenesis, the authors favored metaplasia of the endome-\ntriosis, as opposed to “colonization” by overlying luminal\nepithelium, citing the presence of ER-positive mucin-\nous cells, the presence of ciliated mucinous cells (not seen\nin normal intestinal epithelium), absence of direct com-\nmunication between endometriotic and native appendiceal\nglands, and the presence of “transitional epithelium”.\nSimilarly, we believe our case represents intestinal me-\ntaplasia rather than colonization, as: 1) no connection\nbetween the overlying native epithelium and the foci of\nendometriosis was found, 2) multiple foci of direct tran-\nsition between endometriotic epithelium and intestinal-\ntype epithelium were present, 3) ER-positive mucinous\ncells at sites of transition from endometriotic to mucinous\nepithelium were identified, and 4) the known potential of\nendometrium to undergo intestinal metaplasia [10,11].\nThe differential diagnosis in the present case is with\nlow-grade appendiceal mucinous neoplasm (LAMN).\nLAMN is characterized by invasive intestinal-type epithe-\nlium with abundant mucin production, minimal architec-\ntural complexity and low-grade cytologic atypia [12]. Two\nfeatures of the present case rule out LAMN: absence of in-\nvasive intestinal epithelium and absence of a primary le-\nsion (adenoma or carcinoma in situ) of the appendicial\nepithelium. Furthermore, there is clinical support against\nLAMN as at second-look surgery one year following re-\nsection of the perforated appendix there was absence of\nboth recurrent neoplasia and diffuse peritoneal mucin.\nThe decision to perform peritonectomy and HIPEC\nwas based on an initial pathological diagnosis of invasive\ncancer. Given the uniqueness of our case it is impossible\nto know what further treatment, if any, would have been\nwarranted had the correct diagnosis initially been made.\nWe therefore suggest that in any appendectomy speci-\nmen with endometriosis and suspicion of neoplasia that\nthe possibility of intestinal metaplasia be considered in\nthe differential diagnosis.\nConsent\nWritten informed consent was obtained from the patient\nfor the publication of this report and any accompanying\nimages.\nCompeting interests\nThe authors declare that they have no competing interests.\nAuthors’ contributions\nAM provided the pathologic diagnosis and drafted the manuscript. PD and\nLS provided clinical information, wrote the case details and contributed to\nthe nonpathological aspects of the discussion. All authors read and\napproved the final manuscript.\nAuthor details\n1Department of Anatomic Pathology and Cytology, Maisonneuve-Rosemont\nHospital, Montreal, Quebec, Canada. 2Department of Surgery,\nMaisonneuve-Rosemont Hospital, Montreal, Quebec, Canada.\nMitchell et al. Diagnostic Pathology 2014, 9:39 Page 4 of 5\nhttp://www.diagnosticpathology.org/content/9/1/39\n\nReceived: 27 October 2013 Accepted: 21 December 2013\nPublished: 21 February 2014\nReferences\n1. Yantiss RK, Clement PB, Young RH: Endometriosis of the intestinal tract: a\nstudy of 44 cases of a disease that may cause diverse challenges in\nclinical and pathologic evaluation. Am J Surg Pathol 2001, 25:513–524.\n2. Clement PB: The pathology of endometriosis: a survey of the many faces\nof a common disease emphasizing diagnostic pitfalls and unusual and\nnewly appreciated aspects. Adv Anat Pathol 2007, 14:241–260.\n3. Mai KT, Burns BF: Development of dysplastic mucinous epithelium from\nendometriosis of the appendix. Histopathology 1999, 35(4):368–372.\n4. Libbrecht L, Snauwaert C, De Vos M, et al : Intestinal metaplasia and\ncolonization of endometriosis in a case of an appendiceal mucinous\nneoplasm. Virchows Arch 2012, 461:227–229.\n5. Machairiotis N, Stylianaki A, Dryllis G, et al : Extrapelvic endometriosis: a\nrare entity or an under-diagnosed condition? Diagn Pathol 2013, 8(1):194.\n6. Yu JH, Lin XY, Wang L, et al: Endobronchial endometriosis presenting as\ncentral-type lung cancer: a case report. Diagn Pathol 2013, 8:53.\ndoi:10.1186/1746-1596-8-53.\n7. Tomas D, Lenicek T, Tuckar N, et al: Primary ovarian leiomyoma associated\nwith endometriotic cyst presenting with symptoms of acute appendicitis: a\ncase report. Diagn Pathol 2009, 4:25. doi:10.1186/1746-1596-4-25.\n8. Emmanuel R, Léa M, Claude P, et al: Ileocolic intussusception due to a\ncecal endometriosis: case report and review of literature. Diagn Pathol\n2012, 7:62. doi:10.1186/1746-1596-7-62.\n9. Tipps AM, Weidner N: Colonization of intestinal endometriosis by benign\ncolonic mucosa: a pattern potentially misdiagnosed as invasive\nmucinous carcinoma. Int J Surg Pathol 2011, 19(2):259–262.\n10. Nicolae A, Goyenaga P, McCluggage WG, et al : Endometrial intestinal\nmetaplasia: a report of two cases, including one associated with cervical\nintestinal and pyloric metaplasia. Int J Gynecol Pathol 2011, 30:492–496.\n11. Wells M, Tiltman A: Intestinal metaplasia of the endometrium.\nHistopathology 1989, 15:431–433.\n12. Misdraji JM, Yantiss RK, Graeme-Cook FM, et al: Appendicial mucinous\nneoplasms: a clinicopathologic analysis of 107 cases. Am J Surg Pathol\n2003, 27:1089–1103.\ndoi:10.1186/1746-1596-9-39\nCite this article as: Mitchell et al. : Dysplastic intestinal-type metaplasia of\nappendiceal endometriosis: a mimic of low grade appendiceal\nmucinous neoplasm. Diagnostic Pathology 2014 9:39.\nSubmit your next manuscript to BioMed Central\nand take full advantage of: \n• Convenient online submission\n• Thorough peer review\n• No space constraints or color figure charges\n• Immediate publication on acceptance\n• Inclusion in PubMed, CAS, Scopus and Google Scholar\n• Research which is freely available for redistribution\nSubmit your manuscript at \nwww.biomedcentral.com/submit\nMitchell et al. Diagnostic Pathology 2014, 9:39 Page 5 of 5\nhttp://www.diagnosticpathology.org/content/9/1/39","source_license":"CC0","license_restricted":false}