Referee report. For: Case Report: Xanthogranulomatous salpingo-oophoritis associated to endometriosis – are these different histologic expressions of the same disease? [version 1; peer review: 1 approved with reservations]

salpingitis, endometriosis, infertility, xanthogranulomatous salpingo-oophoritis ALL Metrics - Views Downloads How to cite this article Portela Carvalho A, Costa Braga A and Ferreira H. Case Report: Xanthogranulomatous salpingo-oophoritis associated to endometriosis – are these different histologic expressions of the same disease? [version 1; peer review: 2 approved with reservations]. F1000Research 2020, 9:94 (https://doi.org/10.12688/f1000research.22206.1) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente Select a format first ▬ ✚ Case Report [version 1; peer review: 2 approved with reservations] PUBLISHED 07 Feb 2020 Author details Author details 1 Department of Obstetrics and Gynecology, Centro Hospitalar do Tâmega e Sousa, Penafiel, Portugal 2 Department of Pathology, Centro Hospitalar do Porto, Porto, Portugal 3 Department of Gynecology, Centro Hospitalar do Porto, Porto, Portugal 2 Department of Pathology, Centro Hospitalar do Porto, Porto, Portugal 3 Department of Gynecology, Centro Hospitalar do Porto, Porto, Portugal Ana Portela Carvalho Roles: Conceptualization, Data Curation, Investigation, Writing – Original Draft Preparation, Writing – Review & Editing Roles: Conceptualization, Data Curation, Investigation, Writing – Original Draft Preparation, Writing – Review & Editing Ana Costa Braga Roles: Data Curation, Investigation, Writing – Original Draft Preparation Roles: Data Curation, Investigation, Writing – Original Draft Preparation Hélder Ferreira Roles: Supervision, Validation, Writing – Review & Editing Roles: Supervision, Validation, Writing – Review & Editing OPEN PEER REVIEW REVIEWER STATUS This article is included in the Endometriosis collection. Xanthogranulomatous inflammation is characterized by the presence of foamy histiocytes associated with other inflammatory cells like lymphocytes, plasma cells and neutrophils. It is a rare inflammatory process, which has been more frequently described in chronic pyelonephritis and cholecystitis. Xanthogranulomatosis usually triggers a large distortion of the affected organ, which is secondary to the severe inflammatory response that characterizes this type of lesion. Only a few cases of xanthogranulomatous salpingo-oophoritis have been published to date. Here, we report the case of a xanthogranulomatous salpingo-oophoritis in a patient with endometriosis, suffering from chronic pelvic pain and long-standing infertility. The association between endometriosis and xanthogranulomatous inflammation is extremely rare and can possibly represent a severe histologic expression of this common disorder. salpingitis, endometriosis, infertility, xanthogranulomatous salpingo-oophoritis Corresponding Author(s) Ana Portela Carvalho ([email protected]) Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2020 Portela Carvalho A et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Portela Carvalho A, Costa Braga A and Ferreira H. Case Report: Xanthogranulomatous salpingo-oophoritis associated to endometriosis – are these different histologic expressions of the same disease? [version 1; peer review: 2 approved with reservations]. F1000Research 2020, 9:94 (https://doi.org/10.12688/f1000research.22206.1) First published: 07 Feb 2020, 9:94 (https://doi.org/10.12688/f1000research.22206.1) Latest published: 07 Feb 2020, 9:94 (https://doi.org/10.12688/f1000research.22206.1) Xanthogranulomatous salpingo-oophoritis (XGSO) is an uncommon form of salpingitis, which is associated with a prominent acute and chronic inflammatory infiltrate with admixed foamy histiocytes1–4. The presence of this xanthogranulomatous inflammation has been described in several organs, most commonly in kidney or gallbladder, in association with chronic pyelonephritis or cholecystitis, respectively1. It is, however, an extremely rare finding in pelvic organs. XGSO has most commonly been associated with pelvic inflammatory disease, but it has also been described in the presence of intrauterine contraceptive devices, extensive endometriosis, ineffective antibiotherapy, abnormalities in lipid metabolism and with the administration of contrast agents1–5. Few cases of XGSO in patients with leiomyomata have also been published1,4,6. Subclinical bacterial infection seems to intervene and several agents have been implicated, such as Actinomyces, Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Staphylococcus viridans, Bacteroides fragilis, Candida glabrata and Group B Streptococci1. Non-infectious causes have also been pointed. Nevertheless, the aetiology of XGSO remains unknown. Patients with XGSO usually present with signs of pelvic inflammatory disease, notably, pelvic pain, fever and abnormal bleeding. Treatment with antibiotics and/or surgery is required and the diagnosis of this condition is only possible after histological examination1,2. The differential diagnosis includes: pseudoxanthomatous salpingitis and granulomatous salpingitis. The presence of acute and chronic inflammatory infiltrate differentiates XGSO from pseudoxanthomatous salpingitis, which is characterized by xanthoma cells and pigment without prominent inflammatory component, and from granulomatous salpingitis, where granulomas are present2,3. Here, we report the case of a XGSO in a patient with chronic pelvic pain and infertility associated with endometriosis. A 35-year-old woman, with no other relevant previous medical or surgical history, presented with 6 years of primary infertility and severe dysmenorrhea and dyspareunia for nearly a year. No other symptoms were described, like dyschezia, dysuria or abnormal vaginal bleeding. The patient had been previous diagnosed with stage III pelvic endometriosis. This diagnosis was histologically established after two abdominal diagnostic laparoscopies in the context of the infertility evaluation. In the last surgery, a left side salpingectomy and adhesiolysis were performed, with limited post-operative improvement. The patient was then referred to our Chronic Pelvic Pain Unit due to clinical worsening. On pelvic examination, a painful area located at the right uterosacral ligament was identified by bimanual exam, without pelvic masses. No other physical abnormalities were detected. A pelvic transvaginal ultrasonography was performed, identifying a large uterus with sonographic signs of adenomyosis. Magnetic resonance imaging showed an hyposignal at T1 and T2 sequences, suggestive of an endometriotic infiltration lesion at the right uterosacral ligament location. This finding correlated with the painful area detected at bimanual exam. Taking in consideration these clinical and imagiological findings, it was decided to perform a laparoscopy. Several adhesions between the uterus and the anterior rectum were identified. The right Fallopian tube was attached to a 2cm nodule in the right ovarium, which was highly suggestive of severe endometriotic infiltration (Figure 1 and Figure 2). In addition to extensive adhesiolysis, a right salpingectomy and oophorectomy were also performed. The right fallopian tube was 3.9cm in length, 0.4 cm in diameter and had a golden yellowish colour. The lumen was dilated, with thickened plicae and wall. The serosal surface was irregular, suggesting focal bilateral adhesions. The ovarian mass consisted of an irregular brown to yellowish nodule of tissue with 2cm of diameter. Both the fallopian tissue and the ovarian nodule were paraffin embedded and haematoxylin-eosin stained slides were examined. Histopathological examination of the fallopian tube showed abundant infiltration of the lamina propria by foamy histiocytes mixed with some inflammatory cells, including lymphocytes, plasma cells and occasional neutrophils, and there was no intervening stroma, conditioning tightly packing of the fallopian tube plicae. The histiocytes were intimately contiguous to the muscle wall and the subserosa of the fallopian tube and there was serosa fibrosis, with appearance of focal adhesions (Figure 3–Figure 7). The histiocytes appeared to contain abundant lipid material. Red cell extravasation was identified throughout the lesion. A similar finding was present in the ovarian nodule, where this pattern of inflammation was in close relation to normal ovarian tissue. No microorganisms were identified using periodic acid–Schiff, methenamine silver, acid-fast bacilli and Gram stains. Immunohistochemical stain was performed on paraffin-embedded sections and demonstrated strong CD68 staining in foamy histiocytes (Figure 8). No pigments, multinucleated giant cells, granulomas or foci of endometriosis were present in both specimens. The fallopian tube epithelium has reactive aspect, without prolifferative foci. These findings were diagnostic of XGSO. This patient had a significant symptomatic improvement after surgical treatment with sustained clinical response. A close follow-up with regular gynaecological appointments was performed, and no symptomatic recurrence, nor surgical adverse outcomes were detected to date. Endometriotic lesions are characterized by the presence of blood and endometrial shedding, representing a favourable trigger for the development of chronic inflammation and fibrosis. Classically, this disorder causes pelvic dysfunction and anatomical distortion that both lead to chronic pelvic pain and infertility. The pathologic finding of xanthogranulomatous inflammation may represent a severe form of endometriotic lesions, which could explain the recurrence of symptoms in this patient. Idrees et al. described a progressive spectrum of pathologic changes, from pure endometriosis to mixed endometriotic and xanthogranulomatous inflammation, and finally to only XGSO lesions2. The endometrioid implant shedding and the chronic inflammatory process characteristic of endometriosis could explain the xanthomatous process and the accumulation of excessive foamy histiocytes2. In this case, we observed a complete replacement of the endometriotic tissue, which was previously documented in prior surgeries, by foamy histiocytes. The current finding of a destructive xanthogranulomatous inflammatory process, in the absence of endometriotic foci, make us speculate that, probably, endometriosis reached a “burnout phase”, as postulated by other authors2. Moreover, no other predisposing conditions to the development of XGSO were identified. In conclusion, a long history of histologically documented endometriosis with multiple previous surgical treatments may lead to the development of a chronic exaggerated inflammatory response, as found in XGSO. A xanthogranulomatous inflammation may represent a rare but aggressive expression of such a common disorder, as is endometriosis. Written informed consent for publication of their clinical details and images was obtained from the patient. All data underlying the results are available as part of the article and no additional source data are required. Faculty Opinions recommendedReferences - 1. Gray Y, Libbey NP: Xanthogranulomatous salpingitis and oophoritis: a case report and review of the literature. Arch Pathol Lab Med. 2001; 125(2): 260–3. PubMed Abstract - 2. Idrees M, Zakashansky K, Kalir T: Xanthogranulomatous salpingitis associated with fallopian tube mucosal endometriosis: a clue to the pathogenesis. Ann Diagn Pathol. 2007; 11(2): 117–21. PubMed Abstract | Publisher Full Text - 3. Furuya M, Murakami T, Sato O, et al.: Pseudoxanthomatous and xanthogranulomatous salpingitis of the fallopian tube: a report of four cases and a literature review. Int J Gynecol Pathol. 2002; 21(1): 56–9. PubMed Abstract | Publisher Full Text - 4. Howey JM, Mahe E, Radhi J: Xanthogranulomatous salpingitis associated with a large uterine leiomyoma. Case Rep Med. 2010; 2010: 970805. PubMed Abstract | Publisher Full Text | Free Full Text - 5. Lavoué V, Vigneau C, Duros S, et al.: Which Donor for Uterus Transplants: Brain-Dead Donor or Living Donor? A Systematic Review. Transplantation. 2017; 101(2): 267–73. PubMed Abstract | Publisher Full Text - 6. Abeysundara PK, Padumadasa GS, Tissera WGM, et al.: Xanthogranulomatous salpingitis and oophoritis associated with endometriosis and uterine leiomyoma presenting as intestinal obstruction. J Obstet Gynaecol Res. 2012; 38(8): 1115–7. PubMed Abstract | Publisher Full Text Author details Author details 1 Department of Obstetrics and Gynecology, Centro Hospitalar do Tâmega e Sousa, Penafiel, Portugal 2 Department of Pathology, Centro Hospitalar do Porto, Porto, Portugal 3 Department of Gynecology, Centro Hospitalar do Porto, Porto, Portugal 2 Department of Pathology, Centro Hospitalar do Porto, Porto, Portugal 3 Department of Gynecology, Centro Hospitalar do Porto, Porto, Portugal Ana Portela Carvalho Roles: Conceptualization, Data Curation, Investigation, Writing – Original Draft Preparation, Writing – Review & Editing Roles: Conceptualization, Data Curation, Investigation, Writing – Original Draft Preparation, Writing – Review & Editing Ana Costa Braga Roles: Data Curation, Investigation, Writing – Original Draft Preparation Roles: Data Curation, Investigation, Writing – Original Draft Preparation Hélder Ferreira Roles: Supervision, Validation, Writing – Review & Editing Roles: Supervision, Validation, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Copyright © 2020 Portela Carvalho A et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. metrics | Views | Downloads | | |---|---|---| | F1000Research | - | - | | PubMed Central Data from PMC are received and updated monthly. | - | - | Citations CITE how to cite this article Portela Carvalho A, Costa Braga A and Ferreira H. Case Report: Xanthogranulomatous salpingo-oophoritis associated to endometriosis – are these different histologic expressions of the same disease? [version 1; peer review: 2 approved with reservations]. F1000Research 2020, 9:94 (https://doi.org/10.12688/f1000research.22206.1) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. track receive updates on this article Track an article to receive email alerts on any updates to this article. Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE ApprovedThe paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approvedFundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 07 Feb 2020 Views 0 How to cite this report: Kalkan Ü. Reviewer Report For: Case Report: Xanthogranulomatous salpingo-oophoritis associated to endometriosis – are these different histologic expressions of the same disease? [version 1; peer review: 2 approved with reservations]. F1000Research 2020, 9:94 (https://doi.org/10.5256/f1000research.24491.r96889) The direct URL for this report is: https://f1000research.com/articles/9-94/v1#referee-response-96889 https://f1000research.com/articles/9-94/v1#referee-response-96889 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Reviewer Report 08 Nov 2021 Approved with Reservations VIEWS 0 This case report provided a new case of a rare pathology of fallopian tube diagnosed as XGSO. The clinical history, histologic findings and quality of macro and micro images are well documented and presented. Although the title is very attractive, ... Continue reading 2. Seidman JD, Woodburn R: Pseudoxanthomatous salpingitis as an ex vivo model of fallopian tube serous carcinogenesis: a clinicopathologic study of 49 cases.Int J Gynecol Pathol. 2015; 34 (3): 275-80 PubMed Abstract | Publisher Full Text I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close This case report provided a new case of a rare pathology of fallopian tube diagnosed as XGSO. The clinical history, histologic findings and quality of macro and micro images are well documented and presented. Although the title is very attractive, the conclusions do not strongly support this attraction in this case report. In XGSO, usually a clinical history of pyometra or PID exists (Furuya et al. (20021)). In this case, there is no data represented that excludes a history of PID. Also, a clear indication of left salpingectomy which was performed in the last surgery is not reported. Was it due to a pyosalpinx/ hydrosalpinx? The pathologic report of left salpingectomy (if accessible) may add to the case report. Usually, pseudoxanthomatous salpingitis is associated with endometriosis (Furuya et al. (20021), Seidman et al. (20152)), and XGSO is rarely associated with endometriosis. In this case, no pigments, multinucleated giant cells, granulomas, or foci of endometriosis were present in the specimens and this mixed inflammatory infiltrate distinguished from the pseudoxanthomatous salpingitis. However, evidence of endometriosis in associated with XGSO by histologic or laparoscopic findings is not shown or documented. The cause of this XGSO may not definitively be claimed that it is due to endometriosis. In XGSO, usually a clinical history of pyometra or PID exists (Furuya et al. (20021)). In this case, there is no data represented that excludes a history of PID. Also, a clear indication of left salpingectomy which was performed in the last surgery is not reported. Was it due to a pyosalpinx/ hydrosalpinx? The pathologic report of left salpingectomy (if accessible) may add to the case report. Usually, pseudoxanthomatous salpingitis is associated with endometriosis (Furuya et al. (20021), Seidman et al. (20152)), and XGSO is rarely associated with endometriosis. In this case, no pigments, multinucleated giant cells, granulomas, or foci of endometriosis were present in the specimens and this mixed inflammatory infiltrate distinguished from the pseudoxanthomatous salpingitis. However, evidence of endometriosis in associated with XGSO by histologic or laparoscopic findings is not shown or documented. The cause of this XGSO may not definitively be claimed that it is due to endometriosis. - Is the background of the case’s history and progression described in sufficient detail? Yes - Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes - Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly - Is the case presented with sufficient detail to be useful for other practitioners? Partly

1. Furuya M, Murakami T, Sato O, Kikuchi K, et al.: Pseudoxanthomatous and xanthogranulomatous salpingitis of the fallopian tube: a report of four cases and a literature review.Int J Gynecol Pathol. 2002; 21 (1): 56-9 PubMed Abstract | Publisher Full Text2. Seidman JD, Woodburn R: Pseudoxanthomatous salpingitis as an ex vivo model of fallopian tube serous carcinogenesis: a clinicopathologic study of 49 cases.Int J Gynecol Pathol. 2015; 34 (3): 275-80 PubMed Abstract | Publisher Full Text Competing Interests: No competing interests were disclosed. Reviewer Expertise: endometriosis, minimally invasive surgery. CITE HOW TO CITE THIS REPORT Kalkan Ü. Reviewer Report For: Case Report: Xanthogranulomatous salpingo-oophoritis associated to endometriosis – are these different histologic expressions of the same disease? [version 1; peer review: 2 approved with reservations]. F1000Research 2020, 9:94 (https://doi.org/10.5256/f1000research.24491.r96889) The direct URL for this report is: https://f1000research.com/articles/9-94/v1#referee-response-96889 https://f1000research.com/articles/9-94/v1#referee-response-96889 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. Views 0 How to cite this report: Wei JJ. Reviewer Report For: Case Report: Xanthogranulomatous salpingo-oophoritis associated to endometriosis – are these different histologic expressions of the same disease? [version 1; peer review: 2 approved with reservations]. F1000Research 2020, 9:94 (https://doi.org/10.5256/f1000research.24491.r83543) The direct URL for this report is: https://f1000research.com/articles/9-94/v1#referee-response-83543 https://f1000research.com/articles/9-94/v1#referee-response-83543 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Reviewer Report 23 Apr 2021 Approved with Reservations VIEWS 0 This case report provided a new case of fallopian tube XGSO in a 35 yrs old women. The clinical history, image and histologic findings were well presented. However, the title and major conclusions are not well supported by this case ... Continue reading I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close This case report provided a new case of fallopian tube XGSO in a 35 yrs old women. The clinical history, image and histologic findings were well presented. However, the title and major conclusions are not well supported by this case report. - Authors concluded that this XGSO was a severe histologic expression of endometriosis based on clinical history. The presented evidences in supporting such connection seems to be lacking or not presented. - XGSO can be related to many different diseases (Int J Gynecol Pathol Sep;39(5):468-472)1. Endometriosis is one of possible cause. Evidence of endometriosis in associated with XGSO by histologic or laparoscopic findings was not shown or documented. The cause of this XGSO may be unknown. - Figures 3-7 are repetitive can be reduced while low power view of configuration of XGSO in fallopian tube should be added. - Author speculated a burnout phase of endometriosis for this XGSO. this can be proved by adding CD10 stain to highlight the rim or residual endometrial stromal cells even in a "Burnout phase" of endometriosis. - Is the background of the case’s history and progression described in sufficient detail? Yes - Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes - Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly - Is the case presented with sufficient detail to be useful for other practitioners? Partly

1. Chiesa-Vottero A: Xanthogranulomatous Salpingitis.Int J Gynecol Pathol. 2020; 39 (5): 468-472 PubMed Abstract | Publisher Full TextCompeting Interests: No competing interests were disclosed. Reviewer Expertise: gynecologic pathology CITE HOW TO CITE THIS REPORT Wei JJ. Reviewer Report For: Case Report: Xanthogranulomatous salpingo-oophoritis associated to endometriosis – are these different histologic expressions of the same disease? [version 1; peer review: 2 approved with reservations]. F1000Research 2020, 9:94 (https://doi.org/10.5256/f1000research.24491.r83543) The direct URL for this report is: https://f1000research.com/articles/9-94/v1#referee-response-83543 https://f1000research.com/articles/9-94/v1#referee-response-83543 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. Alongside their report, reviewers assign a status to the article: - Approved - Approved with reservations - Not approved | Invited Reviewers | || |---|---|---| | 1 | 2 | | | Version 1 07 Feb 20 | read | read | Sign up for content alerts You are now signed up to receive this alert Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. Consider the following examples, but note that this is not an exhaustive list: Examples of 'Non-Financial Competing Interests' - Within the past 4 years, you have held joint grants, published or collaborated with any of the authors of the selected paper. - You have a close personal relationship (e.g. parent, spouse, sibling, or domestic partner) with any of the authors. - You are a close professional associate of any of the authors (e.g. scientific mentor, recent student). - You work at the same institute as any of the authors. - You hope/expect to benefit (e.g. favour or employment) as a result of your submission. - You are an Editor for the journal in which the article is published. Examples of 'Financial Competing Interests' - You expect to receive, or in the past 4 years have received, any of the following from any commercial organisation that may gain financially from your submission: a salary, fees, funding, reimbursements. - You expect to receive, or in the past 4 years have received, shared grant support or other funding with any of the authors. - You hold, or are currently applying for, any patents or significant stocks/shares relating to the subject matter of the paper you are commenting on. Sign up for content alerts and receive a weekly or monthly email with all newly published articles Already registered? Sign in close Error Sign In If you've forgotten your password, please enter your email address below and we'll send you instructions on how to reset your password. Email us for further assistance. The email address should be the one you originally registered with F1000. Email address not valid, please try again You registered with F1000 via Google, so we cannot reset your password. To sign in, please click here. If you still need help with your Google account password, please click here. You registered with F1000 via Facebook, so we cannot reset your password. To sign in, please click here. If you still need help with your Facebook account password, please click here. Code not correct, please try again Server error, please try again. If your email address is registered with us, we will email you instructions to reset your password. If you think you should have received this email but it has not arrived, please check your spam filters and/or contact for further assistance. Please wait...