{"paper_id":"26785f57-09ec-4f81-a575-91fd57dc374d","body_text":"DOI: https://doi.org/10.4038/jdp.v20i1.7873 Journal of Diagnostic Pathology 2025;20(1):10-14. \n 13 \nCase report \nPotential histopathological pitfalls in biopsies for endometriosis, related to the \nuse of cellulose based material in prior surgical procedures \nE.K.D.M. Wickramaratne¹, F. Busch², M. Byrnes³, A.Tan¹ \n¹ Clinipath Pathology, Western Australia, Australia. \n² Women Centre, Western Australia, Australia. \n³ Joondalup Private Hospital, Australia. \nSubmitted on 13.05.2025.  Accepted for publication on 27.07.2025. \n______________________________________________________________________________________\nAbstract \nCellulose-based materials used in endometriosis surgeries, can trigger histiocytic reactions that mimic \nmucinous lesions. These two cases highlight diagnostic challenges due to misleading special stain \npositivity. Accurate biopsy interpretation requires attention to histologic features and detailed \nsurgical history to avoid misdiagnosis. \nKeywords: endometriosis, cellulose based material, mucinous lesions, granuloma \n__________________________________________________________________________________ \nIntroduction \nEndometriosis is a recurring condition affecting \nwomen of reproductive age. Peritoneal \nbiopsies are routinely employed for its \ndiagnosis. According to a study done in 2023, \nup to 28% of patients may require additional \nsurgical intervention within ten years following \ncomplete excision of endometriosis due to \nreappearance of symptoms (1). As a result, \nrepeat biopsies are not uncommon in these \ncases; however, endometriosis may not always \nbe detected in subsequent biopsies. Instead, \npost-surgical changes may be observed.  \nIntraoperative use of haemostatic products \ncan induce tissue reactions that may lead to \ndiagnostic histopathology challenges. \nCellulose based materials (CBM) are among \nthe factors contributing to such complications. \nOxidized regenerated cellulose (ORC), which is \na cellulose -based material (CBM), marketed \nunder the brand Surgicel®, is a widely utilized \nhaemostatic agent in surgical procedures. This \nproduct facilitates clot formation and \neffectively manages minor bleeding (2). While \ngenerally safe and efficien t, its use has been \nassociated with complications such as foreign \nbody reactions and granuloma formation, \nwhich can manifest months or years post -\nsurgery. Special histochemical stains on \nsubsequent biopsies can complicate the \ndiagnosis, showing features th at mimic \nmucinous lesions, characterized by \nintracytoplasmic positivity for mucin stains \nsuch as  alcian blue, mucicarmine and and \nPeriodic Acid-Schiff with diastase \ndigestion(PAS-D)(3). In addition, they can be \npositive for fungal stains such as Grocott \nMethenamine Silver (GMS) and Periodic Acid -\nSchiff (PAS). Another CBM, Oxiplex gel, is used \nintraoperatively to reduce intra -abdominal \nadhesion formation. Comprising \ncarboxymethylcellulose and polyethylene \noxide, Oxiplex gel can induce tissue reactions \nsimilar to those seen with ORC(4).  \nIn this report, we present two cases where the \nprior application of CBM during surgical \nprocedures led to confusing results with \nCorresponding author:  Dr  E.K.D.M. Wickramaratne \nClinipath Pathology, 310, Selby Street North, Osborne Park, \nWestern Australia \ndiliniwickramaratne@gmail.com \nThis is an open access article licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.  \n(CC BY-SA 4.0), which permits unrestricted use, distribution and reproduction in any medium, provided the original author \nand source are attributed and materials are shared under the same license. \n\n\nDOI:                                                                                   Journal of Diagnostic Pathology 2025;20(1):10-14. \n \n \n \n \n11 \nspecial stains in peritoneal biopsies performed \nfor the investigation of endometriosis. \n \nCase History \nCase 1 \nA 34-year-old woman with a history of \nextensive endometriosis underwent prior \nsurgical intervention for endometrioma \ndrainage. During the previous procedure, \nSurgicel® was applied as a haemostatic agent. \nThe subsequent peritoneal biopsy showed \ngranulomas and aggregates of foamy \nhistiocytes. These cells demonstrated \npositivity for mucin stains, including Alcian \nblue, mucicarmine and PAS-D. Additionally, the \nspecimen was positive for the fungal stain GMS \n(Figures 1 and 2). No evidence of \nendometriosis was identified in this biopsy. \n \nCase 2 \nA 40-year-old woman presented with chronic \npelvic pain . She had a history of primary \nsubfertility and had undergone two previous \nlaparoscopic procedures abroad, with one \nperformed in South Africa approximately 11 \nyears prior (records unavailable) and another \nin New Zealand approximately 8-9 years prior. \nIn February 2019, a laparoscopy revealed \nextensive intra -abdominal adhesions . \nHistological assessment confirmed \nendometriosis, which was excised from the \nanterior broad ligament peritonea, pelvic \nsidewalls and the pouch of Douglas. Oxiplex \nwas applied to all surgical sites. In July 2022, \nthe patient underwen t laparoscopic \nadhesiolysis for treatment of histologically \nconfirmed endometriosis from the right \nuterosacral ligament and right pelvic sidewall. \nOxiplex was used again during the procedure. \nA biopsy from the right anterior broad \nligament peritoneum revealed only reactive \nchanges, with no histological evidence of \nendometriosis. The specimen exhibited groups \nof histiocytic cells associated with foreign \nmaterial, which were positive for mucin stains \nAlcian blue and mucicarmine. PAS staining was \npositive but not resistant to diastase digestion. \nGMS also demonstrated positivity.  \nThe features of the two cases are summarised \nin table 1. \nA \n B \nFigure  1: A - Haematoxylin and eosin-stained section of case 1 showing aggregates of large cells \ncontaining mucin-like material (x400), B - PAS-D positivity in the large mucinous-like cells (x100) \n\nDOI:                                                                                   Journal of Diagnostic Pathology 2025;20(1):10-14. \n \n \n \n \n12 \n   \n Case 1 Case 2 \nAge (years) 34 40 \nNumber of previous surgeries 1 4 \nType of haemostat used Surgicel® Oxiplex (2 previous surgeries) \nHistology Granulomas and aggregates \nof foamy histiocytes.  \nNo endometriosis. \nGroups of histiocytes with \nforeign material.  \nNo endometriosis. \nSpecial stains Alcian blue Positive Positive \nMucicarmine Positive  Positive  \nPAS Positive  \n(Resistant to diastase) \nPositive  \n(Not resistant to diastase) \nGMS Positive Positive \nDiscussion \nThese two cases involved distinct CBM types \nbut showed similar histological features and \nspecial stain characteristics . The first case \ninvolved Surgicel®, which is an ORC derived \nfrom decomposed wood pulp, regenerated \ninto continuous cellulose fibers (5). Its \nhaemostatic properties involve pseudo -clot \nformation, increased coagulation factor \nconcentration, and lowering of pH. \nAdditionally, Surgicel® exhibits in vitro \nbactericidal properties against many \nbacteria(6). Typically left in -situ post -surgery \nfor absorption (5), its degradation timeline \nvaries ( two to six weeks), with granuloma \nformation reported between two to thirty-six \nmonths post -implantation(6). Surgicel's pH -\nlowering effect can exacerbate local \ninflammation(2,5). Degradation reactions \ninclude blood -material interactions, \nFigure  2: Figure  2: A - Alcian blue positivity in the large cells mucinous-like cells in case 1 (x40), \nB - GMS positivity in the large mucinous-like cells (x40) \nTable 1: Summary of clinical and histological findings of the cases \n\n\nDOI:                                                                                   Journal of Diagnostic Pathology 2025;20(1):10-14. \n \n \n \n \n13 \nprovisional matrix formation, and acute and \nchronic inflammation with foreign body \nreactions(2,5,6).  First described by Ito et al in \n1989 as a granuloma to oxidized cellulose (7), \nSurgicel-induced granulomas have since been \nreported in various anatomical sites including \nthe gastrointestinal tract, ovaries, thyroid, \nmediastinum, nasal cavity, liver, kidney, heart, \nbrain and adrenal glands(2,7,8). \nPatients may present with non -specific \nsymptoms such as fever, anorexia and weight \nloss mimicking malignancy(5). These reactions \ncan be mistaken for abscesses or tumour \nrecurrence on postoperative imaging as well, \nleading to additional procedures (6,8). \nRecognition of these granulomas is important \nand pathologists should be familiar with this \ncondition(2). In the two cases described here, \nthe cells contained basophilic material \nresembling mucin in the haematoxylin and \neosin stained  sections, which were also \npositive for mucin stains raising the suspicion \nof a mucinous lesion. These histopathological \nchanges have been previously described in \nother cases, as laminated fragments within \nphagocytic cells with a proteinaceous \nbackground(2). Gao et al. reported a \nhistopathological appearance characterized by \nplump-to-flattened epithelioid cells containing \nbasophilic material associated with \nmultinucleated foreign body -giant cells. \nHowever, unlike in the two cases described, \nboth the epithelioid cells and the basophil ic \nmaterial tested negative for mucin on PAS \nstain(7). \nStudies have also described instances where \nmucin stains, such as Alcian blue and similar \ndyes have a high affinity to cellulose(9). \nStaining methods like Grocott methenamine \nsilver (GMS), Congo red, and PAS can also \nhighlight cellulose, due to properties similar to \nthose of native wood (10). In the two  cases \nreported GMS showed false positivity, similar \nto that previously described. In 1994 Kershisnik \net al. reported cases of five women treated \nwith oxidized regenerated cellulose during \nabdominal surgery, that showed collections of \nlarge cells beneath the mesothelial surface \nwith small, bland nuclei and abundant granular \nbasophilic cytoplasm. The cells exhibited bright \nred staining with mucicarmine, along with \nAlcian blue and PAS -D positivity. Such lesions \ncan be mistaken for mucinous lesions  and \ndiagnosis can be particularly challenging due to \nstrong mucicarmine and mucin stain positivity \nin histiocytic cytoplasm(3). In 2009 Tang et al. \nrepoted as case related to ORC in which \nmicroscopic examination of rectal serosa \nrevealed mononuclear cells within the sub \nmesothelial stroma, displaying positive \nstaining with mucicarmine and PAS-D, thereby \ncomplicating diagnosis (11). To minimize the \nrisk of Surgicel granuloma formation, only the \nminimal amount required to achieve \nhaemostasis should be used, and any excess \nshould be promptly removed once bleeding is \ncontrolled (5). It is also important to document \nits application in the surgical records (2). \nIn the second case, histological features were \nattributed to Oxiplex. Intra -abdominal \nsurgeries carry risks of peritoneal adhesions, \nwhich can lead to chronic pelvic pain, impaired \nfertility, and, in severe cases, intestinal \nobstruction with ileus. To miti gate these risks, \na laparoscopically applicable absorbable gel, \nOxiplex (Intercoat, Ethicon, Norderstedt, \nGermany), was recently introduced(4). This gel \ncontains carboxymethylcellulose and \npolyethylene oxide, both known to reduce \nadhesion formation by pote ntially coating \ntissues and inhibiting fibrin interactions on \nperitoneal surfaces(4). However, this material \ncan also cause foreign body type reactions in \ntissues causing later histopathological \nevaluation challenging. A case report \nhighlighted initial diagnostic confusion during \nfrozen section analysis due to excessive foreign \nbody reacti on to pools of Oxiplex gel, \nresembling pseudomyxoma peritonei (4). This \nconfusion can arise, particularly in frozen \nsections, if the pathologist is unaware of \nOxiplex gel use in the patient's history. \nNotably, mucin staining with PAS was negative \nin this case, unlike the findings in our cases. \n \nConclusion \nCareful histological examination and clinical \nhistory are crucial for an accurate diagnosis. \nPathologists must be aware of the pitfalls of \nmisinterpreting mucin stains and recognise \n\nDOI:                                                                                   Journal of Diagnostic Pathology 2025;20(1):10-14. \n \n \n \n \n14 \nmimickers of mucinous morphology. Key \nhistological features include the histiocytic \nnature of lesions and the absence of \ncytological atypia, along with a history of prior \nuse of CBMs at the surgical site. Special stains \ncan be misleading, falsely staining for mucin, \nhence careful microscopic examination and an \naccurate clinical history are required for \ndiagnosis.  Distinguishing between \nendometriotic deposits and foreign body \nreactions during laparoscopy is difficult as both \nconditions have a similar appear ance \nintraoperatively.  When reporting these cases, \nadditional tissue levels to identify \nendometriotic glands and stroma is important \nto confirm the presence or absence of \nendometriosis as they can also co -exist. \nCombining detailed clinical history with \nthorough pathological examination is essential \nfor accurately diagnosing biopsies from \npatients investigated and ma naged for \nendometriosis.   \n \nReferences \n1. 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Analytical staining review. \nBioresources. 2019;14(3):7387-7464. \n10. Lewin-Smith MR, Kalasinsky VF, Mullick FG. \nHistochemical identification of \nmicrocrystalline cellulose, calcium oxalate, and \ntalc in tissue sections. Arch Pathol Lab Med. \n2011 Aug;135(8):963. \n11. Tang KW -K, Lamaro V, Jaworski R. \nPeritoneal histiocytic reaction associated with \noxidised regenerated cellulose, a form of \nmucicarminophilic histiocytosis. Pathology. \n2009 Oct;41(6):598 -600. \ndoi:10.1080/00313020903071579.","source_license":"CC0","license_restricted":false}