{"paper_id":"ec4665db-f2e0-4255-aa96-7989e22b9aaf","body_text":"C A S E R E P O R T Open Access\nPolypoid nodular histiocytic hyperplasia\nassociated with endometrioid adenocarcinoma of\nthe endometrium: report of a case\nShabnam Akhter, W Dwayne Lawrence and M Ruhul Quddus *\nAbstract\nA 45 year old woman underwent Laparoscopy-assisted total hysterectomy with staging procedure following a\ndiagnosis of endometrial endometrioid adenocarcinoma on her endometrial biopsy. The hysterectomy specimen\nshowed a FIGO I stage 1a, endometrioid carcinoma. A separate polypoid lesion in the endometrium, distinct from the\ncarcinoma, was also identified. Microscopically the polypoid lesion was “nodular histiocytic hyperplasia ”. The H&E,\nimmunohistochemical staining findings and the differential diagnoses are discussed in this report. Although\ndescription of similar lesions is available in the literature, the current lesion is unique as it is identified in a\nhysterectomy specimen in its entirety and its association with an endometrial endometrioid carcinoma.\nVirtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/\nvs/1060511915121922\nKeywords: Endometrium, Nodular histiocytic hyperplasia, Endometrioid carcinoma\nIntroduction\nNodular histiocytic hyperplasia, initially thought to be of\nmesothelial origin because of their sites of occurrences,\nwas reported in hernia sac [1]. Subsequently similar le-\nsions have been reported from various other body sites,\ne.g., the pericardial sacs and cardiac valves [2], periton-\neum [3] and pleura [4]. Their presence in endometrial\nbiopsy may mimic neoplasia. A recent series published\nseven cases of nodular histiocytic hyperplasia [5]. The\ncases, so far reported in the literature, are associated\nwith benign lesions only. Since the previously reported\ncases were encountered in endometrial biopsies the le-\nsions were fragmented. We report here a case of a nodu-\nlar histiocytic hyperplasia associated with FIGO I/III\nendometrial endometrioid adenocarcinoma. We also de-\nscribe the lesion in its entirety; as noted above, all previ-\nous descriptions of this entity were based on their\npresence in biopsy specimens .\nCase presentation\nA 45 year-old woman with a history of uterine fibroids\npresented with vaginal bleeding. She was Gravida 1 and\nPara 0, with a history of termination of pregnancy. A\npelvic ultrasound showed a 9.1 x 8.0 x 4.0 cm partially\ndistorted uterus with multiple hypoechoeic nodular\nareas, the largest being 4 x 3 cm and a thickened,\n1.8 cm, endometrial stripe.\nPathologic findings\nAn endometrial biopsy revealed a FIGO I endometrial\nendometrioid type adenocarcinoma. After weighing-in\nall the options presented to her, the patient opted for a\nLaparoscopy-assisted vaginal hysterectomy with bilateral\nsalpingo-oophorectomy and staging procedure.\nGross examination of the specimen revealed a 172\ngms, 9.6 x 6.5 x 5.6 cm distorted uterus with multiple\nsubserosal and intramural fibroids. Upon opening the\nuterus, a 4.5 x 4.2 cm shaggy polypoid lesion was identi-\nfied in the endometrial cavity involving both uterine\nwalls. In addition a 0.7 x 0.5 cm polypoid lesion\n(Figure 1a) was found on the anterior wall of the endo-\nmyometrium with smooth surface. The fibroids were\nnoted in the intramural and subserosal locations.\n* Correspondence: mquddus@wihri.org\nDepartment of Pathology and Laboratory Medicine, Women & Infants\nHospital, Alpert Medical School of Brown University, 101 Dudley Street,\nProvidence, Rhode Island 02905, USA\n© 2014 Akhter 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/4.0), 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.\nAkhter et al. Diagnostic Pathology 2014, 9:93\nhttp://www.diagnosticpathology.org/content/9/1/93\n\nFigure 1 Photomicrographs of Nodular Histiocytic Hyperplasia. 1a (H&E): Low power magnification of polypoid nodular histiocytic\nhyperplasia; 1b (H&E): Closely packed histiocytes near the base of the polyp; 1 c (H&E): pink hyalinized fibrous bands separating aggregates of\nhistiocytes; 1d (H&E): thick-walled blood vessel mimicking “onion-skinning”;1 e (H&E): more sclerosis towards the surface of the polyp; 1 f (IHC):\nhistiocytic immunohistochemistry marker (CD68) showing diffuse positivity; 1 g (IHC): Pancytokeratin marker (AE1/AE3) is completely negative\n(surface epithelium is reactive serving as positive internal control); 1 h (IHC): HMB45 is negative.\nFigure 2 Photomicrographs of Endometrioid adenocarcinomaarising in a background of secretory Endometrium.2a (H&E): Low power view\nof FIGO I endometrioid carcinoma; 2 b (H&E): high power view of the same tumor; 2 c (H&E): Carcinoma is arising in a background of secretory\nendometrium.\nAkhter et al. Diagnostic Pathology 2014, 9:93 Page 2 of 4\nhttp://www.diagnosticpathology.org/content/9/1/93\n\nMicroscopically, a smooth surfaced polypoid lesion\nwas found to consist mostly of aggregates of histiocytes\nthat were more closely packed near the endomyometrial\njunction, i.e., the base of the lesion (Figure 1b). Pink hya-\nlinized fibrous bands are noted throughout the polypoid\nlesion (Figure 1c). Many blood vessels with thickened\nhyalinized walls are present throughout the lesion, more\ncommonly towards the surface (Figure 1d). Towards the\nsurface, the histiocytes were relatively sparse and sepa-\nrated by sclerosis (Figure 1e). The polyp was lined by\na thin, attenuated, layer of endometrial epithelium\n(Figure 1e). The histiocytes resembled perivascular epi-\nthelioid cells. And presence of thick walled blood vessels\nwithin the lesion raised the question of a perivascular\nepithelioid cell tumor (PEComa). Immunohistochemical\nstains reveal that the lesional cells are strongly and dif-\nfusely reactive to a histiocytic marker, CD68, (Figure 1f )\nand non-reactive to HMB45 (Figure 1h), pancytokeratin\n(AE1/AE3), (1 g) Epithelial membrane antigen (EMA),\nDesmin, Smooth Muscle Actin (SMA), CD10, Vimentin.\nFIGO grade I stage 1a endometrioid adenocarcinoma\nwas noted in the endometrium as well (Figure 2a and\nFigure 2b). The tumor involves areas of adenomyosis;\nhowever, true myometrial invasion was not present. The\ncarcinoma was arising in background of functional endo-\nmetrium (Figure 2c). The lower uterine segment and\ncervix were free of tumor. No lymph-vascular space in-\nvasion was identified. The bilateral ovaries and fallopian\ntubes were unremarkable. The regional lymph node dis-\nsection was all negative for metastatic carcinoma.\nDiscussion and conclusions\nNodular histiocytic hyperplasia is a rare lesion often inci-\ndentally encountered in endometrial biopsies. Majority of\nthese lesions are reported in the literature as single case\nreport. The largest series, so far has been reported in the\nliterature, is based on 7 cases [5]. The lesion, when en-\ncountered in endometrial biopsies and present in small\nfragments, may mimic a neoplasm. So far all the re-\nported cases are, however, associated with benign dis-\neases. The current report is based on a case of nodular\nhistiocytic hyperplasia associated with a FIGO I/III\nendometrial endometrioid adenocarcinoma. The lesion\nitself is identified grossly in its entirety as a distinct en-\ntity presenting as an endometrial polyp .\nThe differential diagnoses of this entity include Lang-\nerhans cell histiocytosis, xanthogranulomatous endomet-\nritis, malakoplakia, signet-ring cell changes of the\nendometrial stromal cells, etc. Available reports in the\nliterature have elaborated how to distinguish nodular\nhistiocytic hyperplasia from their mimics. The current\ncase showed some resemblance with perivascular epithe-\nlioid cell tumor (PEComa) or an epithelioid smooth\nmuscle tumor with many small hyalinized blood vessels.\nMicroscopic and multifocal PEComa of the female geni-\ntal tract have been reported [6,7]. One interesting find-\ning noted in the current case is the presence of\nhyalinized fibrous strands throughout the lesion; af e a -\nture often seen in endometrial stromal tumors. The cyto-\nlogic appearance of the tumor cells seen in endometrial\nstromal tumor is, however, completely different from\nwhat was seen in nodular histiocytic hyperplasia. The\ncells in endometrial stromal tumor are small, mostly\nround and darkly stained, especially in low grade stro-\nmal sarcoma .\nSpecial stains that were performed to rule out the\nmimics show the lesional cells of nodular histiocytic\nhyperplasia are strongly and diffusely reactive to histio-\ncytic marker, CD68. All other markers including, epithe-\nlial markers (AE1/AE3), smooth muscle markers, and\nendometrial stromal cell marker (CD10) were non-\nreactive. HMB45, a marker for PEComa, was also\nnegative.\nThe site of nodular histiocytic hyperplasia was clearly\nlocated on the surface of endometrium with smooth lin-\ning and protruding into the endometrial cavity .\nIt is speculated that the nodular histiocytic aggregates\nmay result from previous endometrial biopsy. The\ncurrent case did have a recent history of endometrial bi-\nopsy one month prior to her hysterectomy. The previous\nbiopsy in this case revealed endometrial carcinoma with\nsquamous differentiation and no evidence of histiocytic\naggregate. It is also of note that the appearance of the\nfoamy histiocytes often seen in endometrial biopsies is\nalso different from the histiocytes present in nodular\nhyperplasia as they lack the foamy cytoplasm.\nMazur and Kurman [8] proposed that these histiocytes\napparently reside in the endometrial cavity and reported\ntheir presence in association with hydrometra and be-\nnign bleeding patterns. The authors postulated that it\nmay represent a response to what they have proposed as\n“intracavitary debris. ” The current case was associated\nwith an endometrioid adenocarcinoma so presence of\nsome “intracavitary debris ” is not unlikely. As noted be-\nfore the polypoid lesion was seen projecting into the\nendometrial cavity.\nA possibly related, but morphologically dissimilar, his-\ntiocytic endometrial lesion has been reported by Iezzoni\nand Mills in their study of non-neoplastic endometrial\nsignet-ring cells [9]. No signet-ring cells are identified in\nthis case.\nKim et al. proposed that the endometrial stromal cells\nshowing progestational changes with atrophic endomet-\nrial glands trapped in the middle may produce histologic\nsimilarities that may vaguely resemble histiocytic aggre-\ngate [10]. Unlike nodular histiocytic aggregate, decidua-\nlized stromal cells do not form a discrete nodule. Kim\net al. also speculated that the nodules may not originate\nAkhter et al. Diagnostic Pathology 2014, 9:93 Page 3 of 4\nhttp://www.diagnosticpathology.org/content/9/1/93\n\nin the endometrium because no vasculature was seen in\ntheir cases [10]. The current case documents many blood\nvessels in the nodule and thus contradicts that specula-\ntion of Kim et al.\nIn conclusion, nodular histiocytic hyperplasia may not\nalways be associated with benign/inflammatory lesions\nas previously reported in the literature. The current case\ndocuments its association with endometrioid carcinoma\nof the endometrium.\nThe patient is currently followed routinely and is dis-\nease free 80 months after surgery.\nConsent\nThe patient has given consent for the use of the images\nand case presentation for educational and scientific pur-\nposes provided the unique patient identification is not\nrevealed.\nCompeting interest\nThe authors declare no competing financial interest. All the authors have\nactively participated in the diagnosis and manuscript writing.\nAuthors’ contributions\nSA is the Stuart Lauchlan International Visiting Fellow in Gynecologic and\nBreast Pathology and participated in writing up the case report and MRQ is\nthe attending Pathologist on the case. WDL offered his expert opinion in\nfinalizing the case. All authors read and approved the manuscript.\nReceived: 19 February 2014 Accepted: 9 April 2014\nPublished: 12 May 2014\nReferences\n1. Rosai J, Dehner LP: Nodular mesothelial hyperplasia in hernia sacs. A\nbenign reactive condition simulating a neoplastic process. Cancer 1975,\n35:165–175.\n2. Luthringer DJ, Virmani R, Weiss SW, Rosai J: A distinctive cardiovascular\nlesion resembling histiocytoid (epithelioid) hemangioma. Evidence\nsuggesting mesothelial participation. Am J Surg Pathol 1990, 14:993–1000.\n3. Clement PB: Reactive tumor-like lesions of the peritoneum. Am J Clin\nPathol 1995, 103:673–76.\n4. Ordonez NG, Ro JY, Ayala AG: Lesions described as nodular mesothelial\nhyperplasia are primarily composed of histiocytes. Am J Sung Pathol 1998,\n22:285–92.\n5. Prakash V, Domfeh AB, Fadare O: Nodular histiocytic aggregates in the\nendometrium: a report of 7 cases. Int J Gynecol Pathol 2013, 33:52–57.\n6. Chia-Lang F, Yun-Ho C, Wei-Yu C: Microscopic endometrial perivascular\nepithelioid cell nodules: a case report with the earliest presentation of a\nuterine perivascular epithelioid cell tumor. Diagn Pathol 2012, 7:117.\n7. Wang Y, Gao L, Zheng W-Q: Multifocal PEComa (PEComatosis) of the\nfemale genital tract and pelvis: a case report and review of the\nliterature. Diagn Pathol 2012, 7:23.\n8. Mazur MT, Kurman RJ: Artifacts and contaminants .I n Diagnosis of\nEndometrial Biopsies and Curettings: A Practical Approach. Edited by Mazur\nMT, Kurman RJ. New York: Springer; 1995:22.\n9. Iezzoni JC, Mills SE: Nonneoplastic endometrial signet-ring cells.\nVacuolated decidual cells and stromal histiocytes mimicking\nadenocarcinoma. Am J Clin Pathol 2001, 15:249–55.\n10. Kim K-R, Lee YH, Ro JY: Nodular histiocytic hyperplasia of the\nendometrium. Int J of Gynecol Pathol 2002, 21:141–146.\ndoi:10.1186/1746-1596-9-93\nCite this article as: Akhter et al. : Polypoid nodular histiocytic hyperplasia\nassociated with endometrioid adenocarcinoma of the endometrium:\nreport of a case. Diagnostic Pathology 2014 9:93.\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\nAkhter et al. Diagnostic Pathology 2014, 9:93 Page 4 of 4\nhttp://www.diagnosticpathology.org/content/9/1/93","source_license":"CC0","license_restricted":false}