Intravascular Papillary Endothelial Hyperplasia Mimicking Sister Mary Joseph Nodule in a Patient With Ovarian Carcinoma: A Case Report

Intravascular Papillary Endothelial Hyperplasia Mimicking Sister Mary Joseph Nodule in a Patient With Ovarian Carcinoma: A Case Report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Intravascular Papillary Endothelial Hyperplasia Mimicking Sister Mary Joseph Nodule in a Patient With Ovarian Carcinoma: A Case Report Tina Elaine Resuello, Charlene Marie Ang-Tiu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1805656/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background : Intravascular Papillary Endothelial Hyperplasia (IPEH) is a rare benign vascular lesion of the skin and subcutaneous tissues that results from the proliferation of endothelial cells within a blood vessel. Case presentation : In this article, we present the case of an IPEH mimicking a Sister Mary Joseph Nodule on the umbilicus of a 53-year old female patient with ovarian cancer. A diagnostic workup was performed with a computerized tomography of abdominal cavity and pelvis showing an expansive cystic tumor formation with probable ovarian origin. Two separate histopathologic readings were done on the cutaneous lesion which revealed contradicting findings of benign versus malignant tumors. Immunohistochemical stains done showed that the lesion was positive for ERG and negative for epithelial differentiation markers. No surgical intervention was done at the time of consultation as a cutaneous metastasis was primarily considered initially. Conclusion: It is crucial to rule out a diagnosis of Sister Mary Joseph nodule, especially in a background of ovarian carcinoma as it may mimic vascular lesions occurring on the umbilicus. Immunohistochemical staining is a significant tool to precisely diagnose such lesions so that it is neither inadequately nor aggressively managed. Intravascular Papillary Endothelial Hyperplasia Masson’s tumor Sister Mary Joseph nodule ovarian cancer case report Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Background Intravascular Papillary Endothelial Hyperplasia (IPEH), also known as Masson’s tumor or Masson's vegetant intravascular hemangioendothelioma (MVH) is a benign tumor that clinically presents as bluish to purplish red cystic masses containing sanguineous material. This case report describes an 53-year-old female diagnosed with an ovarian new growth presenting with umbilical skin lesions grossly resembling what was first thought of as a Sister Mary Joseph’s (SMJ) nodule given the patient’s background of a pre-existing carcinoma. It was upon further testing with immunohistochemistry that the final diagnosis was confirmed. Cutaneous metastasis, like the SMJ nodule, although extremely rare is an important physical finding as it is a sign of advanced stage of malignancy. Hence, it was at the outset, considered in the case. However, it is also of significant to arrive with an accurate diagnosis in this case because it influences the management of the primary tumor and alleviates additional stress to the patient. Case Presentation A 53-year old Filipino female patient presented with a 2-year history of slowly progressing abdominal enlargement with subsequent appearance of multiple, slightly tender papules and nodules on the umbilicus. The appearance of cutaneous lesions started 2 months prior to the referral of the Department of Obstetrics and Gynecology (OB-GYN) to the Department of Dermatology. Review of systems revealed accompanying significant weight loss and abdominal discomfort. The past medical and personal and social history were unremarkable. She had no history of previous surgeries. The family medical history revealed a history of diabetes mellitus in a sibling and myoma on the paternal side. On physical examination, the patient had evident ascites with a presence of skin-colored and hyperpigmented papules, few nodules and cystic mass on the umbilicus. Dermoscopy of the cutaneous lesions revealed patchy pseudo reticular network with thick brown lines surrounding a structureless area and a milky red structureless area some with white veil and multiple shiny white lines and strands (Fig. 3 ). These dermoscopic features points out to a probable vascular lesion. Previous outpatient diagnostic workup done by the Department of OB-GYN revealed a normal sized anteverted uterus with thick endometrium suggestive of endometrial pathology and a pelvoabdominal mass probably an ovarian new growth with undetermined laterality, malignant by International Ovarian Tumor Analysis. A computerized tomography of the abdominal cavity and pelvis showed a huge complex mass, predominantly cystic, measuring 24.6 x 25.4 x 20.5 cm. Mass effect is seen displacing the surrounding structures peripherally. The uterus is unremarkable. Free fluid collection is seen in the peritoneal and pelvic cavities (Fig. 4 ,5). Blood test demonstrated mild microcytic, hypochromic anemia, mild hyponatremia and hypocalcemia and increased levels of Cancer antigen 125 at > 500 mg/dL. Chest radiograph showed pleural effusion on the bilateral lung. The Department of Dermatology did a 4 mm skin punch biopsy at 2 sites on the umbilicus. The histopathological result of skin biopsy revealed metastatic deposits of tumor cells over the dermis in an Indian file formation. Dilated lymph vessels and thinning of endothelial wall, containing atypical pleomorphic cells spill over the dermal interstitial fibers (Fig. 6 ). These results were indicative of a cutaneous metastasis from a primary source. A separate reading was done by the Department of Pathology which revealed dilated vascular spaces lined by pleomorphic cells exhibiting mild atypia. Their primary consideration was intravascular papillary endothelial hyperplasia arising in a pre-existing lymphagioma or papillary hemangioma. Immunohistochemistry was performed paraffin-embedded tumor tissue. Tissue cells showed positive staining for ERG, which is a specific immunohistochemical marker for vascular differentiation, including benign and malignant vascular tumors 1 (Fig. 7). The cells of interest were negative for CK7, CK20, p63 and Pax8. Histomorphology and immunohistochemical profile supports the diagnosis of intravascular papillary endothelial hyperplasia. Prior to performing the immunohistochemical staining, the patient was initially referred back to the OB-GYN Department with the apprising of a poor prognosis due to a consideration of a metastasis. Few days after her initial visit to Dermatology Department, patient noted recurrence of bleeding and was given first-aid management. The patient was then lost-to-follow-up due to the ongoing community quarantine in the area because of the COVID-19 pandemic. Until three months later, she was admitted by the primary service, co-managed by the Department of Internal Medicine, for management of worsening pleural effusion. Unfortunately, the patient was not optimized for further treatment of the primary tumor as a result of her deteriorating functional capacity. Meanwhile, the skin lesions have remained the same in size, without development of new lesions. Less than a week after admission, the patient expired due to pulmonary complications. Discussion Intravascular Papillary Endothelial Hyperplasia (IPEH), also known by its eponym Masson’s tumor was first described by Pierre Masson in 1923 in an inflamed hemorrhoid of a 68-year old patient which he believed was a neoplastic lesion. He first called it Hémangioendothéliome végétant intravasculaire but later it was described as a reactive phenomenon by Henschen 3 . IPEH is a benign vascular lesion comprising around 2% of the vascular tumors of the skin and subcutaneous tissue. The condition is slightly predominant among females with a female to male ratio of 1.2:1 4 . It has a common incidence between the 3rd to 4th decade of life 5 . IPEH presents clinically as a sharply demarcated firm, bluish or purplish-red nodule or mass, measuring 0.5 to 5 cm, commonly seen on the fingers, trunk, head and neck. Based on the author’s search, there were no previous reports yet of IPEH occurring on the umbilicus. Three variants have been described: (1) the primary form occurs within a dilated vessel, (2) the secondary or mixed form which occurs in association with a thrombus in the setting of a preexisting lesion, e.g. within a hemangioma, arteriovenous malformation, pyogenic granuloma, or varix and (3) the undermined type found in an extravascular location, in which the lesion develops in the bed of a hematoma and trauma is a prerequisite 2 . Our patient exhibits features of the second type. The pathogenesis of IPEH is still poorly understood but literature review postulates a benign neoplastic process that involves proliferation of the endothelial cells in a papillary formation into the vascular lumen, which can be followed by obstruction and secondary degeneration. It typically follows a traumatic vascular stasis or thrombus. Basic fibroblast growth factor (FGF) appears to be released by the invading macrophages to the trauma site, initiating proliferation of endothelial cells 4 and activating a positive feedback loop of endothelial proliferation 5 . It is imperative to exclude several differential diagnoses of a patient presenting with an umbilical mass or nodule such as a primary umbilical neoplasm, cutaneous metastasis, umbilical hernia, umbilical endometriosis or epidermal inclusion cysts. In this patient, a diagnosis of cutaneous metastasis was originally considered because of the background of an ovarian carcinoma despite contradicting histopathologic findings on H&E stain. The definitive diagnosis of IPEH is obtained by tissue biopsy of the lesions and histologically, should be differentiated with hemangioma, pyogenic granuloma, and angiosarcoma. On tissue biopsy, the lesions of IPEH display dilated vessels that contains papillary proliferation of plump endothelial cells that are one to two cell thick 3 . It frequently overlies a fibrous tissue 6 . It lacks cellular atypia, although there are reported cases with moderate atypia 7 . Fibrin deposition and thrombi formation may be present without areas of necrosis 8 . Although seldom necessary, immunohistochemistry assists in arriving at the exact diagnosis. The cells of IPEH are differentiated endothelial cells, and thus, express markers such as vimentin, CD31, CD34, von Willebrand factor (vWF, factor VIII–related protein), factor XIIIa, and ULEX europaeus agglutinin (UEA-1) 3 . In our case, immunostaining has been instrumental to rule out the diagnosis of cutaneous metastasis and confirming the diagnosis of IPEH. Thus, the author strongly recommends that immunohistochemistry staining be done when the initial H&E findings are equivocal. The treatment of IPEH requires complete surgical resection with or without wide margins of excision 9 . Sclerotherapy using sodium tetradecyl sulfate followed by surgery resulted in good aesthetic results and minimal intra-operative bleeding in a few reported cases. Recurrence of lesions is uncommon 3 . Conclusion Sister Mary Joseph nodule, especially in a background of Ovarian carcinoma should still be considered as a valuable differential diagnosis as it may mimic vascular lesions occurring on the umbilicus. Although histopathology remains the gold standard in the diagnosis of intravascular papillary endothelial hyperplasia, immunohistochemical staining is vital to precisely diagnose this lesion so that it is neither inadequately nor aggressively managed. It helps direct treatment options especially in patients with a consideration a cutaneous metastasis from a primary malignancy. It also crucial to prevent recurrence and morbidity. Abbreviations IPEH : Intravascular Papillary Endothelial Hyperplasia MVH : Masson's vegetant intravascular hemangioendothelioma SMJ : Sister Mary Joseph OB-GYN : Obstetrics and Gynecology H&E : hematoxylin and eosin vWF : von Willebrand factor UEA-1 : ULEX europaeus agglutinin Declarations Ethics Approval and Consent to Participate. This study was exempted from ethics review by the Rizal Medical Center Institutional Review Board (RMC-IRB) with Code No. 2022-D-CR-#007 on April 22, 2022. Informed consent was obtained from the subject. Consent for publication. Informed consent for publication was obtained. Any demographic details that are associated with the patient are omitted and the identity of the patient is completely anonymized. Availability of data and materials. The dataset supporting the conclusions of this article is included within the article. Competing interest. The authors declare that they have no conflict of interest. Funding. This article received no external funding. Authors’ contributions. Both authors have substantially contributed in the diagnosis and management of the patient, drafting the manuscript, read and approved the final manuscript. Acknowledgements. The authors appreciate the contributions of Dr. Joaquin Antonio S. Patag, the dermatopathologist of the Department of Pathology and Laboratory Medicine of Rizal Medical Center. References Michal M. Stains & molecular markers: ERG. PathologyOutlines.com website. https://www . http://www.pathologyoutlines.com/topic/stainsERG.html Accessed September 15th, 2020. Sood N, Soin N. Masson's Tumour: Two Case Reports with a Brief Review of Literature. Journal of Clinical & Diagnostic Research. 2019 Jun 1;13(6). Guledgud MV, Patil K, Saikrishna D, Madhavan A, Yelamali T. Intravascular papillary endothelial hyperplasia: diagnostic sequence and literature review of an orofacial lesion. Case Reports in Dentistry. 2014 Jan 1;2014. Mahapatra QS, Sahai K, Malik A, Mani NS. Intravascular papillary endothelial hyperplasia: an unusual histopathological entity. Indian dermatology online journal. 2015 Jul;6(4):277. Pesce V, Bizzoca D, Notarnicola A, Piazzolla A, Vicenti G, Cimmino A, Fortarezza F, Maccagnano G, Solarino G, Moretti B. An intravascular papillary endothelial hyperplasia of the hand radiologically mimicking a hemangiopericytoma: a case report and literature review. SAGE Open Medical Case Reports. 2018 Jan 9;6:2050313X17752851. Díaz-Flores L, Gutiérrez R, Madrid JF, García-Suárez MP, González-Álvarez MP, Díaz-Flores Jr L, Sáez FJ. Intravascular papillary endothelial hyperplasia (IPEH). Evidence supporting a piecemeal mode of angiogenesis from vein endothelium, with vein wall neovascularization and papillary formation. Histology and histopathology. 2016 Jun 21;31(11):1271-9. Espinosa A, González J, García-Navas F. Intravascular papillary endothelial hyperplasia at foot level: a case report and literature review. The Journal of Foot and Ankle Surgery. 2017 Jan 1;56(1):72–4. Hale C. Intravascular papillary endothelial hyperplasia. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/skintumornonmelanocyticintravascularpapillary.html Accessed September 15th, 2020. Boukovalas S, Dillard R, Qiu S, Cole EL. Intravascular papillary endothelial hyperplasia (Masson’s tumor): diagnosis the plastic surgeon should be aware of. Plastic and Reconstructive Surgery Global Open. 2017 Jan;5(1). Hashimoto H, Daimaru Y, Enjoji M. Intravascular papillary endothelial hyperplasia. A clinicopathologic study of 91 cases. The American journal of dermatopathology. 1983 Dec 1;5(6):539 – 46. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1805656","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":119183330,"identity":"4bc1130d-60f1-472f-94b2-9bf17957f100","order_by":0,"name":"Tina Elaine Resuello","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5UlEQVRIie2RsQrCMBBAEwLX5dTVUv2Hg0LFxX5MoZOD4KI4OLhWXP2S7FKwix9QcNAqOOsgKDqY1smlqZtg3vCGcI9cCGMGwy8icg0YKvO9EtZ1BRYJFYmg/AC0CXsnOdAsrEt8q7Y6n6nX6ljz0/ja77WAieyQli5WD+wlBdiNEm/bloFaDFy3X5ogOUjKaQhbWwqVIDiaxH08aYq0O8HQltNKiecwitUtAPwi4wpJjF43ogRpEwqHywRBaN5iLTZuehtNfErW/HKXE79hzbJjWfKBKH5JVB3P4bdvpg0Gg+FveAFggTi/NhEppgAAAABJRU5ErkJggg==","orcid":"","institution":"Rizal Medical Center","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Tina","middleName":"Elaine","lastName":"Resuello","suffix":""},{"id":119183331,"identity":"8290202b-2ca5-4b86-9e06-d0fe34212f86","order_by":1,"name":"Charlene Marie Ang-Tiu","email":"","orcid":"","institution":"Rizal Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Charlene","middleName":"Marie","lastName":"Ang-Tiu","suffix":""}],"badges":[],"createdAt":"2022-06-29 01:44:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1805656/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1805656/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":23909337,"identity":"bf21a753-b757-4bd0-8316-67fd7a416754","added_by":"auto","created_at":"2022-07-15 15:51:19","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":145733,"visible":true,"origin":"","legend":"\u003cp\u003eAbdomen distended and tense. Percussion reveals ascites with shifting dullness\u003c/p\u003e","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1805656/v1/71ce7cdf3591b45942d29ec7.jpg"},{"id":23909343,"identity":"81496297-7afd-45c7-b645-51df573f5ea3","added_by":"auto","created_at":"2022-07-15 15:51:19","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":195975,"visible":true,"origin":"","legend":"\u003cp\u003eMultiple skin-colored to pinkish papules, few nodules and solitary cystic mass\u003c/p\u003e","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1805656/v1/0a4216ac92e1ec300393c907.jpg"},{"id":23909338,"identity":"63fec96f-a382-49d1-9abf-9c15f23a083f","added_by":"auto","created_at":"2022-07-15 15:51:19","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":92776,"visible":true,"origin":"","legend":"\u003cp\u003eDermoscopy of the lesion\u003c/p\u003e","description":"","filename":"Fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1805656/v1/baaad3f0c30a719f7cdb3100.jpg"},{"id":23909341,"identity":"33824243-112c-4bb9-8e36-e9fc1d8963c0","added_by":"auto","created_at":"2022-07-15 15:51:19","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":66468,"visible":true,"origin":"","legend":"\u003cp\u003eCT of abdominal cavity and pelvis showing an expansive tumor formation\u003c/p\u003e","description":"","filename":"Fig4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1805656/v1/2796efb23e91cb91ac95c992.jpg"},{"id":23909964,"identity":"e6cbdae7-98cd-40ea-8959-ee9cdecd7ff1","added_by":"auto","created_at":"2022-07-15 15:56:19","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":91389,"visible":true,"origin":"","legend":"\u003cp\u003eCT of abdominal cavity and pelvis with signs of tumor propagation to the front\u003c/p\u003e","description":"","filename":"Fig5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1805656/v1/e50ab131ffd02386c644d749.jpg"},{"id":23909342,"identity":"9c988fa8-54ac-4655-8421-06bb87dba8d7","added_by":"auto","created_at":"2022-07-15 15:51:19","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":132766,"visible":true,"origin":"","legend":"\u003cp\u003eHistopathology showing dermal nests of neoplastic cells underneath intact epidermis (H\u0026amp;E, 40x)\u003c/p\u003e","description":"","filename":"Fig6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1805656/v1/a2b7e4d909360b5e3f19cb83.jpg"},{"id":23909963,"identity":"8e40a2e2-4254-4cea-b2b5-a0de15919ce4","added_by":"auto","created_at":"2022-07-15 15:56:19","extension":"jpg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":141228,"visible":true,"origin":"","legend":"\u003cp\u003eImmunohistostaining showing positivity for ERG in the cells of interest\u0026nbsp;\u003c/p\u003e","description":"","filename":"Fig7.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1805656/v1/8cc1c77af6995b2360650056.jpg"},{"id":31327630,"identity":"d018b7cd-bc1e-42bb-b6e0-5f046e4a1dd9","added_by":"auto","created_at":"2023-01-09 20:44:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":695633,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1805656/v1/a3a4be55-aa3b-476d-9972-f01e6eef5c12.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Intravascular Papillary Endothelial Hyperplasia Mimicking Sister Mary Joseph Nodule in a Patient With Ovarian Carcinoma: A Case Report","fulltext":[{"header":"Background","content":"\u003cp\u003eIntravascular Papillary Endothelial Hyperplasia (IPEH), also known as Masson\u0026rsquo;s tumor or Masson's vegetant intravascular hemangioendothelioma (MVH) is a benign tumor that clinically presents as bluish to purplish red cystic masses containing sanguineous material. This case report describes an 53-year-old female diagnosed with an ovarian new growth presenting with umbilical skin lesions grossly resembling what was first thought of as a Sister Mary Joseph\u0026rsquo;s (SMJ) nodule given the patient\u0026rsquo;s background of a pre-existing carcinoma. It was upon further testing with immunohistochemistry that the final diagnosis was confirmed. Cutaneous metastasis, like the SMJ nodule, although extremely rare is an important physical finding as it is a sign of advanced stage of malignancy. Hence, it was at the outset, considered in the case. However, it is also of significant to arrive with an accurate diagnosis in this case because it influences the management of the primary tumor and alleviates additional stress to the patient.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 53-year old Filipino female patient presented with a 2-year history of slowly progressing abdominal enlargement with subsequent appearance of multiple, slightly tender papules and nodules on the umbilicus. The appearance of cutaneous lesions started 2 months prior to the referral of the Department of Obstetrics and Gynecology (OB-GYN) to the Department of Dermatology. Review of systems revealed accompanying significant weight loss and abdominal discomfort. The past medical and personal and social history were unremarkable. She had no history of previous surgeries. The family medical history revealed a history of diabetes mellitus in a sibling and myoma on the paternal side. On physical examination, the patient had evident ascites with a presence of skin-colored and hyperpigmented papules, few nodules and cystic mass on the umbilicus. Dermoscopy of the cutaneous lesions revealed patchy pseudo reticular network with thick brown lines surrounding a structureless area and a milky red structureless area some with white veil and multiple shiny white lines and strands (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). These dermoscopic features points out to a probable vascular lesion.\u003c/p\u003e\n\u003cp\u003ePrevious outpatient diagnostic workup done by the Department of OB-GYN revealed a normal sized anteverted uterus with thick endometrium suggestive of endometrial pathology and a pelvoabdominal mass probably an ovarian new growth with undetermined laterality, malignant by International Ovarian Tumor Analysis. A computerized tomography of the abdominal cavity and pelvis showed a huge complex mass, predominantly cystic, measuring 24.6 x 25.4 x 20.5 cm. Mass effect is seen displacing the surrounding structures peripherally. The uterus is unremarkable. Free fluid collection is seen in the peritoneal and pelvic cavities (Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e,5). Blood test demonstrated mild microcytic, hypochromic anemia, mild hyponatremia and hypocalcemia and increased levels of Cancer antigen 125 at \u0026gt;\u0026thinsp;500 mg/dL. Chest radiograph showed pleural effusion on the bilateral lung. The Department of Dermatology did a 4 mm skin punch biopsy at 2 sites on the umbilicus. The histopathological result of skin biopsy revealed metastatic deposits of tumor cells over the dermis in an Indian file formation. Dilated lymph vessels and thinning of endothelial wall, containing atypical pleomorphic cells spill over the dermal interstitial fibers (Fig. \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e). These results were indicative of a cutaneous metastasis from a primary source. A separate reading was done by the Department of Pathology which revealed dilated vascular spaces lined by pleomorphic cells exhibiting mild atypia. Their primary consideration was intravascular papillary endothelial hyperplasia arising in a pre-existing lymphagioma or papillary hemangioma. Immunohistochemistry was performed paraffin-embedded tumor tissue. Tissue cells showed positive staining for ERG, which is a specific immunohistochemical marker for vascular differentiation, including benign and malignant vascular tumors\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e (Fig. 7). The cells of interest were negative for CK7, CK20, p63 and Pax8. Histomorphology and immunohistochemical profile supports the diagnosis of intravascular papillary endothelial hyperplasia.\u003c/p\u003e\n\u003cp\u003ePrior to performing the immunohistochemical staining, the patient was initially referred back to the OB-GYN Department with the apprising of a poor prognosis due to a consideration of a metastasis. Few days after her initial visit to Dermatology Department, patient noted recurrence of bleeding and was given first-aid management. The patient was then lost-to-follow-up due to the ongoing community quarantine in the area because of the COVID-19 pandemic. Until three months later, she was admitted by the primary service, co-managed by the Department of Internal Medicine, for management of worsening pleural effusion. Unfortunately, the patient was not optimized for further treatment of the primary tumor as a result of her deteriorating functional capacity. Meanwhile, the skin lesions have remained the same in size, without development of new lesions. Less than a week after admission, the patient expired due to pulmonary complications.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIntravascular Papillary Endothelial Hyperplasia (IPEH), also known by its eponym Masson\u0026rsquo;s tumor was first described by Pierre Masson in 1923 in an inflamed hemorrhoid of a 68-year old patient which he believed was a neoplastic lesion. He first called it H\u0026eacute;mangioendoth\u0026eacute;liome v\u0026eacute;g\u0026eacute;tant intravasculaire but later it was described as a reactive phenomenon by Henschen\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. IPEH is a benign vascular lesion comprising around 2% of the vascular tumors of the skin and subcutaneous tissue. The condition is slightly predominant among females with a female to male ratio of 1.2:1\u003csup\u003e4\u003c/sup\u003e. It has a common incidence between the 3rd to 4th decade of life\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIPEH presents clinically as a sharply demarcated firm, bluish or purplish-red nodule or mass, measuring 0.5 to 5 cm, commonly seen on the fingers, trunk, head and neck. Based on the author\u0026rsquo;s search, there were no previous reports yet of IPEH occurring on the umbilicus. Three variants have been described: (1) the primary form occurs within a dilated vessel, (2) the secondary or mixed form which occurs in association with a thrombus in the setting of a preexisting lesion, e.g. within a hemangioma, arteriovenous malformation, pyogenic granuloma, or varix and (3) the undermined type found in an extravascular location, in which the lesion develops in the bed of a hematoma and trauma is a prerequisite\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Our patient exhibits features of the second type.\u003c/p\u003e \u003cp\u003eThe pathogenesis of IPEH is still poorly understood but literature review postulates a benign neoplastic process that involves proliferation of the endothelial cells in a papillary formation into the vascular lumen, which can be followed by obstruction and secondary degeneration. It typically follows a traumatic vascular stasis or thrombus. Basic fibroblast growth factor (FGF) appears to be released by the invading macrophages to the trauma site, initiating proliferation of endothelial cells\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e and activating a positive feedback loop of endothelial proliferation\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIt is imperative to exclude several differential diagnoses of a patient presenting with an umbilical mass or nodule such as a primary umbilical neoplasm, cutaneous metastasis, umbilical hernia, umbilical endometriosis or epidermal inclusion cysts. In this patient, a diagnosis of cutaneous metastasis was originally considered because of the background of an ovarian carcinoma despite contradicting histopathologic findings on H\u0026amp;E stain. The definitive diagnosis of IPEH is obtained by tissue biopsy of the lesions and histologically, should be differentiated with hemangioma, pyogenic granuloma, and angiosarcoma. On tissue biopsy, the lesions of IPEH display dilated vessels that contains papillary proliferation of plump endothelial cells that are one to two cell thick\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. It frequently overlies a fibrous tissue\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. It lacks cellular atypia, although there are reported cases with moderate atypia\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Fibrin deposition and thrombi formation may be present without areas of necrosis\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAlthough seldom necessary, immunohistochemistry assists in arriving at the exact diagnosis. The cells of IPEH are differentiated endothelial cells, and thus, express markers such as vimentin, CD31, CD34, von Willebrand factor (vWF, factor VIII\u0026ndash;related protein), factor XIIIa, and ULEX europaeus agglutinin (UEA-1)\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. In our case, immunostaining has been instrumental to rule out the diagnosis of cutaneous metastasis and confirming the diagnosis of IPEH. Thus, the author strongly recommends that immunohistochemistry staining be done when the initial H\u0026amp;E findings are equivocal.\u003c/p\u003e \u003cp\u003eThe treatment of IPEH requires complete surgical resection with or without wide margins of excision\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Sclerotherapy using sodium tetradecyl sulfate followed by surgery resulted in good aesthetic results and minimal intra-operative bleeding in a few reported cases. Recurrence of lesions is uncommon\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eSister Mary Joseph nodule, especially in a background of Ovarian carcinoma should still be considered as a valuable differential diagnosis as it may mimic vascular lesions occurring on the umbilicus. Although histopathology remains the gold standard in the diagnosis of intravascular papillary endothelial hyperplasia, immunohistochemical staining is vital to precisely diagnose this lesion so that it is neither inadequately nor aggressively managed. It helps direct treatment options especially in patients with a consideration a cutaneous metastasis from a primary malignancy. It also crucial to prevent recurrence and morbidity.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eIPEH\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003eIntravascular Papillary Endothelial Hyperplasia\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eMVH\u003c/em\u003e\u003c/strong\u003e: Masson\u0026apos;s vegetant intravascular hemangioendothelioma\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eSMJ\u003c/em\u003e\u003c/strong\u003e: Sister Mary Joseph\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eOB-GYN\u003c/em\u003e\u003c/strong\u003e: Obstetrics and Gynecology\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eH\u0026amp;E\u003c/em\u003e\u003c/strong\u003e: hematoxylin and eosin\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003evWF\u003c/em\u003e\u003c/strong\u003e: von Willebrand factor\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eUEA-1\u003c/em\u003e\u003c/strong\u003e: ULEX europaeus agglutinin\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics Approval and Consent to Participate.\u0026nbsp;\u003c/strong\u003eThis study was exempted from ethics review by the Rizal Medical Center Institutional Review Board (RMC-IRB) with Code No. 2022-D-CR-#007 on April 22, 2022. Informed consent was obtained from the subject.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication.\u003c/strong\u003e Informed consent for publication was obtained. Any demographic details that are associated with the patient are omitted and the identity of the patient is completely anonymized.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials.\u0026nbsp;\u003c/strong\u003eThe dataset supporting the conclusions of this article is included within the article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interest.\u003c/strong\u003e The authors declare that they have no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding.\u0026nbsp;\u003c/strong\u003eThis article received no external funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions.\u0026nbsp;\u003c/strong\u003eBoth authors have substantially contributed in the diagnosis and management of the patient, drafting the manuscript, read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements.\u0026nbsp;\u003c/strong\u003eThe authors appreciate the contributions of Dr. Joaquin Antonio S. Patag, the dermatopathologist of the Department of Pathology and Laboratory Medicine of Rizal Medical Center.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMichal M. Stains \u0026amp; molecular markers: ERG. PathologyOutlines.com website. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www\u003c/span\u003e\u003cspan address=\"https://www\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.pathologyoutlines.com/topic/stainsERG.html\u003c/span\u003e\u003cspan address=\"http://www.pathologyoutlines.com/topic/stainsERG.html\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e Accessed September 15th, 2020.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSood N, Soin N. Masson's Tumour: Two Case Reports with a Brief Review of Literature. Journal of Clinical \u0026amp; Diagnostic Research. 2019 Jun 1;13(6).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuledgud MV, Patil K, Saikrishna D, Madhavan A, Yelamali T. Intravascular papillary endothelial hyperplasia: diagnostic sequence and literature review of an orofacial lesion. Case Reports in Dentistry. 2014 Jan 1;2014.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMahapatra QS, Sahai K, Malik A, Mani NS. Intravascular papillary endothelial hyperplasia: an unusual histopathological entity. Indian dermatology online journal. 2015 Jul;6(4):277.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePesce V, Bizzoca D, Notarnicola A, Piazzolla A, Vicenti G, Cimmino A, Fortarezza F, Maccagnano G, Solarino G, Moretti B. An intravascular papillary endothelial hyperplasia of the hand radiologically mimicking a hemangiopericytoma: a case report and literature review. SAGE Open Medical Case Reports. 2018 Jan 9;6:2050313X17752851.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eD\u0026iacute;az-Flores L, Guti\u0026eacute;rrez R, Madrid JF, Garc\u0026iacute;a-Su\u0026aacute;rez MP, Gonz\u0026aacute;lez-\u0026Aacute;lvarez MP, D\u0026iacute;az-Flores Jr L, S\u0026aacute;ez FJ. Intravascular papillary endothelial hyperplasia (IPEH). Evidence supporting a piecemeal mode of angiogenesis from vein endothelium, with vein wall neovascularization and papillary formation. Histology and histopathology. 2016 Jun 21;31(11):1271-9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEspinosa A, Gonz\u0026aacute;lez J, Garc\u0026iacute;a-Navas F. Intravascular papillary endothelial hyperplasia at foot level: a case report and literature review. The Journal of Foot and Ankle Surgery. 2017 Jan 1;56(1):72\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHale C. Intravascular papillary endothelial hyperplasia. PathologyOutlines.com website. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.pathologyoutlines.com/topic/skintumornonmelanocyticintravascularpapillary.html Accessed\u003c/span\u003e\u003cspan address=\"https://www.pathologyoutlines.com/topic/skintumornonmelanocyticintravascularpapillary.html Accessed\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e September 15th, 2020.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBoukovalas S, Dillard R, Qiu S, Cole EL. Intravascular papillary endothelial hyperplasia (Masson\u0026rsquo;s tumor): diagnosis the plastic surgeon should be aware of. Plastic and Reconstructive Surgery Global Open. 2017 Jan;5(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHashimoto H, Daimaru Y, Enjoji M. Intravascular papillary endothelial hyperplasia. A clinicopathologic study of 91 cases. The American journal of dermatopathology. 1983 Dec 1;5(6):539 \u0026ndash; 46.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Intravascular Papillary Endothelial Hyperplasia, Masson’s tumor, Sister Mary Joseph nodule, ovarian cancer, case report","lastPublishedDoi":"10.21203/rs.3.rs-1805656/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1805656/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Intravascular Papillary Endothelial Hyperplasia (IPEH) is a rare benign vascular lesion of the skin and subcutaneous tissues that results from the proliferation of endothelial cells within a blood vessel. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eCase presentation\u003c/strong\u003e: In this article, we present the case of an IPEH mimicking a Sister Mary Joseph Nodule on the umbilicus of a 53-year old female patient with ovarian cancer. A diagnostic workup was performed with a computerized tomography of abdominal cavity and pelvis showing an expansive cystic tumor formation with probable ovarian origin. Two separate histopathologic readings were done on the cutaneous lesion which revealed contradicting findings of benign versus malignant tumors. Immunohistochemical stains done showed that the lesion was positive for ERG and negative for epithelial differentiation markers. No surgical intervention was done at the time of consultation as a cutaneous metastasis was primarily considered initially. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e It is crucial to rule out a diagnosis of Sister Mary Joseph nodule, especially in a background of ovarian carcinoma as it may mimic vascular lesions occurring on the umbilicus. Immunohistochemical staining is a significant tool to precisely diagnose such lesions so that it is neither inadequately nor aggressively managed.\u0026nbsp;\u003c/p\u003e","manuscriptTitle":"Intravascular Papillary Endothelial Hyperplasia Mimicking Sister Mary Joseph Nodule in a Patient With Ovarian Carcinoma: A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-07-15 15:51:17","doi":"10.21203/rs.3.rs-1805656/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5ef4e083-eca8-4a94-a289-865b8a91627d","owner":[],"postedDate":"July 15th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-01-09T20:44:17+00:00","versionOfRecord":[],"versionCreatedAt":"2022-07-15 15:51:17","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1805656","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1805656","identity":"rs-1805656","version":["v1"]},"buildId":"omnImTCwR2MFx8CMYfrG7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}