¹Department of Dermatology, Stanford University School of Medicine, Redwood City, California
²Dermatology Service, South Texas Veterans Health Care System, San Antonio
³Florida Dermatology and Skin Cancer Centers, Lake Wales
⁴Department of Dermatology, Yale School of Medicine, Yale University, New Haven, Connecticut
⁵Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
⁶Division of Dermatology, University of Kansas, Kansas City
⁷Department of Pathology (Dermatopathology), The University of Texas MD Anderson Cancer Center, Houston
⁸Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
⁹Section of Dermatology, University of Chicago, Chicago, Illinois
¹⁰University Hospitals Cleveland Medical Center, Department of Dermatology, Case Western Reserve University, Cleveland, Ohio
¹¹Division of Dermatology, Pennsylvania State College of Medicine, Hershey
¹²Division of Oncology, Department of Medicine, Northwestern University Medical Center, Chicago, Illinois
¹³Department of Surgery, Brigham and Women’s Hospital, Harvard University, Boston, Massachusetts
¹⁴Department of Dermatology, Yonsei University College of Medicine, Seoul, South Korea
¹⁵Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota
¹⁶Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Stanford Women’s Cancer Center, Cancer Institute, Stanford University School of Medicine, Stanford, California
¹⁷Department of Dermatology, University of California Davis, Sacramento
¹⁸Department of Dermatology, University of Tsukuba, Tsukuba, Japan
¹⁹Department of Dermatology, University of Missouri School of Medicine, Columbia
²⁰Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, Minnesota
²¹Department of Gynecologic Oncology, Metaxa Cancer Hospital, Piraeus, Greece
²²Department of Dermatology, University of California San Diego, San Diego
²³Department of Dermatology, Ed. Herriot Hospital Group (Pav. R), Lyon, France
²⁴Department of Pathology, University of Massachusetts Medical School–Baystate, Baystate Health, Springfield
²⁵Division of Plastic and Reconstructive Surgery, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
²⁶Division of Hematology, Oncology and Cell Therapy, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois
²⁷Division of Dermatology, Cooper Hospital, Rowan University, Camden, New Jersey
²⁸Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
²⁹Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, New York
³⁰Department of Gynaecology, University College, London, United Kingdom
³¹Department of Dermatology, University of Minnesota, Minneapolis
³²Department of Radiation Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
³³Dermatology Service, Memorial Sloan Kettering Cancer Center, New York, New York
³⁴Department of Dermatology, Henry Ford Hospital, Detroit, Michigan
³⁵Division of Surgery, Department of Urology, The University of Texas MD Anderson Cancer Center, Houston
³⁶Department of Pathology, Upstate Medical University, Syracuse, New York
³⁷Department of Urology, Upstate Medical University, Syracuse, New York
³⁸Department of Radiology, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia
³⁹Department of Colorectal Surgery, Royal Prince Alfred Hospital, Sydney, Australia
⁴⁰Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston
⁴¹Department of Radiotherapy, School of Medicine, University of Crete, Heraklion, Crete, Greece
⁴²Spokane Urology, Spokane, Washington
⁴³Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
⁴⁴Division of Cancer Medicine, Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston
⁴⁵Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada
⁴⁶Electrical Engineering, Kanagawa University, Kanagawa-ku, Yokohama, Japan
⁴⁷Cushing/Whitney Medical Library, Yale School of Medicine, Yale University, New Haven, Connecticut
⁴⁸Department of Otolaryngology–Head and Neck Surgery and Surgery (Organ Transplantation), Feinberg School of Medicine, Northwestern University, Chicago, Illinois
⁴⁹Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
⁵⁰Department of Medical Social Sciences, Feinberg School of Medicine, Northwestern University, Chicago, Illinois

Read article on JAMA Network

Read Article Claim CME

Abstract

Importance Extramammary Paget disease (EMPD) is a frequently recurring malignant neoplasm with metastatic potential that presents in older adults on the genital, perianal, and axillary skin. Extramammary Paget disease can precede or occur along with internal malignant neoplasms.

Objective To develop recommendations for the care of adults with EMPD.

Evidence Review A systematic review of the literature on EMPD from January 1990 to September 18, 2019, was conducted using MEDLINE, Embase, Web of Science Core Collection, and Cochrane Libraries. Analysis included 483 studies. A multidisciplinary expert panel evaluation of the findings led to the development of clinical care recommendations for EMPD.

Findings The key findings were as follows: (1) Multiple skin biopsies, including those of any nodular areas, are critical for diagnosis. (2) Malignant neoplasm screening appropriate for age and anatomical site should be performed at baseline to distinguish between primary and secondary EMPD. (3) Routine use of sentinel lymph node biopsy or lymph node dissection is not recommended. (4) For intraepidermal EMPD, surgical and nonsurgical treatments may be used depending on patient and tumor characteristics, although cure rates may be superior with surgical approaches. For invasive EMPD, surgical resection with curative intent is preferred. (5) Patients with unresectable intraepidermal EMPD or patients who are medically unable to undergo surgery may receive nonsurgical treatments, including radiotherapy, imiquimod, photodynamic therapy, carbon dioxide laser therapy, or other modalities. (6) Distant metastatic disease may be treated with chemotherapy or individualized targeted approaches. (7) Close follow-up to monitor for recurrence is recommended for at least the first 5 years.

Conclusions and Relevance Clinical practice guidelines for EMPD provide guidance regarding recommended diagnostic approaches, differentiation between invasive and noninvasive disease, and use of surgical vs nonsurgical treatments. Prospective registries may further improve our understanding of the natural history of the disease in primary vs secondary EMPD, clarify features of high-risk tumors, and identify superior management approaches.

Claim CME

Buy This Activity

Article Information

Accepted for Publication: August 31, 2021.

Published Online: January 20, 2022. doi:10.1001/jamaoncol.2021.7148

Corresponding Author: Murad Alam, MD, MSCI, MBA, Feinberg School of Medicine, Northwestern University, 676 N St Clair St, Ste 1600, Chicago, IL 60611 (m-alam@northwestern.edu).

Author Contributions: Drs Kibbi and Alam had full access to the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Kibbi, Owen, and Worley contributed equally to this manuscript and are co–first authors. Dr Alam was the Guidelines Chair. Drs Kibbi, Owen, and Worley contributed equally to the drafting and revision of the manuscript.

Concept and design: Kibbi, Owen, Worley, Aung, Barker, Cartee, Choi, Chung, Dorigo, Fujisawa, Halfdanarson, Kanitakis, Khan, Lawrence, Maher, Ross, Solomon, Tolia, Arai, Brackett, Poon, Alam.

Acquisition, analysis, or interpretation of data: Kibbi, Owen, Worley, Wang, Harikumar, Downing, Aasi, Bolotin, Bordeaux, Chandra, Cho, Cliby, Dorigo, Eisen, Fujisawa, Golda, Halfdanarson, Iavazzo, Jiang, Kim, Kuzel, Leitao, MacLean, Maher, Mittal, Nehal, Ozog, Pettaway, Ross, Rossi, Servaes, Thomas, Voelzke, Waldman, Wong, Zhou, Brackett, Ibrahim, Kang, Poon, Alam.

Drafting of the manuscript: Kibbi, Owen, Worley, Wang, Fujisawa, Halfdanarson, MacLean, Ross, Solomon, Wong, Arai, Brackett, Kang, Alam.

Critical revision of the manuscript for important intellectual content: Kibbi, Owen, Worley, Harikumar, Downing, Aasi, Aung, Barker, Bolotin, Bordeaux, Cartee, Chandra, Cho, Choi, Chung, Cliby, Dorigo, Eisen, Golda, Halfdanarson, Iavazzo, Jiang, Kanitakis, Khan, Kim, Kuzel, Lawrence, Leitao, MacLean, Maher, Mittal, Nehal, Ozog, Pettaway, Ross, Rossi, Servaes, Solomon, Thomas, Tolia, Voelzke, Waldman, Wong, Zhou, Arai, Ibrahim, Kang, Poon, Alam.

Statistical analysis: Kibbi, Owen, Worley, Harikumar, Wong.

Obtained funding: Alam.

Administrative, technical, or material support: Kibbi, Worley, Fujisawa, Iavazzo, Ozog, Pettaway, Rossi, Solomon, Wong, Brackett, Ibrahim, Kang, Poon.

Supervision: Barker, Bolotin, Bordeaux, Cartee, Cliby, Eisen, Jiang, Kim, Kuzel, Lawrence, Nehal, Pettaway, Thomas, Voelzke, Arai, Alam.

Conflict of Interest Disclosures: Dr Worley reported serving as an advisory board member for Castle Biosciences outside of the submitted work. Dr Barker reported receiving grants from the National Institutes of Health through subcontracts from Physical Sciences Incorporated, EMD Serono, Alpha Tau Medical, Merck, and Amgen; personal fees from the American Society for Radiation Oncology, the American Brachytherapy Society, and Regeneron; and nonfinancial support from Alpha Tau Medical, H. Lee Moffitt Cancer Center, and Regeneron outside the submitted work. Dr Bolotin reported serving as an investigator without compensation on clinical trials for Replimune and Pelle Pharm outside the submitted work. Dr Chandra reported serving as an advisory board member for Exicure, Novartis, Bristol Myers Squibb, Sanofi Genzyme, and Regeneron outside the submitted work. Dr Choi reported receiving personal fees from Regeneron, Parexel, OnQuality Pharmaceuticals, Bristol Myers Squibb, and Kyowa Kirin International outside the submitted work. Dr Halfdanarson reported receiving personal fees from Curium, Lexicon, Terumo, and ScioScientific; receiving research support paid to the institution from Thermo Fisher Scientific, Basilea, Turnstone Biologics, Agios, and Novartis; and serving as a consultant with fees paid to the institution for ITM, Ipsen, and Novartis outside the submitted work. Dr Leitao reported receiving funding in part through the National Institutes of Health/National Cancer Institute Cancer Center Support Grant P30 CA008748; serving on the advisory board for and receiving personal fees from Ethicon/J&J and Takeda; and receiving grants to the institution from KCI/Acelity outside the submitted work. Dr Ross reported being an employee of Foundation Medicine Inc, being an equity owner in Roche Holdings, serving on the board of directors of and being an equity owner in Celsius Therapeutics Inc, and serving as a consultant to and being equity owner of Tango Therapeutics Inc. Dr Rossi reported serving as a consultant for Almirall, Merz, Dynamed, Canfield Scientific, Evolus, Biofrontera, Quantia MD, Lam Therapeutics, Regeneron, and Cutera; receiving travel support from Mavig and L’Oreal; serving on the advisory board for Allergan Inc and Skinfix; being founder of DAR Companies; receiving research grants from ASLMS: A Ward Memorial Research Grant and Skin Cancer Foundation; receiving research/study funding from Regen, LeoPharma, and Biofrontera; serving on the editorial boards of Lasers in Surgery and Medicine, Cutis, Journal of the American Academy of Dermatology, and Dermatologic Surgery; being a board member of ASDS; and being a committee member and/or chair for AAD, ASDS, and ASLMS. Dr Thomas reported serving as an advisory board committee member for Regeneron and Merck outside the submitted work. Dr Wong reported serving on the advisory board for Merck Pharmaceuticals, Bristol Myers Squibb, EMD Serona, Pfizer, Regeneron, and Castle Biosciences outside the submitted work. No other disclosures were reported.

Funding/Support: This article was partially supported by unrestricted research funding from the Section of Cutaneous Surgery in the Northwestern University Department of Dermatology. This research was funded, in part, by National Institutes of Health/National Cancer Institute Cancer Center Support Grant P30 CA008748 (to Dr Leitao).

Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We thank Nobuo Arai, a patient representative who contributed his perspective based on personal experiences with extramammary Paget disease and helped shape the summary statements.

References

Morris CR , Hurst EA . Extramammary Paget disease: a review of the literature—part I: history, epidemiology, pathogenesis, presentation, histopathology, and diagnostic work-up. Dermatol Surg. 2020;46(2):151-158. doi:10.1097/DSS.0000000000002064 PubMed Google Scholar Crossref

Zhang G , Zhou S , Zhong W , et al. Whole-exome sequencing reveals frequent mutations in chromatin remodeling genes in mammary and extramammary Paget’s diseases. J Invest Dermatol. 2019;139(4):789-795. doi:10.1016/j.jid.2018.08.030 PubMed Google Scholar Crossref

Baehrendtz H, Einhorn N, Pettersson F, Silfversward C. Paget’s disease of the vulva: the Radiumhemmet series 1975-1990. Int J Gynecol Cancer. 1994;4(1):1-6. doi:10.1046/j.1525-1438.1994.04010001.x Crossref

Isik O , Aytac E , Brainard J , Valente MA , Abbas MA , Gorgun E . Perianal Paget’s disease: three decades experience of a single institution. Int J Colorectal Dis. 2016;31(1):29-34. doi:10.1007/s00384-015-2342-3 PubMed Google Scholar Crossref

Chung PH, Kampp JT, Voelzke BB. Patients’ experiences with extramammary Paget disease: an online pilot study querying a patient support group. Urology. 2018;111:214-219. doi:10.1016/j.urology.2017.08.045 Crossref

Stenson A, Behjatnia B, Shamonki J, et al. Her2neu over-expression and PI3kinase/Akt pathway activation in Paget’s disease of the vulva. Reprod Sci. 2008;15(2):307A.

Rastogi S , Thiede R , Sadowsky LM , et al. Sex differences in initial treatment for genital extramammary Paget’s disease in the United States: a systematic review. J Am Acad Dermatol. Published online April 20, 2019. doi:10.1016/j.jaad.2019.04.046 PubMed Google Scholar Crossref

Fujisawa Y , Funakoshi T , Nakamura Y , et al. Nation-wide survey of advanced non-melanoma skin cancers treated at dermatology departments in Japan. J Dermatol Sci. 2018;92(3):230-236. doi:10.1016/j.jdermsci.2018.10.004 PubMed Google Scholar Crossref

Kodama S , Kaneko T , Saito M , Yoshiya N , Honma S , Tanaka K . A clinicopathologic study of 30 patients with Paget’s disease of the vulva. Gynecol Oncol. 1995;56(1):63-70. doi:10.1006/gyno.1995.1010 PubMed Google Scholar Crossref

10.

Hendi A , Brodland DG , Zitelli JA . Extramammary Paget’s disease: surgical treatment with Mohs micrographic surgery. J Am Acad Dermatol. 2004;51(5):767-773. doi:10.1016/j.jaad.2004.07.004 PubMed Google Scholar Crossref

11.

Konstantinova AM , Shelekhova KV , Stewart CJ , et al. Depth and patterns of adnexal involvement in primary extramammary (anogenital) Paget disease: a study of 178 lesions from 146 patients. Am J Dermatopathol. 2016;38(11):802-808. doi:10.1097/DAD.0000000000000552 PubMed Google Scholar Crossref

12.

Kang Z , Zhang Q , Zhang Q , et al. Clinical and pathological characteristics of extramammary Paget’s disease: report of 246 Chinese male patients. Int J Clin Exp Pathol. 2015;8(10):13233-13240.PubMed Google Scholar

13.

Choi YD , Cho NH , Park YS , Cho SH , Lee G , Park K . Lymphovascular and marginal invasion as useful prognostic indicators and the role of c-erbB-2 in patients with male extramammary Paget’s disease: a study of 31 patients. J Urol. 2005;174(2):561-565. doi:10.1097/01.ju.0000165148.16655.7c PubMed Google Scholar Crossref

14.

Shiomi T , Noguchi T , Nakayama H , et al. Clinicopathological study of invasive extramammary Paget’s disease: subgroup comparison according to invasion depth. J Eur Acad Dermatol Venereol. 2013;27(5):589-592. doi:10.1111/j.1468-3083.2012.04489.x PubMed Google Scholar Crossref

15.

Nakamura Y , Fujisawa Y , Ishikawa M , et al. Usefulness of sentinel lymph node biopsy for extramammary Paget disease. Br J Dermatol. 2012;167(4):954-956. doi:10.1111/j.1365-2133.2012.11017.x PubMed Google Scholar Crossref

16.

Ogata D , Kiyohara Y , Yoshikawa S , Tsuchida T . Usefulness of sentinel lymph node biopsy for prognostic prediction in extramammary Paget’s disease. Eur J Dermatol. 2016;26(3):254-259. doi:10.1684/ejd.2016.2744 PubMed Google Scholar Crossref

17.

Hata M , Koike I , Wada H , et al. Radiation therapy for extramammary Paget’s disease: treatment outcomes and prognostic factors. Ann Oncol. 2014;25(1):291-297. doi:10.1093/annonc/mdt478 PubMed Google Scholar Crossref

18.

Fujisawa Y , Yoshino K , Kiyohara Y , et al. The role of sentinel lymph node biopsy in the management of invasive extramammary Paget’s disease: multi-center, retrospective study of 151 patients. J Dermatol Sci. 2015;79(1):38-42. doi:10.1016/j.jdermsci.2015.03.014 PubMed Google Scholar Crossref

19.

Shu B , Shen XX , Chen P , Fang XZ , Guo YL , Kong YY . Primary invasive extramammary Paget disease on penoscrotum: a clinicopathological analysis of 41 cases. Hum Pathol. 2016;47(1):70-77. doi:10.1016/j.humpath.2015.09.005 PubMed Google Scholar Crossref

20.

Goldblum JR , Hart WR . Vulvar Paget’s disease: a clinicopathologic and immunohistochemical study of 19 cases. Am J Surg Pathol. 1997;21(10):1178-1187. doi:10.1097/00000478-199710000-00008 PubMed Google Scholar Crossref

21.

Goldblum JR , Hart WR . Perianal Paget’s disease: a histologic and immunohistochemical study of 11 cases with and without associated rectal adenocarcinoma. Am J Surg Pathol. 1998;22(2):170-179. doi:10.1097/00000478-199802000-00004 PubMed Google Scholar Crossref

22.

Thomas SC , Marquez CD , Porteus C , Jiang K . Anal canal adenocarcinoma with associated perianal Paget’s disease: an underrecognized entity with institutional experience. Lab Invest. 2017;97(suppl 1):203A. doi:10.1038/labinvest.2016.168 Google Scholar Crossref

23.

Tanaka R , Sasajima Y , Tsuda H , et al. Human epidermal growth factor receptor 2 protein overexpression and gene amplification in extramammary Paget disease. Br J Dermatol. 2013;168(6):1259-1266. doi:10.1111/bjd.12249 PubMed Google Scholar Crossref

24.

Hikita T , Ohtsuki Y , Maeda T , Furihata M . Immunohistochemical and fluorescence in situ hybridization studies on noninvasive and invasive extramammary Paget’s disease. Int J Surg Pathol. 2012;20(5):441-448. doi:10.1177/1066896912444159 PubMed Google Scholar Crossref

25.

Masuguchi S , Jinnin M , Fukushima S , et al. The expression of HER-2 in extramammary Paget’s disease. Biosci Trends. 2011;5(4):151-155. doi:10.5582/bst.2011.v5.4.151 PubMed Google Scholar Crossref

26.

Hata H , Kitamura S , Inamura Y , et al. mTOR expression correlates with invasiveness and progression of extramammary Paget’s disease. J Eur Acad Dermatol Venereol. 2016;30(7):1238-1239. doi:10.1111/jdv.13168 PubMed Google Scholar Crossref

27.

Chen SY , Takeuchi S , Moroi Y , et al. Concordant overexpression of phosphorylated ATF2 and STAT3 in extramammary Paget’s disease. J Cutan Pathol. 2009;36(4):402-408. doi:10.1111/j.1600-0560.2008.01076.x PubMed Google Scholar Crossref

28.

Kang Z , Xu F , Zhang QA , et al. Correlation of DLC1 gene methylation with oncogenic PIK3CA mutations in extramammary Paget’s disease. Mod Pathol. 2012;25(8):1160-1168. doi:10.1038/modpathol.2012.65 PubMed Google Scholar Crossref

29.

Kang Z , Xu F , Zhang QA , et al. Oncogenic mutations in extramammary Paget’s disease and their clinical relevance. Int J Cancer. 2013;132(4):824-831. doi:10.1002/ijc.27738 PubMed Google Scholar Crossref

30.

Battles OE , Page DL , Johnson JE . Cytokeratins, CEA, and mucin histochemistry in the diagnosis and characterization of extramammary Paget’s disease. Am J Clin Pathol. 1997;108(1):6-12. doi:10.1093/ajcp/108.1.6 PubMed Google Scholar Crossref

31.

Qian Y , Zhang N , Chen S , Chu S , Feng A , Liu H . PI3K, Rac1 and pPAK1 are overexpressed in extramammary Paget’s disease. J Cutan Pathol. 2012;39(11):1010-1015. doi:10.1111/j.1600-0560.2012.01973.x PubMed Google Scholar Crossref

32.

Zarei S , Kilts T , Schoolmeester J , et al. HER2 amplification status in extramammary Paget disease (EMPD) evaluated by IHC, FISH and chromosomal microarray: review of 78 cases. Lab Invest. 2019;99:2.Google Scholar

33.

Karam A , Dorigo O . Treatment outcomes in a large cohort of patients with invasive extramammary Paget’s disease. Gynecol Oncol. 2012;125(2):346-351. doi:10.1016/j.ygyno.2012.01.032 PubMed Google Scholar Crossref

34.

Kilts T , Long B , Glasgow A , Habermann E , Bakkum-Gamez J , Cliby W . Invasive extramammary Paget’s disease in the United States. Int J Gynecol Cancer. 2018;28(suppl 2):90-91. doi:10.1097/01.IGC.0000546279.09648.02 Google Scholar Crossref

35.

Schmitt AR , Long BJ , Weaver AL , et al. Evidence-based screening recommendations for occult cancers in the setting of newly diagnosed extramammary Paget disease. Mayo Clin Proc. 2018;93(7):877-883. doi:10.1016/j.mayocp.2018.02.024 PubMed Google Scholar Crossref

36.

Hatta N , Yamada M , Hirano T , Fujimoto A , Morita R . Extramammary Paget’s disease: treatment, prognostic factors and outcome in 76 patients. Br J Dermatol. 2008;158(2):313-318. doi:10.1111/j.1365-2133.2007.08314.x PubMed Google Scholar Crossref

37.

Ogawa T , Nagashima Y , Wada H , et al. Extramammary Paget’s disease: analysis of growth signal pathway from the human epidermal growth factor receptor 2 protein. Hum Pathol. 2005;36(12):1273-1280. doi:10.1016/j.humpath.2005.09.009 PubMed Google Scholar Crossref

38.

Zhu Y , Ye DW , Yao XD , et al. Clinicopathological characteristics, management and outcome of metastatic penoscrotal extramammary Paget’s disease. Br J Dermatol. 2009;161(3):577-582. doi:10.1111/j.1365-2133.2009.09203.x PubMed Google Scholar Crossref

39.

Yan D , Dai H , Jin M , Zhao Y . Clinicopathologic characteristics of extramammary Paget’s disease of the scrotum associated with sweat gland adenocarcinoma—a clinical retrospective study. J Chin Med Assoc. 2011;74(4):179-182. doi:10.1016/j.jcma.2011.01.040 PubMed Google Scholar Crossref

40.

Jung JH , Kwak C , Kim HH , Ku JH . Extramammary Paget disease of external genitalia: surgical excision and follow-up experiences with 19 patients. Korean J Urol. 2013;54(12):834-839. doi:10.4111/kju.2013.54.12.834 PubMed Google Scholar Crossref

41.

Zhu Y , Ye DW , Chen ZW , Zhang SL , Qin XJ . Frozen section–guided wide local excision in the treatment of penoscrotal extramammary Paget’s disease. BJU Int. 2007;100(6):1282-1287. doi:10.1111/j.1464-410X.2007.07188.x PubMed Google Scholar Crossref

42.

Mijiddorj T , Kajihara I , Tasaki Y , et al. Serum cell-free DNA levels are a useful marker for extramammary Paget disease. Br J Dermatol. 2019;181(3):505-511. doi:10.1111/bjd.17709 PubMed Google Scholar Crossref

43.

Kato H , Watanabe S , Kariya K , Nakamura M , Morita A . Efficacy of low-dose 5-fluorouracil/cisplatin therapy for invasive extramammary Paget’s disease. J Dermatol. 2018;45(5):560-563. doi:10.1111/1346-8138.14247 PubMed Google Scholar Crossref

44.

Nakamura Y , Tanese K , Hirai I , Amagai M , Kawakami Y , Funakoshi T . Serum cytokeratin 19 fragment 21-1 and carcinoembryonic antigen combination assay as a biomarker of tumour progression and treatment response in extramammary Paget disease. Br J Dermatol. 2019;181(3):535-543. doi:10.1111/bjd.17789 PubMed Google Scholar Crossref

45.

van der Linden M , van Esch E , Bulten J , et al. The immune cell infiltrate in the microenvironment of vulvar Paget disease. Gynecol Oncol. 2018;151(3):453-459. doi:10.1016/j.ygyno.2018.09.026 PubMed Google Scholar Crossref

46.

Yélamos O , Hibler BP , Cordova M , et al. Handheld reflectance confocal microscopy for the detection of recurrent extramammary Paget disease. JAMA Dermatol. 2017;153(7):689-693. doi:10.1001/jamadermatol.2017.0619 PubMed Google Scholar Crossref

47.

Guitera P , Scolyer RA , Gill M , et al. Reflectance confocal microscopy for diagnosis of mammary and extramammary Paget’s disease. J Eur Acad Dermatol Venereol. 2013;27(1):e24-e29. doi:10.1111/j.1468-3083.2011.04423.x PubMed Google Scholar Crossref

48.

Navarrete-Dechent C , Aleissa S , Cordova M , et al. Treatment of extramammary Paget disease and the role of reflectance confocal microscopy: a prospective study. Dermatol Surg. 2021;47(4):473-479. doi:10.1097/DSS.0000000000002934 PubMed Google Scholar Crossref

49.

Escobar PF , Belinson JL , White A , et al. Diagnostic efficacy of optical coherence tomography in the management of preinvasive and invasive cancer of uterine cervix and vulva. Int J Gynecol Cancer. 2004;14(3):470-474. doi:10.1111/j.1048-891x.2004.14307.x PubMed Google Scholar Crossref

50.

Ohara K , Fujisawa Y , Yoshino K , et al. A proposal for a TNM staging system for extramammary Paget disease: retrospective analysis of 301 patients with invasive primary tumors. J Dermatol Sci. 2016;83(3):234-239. doi:10.1016/j.jdermsci.2016.06.004 PubMed Google Scholar Crossref

51.

Park S , Grossfeld GD , McAninch JW , Santucci R . Extramammary Paget’s disease of the penis and scrotum: excision, reconstruction and evaluation of occult malignancy. J Urol. 2001;166(6):2112-2116. doi:10.1016/S0022-5347(05)65516-4 PubMed Google Scholar Crossref

52.

Onaiwu CO , Salcedo MP , Pessini SA , et al. Paget’s disease of the vulva: a review of 89 cases. Gynecol Oncol Rep. 2016;19:46-49. doi:10.1016/j.gore.2016.12.010 PubMed Google Scholar Crossref

53.

Hatta N , Morita R , Yamada M , et al. Sentinel lymph node biopsy in patients with extramammary Paget’s disease. Dermatol Surg. 2004;30(10):1329-1334. doi:10.1111/j.1524-4725.2004.30377.x PubMed Google Scholar Crossref

54.

Ewing T , Sawicki J , Ciaravino G , Rumore GJ . Microinvasive Paget’s disease. Gynecol Oncol. 2004;95(3):755-758. doi:10.1016/j.ygyno.2004.09.008 PubMed Google Scholar Crossref

55.

Fujisawa Y , Nakamura Y , Kawachi Y , Otsuka F . Indocyanine green fluorescence–navigated sentinel node biopsy showed higher sensitivity than the radioisotope or blue dye method, which may help to reduce false-negative cases in skin cancer. J Surg Oncol. 2012;106(1):41-45. doi:10.1002/jso.23045 PubMed Google Scholar Crossref

56.

Isei T , Okamoto H . Usefulness of sentinel node navigation surgery with near-infrared fluorescence navigation using indocyanine green in patients with extramammary Paget’s disease. J Ger Soc Dermatol. 2013;7:104-105. doi:10.1111/ddg.12163 Crossref

57.

Park SO , Ha JH , Hong KY , Chang H . Usefulness of mapping biopsy in the treatment of penoscrotal extramammary Paget’s disease. Ann Surg Oncol. 2017;24(11):3229-3236. doi:10.1245/s10434-017-5947-7 PubMed Google Scholar Crossref

58.

Wan M , Ma H , Zhao Y , Xie L , Chen Z . Clinical benefits of preoperative conventional fluorescence diagnosis in surgical treatment of extramammary Paget disease. Dermatol Surg. 2018;44(3):375-382. doi:10.1097/DSS.0000000000001329 PubMed Google Scholar Crossref

59.

Murata T , Honda T , Egawa G , et al. Three-dimensional evaluation of subclinical extension of extramammary Paget disease: visualization of the histological border and its comparison to the clinical border. Br J Dermatol. 2017;177(1):229-237. doi:10.1111/bjd.15282 PubMed Google Scholar Crossref

60.

Kato T , Fujimoto N , Fujii N , Tanaka T . Mapping biopsy with punch biopsies to determine surgical margin in extramammary Paget’s disease. J Dermatol. 2013;40(12):968-972. doi:10.1111/1346-8138.12347 PubMed Google Scholar Crossref

61.

Nagai Y , Kazama S , Yamada D , et al. Perianal and vulvar extramammary Paget disease: a report of six cases and mapping biopsy of the anal canal. Ann Dermatol. 2016;28(5):624-628. doi:10.5021/ad.2016.28.5.624 PubMed Google Scholar Crossref

62.

St Peter SD , Pera M , Smith AA , Leslie KO , Heppell J . Wide local excision and split-thickness skin graft for circumferential Paget’s disease of the anus. Am J Surg. 2004;187(3):413-416. doi:10.1016/j.amjsurg.2003.12.021 PubMed Google Scholar Crossref

63.

Niikura H , Yoshida H , Ito K , et al. Paget’s disease of the vulva: clinicopathologic study of type 1 cases treated at a single institution. Int J Gynecol Cancer. 2006;16(3):1212-1215. doi:10.1136/ijgc-00009577-200605000-00040 PubMed Google Scholar Crossref

64.

Kaku-Ito Y , Ito T , Tsuji G , et al. Evaluation of mapping biopsies for extramammary Paget disease: a retrospective study. J Am Acad Dermatol. 2018;78(6):1171-1177.e4. doi:10.1016/j.jaad.2017.12.040 PubMed Google Scholar Crossref

65.

Mikhael E , Seoud M. Vulvar Paget’s disease: 20 years of experience: changing pattern of treatment. Int J Gynecol Cancer. 2016;26(suppl 3):1139. doi:10.26226/morressier.5770e29ed462b80290b4c8b4 Google Scholar

66.

Hirai I , Tanese K , Nakamura Y , Ishii M , Kawakami Y , Funakoshi T . Combination cisplatin-epirubicin-paclitaxel therapy for metastatic extramammary Paget’s disease. Oncologist. 2019;24(6):e394-e396. doi:10.1634/theoncologist.2018-0856 PubMed Google Scholar Crossref

67.

Yoshino K , Fujisawa Y , Kiyohara Y , et al. Usefulness of docetaxel as first-line chemotherapy for metastatic extramammary Paget’s disease. J Dermatol. 2016;43(6):633-637. doi:10.1111/1346-8138.13200 PubMed Google Scholar Crossref

68.

Nakamura Y , Hirai I , Ishii M , Kawakami Y , Tanese K , Funakoshi T . Efficacy and safety of weekly docetaxel regimen for advanced extramammary Paget’s disease: retrospective single institute analysis. Ann Oncol. 2018;29(suppl 9):ix108. doi:10.1093/annonc/mdy439.010 Google Scholar Crossref

69.

Chang K , Li GX , Kong YY , et al. Chemokine receptors CXCR4 and CXCR7 are associated with tumor aggressiveness and prognosis in extramammary Paget disease. J Cancer. 2017;8(13):2471-2477. doi:10.7150/jca.19127 PubMed Google Scholar Crossref

70.

Damavandy AA , Terushkin V , Zitelli JA , et al. Intraoperative immunostaining for cytokeratin-7 during Mohs micrographic surgery demonstrates low local recurrence rates in extramammary Paget’s disease. Dermatol Surg. 2018;44(3):354-364. doi:10.1097/DSS.0000000000001355 PubMed Google Scholar Crossref

71.

Smith KJ , Tuur S , Corvette D , Lupton GP , Skelton HG . Cytokeratin 7 staining in mammary and extramammary Paget’s disease. Mod Pathol. 1997;10(11):1069-1074.PubMed Google Scholar

72.

Harris DW , Kist DA , Bloom K , Zachary CB . Rapid staining with carcinoembryonic antigen aids limited excision of extramammary Paget’s disease treated by Mohs surgery. J Dermatol Surg Oncol. 1994;20(4):260-264. doi:10.1111/j.1524-4725.1994.tb01622.x PubMed Google Scholar Crossref

73.

Hruza GJ . Mohs surgery for extramammary Paget disease. NEJM Journal Watch. November 24, 2004. Accessed November 26, 2020. https://www.jwatch.org/jd200411240000002/2004/11/24/mohs-surgery-extramammary-paget-disease

74.

Nomura H , Matoda M , Okamoto S , et al. Clinicopathologic features and treatment outcomes of primary extramammary Paget disease of the vulva. J Low Genit Tract Dis. 2015;19(2):145-148. doi:10.1097/LGT.0000000000000063 PubMed Google Scholar Crossref

75.

Yoon SN , Park IJ , Kim HC , et al. Extramammary Paget’s disease in Korea: its association with gastrointestinal neoplasms. Int J Colorectal Dis. 2008;23(11):1125-1130. doi:10.1007/s00384-008-0499-8 PubMed Google Scholar Crossref

76.

Wang L , Feng C , Zhou M , et al. Tumor wide horizontal invasion predicts local recurrence for scrotal extramammary Paget’s disease. Sci Rep. 2017;7:44933. doi:10.1038/srep44933 PubMed Google Scholar Crossref

77.

Yao H , Zheng D , Xie M , Wang Z . A new look at reconstruction strategy: classification and management for extramammary Paget’s disease. J Sex Med. 2019;16(4)(suppl 1):S128. doi:10.1016/j.jsxm.2019.01.274 Google Scholar Crossref

78.

Hata M , Koike I , Wada H , et al. Definitive radiation therapy for extramammary Paget’s disease. Anticancer Res. 2012;32(8):3315-3320.PubMed Google Scholar

79.

Tackenberg S, Gehrig A, Dummer R, Navarini AA. External beam radiotherapy of extramammary Paget disease. Cutis. 2015;95(2):109-112.

80.

Carrozzo AM, Cipriani C, Donati P, Muscardin L, Sedda AF. Dermo beta brachytherapy with 188Re in extramammary Paget’s disease. G Ital Dermatol Venereol. 2014;149(1):115-121.

81.

Shaco-Levy R, Bean SM, Vollmer RT, et al. Paget disease of the vulva: a study of 56 cases. Eur J Obstet Gynecol Reprod Biol. 2010;149(1):86-91. doi:10.1016/j.ejogrb.2009.11.003 Crossref

82.

Yanagi T, Kato N, Yamane N, Osawa R. Radiotherapy for extramammary Paget’s disease: histopathological findings after radiotherapy. Clin Exp Dermatol. 2007;32(5):506-508. doi:10.1111/j.1365-2230.2007.02425.x Crossref

83.

Hata M, Koike I, Wada H, et al. Postoperative radiation therapy for extramammary Paget’s disease. Br J Dermatol. 2015;172(4):1014-1020. doi:10.1111/bjd.13357 Crossref

84.

Cai Y, Sheng W, Xiang L, Wu X, Yang H. Primary extramammary Paget’s disease of the vulva: the clinicopathological features and treatment outcomes in a series of 43 patients. Gynecol Oncol. 2013;129(2):412-416. doi:10.1016/j.ygyno.2013.02.029 Crossref

85.

Piura B, Rabinovich A, Dgani R. Extramammary Paget’s disease of the vulva: report of five cases and review of the literature. Eur J Gynaecol Oncol. 1999;20(2):98-101.

86.

Kato M, Yoshino K, Maeda T, et al. Single-agent taxane is useful in palliative chemotherapy for advanced extramammary Paget disease: a case series. Br J Dermatol. 2019;181(4):831-832. doi:10.1111/bjd.17922 Crossref

87.

Nakamura Y, Tanese K, Hirai I, et al. Weekly docetaxel monotherapy for metastatic extramammary Paget’s disease: retrospective single-institute analysis. J Dermatol. 2020;47(4):418-422. doi:10.1111/1346-8138.15255 Crossref

88.

Tokuda Y, Arakura F, Uhara H. Combination chemotherapy of low-dose 5-fluorouracil and cisplatin for advanced extramammary Paget’s disease. Int J Clin Oncol. 2015;20(1):194-197. doi:10.1007/s10147-014-0686-2 Crossref

89.

Ishida Y, Iga N, Otsuka A, Kabashima K. Mutational landscape of extramammary Paget disease. J Invest Dermatol. 2018;138(5 suppl 1):S22.

90.

Kiniwa Y, Yasuda J, Saito S, et al. Identification of genetic alterations in extramammary Paget disease using whole exome analysis. J Dermatol Sci. 2019;94(1):229-235. doi:10.1016/j.jdermsci.2019.03.006 Crossref

91.

Gatalica Z, Vranic S, Krušlin B, et al. Comparison of the biomarkers for targeted therapies in primary extra-mammary and mammary Paget’s disease. Cancer Med. 2020;9(4):1441-1450. doi:10.1002/cam4.2820 Crossref

92.

Marabelle A, Fakih M, Lopez J, et al. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol. 2020;21(10):1353-1365. doi:10.1016/S1470-2045(20)30445-9 Crossref

93.

Karam A, Berek JS, Stenson A, Rao J, Dorigo O. HER-2/neu targeting for recurrent vulvar Paget’s disease: a case report and literature review. Gynecol Oncol. 2008;111(3):568-571. doi:10.1016/j.ygyno.2007.12.014 Crossref

AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

Evidence-Based Clinical Practice Guidelines for Extramammary Paget Disease

See More About

AMA CME Accreditation Information

Want full access to the AMA Ed Hub?

AMA Membership provides:

Sign in to access

Want full access to the AMA Ed Hub?

Sign in to customize your interests

With a personal account, you can:

Name Your Search

Sign in to save your search

With a personal account, you can:

Lookup An Activity

My Saved Searches

My Saved Courses

Purchase access