Clinical Diagnosis and Treatment of Perianal Paget's Disease

doi:10.12114/j.issn.1007-9572.2020.00.050

Abstract

Abstract: Perianal Paget's disease is a rare malignant disease.Due to its atypical clinical manifestations，the disease is easily confused with chronic perianal eczema，abalone and other diseases，and there is no unified standard and consensus in clinical diagnosis，treatment，recurrence factors and prognosis judgment，so the misdiagnosis rate in clinical practice is high.Therefore，this paper will make a review of perianal Paget's disease from the aspects of epidemiology，classification，pathological features，clinical manifestations，differential diagnosis，treatment，recurrence and prognosis，so as to improve the clinicians' understanding of this disease.

Key words: Paget disease, extramammary；Paget's disease of perianal；Pathology；Diagnosis；Differential；Therapy；Prognosis

摘要： 肛周Paget's病是一种罕见的恶性疾病，其临床表现不典型，易与肛周慢性湿疹、鲍温病等相混淆，且在临床诊断、治疗、复发因素及预后判断等方面尚无统一标准与共识，临床上误诊率较高。为此本文从流行病学、分类及发病机制、临床表现、诊断依据、鉴别诊断、治疗手段及复发和预后方面对肛周Paget's病做一综述，以提高临床医师对该病的认识。

关键词: 佩吉特病, 乳腺外；肛周Paget's病；病理学；诊断, 鉴别；治疗；预后

YAN Guilin,DU Yuanfang,PU Yongping, et al. Clinical Diagnosis and Treatment of Perianal Paget's Disease　[J]. Chinese General Practice, 2020, 23(27): 3496-3502. DOI: 10.12114/j.issn.1007-9572.2020.00.050.
颜桂林,杜媛芳,蒲永平等. 肛周Paget's病临床诊治进展[J]. 中国全科医学, 2020, 23(27): 3496-3502. DOI: 10.12114/j.issn.1007-9572.2020.00.050.

References

［1］PAGET J.On disease of the mammary areola preceding cancer of the mammary gland.St.Barth［J］．Hosp Rep，1874，10．DOI:10.3322/canjclin.21.5.303.
［2］LLOYD J，FLANAGAN A M.Mammary and extramammary Paget's disease［J］．J Clin Pathol，2000，53（10）：742-749．DOI:10.1136/jcp.53.10.742.
［3］MARCHESA P，FAZIO V W，OLIART S，et al．Long-term outcome of patients with perianal Paget's disease［J］．Ann Surg Oncol，1997，4（6）：475-480．DOI:10.1007/bf02303671.
［4］MCCARTER M D，QUAN S H，BUSAM K，et al．Long-term outcome of perianal Paget's disease［J］．Dis Colon Rectum，2003，46（5）：612-616．DOI:10.1007/s10350-004-6618-x.
［5］LAM C，FUNARO D.Extramammary Paget's disease：summary of current knowledge［J］．Dermatol Clin，2010，28（4）：807-826．DOI:10.1016/j.det.2010.08.002.
［6］MENGJUN B，ZHENG-QIANG W，TASLEEM M M..Extramammary Paget's disease of the perianal region：a review of the literature emphasizing management［J］．Dermatologic Surgery，2013，39（1pt1）:69-75．DOI：10.1111/dsu.12019.
［7］TANAKA V D，SANCHES J A，TOREZAN L，et al．Mammary and extramammary Paget's disease：a study of 14 cases and the associated therapeutic difficulties［J］．Clinics （Sao Paulo），2009，64（6）：599-606．DOI:10.1590/s1807-59322009000600018.
［8］KANITAKIS J.Mammary and extramammary Paget's disease［J］．J Eur Acad Dermatol Venereol Jeadv，2007，21（5）:2147483647-0．DOI:10.1111/j.1468-3083.2007.02154.x.
［9］SHEPHERD V，DAVIDSON E J，DAVIES-HUMPHREYS J.Extramammary Paget's disease［J］．BJOG，2005，112（3）:273-279．DOI：10.1111/j.1471-0528.2004.00438.x.
［10］CHANDA J J.Extramammary Paget's disease：prognosis and relationship to internal malignancy［J］．J Am Acad Dermatol，1985，13（6）:1009-1014．DOI：10.1016/s0190-9622（85）70254-x.
［11］HATTA N，YAMADA M，HIRANO T，et al．Extramammary Paget's disease：treatment，prognostic factors and outcome in 76 patients［J］．British Journal of Dermatology，2008，158（2）:313-318．DOI：10.1111/j.1365-2133.2007.08314.x.
［12］MINICOZZI A，BORZELLINO G，MOMO R，et al．Perianal Paget's disease：presentation of six cases and literature review［J］．Int J Colorectal Dis，2010，25（1）：1-7．DOI:10.1007/s00384-009-0797-9.
［13］BUTLER J D，HERSHAM M J，WILSON C A，et al．Perianal Paget's disease［J］．Benign Anorectal Disorders，1971，85（5）:476-480．DOI：10.1111/j.1365-2133.1971.tb14057.x.
［14］CHAUDHURI S P，SMOLLER B R.Extramammary Paget's disease:diagnosis and disease pattern［J］．Cutis，1992，50（3）:195-196．DOI:10.1111/j.1600-0536.1992.tb05269.x.
［15］PEREZ D R，TRAKARNSANGA A，SHIA J，et al．Management and outcome of perianal Paget's disease：a 6-decade institutional experience［J］．Dis Colon Rectum，2014，57（6）：747-751．DOI:10.1097/DCR.0000000000000100.
［16］ACKERMAN A B.Differential diagnosis in dermatopathology，Part Ⅱ［J］．J Dermac Surg Oncol，1981，7（2）:148．DOI：10.1111/j.1524-4725.1981.tb01769.x.
［17］MORITANI Y，TOMIOKA N，IZUMI A，et al．A case of anal gland carcinoma accompanied by Pagetoid spread［J］．Nippon Daicho Komonbyo Gakkai Zasshi，2009，62（2）：121-126．DOI：10.3862/jcoloproctology.62.121.
［18］BROWN H M，WILKINSON E J.Uroplakin-Ⅲ to distinguish primary vulvar Paget disease from Paget disease secondary to urothelial carcinoma［J］．Hum Pathol，2002，33（5）：545-548．DOI:10.1053/hupa.2002.124787.
［19］MOLL R，LAUFER J，WU X R，et al．Uroplakin Ⅲ，a specific membrane protein of urothelial umbrella cells，as a histological markers for metastatic transitional cell carcinomas［J］．Verh Dtsch Ges Pathol，1993，77：260-265.
［20］OHNISHI T，WATANABE S.The use of cytokeratins 7 and 20 in the diagnosis of primary and secondary extramammary Paget's disease［J］．Br J Dermatol，2000，142（2）：243-247．DOI:10.1046/j.1365-2133.2000.03291.x.
［21］ZHANG P J，SHAH M，SPIEGEL G W，et al．Cytokeratin 7 immunoreactivity in rectal adenocarcinomas［J］．Appl Immunohistochem Mol Morphol，2003，11（4）：306-310．DOI:10.1097/00129039-200312000-00005.
［22］LORA V，KANITAKIS J.CDX2 expression in cutaneous metastatic carcinomas and extramammary Paget's disease［J］．Anticancer Res，2009，29（12）：5033-5037.
［23］BARBARESCHI M，MURER B，COLBY T V，et al．CDX-2 homeobox gene expression is a reliable marker of colorectal adenocarcinoma metastases to the lungs［J］．Am J Surg Pathol，2003，27（2）：141-149．DOI:10.1097/00000478-200302000-00001.
［24］FRAGGETTA F，PELOSI G，CAFICI A，et al．CDX2 immunoreactivity in primary and metastatic ovarian mucinous tumours［J］．Virchows Arch，2003，443（6）：782-786．DOI:10.1007/s00428-003-0910-3.
［25］YATABE Y，KOGA T，MITSUDOMI T，et al．CK20 expression，CDX2 expression，K-ras mutation，and goblet cell morphology in a subset of lung adenocarcinomas［J］．J Pathol，2004，203（2）：645-652．DOI:10.1002/path.1566.
［26］DE NISI M C，D'AMURI A，TOSCANO M，et al．Usefulness of CDX2 in the diagnosis of extramammary Paget disease associated with malignancies of intestinal type［J］．Br J Dermatol，2005，153（3）：677-679．DOI:10.1111/j.1365-2133.2005.06798.x.
［27］KONDO Y，KASHIMA K，DAA T，et al．The ectopic expression of gastric mucin in extramammary and mammary Paget's disease［J］．Am J Surg Pathol，2002，26（5）：617-623．DOI:10.1097/00000478-200205000-00007.
［28］YOSHII N，KITAJIMA S，YONEZAWA S，et al．Expression of mucin core proteins in extramammary Paget's disease［J］．Pathol Int，2002，52（5/6）：390-399．DOI:10.1046/j.1440-1827.2002.01364.x.
［29］LIEGL B，LEIBL S，GOGG-KAMERER M，et al．Mammary and extramammary Paget's disease：an immunohistochemical study of 83 cases［J］．Histopathology，2007，50（4）:439-447．DOI：0.1111/j.1365-2559.2007.02633.x.
［30］KUAN S F，MONTAG A G，HART J，et al．Differential expression of mucin genes in mammary and extramammary Paget's disease［J］．Am J Surg Pathol，2001，25（12）：1469-1477．DOI:10.1097/00000478-200112000-00001.
［31］王晓开，宋福林.鲍温病临床病理特征研究［J］．临床军医杂志，2019，47（1）：57-59．DOI:10.16680/j.1671-3826.2019.01.19
WANG X K，SONG F L.Clinical pathological observation of Bowen's disease［J］．Clinical Journal of Medical Officers，2019，47（1）：57-59．DOI:10.16680/j.1671-3826.2019.01.19．
［32］MATSUMOTO M，ISHIGURO M，IKENO F，et al．Combined Bowen disease and extramammary Paget disease［J］．J Cutan Pathol，2007，34（Suppl 1）：47-51．DOI:10.1111/j.1600-0560.2007.00732.x.
［33］HASSAN I，HORGAN A F，NIVATVONGS S.V-Y island flaps for repair of large perianal defects［J］．Am J Surg，2001，181（4）：363-365．DOI:10.1016/s0002-9610（01）00578-5.
［34］MARDINI S，TSAI F C，WEI F C.The thigh as a model for free style free flaps［J］．Clin Plast Surg，2003，30（3）：473-480．DOI:10.1016/s0094-1298（03）00047-6.
［35］KISHI K，NAKAJIMA H，IMANISHI N，et al．Anal and perianal reconstruction after extramammary Paget's disease using a posterior thigh flap with a thin square wing［J］．J Plast Reconstr Aesthet Surg，2010，63（8）：1353-1356．DOI:10.1016/j.bjps.2009.06.022.
［36］SHEN K X，LUO H，HU J，et al．Perianal Paget disease treated with wide excision and thigh skin flap reconstruction：a case report and review of literature［J］．Medicine （Baltimore），2018，97（30）：e11638．DOI:10.1097/MD.0000000000011638.
［37］STAVROU M，MARTIN L，EL-MADANI F，et al．Perianal Paget's disease-report of a rare case［J］．Int J Surg Case Rep，2012，3（10）：483-485．DOI:10.1016/j.ijscr.2012.05.017.
［38］SHUTZE W P，GLEYSTEEN J J.Perianal Paget's disease.Classification and review of management：report of two cases［J］．Dis Colon Rectum，1990，33（6）：502-507．DOI:10.1007/bf02052147.
［39］HENDI A，BRODLAND D G，ZITELLI J A.Extramammary Paget's disease：surgical treatment with mohs micrographic surgery［J］．J Am Acad Dermatol，2004，51（5）：767-773．DOI:10.1016/j.jaad.2004.07.004．［LinkOut］
［40］MARCHESA P，FAZIO V W，OLIART S，et al．Long-term outcome of patients with perianal Paget's disease［J］．Ann Surg Oncol，1997，4（6）：475-480．DOI:10.1007/bf02303671.
［41］MINICOZZI A，BORZELLINO G，MOMO R，et al．Perianal Paget's disease：presentation of six cases and literature review［J］．Int J Colorectal Dis，2010，25（1）：1-7．DOI:10.1007/s00384-009-0797-9.
［42］GUNN R A，GALLAGER H S.Vulvar Paget's disease.A topographic study［J］．Cancer，1980，46（3）：590-594．
［43］M?LLER M G，LUGO-BARUQUI J A，MILIKOWSKI C，et al．Staged marginal contoured and central excision technique in the surgical management of perianal Paget's disease［J］．Am J Surg，2014，207（4）：485-492．DOI:10.1016/j.amjsurg.2013.04.005.
［44］HENDI A，BRODLAND D G，ZITELLI J A.Extramammary Paget's disease：surgical treatment with mohs micrographic surgery［J］．J Am Acad Dermatol，2004，51（5）：767-773．DOI:10.1016/j.jaad.2004.07.004．
［45］SOLER A M，WARLOE T，BERNER A，et al．A follow-up study of recurrence and cosmesis in completely responding superficial and nodular basal cell carcinomas treated with methyl 5-aminolaevulinate-based photodynamic therapy alone and with prior curettage［J］．Br J Dermatol，2001，145（3）：467-471．DOI:10.1046/j.1365-2133.2001.04407.x.
［46］VINCIULLO C，ELLIOTT T，FRANCIS D，et al．Photodynamic therapy with topical methyl aminolaevulinate for“difficult-to-treat” basal cell carcinoma［J］．Br J Dermatol，2005，152（4）：765-772．DOI:10.1111/j.1365-2133.2005.06484.x.
［47］HOUSEL J P，IZIKSON L，ZEITOUNI N C.Noninvasive extramammary Paget's disease treated with photodynamic therapy：case series from the Roswell Park Cancer Institute［J］．Dermatol Surg，2010，36（11）：1718-1724．DOI:10.1111/j.1524-4725.2010.01734.x.
［48］LI Q，GAO T W，JIAO B，et al．Long-term follow-up of in situ extramammary Paget's disease in Asian skin typesⅣ/Ⅴtreated with photodynamic therapy［J］．Acta Derm Venereol，2010，90（2）：159-164．DOI:10.2340/00015555-0818.
［49］NARDELLI A A，STAFINSKI T，MENON D.Effectiveness of photodynamic therapy for mammary and extra-mammary Paget's disease：a state of the science review［J］．BMC Dermatol，2011，11：13．DOI:10.1186/1471-5945-11-13.
［50］FONTANELLI R，PAPADIA A，MARTINELLI F，et al．Photodynamic therapy with M-ALA as non surgical treatment option in patients with primary extramammary Paget's disease［J］．Gynecol Oncol，2013，130（1）：90-94．DOI:10.1016/j.ygyno.2013.04.008.
［51］NAVI D，HUNTLEY A.Imiquimod 5 percent cream and the treatment of cutaneous malignancy［J］．Dermatol Online J，2004，10（1）：4.
［52］ZAMPOGNA J C，FLOWERS F P，ROTH W I，et al．Treatment of primary limited cutaneous extramammary Paget's disease with topical imiquimod monotherapy：two case reports［J］．J Am Acad Dermatol，2002，47（4 Suppl）：S229-235．DOI:10.1067/mjd.2002.126584.
［53］VEREECKEN P，AWADA A，GHANEM G，et al．A therapeutic approach to perianal extramammary Paget's disease：topical Imiquimod can be useful to prevent or defer surgery［J］．Med Sci Monit，2007，13（6）:CS75-7.
［54］WANG L C，BLANCHARD A，JUDGE D E，et al．Successful treatment of recurrent extramammary Paget's disease of the vulva with topical imiquimod 5% cream［J］．J Am Acad Dermatol，2003，49（4）：769-772．DOI:10.1067/s0190-9622（03）02107-8.
［55］LOUIS-SYLVESTRE C，HADDAD B，PANIEL B J.Paget's disease of the vulva：results of different conservative treatments［J］．Eur J Obstet Gynecol Reprod Biol，2001，99（2）：253-255．DOI:10.1016/s0301-2115（01）00394-3.
［56］ADKISSON C D，LANDMANN R G.A Hemorrhoid by any other name［J］．Mayo Clin Proc，2011，86（4）：e25．DOI:10.4065/mcp.2010.0413.
［57］HATA M，OMURA M，KOIKE I，et al．Role of radiotherapy as curative treatment of extramammary Paget's disease［J］．Int J Radiat Oncol Biol Phys，2011，80（1）：47-54．DOI:10.1016/j.ijrobp.2010.01.073.
［58］DILMé-CARRERAS E，IGLESIAS-SANCHO M，MáRQUEZ-BALBáS G，et al．Radiotherapy for extramammary Paget disease of the anogenital region［J］．J Am Acad Dermatol，2011，65（1）：192-194．DOI:10.1016/j.jaad.2009.11.689.
［59］YANAGI T，KATO N，YAMANE N，et al．Radiotherapy for extramammary Paget's disease：histopathological findings after radiotherapy［J］．Clin Exp Dermatol，2007，32（5）：506-508．DOI:10.1111/j.1365-2230.2007.02425.x.
［60］MORENO-ARIAS G A，CONILL C，CASTELLS-MAS A，et al．Radiotherapy for genital extramammary Paget's disease in situ［J］．Dermatol Surg，27（6）:587-590．DOI:10.1097/00042728-200106000-00016.