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J Clin Pathol. Oct 2000; 53(10): 742–749.
PMCID: PMC1731095

Mammary and extramammary Paget's disease

Abstract

Mammary and extramammary Paget's disease are uncommon intraepithelial adenocarcinomas. Both conditions have similar clinical features, which mimic inflammatory and infective diseases. Histological diagnostic confusion can arise between Paget's disease and other neoplastic conditions affecting the skin, with the most common differential diagnoses being malignant melanoma and atypical squamous disease. The glandular differentiation of both mammary Paget's disease and extramammary Paget's disease is indicated by morphological appearances, the presence of intracellular mucin in many cases, and positive immunohistochemical staining for glandular cytokeratins, epithelial membrane antigen, and carcinoembryonic antigen. This article provides an overview of mammary and extramammary Paget's disease and discusses recent evidence regarding the cell of origin. The concepts of primary and secondary Paget's disease are presented and the differential diagnosis is discussed with reference to immunohistochemical markers that might be of diagnostic value.

Key Words: mammary Paget's disease • extramammary Paget's disease

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Selected References

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  • Curtin JP, Rubin SC, Jones WB, Hoskins WJ, Lewis JL., Jr Paget's disease of the vulva. Gynecol Oncol. 1990 Dec;39(3):374–377. [PubMed]
  • 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 Jan;56(1):63–70. [PubMed]
  • Fishman DA, Chambers SK, Schwartz PE, Kohorn EI, Chambers JT. Extramammary Paget's disease of the vulva. Gynecol Oncol. 1995 Feb;56(2):266–270. [PubMed]
  • Tsukada Y, Lopez RG, Pickren JW, Piver MS, Barlow JJ. Paget's disease of the vulva: a clinicopathologic study of eight cases. Obstet Gynecol. 1975 Jan;45(1):73–78. [PubMed]
  • Lee SC, Roth LM, Ehrlich C, Hall JA. Extramammary Paget's disease of the vulva. A clinicopathologic study of 13 cases. Cancer. 1977 Jun;39(6):2540–2549. [PubMed]
  • Molinie V, Paniel BJ, Lessana-Leibowitch M, Moyal-Barracco M, Pelisse M, Escande JP. Maladie de Paget vulvaire: 36 cas. Ann Dermatol Venereol. 1993;120(8):522–527. [PubMed]
  • Goldblum JR, Hart WR. Vulvar Paget's disease: a clinicopathologic and immunohistochemical study of 19 cases. Am J Surg Pathol. 1997 Oct;21(10):1178–1187. [PubMed]
  • 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 Feb;22(2):170–179. [PubMed]
  • Olson DJ, Fujimura M, Swanson P, Okagaki T. Immunohistochemical features of Paget's disease of the vulva with and without adenocarcinoma. Int J Gynecol Pathol. 1991;10(3):285–295. [PubMed]
  • Cappuccini F, Tewari K, Rogers LW, DiSaia PJ. Extramammary Paget's disease of the vulva: metastases to the bone marrow in the absence of an underlying adenocarcinoma--case report and literature review. Gynecol Oncol. 1997 Jul;66(1):146–150. [PubMed]
  • Evans AT, Neven P. Invasive adenocarcinoma arising in extramammary Paget's disease of the vulva. Histopathology. 1991 Apr;18(4):355–360. [PubMed]
  • Jones RE., Jr Mammary Paget's disease without underlying carcinoma. Am J Dermatopathol. 1985 Aug;7(4):361–365. [PubMed]
  • Kollmorgen DR, Varanasi JS, Edge SB, Carson WE., 3rd Paget's disease of the breast: a 33-year experience. J Am Coll Surg. 1998 Aug;187(2):171–177. [PubMed]
  • Yim JH, Wick MR, Philpott GW, Norton JA, Doherty GM. Underlying pathology in mammary Paget's disease. Ann Surg Oncol. 1997 Jun;4(4):287–292. [PubMed]
  • Burke ET, Braeuning MP, McLelland R, Pisano ED, Cooper LL. Paget disease of the breast: a pictorial essay. Radiographics. 1998 Nov-Dec;18(6):1459–1464. [PubMed]
  • Paone JF, Baker RR. Pathogenesis and treatment of Paget's disease of the breast. Cancer. 1981 Aug 1;48(3):825–829. [PubMed]
  • Lagios MD, Westdahl PR, Rose MR, Concannon S. Paget's disease of the nipple. Alternative management in cases without or with minimal extent of underlying breast carcinoma. Cancer. 1984 Aug 1;54(3):545–551. [PubMed]
  • Bulens P, Vanuytsel L, Rijnders A, van der Schueren E. Breast conserving treatment of Paget's disease. Radiother Oncol. 1990 Apr;17(4):305–309. [PubMed]
  • Campana F, Vielh P, Fourquet A, Schlienger P, Jullien D, Durand JC, Salmon R, Vilcoq JR. Maladie de Paget du mamelon sans tumeur mammaire associée cliniquement ou radiologiquement décelable. A propos de 51 cas traités à l'Institut Curie. J Gynecol Obstet Biol Reprod (Paris) 1987;16(8):1069–1073. [PubMed]
  • Fourquet A, Campana F, Vielh P, Schlienger P, Jullien D, Vilcoq JR. Paget's disease of the nipple without detectable breast tumor: conservative management with radiation therapy. Int J Radiat Oncol Biol Phys. 1987 Oct;13(10):1463–1465. [PubMed]
  • Desai DC, Brennan EJ, Jr, Carp NZ. Paget's disease of the male breast. Am Surg. 1996 Dec;62(12):1068–1072. [PubMed]
  • Kakinuma H, Iwasawa U, Kurakata N, Suzuki H. A case of extramammary Paget's disease with depigmented macules as the sole manifestation. Br J Dermatol. 1994 Jan;130(1):102–105. [PubMed]
  • Fligiel Z, Kaneko M. Extramammary Paget's disease of the external ear canal in association with ceruminous gland carcinoma. A case report. Cancer. 1975 Sep;36(3):1072–1076. [PubMed]
  • WHORTON CM, PATTERSON JB. Carcinoma of Moll's glands with extramammary Paget's disease of the eyelid. Cancer. 1955 Sep-Oct;8(5):1009–1015. [PubMed]
  • Theaker JM. Extramammary Paget's disease of the oral mucosa with in situ carcinoma of minor salivary gland ducts. Am J Surg Pathol. 1988 Nov;12(11):890–895. [PubMed]
  • Shimizu S, Kobayashi H, Suchi T, Torii Y, Narita K, Aoki S. Extramammary Paget's disease arising in mature cystic teratoma of the ovary. Am J Surg Pathol. 1991 Oct;15(10):1002–1006. [PubMed]
  • Stephenson TJ, Cotton DW. Paget's disease in an epidermal cyst. Dermatologica. 1987;174(4):186–190. [PubMed]
  • Fanning J, Lambert HC, Hale TM, Morris PC, Schuerch C. Paget's disease of the vulva: prevalence of associated vulvar adenocarcinoma, invasive Paget's disease, and recurrence after surgical excision. Am J Obstet Gynecol. 1999 Jan;180(1 Pt 1):24–27. [PubMed]
  • van der Putte SC. Anogenital "sweat" glands. Histology and pathology of a gland that may mimic mammary glands. Am J Dermatopathol. 1991 Dec;13(6):557–567. [PubMed]
  • van der Putte SC, van Gorp LH. Adenocarcinoma of the mammary-like glands of the vulva: a concept unifying sweat gland carcinoma of the vulva, carcinoma of supernumerary mammary glands and extramammary Paget's disease. J Cutan Pathol. 1994 Apr;21(2):157–163. [PubMed]
  • Powell FC, Bjornsson J, Doyle JA, Cooper AJ. Genital Paget's disease and urinary tract malignancy. J Am Acad Dermatol. 1985 Jul;13(1):84–90. [PubMed]
  • Koga F, Gotoh S, Suzuki S. [A case of invasive bladder cancer with Pagetoid skin lesion of the vulva and anogenital Paget's disease]. Nihon Hinyokika Gakkai Zasshi. 1997 Apr;88(4):503–506. [PubMed]
  • McKee PH, Hertogs KT. Endocervical adenocarcinoma and vulval Paget's disease: a significant association. Br J Dermatol. 1980 Oct;103(4):443–448. [PubMed]
  • Hayashibara Y, Ikeda S. [Extramammary Paget's disease with internal malignancies]. Gan To Kagaku Ryoho. 1988 Apr;15(4 Pt 2-3):1569–1575. [PubMed]
  • Nakano S, Narita R, Tabaru A, Ogami Y, Otsuki M. Bile duct cancer associated with extramammary Paget's disease. Am J Gastroenterol. 1995 Mar;90(3):507–508. [PubMed]
  • Popiolek DA, Hajdu SI, Gal D. Synchronous Paget's disease of the vulva and breast. Gynecol Oncol. 1998 Oct;71(1):137–140. [PubMed]
  • Allan SJ, McLaren K, Aldridge RD. Paget's disease of the scrotum: a case exhibiting positive prostate-specific antigen staining and associated prostatic adenocarcinoma. Br J Dermatol. 1998 Apr;138(4):689–691. [PubMed]
  • Burrows NP, Jones DH, Hudson PM, Pye RJ. Treatment of extramammary Paget's disease by radiotherapy. Br J Dermatol. 1995 Jun;132(6):970–972. [PubMed]
  • Costello TJ, Wang HH, Schnitt SJ, Ritter R, Antonioli DA. Paget's disease with extensive involvement of the female genital tract initially detected by cervical cytosmear. Arch Pathol Lab Med. 1988 Sep;112(9):941–944. [PubMed]
  • Geisler JP, Gates RW, Shirrell W, Parker SM, Maloney CD, Wiemann MC, Geisler HE. Extramammary Paget's disease with diffuse involvement of the lower female genito-urinary system. Int J Gynecol Cancer. 1997 Jan;7(1):84–87. [PubMed]
  • Lloyd J, Evans DJ, Flanagan AM. Extension of extramammary Paget disease of the vulva to the cervix. J Clin Pathol. 1999 Jul;52(7):538–540. [PMC free article] [PubMed]
  • Stacy D, Burrell MO, Franklin EW., 3rd Extramammary Paget's disease of the vulva and anus: use of intraoperative frozen-section margins. Am J Obstet Gynecol. 1986 Sep;155(3):519–523. [PubMed]
  • Coldiron BM, Goldsmith BA, Robinson JK. Surgical treatment of extramammary Paget's disease. A report of six cases and a reexamination of Mohs micrographic surgery compared with conventional surgical excision. Cancer. 1991 Feb 15;67(4):933–938. [PubMed]
  • Bergen S, DiSaia PJ, Liao SY, Berman ML. Conservative management of extramammary Paget's disease of the vulva. Gynecol Oncol. 1989 May;33(2):151–156. [PubMed]
  • Besa P, Rich TA, Delclos L, Edwards CL, Ota DM, Wharton JT. Extramammary Paget's disease of the perineal skin: role of radiotherapy. Int J Radiat Oncol Biol Phys. 1992;24(1):73–78. [PubMed]
  • Jones RE, Jr, Austin C, Ackerman AB. Extramammary Paget's disease. A critical reexamination. Am J Dermatopathol. 1979 Summer;1(2):101–132. [PubMed]
  • Sitakalin C, Ackerman AB. Mammary and extramammary Paget's disease. Am J Dermatopathol. 1985 Aug;7(4):335–340. [PubMed]
  • Samarasinghe D, Frost F, Sterrett G, Whitaker D, Ingram D, Sheiner H. Cytological diagnosis of Paget's disease of the nipple by scrape smears: a report of five cases. Diagn Cytopathol. 1993;9(3):291–295. [PubMed]
  • Husseinzadeh N, Recinto C. Frequency of invasive cancer in surgically excised vulvar lesions with intraepithelial neoplasia (VIN 3). Gynecol Oncol. 1999 Apr;73(1):119–120. [PubMed]
  • Roth LM, Lee SC, Ehrlich CE. Paget's disease of the vulva. A histogenetic study of five cases including ultrastructural observations and review of the literature. Am J Surg Pathol. 1977 Sep;1(3):193–206. [PubMed]
  • Hitchcock A, Topham S, Bell J, Gullick W, Elston CW, Ellis IO. Routine diagnosis of mammary Paget's disease. A modern approach. Am J Surg Pathol. 1992 Jan;16(1):58–61. [PubMed]
  • Reed W, Oppedal BR, Eeg Larsen T. Immunohistology is valuable in distinguishing between Paget's disease, Bowen's disease and superficial spreading malignant melanoma. Histopathology. 1990 Jun;16(6):583–588. [PubMed]
  • Nakamura G, Shikata N, Shoji T, Hatano T, Hioki K, Tsubura A. Immunohistochemical study of mammary and extramammary Paget's disease. Anticancer Res. 1995 Mar-Apr;15(2):467–470. [PubMed]
  • Helm KF, Goellner JR, Peters MS. Immunohistochemical stains in extramammary Paget's disease. Am J Dermatopathol. 1992 Oct;14(5):402–407. [PubMed]
  • Jones RR, Spaull J, Gusterson B. The histogenesis of mammary and extramammary Paget's disease. Histopathology. 1989 Apr;14(4):409–416. [PubMed]
  • Guarner J, Cohen C, DeRose PB. Histogenesis of extramammary and mammary Paget cells. An immunohistochemical study. Am J Dermatopathol. 1989 Aug;11(4):313–318. [PubMed]
  • Cohen C, Guarner J, DeRose PB. Mammary Paget's disease and associated carcinoma. An immunohistochemical study. Arch Pathol Lab Med. 1993 Mar;117(3):291–294. [PubMed]
  • Ordóez NG, Awalt H, Mackay B. Mammary and extramammary Paget's disease. An immunocytochemical and ultrastructural study. Cancer. 1987 Mar 15;59(6):1173–1183. [PubMed]
  • Guldhammer B, Nørgaard T. The differential diagnosis of intraepidermal malignant lesions using immunohistochemistry. Am J Dermatopathol. 1986 Aug;8(4):295–301. [PubMed]
  • Gillett CE, Bobrow LG, Millis RR. S100 protein in human mammary tissue--immunoreactivity in breast carcinoma, including Paget's disease of the nipple, and value as a marker of myoepithelial cells. J Pathol. 1990 Jan;160(1):19–24. [PubMed]
  • Bacchi CE, Goldfogel GA, Greer BE, Gown AM. Paget's disease and melanoma of the vulva. Use of a panel of monoclonal antibodies to identify cell type and to microscopically define adequacy of surgical margins. Gynecol Oncol. 1992 Aug;46(2):216–221. [PubMed]
  • Lundquist K, Kohler S, Rouse RV. Intraepidermal cytokeratin 7 expression is not restricted to Paget cells but is also seen in Toker cells and Merkel cells. Am J Surg Pathol. 1999 Feb;23(2):212–219. [PubMed]
  • van der Putte SC, Toonstra J, Hennipman A. Mammary Paget's disease confined to the areola and associated with multifocal Toker cell hyperplasia. Am J Dermatopathol. 1995 Oct;17(5):487–493. [PubMed]
  • Lee JY, Chao SC. Clear cell papulosis of the skin. Br J Dermatol. 1998 Apr;138(4):678–683. [PubMed]
  • Mazoujian G, Pinkus GS, Haagensen DE., Jr Extramammary Paget's disease--evidence for an apocrine origin. An immunoperoxidase study of gross cystic disease fluid protein-15, carcinoembryonic antigen, and keratin proteins. Am J Surg Pathol. 1984 Jan;8(1):43–50. [PubMed]
  • Smith KJ, Tuur S, Corvette D, Lupton GP, Skelton HG. Cytokeratin 7 staining in mammary and extramammary Paget's disease. Mod Pathol. 1997 Nov;10(11):1069–1074. [PubMed]
  • Watanabe S, Ohnishi T, Takahashi H, Ishibashi Y. A comparative study of cytokeratin expression in Paget cells located at various sites. Cancer. 1993 Dec 1;72(11):3323–3330. [PubMed]
  • Nowak MA, Guerriere-Kovach P, Pathan A, Campbell TE, Deppisch LM. Perianal Paget's disease: distinguishing primary and secondary lesions using immunohistochemical studies including gross cystic disease fluid protein-15 and cytokeratin 20 expression. Arch Pathol Lab Med. 1998 Dec;122(12):1077–1081. [PubMed]
  • Kirkham N, Berry N, Jones DB, Taylor-Papadimitriou J. Paget's disease of the nipple. Immunohistochemical localization of milk fat globule membrane antigens. Cancer. 1985 Apr 1;55(7):1510–1512. [PubMed]
  • Lloveras B, Googe PB, Goldberg DE, Bhan AK. Estrogen receptors in skin appendage tumors and extramammary Paget's disease. Mod Pathol. 1991 Jul;4(4):487–490. [PubMed]
  • Swanson PE, Mazoujian G, Mills SE, Campbell RJ, Wick MR. Immunoreactivity for estrogen receptor protein in sweat gland tumors. Am J Surg Pathol. 1991 Sep;15(9):835–841. [PubMed]
  • Keatings L, Sinclair J, Wright C, Corbett IP, Watchorn C, Hennessy C, Angus B, Lennard T, Horne CH. c-erbB-2 oncoprotein expression in mammary and extramammary Paget's disease: an immunohistochemical study. Histopathology. 1990 Sep;17(3):243–247. [PubMed]
  • Wolber RA, Dupuis BA, Wick MR. Expression of c-erbB-2 oncoprotein in mammary and extramammary Paget's disease. Am J Clin Pathol. 1991 Aug;96(2):243–247. [PubMed]
  • Meissner K, Rivière A, Haupt G, Löning T. Study of neu-protein expression in mammary Paget's disease with and without underlying breast carcinoma and in extramammary Paget's disease. Am J Pathol. 1990 Dec;137(6):1305–1309. [PMC free article] [PubMed]
  • Scheistrøen M, Tropé C, Kaern J, Pettersen EO, Alfsen GC, Nesland JM. DNA ploidy and expression of p53 and C-erbB-2 in extramammary Paget's disease of the vulva. Gynecol Oncol. 1997 Jan;64(1):88–92. [PubMed]
  • Takata M, Hatta N, Takehara K. Tumour cells of extramammary Paget's disease do not show either p53 mutation or allelic loss at several selected loci implicated in other cancers. Br J Cancer. 1997;76(7):904–908. [PMC free article] [PubMed]
  • Kanitakis J, Thivolet J, Claudy A. p53 protein expression in mammary and extramammary Paget's disease. Anticancer Res. 1993 Nov-Dec;13(6B):2429–2433. [PubMed]
  • Wienecke R, Eckert F, Kaudewitz P, de Viragh PA, Heidl G, Volkenandt M. p53 protein in benign and malignant sweat gland tumors. Am J Dermatopathol. 1994 Apr;16(2):126–129. [PubMed]
  • Crawford D, Nimmo M, Clement PB, Thomson T, Benedet JL, Miller D, Gilks CB. Prognostic factors in Paget's disease of the vulva: a study of 21 cases. Int J Gynecol Pathol. 1999 Oct;18(4):351–359. [PubMed]
  • Mori O, Hachisuka H, Nakano S, Sasai Y, Shiku H. Expression of ras p21 in mammary and extramammary Paget's disease. Arch Pathol Lab Med. 1990 Aug;114(8):858–861. [PubMed]

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