Most patients with extramammary Paget’s disease (EMPD) show a good prognosis; however, some patients develop fatal metastases. Early detection is important for improving prognosis, due to the difficulties associated with the treatment of distant EMPD metastases. Several studies have emphasized the importance of the invasion level of the primary lesion for predicting the presence of metastasis, and deeper invasion or increased thickness is correlated with poorer prognosis. Vascular tumor invasion of the primary lesion can also predict the risk of metastasis. Lymph node metastasis is a strong indicator for poor prognosis, and the number of lymph node metastases affects patient outcome, in that there is a significant difference in survival between patients with zero or one lymph node metastasis and those with more than two lymph node metastases. Serum markers may be able to predict the presence of systemic metastases, and carcinoembryonic antigen and cytokeratin 19 fragment 21-1 reflect disease progression and may be clinically valuable. Although several genetic alterations have been determined for EMPD, factors determining prognosis should be further explored.
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References and Recommended Reading
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Lam C, Funaro D. Extramammary Paget’s disease: summary of current knowledge. Dermatol Clin. 2010;28:807–26.
Pierie JP, Choudry U, Muzikansky A, Finkelstein DM, Ott MJ. Prognosis and management of extramammary Paget’s disease and the association with secondary malignancies. J Am Coll Surg. 2003;196:45–50.
•• Ohara K, Fujisawa Y, Yoshino K, Kiyohara Y, Kadono T, Murata Y, 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;83:234–9. Important proposal of TNM staging system.
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;158:313–8.
Ito Y, Igawa S, Ohishi Y, Uehara J, Yamamoto AI, Iizuka H. Prognostic indicators in 35 patients with extramammary Paget’s disease. Dermatol Surg. 2012;38:1938–44.
•• Ito T, Kaku Y, Nagae K, Nakano-Nakamura M, Nakahara T, Oda Y, et al. Tumor thickness as a prognostic factor in extramammary Paget’s disease. J Dermatol. 2015;42:269–75. Important trial on prognostic factor in EMPD.
Siesling S, Elferink MA, van Dijck JA, Pierie JP, Blokx WA. Epidemiology and treatment of extramammary Paget disease in the Netherlands. Eur J Surg Oncol. 2007;33:951–5.
Karam A, Dorigo O. Treatment outcomes in a large cohort of patients with invasive Extramammary Paget’s disease. Gynecol Oncol. 2012;125:346–51.
Lee SJ, Choe YS, Jung HD, Ahn SK, Cha YC, Cho KH, et al. A multicenter study on extramammary Paget’s disease in Korea. Int J Dermatol. 2011;50:508–15.
Cheng PS, Lu CL, Cheng CL, Lai FJ. Significant male predisposition in extramammary Paget disease: a nationwide population-based study in Taiwan. Br J Dermatol. 2014;171:191–3.
• Yao H, Xie M, Fu S, Guo J, Peng Y, Cai Z, et al. Survival analysis of patients with invasive extramammary Paget disease: implications of anatomic sites. BMC Cancer. 2018;18:403. Survival analysis on large number of Patients.
• Iacoponi S, Zalewski K, Fruscio R, Diaz-De la Noval B, De Iaco P, Ceccaroni M, et al. Prognostic factors for recurrence and survival among patients with invasive vulvar Paget disease included in the VULCAN study. Int J Gynaecol Obstet. 2016;133:76–9. Multicenter study on prognostic factors.
McCarter MD, Quan SH, Busam K, Paty PP, Wong D, Guillem JG. Long-term outcome of perianal Paget’s disease. Dis Colon Rectum. 2003;46:612–6.
Mengjun B, Zheng-Qiang W, Tasleem MM. Extramammary Paget’s disease of the perianal region: a review of the literature emphasizing management. Dermatol Surg. 2013;39:69–75.
Chanda JJ. Extramammary Paget’s disease: prognosis and relationship to internal malignancy. J Am Acad Dermatol. 1985;13:1009–14.
Tsutsumida A, Yamamoto Y, Minakawa H, Yoshida T, Kokubu I, Sugihara T. Indications for lymph node dissection in the treatment of extramammary Paget’s disease. Dermatol Surg. 2003;29:21–4.
Yoon SN, Park IJ, Kim HC, Yu CS, Lee MW, Koh JK, et al. Extramammary Paget’s disease in Korea: its association with gastrointestinal neoplasms. Int J Color Dis. 2008;23:1125–30.
Kang Z, Xu F, Zhu Y, Fu P, Zhang QA, Hu T, et al. Genetic analysis of mismatch repair genes alterations in extramammary Paget disease. Am J Surg Pathol. 2016;40:1517–25.
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;22:170–9.
De Nisi MC, D'Amuri A, Toscano M, Lalinga AV, Pirtoli L, Miracco C. Usefulness of CDX2 in the diagnosis of extramammary Paget disease associated with malignancies of intestinal type. Br J Dermatol. 2005;153:677–9.
van der Linden M, Schuurman MS, Bulten J, Massuger L, IntHout J, van der Aa MA, et al. Stop routine screening for associated malignancies in cutaneous non-invasive vulvar Paget disease? Br J Dermatol. 2018.
Feuer GA, Shevchuk M, Calanog A. Vulvar Paget’s disease: the need to exclude an invasive lesion. Gynecol Oncol. 1990;38:81–9.
Cohen JM, Granter SR, Werchniak AE. Risk stratification in extramammary Paget disease. Clin Exp Dermatol. 2015;40:473–8.
Fine BA, Fowler LJ, Valente PT, Gaudet T. Minimally invasive Paget’s disease of the vulva with extensive lymph node metastases. Gynecol Oncol. 1995;57:262–5.
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;47:70–7.
Oji M, Furue M, Tamaki K. Serum carcinoembryonic antigen level in Paget’s disease. Br J Dermatol. 1984;110:211–3.
Zhu Y, Ye DW, Yao XD, Zhang SL, Dai B, Zhang HL, et al. Clinicopathological characteristics, management and outcome of metastatic penoscrotal extramammary Paget’s disease. Br J Dermatol. 2009;161:577–82.
Kato J, Sumikawa Y, Hida T, Kamiya T, Horimoto K, Kamiya S, et al. Serum cytokeratin 19 fragment 21-1 is a useful tumor marker for the assessment of extramammary Paget’s disease. J Dermatol. 2017;44:666–70.
Inoguchi N, Matsumura Y, Kanazawa N, Morita K, Tachibana T, Sakurai T, et al. Expression of prostate-specific antigen and androgen receptor in extramammary Paget’s disease and carcinoma. Clin Exp Dermatol. 2007;32:91–4.
Kang Z, Zhang Q, Zhang Q, Li X, Hu T, Xu X, et al. Clinical and pathological characteristics of extramammary Paget’s disease: report of 246 Chinese male patients. Int J Clin Exp Pathol. 2015;8:13233–40.
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;108:6–12.
Goldblum JR, Hart WR. Vulvar Paget’s disease: a clinicopathologic and immunohistochemical study of 19 cases. Am J Surg Pathol. 1997;21:1178–87.
Ohnishi T, Watanabe S. The use of cytokeratins 7 and 20 in the diagnosis of primary and secondary extramammary Paget’s disease. Br J Dermatol. 2000;142:243–7.
Yoshii N, Kitajima S, Yonezawa S, Matsukita S, Setoyama M, Kanzaki T. Expression of mucin core proteins in extramammary Paget’s disease. Pathol Int. 2002;52:390–9.
Liegl B, Leibl S, Gogg-Kamerer M, Tessaro B, Horn LC, Moinfar F. Mammary and extramammary Paget’s disease: an immunohistochemical study of 83 cases. Histopathology. 2007;50:439–47.
Hata H, Abe R, Hoshina D, Saito N, Homma E, Aoyagi S, et al. MUC5AC expression correlates with invasiveness and progression of extramammary Paget’s disease. J Eur Acad Dermatol Venereol. 2014;28:727–32.
• Fukuda K, Funakoshi T. Metastatic extramammary Paget’s disease: pathogenesis and novel therapeutic approach. Front Oncol. 2018;8:38. Excellent review on treatment of metastatic EMPD.
Takata M, Fujimoto A, Aoki H, Hatta N, Ooi A, Takehara K. erbB-2 overexpression but no activation of beta-Catenin gene in extramammary Paget’s disease. J Invest Dermatol. 1999;113:258–62.
Tanaka R, Sasajima Y, Tsuda H, Namikawa K, Tsutsumida A, Otsuka F, et al. Human epidermal growth factor receptor 2 protein overexpression and gene amplification in extramammary Paget disease. Br J Dermatol. 2013;168:1259–66.
Aoyagi S, Akiyama M, Shimizu H. High expression of Ki-67 and cyclin D1 in invasive extramammary Paget’s disease. J Dermatol Sci. 2008;50:177–84.
Liu H, Moroi Y, Yasumoto S, Kokuba H, Imafuku S, Koga T, et al. Expression of insulin-like growth factor-1 receptor, p-AKT and p-ERK1/2 protein in extramammary Paget’s disease. Br J Dermatol. 2006;155:586–91.
Liu HJ, Moroi Y, Masuda T, Yasumoto S, Kokuba H, Imafuku S, et al. Expression of phosphorylated Stat3, cyclin D1 and Bcl-xL in extramammary Paget disease. Br J Dermatol. 2006;154:926–32.
Chen S, Moroi Y, Urabe K, Takeuchi S, Kido M, Hayashida S, et al. Differential expression of two new members of the p53 family, p63 and p73, in extramammary Paget's disease. Clin Exp Dermatol. 2008;33:634–40.
Chen SY, Moroi Y, Urabe K, Takeuchi S, Kido M, Hayashida S, et al. Concordant overexpression of p-FAK and p-ERK1/2 in extramammary Paget’s disease. Arch Dermatol Res. 2008;300:195–201.
Qian Y, Takeuchi S, Chen SJ, Dugu L, Tsuji G, Xie L, et al. Nerve growth factor, brain-derived neurotrophic factor and their high-affinity receptors are overexpressed in extramammary Paget’s disease. J Cutan Pathol. 2010;37:1150–4.
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;39:1010–5.
Kang Z, Xu F, Zhang QA, Lin J, Wu Z, Zhang X, et al. Correlation of DLC1 gene methylation with oncogenic PIK3CA mutations in extramammary Paget’s disease. Mod Pathol. 2012;25:1160–8.
Duttagupta R, Jiang R, Gollub J, Getts RC, Jones KW. Impact of cellular miRNAs on circulating miRNA biomarker signatures. PLoS One. 2011;6:e20769.
Guo H, Qi RQ, Lv YN, Wang HX, Hong YX, Zheng S, et al. miR-31 is distinctively overexpressed in primary male extramammary Paget’s disease. Oncotarget. 2016;7:24559–63.
Kudo G, Toyama H, Hasegawa K, Kuroda M, Hattori H, Ishiguro M, et al. Sentinel lymph node navigation surgery in Paget’s disease of the vulva. Clin Nucl Med. 2002;27:909–10.
Hatta N, Morita R, Yamada M, Echigo T, Hirano T, Takehara K, et al. Sentinel lymph node biopsy in patients with extramammary Paget’s disease. Dermatol Surg. 2004;30:1329–34.
Ewing T, Sawicki J, Ciaravino G, Rumore GJ. Microinvasive Paget’s disease. Gynecol Oncol. 2004;95:755–8.
Nakamura Y, Fujisawa Y, Ishikawa M, Nakamura Y, Ishitsuka Y, Maruyama H, et al. Usefulness of sentinel lymph node biopsy for extramammary Paget disease. Br J Dermatol. 2012;167:954–6.
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;26:254–9.
• Fujisawa Y, Yoshino K, Kiyohara Y, Kadono T, Murata Y, Uhara H, 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;79:38–42. Multicenter trial on sentinel lymph node biopsy in invasive EMPD.
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Hatta, N. Prognostic Factors of Extramammary Paget’s Disease. Curr. Treat. Options in Oncol. 19, 47 (2018). https://doi.org/10.1007/s11864-018-0567-4
- Lymph node
- Serum marker