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Prognostic Factors of Extramammary Paget’s Disease

  • Skin Cancer (T Ito, Section Editor)
  • Published:
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Opinion statement

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

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Lam C, Funaro D. Extramammary Paget’s disease: summary of current knowledge. Dermatol Clin. 2010;28:807–26.

    Article  PubMed  CAS  Google Scholar 

  2. 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.

    Article  PubMed  Google Scholar 

  3. •• 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.

  4. 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.

    PubMed  CAS  Google Scholar 

  5. 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.

    Article  PubMed  CAS  Google Scholar 

  6. •• 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.

  7. 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.

    Article  PubMed  CAS  Google Scholar 

  8. Karam A, Dorigo O. Treatment outcomes in a large cohort of patients with invasive Extramammary Paget’s disease. Gynecol Oncol. 2012;125:346–51.

    Article  PubMed  Google Scholar 

  9. 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.

    Article  PubMed  Google Scholar 

  10. 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.

    Article  PubMed  CAS  Google Scholar 

  11. • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  12. • 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.

  13. 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.

    Article  PubMed  Google Scholar 

  14. 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.

    Article  PubMed  CAS  Google Scholar 

  15. Chanda JJ. Extramammary Paget’s disease: prognosis and relationship to internal malignancy. J Am Acad Dermatol. 1985;13:1009–14.

    Article  PubMed  CAS  Google Scholar 

  16. 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.

    PubMed  Google Scholar 

  17. 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.

    Article  Google Scholar 

  18. 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.

    Article  PubMed  Google Scholar 

  19. 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.

    Article  PubMed  CAS  Google Scholar 

  20. 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.

    Article  PubMed  Google Scholar 

  21. 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.

  22. Feuer GA, Shevchuk M, Calanog A. Vulvar Paget’s disease: the need to exclude an invasive lesion. Gynecol Oncol. 1990;38:81–9.

    Article  PubMed  CAS  Google Scholar 

  23. Cohen JM, Granter SR, Werchniak AE. Risk stratification in extramammary Paget disease. Clin Exp Dermatol. 2015;40:473–8.

    Article  PubMed  CAS  Google Scholar 

  24. 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.

    Article  PubMed  CAS  Google Scholar 

  25. 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.

    Article  PubMed  Google Scholar 

  26. Oji M, Furue M, Tamaki K. Serum carcinoembryonic antigen level in Paget’s disease. Br J Dermatol. 1984;110:211–3.

    Article  PubMed  CAS  Google Scholar 

  27. 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.

    Article  PubMed  CAS  Google Scholar 

  28. 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.

    Article  PubMed  CAS  Google Scholar 

  29. 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.

    PubMed  CAS  Google Scholar 

  30. 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.

    PubMed  PubMed Central  CAS  Google Scholar 

  31. 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.

    Article  PubMed  CAS  Google Scholar 

  32. Goldblum JR, Hart WR. Vulvar Paget’s disease: a clinicopathologic and immunohistochemical study of 19 cases. Am J Surg Pathol. 1997;21:1178–87.

    Article  PubMed  CAS  Google Scholar 

  33. 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.

    Article  PubMed  CAS  Google Scholar 

  34. 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.

    Article  PubMed  CAS  Google Scholar 

  35. 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.

    Article  PubMed  CAS  Google Scholar 

  36. 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.

    Article  PubMed  CAS  Google Scholar 

  37. • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  38. 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.

    Article  PubMed  CAS  Google Scholar 

  39. 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.

    Article  PubMed  CAS  Google Scholar 

  40. 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.

    Article  PubMed  CAS  Google Scholar 

  41. 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.

    Article  PubMed  CAS  Google Scholar 

  42. 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.

    Article  PubMed  CAS  Google Scholar 

  43. 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.

    Article  PubMed  CAS  Google Scholar 

  44. 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.

    Article  PubMed  CAS  Google Scholar 

  45. 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.

    Article  PubMed  Google Scholar 

  46. 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.

    Article  PubMed  Google Scholar 

  47. 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.

    Article  PubMed  CAS  Google Scholar 

  48. Duttagupta R, Jiang R, Gollub J, Getts RC, Jones KW. Impact of cellular miRNAs on circulating miRNA biomarker signatures. PLoS One. 2011;6:e20769.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. 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.

  50. 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.

    Article  PubMed  Google Scholar 

  51. 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.

    PubMed  Google Scholar 

  52. Ewing T, Sawicki J, Ciaravino G, Rumore GJ. Microinvasive Paget’s disease. Gynecol Oncol. 2004;95:755–8.

    Article  PubMed  Google Scholar 

  53. 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.

    Article  PubMed  CAS  Google Scholar 

  54. 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.

    PubMed  Google Scholar 

  55. • 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.

    Article  PubMed  Google Scholar 

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Correspondence to Naohito Hatta MD, PhD.

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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

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