Diagnosis -- Extramammary Paget disease

FINAL DIAGNOSIS

Extramammary Paget disease

DISCUSSION

Extramammary Paget disease is an extremely rare entity which has been more commonly described in older adults 1-2. A SEER analysis performed in 2011 found 328 cases of penis and anorectal EMPD from 1973 to 2007 3. Median age for the diagnosis of scrotal and penile disease was 70.4 years and 73.6 years respectively 3. The disease has been associated with genitourinary or gastrointestinal cancers, either synchronously or metachronously 4-12. Although the exact incidence of secondary malignancy in this cases is unknown, the incidence of a separate primary malignancy was 45% in a study by Hegarty et al 13. In our case, the patient had an associated urothelial carcinoma. Immunohistochemical stains can be helpful in the differentiation of primary EMPD & secondary EMPD. GCDFP-15 can be positive in some primary EMPD cases while it tends to be negative in secondary EMPD, especially secondary to colorectal or urothelial carcinoma 14-16. In our case, GCDFP-15 was negative. CK7 and CK20 is another group of stains which is useful in differentiating primary and secondary EMPD. Most commonly, primary EMPD tends to be CK7 +, CK 20 -, secondary EMPD from colorectal carcinoma tends to be CK 7-, CK20 + while EMPD secondary to urothelial carcinoma tends to be CK 7 and CK20 + 17-21. However, aberrant staining pattern in these scenarios has also been described 18-21. Our case showed positivity for CK7 but was negative for CK20. It was also positive for uroplakin II/III which can be another marker useful in the diagnosis of secondary EMPD. The patient was treated with surgery, chemotherapy for underlying urothelial carcinoma and had not demonstrated any disease recurrence, until last follow up. Because of the rarity of this disease, different treatment modalities have been tried. However, wide local excision is used more commonly in the management of EMPD. We present this case so as to make the pathology community aware of this rare lesion and to emphasize that immunohistochemical workup, clinical correlation are helpful in differentiation of primary and secondary EMPD.

REFERENCES

  1. Ghazawi, F.M.; Iga, N.; Tanaka, R.; Fujisawa, Y.; Yoshino, K.; Yamashita, C.; Yamamoto, Y.; Fujimura, T.; Yanagi, T.; Hata, H.; et al. Demographic and clinical characteristics of extramammary Paget's disease patients in Japan from 2000 to 2019. J. Eur. Acad. Dermatol. Venereol. 2021, 35, e133-e135. [CrossRef] [PubMed]
  2. Karam, A.; Dorigo, O. Treatment outcomes in a large cohort of patients with invasive Extramammary Paget's disease. Gynecol. Oncol. 2012, 125, 346-351. [CrossRef] [PubMed]
  3. Master VA, Herrel L, Johnson TV, Delman KA. Extramammary Paget's disease of the penis and anogenital area: seer analysis [abstract 220]. J Clin Oncol 2011;29:. [Available online at: http://meetinglibrary.asco.org/content/72169-104; cited May 29, 2013]
  4. Voigt H, Bassermann R, Nathrath W. Cytoreductive combination chemotherapy for regionally advanced unresectable extramammary Paget carcinoma. Cancer 1992;70:704-8.
  5. Becker-Wegerich PM, Fritsch C, Schulte KW, et al. Carbon dioxide laser treatment of extramammary Paget's disease guided by photodynamic diagnosis. Br J Dermatol 1998;138:169-72.
  6. Zollo JD, Zeitouni NC. The Roswell Park Cancer Institute experience with extramammary Paget's disease. Br J Dermatol 2000;142:59-65.
  7. Powell FC, Bjornsson J, Doyle JA, Cooper AJ. Genital Paget's disease and urinary tract malignancy. J Am Acad Dermatol 1985;13:84-90.
  8. Chanda JJ. Extramammary Paget's disease: prognosis and relationship to internal malignancy. J Am Acad Dermatol 1985;13:1009-14.
  9. Ojeda VJ, Heenan PJ, Watson SH. Paget's disease of the groin associated with adenocarcinoma of the urinary bladder. J Cutan Pathol 1987;14:227-3.
  10. Koh KB, Nazarina AR. Paget's disease of the scrotum: report of a case with underlying carcinoma of the prostate. Br J Dermatol 1995;133:306-7.
  11. Lai YL, Yang WG, Tsay PK, Swei H, Chuang SS, Wen CJ. Penoscrotal extramammary Paget's disease: a review of 33 cases in a 20-year experience. Plast Reconstr Surg 2003;112:1017-23.
  12. Li YC, Lu LY, Yang YT, Chang CC, Chen LM. Extramammary Paget's disease of the scrotum associated with hepatocellular carcinoma. J Chin Med Assoc 2009;72:542-6.
  13. Zhao, Y.; Gong, X.; Li, N.; Zhu, Q.; Yu, D.; Jin, X. Primary extramammary Paget's disease: A clinicopathological study of 28 cases. Int. J. Clin. Exp. Pathol. 2019, 12, 3426-3432. [PubMed]
  14. McKee, P.H.; Hertogs, K.T. Endocervical adenocarcinoma and vulval Paget's disease: A significant association. Br. J. Dermatol. 1980, 103, 443-448.
  15. Wang, Y.C.; Li, A.F.; Yang, S.H.; Ma, H.H.; Liang, W.Y. Perianal Paget's Disease: The 17-Year-Experience of a Single Institution in Taiwan. Gastroenterol. Res. Pract. 2019, 2019, 2603279.
  16. 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, 243-247.
  17. Goldblum, J.R.; Hart, W.R. Perianal Paget's disease: A histologic and immunohistochemical study of 11 cases with and without associated rectal adenocarcinoma. Am. J. Surg. Pathol. 1998, 22, 170-179.
  18. Goldblum, J.R.; Hart, W.R. Vulvar Paget's disease: A clinicopathologic and immunohistochemical study of 19 cases. Am. J. Surg. Pathol. 1997, 21, 1178-1187.
  19. Liao, X.; Liu, X.; Fan, X.; Lai, J.; Zhang, D. Perianal Paget's disease: A clinicopathological and immunohistochemical study of 13 cases. Diagn. Pathol. 2020, 15, 29.
  20. Lopez-Beltran, A.; Luque, R.J.; Moreno, A.; Bollito, E.; Carmona, E.; Montironi, R. The pagetoid variant of bladder urothelial carcinoma in situ A clinicopathological study of 11 cases. Virchows Arch. 2002, 441, 148-153.
  21. Hegarty PK, Suh J, Fisher MB, Taylor J, Nguyen TH, Ivan D, Prieto VG, Pagliaro LC, Pettaway CA. Penoscrotal extramammary Paget's disease: the University of Texas M. D. Anderson Cancer Center contemporary experience. J Urol. 2011 Jul;186(1):97-102. https://doi.org/10.1016/j.juro.2011.02.2685. Epub 2011 May 14. PMID: 21571343.
FIVE QUESTIONS

1. Extra-mammary Paget disease (EMPD) of the penoscrotal region is seen in:

  1. Infants
  2. Young adults
  3. Older adults
  4. None of the above

2. Primary Extramammary Paget disease commonly tend to show the following pattern of IHC staining:

  1. CK7+, CK20+
  2. CK7+, CK20-
  3. CK7-, CK20-
  4. CK7-, CK20+

3. The most commonly used treatment for management of EMPD is:

  1. Radiation
  2. Chemotherapy
  3. Wide Local Excision
  4. No treatment required

4. Incidence of a separate primary malignancy associated with EMPD, according to a study by Hegarty et al is:

  1. 50%
  2. 45%
  3. 100%
  4. 5%

5. EMPD secondary to colorectal carcinoma tends to be:

  1. CK7+, CK20+
  2. CK7-, CK20-
  3. CK7-, CK20+
  4. CK7+, CK20-

Pranav P. Patwardhan, MD, and Gabriela M. Quiroga-Garza, MD



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