A simplified classification of EMPD has been proposed and the authors are in agreement with this classification: Type I EMPD is defined by Paget cells confined entirely to the epidermis and the epithelial structure of its adnexa, with or without dermal invasion. Type II EMPD exists within the epidermis, the epithelial structure of its adnexa, and the contiguous epithelium of the genitourinary or gastrointestinal tract.5 Many of the underlying cancers seen in EMPD patients are likely coincidental and unrelated to the EMPD or represent contiguous disease extending into the lower gastrointestinal or genitourinary tract (Type II).5 The search for underlying cancers in EMPD patients should be focused on contiguous disease extending into the urethra, anal canal, and vaginal/cervical mucosa if there is clinical suspicion or if indicated by the scouting biopsies or surgical margins. Regardless of EMPD, all patients should have age appropriate screening for other cancers per recommended guidelines.
EMPD predominantly affects females, though the male:female ratio nears 1:1 amongst Asian patients.3 Involvement of the male genitalia comprises only 14% of EMPD cases; these lesions are usually unilateral and appear on the scrotum, penis, groin, and perianal regions.1 Bilateral involvement of the male genitalia is even more rare, and there have been few case reports of bilateral EMPD involving the genitalia and/or axilla.6,7 Thus, our patient presents a rare case of EMPD with bilateral involvement of the scrotum that connected subclinically in a contiguous fashion, as revealed by MMS with CK7 staining.
Surgical removal is the mainstay of treatment for EMPD; however, wide local excision results in high recurrence rates, ranging from 22% to 60%, which may be due to the wide subclinical spread of EMPD outside of empirical surgical margins.8,9 There is growing evidence that MMS results in more favorable patient outcomes, with recurrence rates ranging from 8% to 26% (16% in primary EMPD, 50% in recurrent EMPD), with an overall cure rate of 100%.8,9 Though MMS allows for 100% margin evaluation and more complete tumor removal than wide local excision, recurrence rates for EMPD treated with MMS remain higher than for other cutaneous malignancies, such as basal cell and squamous cell carcinomas (3.5% recurrence), treated with MMS.10 The relatively high recurrence of EMPD after MMS is proposed to be due to the difficulty in recognizing single tumor cells on routine staining.3 Thorough identification of tumor cells is especially important for EMPD lesions, which may show a highly irregular, subclinical growth pattern with finger-like projections that do not stain with hematoxylin & eosin, yet stain with CK7.2 In a retrospective, multi-center, cross-sectional study of patients treated with MMS with CK7 staining, all primary and recurrent EMPD tumors that were excised entirely by MMS and fully evaluated with intraoperative CK7 immunostaining had a composite local recurrence rate of 3.3%, similar to that of basal cell and squamous cell carcinoma treated with MMS.3
In this patient, standard surgical excision of the two separate lesions based on clinical exam alone would likely have resulted in incomplete removal. Our experience adds to a growing body of literature demonstrating that MMS with CK7 staining results in the most complete removal of EMPD and provides for the lowest risk of recurrence.3,9 In addition, it supports the previous finding that the tumor extends far beyond the visible margins in a finger-like contiguous pattern.2 Preoperative scouting biopsies with CK7 staining is strongly advised in planning surgical excision.
EMPD predominantly affects females, though the male:female ratio nears 1:1 amongst Asian patients.3 Involvement of the male genitalia comprises only 14% of EMPD cases; these lesions are usually unilateral and appear on the scrotum, penis, groin, and perianal regions.1 Bilateral involvement of the male genitalia is even more rare, and there have been few case reports of bilateral EMPD involving the genitalia and/or axilla.6,7 Thus, our patient presents a rare case of EMPD with bilateral involvement of the scrotum that connected subclinically in a contiguous fashion, as revealed by MMS with CK7 staining.
Surgical removal is the mainstay of treatment for EMPD; however, wide local excision results in high recurrence rates, ranging from 22% to 60%, which may be due to the wide subclinical spread of EMPD outside of empirical surgical margins.8,9 There is growing evidence that MMS results in more favorable patient outcomes, with recurrence rates ranging from 8% to 26% (16% in primary EMPD, 50% in recurrent EMPD), with an overall cure rate of 100%.8,9 Though MMS allows for 100% margin evaluation and more complete tumor removal than wide local excision, recurrence rates for EMPD treated with MMS remain higher than for other cutaneous malignancies, such as basal cell and squamous cell carcinomas (3.5% recurrence), treated with MMS.10 The relatively high recurrence of EMPD after MMS is proposed to be due to the difficulty in recognizing single tumor cells on routine staining.3 Thorough identification of tumor cells is especially important for EMPD lesions, which may show a highly irregular, subclinical growth pattern with finger-like projections that do not stain with hematoxylin & eosin, yet stain with CK7.2 In a retrospective, multi-center, cross-sectional study of patients treated with MMS with CK7 staining, all primary and recurrent EMPD tumors that were excised entirely by MMS and fully evaluated with intraoperative CK7 immunostaining had a composite local recurrence rate of 3.3%, similar to that of basal cell and squamous cell carcinoma treated with MMS.3
In this patient, standard surgical excision of the two separate lesions based on clinical exam alone would likely have resulted in incomplete removal. Our experience adds to a growing body of literature demonstrating that MMS with CK7 staining results in the most complete removal of EMPD and provides for the lowest risk of recurrence.3,9 In addition, it supports the previous finding that the tumor extends far beyond the visible margins in a finger-like contiguous pattern.2 Preoperative scouting biopsies with CK7 staining is strongly advised in planning surgical excision.
DISCLOSURES
The authors have no relevant conflicts.
REFERENCES
1. Simonds RM, Segal RJ, Sharma A. Extramammary Pagets disease: a review of the literature. Int. J. Dermatol. 2019;58(8):871-879. doi:10.1111/ijd.14328.
2. Hendi A, Perdikis G, Snow JL. Unifocality of extramammary Paget disease. J Am Acad Dermatol. 2008;59:811–3.
3. Damavandy AA, Terushkin V, Zitelli JA, et al. intraoperative immunostaining for cytokeratin-7 during mohs micrographic surgery demonstrates low local recurrence rates in extramammary Paget's disease. Dermatol Surg. 2018 Mar;44(3):354-364.
4. Morris CR, Hurst EA. Extramammary Paget Disease. Dermatol Surg. 2020;46(2):151-158. doi: 10.1097/DSS.0000000000002064.
5. Jones Jr RE, Austin C, Ackerman AB. Extramammary Paget's disease. A critical reexamination. Am J Dermatopathol. 1979;1(2):101-32.
6. Kageyama N, Izumi AK. Bilateral scrotal extramammary Paget’s disease in a Chinese man. Int J Dermatol. 1997;36:695–7.
7. Leelavathi M, Norazirah MN, Nur Amirah AP. Multiple concurrent primary extramammary Paget's disease. Malays Fam Physician. 2016;11(1):18-21.
8. O’connor WJ, Lim KK, Zalla MJ, et al. Comparison of Mohs micrographic surgery and wide excision for extramammary Paget’s disease. Dermatol Surg. 2003;29:723–7.
9. Hendi A, Brodland DG, Zitelli JA. Extramammary Paget’s disease: surgical treatment with Mohs micrographic surgery. J Am Acad Dermatol. 2004;51:767–73.
10. Chren MM, Linos E, Torres JS, et al. Tumor recurrence 5 years after treatment of cutaneous basal cell carcinoma and squamous cell carcinoma. J Invest Dermatol. 2013;133(5):1188–1196.
2. Hendi A, Perdikis G, Snow JL. Unifocality of extramammary Paget disease. J Am Acad Dermatol. 2008;59:811–3.
3. Damavandy AA, Terushkin V, Zitelli JA, et al. intraoperative immunostaining for cytokeratin-7 during mohs micrographic surgery demonstrates low local recurrence rates in extramammary Paget's disease. Dermatol Surg. 2018 Mar;44(3):354-364.
4. Morris CR, Hurst EA. Extramammary Paget Disease. Dermatol Surg. 2020;46(2):151-158. doi: 10.1097/DSS.0000000000002064.
5. Jones Jr RE, Austin C, Ackerman AB. Extramammary Paget's disease. A critical reexamination. Am J Dermatopathol. 1979;1(2):101-32.
6. Kageyama N, Izumi AK. Bilateral scrotal extramammary Paget’s disease in a Chinese man. Int J Dermatol. 1997;36:695–7.
7. Leelavathi M, Norazirah MN, Nur Amirah AP. Multiple concurrent primary extramammary Paget's disease. Malays Fam Physician. 2016;11(1):18-21.
8. O’connor WJ, Lim KK, Zalla MJ, et al. Comparison of Mohs micrographic surgery and wide excision for extramammary Paget’s disease. Dermatol Surg. 2003;29:723–7.
9. Hendi A, Brodland DG, Zitelli JA. Extramammary Paget’s disease: surgical treatment with Mohs micrographic surgery. J Am Acad Dermatol. 2004;51:767–73.
10. Chren MM, Linos E, Torres JS, et al. Tumor recurrence 5 years after treatment of cutaneous basal cell carcinoma and squamous cell carcinoma. J Invest Dermatol. 2013;133(5):1188–1196.
AUTHOR CORRESPONDENCE
Ali Hendi MD mohsmd@yahoo.com
