Annals of Surgical Oncology Cite Track
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10.1245/s10434-006-9003-2
Annals of Surgical Oncology 13:1235-1240 (2006)
© 2006 Society of Surgical Oncology
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Original Article

Extramammary Paget’s Disease: Isolated Localization on the Groin—Wide Local Excision With Immediate Reconstruction

Alexander Dionyssopoulos, MD, PhD1,2, Ioanna Mandekou-Lefaki, MD, PhD3, Efstratios Vakirlis, MD1, Ioannis Manoliadis, MD, PhD4, Andreas Nikolis, MD, MSc5 and Eleni Dionyssopoulou, MD6

1 Division of Skin Oncologic Surgery–Plastic Surgery, First Department of Dermatology, Aristotle University of Thessaloniki, Thessaloniki, Greece
2 Department of Plastic Surgery, St.-Luc Hospital, Thessaloniki, Greece
3 Division of Cutaneous Pathology and Oncology, State Clinic, Hospital for Skin and Venereal Diseases, Thessaloniki, Greece
4 Department of Urology, Interbalkan Hospital, Thessaloniki, Greece
5 Division of Plastic Surgery, Notre Dame Hospital, University of Montreal Health Center, Qué bec, PQ, Canada
6 Department of Pathology, Division of Cytology, AHEPA Hospital, Thessaloniki, Greece

Correspondence: Address correspondence and reprint requests to: Alexander Dionyssopoulos, MD, PhD; Division of Skin Oncologic Surgery–Plastic Surgery, First Department of Dermatology, Aristotle University of Thessaloniki, 25, Karolou Diehl Street, 54623, Thessaloniki, Greece; E-mail: alexdion{at}med.auth.gr


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 CASE REPORT
 DISCUSSION
 CONCLUSION
 REFERENCES
 
Background: Extramammary Paget’s disease is a rare cutaneous malignancy, which occurring frequently in the elderly and affecting primarily the genital, perianal, and axillary regions. Unfortunately, surgical and ablative treatment modalities for extramammary Paget’s disease have a high recurrence rate and are often associated with significant morbidity.

Methods: We present a case of a 51-year-old Caucasian man with Paget’s disease of the right groin. The isolated localization of Paget’s disease in the groin is extremely rare. Wide local excision of the tumor is currently the standard of care treatment. All publications found in the literature reporting this rare entity were reviewed for the purpose of further delineating a treatment regimen for this rare pathology.

Results: Six years after surgery, the patient remains disease free with a very acceptable aesthetic result. Currently, only 11 cases of Paget’s disease have been reported with an isolated localization to the groin.

Conclusions: Paget’s disease of the groin has an extremely low incidence. Various treatments are described in the literature, early wide local excision may be the treatment of choice.

Key Words: Extramammary Paget’s disease • Groin • Wide local excision • Reconstruction • Rotation L-shaped cutaneous flap for lozenge gap • Dufourmentel’s LLL flap


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
CASE REPORT
 DISCUSSION
 CONCLUSION
 REFERENCES
 
Extramammary Paget’s disease (EMPD) was first described in 1889 by Crocker,1 who reported a case involving the penis and the scrotum. EMPD is a rare intraepithelial neoplasm that usually affects individuals between 50 and 80 years of age. The common areas of involvement include the vulva, perineum, scrotum, penis, and axilla. Other sites reported in the literature include the anterior chest, external ear canal, and eyelids, as well as the knee region.2 Diagnosis is often missed or delayed given the propensity of this lesion to be mistaken for fungal infection, contact dermatitis, lichen sclerosus, psoriasis, episdermolytic hyperkeratosis, kraurosis vulvae, leukosplakias, mycosis fungoides, pagetoid melanoma, Degos’ acanthoma, histiocytosis, pagetoid basal cell carcinoma, Queyrat’s erythroplasia, and Bowen’s disease.2 The diagnosis is confirmed with a biopsy demonstrating the presence of Paget cells, usually restricted to the epidermis.

The nature of EMPD remains unclear. Although it has been well accepted that mammary Paget’s disease always arises in association with an underlying breast carcinoma, EMPD has proven to be more heterogeneous in its presentation, with a vast majority of cases arising in apocrine gland–bearing tissue.3–5 Pierie et al.6 report a 42% rate of secondary malignancy in patients with EMPD. A significant number of groin EMPD do not arise in association with an underlying malignancy, and new findings support the theory that primary EMPD arises multifocally from multipotential epidermal cells.4

Standard therapy is local excision with wide margins of 2 cm to reduce the risk of recurrence. Recurrence rates have been reported between 30% and 70%,7 with the highest rates reported in the perianal regions.4

Paget’s disease of the groin is a very infrequent, rare, and often diffcult-to-diagnose condition. In an extensive review of the literature, only 11 cases have been identified, including this current report.


   CASE REPORT
TOP
 ABSTRACT
 INTRODUCTION
 CASE REPORT
DISCUSSION
 CONCLUSION
 REFERENCES
 
A 51-year-old Caucasian man presented to our department with a pruritic skin lesion of the right groin. Clinically the lesion was characterized by an erythematosquamous eczematoid plaque, 3.5 x 3 cm, with a sharp demarcation between healthy and involved skin (Fig. 1Go). The patient reported a 2-year history of pruritus of the right groin. Over this time period, the patient received a variety of topical treatments, including corticosteroids and emollient creams. The patient had no personal or family history of malignancy.


Figure 1
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  		FIG. 1. Erythematosquamous eczematoid plaque of the right groin (extramammary Paget’s disease).

 
The physical examination revealed no evidence of lymphadenopathy or other suspicious skin lesions. After open biopsy, the pathologic analysis of the lesion demonstrated an epidermis that was extensively infiltrated by Paget cells. Hematological and biochemical examinations of blood and urine samples were within normal limits. The results of radiological investigations including chest x-ray and computed tomography scans of the chest, abdomen, and pelvis were normal. The gastrointestinal tract examination results were normal, as were those of fiberoptic colonoscopy and barium enemas. The genitourinary tract was without any significant findings, with a normal cystoscopic evaluation. The serum prostate-specific antigen level, the serum carcinoembryonic antigen level, and the alfa fetoprotein level were also within the normal range.

After this thorough investigation for an underlying malignancy, a decision was undertaken to perform a wide local excision of the tumor with an important margin of 2 cm of the surrounding skin, including the superficial fascia. Negative frozen-section margins of the operative specimen confirmed an adequate resection. The defect measured 7.5 x 7 cm. Immediate reconstruction was performed by using a rotation L-shaped cutaneous flap for lozenge gap (or Dufourmentel’s LLL flap; Fig. 2Go, 3Go). No lymph node dissection was performed given the negative clinical and radiological evaluations. The wounds healed uneventfully, but the patient developed a persistent postoperative edema of the flap that lasted approximately 3 months. This edema resolved without any further sequelae. At the 1-year follow-up, the patient presented with a hypertrophic scar in one of the three branches of the L-shaped flap for lozenge gap without any distortion of the skin or development of any functional issues (Fig. 4Go). Six years later, the patient remains disease free with a very acceptable aesthetic result (Fig. 5Go).


Figure 2
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  		FIG. 2. Dufourmentel’s L-shaped cutaneous flap for lozenge gap.

 

Figure 3
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  		FIG. 3. The result at the end of the operation.

 

Figure 4
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  		FIG. 4. One-year postoperative result: a hypertophic scar.

 

Figure 5
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  		FIG. 5. Six-year postoperative result.

 
Final histopathologic evaluations demonstrated an epidermis that was hyperplastic and diffusely infiltrated by atypical neoplastic cells (Fig. 6Go). Tumor cells were present as solitary units and in nests at all levels of the epidermis, including the basal layer. The cells were large with abundant pink-staining cytoplasm and vesicular nuclei. Mitotic figures were present. Immunoperoxidase staining with carcino-embryonic antigen showed positive brown deposits within the neoplastic cell. Therefore, the histopathologic examination confirmed the diagnosis of EMPD with tumor-free surgical margins.


Figure 6
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  		FIG. 6. The epidermis was hyperplastic and diffusely infiltrated by atypical neoplastic cells (original magnification, 4 x 100).

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 CASE REPORT
 DISCUSSION
CONCLUSION
 REFERENCES
 
The exclusive localization of EMPD in the groin is an extremely rare malignancy. Discrepancy arises when the anatomical description of "groin-EMPD" includes the genital organs. As such, for the purpose of this manuscript, EMPD of the groin is limited to the region comprised of the inguinal canal and femoral triangle (defined superiorly by the inguinal ligament, medially by the medial border of the long adductor muscle, and laterally by the medial border of the serratus muscle). Only 10 cases3,4,8–12 have been previously described in the literature. Other reported cases have demonstrated a more extensive localization (not only in the groin), such as in the pubic area and axilla,13 in the female genitalia,7 and in the scrotum and penis.3,11,14,15 The rarity of this disease has precluded large prospective studies16 for developing a treatment algorithm. Case series reporting on patients with groin lesions often include patients with isolated (groin involved solely) or extended (genital and groin involvement) involvement in the same group.3,14

Of eleven reported patients with exclusive localization of EMPD to the groin ten were male 3,4,8–12 (we could not find the sex of one patient reported by Fu et al.9 because the article was in Chinese). It seems that the isolated localization of Paget’s disease in the groin appears only in men, and occurs in patients older than 50 years. The age of the reported cases ranged from 50 to 81 years (mean, 68.0 years). No relationship has been reported between the age of the patients and the recurrence rate or the survival rate.

The most common presenting symptom was pruritus; other complaints included irritation, a sensation of burning tenderness, pain, bleeding, and edema.5 Clinically EMPD of the groin is manifested as a nonhealing eczematous lesion.3 Since various types of dermatoses may mimic EMPD, the disease may be long-standing before a diagnosis is made.4

Several subtypes of EMPD have been suggested, including (1) primary limited cutaneous disease, (2) primary skin disease with secondary contiguous or lymphatic metastases, (3) secondary EMPD arising from underlying carcinoma, and (4) EMPD in association with a variety of visceral malignancies. Rare cases of direct epidermal invasion from urothelial and anorectal carcinomas have been reported as well.4

Primary EMPD is derived from the epidermis,17 as was the current case. Secondary EMPD denotes an epidermotropism wherein intraepidermal invasion or metastasis occurs from visceral malignancies or urogenital organs. Generally EMPD is characterized histologically by intraepidermal proliferation of unique tumor cells named Paget cells.17 Strong cytoplasmic staining for periodic acid–Schiff, mucicarmine, and Alcian blue, indicating the presence of mucopolysaccharides, characterizes Paget cells of EMPD. EMPD also stains with a) carcino-embryonic antigen positive (in 84% to 100% of cases3), b) epithelial membrane antigens (positive in 90–100%), c) aldehyde fuchsin, d) colloidal iron, e) Gross Cystic Disease Fluid Protein -15, f) Cam 5.2 and g) cytokeratins 7 and 8. Immunohistochemical stains, such as S-100 protein (sensitive for melanoma; negative for EMPD) and prekeratin (sensitive for Bowen’s disease), can provide an accurate diagnosis.4

Once the diagnosis is established, the patients must be risk stratified. First, a thorough search for a contiguous, underlying, or distant malignancy must be undertaken. The most common EMPD-related cancers are rectal, genitourinary, breast, hepatic, pancreatic, and adnexal (e.g., porocarcinoma) carcinomas.4 In the 11 patients with EMPD of the groin, 9 (90.9%) had no prior associated cancer, and 1 (9.1%) had had adenocarcinoma of the bladder.8 Chanda14 supported an association between the anatomical site of EMPD and the location of the internal malignancy. It seems that in EMPD of the groin, it is rare to find an underlying adenocarcinoma.

When an underlying malignancy is present, up to 50% of lesions have already metastasized, thereby limiting the average survival to 3 years.4 A 5-year survival rate was 100% in the carcinoma-in-situ or microinvasion to the papillary dermis group in Tsu-tsumida and colleagues’ report.18

Surgical treatment is the first priority for successful management of EMPD. A wide local excision with a minimum of 1–2 cm normal skin margins, including superficial or deep fascia, is adequate for treatment for EMPD.3,18 Park et al. 19 have demonstrated that curative treatment may include wide local excision with negative frozen section margins, leading to no recurrence for a period of 2.5 years following surgery. Furthermore, in the same study, the authors report on the difficulty of reporting outcomes when the pathology is rare and treatment regiments are multiple as their own review of the literature of penile and scrotal EMPD demonstrates a recurrence rate between 67–100%. Yang et al further support the notion that frozen section analysis is required as 35% of patients with 1–2 cm gross margins developed a recurrrence.20 Although neither study evaluated EMPD of the groin alone, the proximity of the two regions complementary lymphatic drainage patterns and likelihood of local spread as the diagnosis is often delayed leads the authors to believe that frozen section analysis should become the standard of care in this pathology. If the patient has evidence of lymph node involvement clinically or histopathologically, inguinal lymph node dissection is an adjunct to wide local excision.18 The critical factor in EMPD is not the radial spread of tumor, but the local vertical invasion.18 The level of tumor invasion has a significant correlation with disease prognosis.

Our patient’s lesion demonstrated a depth commensurate with carcinoma-in-situ without evidence of lymph node involvement. In the case of carcinoma-in-situ or microinvasion to the papillary dermis without clinical or pathologic lymph node metastasis, lymph node dissection is not required.17

There is no consensus on the gold standard treatment for EMPD. The ideal therapy should offer both minimal tissue destruction and low recurrence rates. Wide local excision with 1–2 cm margins or Mohs micrographic surgery is commonly used. Patients who were found to have an associated malignancy require further surgical excision and adjuvant chemotherapy (carboplatin, 5-fluorouracil, vincristine, and so on) and/or radiotherapy appropriate for their carcinoma. For those with limited cutaneous disease, many treatment options have been suggested. Mohs surgery, curettage, carbon dioxide laser ablation, photodynamic therapy, topical 5-fluorouracil in a 1% preparation, topical bleomycin, radiotherapy, and imiquimod have been used as monotherapy or a combination therapy, but all appear to yield reasonable recurrence rates.

We believe that surgery with wide local excision is the treatment of choice. Guidelines for the surgical treatment of EMPD of the groin are diffcult to establish because of the rarity of the lesion and the limited experience of each author. Every author treated one or two cases, and the number of the patients with this malignancy is limited too, which mean that it is not possible to conduct a study with large number of patients with limited EMPD comparing the different treatment modalities and with a long-term follow-up.

Following wide local excision, it is often necessary to reconstruct the resulting defect with either local flaps, regional flaps, or skin grafting when indicated for closure.16 The L-shaped flap for lozenge gap described by Dufourmentel 21 in 1962 is frequently used in daily practice for coverage of deficits after excision of cancerous lesions.22 This type of rotation flap minimizes skin distortion and the occurrence of dog-ears after reconstruction.21,22

The theories of Coit et al.23 or Tonuchi et al.24 could explain the appearance of persistent postoperative edema, the only complication in present case. According to the first theory,23 skin flaps in groin dissections are relatively thin, and it is likely that the underlying mechanism of edema is primarily ischemic. The second theory24 attributes the edema to the presence of transected lymphatics.

It has not been established whether more aggressive surgery is likely to be more effective than wide margin excision (with negative frozen section analysis) in preventing recurrence. Zollo and Zeitouni5 and Coldiron et al.7 reported that recurrence rates were lower in patients treated with Mohs micrographic surgery than wide local excision. There is a paucity of reports on recurrence rates in isolated EMPD of the groin. We have not found any relationship, in the bibliography, between the different kinds of treatments and the recurrence of tumor. Likewise, there is no long-term follow-up for the patients with EMPD of the groin, because most patients are lost to follow-up 2 to 4 months after surgery.4,8,10,12


   CONCLUSION
TOP
 ABSTRACT
 INTRODUCTION
 CASE REPORT
 DISCUSSION
 CONCLUSION
REFERENCES
 
Paget’s disease of the groin has an extremely low incidence and occurs primary in males. Its presence as an isolated disease process suggests a different origin rather than a simple extension of aberrant cells from the genital area. EMPD as a multifocal malignant transformation of pluripotent germinative epidermal cells has been previously reported.17

We believe that early wide local excision with microscopically free margins and immediate reconstruction is a valid treatment choice. The low incidence and prevalence of this disease entity make the possibility of a future prospective randomized trial diffcult in truly evaluating the most appropriate management of this pathology. Long-term follow-up of these patients will be essential to detect any subsequent or coinciding malignancies or metastatic disease.


   ACKNOWLEDGMENTS
 
The authors thank Professor A. Mylonas, MD, Ph.D for gastrointestinal investigation and K. Syllas, MD, Pathologist for the microphotograph.

Received for publication October 19, 2005. Accepted for publication January 20, 2006.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 CASE REPORT
 DISCUSSION
 CONCLUSION
 REFERENCES
 

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  9. Fu M, Gao S, Wang P. 19 cases of Paget’s disease. Zhonghua Wai Ke Za Zhi 1999; 37:429–31.[Medline]
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  13. Van Hamme C, Marot L, Dachelet C, Dumont M, Salamon E, Lachapelle JM. Paget’s extramammary disease of the axillae and perineum. Ann Dermatol Venereol 2002; 129:717–9.[Medline]
  14. Chanda JJ. Extramammary Paget’s disease. Prognosis and relationship to internal malignancy. J Am Acad Dermatol 1985; 13:1009–14.[Medline]
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  16. Marchesa P, Fazio VW, Oliart S, Goldblum JR, Lavery IC, Milsom JW. Long-term outcome of patients with perianal Paget’s disease. Ann Surg Oncol 1997; 4:475–80.[Abstract]
  17. Chandawarkar RY, Ricchuiti D, Amjad I, Marsico RE, Wells MD. Extramammary Paget’s disease of the perineum: avoiding pitfalls in diagnosis and management. Can J Plast Surg 2003; 11:205–8.
  18. 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.[CrossRef][Medline]
  19. Park S, Grossfeld GD, McAninch JW, Santucci R. Extramammary Paget’s disease of the penis and scrotum: excision, reconstruction and evaluation of occult malignancy. J Urol 2001; 166(6):2112–2116; discussion 2117.[CrossRef][Medline]
  20. Yang WJ, Kim DS, Im YJ, Cho KS, Rha KH, Cho NH, Choi YD. Extramammary Paget’s disease of penis and scrotum. Urology 2005; 65(5):972–975.[CrossRef][Medline]
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  22. Servant JM, Dufourmentel CL. (1984) Treatment of facial lesions. In: Goldwyn, eds. The Unfavorable Result in Plastic Surgery. Boston: Brown & Co, 1(19):348–50.
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