Invasive extramammary Paget’s disease of the scrotum: A case report

Abstract

Extramammary Paget’s disease is a rare cutaneous malignancy that typically presents as carcinoma in situ, and instances of invasive extramammary Paget’s disease are exceptionally rare. Herein, we describe a rare case of invasive extramammary Paget’s disease of the scrotum. A 91-year-old male presented with an over 10-year history of a granulomatous rash with serous discharge, refractory to various topical therapies and weekly wound care. Physical examination revealed a well-demarcated, erythematous, mamillated, eroded plaque with arcuate borders involving the left inguinal crease and scrotum. A punch biopsy showed intra-epidermal and invasive carcinoma with focal pagetoid spread and intracytoplasmic mucin. The favored diagnosis was primary, invasive extramammary Paget’s disease. The patient underwent a wide local excision and routine imaging surveillance and remains recurrence-free at 1-year follow-up. Given that extramammary Paget’s disease remains commonly misdiagnosed, leading to delays in treatment, dermatologists should be aware of this diagnosis, particularly for elderly patients presenting with non-specific genital lesions recalcitrant to routine treatment.

Introduction

Extramammary Paget’s disease (EMPD) is a rare cutaneous malignancy that generally affects areas of apocrine sweat glands of older individuals with peak incidence at 65 years old.1 EMPD can be classified as primary, where the lesion is cutaneous in origin, or secondary, developing from a non-cutaneous malignancy.2 Due to its typically indolent course of growth, EMPD commonly presents as carcinoma in situ, and instances of invasive EMPD are rare.3 Herein, we present a case of primary invasive EMPD of the scrotum in an elderly patient, successfully treated with wide local excision.

Case report

A 92-year-old male was referred to the Dermatology clinic for a 10-week history of asymptomatic “granulomatous rash in groin.” Despite various topical therapies, including antifungal agents and corticosteroids as well as weekly wound care, the lesion remained persistent and progressed with increasing nodularity and pain with serous discharge. The patient was otherwise well and endorsed no systemic or constitutional symptoms. Past medical history was significant for non-melanoma skin cancer of the head and neck, but otherwise, no previous history of malignancy.

Skin examination revealed a well-demarcated, erythematous, mamillated, eroded plaque with arcuate borders and nodules involving the left inguinal crease and scrotum (Figure 1). There was no palpable cervical, inguinal, or axillary lymphadenopathy. Two punch biopsies were performed for hematoxylin and eosin staining.

Pathology showed intra-epidermal and invasive carcinoma with focal pagetoid spread and intracytoplas-mic mucin suggestive of EMPD. Subsequent malignancy workup, including an ultrasound of the scrotum, cystoscopy, colonoscopy, and computed tomography of the chest, abdomen, and pelvis, was negative.

Based on the clinical and histopathological findings, the favored diagnosis was primary, invasive EMPD, and the patient was referred to general surgery. Given his advanced age and refusal of invasive therapies, a sentinel lymph node biopsy (SLNB) was not indicated, and a PET scan was offered but the patient declined. He underwent a wide local excision with a VAC dressing placed on the surgical site postoperatively while awaiting surgical pathology for margin assessment. Final negative margins were confirmed circumferentially, with the closest margin <0.1 mm and the remaining margins clear by at least 5 mm. The patient underwent re-excision of the closest margin with subsequent reconstruction. He has undergone routine imaging surveillance and remains recurrence-free at 1-year follow-up.

Discussion

EMPD is a rare dermatologic condition that characteristically presents in apocrine-rich areas, such as the vulva, scrotum, perineum, or penis, as an asymmetrical plaque that can become ulcerated or erosive. The pathogenesis of EMPD is not well understood but has recently been hypothesized to be associated with Toker cells which are found in mammary and vulvar tissue.4,5 Clinically, the classic appearance of noninvasive EMPD is patches or plaques with “strawberries and cream” appearance, with scattered areas of red erosion and white scale,6 while more nodular or indurated areas may indicate invasive EMPD3 and is associated with symptoms such as pruritis, pain, or burning. Typically, EMPD lesions can be nonspecific and are commonly misdiagnosed as inflammatory or infectious dermatoses such as inverse psoriasis or intertrigo.5

Biopsy can aid in the diagnosis of EMPD, with histology showing Paget cells, which are indicated by ample pale cytoplasm and large pleomorphic nuclei. The presence of Paget cells can be confirmed by staining with colloidal iron, periodic acid-Schiff (PAS), Alcian blue, or mucicarmine. Paget cells also stain positive for low molecular weight cytokeratins, PAS, and gross cystic disease fluid protein-15.7

EMPD can be classified as primary or secondary; primary EMPD is of cutaneous origin, whereas secondary EMPD is associated with metastases or direct extension of an adenocarcinoma from another site, such as the rectum, bladder, or urethra. Extensive workup should be conducted when diagnosed with EMPD to rule out an underlying malignancy, such as in the case of secondary EMPD. Workup can include abdominal ultrasound/computed tomography, cervicovaginal smear, cystoscopy, and blood work, including serum tumor markers such as CA19-9 and CEA.8

Due to the typically indolent growth pattern, the majority of EMPD cases present as carcinoma in situ. However, in rare cases, EMPD can become invasive, with Paget cells invading into the dermis, leading to regional and distant metastases. Invasive and metastatic EMPD is associated with worse outcomes and decreased overall survival, as current treatment options, including chemotherapy, have limited efficacy.2 Although invasive EMPD may be associated with lymph node extension, the role of SLNB is not well established, as current evidence is based on case reports or small sample-sized retrospective studies. SLNB may be useful in gathering additional prognostic information, but there is currently limited data that support SLNB influencing patient prognosis, and is not recommended at this time.2,3 In addition, PET scan may be an acceptable alternative to SLNB in certain patient populations for staging and prognosis.9

The gold standard of treatment of invasive EMPD is surgery, either wide local excision or Mohs micrographic surgery, depending on the size and location of the lesion. Recurrence occurs at a relatively high rate due to ill-defined clinical margins (30%–60%)3 and Mohs surgery has lower recurrence rates compared to wide local excision. For patients who are not surgical candidates, treatment options include radiotherapy (either alone or as an adjuvant), imiquimod, or carbon dioxide laser. Due to high recurrence rates and potential for metastasis, it is important to continue to monitor patients clinically and consider surveillance imaging for recurrence, metastases, or development of underlying malignancy for at least 5 years after diagnosis.10

In summary, although EMPD typically remains intraepidermal, in rare cases, EMPD can become invasive, leading to significant morbidity and mortality. Here, we report a rare case of invasive EMPD of the scrotum successfully treated with wide local excision. Given that EMPD remains commonly misdiagnosed leading to delays in treatment, clinicians should be aware of this diagnosis, particularly for elderly patients presenting with nonspecific genital lesions recalcitrant to routine treatment. Clinicians should also recognize the potential of EMPD to become invasive and consider expedited workup and treatment as necessary.

Consent for publication

The patient provided written permission for publication of this case report and associated images.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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