November 2023 Case

A female patient in her 70s presented to her gynecologist with a primary complaint of itching in her vulvar area for approximately 2 years. She denied any vaginal bleeding, pain, or change in bowel or bladder habits. On physical exam, there were two velvety patches seen on the right vulva. The patient underwent excisional biopsies.

Primary Paget disease of the vulva

Primary Paget disease of the vulva is a rare in situ adenocarcinoma that arises in the labium minus or majus and most commonly affects postmenopausal women. Patients may present with itching or burning that has been present for years before undergoing a biopsy. On physical examination, the vulvar lesion is raised and may look erythematous or eczematous and can extend to the vagina and cervix. On microscopy, the tumor cells may be singly dispersed or arranged in a nested pattern. The nuclei are large and vesicular with prominent nucleoli. There is abundant pale, eosinophilic cytoplasm and intracytoplasmic mucin can be seen. The tumor is most commonly positive for CK7, GATA3, CEA, and GCDFP-15 and negative for PAX8, SOX10, and HPV ISH. This panel is helpful when differentiating it from other entities. However, there are reports of p16 and PAX8 positivity in Paget disease of the vulva, so careful interpretation of morphologic features and ancillary studies is important.

In some cases, there may be melanin pigment throughout the epidermis and dermis, which gives rise to a melanoma differential. In this situation, SOX10 and Melan-A will stain the background melanocytes; however, the Paget tumor cells will be negative. Other differentials include vulvar intraepithelial neoplasia, HPV-independent (dVIN), high-grade squamous intraepithelial lesion (HSIL) with pagetoid spread, and secondary Paget disease. dVIN can microscopically look like Paget with the nested, pale tumor cells, as well as mucinous differentiation, however, it will be negative for CK7 and GCDFP-15. HSIL can mimic Paget with mucinous areas, melanin pigment, and pagetoid spread too. To best differentiate HSIL from Paget, high-risk HPV ISH is useful, as it will be positive in HSIL and negative in Paget. The last differential is secondary Paget, which is much less common and originates in another location before metastasizing, such as the rectum, cervix, or bladder. These would stain for CDX2, CK20, or uroplakin-3, respectively.

The management for primary Paget disease of the vulva is local excision; however, these often recur due to incomplete excision because they can extend further than the clinical impression. When they do recur, they typically stay within the epidermis. However, careful examination of the dermis and deeper levels are necessary to rule out an invasive component. Recently, it has been discussed that patients with ERBB2 amplified tumors may benefit from anti-HER-2/neu therapy. A study of 47 cases, which included multiple sites such as the vulva, perineum, scrotum, and axilla (majority vulva), showed that nearly a third of patients were positive and could be candidates for targeted therapy; however, this finding was also suggestive of more aggressive behavior.

Primary Paget disease of the vulva is rare but is important to keep in mind due to other entities' ability to mimic it morphologically.