Vulval Paget’s disease (VPD) is named after Sir James Paget, an English surgeon and pathologist, working in the nineteenth century. He wrote an article describing a series of 15 women with an eczematous nipple ulceration with an underlying adenocarcinoma [1]. Several years later, in 1889, the English dermatologist Radcliffe Crocker published a case of a comparable lesion on the male genitalia [2]. This was followed by a report of Paget’s disease of the vulva in 1901 by the French dermatologist Dubreuilh [3]. In this article, Dubreuilh describes the histological changes in VPD, but the pathognomonic Paget cell recognised today was not yet identified as such. These Paget cells can be seen in the epidermis in cases of non‐invasive VPD, but if seen in the dermis, this indicates invasive disease.

Epidemiology

The exact incidence of VPD is unknown. One epidemiologic study about the incidence of extramammary Paget disease, including all locations of extramammary Paget disease which were reported with the Netherlands Cancer Registry between 1989 and 2001, showed that the reported incidence rate of 0.11 per 100,000 person‐years seemed to be an overestimate [4].

Recently, one Dutch study was published using 15 years of data of the Dutch national pathology database [5]. It reported 199 patients with a first diagnosis of VPD between 2000 and 2015: 164 were non‐invasive and 35 micro‐invasive in a country with approximately 17 million inhabitants.

Pathophysiology

The origin of Paget cells has been a topic of debate since their discovery. In 1949, Foraker and Miller described the two main views on the origin of Paget cells, which were that they may either be an altered epidermal cell or a cancerous cell originating from mammary glands [6]. In the last 50 years, several attempts have been made to discover the origin of Paget cells. From the beginning, there are three main theories on the development of VPD. First, the epidermotropic theory, which suggests Paget cells arise in the basal layer or skin appendages and spread through the epidermis. Second, the transformation theory, in which keratinocytes transform into abnormal Paget cells. Lastly, the Toker cell theory, which suggests that precursor Toker cells arise and transform into Paget cells [7–9].

The epidermotropic theory seems to be the most established theory, since it is supported by several studies. Fetherston and Friedrich described in 1972 how Paget cells do not seem to be malignant themselves, but an adjacent carcinoma may be present. They also suggested how Paget cells originate from the stem cells of the basal layer and/or skin appendages [10]. Several studies confirm the skin appendages as the source of Paget cells [11, 12], while others suggest that the anogenital mammary‐like‐glands are the site where Paget cells arise [13–15].

Between 2000 and 2005, Brown and Wilkinson published several studies on secondary VPD [16–18]. These studies distinguish cutaneous VPD as an intraepidermal adenocarcinoma from extracutaneous or secondary VPD. Secondary VPD originates from an internal neoplasm with epidermal metastasis or direct extension. These internal neoplasms are most often anal or rectal adenocarcinomas or urothelial transitional cell carcinomas.

Classification

The nipple lesion with underlying breast cancer, as first described by Sir James Paget, is now known as mammary Paget disease. Comparable skin lesions elsewhere on the human body are called extramammary Paget disease (EMPD). EMPD is generally seen in the hair‐bearing skin, most commonly the anogenital skin in males and females [19]. However, EMPD has also been reported in other regions, such as the back [20], cheek [21], and chest [22]. These locations have led to the suggestion that EMPD may arise along the so‐called milk lines.

VPD was classified by Wilkinson and Brown in 2002 according to its origin – as primary cutaneous or secondary extracutaneous [17]. In that classification, primary cutaneous VPD is further subdivided into non‐invasive, invasive, or related to vulval adenocarcinoma. In the last decade, several cases of micro‐invasive VPD have been reported as well. Also, the distinction between invasive VPD and vulvar adenocarcinoma has faded and is not so clear‐cut. Based on recent literature, a useful classification in shown in Table 42.1.

Histological features

VPD is characterised by the presence of the so‐called Paget cells. These Paget cells are large, vacuolated, oval or polyhedral cells with large nuclei and a pale cytoplasm [23]. They can be found as single cells or in small clusters throughout the epidermis (Figure 42.1). They are also often seen around the skin adnexa including the hair follicles and the eccrine and apocrine glands [12]. Paget cells are known to be widespread throughout the epidermis, including sites without any visible skin lesion [24]. Reactive changes are also seen, such as acanthosis, papillomatosis, and hyperkeratosis. If Paget cells infiltrate the dermis or submucosa, then it is invasive.

Immunohistochemistry can help to distinguish primary and secondary VPD. In primary VPD, Paget cells stain positive for CK7 and negative for CK20, whereas in secondary VPD, they are negative for CK7 but positive for CK20 [23]. Other markers such as Uroplakin‐III can help in determining a urological origin for secondary VPD, or CDX2 for an intestinal origin [25]. Several other stains have been reported, but have not proved to be a perfect in diagnosing VPD. Recently, further attempts have been made to investigate the tumour microenvironment of VPD, but this has not led to implications for clinical practice [26–28].

Clinical features

VPD is most commonly seen in elderly Caucasian women. The main symptoms reported by patients are pruritus and/or soreness [29, 30], although 5–15% of patients report no symptoms at time of diagnosis [31, 32].

VPD presents as an erythematous plaque. Lesions can be small and located at the hair‐bearing skin of the vulva, or be extensive involving the mons pubis, labia majora, perineum, groins, and buttocks. The typical erosions and maceration have been likened to cake icing or strawberries and cream appearance (Figures 42.2–42.4). However, various other presentations have been described, such as ulceration, mass lesions, and pigmented lesions [30].

Due to the various clinical presentations and its rarity, there is often a significant delay in making the diagnosis. This may be added to by patient delay in seeking advice especially if there are no symptoms. Patients often report symptoms for several weeks to years, before being diagnosed with VPD [33].

Differential diagnosis

The clinical differential diagnosis of VPD consists of other erythematous inflammatory conditions such as eczema, vulvovaginal candidiasis, psoriasis, lichen simplex chronicus, lichen planus, differentiated vulvar intraepithelial neoplasia, and high‐grade squamous intraepithelial lesions. Histologically the differential diagnosis includes histiocytosis, melanoma in situ, pagetoid spitz naevus, sebaceous carcinoma, clear cell papulosis, eccrine porocarcinoma, cutaneous T‐cell lymphoma, and Langerhans cell microabscesses [23, 34–36].

Complications

Stay updated, free articles. Join our Telegram channel

Join