Clinical and dermoscopic characteristics of extramammary Paget disease: a study of 35 cases

Dear Editor, Extramammary Paget disease (EMPD) is a rare malignant tumour characterized by erythematous scaly patches or plaques occurring in apocrine‐gland‐bearing skin such as the vulva, penis, scrotum, perineum, perianal area and axilla. Because of its nonspecific clinical presentation and low incidence, EMPD can be a challenge to diagnose. Therefore, its misdiagnosis as an inflammatory or infectious skin condition (eczema, psoriasis or candidiasis) is common, and EMPD lesions may worsen before appropriate treatment is initiated.1 2 Early diagnosis and treatment of EMPD are crucial for a favourable prognosis, because a delayed diagnosis can result in a more extensive lesion, dermal invasion or distant metastasis. Although the utility of dermoscopy has been reported for various pigmented and nonpigmented tumours,3 4 5 6 7 the dermoscopic patterns of EMPD have rarely been reported in the literature.8 9 Investigation of clinical and dermoscopic patterns of EMPD could elucidate further characteristics of this rare tumour. For this study patients were recruited from dermatology clinics at two university hospitals in South Korea between 2006 and 2014. We identified 35 patients with histopathologically confirmed EMPD and available clinical and dermoscopic images. For the control group we included 46 EMPD‐mimicking lesions on the genital or perianal area: 22 eczematous dermatitis (ED), 16 fungal infection (FI), seven Bowen disease (BD) and one basal cell carcinoma (BCC). This study was conducted in accordance with the principles of the Declaration of Helsinki, and institutional approval and informed patient consent were obtained. Demographic data were collected and images were acquired using a dermoscope (DermLite II Pro HR or DL3; 3Gen, San Juan Capistrano, CA, U.S.A.). Three board‐certified dermatologists, experienced in dermoscopy, evaluated the clinical and dermoscopic images. Biopsy specimens were re‐examined to determine any correlation between dermoscopic and dermatopathological findings, with the examiner blinded to the dermoscopic images. Statistical analysis between the EMPD and control groups was performed using SPSS version 21 (IBM, Armonk, NY, U.S.A.). We used the χ2‐test or Fisher's exact test to compare proportions. A P‐value < 0·05 was regarded as statistically significant. The mean patient age was 66 years (range 51–80), and 80% (n = 28) of patients were men. The mean duration of disease before definitive diagnosis was 27 months (range 1–84). The mean diameter of the tumours was 57 mm (range 20–200). EMPD lesions occurred in the genital area in 30 patients, in the perianal area in four patients and in the axilla in one patient. All patients were diagnosed with localized primary EMPD; 31 (89%) had intraepithelial EMPD and four (11%) had invasive EMPD. The results of the clinical and dermoscopic analyses of EMPD and EMPD‐mimicking lesions are shown in Table 1 and Figure 1. EMPD was characterized clinically by erythematous patches/plaques, scales, oozing, ulcers, nodules, focal hyperpigmentation and hypopigmentation. Statistical analysis of clinical features indicated that erythema and ulcers were more significantly associated with EMPD than with FI (P = 0·008 and P = 0·039, respectively). Dermoscopically, milky‐red areas, vascular patterns, surface scales, ulcers, pigmentary structures, shiny white lines and white structureless areas were observed in EMPD. Statistical analysis revealed that milky‐red areas were significantly more prevalent in EMPD than in ED (P < 0·001), FI (P < 0·001) or BD (P = 0·048). Dermoscopic vascular structures were more common in EMPD than in ED (P = 0·015) or FI (P < 0·001). Ulcers were more frequent in EMPD than in FI (P = 0·039). The differentiation of BCC from EMPD was straightforward because of distinctive dermoscopic patterns of arborizing vessels and blue‐grey ovoid nests. Frequencies of the clinical and dermoscopic characteristics in extramammary Paget disease (EMPD) and EMPD‐mimicking lesions ED, eczematous dermatitis; FI, fungal infection; BD, Bowen disease. Statistical analysis was conducted using the χ2‐test or Fisher's exact test (for cells with an expected count of less than five). aFeature of statistical significance. Frequencies of the clinical and dermoscopic characteristics in extramammary Paget disease (EMPD) and EMPD‐mimicking lesions ED, eczematous dermatitis; FI, fungal infection; BD, Bowen disease. Statistical analysis was conducted using the χ2‐test or Fisher's exact test (for cells with an expected count of less than five). aFeature of statistical significance. Clinical features (inserts) and dermoscopic patterns of extramammary Paget disease (a–f) and lesions mimicking extramammary Paget disease (g–l). (a) Dotted vessels (black circle) with surface scales (white arrows). (b) Glomerular vessels (black circles) with a milky‐red area (red asterisk). (c) Glomerular vessels (black circles) with shiny white lines (green arrows) and a milky‐red area (red asterisk). (d) Polymorphous vessels (black circle) with a milky‐red area (red asterisk) and an ulcer (yellow arrows). (e) Dotted vessels (black circle) with grey/black dots (black arrows), surface scales (white arrows) and milky‐red area (red asterisk). (f) Dotted vessels (black circle) with surface scales (white arrows), milky‐red area (red asterisk), grey/black dots (black arrows), shiny white lines (green arrows) and white structureless area (white asterisk). (g) Scrotal eczema. Surface scales (white arrows) and an ulcer (yellow arrow). (h) Lichen simplex chronicus. Surface scales (white arrows). (i) Inflammatory linear epidermal naevus. Shiny white lines (green arrows). (j) Tinea cruris. Surface scales (white arrows). (k) Bowen disease. Glomerular vessels (black circle) with grey/black dots (black arrows), surface scales (white arrows) and milky‐red area (red asterisk). (l) Basal cell carcinoma. Arborizing vessels (black circle) with a blue‐grey ovoid nest (red arrow) and surface scales (white arrow). The correlation between dermoscopic and histopathological findings was excellent. Paget cells were observed within the epidermis in all cases. Capillary proliferation in the papillary dermis was seen in 86% of cases (n = 30). Statistical analysis showed that vascular proliferation was correlated with milky‐red areas (P = 0·002) and vascular patterns (P = 0·047). Proliferation and dilatation of capillaries were more pronounced in cases with glomerular vessels than in cases with dotted vessels. Polymorphous vessels were associated with invasion of EMPD (P = 0·019). Dermal melanophages were present in 14 cases (40%). Melanophages were associated with pigmentary structures (P = 0·011) (Fig. S1; see Supporting Information). Different morphological types of vessels on dermoscopy are associated with different skin tumours. Consequently, the recognition of distinctive vascular patterns can be helpful for the diagnosis of skin tumours.10 In our results, dotted vessels (51%) and glomerular vessels (20%) were common types of vascular patterns in EMPD. Previous studies suggest that dotted and glomerular vessels are common findings in BD.4 11 12 We assume that BD and EMPD could have similar vascular patterns because both diseases are intraepidermal malignancies. Although vascular patterns were not helpful in the differentiation between EMPD and BD, they were helpful in differentiating EMPD from benign dermatoses such as ED and FI. Milky‐red areas represent background areas with a milky‐red or red colour. This represents an increased vascular volume and may be a reflection of tumour‐related neoangiogenesis.13 In our study, milky‐red areas were significantly more frequent in EMPD than in ED, FI or BD. Pigmented EMPD is considered very rare; to date, only 11 cases have been described in the literature.14 In our study, focal hyperpigmentation was observed in 26% of the patients with EMPD. Dermoscopically, grey or brown dots and grey structureless areas were observed in 31% of cases. Contrary to previous reports, our study suggests that focal hyperpigmentation is not uncommon in EMPD. Depigmentation can be observed in EMPD.15 In our study, hypopigmented patches were found in 9% of the patients with EMPD. Although local depigmentation may not be specific for EMPD, it can easily be misdiagnosed as postinflammatory hypopigmentation or other hypopigmented skin lesions. Therefore, recognition and careful evaluation of depigmented areas are important because the determination of treatment margins in EMPD can be challenging. This study provides information regarding the clinical and dermoscopic characteristics of EMPD. Increased awareness of these characteristics may improve the diagnostic accuracy of EMPD and enable a prompt biopsy. This will result in the early detection and timely management of this rare tumour. Limitations of our study include enrolment of only Asian patients and lack of various dermatoses in the control group, especially genital psoriasis. Future studies with large samples and different ethnic groups are necessary to validate our findings. Funding sources: none. Conflicts of interest: none declared. Fig S1. Histopathological findings of extramammary Paget disease.