Dear Editor:
An 85-year-old woman presented with an erythematous scaly patch on her left cheek (Fig. 1A). The lesion occurred 5 years previously. The patient had no specific medical history. Biopsy of the specimen showed parakeratosis with crust formation in the horny layer, full epidermal thickness atypical keratinocytes, nests of pagetoid cells with vacuolated, pale cytoplasm, and mitotic figures in the epidermis (Fig. 1B, C). The atypical cells were positive for CK7 and negative for HER2 (CerbB2), HMB-45, and Melan-A (Fig. 1D). Given the biopsy reports of EMPD, additional immunohistochemical stains were performed. The neoplastic cells were positive for p63 and negative for CK20 and Mucicarmine (Fig. 1E, F). On the basis of these findings, we established the diagnosis of pagetoid Bowen's disease. The patient was treated with cryotherapy once a month for 6 months and the lesion showed clear improvement.
Fig. 1. (A) Clinical picture of the case. Erythematous scaly patch on the cheek. (B~F) Histological picture of the case. (B) Parakeratosis with crust formation in the horny layer and cellular infiltration in the dermis (H&E, ×100). (C) Nests of pagetoid cells with a pale eosinophilic cytoplasm and mitotic figure (H&E, ×400). (D) Tumor cells in the epidermis showed focal positivity for CK7 (CK7, ×200). (E) Both normal keratinocytes and tumor cells showed positivity for p63 (p63, ×200). (F) Immunohistochemical stain was negative for Mucicarmine (Mucicarmine, ×200). We received the patient's consent form about publishing all photographic materials.
About 5% of Bowen's disease cases show a pagetoid growth pattern with atypical keratinocytes arranged singly and in nests1. Pagetoid Bowen's disease is an intraepidermal pagetoid neoplasm that is histologically characterized by the pagetoid spreading of atypical cells with vacuolated, pale cytoplasm in epidermis1. The most common diagnoses of intraepidermal pagetoid neoplasms are pagetoid Bowen's disease, extramammary Paget's disease (EMPD), and melanoma in situ1,2. There were some previous reports for differentiating these diseases using histological characteristics, including types of corneum, presence of crushed basal keratinocytes, presence of atypical clear cells in epidermis, presence of large cells with pale cytoplasm, and level of pagetoid atypical cells within the epidermis, as visualized with routine hematoxylin and eosin-stained sections1. Although these criteria reduce reliance on immunohistochemical stainings, immunohistochemistry is required for clear distinction in some cases. CK7 has been used for differentiating EMPD from pagetoid Bowen's disease because CK7 is absent in normal and malignant keratinocytes and expressed in secretory cells of eccrine or apocrine glands. However, some previous reports of pagetoid Bowen's disease showed CK7 positivity3. Our case also expressed focal CK7, resulting in the need for additional immunohistochemical analysis for clear distinction (Table 1). The exact reason behind CK7 expression in pagetoid Bowen's disease is still unclear; however previous studies have suggested that bidirectional stem cell differentiation to squamous or secretory cells is the main contributor4. Other studies attribute the heterogeneity of CK7 expression to phenotypic changes of squamous cell carcinoma tumor cells toward Toker's cells-like phenotype4. In our case, some tumor cells showed positivity for CK7, and not for p63 staining (Fig. 1D, E). If on one way, this may be a consequence of a technical issue of tissue processing, on the other, our results support the bidirectional stem cell differentiation hypothesis. Some studies showed the usefulness of newer immunohistochemical stains, including cystic fibrosis transmembrane conductance regulator, monoclonal antibody Ber-EP4, and p63, for distinction between pagetoid Bowen's disease and EMPD3,5. Our case also showed a positive p63 stain. To our knowledge, reports of CK7 positive pagetoid Bowen's disease are rare in Korea. Herein, we report a case of pagetoid Bowen's disease exhibiting focal staining with CK7, this unusual immunophenotype leading to misdiagnosis as EMPD.
Table 1. Summary of immunohistochemical stains.
| Variable | This case | Bowen's disease | EMPD | Malignant melanoma |
|---|---|---|---|---|
| CK7 | Focal+ | +/− | + | − |
| Melan-A | − | − | − | + |
| HMB-45 | − | − | − | + |
| C-erbB2 (HER2) | − | − | +/− | − |
| p63 | + | + | − | − |
| CK20 | − | − | +/−† | − |
| Mucicarmine | − | − | + | − |
EMPD: extramammary Paget's disease. †Secondary EMPD.
Footnotes
CONFLICTS OF INTEREST: The authors have nothing to disclose.
FUNDING SOURCE: None.
References
- 1.Elbendary A, Xue R, Valdebran M, Torres KMT, Parikh K, Elattar I, et al. Diagnostic criteria in intraepithelial pagetoid neoplasms: a histopathologic study and evaluation of select features in Paget disease, Bowen disease, and melanoma in situ. Am J Dermatopathol. 2017;39:419–427. doi: 10.1097/DAD.0000000000000704. [DOI] [PubMed] [Google Scholar]
- 2.Holder JE, Colloby PS, Fletcher A, Camp RD. Amelanotic superficial spreading malignant melanoma mimicking Bowen’s disease. Br J Dermatol. 1996;134:519–521. [PubMed] [Google Scholar]
- 3.Lee J, Kim M, Moon J, Yoon HS, Cho S, Park HS. Pagetoid Bowen disease initially misdiagnosed as ectopic extramammary Paget’s disease. Ann Dermatol. 2018;30:218–221. doi: 10.5021/ad.2018.30.2.218. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Misago N, Toda S, Narisawa Y. Heterogeneity of cytokeratin 7 expression in pagetoid Bowen’s disease. J Cutan Pathol. 2012;39:724–726. doi: 10.1111/j.1600-0560.2012.01869.x. [DOI] [PubMed] [Google Scholar]
- 5.Bains R, Gleason BC, Thomas AB, Victor TA, Cibull TL. Cystic fibrosis transmembrane conductance regulator is helpful in the distinction of extra-mammary Paget’s disease from squamous cell carcinoma in situ (Bowen’s disease) J Cutan Pathol. 2011;38:581–584. doi: 10.1111/j.1600-0560.2011.01685.x. [DOI] [PubMed] [Google Scholar]