Differentiating pagetoid Bowen disease from Paget disease on the nipple‐areola complex: Two unique, challenging cases

Abstract

Pagetoid Bowen disease is a subtype of Bowen disease that accounts for 5% of Bowen disease. It is extremely rare for Bowen disease to appear on the nipple-areola complex, with only seven cases described in the previous literature. Of those seven cases, only one was of the pagetoid subtype. We report two cases of pagetoid Bowen disease on this location, one of them being the first case of pagetoid Bowen disease affecting the nipple reported to date. On this location, it is crucial to perform a meticulous differential diagnosis to rule out Paget disease, because of its contrasting therapeutic and prognostic implications. In order to do this, clinical and histopathological aspects must be considered. From a clinical point of view, previous literature has stated that nipple involvement can be a clue that points to Paget disease. However, one of our cases shows that this is not always true. Regarding histopathological analysis, a complete excision of the tumor might be necessary to observe clear features of Bowen disease, such as full-thickness atypia of the epidermis and intercellular bridges. An immunohistochemical panel comprising carcinoembryonic antigen, gross cystic disease fluid protein, epithelial membrane antigen, p63, CK34betaE12, periodic acid-Schiff, estrogen receptor, and progesterone receptor can be decisive in complicated cases.

Nipple Lesions of the Breast

“…Squamous cell carcinoma (SCC) involving the nipple is very uncommon, and fewer than 20 cases are reported in the English literature, 83,[95][96][97][98][99][100][101][102][103][104][105][106][107][108] most of which occurred in patients who had received adjuvant radiation therapy for breast cancer. 97,98 SCC confined to the epidermis and superficial adnexal epithelium (SCC in situ or Bowen's disease) 109 limited to the NAC is even less common, with only about 10 reported cases 83,97,100,[103][104][105][106][107] including 3 cases showing pagetoid growth. 83,107 However, the clinical presentation of SCC in situ of the nipple with a scaly, erythematous or pigmented patch (or plaque) might suggest MPD.…”

“…SCC in situ involving the full-thickness of the epidermis usually is easily recognized in surgical excision specimens. 83,107 Typically, MPD is positive for CK7, GATA3, CEA, GCDFP-15, PAS and Mayer's mucicarmine and negativity for high-molecular-weight cytokeratins (CK5/ 6, 34betaE12 110 ), p63 or p40 support the diagnosis of MPD. However, recently Barrutia et al described 2 cases of CK5/6negative pagetoid SCC in situ.…”

“…82 Also, CEA, PAS, and Mayer's mucicarmine are positive in MPD, strengthening the glandular origin of these cells. 83,84…”

“…97,98 SCC confined to the epidermis and superficial adnexal epithelium (SCC in situ or Bowen's disease) 109 limited to the NAC is even less common, with only about 10 reported cases 83,97,100,[103][104][105][106][107] including 3 cases showing pagetoid growth. 83,107 However, the clinical presentation of SCC in situ of the nipple with a scaly, erythematous or pigmented patch (or plaque) might suggest MPD. Histologically, SCC in situ is characterized by full-thickness involvement of the epidermis by dysplastic squamous cells, and separating it from MPD with full-thickness atypia may be challenging, particularly if SCC in situ has pagetoid features and the biopsy yield only a small tissue specimen.…”

“…However, recently Barrutia et al described 2 cases of CK5/6negative pagetoid SCC in situ. 83 Moreover, there are rare reports of CK7-positive SCC in situ 83,101,[111][112][113][114][115][116][117] as well as 2 cases of CK7-negative GATA3-positive MPD associated with underlying DCIS having the same immunoprofile. 118 Rare cases of MPD are negative for both CK7 and HER2/ neu.…”