Correspondence
A Case of Pagetoid Bowen’s Disease
Tian Zhu, Tao Wang, Dong‑Lai Ma, Ya‑Nan Wang, Li Li
Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
To the Editor: A 65‑year‑old woman presented with a cutaneous
red‑brown plaque on the left posterior thigh for the past 7 years.
Initially, the lesion was a slightly elevated, well‑demarcated
plaque with a smooth surface and was about 1 cm in diameter,
without any symptoms. Over the years, it slowly extended into
an elevated plaque with rough surface, frequently bleeding after
slight friction. Physical examination revealed an obviously
elevated, well‑demarcated red‑brown plaque (3.0 cm × 2.7 cm)
covered by crusts on the left posterior thigh [Figure  1a],
with slightly tenderness. Biopsy showed hyperkeratosis and
parakeratosis. Acanthosis with irregular elongation of the rete
ridges was in the involved epidermis [Figure 1b]. There were
clear cells (some contained large cytologically atypical nuclei
stained dark)  [Figure  1c] in the stratum spinosum, and the
basement membrane was not involved. Immunohistochemical
findings revealed negative for PAS [Figure 1d], S100, HMB‑45,
CEA, and GCDFP15 [Figure 1e], positive for Ki‑67 (<30%),
CK34βE12 [Figure 1f], and P63 [Figure 1g], and weakly
positive for CAM5.2  [Figure  1h]. The diagnosis of pagetoid
Bowen’s disease (BD) is definite. Later, a wide local excision
(1.0 cm margin) was performed with negative margins of
resection. Among all the histological variants of BD, pagetoid
BD has been reported to occur in only 4.6% of BD. Unlike
typical BD, pagetoid BD commonly presents in the upper and
lower extremities, followed by head/neck and trunk area, with
very rare cases appearing in the external genitalia location.[1]
In this case, the lesion first appeared to be nevoid, suggesting
that it might be secondary to a preexisting nevocellular nevus.
It is also reported that a few cases of classic BD arise in
the preexisting skin lesions such as seborrheic keratosis. [2]
Histologically, pagetoid BD is characterized by nests of atypical
keratinocytes with round nuclei and abundant pale cytoplasm
located either singularly or in groups within the epidermis,
and the main differential diagnosis of pagetoid cells includes
extra‑mammary pagetoid disease  (EMPD) and malignant
melanoma in situ (MIS). Similar to classic BD, pagetoid
BD always shows full‑level involvement of the epidermis,
scattered multinucleated tumor giant cells, keratohyalin
granules, single‑cell keratinization, and intercellular bridges
visible between pagetoid cells, while EMPD lesion contains
pagetoid cells well demarcated from nearby epidermal cells,
flattened basal layer, stratum corneum involved, acinar
structures, and no intercellular bridge. Well‑demarcated
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DOI:
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Chinese Medical Journal ¦ December 20, 2017 ¦ Volume 130 ¦ Issue 24
pagetoid cells and stratum corneum involved can occur in MIS
lesion; in contrast, follicular extension shows up in MIS only.
Immunohistochemical tests are always helpful. The melanocytic
markers such as S100, melan‑A, and HMB‑45 show great value
in distinguishing MIS from pagetoid BD as only MIS lesions
tend to be stained positive. CK34βE12 shows that the cells may
stem from keratinocyte. CEA and GCDFP15 illustrate that the
cells are probably from sweat glands. CAM5.2 and Ber‑EP4
are generally considered to support the diagnosis of EMPD;[3]
however, some cases of pagetoid BD show positive for them.[4]
Recent studies suggest that p63 might be a useful marker as
it stains atypical keratinocytes of BD but not EMPDs.[5] This
patient’s tissue [Supplementary Table 1] shows positive for P63,
Ki‑67 (<30%), and CK34βE12, weakly positive for CAM5.2,
and negative for PAS, S100, HMB‑45, CEA, and GCDFP15.
Based on these findings, MIS and EMPD can be excluded; a
diagnosis of pagetoid BD was confirmed.
Supplementary information is linked to the online version of the
paper on the Chinese Medical Journal website.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient
consent forms. In the form, the patient has given her consent for
her images and other clinical information to be reported in the
journal. The patient understands that her name and initial will not
be published and efforts will be made to conceal their identity, but
anonymity cannot be guaranteed.
Financial support and sponsorship
This work was supported by grants from the National Natural
Science Foundation of China  (No.  81371731) and the Milstein
Medical Asian American Partnership Foundation.
Conflicts of interest
There are no conflicts of interest.
Address for correspondence: Dr. Li Li,
Department of Dermatology, Peking Union Medical College
Hospital, Chinese Academy of Medical Sciences,
Beijing 100730, China
E‑Mail: lilipumch2007@sina.com
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© 2017 Chinese Medical Journal  ¦  Produced by Wolters Kluwer ‑ Medknow
Received: 08‑10‑2017 Edited by: Li‑Shao Guo
How to cite this article: Zhu T, Wang T, Ma DL, Wang YN, Li L. A Case
of Pagetoid Bowen's Disease. Chin Med J 2017;130:3023-4.
3023
 a b c d

e f g h
Figure 1: (a) The elevated, well‑demarcated red‑brown lesion with crusts on the left thigh. (b) Nests of atypical keratinocytes within the
epidermis, as well as hyperkeratosis, parakeratosis, and acanthosis (H and E, original magnification ×50). (c) Large clear cells with pale‑staining
cytoplasm (H and E, original magnification ×400). (d) Atypical cells showed negative staining with PAS (original magnification ×200). (e) The
pagetoid cells show negative for GCDFP15 (original magnification ×100). (f) The pagetoid cells are uniformly positive for CK34βE12 (original
magnification ×100). (g) The pagetoid cells show strong nuclear positive for P63 (original magnification ×100). (h) The pagetoid cells show
weakly positive for CAM5.2 (original magnification ×100).

References Pathol 2008;35:366‑72. doi: 10.1111/j.1600‑0560.2007.00814.x.

1. Armes JE, Lourie R, Bowlay G, Tabrizi S. Pagetoid squamous cell
carcinoma in situ of the vulva: Comparison with extramammary
Paget disease and nonpagetoid squamous cell neoplasia. Int J Gynecol
Pathol 2008;27:118‑24. doi: 10.1097/pgp.0b013e318142acf0.
2. Mota AN, Piñeiro‑Maceira J, Alves Mde F, Tarazona MJ. Pigmented
Bowen’s disease. An Bras Dermatol 2014;89:825‑7. doi: 10.1590/
abd1806‑4841.20142725.
3. Sellheyer K, Krahl D. Ber‑EP4 enhances the differential diagnostic
accuracy of cytokeratin 7 in pagetoid cutaneous neoplasms. J Cutan
4. Sah  SP, Kelly  PJ, McManus  DT, McCluggage  WG. Diffuse CK7,
CAM5.2 and BerEP4 positivity in pagetoid squamous cell carcinoma
in situ (pagetoid Bowen’s disease) of the perianal region: A mimic of
extramammary Paget’s disease. Histopathology 2013;62:511‑4. doi:
10.1111/his.12003.
5. Chang J, Prieto VG, Sangueza M, Plaza JA. Diagnostic utility of p63
expression in the differential diagnosis of pagetoid squamous cell
carcinoma in situ and extramammary Paget disease: A histopathologic
study of 70 cases. Am J Dermatopathol 2014;36:49‑53. doi: 10.1097/
DAD.0b013e3182839541.

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Supplementary Table 1: Immunohistochemical results in
pagetoid BD, EMPD, and MIS
Antibody reagent Pagetoid BD EMPD MIS
PAS – + –
S100 – – +
HMB‑45 – – +
Melan‑A – – +
CEA – + –
GCDFP15 – + –
Ki‑67 + (<30%) – +
CK34βE12 + – –
P63 + – –
CAM5.2 ± + –
EMPD: Extra‑mammary pagetoid disease; BD: Bowen’s disease;
MIS: Malignant melanoma in situ. –: Negative; +: Positive; ±: Weakly
positive.