GG de Blois

GH Pitman

J Lloyd

JD Zollo

Jian Yang

KE Simon

KO Alsaad

LM Roth

MD McCarter

N Hatta

P Besa

RE Jones

RL Guerry

S Park

SC Lee

SCJ Van der Putte

Wenlin Yang

Xia Wang

Y Merot

BMC Cancer

English

PubMed

Springer - Publisher Connector

CASE REPORT Open Access
Extramammary Paget’s disease with the
appearance of a nodule: a case report
Xia Wang, Wenlin Yang*, Jian Yang
Abstract
Background: Extramammary Paget’s disease (EMPD) remains a rare condition with only a limited number of cases
reported in the literature. EMPD is mainly composed of intraepidermal Paget cells, and possesses variable clinical
behaviors and histological appearances, leading to difficulty in the diagnosis of this disease.
Case presentation: We here report a case of primary EMPD with the appearance of a nodule on the background
of erythema. Histological assessment showed Paget cell infiltration throughout the epidermis with dermal spread.
Using immunohistochemistry, the expressions of CK7, CK19, CK20, GCDFP-15, CEA, S-100 protein and bcl-2 were
examined to elucidate the cellular differentiation of the carcinoma.
Conclusion: According to the histological assessment, this case was diagnosed as primary EMPD with carcinoma
cells invading into the dermis, but without lymph node infiltration.
Background
EMPD of the vulva is a rare intraepithelial adenocarci-
noma which accounts for less than 1% of carcinomas in
vulva, while the majority of the patients are postmeno-
pausal Caucasian females[1-3]. The cancer cells in the
neoplasm usually stay “in situ” and only rarely invade
into the dermis to be metastatic via the lymphatic sys-
tem [4,5]. One has to differentiate neoplasms with Paget
phenomenon from carcinomas metastasized from adja-
cent organs such as the urinary system and rectum [6].
Here, we present an unusual case of EMPD with carci-
noma cells invading into the dermis without lymph
node infiltration in a Chinese woman.
Case presentation
A 66-year-old Chinese woman presented with a slowly
growing vulvar mass with pruritus. Two years prior to
presentation, she noted a painless red firm nodule on
her vulva. Subsequently, erythema around the nodule
appeared. The nodule and erythema had gradually
enlarged during the 2-year period. Physical examination
revealed a 2 cm × 2 cm × 2 cm slightly erosive, nodular
red firm mass on the centre of 5 cm × 7 cm area of
irregular eczematoid erythema covering her mons pubis
(Fig.1). There was no swelling of lymph nodes in bilat-
eral groins. Biopsy of inguinal lymph node was negative.
The complete mass and part of the erythema were
excised for histological evaluation. The patient’s medical
history was unremarkable. Metastasis from other can-
cers was excluded by routine blood tests, cystoscopy,
oesophagogastroduodenoscopy, colonoscopy, abdomino-
pelvic computed tomography (CT), chest radiography
and positron emission tomography-CT. All these exami-
nations were normal. At 3-month follow-up, the patient
had local mass recurrence and non-palpable inguinal
lymph nodes.
Hematoxylin and Eosin staining of the biopsy from the
lesion showed large round cells with ample pale-staining
cytoplasm, pleomorphic nuclei, and occasional promi-
nent nucleoli infiltrating throughout the epidermis, indi-
cative of Paget cells (Fig. 2A). This carcinoma spread
dermal, and a poorly differentiated adenocarcinoma was
present in the dermis.(Fig. 2B). Immunohistochemical
stainings for gross cystic disease fluid protein-15
(GCDFP-15) (Fig. 3A), cytokeratin7(CK7) (Fig. 3B), cyto-
keratin 19 (CK19) and carcinoembryonic antigen (CEA)
were strongly positive. Epithelial membrane antigen
(EMA) was positive, while S-100 protein, bcl-2 and
CK20 (Fig. 3C) were all negative. Neoplastic cells were
positive for periodic acid-Schiff (PAS). Moreover, the
Paget cells and low-differentiated adenocarcinoma
* Correspondence: wenliny@21cn.com
Department of Dermatology, the Second Affiliated Hospital of Guangzhou
Medical University, Guangzhou 510260, P. R. China
Wang et al. BMC Cancer 2010, 10:405
http://www.biomedcentral.com/1471-2407/10/405
© 2010 Wang et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
shared common immunohistological features. These
immunohistochemical appearances supported the diag-
nosis of EMPD.
Discussion
EMPD is an intraepidermal adenocarcinoma, which
usually develops in locations with apocrine glands.
Nevertheless, when the carcinoma cells infiltrate into
the dermis and form a nodule, this disease turns into an
invasive carcinoma belonging to adnexal adenocarci-
noma of the skin [7]. Typically involved anatomical sites
are the vulvar, perianal, perineal, scrotal and penile
regions. Clinically, the lesions present as well-defined,
moist, erythematous plaques usually accompanied by
pruritus. The study reported by Hatta et al [8] revealed
that erythema was a clinical characteristic of all lesions;
furthermore, nodules were present in 24%, erosion in
49% and hypopigmentation in 25% cases. In addition,
39% of patients exhibited lymphopathy.
Primary adenocarcinomas of the vulva have been clas-
sified into sweat gland cancers, EMPD [9,10],
and"breast-like’’adenocarcinomas of the vulva [11,12].
Histologically, sweat gland carcinomas of the vulva pos-
sess adenopapillary cords and tubules, occasionally com-
prising pagetoid cells. Although EMPD mainly consists
of intraepidermal Paget cells, dermal invasion with cords
and sheets has also been recorded [13]. The current opi-
nion is that the malignancy spreads from superficial to
deep [14], rather than from deep to superficial [13,15].
Primary breast carcinoma of the vulva exhibits histologi-
cal characteristics similar to breast carcinoma. These
three carcinomas may possess some consistent histo-
pathological features. Van der Putte and van Gorp [16]
put forward the term “adenocarcinoma of the mam-
mary-like glands of the vulva”, leading to a novel unify-
ing notion for the three diseases mentioned above.
The level of invasion of the paget cells in EMPD can
be classified into three grades: in situ in the epidermis,
microinvasion to the papillary dermis, and deep invasion
Figure 1 The clinical features of the patient with EMPD. Red
firm mass on the centre of irregular warm eczematoid erythema
covering the woman mons pubis.
Figure 2 Histological assessment of EMPD. (A) H&E staining
indicated Paget cells into the epidermis (original magnification ×
100), and (B) The dermis contained a poorly differentiated
adenocarcinoma (original magnification × 200).
Figure 3 Immunohistochemical assessment of EMPD. (A) The carcinoma showed positivity for GCDFP-15(original magnification × 100).(B) The
carcinoma showed positivity for CK7 (original magnification × 200).(C) The carcinoma showed negative for CK20 (original magnification × 200)
Wang et al. BMC Cancer 2010, 10:405
http://www.biomedcentral.com/1471-2407/10/405
Page 2 of 4
into the reticular dermis or subcutaneous tissue [17].
According to the above classification method, this case
can fall into the third grade. Hatta et al [8] reported
that male patients outnumbered female patients (male-
female ratio, 2.6 to 1) in Japanese, in contrast to pre-
vious reports from western countries. The discrepancy
between the studies can be explained by genetic variety
of different regions. Further epidemiological studies for
this disease are needed to clarify this point.
In this case, the lesion was present as a painless,
slowly-growing, red firm mass on the centre of irregular
eczematoid erythema covering the elderly woman’s
mons pubis. Histological assessment showed EMPD
with carcinoma cells invading into the dermis, which are
often characteristics of the metastatic lesion of breast.
However, metastasis from breast carcinoma and internal
malignancies was excluded by physical and auxiliary
examinations. When carcinoma cells infiltrate into the
dermis and advance to Paget’s carcinoma, it is referred
to as adenocarcinoma of the skin and has a poor prog-
nosis. Up to now, no established guideline has been
made for the diagnosis of EMPD, the nonspecific clinical
findings of EMPD often lead to misdiagnosis and
extended periods of topical and systemic medical
mismanagement.
Because the disease is rare, there is little knowledge of
the most effective treatment. Primary treatment is surgi-
cal and involves wide local excision with frozen section
evaluation of margins. Invasion level and multiple lymph
node metastases are important prognostic factors in
EMPD. Unfortunately, there is a high rate of recurrence.
Some suggest prophylactic regional lymph node dissec-
tion, especially for high grade carcinomas, whereas
others recommend removal of only clinically involved
nodes [9]. Reports on the results of radiotherapy are
conflicting: these carcinomas are radioresistant, or radio-
therapy increases local control [3]. Radiation therapy
may be used as a supplement to aggressive surgery. We
recommend that treatment for EMPD includes surgery
in the form of wide local excision and adjuvant radio-
therapy with caution and individualization.
Conclusions
Primary EMPD of the vulva is exceptional. Up to now,
no gold diagnostic standard has been established for
EMPD, leading to the difficulty in diagnosis of this dis-
ease. To improve its prognosis, further investigation
needs to be performed for the early detection of primary
EMPD and its metastasis.
Consent
Written informed consent was obtained from the patient
for publication of this case report and any accompanying
images. A copy of the written consent is available for
review by the Editor-in-Chief of this journal.
Abbreviations
EMPD: Extramammary Paget’s disease; CT: computed tomography; GCDFP-
15: gross cystic disease fluid protein-15; CK7: cytokeratin 7; CK19: cytokeratin
19; CK20: cytokeratin 20; CEA: carcinoembryonic antigen; EMA: epithelial
membrane antigen; bcl-2: b cell lymphoma/lewkmia-2; PAS: periodic acid-
schiff
Acknowledgements
We are grateful to Dr. Zhuofang Hao, Dr. Shizhang Huang and Dr. Degui
Liao in the Pathology Department of our hospital for their contribution to
this project. This work was supported by Science and Technology Planning
Project of Guangdong Province, P R. China (No. 2008B030301249).
Authors’ contributions
XW drafted the manuscript and in the data collection. WLY participated in
the design and coordination of the case-study and revised the manuscript
for important intellectual content. JY carried out the histological examination
and diagnosed, investigated, followed up and managed the patient. All
authors have read and approved the final manuscript.
Authors’ information
Xia Wang, Resident Doctor, Department of Dermatology, the Second
Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, P. R.
China. E-mail: wxpiglet@yahoo.com.cn.
WenLin Yang, Professor, Department of Dermatology, the Second Affiliated
Hospital of Guangzhou Medical University, Guangzhou 510260, P. R. China. E-
mail: wenliny@21cn.com.
Jian Yang, Professor, Department of Dermatology, the Second Affiliated
Hospital of Guangzhou Medical University, Guangzhou 510260, P. R. China. E-
mail: Yangj123@21cn.com.
Competing interests
The authors declare that they have no competing interests.
Received: 20 March 2010 Accepted: 4 August 2010
Published: 4 August 2010
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Cite this article as: Wang et al.: Extramammary Paget’s disease with the
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Page 4 of 4


Extramammary Paget's disease with the appearance of a nodule: a case report

Abstract
          
            Background
            Extramammary Paget's disease (EMPD) remains a rare condition with only a limited number of cases reported in the literature. EMPD is mainly composed of intraepidermal Paget cells, and possesses variable clinical behaviors and histological appearances, leading to difficulty in the diagnosis of this disease.
          
          
            Case presentation
            We here report a case of primary EMPD with the appearance of a nodule on the background of erythema. Histological assessment showed Paget cell infiltration throughout the epidermis with dermal spread. Using immunohistochemistry, the expressions of CK7, CK19, CK20, GCDFP-15, CEA, S-100 protein and bcl-2 were examined to elucidate the cellular differentiation of the carcinoma.
          
          
            Conclusion
            According to the histological assessment, this case was diagnosed as primary EMPD with carcinoma cells invading into the dermis, but without lymph node infiltration.
          </jats:sec

Crossref

AM: Mammary and extramammary Paget’s disease.

CE: Paget’s disease of the vulva. A histogenetic study of five cases including ultrastructural observations and review of the literature. Am J Surg Pathol

Extramammary Paget’s disease of the penis and scrotum: excision, reconstruction and evaluation of occult malignancy.

Extramammary Paget’s disease of the vulva. A clinicopathologic study of 13 cases.

Extramammary Paget’s disease: treatment, prognostic factors and outcome in 76 patients.

Extramammary Paget’s disease. A critical reexamination.

GF: Extramammary Paget’s disease of the perianal and perineal regions. Evidence of apocrine derivation. Arch Dermatol

Gorp LHM: Adenocarcinoma of the mammary-like glands of the vulva: a concept unifying sweat gland carcinoma of the vulva, carcinoma of supernumerary mammary glands and extramammary Paget’s disease.

Guillem JG: Long-term outcome of perianal Paget’s disease. Dis Colon Rectum

Herter FP: Extramammary Paget’s disease. Plast Reconstr Surg

JT: Extramammary Paget’s disease of the perineal skin: role of radiotherapy.

Pratt-Thomas HR: Carcinoma of supernumerary breast of vulva with bilateral mammary.

SB: Extramammary Paget’s disease: Arising in knee region in association with sweat gland carcinoma. Arch Pathol Lab Med

Vulvar apocrine adenocarcinoma: a case with nodal metastasis and intranodal mucinous differentiation. Pathol Res Pract

Zeitouni NC: The Roswell Park Cancer Institute experience with extramammary Paget’s disease.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2921398

Extramammary Paget's disease with the appearance of a nodule: a case report

Abstract

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