Staging and Assessment of Lymph Node Involvement by 18F-

Fluorodeoxyglucose–Positron Emission Tomography in

Invasive Extramammary Paget’s Disease
SATORU AOYAGI, MD, KAZUKO C. SATO-MATSUMURA, MD, PHD, AND HIROSHI SHIMIZU, MD, PHD

Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan

BACKGROUND. 18F-Fluorodeoxyglucose (FDG)–positron emission
tomography (PET) is a functional and metabolic imaging modal-
ity that is efficacious in nodal staging and detection of extranodal
involvement for malignant tumors.
OBJECTIVE. We describe the novel use of PET for staging patients
with invasive extramammary Paget’s disease (EMPD) and discuss
the potential advantages of this technology relative to other diag-
nostic modalities.
METHODS . We evaluated three patients with invasive EMPD
whose staging was made by PET at Hokkaido University Hospi-
tal.
RESULTS. All lymph nodes detected by PET were over 10 mm. Dis-
tant internal metastases were not seen in all cases. PET failed to
detect 10 and 5 to 7 mm nodal involvement but succeeded in
detecting nodes over 10 mm.
CONCLUSIONS. These data suggest that PET may be useful in
determining disease activity at the time of initial diagnosis but is
less useful and proves difficult to detect a small or subclinical
involvement. This is the first report of PET being used for inva-
sive EMPD.

SATORU AOYAGI, MD, KAZUKO C. SATO-MATSUMURA, MD, PHD, AND HIROSHI SHIMIZU, MD, PHD,
HAVE INDICATED NO SIGNIFICANT INTEREST WITH COMMERCIAL SUPPORTERS.

18
F-FLUORODEOXYGLUCOSE (FDG)–positron emis- tumor, 4
5 cm in size, on the left genital region and dif-
sion tomography (PET) is widely accepted in the field of fuse pinkish erythema around the nodule and scrotum
oncology to detect the metastasis of malignancy. In the (Figure 1).
dermatologic field, PET has been used mostly for malig- A spindle-shaped biopsy specimen of the nodule on the
nant melanoma1 and recently for malignant adnexal left genital region, stained with hematoxylin-eosin,
tumors,2 cutaneous lymphoma,3 and Merkel cell carci- revealed an intraepidermal and intradermal invasion of
noma.4 However, there are no reports of PET being used solid tumor cells characterized by small hyperchromatic
for extramammary Paget’s disease (EMPD). We describe
the novel use of PET for staging patients with invasive
EMPD and discuss the potential advantages of this tech-
nology relative to other diagnostic modalities.

Case 1
A 61-year-old Japanese man presented with a large reddish
nodular tumor on the left genital region and lymph node
swelling of the left inguinal region. The erythema had
enlarged continuously over the previous 5 years and sub-
sequently the nodule arose during the past 6 months with
a swollen left inguinal lymph node. A physical examina-
tion showed a fresh, reddish, elastic hard, wet-surfaced

Address correspondence and reprint requests to: Satoru Aoyagi, MD,

Department of Dermatology, Hokkaido University Graduate School
of Medicine, N15 W7, Kita-ku, Sapporo, 060-8638, Japan, or e- Figure 1. A fresh reddish, elastic hard, wet-surfaced tumor, 4
5 cm
mail: aoyagi.ms@mac.com. in size, on the left genital region and diffuse pinkish erythema
around the nodule and scrotum in case 1.

© 2005 by the American Society for Dermatologic Surgery, Inc. • Published by BC Decker Inc
ISSN: 1076–0512 • Dermatol Surg 2005;31:595–598.
596 AOYAGI ET AL: 18F-FDG–PET FOR EXTRAMAMMARY PAGET’S DISEASE Dermatol Surg 31:5:May 2005

nuclei surrounded by a translucent cytoplasm. The epider- were added to the treatment. CT and PET could not detect
mis was infiltrated by single and clustered Paget cells. The a micrometastasis of the right inguinal lymph node. A pos-
dermis showed massive stromal invasion by tumor cells. itive sentinel node was 5 to 7 mm. The patient was free of
Immunohistochemical analysis demonstrated that the disease 18 months after surgery for recurrence and metas-
cytoplasm of the tumor cells was positive for periodic tasis.
acid–Schiff (PAS) and carcinoembryonic antigen (CEA)
but not for keratin 20, suggesting a diagnosis of invasive
EMPD.
The patient underwent 18 F-FDG injection and PET
using a whole-body scanner (ECAT EXACT47,
Siemens/CTI, Knoxville, TN, USA). The patient had fasted
for at least 5 hours prior to the procedure. A whole-body
emission image was obtained 60 minutes after the injec-
tion of 185 MBq FDG using the three-dimensional
method. Left inguinal and external iliac lymph node
metastases were detected by computed tomography (CT)
and PET, but gallium scintigraphy detected only the left
inguinal node. The diagnosis was primary invasive EMPD.
The standardized uptake value (SUV) of the lesion by PET
was 2.0 for the inguinal and 2.7 for the left external iliac
node (Figure 2). The SUV, a simple semiquantitative index
of glucose metabolism in tissues and tumor, is defined as
[PET scanner measurement of tissue tracer concentra-
tion/activity injected]/body weight (kg).
The patient was treated with a wide local excision by a
3 cm margin, resection of the left testis, left inguinal lymph
node dissection, radiation, and chemotherapy. Seven
months after surgery, CT showed enlargement of the left
total iliac lymph node from 4 to 10 mm, but, at that time,
PET could not detect it. The patient died of widespread
metastatic EMPD 23 months after surgery.

Case 2
A 59-year-old Japanese man presented with a reddish
nodular tumor on the right genital region that had
enlarged in the past month. A physical examination
showed a fresh, reddish, elastic hard tumor, 1
2 cm in
size, on the right side of the scrotum and diffuse pinkish
erythema with depigmented macule on the scrotum. There
was no lymph node swelling of the inguinal region. A spin-
dle-shaped biopsy specimen of the nodule on the right side
of the scrotum, stained with hematoxylin-eosin, revealed
an intraepidermal and intradermal invasion of Paget cells.
Immunohistochemical analysis demonstrated that the
cytoplasm of the tumor cells was positive for PAS and CEA
but not for keratin 20, suggesting a diagnosis of invasive
EMPD. PET was performed after the aforementioned pro-
tocol. A clinical examination, CT, and PET showed no
other metastasis on the internal organ and lymph nodes.
The diagnosis was primary invasive EMPD.
The patient was treated with a wide local excision by a
3 cm margin and sentinel biopsy. Then, because the right Figure 2. 18F-Fluorodeoxyglucose–positron emission tomographic
inguinal sentinel lymph node was found to be positive, scan demonstrating abnormal radiotracer uptake (arrows) of the
right inguinal lymph node dissection and chemotherapy left inguinal lymph node in case 1 (vertical view).
Dermatol Surg 31:5:May 2005 AOYAGI ET AL: 18F-FDG–PET FOR EXTRAMAMMARY PAGET’S DISEASE 597

Case 3 Zeitouni reported 30 cases of EMPD, and of these, there

were nine invasive cases, and only three cases involved
A 71-year-old Japanese man presented with a reddish
males.5 All three cases had lymphatic system involvement.
nodular tumor on the right genital region, which had
In invasive EMPD, the most common site of metastasis
enlarged during the previous 2 years. A physical examina-
is the bilateral inguinal lymph node, but there can also be
tion showed a reddish, elastic hard tumor, 5
5 cm in
size, on the right side of the penis and diffuse pinkish
plaque on the scrotum (Figure 3). There were also several
lymph node swellings of the bilateral inguinal region. A
spindle-shaped biopsy specimen of the nodule on the right
side of the penis, stained with hematoxylin-eosin, revealed
an intraepidermal and intradermal invasion of Paget cells.
Immunohistochemical analysis suggested a diagnosis of
invasive EMPD. A clinical examination and CT also
showed enlargement of the superficial inguinal lymph
nodes on both sides. PET was performed after the afore-
mentioned protocol. The SUV of the lesion was 2.4 for the
bilateral inguinal node (Figure 4). All detected lymph
nodes were over 10 mm. The diagnosis was primary inva-
sive EMPD.
The patient was treated with a wide local excision by a
3 cm margin, total penectomy, resection of the right testis,
bilateral inguinal lymph node dissection, radiation, and
chemotherapy. The patient was free of disease 17 months
after surgery for recurrence and metastasis.
In our three cases, PET failed to detect 10 and 5 to
7 mm nodal involvement but succeeded in detecting those
over 10 mm. Distant internal metastases were not seen in
all cases before surgery.

Discussion
Invasive EMPD of the penis and scrotum is a rare disease
that afflicts older men. It most commonly remains in the
epidermis, but cases of dermal invasion with local metas-
tasis or distant metastasis have been reported. Zollo and

Figure 3. A reddish, elastic hard tumor, 5
5 cm in size, on the right Figure 4. 18F-Fluorodeoxyglucose–positron emission tomographic
side of the penis and diffuse pinkish plaque on the scrotum in case scan demonstrating abnormal radiotracer uptake (arrows) of the
3. bilateral inguinal lymph node in case 3 (vertical view).
598 AOYAGI ET AL: 18F-FDG–PET FOR EXTRAMAMMARY PAGET’S DISEASE
lymph node swelling owing to secondary inflammation in
such a case. Therefore, it is sometimes difficult to deter-
mine if node swelling is due to metastasis or inflamma-
tion. In such a case, CT, ultrasonography, gallium scintig-
raphy, and magnetic resonance imaging have usually been
performed to detect nodal involvement, but, in some
cases, it is difficult to detect perfectly. Sentinel node
biopsy is also the most valuable tool for detecting sub-
clinical lymph node metastasis, but it is an invasive tech-
nique.
PET is especially useful in differentiating benign from
malignant lymph nodes detected by conventional tech-
niques. But in a recent study of lymph node metastases
from melanoma before surgery, PET had only 23% sensi-
tivity for lymph node metastases under 5 mm, and the sen-
sitivity increased to 83% and 100% for lymph node
metastases 6 to 10 mm and over 10 mm, respectively.6
Although sentinel detection of subclinical nodal metas-
tases had a sensitivity of 86 to 100%, PET detected only
14 to 22%.7,8 It can be said that the efficacy of nodal stag-
ing of melanoma is dependent on the size of the tumor.
Our experience with the staging and assessment of lymph
node involvement before surgery in invasive EMPD sup-
ports the same result for malignant melanoma.
In summary, PET is not a more sensitive technique for
initial staging of invasive EMPD than sentinel node biopsy.
This modality cannot be effectively used for the screening
of metastasis of lymph node in this tumor or to detect sub-
clinical nodal metastasis of the lymph node. But it showed
a higher efficiency in differentiating benign from malig-
nant lymph node swelling by clinical examination than CT
Dermatol Surg 31:5:May 2005
and gallium scintigraphy. EMPD sometimes shows aggres-
sive behavior, such as invasion of the dermis and metasta-
sizing via the lymphatic system. It is most important to
detect early metastases. Our cases show the ability of PET
only to detect lymph node involvement missed by mor-
phologic imaging procedures, but further studies with
more cases are needed to validate the usefulness of PET in
invasive EMPD.
References
1. Mijnhout GS, Hoekstra OS, van Tulder MW, et al. Systemic review
of the diagnostic accuracy of 18F-fluorodeoxyglucose positron emis-
sion tomography in melanoma patients. Cancer 2001;91:1530–42.
2. Jung J, Cho SB, Yun M, et al. Metastatic malignant proliferating
trichilemmal tumor detected by positron emission tomography. Der-
matol Surg 2003;29:872–4.
3. Shapiro M, Yun M, Junkins-Hopkins JM, et al. Assessment of tumor
burden and treatment response by 18F-fluorodeoxyglucose injection
and positron emission tomography in patient with cutaneous T- and
B-cell lymphomas. J Am Acad Dermatol 2002;47:623–8.
4. Nguyen BAD. Positron emission tomographic imaging of Merkel cell
carcinoma. Clin Nucl Med 2002;27:922–3.
5. Zollo JD, Zeitouni NC. The Roswell Park Cancer Institute experi-
ence with extramammary Paget’s disease. Br J Dermatol
2000;142:59–65.
6. Crippa F, Leutner M, Belli F, et al. Which kind of lymph node metas-
tases can FDG PET detected? A clinical study in melanoma. J Nucl
Med 2000;41:1491–4.
7. Belhocine T, Pierard G, de Labrassinne M, et al. Staging of regional
nodes in AJCC stage I and II melanoma: 18FDG PET imaging versus
sentinel node detection. Oncologist 2002;7:271–8.
8. Longo MI, Lazaro P, Bueno C, et al. Fluorodeoxyglucose-positron
emission tomography imaging versus sentinel node biopsy in the pri-
mary staging of melanoma patients. Dermatol Surg 2003;29:245–8.