ORIGINAL ARTICLE

Kikuchi-Fujimoto Disease
PET/CT Assessment of a Rare Cause of Cervical Lymphadenopathy
Tetsuya Tsujikawa, MD, PhD,* Tatsuro Tsuchida, MD, PhD,* Yoshiaki Imamura, MD, PhD,†
Masato Kobayashi, PhD,‡ Satoko Asahi, MD,* Kazuhiro Shimizu, MD,* Kazunobu Tsuji, MD,*
Hidehiko Okazawa, MD, PhD,§ and Hirohiko Kimura, MD, PhD*

Purpose: Kikuchi-Fujimoto disease (KFD), formerly called subacute necrotizing lymphadenitis, is a rare cause of cervical lymphadenopathy. The
purpose of this study was to evaluate the usefulness of FDG PET/CT for
distinguishing KFD from non-Hodgkin lymphoma (NHL).
Materials and Methods: Twenty-two patients with cervical lymphadenopathy (8 with KFD and 14 with NHL) underwent CT and FDG PET/CT scans
to examine the cervical lymphadenopathy. Regional values of FDG uptake
were evaluated using the standardized uptake value (SUV) and partial
volume corrected SUV (corSUV) based on the count recovery coefficient.
Tumor size (mm), SUV, and corSUV were compared among KFD, indolent
NHL, and aggressive NHL.
Results: KFD lesions tended to be smaller (13.8 ⫾ 5.4 mm) than those ofindolent (25.4 ⫾ 11.8) and aggressive (29.7 ⫾ 18.8) NHL, whereas there
were no significant differences in size. As for SUV, a significant difference
was observed only between indolent and aggressive (6.4 ⫾ 1.5 and 17.3 ⫾ 9.3,
P ⬍ 0.05) NHL; however, KFD showed a significantly greater corSUV (23.8 ⫾10.6) as compared with indolent NHL (9.2 ⫾ 5.1, P ⬍ 0.05), which did not show
a significant difference from aggressive NHL (21.4 ⫾ 10.2). FDG PET/CT
detected thoracoabdominal lesions in 2 patients (25%) with KFD.
Conclusions: KFD shows high FDG uptake for size, which may reflect thepathologic characteristics, including necrotizing lymphocytes and numerous
histiocytes (macrophages) surrounding small necrotic foci. FDG PET/CT
will be useful for detecting noncervical lesions of KFD and distinguishing
KFD from NHLs using both SUV and corSUV.
Key Words: Kikuchi-Fujimoto disease, FDG, PET/CT(Clin Nucl Med 2011;36: 661– 664)

K

ikuchi-Fujimoto disease (KFD) or histiocytic necrotizing lymphadenitis, formerly called subacute necrotizing lymphadenitis, isa self-limiting cause of cervical lymphadenopathy. First describedindependently in 1972 by Kikuchi and Fujimoto et al,1,2 KFD is anextremely rare disease known to have a worldwide distribution withhigher prevalence among Japanese and other Asiatic individuals.3
Characteristic histopathologic features of KFD include variable degrees of necrosis in cortical and paracortical areas with
abundant karyorrhectic debris, numerous histiocytes at the margin of
the necrotic areas, and the absence of granulocytes4,5; however,despite the histopathologic features of KFD, previous studies havereported that most lymph nodes were homogeneously enhanced
Received for publication December 22, 2010; revision accepted February 14, 2011.
From the *Department of Radiology, University of Fukui, Fukui, Japan; †Divisionof Surgical Pathology, University of Fukui, Fukui, Japan; ‡School of Health
Sciences, College of Medical, Pharmaceutical and Health Sciences, Kanazawa
University, Kanazawa, Japan; and §Biomedical Imaging Research Center,
University of Fukui, Fukui, Japan.
Reprints: Tetsuya Tsujikawa, MD, PhD, Department of Radiology, University of
Fukui, 23–3 Matsuoka-Shimoaizuki, Eiheiji-cho, Fukui 910 –1193, Japan.
E-mail: awaji@u-fukui.ac.jp.
Copyright © 2011 by Lippincott Williams & Wilkins
ISSN: 0363-9762/11/3608-0661

Clinical Nuclear Medicine • Volume 36, Number 8, August 2011

without evidence of gross necrosis on computed tomography(CT).6 – 8 Several case reports and a recent study using positronemission tomography (PET) with 2-关F-18兴fluoro-2-deoxy-D-glucose(FDG) have suggested that the lymph nodes of patients with KFD
exhibit FDG avidity9 –13; that is, CT and FDG PET findings of KFD
mimic those of malignant lymphoma.
On the other hand, it is reported that affected lymph nodes in
KFD are not very large (diameter of ⬍3–3.5 cm).6,13 Because thepartial volume effect (PVE) is one of the most important factors
affecting FDG uptake on PET imaging,14,15 the purpose of this study
was to evaluate the usefulness of FDG PET/CT to distinguish among
KFD, indolent non-Hodgkin lymphoma (NHL) and aggressive NHL
using regional FDG uptake with and without partial volume correction. In addition, we described the histopathologic correlation with
PET imaging features of KFD.

MATERIALS AND METHODSPatients
A search of our institution’s pathology, radiology, and medical records between November 2006 and March 2010 revealed 8
patients with KFD and 14 patients with NHL (5 indolent and 9
aggressive) whose data were considered for inclusion in this retrospective study. Patient data were included if they were referred toour institution for examination of cervical lymphadenopathy with orwithout fever, if they had a pathologically proven diagnosis of KFDor NHL by excisional biopsy from cervical lymph nodes, and if they
had undergone both CT and FDG PET/CT at the time of diagnosis.
Exclusion criteria were as follows: lack of pathologic diagnosis,
main affected area other than cervical nodes.

CT and PET/CT Imaging
Eighteen CT examinations of the neck were performed with amultidetector CT scanner with 16 detectors (LightSpeed Ultra; GE
Medical Systems, Milwaukee, WI) before and after intravenous
administration of nonionic iodinated contrast material (iopamidol,
Iopamiron 300; Schering, Berlin, Germany). Three CT examinations
were performed without contrast material. The CT parameters wereas follows: peak tube voltage of 120 to 400 mAs, rotation time of 0.5
seconds, reconstruction thickness of 5 mm, pitch of 8, and with
16-row detector configuration.
All whole-body PET scans with FDG were performed with a
combined PET/CT scanner (Discovery LS; GE Medical Systems),
which permits simultaneous acquisition of 35 image slices in 3-dimensional acquisition mode with interslice spacing of 4.25 mm. The
PET/CT scanner incorporates an integrated 4-slice multidetector CT
scanner, which was used for attenuation correction. CT scanningparameters were as follows: Auto mA (upper limit, 40 mA; noise
index, 20), 140 kV, 5-mm section thickness, 15-mm table feed, andpitch of 4. After at least 4 hours fasting, patients received an
intravenous injection of 185 MBq FDG and image acquisition began
50 minutes after injection. A whole-body emission scan was performed from the head to the inguinal region with 2 minutes per bed
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position (7 to 8 bed positions). PET data were reconstructed by theiterative reconstruction method selecting 14 subsets and 2 iterations.
The reconstructed images were then converted to a semiquantitative
image corrected by the injection dose and subject’s body weight (⫽standardized uptake value 关SUV兴).

Phantom Study
NEMA 2001 body phantom, which is an elliptical phantom
with 6 individually fillable spheres whose diameters range from10, 13, 17, 22, 28, and 37 mm, was prepared. The concentrationof F-18 FDG in all the spheres was 10 kBq/mL and lowest lesser
one in the background was 2 kBq/mL. The PET/CT system andimaging protocol were the same as the clinical scan except thatthe emission scan was obtained for 5 minutes. Circular regions ofinterest (ROIs) were placed over the surface with the greatest
diameter of each hot sphere on the image, and the ROI of the hotsphere invisible on the image was located using the corresponding CT image. The relative recovery coefficient (RC) was calculated using the following formula:RC ⫽ A/B,
where A is the maximum pixel count of each hot sphere and B is the
maximum pixel count of the greatest sphere without PVE.
The regression count recovery curve was obtained and used
for further analysis.

Image Analysis
For PET/CT image analysis, single ROIs as large as possible
were placed over the cervical lymph node showing the highest FDG
uptake using information obtained from CT images by the consensusof 2 experienced nuclear medicine physicians. SUV was determinedas the highest activity within an ROI and the maximum diameter ofthe lymph node was recorded per patient. RC of the lesion wasdetermined using the regression curve. Partial volume corrected
SUV (corSUV) was calculated as16 –18:
corSUV ⫽ (SUV ⫺ backSUV)/RC ⫹ backSUV,
where backSUV denotes SUV of background (cervical muscles).

Clinical Nuclear Medicine • Volume 36, Number 8, August 2011

Statistical Analysis
All patients were divided into 3 groups consisting of KFD,
indolent NHL, and aggressive NHL. Tumor size (mm), SUV, andcorSUV were compared among the 3 groups by 1-way ANOVA witha post hoc Games-Howell test, which has robustness for analysis
even in unequal variance. A probability value of less than 0.05 wasconsidered to indicate significant difference. Statistical analysis was
performed using a software package (PASW Statistics, formerly
called SPSS Statistics, 17.0; SPSS Inc).

RESULTS
Figure 1 shows that the lesions of KFD had a tendency to besmaller (13.8 ⫾ 5.4 mm) than those of indolent NHL (25.4 ⫾ 11.8)
and aggressive NHL (29.7 ⫾ 18.8), whereas there were no significant differences in size. As for SUV, a significant difference wasobserved only between indolent NHL and aggressive NHL (6.4 ⫾1.5 and 17.3 ⫾ 9.3, P ⬍ 0.05). On the other hand, KFD showed asignificantly greater corSUV (23.8 ⫾ 10.6) than indolent NHL (9.2
⫾ 5.1, P ⬍ 0.05), which did not show a significant difference fromaggressive NHL (21.4 ⫾ 10.2).
Six patients had homogeneous lymph nodes on CT images.
Affected nodes contained low-attenuation areas suggesting grossnodal necrosis in 2 cases (25%). A representative case of a 16-yearold boy with histopathologic findings is given in Figure 2. FDG
PET/CT showed intense accumulation of FDG on right cervicallymphadenopathy (Fig. 2A). A CT scan showed multiple small andmedium homogenously enhanced nodes without evidence of gross
necrosis (Fig. 2B). Despite the CT findings, histologically, a lymph
node showed a well-circumscribed paracortical focus of necrosis
with a mixture of karyorrhectic nuclear debris, single cell necrosis,
transformed lymphocytes, and foamy histiocytes (macrophages).
Polymorphonuclear leukocytes were absent (Figs. 2C, D).
Whole-body PET/CT detected thoracoabdominal lesions in 2
patients with KFD. In one of the patients, affected lymph nodes
along the celiac artery were first noted on whole-body PET/CT(Figs. 3C–E), not on nonenhanced abdominal CT (not shown).

FIGURE 1. Box-and-whisker plots of each lesion size, FDG uptake (SUV), and partial volume corrected FDG uptake (corSUV)
among KFD, indolent NHL, and aggressive NHL. KFD had a tendency to be smaller (13.8 ⫾ 5.4 mm) than those of indolent
NHL (25.4 ⫾ 11.8) and aggressive NHL (29.7 ⫾ 18.8), whereas there were no significant differences in size among them. As
for SUV, a significant difference was observed only between indolent NHL and aggressive NHL (6.4 ⫾ 1.5 and 17.3 ⫾ 9.3,
P ⬍ 0.05). On the other hand, KFD showed a significantly greater corSUV (23.8 ⫾ 10.6) than those of indolent NHL (9.2 ⫾
5.1, P ⬍ 0.05), which did not show a significant difference from aggressive NHL (21.4 ⫾ 10.2). K indicates Kikuchi-Fujimoto
disease; I, indolent NHL; A, aggressive NHL.
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Clinical Nuclear Medicine • Volume 36, Number 8, August 2011

PET/CT Assessment of Kikuchi-Fujimoto Disease

FIGURE 2. A 16-year-old male patient with KFD.
Maximum intensity projection image of FDG PET/CT (A) shows intense accumulation of FDG inright cervical lymphadenopathy (arrow). Neck CT
scan with contrast enhancement (B) shows
multiple small and medium homogenously
enhanced nodes without evidence of gross
necrosis (arrow). Histologic images of rightcervical lymph node on hematoxylin-eosin (C, D)
show a well-circumscribed paracortical focus of
necrosis with a mixture of karyorrhectic nuclear
debris, single cell necrosis, transformed
lymphocytes, and foamy histiocytes (macrophages).
Polymorphonuclear leukocytes are absent.

FIGURE 3. A 26-year-old female patient with KFD.
Maximum intensity projection image of FDG PET/CT (A) shows intense accumulation of FDG inbilateral cervical, right supraclavicular (arrows),
and abdominal lymphadenopathy (redarrowhead). Neck CT scan without contrast
enhancement (B) shows multiple bilateral cervicallymphadenopathy (arrows). Affected lymph nodes
along the celiac artery were first noted onwhole-body PET/CT (C–E), not on nonenhanced
abdominal CT (not shown).
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Tsujikawa et al

DISCUSSION
KFD is a self-limiting cause of cervical lymphadenopathy,
especially in young Asians, and it was previously reported to mimic
malignant lymphoma on diagnostic imaging, such as CT and FDG
PET.6 –13 On the other hand, several recent investigations described
FDG uptake as being useful in differentiating different subgroups oflymphoma, that is, being lower in indolent than in aggressive
lymphoma.19 –21 This study revealed that affected lymph nodes inpatients with KFD had a tendency to be smaller than those of NHL;however, FDG uptake with partial volume correction (corSUV) ofnodes in patients with KFD was higher than that of indolent NHL
and almost the same as that of aggressive NHL. These results
indicate that affected nodes of KFD show high FDG uptake for theirsize, which is expected to be a result of small necrotic foci and acollection of histiocytes (macrophages) in affected lymph nodes.
Necrotic foci themselves should not show FDG accumulation, but
necrotizing lymphocytes and numerous histiocytes (macrophages)
surrounding small necrotic foci are expected to show intense FDG
uptake. Since it is assumed that FDG uptake in inflammatory tissue
is due to accumulation in inflammatory cells, such as macrophages,22,23 lymphocytes,24 and granulocytes,25 in KFD macrophages and lymphocytes can cause high FDG avidity. Thus, when
diagnosing FDG-avid small lymphadenopathy in young patients,
KFD should be considered in the differential diagnosis. Additional
corSUV measurement can be useful for revealing the pathologic
features of KFD.
In addition to the degree of tracer uptake, FDG PET/CT wasvery useful for determining the extent of the disease. One-fourth ofpatients with KFD in this study (2 cases) had noncervical lesions, in
one of which abdominal lymphadenopathy could be detected only
by PET/CT. These results showed the same tendency as aggressive
lymphoma. The use of PET/CT is likely to detect more noncervicallesions of KFD than ever before; however, the detection of thoracoabdominal lesions may confuse the diagnosis of KFD with that ofstage of ⱖ2 lymphoma. We should be sensitive when diagnosing
systemic lymphadenopathy in young patients, and consider the
degree of lesion FDG uptake for size.
There are several limitations of this study. Hot spheres (10kBq/mL) with a warm background (2 kBq/mL) when considering
clinical cases were used for determining RC; however, in the human
body, the ratio of a tumor to background activity in surrounding
tissue varies according to its location. In addition, geometricfactors and the heterogeneity of the lesions seemed to influence
RC. Although it is difficult to compensate for PVE entirely on
clinical PET imaging, the PET/CT system should be improved,
and imaging and analysis protocols should be standardized tofurther reduce PVE and for more appropriate quantification of
FDG PET studies in the future.

CONCLUSION
Affected lymph nodes of KFD show high FDG uptake forsize, which may reflect the pathologic characteristics, including
small necrotic areas and a collection of histiocytes. FDG PET/CT
will be useful for detecting noncervical lesions of KFD and distinguishing KFD from NHLs using both SUV and corSUV.
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