comparison of pet-ct and mri for the detection of bone marrow invasion in patients with squamous...

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Comparison of PET/CT and MRI for the detection of bone marrow invasion in

patients with squamous cell carcinoma of the oral cavity

Yasser G. Abd El-Hafez a,b, Chien-Cheng Chen c, Shu-Hang Ng c, Chien-Yu Lin d, Hung-Ming Wang e,Sheng-Chieh Chan a, I-How Chen f, Shiang-Fu Huan f, Chung-Jan Kang f, Li-Yu Lee g, Chih-Hung Lin h,Chun-Ta Liao f,, Tzu-Chen Yen a,

a Nuclear Medicine Department, Molecular Imaging Center, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan, ROCb Radiotherapy and Nuclear Medicine Department, South Egypt Cancer Institute, Assiut University, Egyptc Department of Diagnostic Radiology, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan, ROCd Department of Radiation Oncology, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan, ROCe Department of Medical Oncology, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan, ROCfDepartment of Otorhinolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan, ROCg Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan, ROCh Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan, ROC

a r t i c l e i n f o

Article history:

Received 24 December 2010

Received in revised form 11 February 2011

Accepted 11 February 2011

Keywords:

Bone invasionOral cancer

Mandible

Maxilla

Squamous cell carcinoma

Positron emission tomography (PET)/

computed tomography (CT)

Fluorodeoxyglucose

Magnetic resonance imaging

s u m m a r y

Our aim was to retrospectively assess the diagnostic performance from combined positron emission

tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) for the detection

of bone marrow invasion of the mandible or maxilla in patients with oral cavity squamous cell carcinoma

(OCSCC).

A total of 114 patients with OCSCC, arising from or abutting the upper or lower alveolar ridge, under-

went staging PET/CT and MRI studies before surgery. The possibility of bone marrow invasion on PET/CT

and MRI was graded retrospectively on a 5-point score. Histopathology was taken as the reference stan-

dard. Sensitivity, specificity, predictive values and likelihood ratios were calculated. Clinical factorsaffecting the performance, like tumor origin and dentate status were also explored.

PET/CT was found to be more specific than MRI (83% vs.61%, respectively,p= 0.0015) but less sensitive

(78% vs. 97%, respectively, p = 0.0391). Dentate status and tumor origin affected the diagnostic perfor-

mance of PET/CT. In patients with positive MRI, sensitivity and specificity of PET/CT were 78% and

100% in dentate patients with alveolar ridge tumors, 75% and 80% in dentate patient with buccal tumors,

90% and 33% in edentulous patients with alveolar ridge tumors and 0% and 63% for edentulous patients

with buccal tumors, respectively.

PET/CT is more specific than MRI and can be used to complement the role of MRI. A negative MRI result

can confidently exclude the presence of bone marrow invasion, while in patients with positive MRI find-

ings, a negative PET/CT may be useful to rule out bone marrow invasion in dentate patients.

2011 Elsevier Ltd. All rights reserved.

Introduction

The preoperative detection of bone marrow invasion involving

both the maxilla and mandible in patients with squamous cell

carcinoma of the oral cavity (OCSCC) is critical to the planning of

surgery and postoperative management. It is accepted that when

the mandibular bone marrow is free of tumor, mandibular continu-

ity can usually be preserved and a marginal mandibulectomy may

be oncologically sufficient for minimal cortical erosion.1,2 However,

once bone marrow invasion has occurred, a much more extensive

and lengthy operation involving segmental mandibulectomy plus

bone reconstruction is necessary to provide an adequate clear bony

margin.3,4 When tumor invades the maxillary marrow spaces,

greater resection margin and extensive reconstruction may be

required.

Computed tomography (CT) and magnetic resonance imaging

(MRI) are the standard modalities used to evaluate primary tumor

status in patients with OCSCC. In general, MRIispreferred because

of its superior soft-tissue contrast resolution,5 but its diagnostic

accuracyin the detection of bone marrow invasion is still a matter

of debate.611 Indeed, few past studies have shown high sensitivity

1368-8375/$ - see front matter 2011 Elsevier Ltd. All rights reserved.doi:10.1016/j.oraloncology.2011.02.010

Corresponding authors. Address: Department of Otorhinolaryngology, Head and

Neck Surgery, Head and Neck Oncology Group, Chang Gung Memorial Hospital,

Chang Gung University, 5 Fu-Hsin Street, Gweishan, Taoyuan 333, Taiwan, ROC.

Tel.: +886 3 328 1200x8466; fax: +886 3 211 0052 (C.-T. Liao). Department of

Nuclear Medicine, Molecular Imaging Center, Chang Gung Memorial Hospital,

Chang Gung University, 5 Fu-Hsin Street, Gweishan, Taoyuan 333, Taiwan, ROC.

Tel.: +886 3 328 1200x2744; fax: +886 3 211 0052 (T.-C. Yen).

E-mail addresses: [email protected] (C.-T. Liao), [email protected].

org.tw(T.-C. Yen).

Oral Oncology 47 (2011) 288295

Contents lists available at ScienceDirect

Oral Oncology

j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / o r a l o n c o l o g y
http://dx.doi.org/10.1016/j.oraloncology.2011.02.010mailto:[email protected]:[email protected].%20org.twmailto:[email protected].%20org.twhttp://dx.doi.org/10.1016/j.oraloncology.2011.02.010http://www.sciencedirect.com/science/journal/13688375http://www.elsevier.com/locate/oraloncologyhttp://www.elsevier.com/locate/oraloncologyhttp://www.sciencedirect.com/science/journal/13688375http://dx.doi.org/10.1016/j.oraloncology.2011.02.010mailto:[email protected].%20org.twmailto:[email protected].%20org.twmailto:[email protected]://dx.doi.org/10.1016/j.oraloncology.2011.02.010


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and specificity,10,11 whereas others demonstrated high sensitivity

but low specificity.69

The preoperative detection of bone marrow invasion may be

theoretically enhanced with the use of combined positron emission

tomography (PET)/CT imaging that detects metabolic anomalies

via differences in tissue glucose uptake. However, relatively few

studies have addressed this question.1215 The purpose of our study

was therefore to assess and compare the diagnostic accuracy of

PET/CT and MRI in detecting bone marrow invasion involving both

the maxilla and mandible in patients with OCSCC and also to ex-

plore possible clinical factors, which might affect the performance

of these modalities.

Materials and methods

Patients

This retrospective study was approved by the Institutional

Review Board at our hospital, and all patients provided written in-

formed consent. The study population consisted of 114 patients

with newly diagnosed OCSCC who were referred to our hospital

between June 2006 and December 2009. Inclusion criteria were a

diagnosis of SCC, originating from the alveolar ridge (upper or low-

er) or other oral cavity subsites but involving the alveolar ridge,

preoperative PET/CT and MRI staging studies and surgical manage-ment. All patients underwent marginal or segmental mandibulec-

tomy, either with or without inferior maxillectomy. Segmental

mandibulectomy was performed in the presence of: (a) bone mar-

row invasion detected by conventional modalities (CT/MRI and

orthopantogram); (b) an edentulous atrophic mandible; and (c) tu-

mors close to the mandible precluding a marginal resection. Tumor

margins were sent for frozen section. If frozen section margins

were positive, additional tissue was excised and sent for frozen

section in order to ensure that margins were tumor-free. The sur-

gical defects were repaired with primary closure or reconstructed

by free or local flaps. Patients were classified as edentulous if they

lost one or more tooth at the site of the tumor, either the upper or

lower alveolar ridge, as seen in the immediate post-surgical

specimens.

Histopathology

The surgical specimens were fixed in 10% formalin solution and

decalcified for a period of one day. Specimens were inked and soft

tissue was removed to grossly evaluate the bone. In the presence

of gross bone invasion, a representative 5 mm section of the

bonetumor interface was prepared. In the absence of gross inva-

sion, 2 sections (5 mm each) were taken from the site with the

deepest tumor invasion. All sections were H&E stained in 5 lm

thickness and reviewed by a single pathologist who was aware of

the clinical staging.

Table 1

General characteristics of the study participants.

Parameter n %

Sex

Male 2 (1.8)

Female 112 (98.2)

Age, years

Median (range)a 50 (2977)

Anatomical subsites

Tongue 6 (5.3)

Floor of the mouth 6 (5.3)

Buccal 47 (41.2)

Alveolar ridge 39 (34.2)

Hard palate 2 (1.8)

Retromolar trigone 14 (12.3)

Dentate status

Dentate 64 (56.1)

Edentulous 50 (43.9)

Metal-related artifacts

No 53 (46.5)

Yes 61 (53.5)

Clinical T-status

T1 3 (2.6)

T2 34 (29.8)

T3 15 (13.2)

T4 62 (54.4)

Pathological T-status

T1 3 (2.6)

T2 38 (33.3)

T3 14 (12.3)

T4 59 (51.8)

Pathological bone marrow invasion

No 77 (67.5)

Yes 37 (32.5)

Site of marrow invasion

Mandible 34 (29.8)

Maxilla 2 (1.8)

Both 1 (0.9)

Bone management

MMb 16 (14)

SMc 36 (31.6)

MM+ MXd 36 (31.6)

SM + MX 26 (22.8)

a The numbers in parentheses indicate the range of the data. Unless otherwise

indicated, values are given as numbers of patients (percentages in parentheses).b Marginal mandibulectomy.c Segmental mandibulectomy.d Maxillectomy.

Table 2

Diagnostic performances of PET/CT and MRI for the detection of bone marrow invasion in patients with squamous cell carcinoma of the oral cavity.

Imaging modality FNa TPb TNc FPd Total Sensitivity

(95% CIe)

Specificity

(95% CIe)

PPVf

(95% CIe)

NPVg

(95% CIe)

Accuracy

(95% CIe)

LR+h

(95% CIe)

LRi (95% CIe)

PET/CT 8 29 64 13 114 78 (7186) 83 (7690) 69 (6178) 89 (8395) 82 (7489) 4.6 (0.88.5) 0.3 (0.71.2)

MRI 1 36 46 29 112j 97 (94100) 61 (5270) 55 (4665) 98 (95101) 73 (6581) 2.5 (0.4 to 5.4) 0.0 (0.3 to 0.4)

a False negative.b True positive.c True negative.d False positive.e Confidence interval.f Positive predictive value.

g Negative predictive value.h Positive likelihood ratio.i

Negative likelihood ratio.j Two cases had severe metal artifacts and could not be interpreted on MRI.

Y.G. Abd El-Hafez et al./ Oral Oncology 47 (2011) 288295 289


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PET/CT imaging

Patients were asked to fast for at least 6 h before the start of

the PET study. Serum glucose level was determined at the time

of intravenous injection of 370 MBq (10 mCi) of 18F-FDG and all

the patients had glucose concentrations 4.8 23 5 10 6 2 67 (4786) 75 (5793) 2.7 (3.9 to 9.3)

SUV of the primary tumor

613.43 30 2 12 12 4 86 (7398) 0.3284 75 (6090) 0.3934 3.4 (3.1 to 9.9)

>13.43 35 6 16 8 5 73 (5887) 62 (4578) 1.9 (2.6 to 6.4)

Patient groupsg

Dentate alveolar ridge 8 1 4 3 0 80 (52108) 0.0025* 100 0.1165 #i

Dentate buccal 10 1 3 4 2 75 (48102) 0.0027* 67 (3796) 1.0000 2.3 (6.9 to 11.4)

Edentulous alveolar ridge 25 2 18 2 3 90 (78102)


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Healthcare, Erlangen, Germany) MRI scanner. The MRI examina-

tions were performed using a head-and-neck synergic coil to cover

the entire neck fromthe skull base to the thoracic inlet. T2- and T1-

weighted fast/turbo spinecho sequences were applied in the axial

plane. Post gadolinium contrast enhanced T1-weighted fast/turbo

spinecho sequences with fat saturation were applied in the axial,

coronal, and sagittal planes at 4-mm slice thickness. All data were

archived in DICOM format and transferred to a stand-alone work-

station for processing. All of the imaging analysis was performed

on a picture archiving and communication system (PACS) worksta-

tion (Centricity 1.0; GE Healthcare, Milwaukee, WI, USA). Tumor

invasion into the bone marrow was diagnosed by replacement of

the marrow fat of the involved mandible or maxilla by contiguous

tumors with abnormal T1 hypointensity, T2 hyperintensity, and

definite contrast enhancement. Bone erosion was considered to

be present if there was any irregular bone thinning while bone

destruction was diagnosed in the presence of complete cortical

bone loss. MR image distortions or artifacts close to the maxilla

or mandible were carefully recorded.

Image interpretation

PET/CT images were reviewed by one nuclear physician (6 years

experience in general nuclear medicine, 2 years in PET/CT) and one

head-and-neck radiologist (20 years experience), and a consensus

was reached via joint reevaluation of the images. All MRI data were

read by an independent head-and-neck radiologist (7 years experi-

ence), who was blinded to PET/CT findings. The readers were aware

of tumor origin and side. The images were evaluated qualitatively

for the presence of bone marrow invasion on a 5-point score, in

which a score of 0 indicated that bone marrow invasion was defi-

nitely absent; a score of 1, bone marrow invasion was probably ab-

sent; a score of 2, ambiguous cases characterized by cortical bone

erosion in the absence of overt bone destruction; a score of 3, bone

marrow invasion was probably present; and a score of 4, bone

marrow invasion was definitely present. A score of 2 or less was

considered negative. SUV was not considered in the image

interpretation.

Statistical analysis

Receiver operating characteristic (ROC) curve analysis was per-

formed to assess discriminative power of PET/CT and MRI for bone

marrow invasion. Histopathology was taken as the reference stan-

dard; sensitivity, specificity, predictive values and likelihood ratios

were calculated for expressing test performance. Categorical data

and paired readings were analyzed using the Chi-squared (v2) test

and the McNemars test, respectively. We determined the optimalcutoff values for tumor size and maximum SUV by ROC analysis

based on the presence of bone marrow invasion. SUVmax was

compared in two sub-groups using Students t-test for independent

samples. All statistical analyses were two-sided and the signifi-

cance level was fixed at 0.05.

Table 5

False-negative and false-positive results of PET/CT for the detection of bone marrow invasion in patients with squamous cell carcinoma of the oral cavity.

No. Anatomical

subsite

Dental

status

Metal-

related

artifacts

Differentiation cTa pTb Tumor

size

(cm)

SUVc

primary

tumor

Bone

management

Marrow

invasion

PET/CT

score

PET/CT

result

MRI

score

MRI

result

1 ARd

Dentate + MDf

T4 T4 3.5 8.1 SMi

+ 2 FNl

4 TPn

2 Buccal Edentulous + MDf T4 T4 5 33.4 SMi + MXj + 2 FNl 4 TPn

3 ARd Edentulous + MDf T4 T4 3.2 16.9 SMi + 0 FNl 4 TPn

4 Buccal Edentulous + WDg T4 T4 9 10.7 SMi + MXj + 2 FNl 4 TPn

5 Buccal Edentulous + PDh T4 T4 6 16.8 SMi + MXj + 2 FNl 4 TPn

6 B uccal Dentate MDf T4 T4 5.2 13.5 SMi + MXj + 2 FNl 4 TPn

7 ARd Edentulous MDf T4 T4 2.8 25.3 SMi + 0 FNl 4 TPn

8 RMTe Dentate MDf T4 T4 5.3 20.9 SMi + 0 FNl 4 TPn

9 RMTe Edentulous WDg T4 T4 3.5 14.3 SMi + MXj 4 FPm 4 FPm

10 Buccal Edentulous + MDf T4 T4 4.8 12.6 MMk + MXj 4 FPm 4 FPm

11 AR d Edentulous + MDf T4 T3 5 12.6 SMi 4 FPm 4 FPm

12 Buccal Edentulous + MDf T4 T4 4.2 20.2 SMi 3 FPm 4 FPm

13 Buccal Edentulous MDf T4 T4 6.5 22 SMi + MXj 3 FPm 4 FPm

14 Buccal Dentate + MDf T4 T4 4.5 13.2 MMk + MXj 4 FPm 4 FPm

15 Buccal Dentate + WDg T4 T3 4.5 11.3 MMk + MXj 3 FPm 4 FPm

16 AR d Edentulous WDg T4 T3 3.8 19.8 SMi + MXj 3 FPm 4 FPm

17 AR d Edentulous + PDh T4 T2 2.5 14.6 MMk + MXj 4 FPm 4 FPm

18 Buccal Dentate + WDg T2 T2 3.5 23.4 MMk + MXj 4 FPm 2 TNo

19 AR d Edentulous + WDg T2 T2 2.3 10.3 MMk 3 FPm 2 TNo

20 AR d Edentulous + PDh T3 T3 5 4.4 SMi + MXj 4 FPm 2 TNo

21 Buccal Edentulous MDf T2 T2 3.5 22.3 MMk + MXj 3 FPm 1 TNo

a Clinical tumor status.b Pathological tumor status.c Standardized uptake value.d Alveolar ridge.e Retromolar trigone.f Moderately differentiated.

g Well differentiated.h Poorly differentiated.i Segmental mandibulectomy.

j Maxillectomy.k Marginal mandibulectomy.l False negative.

m False positive.n

True positive.o True negative.



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Results

General characteristics

One hundred fourteen patients with squamous cell carcinoma

of the oral cavity were enrolled (Table 1). The median time interval

between diagnostic studies (PET/CT and MRI) and surgery was

2 days (range: 121 days for PET/CT; 156 days for MRI). The twostudies (PET/CT and MRI) were done within 4 weeks of each other,

except for one patient, who underwent MRI 54 days before PET/CT.

Histopathological examination revealed the presence of marrow

invasion in 37 patients (32.5%). More than 85% of the patients

had the habits of cigarette smoking and betel quid chewing. The

predominant tumor origins were buccal mucosa (41.2%) and alve-

olar ridge (34.2%).

Sixty-one patients had metal-related artifacts; in two of them,

the MRI was severely distorted and uninterpretable. These two pa-

tients were excluded from any subsequent comparative analyses.

The presence of metal artifacts did not affect the performance of

PET/CT. However, we encountered a single false negative result

due to misregistration between PET and CT. The FDG activity

seemed to be displaced by a fewmillimeters from the site of CT-de-

tected cortical erosion (scored 2 by consensus).

Diagnostic performance

MRI showed the highest sensitivity and negative predictive val-

ues (97% and 98%, respectively) with only one false negative result

(Table 2). However, low specificity and positive predictive valueswere encountered (61% and 55%, respectively). Twenty-nine false-

positive results were seen. Sensitivity and specificity of PET/CT

were 78% and 83% respectively with 8 false negative and 13 false-

positive results. Combined PET/CT was significantly more specific

(83%vs. 61%, p = 0.0015) and less sensitive than MRI (78%vs. 97%,

p= 0.0391). The overall accuracy was comparable (Table 3).

Clinical factors affecting PET/CT performance

Tumor origin and dentate status were found to affect the diag-

nostic performance of PET/CT. Bone marrow invasion was signifi-

cantly higher in edentulous patients than in dentate patients (23/

50 vs. 14/64, p= 0.009). In dentate patients, PET/CT had higher

Figure 1 Imaging findings of a 56-year-old man with a diagnosis of squamous cell carcinoma of the left buccal mucosa, (A) coronal fused PET/CT image of the tumor mass

without FDG uptake within the marrow cavity of the mandible. The corresponding non-contrast-enhanced CT image (B) demonstrated the presence of cortical bone erosion

only. Post gadolinium contrast enhancement coronal T2 (C) and T1 (D) MR weighted images showed a left buccal-gum cancer, with hyperintensity and enhancement in thebone marrow of left mandible, suggesting bone marrow invasion. Pathological results were positive for marrow invasion.

292 Y.G. Abd El-Hafez et al. / Oral Oncology 47 (2011) 288295


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specificity (94% vs. 63%, p= 0.0001) and positive likelihood ratio

([LR+], 13.1 vs. 2.1). A total of 13 false-positive results were

encountered, 10 of them were seen in edentulous patients. Inter-

estingly, all the false-positive results were in patients who had

the habit of betel quid chewing.

Alveolar ridge and buccal mucosa represented the two major

tumor origins in our study (n= 39 and 47, respectively). Tumorsoriginating in the alveolar ridge were significantly associated with

more bone marrow invasion (25/39vs. 7/47,p< 0.0001). Consider-

ing only these two subsites, PET/CT offered significant advantages

in terms of sensitivity (88% vs.43%,p< 0.0001) and positive predic-

tive value (81% vs. 30%, p < 0.0001) in alveolar ridge tumors com-

pared with buccal tumors.

There was a trend toward higher sensitivity, specificity, and LR+

when the size of the tumors was less than 4.8 cm or the SUV values

less than 13.43 mg/mL.

MRI was positive in 65 patients; 29 of them were falsely posi-

tive. Given this high false positive rate, we tried to identify a sub-

group of patients with MRI-positive findings in whom PET/CT may

be useful (Table 4). Among these 65 patients, MRI gave false-posi-

tive results in 53.6% of dentate patients (15/28). PET/CT success-fully excluded the presence of bone marrow invasion in 13 of

these 15 cases. In alveolar ridge tumors (n = 33), PET/CT also ex-

cluded disease in 5 out of 8 falsely positive MRI results. False-neg-

ative and false-positive results of PET/CT for the detection of bone

marrow invasion in this study are shown in Table 5.

Discussion

Assessment of facial bones invasion by OSCC is important for

head and neck surgical oncologists before treatment planning. In

the past, we largely relied on the findings from physical examina-

tion plus conventional images, such as panorex X-ray, CT and/or

MRI with unsatisfying results, especially when patients had a cer-

tain degree of dental problems. Studies from other groups have

shown that both PET/CT and SPECT/CT may be clinically useful,

with varying degrees of sensitivity (58.3100%, 92%, 41.7100%,

39.1100%) and specificity (85100%, 86%, 57.1100%, 4097.1%)

for PET/CT, SPECT/CT, CT, and MRI, respectively.1215 In this study,

we found a sensitivity and specificity of 78% and 83% for PET/CT,

and 97% and 61% for MRI, respectively. Our data suggest that

PET/CT may complement the role of MRI for diagnosing bone mar-row invasion in patients with oral cavity cancer. A negative MRI

Figure 2 Imaging findings of a 41-year-old manwith a diagnosis of squamous cell carcinomaof theright buccal mucosa, (A)transaxial fused PET/CT image of thetumor mass

that shows intense FDG uptake (SUVmax = 22.3) and it violates the bone boundary of the maxilla. The corresponding coronal non-contrast-enhanced CT image (B)

demonstrated the presence of cortical discontinuity, and also evidence of some periodontal disease. The lesion scored 4 on PET/CT by consensus. Post gadolinium contrast

enhancement axial T2 (C) and T1 (D) MR weighted images showed right upper gum cancer without abnormal signal intensity at right maxilla, suggestive of no bone marrow

invasion. Pathological result was negative for marrow invasion.



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scan could confidently exclude the presence of marrow invasion in

patients with OCSCC. However, positive results obtained with this

modality cannot always be considered true positive and PET/CT

scan may help to make the diagnosis. We encountered a single

false negative MRI result. Our findings concerning the high nega-

tive predictive value of MRI were well in line with the results of

previous studies.611

In our experience, there are two possible reasons to explain the

higher false-positive results. First, Taiwan is an endemic area for

betel quid chewing, and oral cancers in association with trismus

with subsequent poor oral hygiene are commonly seen in clinical

practice.16,17 Betel quid chewing was observed in 87% of patients

in this study. There were 28 false-positive results out of 99 patients

chewing betel quid compared to 1/15 patients not having this habit

(positive predictive value = 51%vs. 88%, p = 0.02). Second, all the

studied tumors were involving the alveolar ridge, which could eli-

cit a local inflammatory response. It has been reported that MRI

may yield falsely positive results in inflammatory odontogenic

disease.18

We encountered 8 false-negative PET/CT findings (Table 5); in 4

of them, the non-optimized CT intended for AC/AL was unable to

detect sites of minimal bone breakthrough. We assume that a more

optimized CT protocol for the head and neck region may add to the

diagnostic yield of PET/CT. The other 4 false-negative PET/CT

results were either due to low tracer uptake in the bone marrow

(patients # 1 and # 6), misregistration of the CT and PET images

(Patient # 5) or retraction of the edentulous alveolar ridge (Patient

# 2), which mislead the localization of FDG uptake ( Fig. 1). PET/CT

showed significantly higher false positive rate in edentulous com-

pared to dentate patients (37% vs. 6%, p= 0.0001). The reason for

that may be explained by: (a) Repeated episodes of periodontitis

are common in edentulous patients which may show avidity to

FDG (Fig. 2).19 (b) The mean SUV of the primary tumor was signif-

icantly higher in edentulous compared to dentate patients (15.2 vs.

12.6,p

= 0.036). High FDG uptake may produce a spillover effect,

leading to overestimation of the exact tumor extension (Fig. 3).20

In this study, the sensitivity and positive predictive value of

PET/CT were significantly lower for buccal compared to alveolar

ridge tumors; however, the negative predictive value, LR+ and

overall accuracy remained comparable. Of note, among all the

false-positive results encountered by PET/CT, the mean SUV within

buccal tumors was higher, though not significantly, than that seen

in alveolar ridge tumors (17.8vs. 12.3,p = 0.1).

Our study is not without important limitations. A head and neck

PET/CT study was not performed in all participants following the

whole-body acquisition. No contrast media were used routinely

for the CT portion of PET/CT. Moreover, the CT portion of PET/CT

was not optimized for diagnostic purpose. In addition, the inevita-

ble partial volume effect in PET/CT should be considered. Finally,

this study is a retrospective single-reader analysis, which reflects

a single center experience. Strengths of our report include the large

sample size, the use of histopathological examination as the gold

standard for comparison, and the homogeneity of diagnosis and

treatment plans.

Figure 3 Imaging findings of a 43-year-old man with a diagnosis of squamous cell carcinoma of the right buccal mucosa, (A) coronal fused PET/CT image of the tumor mass

that shows intense FDG uptake (SUVmax = 22) and it violates the bone boundary of the mandible. The corresponding coronal non-contrast-enhanced CT image (B)

demonstrated the presence of cortical erosion in the edentulous alveolar socket and possible breakthrough. Post gadolinium contrast enhancement coronal T2 (C) and T1 (D)

MR weighted images showed right buccal-gum cancer with mild bone erosion on the edentate alveolar socket. No abnormal signal intensity at right mandible, indicatingbone cortex invasion without bone marrow involvement. Pathological result was positive for both periosteal and cortical invasion but negative for marrow invasion.

294 Y.G. Abd El-Hafez et al. / Oral Oncology 47 (2011) 288295


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Conclusion

PET/CT is more specific than MRI and can be used to comple-

ment the role of MRI. A negative MRI result can confidently exclude

the presence of bone marrow invasion in patients with squamous

cell carcinomas of the oral cavity. In dentate patients with positive

MRI findings, a negative PET/CT may be useful to rule out bone

marrow invasion in dentate patients. PET/CT had a significantlyhigher sensitivity and positive predictive value in alveolar ridge tu-

mors compared to buccal mucosa tumors.

Conflict of Interest

None declared.

Acknowledgements

This work was supported in part by a Grant-in-Aid for FDG PET

Research in Oral Cancer from Chang Gung Memorial Hospital-Link-

ou (CMRPG370062).

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