BioMed Research International
Volume 2015 (2015), Article ID 354970, 5 pages
http://dx.doi.org/10.1155/2015/354970

Clinical Study

¹⁸F-FDG Uptake Characteristics in Differentiating Benign from Malignant Nasopharyngeal Lesions in Children

Chao Ma, Renjian Zou, Yanlei Huo, Suyun Chen, Shaoyan Wang, Shuqi Wu, Zhiyi Ye, Zhenyu Wu, Feng Fang, and Hui Wang

Nuclear Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China

Received 12 January 2015; Revised 7 May 2015; Accepted 17 June 2015

Academic Editor: Dominic Fan

Copyright © 2015 Chao Ma et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract.

The characteristics of FDG uptake in the physiologic and malignant nasopharynx were investigated in the paper which was correlated with either pathologic findings or clinical follow-up. Three patients had pathologically established nasopharyngeal malignancy. In the 3 nasopharyngeal malignancies, 2 had diffusely and expansively increased FDG uptake, and one had asymmetric uptake. Our results indicated that the difference between adenoid hypertrophy and malignancy is asymmetric or diffusely expansive ¹⁸F-FDG uptake with or without correlating morphologic lesion on diagnostic CT in children under 10 years of age. The typical characteristics of physiologic and inflammatory ¹⁸F-FDG uptake in nasopharynx are symmetrically trapezoid. Diffusely increased nasopharyngeal FDG uptake can be considered physiologic if is less than 7.6 but should be carefully assessed by pharyngorhinoscopy if is greater than 11 and there is no correlating morphologic lesion on diagnostic CT. The diffusely, expansively increased uptake, and asymmetric uptake in particular, should be considered as malignancy. Further biopsy is especially indicated in patients with retropharyngeal space and bilateral cervical lymph node abnormality but no history of malignancy.

1. Introduction

Pediatric nasopharyngeal carcinoma (NPC) is rare and usually poorly differentiated [1]. ¹⁸F-FDG PET/CT is a valuable imaging modality for evaluating and monitoring NPC in children [2] and adults [3–6]. Asymmetric ¹⁸F-FDG uptake in the nasopharynx on PET with a correlating morphologic lesion on fully diagnostic CT may well indicate nasopharyngeal malignancy. However, diffusely increased ¹⁸F-FDG uptake in the pediatric nasopharynx is common for both physiologic and inflammatory changes. Therefore, it is difficult to tell whether diffusely increased ¹⁸F-FDG uptake in the nasopharynx on PET without a correlating morphologic lesion on diagnostic CT suggests nasopharyngeal malignancy. No studies of the probability of NPC vis-à-vis ¹⁸F-FDG uptake have, to our knowledge, been performed. In this investigation, we studied the utility of nasopharyngeal ¹⁸F-FDG uptake in children under 10 years of age to determine the characteristics of FDG uptake in the physiologic and malignant nasopharynx.

2. Materials and Methods

2.1. Study Population

From May 2011 to May 2013, 154 children under 10 years of age with either established or suspected malignancy were enrolled in the study and underwent ¹⁸F-FDG PET scanning. The study was approved by the research ethics committee of our hospital. Written informed consent was obtained from the parents or guardians of all included patients before ¹⁸F-FDG PET/CT. The distribution of malignancy and suspected malignancy is listed in Table 1.

Table 1: Distribution of malignancy in study population.

Diagnosis
Number of patients

Established malignancy
Osteosarcoma
6

Lymphoma
7

Rhabdomyosarcoma
13

Neuroblastoma
32

Wilms tumor
21

Langerhans cell histiocytosis
8

Brain tumor
27

Thyroid cancer
3

Hepatoblastoma
4

Germ cell tumors
2

Thymoma
2

Yolk sac tumor
5

Medulloblastoma
2

Primitive neuroectodermal tumors
4

Lymphoma involvement of nasopharynx
1

Suspected tumors and fever of unknown origin
Nasopharyngeal carcinoma
2

Others
15

2.2. ¹⁸F-FDG PET/CT Imaging Protocol

¹⁸F-fluorine was produced at the PET Centre of Xinhua Hospital, Shanghai. Blood glucose level was measured prior to injection of ¹⁸F-FDG and was normal in all. The patients received a 5.18 MBq/kg dose of ¹⁸F-FDG (±10%; maximum, 444 MBq) intravenously after an overnight fast or, for afternoon studies, a minimally 4-hour fast. After injection, the patients stayed in the PET preparation room and rested for 1 hour. Relaxation with no movement or minimal movement during the uptake phase was encouraged. Just before the end of the 1-hour uptake period, the patients voided their bladders.

Transmission CT images for attenuation correction and lesion localization, and PET emission images, were acquired approximately 1 hour after injection using a Biograph PET/CT system (Siemens). The CT images were acquired using slice thickness of 0.3 cm, 0.8 s tube rotation, table speed of 1.5 cm/rotation, pitch of 1.5 : 1, 120 kV, 90 mA, and dose modulation. The PET images were obtained from the vertex of the skull to the mid-thigh level for 5 min per bed position in 2-dimensional mode. The PET/CT scans for each patient were reviewed by 2 nuclear medicine physicians without knowledge of any clinical information. in the nasopharynx was determined from manually placed regions of interest over the area of tumor activity in multiple planes. Follow-up clinical and pathologic information were recorded for correlation with tumor uptake of ¹⁸F-FDG ().

2.3. Statistical Analysis

We analyzed the association between in the nasopharynx and clinical and pathologic results using the 50th, 75th, 90th, and 95th percentiles for differentiation between benign and malignant nasopharyngeal lesions in children (SPSS software, version 13.0; IBM).

3. Results

The children had a median age of 4 years, and the male-to-female ratio was 91 : 63. One hundred thirty-seven had established malignancy and underwent PET/CT for staging, postoperative restaging, or therapeutic assessment. The other 17 underwent PET/CT because of suspected malignancy or fever of unknown origin.

The benign increased uptake of ¹⁸F-FDG in nasopharynx of children under 10 years of age is symmetric and trapezoid (see Figure 1). Nasopharyngeal carcinomas (NPC) (2/17, 12%) were confirmed in 17 suspected malignancies of unknown origin. In 137 established malignancies, 1 (1/137, 0.73%) case had lymphoma involvement. Three patients had pathologically established nasopharyngeal malignancy, two had diffusely and expansively increased FDG uptake, and one had asymmetric uptake. The clinical and imaging characteristics of these three children are listed in Table 2. The value in patient numbers 1−3 was 18, 11, and 8.2, respectively. Patient number 1 with incidental NPC (, 18; Figure 2) and lymphoma involvement (, 11) had diffusely increased ¹⁸F-FDG uptake in the nasopharynx (which was not shown). Patient number 3 (Figure 3) had asymmetric ¹⁸F-FDG uptake in the nasopharynx (, 8.2) and multiple metastases on PET with correlating morphologic lesions on diagnostic CT.

Table 2: Clinical features and characteristics of ¹⁸F-FDG PET/CT in three children with nasopharyngeal malignancy.

Patient number
Age (y)
Sex
Diagnosis at PET scan
PET/CT findings
Results of follow-up

1
10
M
Suspected neurogenic tumors by biopsy of left cervical lymph nodes
Diffusely increased ¹⁸F-FDG uptake in nasopharynx (SUV, 18), retropharyngeal space, and bilateral cervical lymph nodes; focal uptake in spleen
NPC

2
5
F
Liver multiple metastases of unknown origin
Inhomogeneously increased ¹⁸F-FDG uptake with irregular thickening in left nasopharynx (SUV, 8.2); multiple liver and bone metastases
NPC

3
6
M
Burkitt lymphoma, tonsils
Diffusely increased ¹⁸F-FDG uptake in nasopharynx mass (SUV 11) and bilateral cervical lymph nodes
Lymphoma involvement of nasopharynx

Figure 1: The normally increased uptake of ¹⁸F-FDG ( 11) in the nasopharynx of a 1-year-old boy is symmetric and trapezoid.

(a)

(b)

(c)

(d)

(e)

Figure 2: CT (top), PET (middle), and PET/CT (bottom) scans of patient number 1 (a–d). (a) and (c) were for initial staging: pretherapy scans showing diffuse soft-tissue thickening and ¹⁸F-FDG accumulation in nasopharynx (, 18) (a) and intense uptake in retropharyngeal lymph node and bilateral cervical lymph nodes (, 8.3) (c). (b) and (d) were for follow-up staging: scans after seven cycles of docetaxel-based chemotherapy and nasopharyngeal and cervical radiotherapy showing slight ¹⁸F-FDG uptake in right nasopharynx (, 4.0) (b) and no uptake in lymph node metastases (d). (e) Photomicrograph of patient number 1 showing poorly differentiated squamous cell carcinoma consistent with NPC (hematoxylin and eosin, ×100).

(a)

(b)

(c)

Figure 3: CT (top), PET (middle), and PET/CT (bottom) scans of patient number 3. (a) Intense inhomogeneous ¹⁸F-FDG uptake in left nasopharyngeal primary mass and asymmetric diffuse soft-tissue thickening in nasopharynx ( 8.2). (b) Multifocal uptake in liver correlating with multiple cystic lesions on CT ( 5.2). (c) ¹⁸F-FDG uptake in ilium (bone marrow, 5.0).

The association between in the nasopharynx and the incidence of NPC using the 50th, 75th, 90th, and 95th percentiles is presented in Table 3. The risk of nasopharyngeal malignancy increased with : 8.6%, 22%, and 40% in patients with of at least 7.60, 9.58, and 10.88, respectively.

Table 3: SUV and malignancy of nasopharynx in study population.

Median
SUV
Incidence of nasopharyngeal malignancy

50th percentile
5.5
3/75 (4%)

75th percentile
7.6
3/35 (8.6%)

90th percentile
9.58
2/9 (22%)

95th percentile
10.88
2/5 (40%)

4. Discussion

¹⁸F-FDG PET/CT is helpful for staging and posttreatment assessment of adult NPC [3–6]. However, in children diffusely increased ¹⁸F-FDG uptake and thickening of the nasopharynx are common for physiologic and inflammatory reasons. Therefore, it is difficult to tell whether increased nasopharyngeal ¹⁸F-FDG uptake without a correlating morphologic lesion on diagnostic CT suggests nasopharyngeal malignancy. In this investigation, we retrospectively reviewed nasopharyngeal ¹⁸F-FDG uptake in 154 children and correlated the with clinical and pathologic results.

Diffusely increased nasopharyngeal uptake in children may be due to physiologic changes, inflammation, or malignancy. It is not difficult to diagnose asymmetrically increased ¹⁸F-FDG uptake if there is a corresponding CT abnormality, as illustrated by patient number 3. In our study, uptake having less than 7.6 in the nasopharynx was considered physiologic. Diffusely increased ¹⁸F-FDG uptake ( > 9.58) without a correlating morphologic lesion on diagnostic CT may be due to inflammation or nasopharyngeal malignancy. Differentiation between nasopharyngeal inflammation and malignancy using PET/CT is difficult. Our results indicated that, in children under 10 years of age, the typical characteristics of physiologic and inflammatory ¹⁸F-FDG uptake in nasopharynx are symmetrically trapezoid with the less than 11. In our study, 7 children had of more than 9.58 in the nasopharynx due to viral or bacterial infections. However, the higher the nasopharyngeal (>10.88), the higher the incidence of nasopharyngeal malignancy (2/5, 40%). Nasopharyngeal malignancy in children may be characterized on PET/CT by asymmetric or expansively diffused, increased nasopharyngeal ¹⁸F-FDG uptake with or without a corresponding CT abnormality with greater than 11. As shown by patient number 1, nasopharyngeal biopsy may well be indicated in patients with of more than 11 in the nasopharynx with retropharyngeal space and bilateral cervical lymph node abnormality but no history of malignancy. Meanwhile, carefully diagnosis should be made in patients with less than 11. Patient number 3 had NPC with of 8.2 and multiple metastases including liver. The asymmetric ¹⁸F-FDG uptake and correlating morphologic lesions on diagnostic CT are of great help to make the diagnosis of NPC.

NPC is rare in the pediatric age group. In the study, NPC (2/17, 12%) were confirmed in 17 suspected malignancies of unknown origin. In 137 established malignancies, 1 (1/137,0.73%) case had lymphoma involvement. Children tend to have the poorly differentiated histologic variant of the disease, which is associated with increased locoregional spread and distant metastasis. Splenic metastases have been reported in adult cancers but are unusual in pediatric solid tumors [7]. Bone (67%) and liver (30%) are the most common metastatic sites [8]. PET/CT is valuable for staging of NPC in children. Of the two cases of NPC in our study, one had regional lymphadenopathy and splenic metastases and the other had multiple metastases in bone (bone marrow) and liver that were clearly shown by ¹⁸F-FDG PET/CT. The rarity of splenic and cystic liver metastases in pediatric NPC has also been highlighted in a case report on a 14-year-old boy [7].

Chemoradiotherapy is the preferred treatment for local disease, whereas chemotherapy is the first choice for children with systemic disease [7]. ¹⁸F-FDG PET/CT is also helpful in therapeutic monitoring of children with NPC. In patient number 1 the incidental detection of NPC by ¹⁸F-FDG PET/CT ( 18) was showed in Figures 2(a) and 2(b). PET/CT imaging showed decreased ¹⁸F-FDG ( 4.0) and negative lymph nodes, which indicated a good response to chemotherapy and local radiotherapy, thus demonstrating the potential usefulness of the technique in metastatic pediatric NPC.

However, there are some limitations of this paper. We excluded malignancy in the other children according to the follow-up PET/CT or CT except for the three patients who had been diagnosed as malignancy. Only three children with nasopharyngeal malignancy were included. Further study will focus on the details about the children with physiologic or inflammatory nasopharyngeal ¹⁸F-FDG uptake, including the distribution pattern (symmetrical or not) and the correlation of SUVs with the children’s age and gender, the soft-tissue thickness of the nasopharynx, and recent history of rhinitis.

5. Conclusion

The difference between adenoid hypertrophy and malignancy is asymmetric or diffusely expansive ¹⁸F-FDG uptake with or without correlating morphologic lesion on diagnostic CT. In children under 10 years of age, the typical characteristics of physiologic and inflammatory ¹⁸F-FDG uptake in nasopharynx are symmetrically trapezoid. Diffusely increased nasopharyngeal ¹⁸F-FDG uptake can be considered physiologic if is less than 7.6 but should be carefully assessed if is greater than 11 and there is no correlating morphologic lesion on diagnostic CT. The diffusely, expansively increased uptake, and asymmetric uptake in particular, should be considered as malignancy. Further biopsy is especially indicated in patients with retropharyngeal space and bilateral cervical lymph node abnormality but no history of malignancy. ¹⁸F-FDG PET/CT is a valuable imaging modality in staging and therapeutic assessment of NPC in children.

Conflict of Interests

The authors declare that there is no conflict of interests regarding the publication of this paper.

Authors’ Contribution

Chao Ma, Renjian Zou, and Yanlei Huo contributed equally to this work.

Acknowledgments

This work was supported by the National Natural Science Fund (Grants 51233007, 81271612, and 81401439), Shanghai Pujiang Program (Grant 13PJD022), and Shanghai Health Bureau Fund (Grant 20124016). The authors thank Dr. Albert Driedger from Department of Nuclear Medicine, Canada Health Sciences Centre, London, Ontario, Canada, for valuable advice on the paper.

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