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DOI: 10.1148/rg.251045045
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RadioGraphics 2005;25:191-207
© RSNA, 2005

EDUCATION EXHIBIT

FDG PET in the Evaluation of Treatment for Lymphoma: Clinical Usefulness and Pitfalls1

Toshiki Kazama, MD, Silvana C. Faria, MD, Vithya Varavithya, MD, Sith Phongkitkarun, MD, Hisao Ito, MD, PhD and Homer A. Macapinlac, MD

1 From the Department of Radiology, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan (T.K., H.I.); and the Division of Diagnostic Imaging, University of Texas M. D. Anderson Cancer Center, Houston, Tex (T.K., S.C.F., V.V., S.P., H.A.M.). Presented as an education exhibit at the 2003 RSNA Scientific Assembly. Received March 16, 2004; revision requested May 21 and received August 24; accepted August 26. H.A.M. is a member of the speakers’ bureau for Siemens and Cardinal Health and received a grant from GE Medical Systems. All remaining authors have no financial relationships to disclose. Address correspondence to T.K. (e-mail: kazamat@fg7.so-net.ne.jp).


   Abstract
Top
 Abstract
LEARNING OBJECTIVES
 Introduction
 FDG PET Technique
 Treatment Response Evaluation
 Pitfalls
 False-Negative Findings
 Summary
 References
 
Positron emission tomography (PET) with 2-[fluorine-18] fluoro-2-deoxy-D-glucose (FDG) may play an important role in the evaluation and management of malignant lymphoma. FDG uptake is predictive of therapeutic response during the course of treatment. After completion of chemotherapy, residual abnormalities representing either residual tumor or necrotic or fibrotic tissue are not uncommon, and FDG PET may be more accurate than computed tomography (CT) or magnetic resonance imaging in assessing residual disease and identifying patients who require more intense treatment. However, posttreatment FDG PET does not help exclude the presence of minimal residual disease, which may lead to disease relapse. Furthermore, FDG is not a tumor-specific substance, and increased accumulation may be seen in a variety of benign entities and scenarios (eg, infection, drug toxicity, granulocyte colony-stimulating factor therapy, radiation therapy, physiologic activity, postoperative or postbiopsy changes, fracture, degenerative change, injection leakage), which may yield false-positive findings. Nevertheless, recognition of these entities and correlation of FDG PET findings with clinical and other radiologic findings—especially those at combined PET and CT or PET-CT fusion imaging—allows improved diagnostic accuracy. If the interpretation of positive findings is exceptionally difficult, short-term follow-up may be helpful.

© RSNA, 2005


   LEARNING OBJECTIVES
Top
 Abstract
 LEARNING OBJECTIVES
Introduction
 FDG PET Technique
 Treatment Response Evaluation
 Pitfalls
 False-Negative Findings
 Summary
 References
 
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   Introduction
Top
 Abstract
 LEARNING OBJECTIVES
 Introduction
FDG PET Technique
 Treatment Response Evaluation
 Pitfalls
 False-Negative Findings
 Summary
 References
 
Malignant lymphoma accounts for approximately 8% of all malignancies and is the sixth most common malignancy in the United States. Although Hodgkin disease and non-Hodgkin lymphoma are both classified as malignant lymphomas, the vast majority of cases are non-Hodgkin lymphoma. Treatment usually consists of a combination of chemotherapy and radiation therapy, which is frequently curative but often induces inflammatory conditions that can be confused with disease progression.

In recent years, positron emission tomography (PET) with 2-[fluorine-18] fluoro-2-deoxy-D-glucose (FDG) has become an established imaging method for the evaluation of lymphoma patients. Studies have shown that FDG PET may be superior to computed tomography (CT), gallium-67 scintigraphy, and bone scintigraphy in the staging and treatment evaluation of lymphoma because of good spatial resolution and the functionality of FDG PET scans (1–4).

In this article, we review FDG PET technique, discuss and illustrate the usefulness of FDG PET in the evaluation of treatment response in lymphoma patients, and describe various imaging pitfalls that may yield false-positive findings in this setting.


   FDG PET Technique
Top
 Abstract
 LEARNING OBJECTIVES
 Introduction
 FDG PET Technique
Treatment Response Evaluation
 Pitfalls
 False-Negative Findings
 Summary
 References
 
The biodistribution of FDG can be affected by various physiologic factors. Blood glucose levels have an impact on FDG uptake through (a) competitive displacement of FDG by plasma glucose and (b) patients being asked to fast for 6 hours prior to imaging. Because the primary route of FDG excretion is renal, good hydration is required. Muscle relaxants may be used to reduce muscle uptake. Patients are asked to remain silent during and after injection to reduce laryngeal muscle uptake. All patients are injected with 10–15 mCi (370–555 MBq) of FDG and scanned approximately 60 minutes later. Most of the images in this article were obtained with a CTI/Siemens HR(+) scanner (Siemens, Knoxville, Tenn). Additional transmission scanning for attenuation correction was performed. Each scan was performed from the head to the pelvic floor. The acquired data were reconstructed using iterative reconstruction with segmented attenuation correction in axial sections and reformatted into coronal and sagittal projections.

Monitoring the response to therapy for lymphoma with FDG PET usually requires performance of a baseline study before treatment.


   Treatment Response Evaluation
Top
 Abstract
 LEARNING OBJECTIVES
 Introduction
 FDG PET Technique
 Treatment Response Evaluation
Pitfalls
 False-Negative Findings
 Summary
 References
 
PET after Completion of Chemotherapy
Achieving complete remission is the main objective of first-line chemotherapy. Complete remission is usually associated with a longer progression-free survival time than is partial remission, which is associated with poorer clinical outcome. However, defining complete remission can be difficult in some patients in whom residual abnormalities remain. Posttherapy residual abnormalities representing the development of fibrosis or tumor necrosis are seen in up to 64% of patients with lymphoma (5–9). Conventional imaging (CT, ultrasonography, magnetic resonance [MR] imaging) cannot reliably help differentiate between active tumor and fibrosis or necrosis. Metabolic FDG PET offers the advantage of func-tional tissue characterization. Currently, FDG PET may be more accurate than anatomic imaging modalities in assessing treatment effects to correctly identify patients with residual disease and predict therapy outcomes (Figs 1, 2) (5–9). In patients with persistent FDG uptake, it might be appropriate to use salvage therapy and possibly hematopoietic stem cell transplantation before a clinically overt relapse occurs. Nevertheless, after completion of chemotherapy, FDG PET cannot help exclude the presence of microscopic residual disease, which may lead to a later relapse (5–9).



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  		Figure 1a.  Residual mass with FDG uptake in a 76-year-old woman with non-Hodgkin lymphoma who had completed chemotherapy. (a) Chest CT scan shows residual soft-tissue attenuation in the mediastinum and right hilum. (b) Corresponding axial PET scan shows residual FDG uptake in the same location. The patient underwent salvage chemotherapy, but tumor relapse occurred.

 


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  		Figure 1b.  Residual mass with FDG uptake in a 76-year-old woman with non-Hodgkin lymphoma who had completed chemotherapy. (a) Chest CT scan shows residual soft-tissue attenuation in the mediastinum and right hilum. (b) Corresponding axial PET scan shows residual FDG uptake in the same location. The patient underwent salvage chemotherapy, but tumor relapse occurred.

 


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  		Figure 2a.  Residual mass without FDG uptake in a 72-year-old man who had just completed chemotherapy. (a) Abdominal CT scan shows residual nodules in the mesentery (arrow). (b) Corresponding axial PET scan shows no FDG uptake in the mesentery; however, physiologic uptake is seen in the intestinal tract (arrows). The patient remains free of disease.

 


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  		Figure 2b.  Residual mass without FDG uptake in a 72-year-old man who had just completed chemotherapy. (a) Abdominal CT scan shows residual nodules in the mesentery (arrow). (b) Corresponding axial PET scan shows no FDG uptake in the mesentery; however, physiologic uptake is seen in the intestinal tract (arrows). The patient remains free of disease.

 
PET after One to Three Cycles of Chemotherapy
There is growing interest in patient response early during treatment. Less than 50% of patients with newly diagnosed aggressive non-Hodgkin lymphoma can expect prolonged disease-free survival with current treatment regimens (10). Patients who do not respond to initial chemotherapy are candidates for salvage chemotherapy or autologous bone marrow transplantation. Recognition of resistant or nonresponding tumor early during chemotherapy may result in lower cumulative treatment toxicity and tumor burden at the start of salvage therapy, thereby potentially improving clinical outcome and prognosis. However, the usefulness of these strategies has yet to be established, and further studies are warranted. Usually, metabolic changes following therapy tend to precede anatomic changes, a phenomenon that allows early response evaluation with functional imaging (7,8,11–13). Effective treatment sharply reduces metabolic tumor activity within days, whereas persistent abnormal uptake is usually associated with treatment failure (Figs 3, 4). In addition, interim PET performed after one or two cycles of chemotherapy may help predict long-term freedom from relapse more accurately than posttreatment PET, which does not help exclude the presence of microscopic residual disease (7,8).



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  		Figure 3a.  No increased FDG uptake at early evaluation in a 21-year-old man with Hodgkin disease who had undergone two cycles of chemotherapy. (a) Chest CT scan shows residual mediastinal lymphadenopathies (arrows). (b) Corresponding axial PET scan shows no increased uptake at the site of the mediastinal masses (arrows). Note, however, the uptake in the spine and sternum (arrowheads) due to granulocyte colony-stimulating factor (G-CSF) therapy. The patient remains disease free after completing chemotherapy.

 


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  		Figure 3b.  No increased FDG uptake at early evaluation in a 21-year-old man with Hodgkin disease who had undergone two cycles of chemotherapy. (a) Chest CT scan shows residual mediastinal lymphadenopathies (arrows). (b) Corresponding axial PET scan shows no increased uptake at the site of the mediastinal masses (arrows). Note, however, the uptake in the spine and sternum (arrowheads) due to granulocyte colony-stimulating factor (G-CSF) therapy. The patient remains disease free after completing chemotherapy.

 


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  		Figure 4a.  Residual increased FDG uptake at early evaluation in a 33-year-old woman with Hodgkin disease who had undergone one cycle of chemotherapy. (a) Axial CT scan shows a large right paramediastinal lesion. (b) Coronal PET scan shows increased FDG uptake (arrow) corresponding to the lesion seen in a. Note also the physiologic uptake in the myocardium and kidneys. Although the patient underwent intensive treatment, she had a poor prognosis.

 


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  		Figure 4b.  Residual increased FDG uptake at early evaluation in a 33-year-old woman with Hodgkin disease who had undergone one cycle of chemotherapy. (a) Axial CT scan shows a large right paramediastinal lesion. (b) Coronal PET scan shows increased FDG uptake (arrow) corresponding to the lesion seen in a. Note also the physiologic uptake in the myocardium and kidneys. Although the patient underwent intensive treatment, she had a poor prognosis.

 
PET before Autologous Stem Cell Transplantation
Treatment consisting of high-dose chemotherapy combined with stem cell transplantation has been shown to be effective in patients who experience a relapse of lymphoma after undergoing conventional chemotherapy but remain chemotherapy sensitive. It has been reported that FDG PET performed after salvage chemotherapy and before a combination of high-dose chemotherapy and stem cell transplantation can help predict patient outcome (14,15). That is, whereas patients with negative pretransplantation FDG PET findings are unlikely to experience relapse, abnormal uptake at pretransplantation FDG PET is associated with tumor progression after transplantation.

PET during or after Radiation Therapy or Radioimmunotherapy
The relationship between radiation therapy and changes in tumor FDG uptake has yet to be established. Generally, FDG uptake 6 months after radiation therapy is associated with tumor recurrence.

Radioimmunotherapy with iodine-labeled anti-B1 antibody developed against the surface antigen CD20 has been recognized as a promising approach for treatment of low-grade non-Hodgkin lymphoma (16). Tumor response to radioimmunotherapy may be more gradual than response to chemotherapy. In a study by Torizuka et al (17), FDG PET metabolic data obtained 1–2 months after radioimmunotherapy correlated well with the ultimate response of non-Hodgkin lymphoma to radioimmunotherapy.

Restaging and Surveillance
A study by Jerusalem et al (18) demonstrated that FDG PET is a useful diagnostic tool in the follow-up of asymptomatic treated patients and the evaluation of symptomatic patients with suspected disease recurrence (Figs 5, 6). Detection of residual tumors at a subclinical level or within a small volume might be beneficial for optimizing the efficacy of subsequent therapy.



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  		Figure 5a.  Enlarging lymph node without FDG uptake in a 70-year-old woman with non-Hodgkin lymphoma that had been in remission for 3 years. (a, b) Serial CT scans obtained 6 months apart show an enlarging lymph node in the peripancreatic region (arrow). (c) Corresponding axial PET scan shows no increased FDG uptake in the peripancreatic region. Note, however, the physiologic uptake in the kidneys and liver. The patient remains free of disease.

 


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  		Figure 5b.  Enlarging lymph node without FDG uptake in a 70-year-old woman with non-Hodgkin lymphoma that had been in remission for 3 years. (a, b) Serial CT scans obtained 6 months apart show an enlarging lymph node in the peripancreatic region (arrow). (c) Corresponding axial PET scan shows no increased FDG uptake in the peripancreatic region. Note, however, the physiologic uptake in the kidneys and liver. The patient remains free of disease.

 


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  		Figure 5c.  Enlarging lymph node without FDG uptake in a 70-year-old woman with non-Hodgkin lymphoma that had been in remission for 3 years. (a, b) Serial CT scans obtained 6 months apart show an enlarging lymph node in the peripancreatic region (arrow). (c) Corresponding axial PET scan shows no increased FDG uptake in the peripancreatic region. Note, however, the physiologic uptake in the kidneys and liver. The patient remains free of disease.

 


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  		Figure 6a.  Stable lymph nodes with FDG uptake in a 61-year-old man with non-Hodgkin lymphoma in remission. (a) CT scan shows prominent lymph nodes in the region of the right external iliac artery (arrows). (b) Corresponding axial PET scan shows FDG uptake in these nodes (arrows). Note also the physiologic uptake in the sigmoid colon (arrowheads). Results of biopsy confirmed the recurrence of non-Hodgkin lymphoma.

 


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  		Figure 6b.  Stable lymph nodes with FDG uptake in a 61-year-old man with non-Hodgkin lymphoma in remission. (a) CT scan shows prominent lymph nodes in the region of the right external iliac artery (arrows). (b) Corresponding axial PET scan shows FDG uptake in these nodes (arrows). Note also the physiologic uptake in the sigmoid colon (arrowheads). Results of biopsy confirmed the recurrence of non-Hodgkin lymphoma.

 

   Pitfalls
Top
 Abstract
 LEARNING OBJECTIVES
 Introduction
 FDG PET Technique
 Treatment Response Evaluation
 Pitfalls
False-Negative Findings
 Summary
 References
 
FDG PET is very useful in the evaluation of treatment response in lymphoma patients. However, FDG is not a tumor-specific substance, and increased accumulation may be seen in a variety of benign conditions, which may give rise to false-positive results. In the posttherapy setting, it has been reported that up to 40% of FDG uptake occurs in nontumor tissues (14). Although several of these imaging pitfalls are easily recognizable and therefore unlikely to present diagnostic problems, others are potentially confusing (Table). Correlation with findings at anatomic imaging such as CT is important and could help identify changes resulting from treatment; PET with CT and PET-CT fusion imaging are especially helpful in this setting (19). If interpretation is exceptionally difficult, short-term follow-up may be helpful (18).


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  		Common Causes of False-Positive FDG PET Findings in Lymphoma Patients

 
Infection
One of the well-known side effects of chemotherapy is bone marrow suppression, which leads to neutropenia, anemia, and thrombocytopenia. Affected patients are at increased risk for infections such as upper respiratory infection, pneumonia, enterocolitis, and cholecystitis (Figs 7–9) (20–23). Anti-inflammatory cells such as activated macrophages or granulation tissue that are present in areas of inflammation have been shown to actively take up FDG (24,25).



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  		Figure 7a.  Pneumonia in a 72-year-old man with non-Hodgkin lymphoma who was undergoing chemotherapy. (a) Coronal PET scan shows FDG uptake in the right lung base (arrow). Note also the physiologic uptake in the kidneys. (b) Chest CT scan shows consolidation with an air bronchogram in the right lung base.

 


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  		Figure 7b.  Pneumonia in a 72-year-old man with non-Hodgkin lymphoma who was undergoing chemotherapy. (a) Coronal PET scan shows FDG uptake in the right lung base (arrow). Note also the physiologic uptake in the kidneys. (b) Chest CT scan shows consolidation with an air bronchogram in the right lung base.

 


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  		Figure 8a.  Cholecystitis in a 47-year-old man with non-Hodgkin lymphoma who was undergoing chemotherapy. (a) Axial PET scan shows FDG accumulation in the gallbladder (arrow). The accumulation in the retroperitoneum (arrowheads) represents lymphoma. (b) Abdominal CT scan shows a gallstone and a fluid collection adjacent to the gallbladder (arrow) as well as retroperitoneal lymphadenopathies (arrowheads).

 


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  		Figure 8b.  Cholecystitis in a 47-year-old man with non-Hodgkin lymphoma who was undergoing chemotherapy. (a) Axial PET scan shows FDG accumulation in the gallbladder (arrow). The accumulation in the retroperitoneum (arrowheads) represents lymphoma. (b) Abdominal CT scan shows a gallstone and a fluid collection adjacent to the gallbladder (arrow) as well as retroperitoneal lymphadenopathies (arrowheads).

 


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  		Figure 9.  Colitis in a 45-year-old man with non-Hodgkin lymphoma who had undergone bone marrow transplantation. The patient presented with fever and abdominal cramping. Coronal PET scan shows increased activity in the colon.

 
Drug Toxicity
Drug toxicity of the lung is not uncommon during or after chemotherapy. Bleomycin is one of the most commonly used drugs for the treatment of Hodgkin disease, with up to 5% of patients to whom it is administered developing pulmonary drug toxicity. Diffuse increased FDG accumulation in the lungs has been reported with this condition (Fig 10) (26).



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  		Figure 10a.  Probable bleomycin toxicity in a 35-year-old man with Hodgkin disease who was treated with doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine. (a) Coronal PET scan shows diffuse increased FDG uptake in the lungs. Note also the physiologic uptake in the myocardium and kidneys and the increased uptake in the bone marrow due to G-CSF therapy. (b) Axial PET scan shows increased FDG uptake at the periphery of the lungs. (c) CT scan shows diffuse ground-glass attenuation.

 


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  		Figure 10b.  Probable bleomycin toxicity in a 35-year-old man with Hodgkin disease who was treated with doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine. (a) Coronal PET scan shows diffuse increased FDG uptake in the lungs. Note also the physiologic uptake in the myocardium and kidneys and the increased uptake in the bone marrow due to G-CSF therapy. (b) Axial PET scan shows increased FDG uptake at the periphery of the lungs. (c) CT scan shows diffuse ground-glass attenuation.

 


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  		Figure 10c.  Probable bleomycin toxicity in a 35-year-old man with Hodgkin disease who was treated with doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine. (a) Coronal PET scan shows diffuse increased FDG uptake in the lungs. Note also the physiologic uptake in the myocardium and kidneys and the increased uptake in the bone marrow due to G-CSF therapy. (b) Axial PET scan shows increased FDG uptake at the periphery of the lungs. (c) CT scan shows diffuse ground-glass attenuation.

 
Granulocyte Colony-stimulating Factor Therapy
G-CSF is a glycoprotein hormone that primarily regulates proliferation and differentiation of granulocyte precursors. G-CSF has been used increasingly to correct chemotherapy-induced neutropenia and has reduced infections (27). Increased FDG uptake is often observed in bone marrow and spleen during and after G-CSF therapy (Figs 3, 10, 11) (28,29). In patients with a prior history of lymphomatous infiltration of bone marrow, normal bone marrow may demonstrate increased activity due to G-CSF therapy, whereas previously infiltrated bone marrow may demonstrate reduced FDG uptake due to resolution of tumor cell uptake (Figs 12, 13).



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  		Figure 11.  Increased FDG uptake due to G-CSF therapy in a 49-year-old woman with a history of non-Hodgkin lymphoma and bone marrow transplantation. Whole-body PET scan shows diffuse increased FDG uptake in the bone marrow and spleen (arrows).

 


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  		Figure 12a.  Increased bone marrow uptake due to G-CSF therapy and lymphomatous infiltration in a 45-year-old man with Hodgkin disease. (a) Baseline sagittal PET scan shows focal FDG uptake in the lower thoracic spine (arrowhead). (b) Corresponding sagittal T1-weighted MR image shows a marrow-replacing lesion in the lower thoracic spine (arrowhead). (c) On a sagittal PET scan obtained after completion of chemotherapy, the previously involved spine shows decreased activity (arrowhead), whereas the normal bone marrow shows increased activity due to G-CSF therapy. (d) Corresponding sagittal T1-weighted MR image shows fatty infiltration of the previously involved lower thoracic spine (arrowhead).

 


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  		Figure 12b.  Increased bone marrow uptake due to G-CSF therapy and lymphomatous infiltration in a 45-year-old man with Hodgkin disease. (a) Baseline sagittal PET scan shows focal FDG uptake in the lower thoracic spine (arrowhead). (b) Corresponding sagittal T1-weighted MR image shows a marrow-replacing lesion in the lower thoracic spine (arrowhead). (c) On a sagittal PET scan obtained after completion of chemotherapy, the previously involved spine shows decreased activity (arrowhead), whereas the normal bone marrow shows increased activity due to G-CSF therapy. (d) Corresponding sagittal T1-weighted MR image shows fatty infiltration of the previously involved lower thoracic spine (arrowhead).

 


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  		Figure 12c.  Increased bone marrow uptake due to G-CSF therapy and lymphomatous infiltration in a 45-year-old man with Hodgkin disease. (a) Baseline sagittal PET scan shows focal FDG uptake in the lower thoracic spine (arrowhead). (b) Corresponding sagittal T1-weighted MR image shows a marrow-replacing lesion in the lower thoracic spine (arrowhead). (c) On a sagittal PET scan obtained after completion of chemotherapy, the previously involved spine shows decreased activity (arrowhead), whereas the normal bone marrow shows increased activity due to G-CSF therapy. (d) Corresponding sagittal T1-weighted MR image shows fatty infiltration of the previously involved lower thoracic spine (arrowhead).

 


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  		Figure 12d.  Increased bone marrow uptake due to G-CSF therapy and lymphomatous infiltration in a 45-year-old man with Hodgkin disease. (a) Baseline sagittal PET scan shows focal FDG uptake in the lower thoracic spine (arrowhead). (b) Corresponding sagittal T1-weighted MR image shows a marrow-replacing lesion in the lower thoracic spine (arrowhead). (c) On a sagittal PET scan obtained after completion of chemotherapy, the previously involved spine shows decreased activity (arrowhead), whereas the normal bone marrow shows increased activity due to G-CSF therapy. (d) Corresponding sagittal T1-weighted MR image shows fatty infiltration of the previously involved lower thoracic spine (arrowhead).

 


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  		Figure 13a.  Increased bone marrow uptake due to G-CSF therapy and lymphomatous infiltration in a 30-year-old woman with relapsed Hodgkin disease. (a) Sagittal PET scan obtained prior to chemotherapy shows heterogeneous intense FDG uptake in the spine (arrows), a finding that suggests lymphomatous involvement. Note the relatively low uptake in the sternum and in several vertebrae (arrowheads). (b) On a sagittal PET scan obtained 2 months after chemotherapy, the previously involved bone marrow demonstrates decreased uptake (arrows), whereas the relatively normal bone marrow shows intense uptake due to G-CSF therapy (arrowheads).

 


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  		Figure 13b.  Increased bone marrow uptake due to G-CSF therapy and lymphomatous infiltration in a 30-year-old woman with relapsed Hodgkin disease. (a) Sagittal PET scan obtained prior to chemotherapy shows heterogeneous intense FDG uptake in the spine (arrows), a finding that suggests lymphomatous involvement. Note the relatively low uptake in the sternum and in several vertebrae (arrowheads). (b) On a sagittal PET scan obtained 2 months after chemotherapy, the previously involved bone marrow demonstrates decreased uptake (arrows), whereas the relatively normal bone marrow shows intense uptake due to G-CSF therapy (arrowheads).

 
Radiation Therapy
The accumulation of FDG in tumor cells may be enhanced following radiation therapy (30). Furthermore, radiation therapy may cause inflammation in normal structures such as the lungs and mucous membranes, thereby inducing pneumonitis (Fig 14), pharyngitis, and esophagitis (24, 31–33).



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  		Figure 14a.  Radiation pneumonitis in a 26-year-old man with non-Hodgkin lymphoma who had undergone radiation therapy 4 months earlier. (a) Coronal PET scan shows intense FDG uptake in the medial chest. Note also the physiologic uptake in the kidneys. (b) Chest CT scan shows consolidation in the paramediastinal lung.

 


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  		Figure 14b.  Radiation pneumonitis in a 26-year-old man with non-Hodgkin lymphoma who had undergone radiation therapy 4 months earlier. (a) Coronal PET scan shows intense FDG uptake in the medial chest. Note also the physiologic uptake in the kidneys. (b) Chest CT scan shows consolidation in the paramediastinal lung.

 
Physiologic Activity
It is not uncommon to see normal physiologic activity more vividly after completion of treatment than before treatment. Variable physiologic FDG uptake is seen in the brain (Fig 15), digestive tract (Figs 2, 6), liver (Figs 5, 16), skeletal muscles (Fig 17), myocardium (Figs 4, 10, 16–18), bone marrow (Fig 19), and genitourinary tract (Figs 4, 5, 7, 10, 14, 18, 20). One of the most notable false-positive FDG uptake sites after therapy is the thymus (Fig 21) (9,34), where accumulation has been noted in younger patients, especially children. CT often shows enlargement of the thymus with no abnormal mass.



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  		Figure 15.  FDG uptake in the sternum and brain in a 17-year-old boy with non-Hodgkin lymphoma who had undergone sternotomy 2 months earlier. Sagittal PET scan shows intense FDG uptake in the sternum (arrowheads) and physiologic uptake in the brain.

 


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  		Figure 16.  Probable brown fat uptake on the nonirradiated side in a 37-year-old man with non-Hodgkin lymphoma who had undergone chemotherapy and radiation therapy to the left side of the neck. Coronal PET scan shows increased FDG uptake in the right supraclavicular region (arrow); however, no abnormality was seen at CT. Physiologic uptake is seen in the vocal cords (arrowhead), myocardium, liver, and digestive tract. The patient remains disease free. Brown fat (supraclavicular area fat) is adipose tissue whose only function is to generate heat. It usually demonstrates the symmetric uptake pattern shown here and is more common in women and during the winter (35,36).

 


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  		Figure 17a.  Thrombus at the tip of a central line in a 76-year-old woman. (a) Coronal PET scan shows focal FDG uptake in the right anterior mediastinum (arrowhead). Note also the physiologic uptake in the myocardium, skeletal muscles, and kidneys. (b) Follow-up PET scan obtained 4 hours later after flushing the central line with saline solution shows persistent uptake (arrowhead). (c) CT scan reveals a thrombus at the tip of the central line (arrow). Follow-up PET performed 2 months later after removal of the central line showed resolution of the uptake.

 


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  		Figure 17b.  Thrombus at the tip of a central line in a 76-year-old woman. (a) Coronal PET scan shows focal FDG uptake in the right anterior mediastinum (arrowhead). Note also the physiologic uptake in the myocardium, skeletal muscles, and kidneys. (b) Follow-up PET scan obtained 4 hours later after flushing the central line with saline solution shows persistent uptake (arrowhead). (c) CT scan reveals a thrombus at the tip of the central line (arrow). Follow-up PET performed 2 months later after removal of the central line showed resolution of the uptake.

 


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  		Figure 17c.  Thrombus at the tip of a central line in a 76-year-old woman. (a) Coronal PET scan shows focal FDG uptake in the right anterior mediastinum (arrowhead). Note also the physiologic uptake in the myocardium, skeletal muscles, and kidneys. (b) Follow-up PET scan obtained 4 hours later after flushing the central line with saline solution shows persistent uptake (arrowhead). (c) CT scan reveals a thrombus at the tip of the central line (arrow). Follow-up PET performed 2 months later after removal of the central line showed resolution of the uptake.

 


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  		Figure 18a.  Rib fracture in a 46-year-old man with Hodgkin disease who had completed treatment. (a, b) Coronal (a) and axial (b) PET scans show focal FDG uptake in the posterior chest wall (arrows). Note also the accumulation in both shoulders (arrowheads in a), a finding that may represent degenerative changes, and the physiologic uptake in the myocardium and kidneys. (c) CT scan clearly shows a rib fracture (arrow).

 


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  		Figure 18b.  Rib fracture in a 46-year-old man with Hodgkin disease who had completed treatment. (a, b) Coronal (a) and axial (b) PET scans show focal FDG uptake in the posterior chest wall (arrows). Note also the accumulation in both shoulders (arrowheads in a), a finding that may represent degenerative changes, and the physiologic uptake in the myocardium and kidneys. (c) CT scan clearly shows a rib fracture (arrow).

 


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  		Figure 18c.  Rib fracture in a 46-year-old man with Hodgkin disease who had completed treatment. (a, b) Coronal (a) and axial (b) PET scans show focal FDG uptake in the posterior chest wall (arrows). Note also the accumulation in both shoulders (arrowheads in a), a finding that may represent degenerative changes, and the physiologic uptake in the myocardium and kidneys. (c) CT scan clearly shows a rib fracture (arrow).

 


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  		Figure 19.  Decreased bone marrow activity due to radiation therapy in a 26-year-old man with Hodgkin disease of the mediastinum. Sagittal PET scan shows decreased FDG uptake in the thoracic spine (arrowheads).

 


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  		Figure 20.  Brown fat in an 18-year-old man with Hodgkin disease who had undergone chemotherapy. Coronal PET scan shows symmetric increased FDG uptake in the shoulders, neck, and paraspinal area. Note also the physiologic uptake in the kidneys.

 


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  		Figure 21a.  Thymic uptake in a 17-year-old boy with Hodgkin disease. (a) Axial PET scan obtained 4 months after completion of chemotherapy shows increased FDG uptake in the anterior mediastinum (arrow). (b, c) CT scans obtained just after completion of chemotherapy (b) and 4 months later (c) show interval enlargement of the thymus with normal architecture (arrow).

 


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  		Figure 21b.  Thymic uptake in a 17-year-old boy with Hodgkin disease. (a) Axial PET scan obtained 4 months after completion of chemotherapy shows increased FDG uptake in the anterior mediastinum (arrow). (b, c) CT scans obtained just after completion of chemotherapy (b) and 4 months later (c) show interval enlargement of the thymus with normal architecture (arrow).

 


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  		Figure 21c.  Thymic uptake in a 17-year-old boy with Hodgkin disease. (a) Axial PET scan obtained 4 months after completion of chemotherapy shows increased FDG uptake in the anterior mediastinum (arrow). (b, c) CT scans obtained just after completion of chemotherapy (b) and 4 months later (c) show interval enlargement of the thymus with normal architecture (arrow).

 
After radiation therapy, normal physiologic uptake (eg, in the bone marrow and salivary glands) may be decreased (Fig 19) (26,37). In some cases, normal uptake in the nonirradiated area appears abnormal (Fig 16).

Postoperative Changes
Healing involves an inflammatory reaction even in the absence of infection. Leukocytic infiltration is present in the granulation tissue associated with wound repair and the resorption of necrotic debris and hematoma. Recent surgery can result in spurious increased FDG uptake in areas of resolving inflammation (Fig 22) (24,38). A healing sternum after sternotomy is a common source of FDG uptake (Fig 15). Focal FDG uptake associated with ostomies or various indwelling stents (eg, tracheostomy [Fig 23], gastrostomy) is not uncommon (32,39).



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  		Figure 22a.  Postsurgical change in a 63-year-old man with Hodgkin disease. A splenic lesion had been found and splenectomy performed 1 month earlier. (a) Sagittal PET scan shows FDG uptake in the anterior abdominal wall (arrowhead) as well as lymphoma lesions of the neck, mediastinum, spine, and retroperitoneum (arrows). (b) Axial PET scan again shows FDG uptake in the anterior abdominal wall (arrow), as well as lymphoma lesions of the pelvis (arrowhead). (c) CT scan shows postsurgical change (arrow) and pelvic lymphadenopathies (arrowhead).

 


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  		Figure 22b.  Postsurgical change in a 63-year-old man with Hodgkin disease. A splenic lesion had been found and splenectomy performed 1 month earlier. (a) Sagittal PET scan shows FDG uptake in the anterior abdominal wall (arrowhead) as well as lymphoma lesions of the neck, mediastinum, spine, and retroperitoneum (arrows). (b) Axial PET scan again shows FDG uptake in the anterior abdominal wall (arrow), as well as lymphoma lesions of the pelvis (arrowhead). (c) CT scan shows postsurgical change (arrow) and pelvic lymphadenopathies (arrowhead).

 


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  		Figure 22c.  Postsurgical change in a 63-year-old man with Hodgkin disease. A splenic lesion had been found and splenectomy performed 1 month earlier. (a) Sagittal PET scan shows FDG uptake in the anterior abdominal wall (arrowhead) as well as lymphoma lesions of the neck, mediastinum, spine, and retroperitoneum (arrows). (b) Axial PET scan again shows FDG uptake in the anterior abdominal wall (arrow), as well as lymphoma lesions of the pelvis (arrowhead). (c) CT scan shows postsurgical change (arrow) and pelvic lymphadenopathies (arrowhead).

 


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  		Figure 23a.  Tracheostomy in a 38-year-old man with non-Hodgkin lymphoma who was undergoing chemotherapy. (a) Sagittal PET scan shows FDG uptake in the lower neck (arrowhead). (b) CT scan of the neck shows a tracheostomy.

 


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  		Figure 23b.  Tracheostomy in a 38-year-old man with non-Hodgkin lymphoma who was undergoing chemotherapy. (a) Sagittal PET scan shows FDG uptake in the lower neck (arrowhead). (b) CT scan of the neck shows a tracheostomy.

 
Fracture and Degenerative Change
Fractures are often seen in patients with malignant disease due to metastasis or radiation therapy and are frequently associated with increased FDG uptake (Fig 18) (24,40). In addition, focal uptake associated with degenerative change is not uncommon (Fig 18) (24).

Injection Leakage
Leakage at the injection site or residual radiotracer in the indwelling catheter used for injection causes accumulation of FDG. Abnormal FDG accumulation in lymph nodes can also be a consequence of spurious delivery of the radiotracer by means of lymphatic drainage, as when the radiotracer extravasates into tissue drained by a regional lymph node group. FDG uptake in axillary lymph nodes due to partial subcutaneous injection into the antecubital fossa has been reported (Fig 24) (41). In patients who receive an injection of FDG through a central venous catheter that has a thrombus at the tip, FDG could become trapped at the thrombus site and mimic mediastinal adenopathy (Fig 17) (42).



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  		Figure 24.  Axillary uptake due to partial subcutaneous radiotracer injection in a 40-year-old woman with Hodgkin disease in remission. Coronal PET scan shows linear FDG uptake in the left upper arm (arrows) associated with focal uptake in the left axilla (arrowhead). The study was performed with the patient’s arms elevated because of the large amount of radiotracer leakage.

 

   False-Negative Findings
Top
 Abstract
 LEARNING OBJECTIVES
 Introduction
 FDG PET Technique
 Treatment Response Evaluation
 Pitfalls
 False-Negative Findings
Summary
 References
 
Because the spatial resolution of PET is not perfect, lesions less than 1 cm often go undetected. Although FDG PET is sensitive in most low-grade lymphomas (eg, follicular lymphoma), some types of indolent lymphoma such as peripheral T-cell lymphoma are not well visualized (43–45). Physiologic uptake can obscure the uptake by lymphoma, especially in the gastrointestinal tract and bone marrow (43–45).


   Summary
Top
 Abstract
 LEARNING OBJECTIVES
 Introduction
 FDG PET Technique
 Treatment Response Evaluation
 Pitfalls
 False-Negative Findings
 Summary
References
 
FDG PET may play an important role in the evaluation and management of malignant lymphoma. FDG uptake is predictive of therapeutic response during or after completion of treatment. Patients with negative PET findings after one or two cycles of treatment have a good prognosis. In patients with persistent uptake, it may be appropriate to change or intensify the treatment; however, the usefulness of these strategies is still in large part theoretic, and further studies are necessary. After completion of chemotherapy, residual abnormal soft tissues are often seen at CT or MR imaging. FDG PET may be more accurate than either of these modalities in assessing residual disease. Nevertheless, after completion of chemotherapy, FDG PET does not help exclude the presence of minimal residual disease, which may lead to later disease relapse. FDG is not a tumor-specific substance, and increased accumulation may be seen in a variety of benign conditions, which may give rise to false-positive results. Chemotherapy often causes neutropenia, and infection is not uncommon in affected patients. Chemotherapy, radiation therapy, surgery, and intervention can induce inflammatory processes. G-CSF may cause increased uptake in bone marrow and spleen. Physiologic activity and injection leakage can also lead to false-positive findings. Clinical information