FDG-PET scanning for detection and staging of extranodal marginal zone lymphomas of the MALT type: a report of 42 cases

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1 Original article Annals of Oncology 16: , 2005 doi: /annonc/mdi093 Published online 24 January 2005 FDG-PET scanning for detection and staging of extranodal marginal zone lymphomas of the MALT type: a report of 42 cases K. P. Beal 1, H. W. Yeung 2 & J. Yahalom 1 * Departments of 1 Radiation Oncology and 2 Nuclear Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA Received 9 August 2004; revised 26 October 2004; accepted 29 October 2004 Background: Although reports have suggested that FDG-PET scans were not useful for staging of extranodal marginal zone lymphomas (MZL), experience at our center suggests otherwise. Thus we reviewed the findings of FDG-PET scans in patients with extranodal MZL seen at our center. Patients and methods: A database of 175 patients with histologically-confirmed diagnoses of extranodal MZL was reviewed. Forty-two patients who had had FDG-PET scans for initial staging were identified. All information was obtained by retrospective review of medical records and PET scans. Results: Thirty-four (81%) patients had focal tracer uptake within verified tumor sites, six (14%) patients did not, and two (5%) patients had indeterminate uptake. Seven of the 34 (21%) patients with uptake within verified tumor sites had uptake in regional lymph nodes and four patients were upstaged due to FDG-PET findings. Eight patients also obtained post-treatment FDG-PET scans. In five of those eight, the repeated FDG-PET scan indicated a complete response, and in three there was an indeterminate or mixed response. Conclusion: FDG-PET scans carried out for initial staging of extranodal MZL detected disease in a high proportion of patients. This study suggests that imaging with FDG-PET scans is useful for both initial staging and follow-up of patients with extranodal MZL. Key words: MALT lymphoma, PET scan Introduction Positron emission tomography (PET) imaging using 18-fluoro- 2-deoxyglucose (FDG) has become widely available and is used for the staging, evaluation, and management of many cancers including lymphomas [1]. Many studies have demonstrated the utility of FDG-PET imaging for Hodgkin s disease [2, 3] and non-hodgkin s lymphomas (NHL) including diffuse large B cell lymphoma (DLBCL), follicular lymphomas, and mantle cell lymphomas among others [4 6]. However, the utility of FDG-PET scans in the staging and management of extranodal marginal zone lymphomas remains unclear. Extranodal marginal zone lymphoma (MZL), also known as mucosal associated lymphoid tissue (MALT) lymphoma, is the third most common NHL following only DLBCL and follicular lymphoma in incidence and it comprises approximately 8% of all NHL [7]. As with other NHL, the optimal treatment of MALT lymphomas depends on the stage of disease [8 10]. *Correspondence to: Dr J. Yahalom, Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY , USA. Tel: ; Fax: ; yahalomj@mskcc.org Understanding the potential contribution of FDG-PET imaging to accurate staging and treatment response evaluation will be helpful in the management of these patients. Further, since most patients with localized disease are effectively treated with involved-field radiotherapy, the accuracy in defining the disease treatment volume can be enhanced by additional imaging information [11]. Many reports show a correlation between high FDG uptake and high histologic grade of lymphoma [12]. Other studies report that although low-grade NHLs do not demonstrate FDG avidity to the same degree that high-grade lymphomas do, they are still FDG avid enough to demonstrate disease [13, 14]. Although there is evidence that FDG-PET scanning detects disease accurately in some low grade histologies such as follicular lymphoma and mantle cell lymphoma [4], a few studies with limited numbers of patients report that FDG-PET imaging is unreliable for extranodal MALT lymphomas [15, 16]. However, our experience at Memorial Sloan-Kettering Cancer Center (MSKCC) suggests otherwise. Thus, we analyzed our patients with MALT lymphoma who had undergone FDG-PET imaging as part of their initial evaluation and present our results here. q 2005 European Society for Medical Oncology

2 474 Patients and methods A database of 175 patients with MALT lymphoma histologically confirmed by hematopathologists at MSKCC was reviewed to select patients who had had FDG-PET scanning as part of their initial evaluation. Fortytwo patients were identified and their FDG-PET scans and clinical information were reviewed. FDG-PET scans were obtained at the ordering physician s discretion. Of the 42 patients, 24 patients had their scans carried out at MSKCC, and 18 at an outside center. While all of the patients who had their scans carried out at an outside center sent a detailed nuclear medicine report, only five of them had their scans reviewed again at MSKCC. One attending physician in the department of nuclear medicine reviewed all of the scans carried out at MSKCC and all of the scans performed at outside centers with images available for review. The patients who had their FDG-PET imaging carried out at MSKCC fasted for 6 h before an injection of intravenous 18-FDG. The injections were given 60 min before images were acquired on a LSO Siemens Biograph PET/CT Scanner or on a GE Discovery LS PET/CT Scanner. Following a low-dose CT scan, multiple PET images were obtained from multiple bed positions from the level of the skull base to the pelvic floor. Iterative image reconstruction was used and attenuation corrected images were evaluated. Scans were considered positive if there was abnormal focal FDG uptake above that of background uptake. Quantification of the abnormal foci was obtained using the Standardized Uptake Value (SUV) normalized to body weight as follows: SUV = (FDG concentration in the lesion)/(injected FDG normalized to body weight). The PET images were compared with CT images for anatomic location. Although the technology employed at the outside centers was varied, 14 of the 18 reports from outside centers indicated that attenuation correction techniques were used to evaluate the images. Results A total of 42 patients who had undergone FDG-PET imaging as part of their initial evaluation were identified out of a database of 175 patients with histologically confirmed MALT lymphoma. It should be noted that while the database compilation started in 1985, PET scanning for MALT lymphoma patients in this series started in The median age was 62 years (range of years), and there were 22 men and 20 women. Thirty-four patients had positive scans with a median SUV of 5.5 (range of ). One patient with bladder MALT lymphoma had an indeterminate scan as the bladder normally has high FDG uptake. Another patient with MALT lymphoma involving the base of skull had an indeterminate scan as her FDG-PET scan was carried out after a biopsy of her lesion and the minimal FDG uptake seen may have been related to post-operative changes versus disease. Six patients had negative FDG-PET scans. Table 1 provides a summary of patient characteristics. The stage distribution of the patients who had positive scans was as follows, I (19), II (3), III (2) and IV (10). Four of these patients with positive scans were upstaged as their FDG-PET scans revealed sites of involvement not seen on computed tomography (CT). One of these four upstaged patients was initially diagnosed with stage I disease involving the nasopharynx but was upstaged to stage II disease when regional lymph nodes were found to be FDG avid and biopsy proven to have low grade lymphoma. Another patient was Table 1. Patient characteristics FDG-PET scan findings Positive Negative Indeterminate Gender Male Female Age Median Range Stage Recurrent 1 Primary site Lung 11 Gastric 6 4 Subcutaneous tissue 4 Orbit 4 2 Oral cavity 2 Retroperitoneum 2 Skin 1 Parotid 1 Pleura 1 Temporal region 1 Nasopharynx 1 Base of skull 1 Bladder 1 initially diagnosed with stage I disease involving the conjunctiva but was upstaged to stage IV disease when subcutaneous tissue in the thigh was found to be FDG avid and biopsy proven to be MALT lymphoma. A third patient initially was diagnosed with perinephric MALT lymphoma and was upstaged to stage IV when his FDG-PET scan revealed uptake in his lungs. Another patient who had an indeterminate scan was upstaged from stage I disease involving the base of skull to stage IV transformed disease when her sacrum was found to be FDG avid and biopsy revealed transformation to DLBCL. The six patients with negative scans had the following stage distribution, I (5), and recurrent (1). The two patients with indeterminate scans had stage I disease (bladder) and stage IV disease, respectively. The patient with stage IV disease initially presented with symptoms related to her biopsy proven base of skull MALT lymphoma. MRI of the skull and CT scanning of the chest, abdomen and pelvis revealed her base of skull to be the only site of involvement. However, as previously mentioned, her FDG-PET scan (which was indeterminate for her base of skull involvement) revealed FDG avidity in her sacrum which was then biopsied revealing DLBCL.

3 475 Of the 34 patients with positive scans, the following primary sites were involved: lung (11), gastric (6), orbit (4), oral cavity (2), subcutaneous tissue (4), parotid (1), skin (1), pleura (1), retroperitoneum and flank (1), kidney and perinephric region (1), temporal region (1), and nasopharynx (1). Of the six patients with negative scans, the following sites were involved: gastric (4), and orbit (2). The two patients with indeterminate scans had bladder and base of skull involvement as previously mentioned. Of the 34 patients with positive FDG-PET scans, 28 patients had adequate follow-up information for analysis. Three others were still undergoing treatment, and three were only seen for initial evaluation and staging at MSKCC. At a median follow-up of 13 months, 13 patients were NED, 11 had persistent or progressive disease at their initial site of disease, two developed a new site of MALT lymphoma, one patient died of his disease, and one patient developed a new cancer (non-lymphomatous). The patient who died of his disease had extensive lung and nodal involvement with significant pulmonary compromise. He had been treated with multiple chemotherapeutic regimens with minimal response and then was treated emergently with radiation therapy (RT) for worsening pulmonary function. He deceased of pulmonary complications before finishing his RT. Of the six patients with negative initial FDG-PET scans, all were NED at a median follow-up of 12.5 months. The patient with an indeterminate scan due to bladder involvement was NED 16 months after completion of radiation therapy. The other patient with an indeterminate scan due to base of skull involvement was NED 7 months after treatment with chemotherapy (CTX) and RT. This patient was treated with CTX in addition to RT to her base of skull (her initial site of MALT lymphoma) and her sacrum which had transformed disease (DLBCL) revealed on her staging FDG-PET scan. Eight patients who initially had positive FDG-PET scans obtained post-treatment FDG-PET scans. Post-treatment scans were ordered at the treating physician s discretion and likely were not ordered routinely as the role of FDG-PET is still not clearly defined for this population. Three of these patients with post-treatment scans initially had a single site of disease (stage I), were treated with RT alone, and attained a complete response clinical and radiographic with negative follow-up FDG-PET scans. Figure 1 illustrates an example of a patient with stage I disease involving the orbit who had a complete response on a follow-up FDG-PET scan 4 months after the completion of RT. One patient had MALT lymphoma of his nasopharynx and was upstaged from a stage I to stage II after his initial staging FDG-PET scan revealed FDG avidity in regional lymph nodes. He was treated with RT alone to his nasopharynx and regional nodes and attained a complete response on a follow-up FDG-PET scan 3 months after the completion of RT which is illustrated in Figure 2. One patient with stage IV disease was treated with RT to her orbit with resolution of FDG uptake in the region treated on a post-treatment FDG-PET scan. One patient with stage IV disease was treated with CTX and had a mixed response on a post-treatment FDG-PET scan. Figure 3 illustrates a patient who had gastric MALT lymphoma proven on multiple pre-treatment biopsies with a highly avid FDG-PET scan who received RT. A repeat biopsy following RT revealed resolution of her gastric MALT lymphoma but presence of a DLBCL which was then treated with CTX. Chemotherapy was initiated 4 months after the completion of her RT, and after three cycles, a follow-up FDG-PET scan showed complete resolution of her FDG avid disease that was pathologically confirmed by endoscopic gastric biopsies. Figure 4 illustrates the PET and corresponding CT images of a patient with MALT lymphoma of the bilateral orbits. Two patients, both with stage I gastric involvement, had indeterminate responses with FDG avid areas in their gastric regions on their post-treatment scans. Post-treatment FDG- PET scans for these two patients were carried out at 3 and 6 months following the last day of treatment, respectively. The SUV for their initial FDG-PET scans was 3.8 and 5.5 while the SUV on the FDG-PET scans following RT for the two patients was 3.9 and 5.0, respectively. Both patients attained a pathologically-confirmed CR and remain disease-free with a median follow-up of 6 and 18 months, respectively. Table 2 provides a summary of patient presentation and treatment information for all patients with positive or indeterminate FDG-PET scans. Discussion Figure 1. PET axial images of MALT lymphoma of right orbit. Pre-treatment (A) and post 2400 cgy radiation therapy (B). Accurate staging and localization of MALT lymphomas help to optimize management, direct local therapy when indicated, and assess treatment results. FDG-PET imaging has been shown to be useful for many types of lymphomas including low grade NHL such as follicular lymphoma [13]. Yet, there is limited information on the utility of FDG-PET imaging for MALT lymphomas other than the data of a few small series reporting negative studies [15, 16]. The above reported group of patients is the largest series examining the role of FDG- PET scanning with MALT lymphomas and is the first to show that MALT lymphomas are FDG avid in the majority (80%) of studied cases. In this study, we show not only that MALT

4 476 Figure 2. PET, CT, and PET-CT fused axial images of MALT lymphoma of nasopharynx and regional lymph nodes. Pre-treatment (A) and post 3600 cgy radiation therapy (B). lymphomas have FDG avidity, but also that FDG-PET scanning for MALT lymphomas is useful for staging and detection of sites of involvement or areas of transformation not appreciated with other standard imaging modalities. Thus far, other than a few case reports of MALT lymphoma with focal tracer uptake on FDG-PET imaging [17, 18], the information on FDG-PET in MALT lymphomas has been limited to small series reporting poor or no uptake in the site(s) of involvement. In 1999, Hoffmann et al. published their findings from a prospective observational study of 10 patients with MALT lymphoma who underwent FDG-PET scanning and reported no focal tracer uptake in any of the 10 patients [15]. In 2003, Hoffmann et al. published their findings from a series of 21 patients with marginal zone lymphoma, 14 of 21 had extranodal marginal zone lymphoma of the MALT type. Once again, they reported that none of the 14 patients with MALT lymphoma had focal tracer uptake in their respective tumor sites upon evaluation with FDG-PET scans [16]. In 2003, Elstrom et al. reported on the utility of FDG-PET scanning in all non-hodgkin s lymphomas [4]. In her series of 172 cases, 12 were marginal zone lymphomas, 67% of which had positive PET scan results. However, the study does not document details of these cases or whether these cases were nodal or extranodal marginal zone lymphomas of the MALT type. Thus Elstrom s study neither supports nor refutes previously published studies. In our series of 42 patients with MALT lymphoma, we found FDG-PET to be a valuable imaging and possibly valuable staging tool. In 34 of 42 patients, there was FDG avidity representing MALT lymphoma. Our data demonstrate that Figure 3. PET coronal image of gastric MALT lymphoma and transformed DLBCL that was identified after radiation therapy. Pre-treatment (A) and post 3960 cgy of radiation therapy and three cycles of chemotherapy (B). MALT lymphoma can be detected with FDG-PET imaging in the majority of patients (81% of patients with histologically confirmed sites of MALT lymphoma). Only six patients in our series did not have uptake in pathologically confirmed sites of disease. Two of these cases involved the orbit, and one of those patients had had his lesion 80% excised (as per the surgeon s report) before her FDG- PET scan. Thus the remaining disease volume in this patient s orbit may have been too small to detect by PET scanning

5 477 Figure 4. PET, CT and PET-CT fused axial images of bilateral MALT lymphoma of the orbits. even if it was FDG avid. The other patient with MALT lymphoma of the orbit and a negative FDG-PET scan had his scan carried out at an outside center and did not provide us with a copy of the exam for review. The remaining four cases of MALT lymphoma and negative FDG-PET scans all had gastric involvement. The lack of FDG uptake may be due to small volume disease in these patients as gastric MALT lymphomas often present with multifocal areas of limited involvement. Yet, 60% (6 of 10) of our PETstudied gastric cases had positive FDG uptake. Although the two negative series published by Hoffman et al. [15, 16] have gastric MALT lymphomas representing the majority of their cases, it still does not fully explain their PET negative results. Another possible explanation for the negative orbit and gastric cases is that the orbit region and stomach both have normal increased glucose uptake which may decrease the accuracy of PET scans at these sites. Another possible explanation as to why all of the patients in the two Hoffman et al. series had negative scans is because of different technical approaches. In those series, attenuation correction of the images was done only when abnormalities were seen in the uncorrected whole body images. Thus lesions with low SUV may have been missed in the uncorrected images, especially over the variable background FDG uptake in the normal stomach. At our center, attenuation correction of PET images is routinely carried out, resulting in higher tumor to background ratios of deep lesions. The two Hoffman series also used older technology and cameras that likely did not have the same resolution as newer cameras such as the ones used at our center. Of interest, our series of 42 patients includes a disproportionately large number of patients (11) with MALT involving the lung who had FDG-PET scans. In our database of 175 patients with MALT lymphoma, only 19 had lung as their primary site of involvement, yet 11 of those patients had FDG-PET scans as part of their workup. This disproportion may be attributed to those patients being evaluated by a thoracic surgeon or pulmonologist who likely have a lower threshold for ordering FDG-PET scans as FDG-PET scans are part of the standard workup for lung cancer [19 21]. The fact that all of our cases of lung MALT lymphoma who had FDG-PET scans had focal FDG uptake in their lungs is important to note as MALT lymphoma is the most common primary lymphoma of the lung [22, 23]. This information may be useful for radiologists who are considering the differential diagnoses of a patient with focal FDG uptake in the lung. Of our 42 MALT patients who initially were evaluated with FDG-PET imaging, patients with positive scans were more likely to have higher stage disease than patients with negative scans. In fact, of the 34 patients with positive scans, three were upstaged following their FDG-PET scans, and one patient with an indeterminate scan was upstaged when she was found to have a site of transformation to DLBCL that had been unidentified on prior imaging with CT. Although the patients with negative FDG-PET scans appear to have better outcome on follow-up analysis, no conclusions can be determined from this study regarding FDG uptake and outcome of MALT lymphoma patients as there may be confounding by stage and site of disease differences in this study. Further analysis with a larger cohort of patients is necessary to determine whether or not there is a relationship between FDG uptake and outcome in MALT lymphomas. There were several limitations to this study. One limitation is that 18 patients had their FDG-PET scans carried out at outside centers and only five patients provided their images for review at our center thus limiting our ability to completely assess the validity of those studies. Of the 13 patients who provided only reports, 11 (85%) had positive studies, and two had negative studies which is a similar percentage of positive studies found in the patients who had their studies carried out at MSKCC [18 of 24 patients (75%) who had scans at MSKCC had positive studies]. Furthermore, because these 18 studies were carried out at outside centers, there was variation in imaging techniques compromising predictive value. Another limitation to this study is that only eight patients had post-treatment FDG-PET scans to evaluate their response to treatment. This limits our ability to analyze the predictive value of the post-treatment FDG-PET findings. Despite these limitations, this study demonstrates that FDG- PET scans are useful for staging and treatment design for patients with extranodal MALT lymphomas. As FDG-PET imaging technology advances and spreads, its role in cancer evaluation undoubtedly will expand. Our study demonstrates that MALT lymphoma is one of the cancers that can benefit from this expansion as FDG-PET imaging may lead to more accurate staging and better management. Since early stage

6 478 Table 2. Summary of patient presentation and treatment information for all patients with positive or indeterminate FDG-PET scans Patient Primary site Gender Age Maximum SUV Stage Up-staged Treatment Post treatment DFG-PET scan Comments Radiation therapy (RT) Surgical excision Chemotherapy Carried out Result (SUV) Months after treatment FDG-PET positive patients 1 Lung Male Yes Yes 2 Lung Female Yes Yes History of previously treated orbital MALT lymphoma 10 years earlier 3 Lung Male Yes 4 Lung Male Yes 5 Lung Male Yes 6 Lung Male Yes 7 Lung Female 71 Not reported 1 Yes 8 Lung Female Yes 9 Lung Female 77 Not reported 2 Yes Yes 10 Lung Male 71 Not reported 3 Yes 11 Lung Male Yes 12 Gastric Female Yes Yes Complete response 6 Post RT biopsy revealed DLBCL treated with chemotherapy to a biopsy proven and PET negative complete response 13 Gastric Female Yes 14 Gastric Male 53 Not reported 4 Stage 4 (multiple gastrointestinal sites) 15 Gastric Female Yes Yes Indeterminate response (3.9) 16 Gastric Male Yes Yes Indeterminate response (5.0) 17 Gastric Male Yes 18 Subcutaneous tissue Male Yes 19 Subcutaneous tissue 20 Subcutaneous tissue 3 Post-treatment PET uptake interpreted as post RT changes; post RT endoscopy and biopsies revealed a complete response 5 Post-treatment PET uptake interpreted as post RT changes; post RT endoscopy and biopsies revealed a complete response Female 72 Not reported 4 Yes Yes Yes Stage 4 (subcutaneous tissue and conjunctival disease) Female

7 Table 2.. (Continued) Patient Primary site Gender Age Maximum SUV Stage Up-staged Treatment Post treatment DFG-PET scan Comments Radiation therapy (RT) Surgical excision Chemotherapy Carried out Result (SUV) Months after treatment 21 Subcutaneous tissue Female Yes Yes Mixed response Orbit Male Yes Yes Complete response 3 23 Orbit Female Yes Yes Complete response 2.5 RT was to orbit, with complete response in orbit on repeat PET scan 24 Orbit Male Yes 25 Orbit Male Yes 26 Oral cavity Female Yes 27 Oral cavity Female Yes Yes 28 Nasopharynx Male Yes Yes Yes Complete response 3 Upstaged due to FDG-PET findings (lung involvement) 29 Parotid Female 66 Not reported 1 Yes Yes Complete response 3 30 Perinephric region Male Yes Upstaged due to FDG-PET findings (lung involvement) 31 Pleura Female Yes 32 Retroperitoneum Female Yes 33 Skin Male 68 4 Yes 34 Temporal region Female FDG-PET indeterminate patients 35 Base of skull Female 56 4 Yes Yes Disease identified in sacrum with FDG-PET scan which was DLBCL 36 Bladder Male 78 1 Yes 479

8 480 patients or patients with symptomatic sites of MALT lymphomas are most effectively treated with RT, the information that FDG-PET scans yield in confirming localized disease is invaluable. In particular, accurate imaging information is useful for the radiation oncologist in order to design appropriate treatment fields [24]. Furthermore, our study demonstrates that FDG-PET findings that were not appreciated on CT scanning may not only upstage patients, but also may identify sites of transformation to more aggressive disease that require a different treatment approach. Future prospective studies are warranted to clarify the contribution of FDG-PET imaging to the staging and follow-up of patients with MALT lymphoma and consider incorporation of PET imaging into the lymphoma staging system. Acknowledgements We appreciate the cooperation of members of the lymphoma disease management team at MSKCC. This project was supported by the Lymphoma Foundation. Dr Beal s fellowship was supported by the Dr Mortimer Lacher Fund. References 1. Talbot JN, Haioun C, Rain JD et al. [18F]-FDG positron imaging in clinical management of lymphoma patients. Crit Rev Oncol Hematol 2001; 38: Hoh CK, Glaspy J, Rosen P et al. Whole-body FDG-PET imaging for staging of Hodgkin s disease and lymphoma. J Nucl Med 1997; 38: Guay C, Lepine M, Verreault J, Benard F. Prognostic value of PET using 18F-FDG in Hodgkin s disease for posttreatment evaluation. J Nucl Med 2003; 44: Elstrom R, Guan L, Baker G et al. Utility of FDG-PET scanning in lymphoma by WHO classification. Blood 2003; 101: Moog F, Bangerter M, Diederichs CG et al. Lymphoma: role of whole-body 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) PET in nodal staging. Radiology 1997; 203: Spaepen K, Stroobants S, Dupont P et al. Prognostic value of positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose ([18F]FDG) after first-line chemotherapy in non-hodgkin s lymphoma: is [18F]FDG-PET a valid alternative to conventional diagnostic methods? J Clin Oncol 2001; 19: Cavalli F, Isaacson PG, Gascoyne RD, Zucca E. MALT lymphomas. Hematology (Am Soc Hematol Educ Program) 2001; Zucca E, Bertoni F, Cavalli F. Pathogenesis and treatment of extranodal lymphomas: the fascinating model of mucosa-associated lymphoid tissue lymphoma. Haematologica 2003; 88: Zucca E, Conconi A, Cavalli F et al. Treatment of extranodal lymphomas. Nongastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue MALT lymphomas. Best Pract Res Clin Haematol 2002; 15: Raderer M, Vorbeck F, Formanek M et al. Importance of extensive staging in patients with mucosa-associated lymphoid tissue (MALT)- type lymphoma. Br J Cancer 2000; 83: Erdi YE, Rosenzweig K, Erdi AK et al. Radiotherapy treatment planning for patients with non-small cell lung cancer using positron emission tomography (PET). Radiother Oncol 2002; 62: Lapela M, Leskinen S, Minn HR et al. Increased glucose metabolism in untreated non-hodgkin s lymphoma: a study with positron emission tomography and fluorine-18-fluorodeoxyglucose. Blood 1995; 86: Jerusalem G, Beguin Y, Najjar F et al. Positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) for the staging of low-grade non-hodgkin s lymphoma (NHL). Ann Oncol 2001; 12: Wirth A, Seymour JF, Hicks RJ et al. Fluorine-18 fluorodeoxyglucose positron emission tomography, gallium-67 scintigraphy, and conventional staging for Hodgkin s disease and non-hodgkin s lymphoma. Am J Med 2002; 112: Hoffmann M, Kletter K, Diemling M et al. Positron emission tomography with fluorine-18-2-fluoro-2-deoxy-d-glucose (F18-FDG) does not visualize extranodal B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT)-type. Ann Oncol 1999; 10: Hoffmann M, Kletter K, Becherer A et al. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) for staging and follow-up of marginal zone B-cell lymphoma. Oncology 2003; 64: Sun SS, Chuang FJ, Kao CH. Mucosa-associated lymphoid tissue lymphoma of the lung detected with Ga-67 SPECT imaging. Clin Nucl Med 2002; 27: Hara M, Sugie C, Tohyama J et al. Increased (18)fluorodeoxyglucose accumulation in mucosa-associated lymphoid tissue-type lymphoma of the lung. J Thorac Imaging 2002; 17: Pieterman RM, van Putten JW, Meuzelaar JJ et al. Preoperative staging of non-small-cell lung cancer with positron-emission tomography. N Engl J Med 2000; 343: Vansteenkiste JF, Stroobants SG. Positron emission tomography in the management of non-small cell lung cancer. Hematol Oncol Clin North Am 2004; 18: Lardinois D, Weder W, Hany TF et al. Staging of non-small-cell lung cancer with integrated positron-emission tomography and computed tomography. N Engl J Med 2003; 348: Fiche M, Caprons F, Berger F et al. Primary pulmonary non-hodgkin s lymphomas. Histopathology 1995; 26: Cadranel J, Wislez M, Antoine M. Primary pulmonary lymphoma. Eur Respir J 2002; 20: Friedberg JW, Chengazi V. PET scans in the staging of lymphoma: Current status. Oncologist 2003; 8: