Lymphoma consists of a heterogeneous group of diseases; marked improvement has been made in diagnosis and treatment. Imaging is important both for staging and assessment of response to therapy. Staging systems have been modified and specific criteria have been developed for assessment of response to therapy with both computed tomography (CT) and fluorine-18 fluorodeoxyglucose positron emission tomography (PET)/CT .
There are several common pitfalls in the diagnosis of lymphoma using PET alone. One of them is that gastric and cerebral lymphoma lesions are sometimes difficult to characterize on PET images due to physiologic gastric and cortical accumulation of FDG. Also, physiologic colonic uptake might be mistaken for lymphomatous infiltration. Another pitfall is that small-volume lesions might be undetectable on both pre- and post-therapy PET scans especially when there is high background activity surrounding the lesions. Accurate correlation with anatomical CT findings is mandatory in avoiding such pitfalls; thus, integrated PET/CT is especially helpful .
Many reports in literature have assessed the role of PET/CT for evaluation of therapeutic response of lymphoma.
In our study, we evaluated both PET/CT and CECT for their role in assessment of response during the course and end of treatment in lymphoma patients.
The imaging evaluation and follow-up of lymphoma patients in the past depended only on CECT findings. However, CECT has relatively low sensitivity in determining lymphomatous involvement of average-sized lymph nodes, bone marrow, spleen, and extranodal tissues. The presence of residual lymph node mass was a frequently encountered diagnostic dilemma as it was difficult to differentiate between post-treatment fibrosis and residual viable tumorous tissue by CECT .
In our study, PET/CT was able to add clinically significant information not obtained by CT. On a regional-based survey of patients, PET/CT showed significantly better results than CECT in accurately identifying lymph node groups as positive or negative for lymphomatous involvement. PET/CT was also capable of detecting more extranodal sites of the disease than CECT. PET/CT can assess therapeutic response more precisely than CECT.
18F-FDG PET/CT does not depend only on nodal size to determine the presence or absence of malignancy (anatomical evaluation), assessment of intra-nodal activity plays a very important role (metabolic evaluation). Average-sized lymph nodes might contain tumoral tissue on 18F-FDG PET/CT images, and enlarged lymph nodes can be reactional in nature. Hence, for this reason, PET proved to be more sensitive and specific than CT for detection of sites of lymphomatous infiltration .
In the follow-up study during treatment, our study revealed that the results of PET and CT were concordant in 44 patients [12 complete responses (CR), 24 partial responses (PR), and 8 progressive diseases (PD)]. For the rest of the cases (45% of our cases, n = 36), the therapeutic response was different.
While at the end of treatment assessment, the results of PET and CT were concordant in 52 patients [20 CR, 12 PR, and 20 PD]. For the rest of the cases (35% of our cases, n = 28), the therapeutic response differed. Thus, PET/CT and contrast-enhanced computed tomography were concurrent in results in 55% of cases during treatment and 75% at the end of treatment with CT sensitivity of 61.1%, specificity of 92.2%, and accuracy of 76.2% during treatment in comparison to 100% sensitivity and specificity of PET/CT, while sensitivity of CT at end of treatment is 57.5% with specificity of 86.7% and accuracy of 71.6%. This is in keeping with the multicenter study; comparison of FDG PET/CT and 64-slice multi-detector-row CT was done in initial staging and response evaluation at the end of treatment in patients with lymphoma by Gómez León et al. ; 181 patients were enrolled; their results confirmed that FDG PET/CECT was clearly superior to ceCT64 for EOT evaluation (P < 0.05). Using FDG PET/CT, there was concordance with the reference standard in 97.8% of the cases (88/90) with κ = 0.91 (P < 0.001), corresponding with a CR in 83.3% (n = 75), a PR in 4.4% (n = 4), and a PD in 10% (n = 9), with good sensitivity and specificity for response assessment. As compared to CECT, there was concordance with the reference standard in 78% of cases (71/91).
Our results are also matching a study done by Othman et al.  were 100 patients were enrolled and showed poor agreement between PET/CT and CECTs (k = 0.32).
Similar results were also obtained in the study by Le Dortz et al. . They retrospectively evaluated the usefulness of positron emission tomography/computed tomography in staging, prognosis evaluation and restaging of patients with follicular lymphoma. In 45 patients, the accuracy of PET/CT for therapeutic response assessment was higher than that of CT (0.97 vs 0.64), especially due to its ability to identify inactive residual masses.
In a study by Omar et al. , the study included 50 patient PET/CTs in initial staging and therapy response assessment of lymphoma compared to contrast-enhanced CT. In the follow-up study during chemotherapy cycles, 18F-FDG PET/CT and CECT were concurrent in results in 11 cases (61%) and discordant in 7 cases (39%). In the follow-up study after the end of chemotherapy cycles, 18F-FDG PET/CT and CECT were concurrent in results in 9 cases (44%) and discordant in 11 cases (56%).
In a study done by Najjar et al. , the sensitivity and specificity were 87% and 100% for FDG-PET, 100% and 100% for physical examination, and 90% and 100% for CT, respectively. In addition, 42 of 97 peripheral lymph node lesions observed by FDG-PET were clinically undetected, whereas the physical examination detected 23 additional nodal lesions. PET and CT both indicated 12 extranodal lymphomatous localizations. FDG-PET showed 7 additional extranodal lesions while 5 additional unconfirmed lesions were observed on CT.
In a study by El Refaei et al.  by PET/CT, 38.5% of the studied population had complete response, 38.5% had partial response, 10.3% had stable disease, and 12.8% had metabolic progression. Morphologic response on CT showed that 30.8% of the studied population had complete response, 48.7% had partial response, 10.3% had stable disease, and 10.3% had morphologic progression.
According to Gómez León et al. , the most frequent reason for the overestimation in CECT of response was the detection of residual lymphadenopathy of pathological size lacking malignant infiltration. Regarding the extra nodal lesions, the most frequent reason for incorrectly detecting lymphomatous infiltration in the lung was the detection of nonspecific inflammation
The study by Tatsumi et al. , 48 sites exhibited discordant findings: 34 sites as PET positive and CT negative and 14 sites as PET negative and CT positive. Among the PET-positive and CT-negative sites, patients had negative CT findings because of the size criterion (more than 10 mm in short axis was considered positive).
In a study done by Fueger et al. , PET/CT correctly diagnosed 92 nodal regions as positive for lymphomatous involvement and 458 as disease free vs 68 and 449 for PET and 64 and 459 for CT, respectively. The respective sensitivities, specificities, and accuracies were 99%, 100%, and 99.8% for PET/CT; 68%, 97.5%, and 92.2% for PET; and 70%, 100%, and 94.7% for CT. PET/CT performed significantly better than PET (P < 0.001 for sensitivity, specificity, and accuracy) and CT (P < 0.001 for sensitivity and accuracy). PET/CT also correctly identified significantly more extranodal lesions (22) than CT (14) and PET (nine).
In cases with PET-negative and CT-positive sites, the patients were considered to have nonviable fibrotic tissue according to clinical information, including follow-up imaging results.
It has been known for many years that CT assessment is not sensitive for tumoral foci that are less than 10 mm in diameter, but no other alternative method than size criteria has been consistently adopted.
Being aware of normal FDG distribution and physiological FDG uptake is of utter importance in oncologic PET/CT examinations. To avoid false-positive and false-negative results, interpreting the CT and PET findings should be done carefully .
Since PET/CT provides both metabolic as well as morphologic data for each lesion, new criteria for diagnosing small foci of malignancy may be suggested with this modality.