Role of 18F-FDG SPECT / CT imaging in the diagnosis and initial staging of lymphoma

Liang-Qian Tong, Yan-Fang Sui, Yan-Hai Yin , Li-Qing Fu, Jia-Ling Zhong, Sheng-Nan Jiang✉

1.Department of Nuclear Medicine, Central South University Xiangya School Affiliated Haikou Hospital, Haikou 570208, Hainan, China

2.Department of Rehabilitation Medicine, Central South University Xiangya School Affiliated Haikou Hospital, Haikou 570208, Hainan, China 3.Department of Nuclear Medicine, Hainan Medicine College Affiliated Hainan Hospital, Haikou 570311, Hainan, China

Keywords:Lymphoma Staging Tomography emission-computed, single-photon Fluorodeoxyglucose

ABSTRACT Objective: To investigate the role of 18F-FDG SPECT/PET in the diagnosis and initial staging of lymphoma. Methods: A retrospective analysis was carried out on 48 patients in Haikou Hospital from January 2015 to June 2018, who were eventually pathologically diagnosed with lymphoma and had undergone 18F-FDG SPECT/PET before definite diagnosis. (1) Patients were divided into Hodgkin's lymphoma group, diffuse large B cell lymphoma group and other non-Hodgkin's lymphoma group according to Pathological classification; and were divided into nodal lymphoma group and extranodal lymphoma group according to the presence of invasion to the tissues beyond lymph node; and were divided into stage I+II group and stage III+IV group according to clinical Ann Arbor staging. The diagnostic consistencies of 18FFDG SPECT/PET and conventional imaging (CI) in each group were calculated, the T/N ratios of the lymphoma lesion were analyzed as well. (2) Clinical Ann Arbor staging, SPECT/PET staging and CI staging were performed in 48 patients, respectively. Then the efficacy of SPECT/PET staging and CI staging was compared, and the consistency of SPECT/PET staging and clinical Ann Arbor staging was compared as well. Results: (1) In this study, the diagnostic consistent rates of 18F-FDG SPECT/PET and CI were 45.8% (22/48) and 16.6% (8/48), respectively (χ2=9.503, P=0.002＜0.01). (2) The diagnostic consistent rate of 18FFDG SPECT/PET in diffuse large B cell lymphoma group and other non-Hodgkin's lymphoma group was higher than that of CI (P < 0.05). There was no statistical significance between the diagnostic consistent rates of 18F-FDG SPECT/PET in the Hodgkin's lymphoma group, diffuse large B cell lymphoma group and other non-Hodgkin's lymphoma group (χ2=1.067, P=0.448＞0.05). (3) The diagnostic consistent rates of 18F-FDG SPECT/PET in nodal group and extranodal group were 100.0% (19/19) and 21.1% (4/19) (χ2=24.783, P=0.000＜0.01) , respectively. (4) The diagnostic consistent rates of 18F-FDG SPECT/PET and CI were 25% (2/8) and 0 (0/8) in lymphoma with early stage(stage I+II group) (χ2=2.268, P=0.131＞0.05), and 50% (20/40) and 20% (8/40) in lymphoma with late stage (stage III+IV group) (χ2=7.912, P=0.002＜0.01), respectively. (5) There was no statistical significance in T/N ratios of lymphoma lesions between different pathological groups, between nodal group and extranodal group, or between the stage I+II group and the stage III+IV group (P > 0.05). (6) The total consistent rates of 18F-FDG SPECT/PET and CI for initial lymphoma staging were 79.2% (38/45) and 64.4% (31/48) (χ2=18.774, P=0.000＜0.01). SPECT/PET staging was well consistent with clinical Ann Arbor staging in initial lymphoma staging (Kappa=0.696, P=0.000＜0.01). Conclusion: The research has showed that the consistent rates of 18F-FDG SPECT/PET in the diagnosis and initial staging of lymphoma are relatively high, and 18F-FDG SPECT/PET plays an important role in the diagnosis and initial staging of lymphoma.

1. Introduction

Lymphoma, a common hematological disease, has an increasing morbidity rate with years. Its morbidity and the mortality have gradually ranked in the top 10 of all kinds of cancers [1, 2]. The confirmed diagnosis of lymphoma mainly depends on the histopathological biopsy and immunohistochemical examination. However, the pathological biopsy is not taken at the initial diagnosis and treatment, but the related imaging examinations (X-ray, CT, MRI, ultrasound, PET/CT or18F-FDG SPECT/PET, etc.) were undertaken previously. Therefore, imaging examinations are important in detecting, diagnosing, staging and prognosticating in lymphoma. Conventional imaging (CI) (including ultrasound, X-ray plain film, CT, MRI, etc.) is widely applied clinically. They are the routine examinations of many neoplastic diseases for the diagnosis and the staging. They are mainly diagnosed and staged according to the focal morphology and distribution, but for all this, there are certain limitations that the CI is mainly performed according to the anatomical body parts or organs.18F-FDG SPECT/PET, similar as18F-FDG PET/CT and often referred to as 18F-FDG SPECT/PET[3], is a kind of functional imaging of Nuclear Medicine, containing anatomical morphological information (CT image). This examination routinely carries out the whole body scanning, provides dual and comprehensive imaging information from the aspects of glucose metabolism and anatomical morphology, and has a unique value in the diagnosis, staging, prognosis evaluation of lymphoma[4, 5].This study retrospectively analyzed the datas of 48 patients in our hospital, who were finally and pathologically diagnosed as lymphoma and18F-FDG SPECT/PET was carried out simutaneously, aiming to probe into the significance of18F-FDG SPECT/PET in the diagnosis and initial staging of lymphoma. The report is as follows.

2. Materials and Methods

2.1 General Materials

A retrospective study was conducted on 48 patients who were finally pathologically diagnosed as lymphoma and simutaneously undertook18F-FDG SPECT/PET before treatment in our hospital from January 2015 to June 2018, among whom are 28 males and 20 females, aged 24-80 years (58.4±14.1 years). All patients had complete datas and were finally diagnosed by biopsy (pathology and immunohistochemistry, etc.) and related laboratory examinations. The final pathological diagnosis were: Hodgkin lymphoma 4 cases, diffuse large B-cell lymphoma 29 cases, and other non-Hodgkin lymphoma 15 cases (NK/T-cell lymphoma 3 cases, marginal zone B-cell lymphoma 2 cases, mantle cell lymphoma 1 case, peripheral T-lymphocyte lymphoma 4 cases, small lymphocyte lymphoma 1 case, mucosa-associated lymphoid tissue lymphoma 4 cases). According to the pathological types, the patients were classified into Hodgkin lymphoma group, diffuse large B-cell lymphoma group and other non-Hodgkin lymphoma group; according to the extranodal tissue invasion, the patients were divided into nodal lymphoma group and extranodal lymphoma group; according to the clinical Ann Arbor staging, the patients were separated into stage I+II group and stage III+IV group. The diagnostic results about the18F-FDG SPECT/PET and the conventional imaging (CI: ultrasound, X-ray plain film, CT, MRI, etc.) before and after a week were consulted through PACS system; the data of qualitative diagnosis and initial staging of these two imaging results were recorded and analyzed.

2.2 18 F-F DG SPECT/PET imaging

2.2.1 Imaging instruments and imaging agents

American GE infinia + Hawkeye 4 SPECT / CT with dualprobes, adopt the consistent circuit probes.18F-FDG radiochemical purity>95%.

2.2.2 Imaging methods[6, 7]

Before the examination, the patients were fasted for more than 4 hours and their blood glucose was measured. The blood glucose was controlled under the level of 7.8 mmol/L. The18F-FDG dose in intravenous injection: 240～259 MBq; the imaging was performed one hour after the injection of18F-FDG. 3 bed-segments were routinely taken for the imaging (from the head to the upper 1/3 of the femoral bone); the patients with the known or suspected lower limb lesions were taken 1～2 additional bed-segments. SPECT/PET bed-segment of 40 cm, Matrix 128×128; CT scan tube voltage of 140 kV, tube current of 2.5 mA, Matrix 512×512. The acquired SPECT/PET images and CT data were transmitted to XelerisTM2 workstation, and the Volumetrix for Hawkeye program were used for post-processing and diagnosing.

2.2.3 Image Analysis and Diagnosis

All the18F-FDG SPECT/PET images were reviewed together by two experienced physicians for Nuclear Medicine. If there was any disagreement, they discussed and resolved the problems through disgussion with each other. T/N ratio was used to reflect the level of glucose metabolism in the lesions[8, 9] (target/non-target ratio, namely, ROI (region of interest) in the lesion and the corresponding or adjacent normal tissues were respectively delineated, and the uptake ratio of the lesion and its opposite or adjacent normal tissues (background) was calculated). The lesions were determined together according to the evaluation of18F-FDG SPECT/PET imaging and the homogeneous CT imaging. Wherein the18F-FDG SPECT/PET images, at least 2 slices continuously showed that the T/N ratio of lesion was abnormally higher than that of the surrounding tissues; CT images showed that the lesions were positive with the exclusion of benign lesions (for example, spinal degeneration, osteoarthropathy and trauma). If one of the18F-FDG SPECT/PET image and the homogeneous CT image was abnormal, it could be determined to be positive. According to the location, number, morphology,18F-FDG uptake, density, medical history and laboratory examinations,18FFDG SPECT/PET imaging and the homogeneous CT imaging, the qualitative diagnosis and initial staging were carried out.

2.3 Lymphoma Staging Standard

Both18F-FDG SPECT/PET imaging staging (SPECT/PET staging) and conventional imaging staging (CI staging) were classified into stage I to IV according to the Ann Arbor staging standard[2], with the clinical Ann Arbor staging standard (overall consideration of the results of bone marrow biopsy, tissue biopsy, imaging examination, laboratory examinations) as the gold standard.

2.4 Statistical Method

SPSS 20.0 statistical software was used for statistical analysis. The main measurement data in this paper was expressed as mean ± standard deviation (x±s ). Chi square test (χ2test, Fisher exact probability method) was used for the comparison between groups of enumeration data. One-way analysis of variance (ANOV) or independent sample t test was used for the comparison between groups of measurement data. P<0.05 was considered statistically significant.

3. Results

3.1 Diagnosis in Different Pathological Groups

The diagnostic consistent rates of18F-FDG SPECT/PET and CI in 48 cases of lymphoma were 45.8% (22/48) and 16.6% (8/48) respectively. The diagnostic consistent rates of18F-FDG SPECT/PET was statistically higher (χ2=9.503, P=0.002＜0.01). The diagnostic consistent rates of18F-FDG SPECT/PET in diffuse large B-cell lymphoma group and other non-Hodgkin lymphoma groups were also higher than that of CI (P<0.05). The diagnostic consistent rate of18F-FDG SPECT/PET in the Hodgkin lymphoma group was 75% (3/4), and was higher than that of CI (25%, 1/4), but there was no statistical difference between them. There was no significantly statistical difference in the consistent rates of18F-FDG SPECT/PET for Hodgkin lymphoma group, diffuse large B-cell lymphoma group and other non-Hodgkin lymphoma groups (χ2=1.067, P=0.448＞0.05). See Table 1.

3.2 Diagnosis in nodal lymphoma group and extranodal lymphoma group

The diagnostic consistent rate of18F-FDG SPECT/PET for nodal lymphoma group was 100.0% (19/19), significantly higher than that of CI (21.1%, 4/19) (χ2=24.783, P=0.000＜0.01). The diagnostic consistent rates of18F-FDG SPECT/PET and CI in extranodal lymphoma group were both relatively low, (10.3% (3/29) and 14.8% (4/29), respectively, and there was no significantly difference between them (χ2=0.162, P=0.687＞0.05). See Table 2.

3.3 Diagnosis in different clinical Ann Arbor staging

The consistent rates of18F-FDG SPECT/PET and CI in the diagnosis of lymphoma with earlier stage (I and II) were both low, and there was no statistical difference between them (χ2=2.268, P=0.131＞0.05); the consistent rate of18F-FDG SPECT/PET in the diagnosis of lymphoma with later stage (III and IV) was significantly higher than that of CI (χ2=7.912, P=0.002＜0.0). See Table 3.

3.4 T/N ratios of lymphoma lesions in different groups

The T/N ratios of Hodgkin lymphoma group, diffuse large B-cell lymphoma group and other non-Hodgkin lymphoma groups were 6.91±4.65, 7.62±5.26 and 5.90±4.14, respectively, with no statistical difference between the groups (F=0.934, P=0.401>0.05); the T/Nratios of the nodal lymphoma group and the extranodal lymphoma group were 6.91±4.65 and 7.62±5.26, respectively, with no statistical difference between the groups (T=0.478, P= 0.635 > 0.05); the T/N ratios of the Stage I+II group and Stage III+IV group were respectively 8.16±6.54 and 7.18±4.71, with no significant difference between the two groups (T = 0.505, P= 0.616 > 0.05).

Table 1 The diagnostic analysis of 18F-FDG SPECT/PET in lymphoma of different pathological groups (n=48)

Table 2 The diagnostic analysis of 18F-FDG SPECT/PET in nodal lymphoma and extranodal lymphoma (n=48)

Table 3 The diagnostic analysis of 18F-FDG SPECT/PET in lymphoma of different clinical Ann Arbor staging (n=48)

3.5 Comparison of 18F-FDG SPECT/PET staging and CI staging

The total consistent rate of18F-FDG SPECT/PET in the initial staging of lymphoma was 79.2% (38/45), which was significantly higher than that of CI staging 35.4% (17/ 48) (χ2=18.774, P=0.000＜0.01). The consistent rates of 18F-FDG SPECT/PET and CI in the initial staging of lymphoma were respectively 80% (4/5) and 6.7% (1/15), and18F-FDG SPECT/PET staging was much better (χ2=10.756, P=0.001＜0.01).

3.6 The consistency of 18F-FDG SPECT/PET staging and clinical Ann Arbor staging

In the initial staging of lymphoma, the number of cases with clinical Ann Arbor stage I, II, III and IV was 4, 4, 14 and 26, respectively.18F-FDG SPECT/PET staging was well consistent with clinical Ann Arbor staging (Kappa=0.696, P=0.000＜0.01), especially for the patients in the Stage I of clinical Ann Arbor staging I (all 4 cases were consistent), stage II (all 4 cases were consistent) and stage III (13 cases were consistent, 1 case was in Stage I of SPECT/CT staging). Among the patients with stage IV of clinical Ann Arbor staging, 17 were in accordance with the criteria, among the patients with stage I, stage II and stage III of18F-FDG SPECT/PET staging, and the cases which were up-regulated to stage IV of clinical Ann Arbor staging were 5, 1 and 3, respectively. All of the 9 patients showed bone marrow invasion by bone marrow biopsy, but no abnormal FDG uptake was found by18F-FDG SPECT/PET.

4. Discussion

The morbidity rate of lymphoma is high in China, and the morbidity rate of male and female are about 1.39/10 0000 and 0.84/10 0000, respectively, [10]. The value of18F-FDG PET/CT in the diagnosis and staging of lymphoma had been widely recognized clinically[11]. With the improvement of economy and medical technology in China, the number of PET/CT in China has also increased year by year, but there are still many hospitals that are not equipped with PET/CT. The principle of18F-FDG SPECT/PET is much similar to that of18F-FDG PET/CT [4]. The main difference is that the resolution of18F-FDG SPECT/PET is relatively low, and the ability to detect and diagnose some tiny lesions or lesions with inconspicuously increased glucose metabolism is low. In spite of this, it has the advantage of economic benefit and efficiency, which can greatly reduce the economic burden for patients and country.

Lymph nodes and lymphoid tissues are widely distributed in different organs and tissues of the human body, which determines that lymphoma lesions may occur in lymph nodes all over the human body, as well as many organs and tissues that are rich with lymphoid tissues. Therefore, their clinical manifestations are diverse and complex; it is often difficult to distinguish from the primary tumors that derives from various organs and tissues (such as nasopharynx, gastrointestinal tract, intracranial, etc.) [12].Imaging examinations play an important role in the diagnosis and treatment. Conventional imaging (CI) (such as X-ray, CT, MRI and ultrasound, etc.), for its wide clinical indications and convenience, is always the conventional choice for most clinicians in screening and diagnosing neoplastic diseases, while18F-FDG SPECT/PET is appealed when there are difficulties for CI in the diagnosis. Among the 48 patients of this study, none of them skipped the CI directly to18F-FDG SPECT/PET. However, the CI were basically performed by anatomic location or organ, so the amount of information obtained was partial and limited, and the total diagnostic consistent rate of CI was relatively low in this study, about 16.6% (8/48). While18F-F DG SPECT/PET scaned a wider range anatomically and included dual-mode information of glucose metabolism and anatomical structure, and the total diagnostic consistent rate is about 45.8% (22/48), which is significantly higher than that of CI (see Table 1). The consistent rate of18F-FDG SPECT/PET was higher than that of CI, part of the reason is that the nuclear medicine doctors integrated the patient's past clinical data when they were carrying out18F-FDG SPECT/PET diagnosis, which included reading the CI images that had been done., , The imaging characteristics of extranodal lymphoma are similar to that of primary tumors of organs or tissues, such as gastrointestinal lymphoma and primary tumors of gastrointestinal tract, nasopharyngeal lymphoma and nasopharyngeal cancer, etc., making it difficult to differentiate and diagnose them. In this study, the diagnostic consistent rates of18F-FDG SPECT/PET and CI for extranodal lymphoma group were relatively low, 10.3% (3/29) and 14.8% (4/29), respectively. There was no statistical difference between the two groups (χ2=0.162, P=0.687) (see Table 2). The nodal lymphoma is characterized by multiple and enlarged lymph nodes and high glucose metabolism, so the diagnostic capability of18F-FDG SPECT/PET in nodal lymphoma is high. In this study, the diagnostic consistent rate was 100.0% (19/19), significantly higher than that of18F-FDG SPECT/PET in extranodal lymphoma (χ2=37.166, P =0.000 < 0.01), andsignificantly higher than that of CI in nodal lymphoma (21.1% (4/19)) (χ2=24.783, P =0.000< 0.01) (see Table 2). Yaohui et al [3] reported that in 100 patients with lymphoma in the initial treatment, the diagnostic accuracy of18F-FDG SPECT/PET was higher than that of CT, and the diagnostic accuracy of these two were 100.0% and 81.7% respectively (P<0.05), and the sensitivity of18F-FDG SPECT/PET to detect extranodal lesions was higher (the sensitivity were 91.3% and 56.5%, P< 0.05). Therefore,18F-FDG SPECT/PET plays important role in the diagnosis of the lymphoma, especially in the nodal lymphoma.

Table 4 The analysis of 18F-FDG SPECT/PET staging and CI staging in lymphoma (n=48)

This study showed that, in the18F-FDG SPECT/PET, there was no significant difference in T/N ratio between different pathological groups (Hodgkin lymphoma, diffuse large B-cell lymphoma, other non-Hodgkin lymphoma), between nodal lymphoma group and extranodal lymphoma group, between stage I+II group and stage III+IV group (P>0.05). That meaned the up-take ability of18FFDG was of no significance. The classification and initial staging of lymphoma was not reliable enough through the FDG metabolism.

The initial staging of lymphoma is of great significance to the treatment options and prognosis. PET/CT has been widely used in the staging of lymphoma [12-15].18F-FDG SPECT/PET has a good ability to detect the lesions by screening the abnormal glucose metabolism [10, 16], and also plays an important role in the initial staging of the lymphoma. In this study, the consistent rate of18FFDG SPECT/PET for the staging of lymphoma was significantly higher than that of CI, and the total consistent rates of them were 79.2% (38/48) and 35.4% (17/48) respectively (χ2=18.774, P=0.000＜0.01). The inconsistent rates of stage I of18F-FDG SPECT/PET and stage I and stage II of CI were relatively higher (the inconsistent rates were 60.0%, 77.8% and 93.3%, respectively) (see Table 5). Analysis of the causes shows that18F-FDG SPECT/PET has the function of whole-body scanning, functional imaging and anatomical morphology imaging, so it has a stronger and more comprehensive ability to detect the lesions. However, most of those inconsistent cases, who were staged stage I of18F-FDG SPECT/PET and stage I and stage II of CI, showed bone marrow involvement by marrow biopsy or invasion of the surrounding tissues and small lymph nodes by postoperative biopsy, and then the staging was changed. In this study, kappa test was applied to analyze the consistency of18FFDG SPECT/PET staging and the clinical Ann Arbor staging, and the results showed that the consistency between the two was good (Kappa=0.696, P=0.000＜0.01). Further analysis showed that among the patients with stage I, stage II and stage III of18F-FDG SPECT/PET staging, the cases which were up-regulated to stge IV of clinical Ann Arbor staging were 5, 1 and 3, respectively. All of the 9 patients showed bone marrow invasion by bone marrow biopsy, but no abnormal FDG uptake was found by18F-FDG SPECT/PET. The reason for the misdiagnosis of bone marrow involvement may be that the glucose metabolism of bone marrow is relatively vigorous, so the radioactive concentration is high on the18F-FDG SPECT/PET images. Besides, the resolution of18F-FDG SPECT/PET is not high enough, and it affects the judgment.

In conclusion,18F-FDG SPECT/PET has a high consistent rate in the diagnosis and initial staging of lymphoma, which can play an important clinical role in the diagnosis and initial staging of lymphoma.