Usefulness and pitfalls of F-18-FDG PET/CT for diagnosing extramedullary acute leukemia

doi:10.1016/j.ejrad.2015.11.019

European Journal of Radiology

Volume 85, Issue 1, January 2016, Pages 205-210

https://doi.org/10.1016/j.ejrad.2015.11.019 Get rights and content

Abstract

Purpose

It is very important to identify whether there is extramedullary involvement in acute leukemia (AL), especially in those with recurrent disease. This retrospective study aimed to assess the role of ¹⁸F-FDG PET/CT for diagnosing extramedullary AL.

Materials and methods

PET/CT examinations were performed in 9 patients with newly diagnosed AL, and 70 patients suspected to have recurrent AL. All the patients were diagnosed with AL by bone marrow biopsy. The diagnosis of extramedullary lesions was established according to the combination of pathology, physical examination, and imaging techniques including magnetic resonance imaging (MRI) and PET/CT, and/or cerebrospinal fluid (CSF) cytologic testing, and clinical follow-up.

Results

Of the 79 patients, including 34 acute lymphocytic leukemia (ALL) and 45 acute myeloid leukemia (AML) cases, 30 patients were diagnosed with extramedullary AL. ¹⁸F-FDG PET/CT demonstrated ¹⁸F-FDG positive lesions in the extramedullary regions in 42 patients. Among them, 28 patients were diagnosed to have extramedullary AL and the other 14 were diagnosed with non-hematological malignancies (false positive disease). The sensitivity, specificity, and accuracy of ¹⁸F-FDG PET/CT in diagnosing extramedullary involvement of AL were 93.3% (28/30), 71.4% (35/49), and 79.7%, respectively. The ¹⁸F-FDG uptake of lesions was not significantly different between extramedullary AL and false positive cases (SUVmax: 6.66 ± 2.65 vs. 5.85 ± 1.88, t = 1.275, P = 0.206). The FDG uptake of extramedullary AL between ALL and AML were also not significantly different (SUVmax: 7.01 ± 2.82 vs. 6.10 ± 2.29, t = 1.332, P = 0.188). The predominant locations of extramedullary AL were the spleen, soft tissue, lymph nodes, central nerve system, liver, testis, and kidney. A total of 48.2% (27/56) of extramedullary AL lesions presented as diffuse FDG uptake compared with 6.25% (1/16) in the false positive lesions (χ² = 9.221, P = 0.002).

Conclusion

¹⁸F-FDG PET/CT is a sensitive, but not specific imaging modality for diagnosing extramedullary AL. Diffuse ¹⁸F-FDG uptake in extramedullary lesions may indicate leukemia involvement.

Introduction

Leukemia is a common hematological malignancy that usually originates from the bone marrow, and results in high numbers of abnormal white blood cells. There are two main types of leukemia, chronic leukemia (CL) and acute leukemia (AL). AL, including acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML), is characterized by a rapid increase in the number of immature blood cells. According to 2009 data from the Central Cancer Registries of China, the incidence of these two types of AL are 1.24/100,000, and 2.57/100,000, respectively, which are similar to those in other Asiatic countries, but higher than in Europe and the United States [1]. Immediate treatment is required for AL due to the rapid progression and accumulation of the malignant cells, which then spill over into the bloodstream and spread to other organs.

Extramedullary AL is when lesions occur at an anatomical site other than the bone marrow. Extramedullary involvement is considered to be an uncommon presentation of AL. However, some data suggest it may be present in up to 30% of patients with AML [2], [3], and has been increasingly reported in ALL patients [4]. Identification of extramedullary involvement, especially recurrent extramedullary AL, has a major impact on treatment because some extramedullary lesions can not be effectively treated by standard chemotherapy and require a more intensive chemotherapy or allogeneic hematopoietic stem cell transplantation (HSCT). In addition, patients with an extramedullary relapse have a poorer outcome. Extramedullary AL can occur in the most sites in the body, and is not easily diagnosed, especially in the recurrent AL patients.

PET/CT is a widely used imaging modality for diagnosing and staging malignant diseases, including the hematologic malignancies, most particularly non-Hodgkin’s lymphoma (NHL) and Hodgkin’s lymphoma (HL) [5]. However, limited data has been reported on the utility of ¹⁸F FDG PET/CT in patients with leukemia. The reason may be attributed to the fact that the diagnosis of leukemia can be established by bone marrow biopsy, and chemotherapy is the main treatment for the leukemia. Some cases reports and articles with a small sample size have highlighted the usefulness of PET/CT in diagnosing extramedullary AL [2], [3], [6], [7], [8], [9], [10], [11], [12], [13], however, the role of ¹⁸F FDG PET/CT in extramedullary AL has not yet been systematically studied. In the present study, the records of 79 patients with AL were retrospectively examined to determine the usefulness and pitfalls of ¹⁸F FDG PET/CT for diagnosing extramedullary AL.

Section snippets

Patients

This study was approved by the Institutional Review Board of Nanfang Hospital, Southern Medical University. Because of the retrospective nature of the study, the requirement of informed consent was waived. Between January 2004 and April 2014, 79 patients with AL received ¹⁸F FDG PET/CT examinations, including 52 males and 27 females with a median age of 37.3 years (range, 4–72 years). Of these patients, 70 received PET/CT scans due to suspected relapse and 9 had newly diagnosed disease. In the

PET/CT imaging

Of the 79 patients, 34 patients were diagnosed with ALL and 45 with AML. Among them, a diagnosis of extramedullary AL was made in 30 patients. ¹⁸F FDG PET/CT demonstrated positive lesions in the extramedullary regions in 42 patients. Of them, 28 patients were diagnosed to have extramedullary AL. In the other 14 patients, positive lesions on PET/CT images were identified to be false positive disease. The sensitivity, specificity, and accuracy of ¹⁸F FDG PET/CT for diagnosing extramedullary AL

Discussion

Due to improvements of treatment, more AL patients now can have a longer life. As a result, it has been reported that the incidence of extramedullary relapse is increasing, especially in the patients that have received HSCT [3], [15], [16], [17], [18]. Usually, the diagnosis of extramedullary relapse is established when the patient had an unbearable symptom and by this time extramedullary recurrent lesions are often large or widespread and outcomes are poor. Therefore, to attain a good outcome

Conflict of interest

A manuscript of “Usefulness and pitfalls of F-18-FDG PET/CT for diagnosing extramedullary acute leukemia” was wrote by Wen-lan Zhou, Hu-bing Wu, Li-juan Wang, et al. All authors have read and approved this version of the article, and due care has been taken to ensure the integrity of the work. Neither the entire paper nor any part of its content has been published or has been accepted elsewhere. It is not being submitted to any other journal.

Acknowledgments

This work was supported by National Natural Science Foundation Project of China (81271641, 81371591), and the President Foundation of Nanfang Hospital, Southern Medical University (2013C005).

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Usefulness and pitfalls of F-18-FDG PET/CT for diagnosing extramedullary acute leukemia

Abstract

Purpose

Materials and methods

Results

Conclusion

Introduction

Section snippets

Patients

PET/CT imaging

Discussion

Conflict of interest

Acknowledgments

Blood

Leuk. Res

J. Am. Acad. Dermatol.

An analysis of incidence and mortality of leukemia in china, 2009

China Cancer

Extramedullary disease in patients with acute myeloid leukemia assessed by (18) F-FDG PET

Eur. J. Haematol.

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Clin. Nucl. Med.

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Clin. Nucl. Med.

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Clin. Nucl. Med.

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