Detection of Extramedullary Infiltrates in Acute Myelogenous Leukemia with Whole-Body Positron Emission Tomography and 2-Deoxy-2-[18F]-Fluoro-D-Glucose

doi:10.1016/S1095-0397(01)00056-5

Molecular Imaging & Biology

Volume 4, Issue 2, March–April 2002, Pages 179-183

https://doi.org/10.1016/S1095-0397(01)00056-5 Get rights and content

Abstract

This work reports on a female patient with acute myelogenous leukemia (AML) FAB M 5a with initial extramedullary leukemia (EML) in skin, breast, and synovia. A year after diagnosis she developed a histologically proven isolated recurrence of the EML in the right upper ankle. The bone marrow was still in complete remission. Conventional x-ray, magnetic resonance imaging (MRI), bone scintigraphy, and 2-deoxy-2-[¹⁸F]-fluoro-D-glucose whole-body positron emission tomography (FDG-PET) were performed. All images showed alterations in the lower leg. Shortly after, an isolated relapse of the AML was diagnosed in the right elbow. FDG-PET demonstrated this lesion as well as an unknown lesion in the subcutis due to EML. In the course of her illness, the patient underwent one more PET examination for therapy control. The present observations suggest that whole-body FDG-PET may be valuable for the detection of EML and for the assessment of chemotherapeutic effects on identified lesions. (Mol Imag Biol 2002;4:179–183)

Introduction

xtramedullary leukemic infiltrates of acute myelogenous leukemia (AML) are also known as granulocytic sarcoma, chloroma or “green cancer” and have been reported for any body site.1, 2 The frequency of extramedullary leukemia (EML) is about 5–10% of all patients with AML varying very much for its different onset forms. EML may appear in the absence of medullary AML (primary EML), at the time of presentation of AML, as an isolated recurrence of AML or with concurrent bone marrow relapse of AML.² Primary EML is not always followed by AML, conversely, EML after AML is commonly followed by a systemic relapse.3, 4 Primary EML is misdiagnosed in about 50%, most commonly as malignant lymphoma.² Possible predisposing risk factors for extramedullary infiltrates include chromosomal abnormalities, blast expresssion of neural-cell adhesion molecule or the expression of several T-cell markers.2, 5 It seems necessary that the blast cells have acquired at least some degree of differentiation to migrate into the tissues. Depending on the morphologic subtype or the patient's age, some locations seem to be more typical than others. In AML FAB M4 and M5, the EML presents itself most commonly as gingival hypertrophy or as infiltration of the skin (leukemia cutis).² In children with AML, lymphadenopathy and splenomegaly appear more often than in adults.2, 3 In adults, involvement of the skeleton, predominantly affecting the metaphyseal regions of the long bones of the lower extremities, is very infrequent. Therapy of EML depends primarily on its time of appearance. The recommended treatment of primary EML is with induction chemotherapy alone, whereas in combined EML/AML, the standard AML chemotherapy protocol should be applied. Isolated EML may be treated with local irradiation or surgery, and possibly with continued intensification chemotherapy.² To our knowledge, we are the first to report the detection of EML by 2-deoxy-2-[18F]-fluoro-D-glucose whole-body positron emission tomography (FDG-PET).

Section snippets

Case Report

In May 1997, a 25-year-old female patient developed intermittent, later constant pain in the right upper ankle, both knees, as well as the left elbow and wrist. Simultaneously, painless subcutaneous nodules appeared. In October 1997, the patient consulted the clinic of Rheumatology at the University Hospital Zurich because of persistent arthralgias. There, the observation of anemia and thrombocytopenia prompted a bone marrow examination that resulted in the diagnosis of AML FAB M5a. The

Discussion

To our knowledge this is the first report of a detection of extramedullary manifestations of AML by FDG-PET. The role of the FDG-PET examination in other hematologic malignancies, such as non-Hodgkin lymphoma (NHL) or Hodgkin's disease (HD), is increasingly important. Due to the high FDG-uptake, even small manifestations of the lymphoma may be detected, which improves the initial staging of the disease and the follow-up of either chemotherapy or irradiation. Compared with computed tomography

References (6)

J.F. Holland et al.
Cancer Medicine
(1997)
J.C. Byrd et al.
Extramedullary myeloid cell tumors in acute nonlymphocytic leukemiaa clinical review
J. Clin. Oncol.
(1995)
J.M. Meis et al.
Granulocytic sarcoma in nonleukemic patients
Cancer
(1986)

There are more references available in the full text version of this article.

Cited by (27)

Myeloid sarcoma, chloroma, or extramedullary acute myeloid leukemia tumor: A tale of misnomers, controversy and the unresolved
2021, Blood Reviews
Citation Excerpt :
18Fluorodeoxy-Glucose Positron Emission Tomography/CT (FDG-PET/CT) appears to be the best imaging modality to assess the presence of eAML. Early reports noted the ability of FDG-PET/CT to both detect eAML and monitor its response to therapy [67,68]. Small case series of FDG-PET/CT when paired with contemporaneous biopsies noted an 80–90% rate of specificity with a maximum standardized uptake value (SUVmax) ranging from 2.1 to 9.7 [69–71].
The World Health Organization classification and definition of “myeloid sarcoma” is imprecise and misleading. A more accurate term is “extramedullary acute myeloid leukemia tumor (eAML).” The pathogenesis of eAML has been associated with aberrancy of cellular adhesion molecules, chemokine receptors/ligands and RAS-MAPK/ERK signaling. eAML can present with or without synchronous or metachronous intramedullary acute myeloid leukemia (AML) so a bone marrow evaluation is always recommended. Accurate diagnosis of eAML requires tissue biopsy. eAML confined to one or a few sites is frequently treated with local therapy such as radiotherapy. About 75–90% of patients with isolated eAML will develop metachronous intramedullary AML with a median latency period ranging from 4 to 12 months; thus, patients with isolated eAML may also be treated with systemic anti-leukemia therapy. eAML does not appear to have an independent prognostic impact; selection of post-remission therapy including allogeneic hematopoietic cell transplant (alloHCT) is typically guided by intramedullary disease risk. Management of isolated eAML should be individualized based on patient characteristics as well as eAML location and cytogenetic/molecular features. The role of PET/CT in eAML is also currently being elucidated. Improving outcomes of patients with eAML requires further knowledge of its etiology and mechanism(s) as well as therapeutic approaches beyond conventional chemotherapy, ideally in the context of controlled trials.
Diagnostic Imaging: Pediatrics
2017, Diagnostic Imaging: Pediatrics
FDG-PET imaging in hematological malignancies
2016, Blood Reviews
Citation Excerpt :
FDG-PET/CT is not regularly used in the assessment of leukemia [1]. However, several case reports have demonstrated the potential of FDG-PET/CT in diagnosis and follow-up of leukemic bone marrow infiltration [123–125]. In a preliminary study [126], utility of FDG-PET/CT to diagnose extramedullary disease in de novo or relapsed AML patients was described.
The majority of aggressive lymphomas is characterized by an up regulated glycolytic activity, which enables the visualization by F-18 FDG-PET/CT. One-stop hybrid FDG-PET/CT combines the functional and morphologic information, outperforming both, CT and FDG-PET as separate imaging modalities. This has resulted in several recommendations using FDG-PET/CT for staging, restaging, monitoring during therapy, and assessment of treatment response as well as identification of malignant transformation. FDG-PET/CT may obviate the need for a bone marrow biopsy in patients with Hodgkin's lymphoma and diffuse large B cell lymphoma. FDG-PET/CT response assessment is recommended for FDG-avid lymphomas, whereas CT-based response evaluation remains important in lymphomas with low or variable FDG avidity. The treatment induced change in metabolic activity allows for assessment of response after completion of therapy as well as prediction of outcome early during therapy. The five-point scale Deauville Criteria allows the assessment of treatment response based on visual FDG-PET analysis. Although the use of FDG-PET/CT for prediction of therapeutic response is promising it should only be conducted in the context of clinical trials. Surveillance FDG-PET/CT after complete remission is discouraged due to the relative high number of false-positive findings, which in turn may result in further unnecessary investigations. Future directions include the use of new PET tracers such as F-18 fluorothymidine (FLT), a surrogate biomarker of cellular proliferation and Ga-68 CXCR4, a chemokine receptor imaging biomarker as well as innovative digital PET/CT and PET/MRI techniques.
Extramedullary Relapse of Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation: An Easily Overlooked but Significant Pattern of Relapse
2012, Biology of Blood and Marrow Transplantation
Citation Excerpt :
Thus, the diagnosis of an EM relapse is often delayed until patients develop the symptoms of a large mass, such as abdominal pain or constipation. However, a number of recent reports have shown that EM infiltration of AML can be detected by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) or FDG-PET/computed tomography (CT) [43-53]. Stölzel et al. [54] recently reported the results of FDG-PET/CT in 10 patients with AML with histologically proven EM disease at diagnosis (n = 5), relapse after alloSCT (n = 4), or relapse after chemotherapy (n = 1).
Acute myeloid leukemia may manifest as myeloid sarcoma in a variety of extramedullary (EM) tissues at diagnosis or at relapse. Although EM relapse after allogeneic hematopoietic stem cell transplantation (alloSCT) has been considered to be rare, recent studies have suggested that it occurs in 5% to 12% of patients who receive alloSCT, accounting for 7% to 46% of total relapses. The incidence of EM relapse after immunomodulation (eg, donor lymphocyte infusion) or a second SCT is even higher. Moreover, patients with EM relapse are more likely to have had preceding acute graft-versus-host disease or chronic graft-versus-host disease relative to those with bone marrow relapse. Collectively, these observations suggest that the preferential occurrence of the graft-versus-leukemia effect underlies the pathogenesis of EM relapse. Establishing an early diagnosis of EM relapse has been challenging because of the immense diversity in the relapse sites; however, recent studies have suggested the usefulness of ¹⁸F-fluorodeoxyglucose positron emission tomography scans in the detection of EM relapse. As a treatment for EM relapse, a combination of local and systemic therapy should be considered, because local therapy alone often results in subsequent systemic relapse. The prognosis for patients who develop EM relapse after SCT remains poor but is slightly better than that after bone marrow relapse. In addition to an early diagnosis with new modalities, clinical studies using new agents that may offer systemic activity while preserving the graft-versus-leukemia effect are warranted as part of an effort to improve the clinical outcome.
Utilization of FDG PET/CT in the management of inflammation and infection in patients with malignancies
2012, PET Clinics
Citation Excerpt :
Therefore the uptake cannot be automatically attributed to infection or tumor infiltration, and further investigations are warranted if clinically indicated.22 In patients with leukemia, PET/CT may be useful in detecting extramedullary involvement; however, studies in this area are limited.43–45 The modality has already proved its value in diagnosing Richter transformation of chronic lymphoid leukemia to diffuse large-cell lymphoma, with a reported 91% sensitivity and 80% specificity.46
Utility of 18F-FDG-PET for detecting acute lymphoblastic leukemia: a case series of pediatric acute lymphoblastic leukemia without hematological symptoms
2022, International Journal of Hematology

View all citing articles on Scopus

View full text

Brief articleDetection of Extramedullary Infiltrates in Acute Myelogenous Leukemia with Whole-Body Positron Emission Tomography and 2-Deoxy-2-[18F]-Fluoro-D-Glucose

Abstract

Introduction

Section snippets

Case Report

Discussion

Cancer Medicine

Extramedullary myeloid cell tumors in acute nonlymphocytic leukemiaa clinical review

J. Clin. Oncol.

Granulocytic sarcoma in nonleukemic patients

Cancer

Brief article
Detection of Extramedullary Infiltrates in Acute Myelogenous Leukemia with Whole-Body Positron Emission Tomography and 2-Deoxy-2-[¹⁸F]-Fluoro-D-Glucose