Nuclear Medicine and Molecular Imaging Pictorial Essay Nuclear Medicine and Molecular Imaging Pictorial Essay Elaine Yuen Phin Lee 1 Marina-Portia nthony 1 nskar Yu-Hung Leung 2 Florence Loong 3 Pek-Lan Khong 1 Lee EYP, nthony MP, Leung YH, Loong F, Khong PL Keywords: acute leukemia, extramedullary, FDG PET/CT, myeloid sarcoma DOI:10.2214/JR.11.7743 Received ugust 23, 2011; accepted after revision October 5, 2011. 1 Department of Diagnostic Radiology, Queen Mary Hospital, University of Hong Kong, Rm 406, lock K, 102 Pokfulam Rd, Hong Kong. ddress correspondence to E. Y. P. Lee (eyplee77@hku.hk). 2 Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong. 3 Department of Pathology, Queen Mary Hospital, University of Hong Kong, Hong Kong. JR 2012; 198:1175 1179 0361 803X/12/1985 1175 merican Roentgen Ray Society Utility of FDG PET/CT in the ssessment of Myeloid Sarcoma OJECTIVE. Myeloid sarcoma (MS) is a rare extramedullary manifestation of acute myeloid leukemia that often presents during remission or disease relapse. With awareness of this clinical entity and the appropriate clinical history, MS can be detected despite its nonspecific radiologic features. CONCLUSION. This article highlights the utility of 18 F-FDG PET/CT, which has high sensitivity in detecting early MS and provides a systemic overview of tumor burden, and its potential role in monitoring of treatment response. M yeloid sarcoma (MS), which is synonymous with chloroma or granulocytic sarcoma, was first described in 1824 by a ritish physician, llan urns [1]. MS is a rare extramedullary manifestation of acute myeloid leukemia (ML). It occurs in 3 5% of ML cases [2]. It can present during remission or relapse of the disease and rarely precedes the diagnosis of ML. One study reported that up to 21% of cases of MS presented as relapse after allogeneic bone marrow transplantation [3]. MS is associated with other hematologic conditions, such as chronic myeloid leukemia and myelodysplastic syndrome; it is more accurately described as leukemic transformation from these hematologic diseases. On histologic examination, MS consists of myeloid blasts, with or without maturation, and stains positive for myeloperoxidase on immunohistochemical analysis (Fig. 1). MS can be misread as lymphoma or another malignancy because the radiologic findings are not specific. However, if there is a history of ML, MS can be considered, and histologic confirmation is prudent. This article aims to illustrate the utility of 18 F-FDG PET/CT in the following three areas: first, it provides early identification of disease and MS sites or of clinically occult disease, before the disease is detected by conventional imaging modalities [4 6]; second, it aids in staging of this systemic illness; and third, it is useful for treatment response assessment after chemotherapy or localized radiotherapy [4, 6, 7]. FDG PET/CT MS has been found by FDG PET to have increased glycolytic activity with moderate uptake of FDG (maximum standardized uptake value, 2.6 9.7) [4]. FDG PET is effective in the detection of MS and is superior or at least equivalent to CT or MRI [4]. In addition, a study has shown that FDG PET/CT is more accurate in lesion detection than CT or FDG PET alone [7]. Early Disease Detection FDG PET/CT is able to detect lesions that are clinically occult or not yet detectable on conventional imaging [4 6, 8]. This can also assist in locating optimal sites for biopsy (Fig. 2). The moderate avidity of FDG in MS lesions creates contrast between MS and normal tissue on FDG PET/CT and, therefore, increases the conspicuity of MS lesions and the diagnostic confidence, which may explain why more lesions are detected on FDG PET/CT than on CT alone (Figs. 3 and 3). Staging ecause FDG PET/CT is a whole-body imaging modality, it offers an initial survey of the disease burden before systemic treatment [5, 8]. It can detect MS lesions in various locations, when the presentation is multifocal. The staging information can then be used to design the treatment strategy (Figs. 3 and 4). No consensus can be reached on the optimal intensity and duration of treatment of MS. However, local treatment alone for MS is gen- JR:198, May 2012 1175
erally insufficient; therefore, a systemic approach with local treatment, when possible, is advised [9]. Multifocal involvement carries a poor prognosis, because disease-free survival has rarely been documented [9] (Fig. 3). MS presents in various sites. The most common sites of involvement are the bones, lymph nodes (Fig. 4), soft tissues (Fig. 5), skin (Fig. 6), and breast (Fig. 7). reast involvement is commonly bilateral [2]. Other less common sites include the genitourinary tract (Figs. 3C and 4), gastrointestinal tract (Figs. 2 and 3D), head and neck regions (Fig. 3E), and intrathoracic sites (Fig. 8). Potential Role in Treatment Response ssessment The FDG avidity of MS can serve as a molecular marker for treatment response assessment. lthough the evidence is limited at present, the emerging role of FDG PET/CT in this area is promising [4, 6, 7] (Figs. 2 and 4). Fig. 1 57-year-old woman with breast myeloid sarcoma. H and E stain ( 40, top) shows that fibrous stroma of breast is diffusely infiltrated by loose cords and clusters of blast cells featuring high nuclear-to-cytoplasmic ratio, fine chromatin pattern, and inconspicuous or small nucleoli. Eosinophil precursors with round nuclei and eosinophilic granules in cytoplasm are also present. Myeloperoxidase stain ( 40, bottom) shows that tumor cells are positive for myeloid marker myeloperoxidase immunohistochemically. Summary lthough MS is a rare manifestation of ML, it will be encountered more frequently in clinical practice as these patients undergo intensive chemotherapy and bone marrow transplantation. MS can be detected in the correct clinical context despite its nonspecific imaging findings. FDG PET/CT has increased sensitivity in early disease detection when it is clinically occult or before it is evident on conventional imaging, and it identifies diseased sites, which facilitates biopsy and diagnosis. FDG PET/CT allows staging of the disease, which can tailor treatment planning. Finally, the emerging role of FDG PET/CT as an assessment tool for treatment response and disease monitoring seems promising and requires further validation with larger studies. References 1. urns. Observations on the surgical anatomy of the head and neck. 2nd ed. Glasgow, Scotland: Wardlaw & Cunninghame, 1824 2. Neiman RS, arcos M, erard C, et al. Granulocytic sarcoma: a clinicopathologic study of 61 biopsied cases. Cancer 1981; 48:1426 1437 3. Mortimer J, linder M, Schulman S et al. Relapse of acute leukemia after marrow transplantation: natural history and results of subsequent therapy. J Clin Oncol 1989; 7:50 57 [Erratum in J Clin Oncol 1989; 7:545] 4. Ueda K, Ichikawa M, Takahashi M, et al. FDG- PET is effective in the detection of granulocytic sarcoma in patients with myeloid malignancy. Leuk Res 2010; 34:1239 1241 5. Karlin L, Itti E, Pautas C, et al. PET-imaging as a useful tool for early detection of the relapse site in the management of primary myeloid sarcoma. Haematologica 2006; 91(suppl 12): ECR54 6. Stolzel F, Röllig C, Radke J, et al. 18 F-FDG-PET/ CT for detection of extramedullary acute myeloid leukemia. Haematologica 2011; 96:1552 1556 7. schoff P, Hantschel M, Oksuz M, et al. Integrated FDG-PET/CT for detection, therapy monitoring and follow-up of granulocytic sarcoma: initial results. Nuklearmedizin 2009; 48:185 191 8. Mantzarides M, onardel G, Fagot T, et al. Granulocytic sarcomas evaluated with F-18-fluorodeoxyglucose PET. Clin Nucl Med 2008; 33:115 117 9. Cunningham I. Extramedullary sites of leukemia relapse after transplant. Leuk Lymphoma 2006; 47:1754 1767 Fig. 2 63-year-old man who presented with bone pain and had marrow necrosis on bone marrow aspirate. He had no gastrointestinal symptoms., xial fused FDG PET/CT image shows hypermetabolic terminal ileal mass (maximum standardized uptake value, 5.0), which was biopsied and proven to be myeloid sarcoma. Diagnosis of acute myeloid leukemia from underlying myelodysplastic syndrome was confirmed., FDG PET maximum-intensity-projection image shows hypermetabolic ileal focus with generalized marrow uptake secondary to marrow necrosis. Follow-up FDG PET/CT (not shown) after induction chemotherapy showed complete resolution of previously hypermetabolic ileal mass and marrow uptake. This correlates well with clinical status and repeated bone marrow aspirate. Resolution of marrow uptake can be appreciated on PET only because there is no associated CT finding. 1176 JR:198, May 2012
Fig. 3 50-year-old man with acute myeloid leukemia who underwent matched sibling bone marrow transplantation., Coronal fused FDG PET/CT image shows hypermetabolic (maximum standardized uptake value [SUV max ], 3.7) enhancing soft tissue extending along left T1 2 intervertebral foramen, consistent with spread of myelogenous leukemic deposit along nerve root., Coronal contrast-enhanced CT image shows enhancing mass in T1 2 intervertebral foramen, which is more readily appreciated after review of fused FDG PET/CT. C, xial fused FDG PET/CT image shows hypermetabolic activity (SUV max, 4.9) in corpus cavernosum and spongiosum of penis. Core needle biopsy revealed myeloid sarcoma. D, xial fused FDG PET/CT image shows hypermetabolic (SUV max, 4.5) amorphous hypodense pancreatic mass compatible with myeloid sarcoma relapse. E, xial fused FDG PET/CT image shows right retroorbital enhancing and hypermetabolic mass (SUV max, 4.6), which is involving superior rectus muscle and causing proptosis. He died 8 months after FDG PET/CT examination despite chemotherapy and peripheral blood stem cell rescue from sister. Fig. 4 55-year-old woman with acute myeloid leukemia who also had blastic transformation from myeloproliferative disease., FDG PET maximum-intensity-projection image shows conglomerate hypermetabolic nodal mass at left supraclavicular fossa (maximum standardized uptake value [SUV max ], 3.4) and hypermetabolic infiltration of left kidney (SUV max, 4.7)., xial fused FDG PET/CT image shows corresponding left kidney infiltration. fter induction and consolidation chemotherapy, follow-up FDG PET/CT examination (not shown) showed complete resolution of disease. D E C JR:198, May 2012 1177
Fig. 5 49-year-old woman who previously had acute myeloid leukemia and bone marrow transplantation., FDG PET maximum-intensity-projection image shows multiple hypermetabolic (maximum standardized uptake value, 2.5 4.9) soft-tissue masses in anterior chest wall, anterior abdominal fat, and upper thighs, which were biopsy-proven myeloid sarcomas., xial fused FDG PET/CT image shows upper thigh lesions. Fig. 6 58-year-old woman with multiple flat skin lesions. xial contrastenhanced CT image shows myeloid sarcomatous skin deposit (white arrow), known as leukemia cutis, which is not hypermetabolic on FDG PET/CT because of its small size. Fig. 7 37-year-old woman with acute myeloid leukemia, after bone marrow transplant, who also had bilateral myeloid sarcomas of breasts. xial fused FDG PET/CT image shows bilateral hypermetabolic breast myeloid sarcomas, left breast mass (maximum standardized uptake value [SUV max ], 6.8), and right breast mass (SUV max, 3.9). 1178 JR:198, May 2012
Fig. 8 34-year-old man with acute myeloid leukemia., FDG PET maximum-intensity-projection image shows heterogeneous hypermetabolic mediastinal focus (arrow)., xial fused FDG PET/CT image shows corresponding soft-tissue mediastinal mass (maximum standardized uptake value [SUV max ], 5.2). C, xial fused FDG PET/CT image shows further hypermetabolic foci in right chest, which are pleural deposits (SUV max, 1.5 7.1). C JR:198, May 2012 1179