We audited whether18F-Fluorodeoxyglucose positron emission tomography-computed tomography (18FDG PET-CT) imaging could discriminate between different diagnoses in HIV-infected patients presenting with lymphadenopathy, with or without fever and/or splenomegaly. Maximum standardised uptake (SUVmax) values were similar in lymphoma and mycobacterial and fungal infections and were lower but similar in those with human herpesvirus (HHV) 8-associated disease and HIV-associated reactive lymphadenopathy. Nodal18FDG avidity, with SUVmax≥10, excluded diagnoses of HHV 8-associated disease and miscellaneous conditions, and HIV-associated reactive lymphadenopathy was additionally excluded in those who had undetectable plasma HIV viral loads. This audit suggests18FDG PET-CT imaging did not permit discrimination between specific diagnoses but has utility in identifying lymph nodes with increased avidity that could be targeted for biopsy and in ruling out significant pathology

JB Bomanji

L Jain

M Noursadeghi

O'Doherty MJ

R Shortman

RF Miller

Royal College of Physicians/Royal College of Radiologists/British Nuclear Medicine Society

S Mackenzie

SG Edwards

Jain, L

Mackenzie, S

Bomanji, JB

Shortman, R

Noursadeghi, M

Edwards, SG

Miller, RF

UCL Discovery

Under review      18F-Fluorodeoxyglucose positron emission tomography-computed tomography imaging in HIV-infected patients with lymphadenopathy, with or without fever and/or splenomegaly    Journal: International Journal of STD & AIDS Manuscript ID IJSA-17-295.R1 Manuscript Type: Audit Reports Date Submitted by the Author: n/a Complete List of Authors: Jain, Lakshmi; Mortimer Market Centre, Sexual health and HIV Mackenzie, Strachan; University College London Division of Infection and Immunity Bomanji, Jamshed; University College London Hospitals NHS Foundation Trust, Institute of Nuclear Medicine Shortman, Robert ; University College London Hospitals NHS Foundation Trust, Institute of Nuclear Medicine Noursadeghi, Mahdad; University College London Division of Infection and Immunity Edwards, Simon; Camden Provider services, mortimer market centre Miller, R; University College London, Research Department of Infection and Population Health;   Keyword: HIV (Human immunodeficiency virus) < Viral disease, Diagnosis < Other, Treatment < Other     ScholarOne, 375 Greenbrier Drive, Charlottesville, VA, 22901Int J STD AIDSUnder review18F-Fluorodeoxyglucose positron emission tomography-computed tomography imaging in HIV-infected patients with lymphadenopathy, with or without fever and/or splenomegaly  L Jain1,2, S Mackenzie1,2, JB Bomanji3, R Shortman3, M Noursadeghi2,4, SG Edwards1,2 and  RF Miller1,2,5,6    1Central and North West London NHS Foundation Trust, London, UK  2T8, University College London Hospitals NHS Foundation Trust, London, UK 3Institute of Nuclear Medicine, University College London Hospitals NHS Foundation Trust, London, UK 4Division of Infection and Immunity, University College London, London, UK,  5Research Department of Infection and Population Health, Institute for Global Health, University College London, London, UK  6Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK  Short title: 18FDG PET-CT imaging in HIV-infected patients  Key words: fever, lymphoma, infection, lymph node biopsy, HIV infection, PUO, Kaposi sarcoma, Castleman disease, 18F-FDG PET-CT imaging  Word count: Manuscript =977 (Intro, Methods, Results, Discussion)                         Abstract =123     Correspondence to: Professor RF Miller, Research Department of Infection and Population Health, University College London, Mortimer Market Centre, off Capper Street, London WC1E 6JB, UK. Email: robert.miller@ucl.ac.uk   Page 1 of 10ScholarOne, 375 Greenbrier Drive, Charlottesville, VA, 22901Int J STD AIDSUnder review1  18F-Fluorodeoxyglucose positron emission tomography-computed tomography imaging in HIV-infected patients with lymphadenopathy, with or without fever and/or splenomegaly  L Jain1,2, S Mackenzie1,2, JB Bomanji3, R Shortman3, M Noursadeghi2,4, SG Edwards1,2 and  RF Miller1,2,5,6    1Central and North West London NHS Foundation Trust, London, UK  2T8, University College London Hospitals NHS Foundation Trust, London, UK 3Institute of Nuclear Medicine, University College London Hospitals NHS Foundation Trust, London, UK 4Division of Infection and Immunity, University College London, London, UK,  5Research Department of Infection and Population Health, Institute for Global Health, University College London, London, UK  6Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK  Short title: 18FDG PET-CT imaging in HIV-infected patients  Key words: fever, lymphoma, infection, lymph node biopsy, HIV infection, PUO, Kaposi sarcoma, Castleman disease, 18F-FDG PET-CT imaging  Word count: Manuscript =977 (Intro, Methods, Results, Discussion)                         Abstract =123     Correspondence to: Professor RF Miller, Research Department of Infection and Population Health, University College London, Mortimer Market Centre, off Capper Street, London WC1E 6JB, UK. Email: robert.miller@ucl.ac.uk      Page 2 of 10ScholarOne, 375 Greenbrier Drive, Charlottesville, VA, 22901Int J STD AIDSUnder review2  Abstract We audited whether 18F-Fuorodeoxyglucose positron emission tomography-computed tomography (18FDG PET-CT) imaging could discriminate between different diagnoses in HIV-infected patients presenting with lymphadenopathy, with or without fever and/or splenomegaly. Maximum standardised uptake (SUVmax) values were similar in lymphoma and mycobacterial and fungal infections, and were lower but similar in those with HHV 8-associated disease and HIV-associated reactive lymphadenopathy. Nodal 18FDG avidity, with SUVmax ≥10, excluded diagnoses of HHV 8-associated disease and miscellaneous conditions, and HIV-associated reactive lymphadenopathy was additionally excluded in those who had undetectable plasma viral loads. This audit suggests 18FDG PET-CT imaging did not permit discrimination between specific diagnoses, but has utility in identifying lymph nodes with increased avidity that could be targeted for biopsy and in ruling out significant pathology.     Page 3 of 10ScholarOne, 375 Greenbrier Drive, Charlottesville, VA, 22901Int J STD AIDSUnder review3  Introduction The immunosuppressed HIV-infected patient can present with lymphadenopathy, with or without a fever and/or splenomegaly [1]. The differential diagnosis for this presentation is wide, and includes Hodgkin and non-Hodgkin lymphoma, human herpesvirus 8 (HHV 8)-associated disease, including Kaposi sarcoma (KS) and multicentric Castleman disease (MCD), Mycobacterium tuberculosis, disseminated Mycobacterium avium complex, leishmaniasis and histoplasmosis [1–3], as well as other conditions such as metastatic carcinoma and HIV-associated “reactive” lymphadenopathy.  Definitive diagnosis often requires tissue sampling with histology and/or microbiological culture in addition to traditional investigations. 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18FDG PET-CT) hybrid imaging, already widely used in the diagnosis, staging and monitoring of malignancies, particularly lymphoma, is increasingly used to image infectious and inflammatory disorders in both immune-competent and immune-suppressed individuals [1, 4–11]. We audited whether 18FDG PET-CT could aid in discriminating between diagnoses in HIV-infected patients presenting with lymphadenopathy, with or without fever and/or splenomegaly.   Methods Consecutive patients who presented with lymphadenopathy, with or without fever and/or splenomegaly, at the HIV service at Mortimer Market Centre (MMC) and University College Hospitals (UCLH) London between January 2008 and December 2016 and who underwent 18FDG PET-CT scanning as part of routine clinical investigation were identified from the UCLH Clinical Data Repository (CDR) system. Information collected from the CDR and the patient’s clinical case notes included their presenting symptoms and signs, the maximum standardised uptake value (SUVmax) in node(s) or other tissue on 18FDG PET-CT imaging, CD4 count, plasma HIV load, and whether the patient was receiving antiretroviral therapy (ART) at the time of diagnosis. The diagnosis of lymphoma, HHV 8-associated disease and HIV-associated reactive lymphadenopathy was made histologically, while that of mycobacterial and fungal infections was made by microbiological culture, as previously described [12]. In each patient 18FDG PET-CT scanning was done prior to tissue sampling, and before results of microbiological culture were available. Patients in whom a tissue diagnosis of malignancy had been made and who subsequently underwent 18FDG PET-CT scanning for staging were Page 4 of 10ScholarOne, 375 Greenbrier Drive, Charlottesville, VA, 22901Int J STD AIDSUnder review4  excluded, as were those with undifferentiated fever, or pyrexia of undetermined origin (PUO). Results were analysed using Mann-Whitney and Kruskal-Wallis tests to compare SUVmax values among different patient groups. GraphPad Prism Version 6.0h (GraphPad software, Inc, La Jolla, CA, USA) was used for statistical analysis; p<0.05 was regarded as statistically significant.   Results One hundred and twenty patients (88 men) presented with lymphadenopathy, with or without fever and/or splenomegaly, and underwent 18FDG PET-CT. Figure 1 shows the clinical features at presentation. Patients were aged 42 years (33–48) [median (interquartile range: IQR)]. Forty-five patients were receiving ART and had an undetectable plasma HIV load (<50 copies/ml) [median (IQR) CD4 =400 (200–520) cells/µl], while 17 others were receiving ART but had detectable viral loads [median (IQR) =1700 (110–2850) copies/ml, CD4 =200 (155–340) cells/µl]. Fifty-eight patients were not receiving ART and had detectable viral loads [median (IQR) HIV plasma load =155,000 (15,250–550,000) copies/ml, and median (IQR) CD4 =185 (80–360) cells/µl].   The final diagnosis was HIV-related reactive lymphadenopathy in 43 patients, lymphoma in 27 (Hodgkin lymphoma in 13, diffuse large B-cell in 7, Burkitt in 3, plasmablastic in 3 and T-cell in 1), HHV 8-associated disease in 19 (KS in 5, MCD in 7 and KS with MCD in 7), mycobacterial infection in 14 (M. tuberculosis in 8, M. avium complex in 6), and fungal infections in 4 (Cryptococcus neoformans in 3, histoplasmosis in 1). Thirteen patients had a wide range of miscellaneous conditions: these were adult-onset Still’s disease, sclerosing peritonitis, intra-abdominal sepsis, metastatic adenocarcinoma, reflux oesophagitis/benign colonic polyp, lobar pneumonia, visceral leishmaniasis, necrotizing granulomatosis, nodular hepatic fibrosis secondary to schistosomiasis, toxoplasmosis, and nodular hepatic fibrosis/portal hypertension with thyrotoxicosis/thyroiditis, each in one patient, and self-limiting febrile episodes with lymphadenopathy in two patients. .  SUVmax values were similar in lymphoma and mycobacterial and fungal infections and were lower but similar in those with HHV 8-associated disease and HIV-associated reactive lymphadenopathy. Individuals with miscellaneous (largely non-infectious and non-malignant Page 5 of 10ScholarOne, 375 Greenbrier Drive, Charlottesville, VA, 22901Int J STD AIDSUnder review5  conditions) had low SUVmax values (Table 1). Across all diagnoses, there were statistically significant differences in median SUVmax when lymphoma was compared with HIV reactive lymphadenopathy (p=0.0007) and with HHV 8-associated diseases (p=0.0008), and when mycobacterial infection was compared with HIV reactive and HHV 8-associated diseases (p=0.004 and p<0.0001, respectively). No statistically significant differences were found between the other groups of diagnoses. Within each diagnostic group, median SUVmax showed no significant differences in those with detectable and those with undetectable viral loads (Table 1). Among all patients, nodal FDG avidity, with SUVmax ≥10, excluded diagnoses of HHV 8-associated disease and miscellaneous conditions, and HIV-associated reactive lymphadenopathy was additionally excluded in those in receipt of ART who had undetectable plasma viral loads. Reversal of the liver:spleen 18FDG avidity ratio was observed more commonly among those with detectable viral loads but did not aid discrimination between diagnoses.   Discussion This audit shows similar avidity of 18FDG uptake, measured by SUVmax, in patients with lymphoma, mycobacterial infection and fungal infection; accordingly, 18FDG-PET-CT imaging did not provide diagnostic information enabling discrimination between these diagnoses. A SUVmax ≥10 enabled HHV 8-associated disease and miscellaneous conditions to be excluded in all patients, and additionally, in those in receipt of ART who had undetectable plasma viral loads HIV-associated reactive lymphadenopathy could be excluded. This observation requires validation in prospective studies before it is used in diagnostic algorithms. In HIV infected patients different pathology may occur concurrently. This audit did not identify any features on 18FDG PET-CT imaging that suggested coexistence of dual or multiple pathology. The utility of 18FDG PET-CT imaging was in identifying lymph nodes with increased avidity that could be targeted for biopsy and in excluding significant pathology. The limitations of this audit are first, it is from a single centre, and second, the sample size is small. Additionally, patients with undifferentiated PUO, and those with an established tissue diagnosis of malignancy prior to 18FDG PET-CT scanning were excluded.   Acknowledgements: We thank Drs N Ranganathan, A Haroon, and G Whitlock for help with data collection. Page 6 of 10ScholarOne, 375 Greenbrier Drive, Charlottesville, VA, 22901Int J STD AIDSUnder review6    References 1. O'Doherty MJ, Barrington SF, Campbell M, Lowe J, Bradbeer CS. PET scanning and the human immunodeficiency virus-positive patient. J Nucl Med 1997; 38:1575-1583. 2. Lowe SM, Kocjan GI, Edwards SG, Miller RF. Diagnostic yield of fine needle aspiration   cytology in HIV-infected patients with lymphadenopathy in the era of highly active antiretroviral therapy. Int J STD AIDS 2008; 9: 553-556. 3. Young MPA, Miller RF. Immunosuppression. Chapter 16 in: Diagnostic Cytopathology: 3rd Edition. Editors: Gray W and Kocjan G. Elsevier Science 2010. 4. Castaigne C, Tondeur M, De Wit S, Hildebrand M, Clumek N, Dusart M. Clinical value of PET/CT for the diagnosis of human immunodeficiency virus associated fever of unknown origin: a retrospective study. Nucl Med Commun 2009; 30: 41-47. 5. Martin C, Castaigne C, Tondeur M, Flamen, P De Wit S. Role and interpretation of fluorodeoxyglucose-positron emission tomography/computed tomography in HIV-infected patients with fever of unknown origin: a prospective study. HIV Med 2013; 14:455-62. 6. Davison JM, Subramaniam RM, Surasi DS, Cooley T, Mercier G, Peller PJ. FDG PET/CT in patients with HIV. AJR 2011; 197:284–294. 7. Barker R, Kazmi F, Stebbing J, Ngan S, Chinn R, Nelson M, O’Doherty M, Bower M. FDG-PET/CT imaging in the management of HIV-associated multicentric Castleman’s disease Eur J Nucl Med Mol Imaging 2009; 36:648-652. 8. Haroon A, Zumla A, Bomanji J. Role of Fluorine 18 Fluorodeoxyglucose positron emission tomography–computed tomography in focal and generalized infectious and inflammatory disorders. Clin Infect Dis 2012; 54: 1333–41. 9. Royal College of Physicians/Royal College of Radiologists/British Nuclear Medicine Society. Evidence-based indications for the use of PET-CT in the UK 2013. London: RCP, RCR; 2013. 10. Boellaard R, Delgado-Bolton R, Oyen WJG, et al. FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl Med. Mol Imaging 2015; 42:328e54. 111. Bharucha T, Rutherford A, Skeoch S, Alavi A, Brown M, Galloway J: FDG-PET/CT in fever of unknown origin working group. Diagnostic yield of FDG-PET/CT in fever of unknown Page 7 of 10ScholarOne, 375 Greenbrier Drive, Charlottesville, VA, 22901Int J STD AIDSUnder review7  origin: a systematic review, meta-analysis, and Delphi exercise. Clinical Radiol. 2017 Jun 6 [Epub ahead of print].  12. Alçada J, Taylor MN, Shaw PJ, Janes SM, Navani N, Miller RF. High prevalence of malignancy in HIV positive patients with mediastinal lymphadenopathy: a study in the era of antiretroviral therapy. Respirology 2014; 19: 339-345.                 Page 8 of 10ScholarOne, 375 Greenbrier Drive, Charlottesville, VA, 22901Int J STD AIDSUnder review8   Table 1. Median SUVmax and diagnosis in 120 patients who underwent 18FDG PET-CT imaging Diagnosis (n) SUVmax median (IQR) HIV-related reactive lymphadenopathy (43)   Undetectable viral load (9)   Detectable viral load (34) 5.6 (3.3–9.4) 3.7 (3.0–6.3) 6.0 (3.3–9.7) Lymphoma (27)   Undetectable viral load (17)   Detectable viral load (10)  12.0 (6.5–14.0) 12.5 (6.8–18.1) 12.0 (5.5–13.3) HHV 8-associated disease (KS/MCD) (19)   Undetectable viral load (5)   Detectable viral load (14) 5.7 (4.5–7.5) 5.7 (3.5–7.1) 5.9 (4.3–8.9) Mycobacterial infection (14)   Undetectable viral load (2)   Detectable viral load (12) 10.9 (9.1–13.9) 8.7  12.3 (9.2–14.6) Fungal infection (4)   Undetectable viral load (3)   Detectable viral load (1) 13.3 (6.4–20.6) 13.5 (4.2–23.0) 13.2 Miscellaneous conditions* (13)   Undetectable viral load (9)   Detectable viral load (4) 2.0 (2.0–6.1) 2.0 (2.0–7.1) 2.0 (2.0–2.5) Page 9 of 10ScholarOne, 375 Greenbrier Drive, Charlottesville, VA, 22901Int J STD AIDSUnder review9        12 3 46 6    6 43 4 Lymphadenopathy Splenomegaly Fever Figure 1. Clinical features at presentation among 120 HIV-infected patients who underwent (8FDG PET-CT imaging Page 10 of 10ScholarOne, 375 Greenbrier Drive, Charlottesville, VA, 22901Int J STD AIDS

18 F-Fluorodeoxyglucose positron emission tomography-computed tomography imaging in HIV-infected patients with lymphadenopathy, with or without fever and/or splenomegaly

We audited whether 18F-Fluorodeoxyglucose positron emission tomography-computed tomography (18FDG PET-CT) imaging could discriminate between different diagnoses in HIV-infected patients presenting with lymphadenopathy, with or without fever and/or splenomegaly. Maximum standardised uptake (SUVmax) values were similar in lymphoma and mycobacterial and fungal infections and were lower but similar in those with human herpesvirus (HHV) 8-associated disease and HIV-associated reactive lymphadenopathy. Nodal 18FDG avidity, with SUVmax ≥10, excluded diagnoses of HHV 8-associated disease and miscellaneous conditions, and HIV-associated reactive lymphadenopathy was additionally excluded in those who had undetectable plasma HIV viral loads. This audit suggests 18FDG PET-CT imaging did not permit discrimination between specific diagnoses but has utility in identifying lymph nodes with increased avidity that could be targeted for biopsy and in ruling out significant pathology

LSHTM Research Online

18F-Fluorodeoxyglucose positron emission tomography-computed tomography imaging in HIV-infected patients with lymphadenopathy, with or without fever and/or splenomegaly.

Amit Salvi

Anthony Waas

Ari Caliskan

Crossref

Fracture of 2D Triaxially Braided Carbon Fiber Composites and Resin Effects on the Energy Absorption

 We audited whether 18F-Fluorodeoxyglucose positron emission tomography-computed tomography (18FDG PET-CT) imaging could discriminate between different diagnoses in HIV-infected patients presenting with lymphadenopathy, with or without fever and/or splenomegaly. Maximum standardised uptake (SUVmax) values were similar in lymphoma and mycobacterial and fungal infections and were lower but similar in those with human herpesvirus (HHV) 8-associated disease and HIV-associated reactive lymphadenopathy. Nodal 18FDG avidity, with SUVmax ≥10, excluded diagnoses of HHV 8-associated disease and miscellaneous conditions, and HIV-associated reactive lymphadenopathy was additionally excluded in those who had undetectable plasma HIV viral loads. This audit suggests 18FDG PET-CT imaging did not permit discrimination between specific diagnoses but has utility in identifying lymph nodes with increased avidity that could be targeted for biopsy and in ruling out significant pathology. </jats:p

International Journal of STD & AIDS

<sup>18</sup>F-Fluorodeoxyglucose positron emission tomography-computed tomography imaging in HIV-infected patients with lymphadenopathy, with or without fever and/or splenomegaly

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76613/1/AIAA-2007-2158-961.pd

18 F-Fluorodeoxyglucose positron emission tomography-computed tomography imaging in HIV-infected patients with lymphadenopathy, with or without fever and/or splenomegaly

Abstract

Similar works

Full text

Available Versions

UCL Discovery

LSHTM Research Online

Crossref

Crossref

Deep Blue Documents