201T1 spect combined with EBV-DNA in cerebrospinal fluid for minimally invasive diagnosis of primary central nervous system lymphoma in patients with HIV infection

A. Ammassari, A. Cingolani, D. Di Giuda, L. M. Larocca, T. Tartaglione, R. Murri, A. De Luca, M. Tavolozza, M. L. Calcagni, M. Scerrati, A. Antinori, G. De Rossi, L. Ortona

Research output: Contribution to journalArticle

Abstract

Purpose - To determine the diagnostic capability of 201T1 single-photon emission computed tomography (SPECT) combined with detection in cerebrospinal fluid (CSF) of EpsteinBarr virus (EBV-DNA for in vivo minimally invasive diagnosis of primary central nervous system lymphoma (PCNSL). Patients and Methods - All HIV-infected patients with focal brain lesions (FBL) observed between June, 1996 and March, 1998 who underwent lumbar puncture and 201T1 SPECT were included. Each CSF sample, besides routine microbiological examinations, was tested by PCR for EBV-DNA. Results - In 13 out of 31 patients, a PCNSL was diagnosed: in all EBV-encoded EBERs expression was found and in 10 EBV-DNA was positive. 201T1 uptake in PCNSL cases ranged from 1.88 to 4.07 (mean 2.77; 95% confidence interval 2.35-3.19) and in non-tumor patients from 0.91 to 3.38 (mean 1.61; 95% confidence interval 1.30-1.94) (p <0.0002). Using as cut-off value the upper limit of the 95% confidence interval of the lesion/background ratio in non-tumor patients, a 201T1 uptake of <1.94 was found in only one PCNSL and 16 non-tumor cases (10 toxoplasmic encephalitis, 3 CMV encephalitis, 1 VZV encephalitis, 1 progressive multifocal leucoencephalopathy, 1 CNS vasculitis). A patient with cryptococcoma and another with tuberculoma had a highly increased 201T1 uptake. EBV-DNA was never detected in non-tumor patients. For the diagnosis of PCNSL hyperactive SPECT lesions showed a 92.3% sensitivity and a 94.1% negative predictive value (NPV), whereas positive EBV-DNA had a 100% specificity and 100% positive predictive value. The absence of increased uptake at SPECT combined with negative EBV-DNA had a NPV of 94.1%. Conclusions - Combined approach with SPECT and EBV-DNA, showed a very high diagnostic accuracy for the discrimination of PCNSL and non-neoplastic FBL in AIDS-patients. Since the likelihood of PCNSL is extremely high in patients with hyperactive lesions and positive EBV-DNA, we think that brain biopsy could be avoided and patients should promptly undergo radiotherapy or multimodal treatment. On the contrary, the extreme improbability of PCNSL in patients showing hypoactive SPECT lesions along with negative EBV-DNA, prompts a first empiric anti-Toxoplasma therapy. In patients with discordant SPECT versus PCR results, brain biopsy, after obtaining negative routinary CSF microbiological investigations, appears to be advisable.

Original languageEnglish
Pages (from-to)457-464
Number of pages8
JournalActa Medica Romana
Volume37
Issue number4
Publication statusPublished - 1999

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Human Herpesvirus 4
HIV Infections
Cerebrospinal Fluid
Lymphoma
Central Nervous System
Single-Photon Emission-Computed Tomography
DNA
Encephalitis
Brain
Confidence Intervals
Central Nervous System Vasculitis
Tuberculoma
Progressive Multifocal Leukoencephalopathy
Biopsy
Combined Modality Therapy
Polymerase Chain Reaction
Spinal Puncture
DNA Viruses
Toxoplasma
Acquired Immunodeficiency Syndrome

ASJC Scopus subject areas

  • Medicine(all)

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201T1 spect combined with EBV-DNA in cerebrospinal fluid for minimally invasive diagnosis of primary central nervous system lymphoma in patients with HIV infection. / Ammassari, A.; Cingolani, A.; Di Giuda, D.; Larocca, L. M.; Tartaglione, T.; Murri, R.; De Luca, A.; Tavolozza, M.; Calcagni, M. L.; Scerrati, M.; Antinori, A.; De Rossi, G.; Ortona, L.

In: Acta Medica Romana, Vol. 37, No. 4, 1999, p. 457-464.

Research output: Contribution to journalArticle

Ammassari, A, Cingolani, A, Di Giuda, D, Larocca, LM, Tartaglione, T, Murri, R, De Luca, A, Tavolozza, M, Calcagni, ML, Scerrati, M, Antinori, A, De Rossi, G & Ortona, L 1999, ' 201T1 spect combined with EBV-DNA in cerebrospinal fluid for minimally invasive diagnosis of primary central nervous system lymphoma in patients with HIV infection', Acta Medica Romana, vol. 37, no. 4, pp. 457-464.
Ammassari, A. ; Cingolani, A. ; Di Giuda, D. ; Larocca, L. M. ; Tartaglione, T. ; Murri, R. ; De Luca, A. ; Tavolozza, M. ; Calcagni, M. L. ; Scerrati, M. ; Antinori, A. ; De Rossi, G. ; Ortona, L. / 201T1 spect combined with EBV-DNA in cerebrospinal fluid for minimally invasive diagnosis of primary central nervous system lymphoma in patients with HIV infection. In: Acta Medica Romana. 1999 ; Vol. 37, No. 4. pp. 457-464.
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abstract = "Purpose - To determine the diagnostic capability of 201T1 single-photon emission computed tomography (SPECT) combined with detection in cerebrospinal fluid (CSF) of EpsteinBarr virus (EBV-DNA for in vivo minimally invasive diagnosis of primary central nervous system lymphoma (PCNSL). Patients and Methods - All HIV-infected patients with focal brain lesions (FBL) observed between June, 1996 and March, 1998 who underwent lumbar puncture and 201T1 SPECT were included. Each CSF sample, besides routine microbiological examinations, was tested by PCR for EBV-DNA. Results - In 13 out of 31 patients, a PCNSL was diagnosed: in all EBV-encoded EBERs expression was found and in 10 EBV-DNA was positive. 201T1 uptake in PCNSL cases ranged from 1.88 to 4.07 (mean 2.77; 95{\%} confidence interval 2.35-3.19) and in non-tumor patients from 0.91 to 3.38 (mean 1.61; 95{\%} confidence interval 1.30-1.94) (p <0.0002). Using as cut-off value the upper limit of the 95{\%} confidence interval of the lesion/background ratio in non-tumor patients, a 201T1 uptake of <1.94 was found in only one PCNSL and 16 non-tumor cases (10 toxoplasmic encephalitis, 3 CMV encephalitis, 1 VZV encephalitis, 1 progressive multifocal leucoencephalopathy, 1 CNS vasculitis). A patient with cryptococcoma and another with tuberculoma had a highly increased 201T1 uptake. EBV-DNA was never detected in non-tumor patients. For the diagnosis of PCNSL hyperactive SPECT lesions showed a 92.3{\%} sensitivity and a 94.1{\%} negative predictive value (NPV), whereas positive EBV-DNA had a 100{\%} specificity and 100{\%} positive predictive value. The absence of increased uptake at SPECT combined with negative EBV-DNA had a NPV of 94.1{\%}. Conclusions - Combined approach with SPECT and EBV-DNA, showed a very high diagnostic accuracy for the discrimination of PCNSL and non-neoplastic FBL in AIDS-patients. Since the likelihood of PCNSL is extremely high in patients with hyperactive lesions and positive EBV-DNA, we think that brain biopsy could be avoided and patients should promptly undergo radiotherapy or multimodal treatment. On the contrary, the extreme improbability of PCNSL in patients showing hypoactive SPECT lesions along with negative EBV-DNA, prompts a first empiric anti-Toxoplasma therapy. In patients with discordant SPECT versus PCR results, brain biopsy, after obtaining negative routinary CSF microbiological investigations, appears to be advisable.",
author = "A. Ammassari and A. Cingolani and {Di Giuda}, D. and Larocca, {L. M.} and T. Tartaglione and R. Murri and {De Luca}, A. and M. Tavolozza and Calcagni, {M. L.} and M. Scerrati and A. Antinori and {De Rossi}, G. and L. Ortona",
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T1 - 201T1 spect combined with EBV-DNA in cerebrospinal fluid for minimally invasive diagnosis of primary central nervous system lymphoma in patients with HIV infection

AU - Ammassari, A.

AU - Cingolani, A.

AU - Di Giuda, D.

AU - Larocca, L. M.

AU - Tartaglione, T.

AU - Murri, R.

AU - De Luca, A.

AU - Tavolozza, M.

AU - Calcagni, M. L.

AU - Scerrati, M.

AU - Antinori, A.

AU - De Rossi, G.

AU - Ortona, L.

PY - 1999

Y1 - 1999

N2 - Purpose - To determine the diagnostic capability of 201T1 single-photon emission computed tomography (SPECT) combined with detection in cerebrospinal fluid (CSF) of EpsteinBarr virus (EBV-DNA for in vivo minimally invasive diagnosis of primary central nervous system lymphoma (PCNSL). Patients and Methods - All HIV-infected patients with focal brain lesions (FBL) observed between June, 1996 and March, 1998 who underwent lumbar puncture and 201T1 SPECT were included. Each CSF sample, besides routine microbiological examinations, was tested by PCR for EBV-DNA. Results - In 13 out of 31 patients, a PCNSL was diagnosed: in all EBV-encoded EBERs expression was found and in 10 EBV-DNA was positive. 201T1 uptake in PCNSL cases ranged from 1.88 to 4.07 (mean 2.77; 95% confidence interval 2.35-3.19) and in non-tumor patients from 0.91 to 3.38 (mean 1.61; 95% confidence interval 1.30-1.94) (p <0.0002). Using as cut-off value the upper limit of the 95% confidence interval of the lesion/background ratio in non-tumor patients, a 201T1 uptake of <1.94 was found in only one PCNSL and 16 non-tumor cases (10 toxoplasmic encephalitis, 3 CMV encephalitis, 1 VZV encephalitis, 1 progressive multifocal leucoencephalopathy, 1 CNS vasculitis). A patient with cryptococcoma and another with tuberculoma had a highly increased 201T1 uptake. EBV-DNA was never detected in non-tumor patients. For the diagnosis of PCNSL hyperactive SPECT lesions showed a 92.3% sensitivity and a 94.1% negative predictive value (NPV), whereas positive EBV-DNA had a 100% specificity and 100% positive predictive value. The absence of increased uptake at SPECT combined with negative EBV-DNA had a NPV of 94.1%. Conclusions - Combined approach with SPECT and EBV-DNA, showed a very high diagnostic accuracy for the discrimination of PCNSL and non-neoplastic FBL in AIDS-patients. Since the likelihood of PCNSL is extremely high in patients with hyperactive lesions and positive EBV-DNA, we think that brain biopsy could be avoided and patients should promptly undergo radiotherapy or multimodal treatment. On the contrary, the extreme improbability of PCNSL in patients showing hypoactive SPECT lesions along with negative EBV-DNA, prompts a first empiric anti-Toxoplasma therapy. In patients with discordant SPECT versus PCR results, brain biopsy, after obtaining negative routinary CSF microbiological investigations, appears to be advisable.

AB - Purpose - To determine the diagnostic capability of 201T1 single-photon emission computed tomography (SPECT) combined with detection in cerebrospinal fluid (CSF) of EpsteinBarr virus (EBV-DNA for in vivo minimally invasive diagnosis of primary central nervous system lymphoma (PCNSL). Patients and Methods - All HIV-infected patients with focal brain lesions (FBL) observed between June, 1996 and March, 1998 who underwent lumbar puncture and 201T1 SPECT were included. Each CSF sample, besides routine microbiological examinations, was tested by PCR for EBV-DNA. Results - In 13 out of 31 patients, a PCNSL was diagnosed: in all EBV-encoded EBERs expression was found and in 10 EBV-DNA was positive. 201T1 uptake in PCNSL cases ranged from 1.88 to 4.07 (mean 2.77; 95% confidence interval 2.35-3.19) and in non-tumor patients from 0.91 to 3.38 (mean 1.61; 95% confidence interval 1.30-1.94) (p <0.0002). Using as cut-off value the upper limit of the 95% confidence interval of the lesion/background ratio in non-tumor patients, a 201T1 uptake of <1.94 was found in only one PCNSL and 16 non-tumor cases (10 toxoplasmic encephalitis, 3 CMV encephalitis, 1 VZV encephalitis, 1 progressive multifocal leucoencephalopathy, 1 CNS vasculitis). A patient with cryptococcoma and another with tuberculoma had a highly increased 201T1 uptake. EBV-DNA was never detected in non-tumor patients. For the diagnosis of PCNSL hyperactive SPECT lesions showed a 92.3% sensitivity and a 94.1% negative predictive value (NPV), whereas positive EBV-DNA had a 100% specificity and 100% positive predictive value. The absence of increased uptake at SPECT combined with negative EBV-DNA had a NPV of 94.1%. Conclusions - Combined approach with SPECT and EBV-DNA, showed a very high diagnostic accuracy for the discrimination of PCNSL and non-neoplastic FBL in AIDS-patients. Since the likelihood of PCNSL is extremely high in patients with hyperactive lesions and positive EBV-DNA, we think that brain biopsy could be avoided and patients should promptly undergo radiotherapy or multimodal treatment. On the contrary, the extreme improbability of PCNSL in patients showing hypoactive SPECT lesions along with negative EBV-DNA, prompts a first empiric anti-Toxoplasma therapy. In patients with discordant SPECT versus PCR results, brain biopsy, after obtaining negative routinary CSF microbiological investigations, appears to be advisable.

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