Differentiation of HIV-associated lymphoma from HIV-associated reactive adenopathy using quantitative FDG PET and symmetry.

PURPOSE: To determine the diagnostic accuracy of a semiautomated (18)F-FDG PET/CT measurement of total lesion glycolysis (TLG), maximum and peak standardized uptake value at lean body mass (SUL-Max and SUL-Peak), qualitative estimates of left/right nodal symmetry and FDG uptake for differentiating lymphoma from reactive adenopathy in HIV-infected patients. METHODS: We retrospectively analyzed 41 whole-body (18)F-FDG PET/CT studies performed in HIV-infected patients for clinical reasons. The study received institutional review board approval. Of the 41 patients, 19 had biopsy-proven untreated lymphoma, and 22 with reactive adenopathy without malignancy on follow-up were used as controls. Nodal and extranodal visual qualitative metabolic scores, SUL-Max, SUL-Peak, CT nodal size, and PERCIST 1.0 threshold-based TLG and metabolic tumor volume (MTV) were determined. The qualitative intensity of nodal involvement and symmetry of uptake were compared using receiver operator curve (ROC) analysis. HIV plasma viral RNA measurements were also obtained. RESULTS: All of the quantitative PET metrics performed well in differentiating lymphoma from reactive adenopathy and performed better than qualitative visual intensity scores. The areas under the ROC curves (AUC) were significantly higher for TLG = 0.96, single SUL-Peak = 0.96, single SUL-Max = 0.97, and MTV = 0.96, compared to 0.67 for CT nodal size (p < 0.001). These PET metrics performed best in separating the two populations in aviremic patients, with AUCs of 1 (AUC 0.91 for CT nodal size). TLG, MTV, SUL-Peak and SUL-Max were more reliable markers among viremic individuals, with AUCs between 0.84 and 0.93, compared to other metrics. PET metrics were significantly correlated with plasma viral load in HIV-reactive adenopathy controls. Asymmetrical FDG uptake had an accuracy of 90.4 % for differentiating lymphoma from reactive adenopathy in HIV-infected patients. CONCLUSION: Quantitative PET metabolic metrics as well as the qualitative assessment of symmetry of nodal uptake appear to be valuable tools for differentiating lymphoma from reactive adenopathy in HIV-infected patients using FDG PET. These parameters appear more robust in aviremic patients.

Burkitt's lymphoma nodular cystic hepatosplenic, in HIV patient. Case report / Linfoma de Burkitt hepatoesplénico quístico nodular, en paciente con VIH. Reporte de caso

Background: Patients with human immunodeficiency virus (HIV) are more likely to develop cancer. Malignant lymphomas are the main cancer group seen in these patients. Diffuse large B-cell lymphoma including central nervous system lymphoma and Burkitt's lymphoma account for 90% of HIV-related non-Hodgkin's lymphomas. Clinical case: A 22-year-old man with fever up to 39 ° C, malaise, excessive tiredness and night sweats, loss of 8 kg of weight, abdominal pain in the right hypochondrium, all 5 months before hospitalization. Hemoglobin: 9.5 g/dL, leukocytes 5.13 x 103/mm3, platelets 124 000 cel/mm3; albumin 2.9 g/dL, alanine aminotransferase 28 IU/L, aspartate aminotransferase 105 IU/L; HIV reactive, beta 2 microglobulin: 20 000 ng/mL. Viral load for HIV 100 034 cp/mL, CD4: 76 cel/mcL (5%). It was performed abdominal ultrasound and denoted cysts in the liver and spleen. Abdominal-pelvic computed tomography with hepatosplenomegaly, retroperitoneal and inguinal adenopathies and free fluid in abdominal cavity. Splenectomy was performed and Burkitt's lymphoma was reported in the histopathological study. Conclusion: HIV predisposes patients to any type of cancer. Intra-abdominal findings should be a warning of lymphoma suspicious and may occur from infiltration of the small intestine, solid organ and soft tissues.

Introducción: los pacientes con virus de inmunodeficiencia humana (VIH) son más propensos a desarrollar cáncer. Los linfomas malignos son el principal grupo de cáncer que se observa en estos pacientes. El linfoma difuso de células grandes B, incluido el del sistema nervioso central y el linfoma de Burkitt, constituyen 90% de los linfomas no Hodgkin relacionados con VIH. Caso clínico: hombre de 22 años de edad, con fiebre de hasta 39 °C, malestar general, cansancio excesivo y sudoración nocturna, pérdida de 8 kg de peso y dolor abdominal en hipocondrio derecho, 5 meses previos a su hospitalización. Se reportó hemoglobina de 9.5 g/dL, leucocitos 5.13 x 103/mm3, plaquetas 124 000 cel/mm3; albúmina 2.9 g/dL; alanino aminotransferasa 28 UI/L, aspartato aminotransferasa 105 UI/L; VIH reactivo, beta 2 microglobulina 20 000 ng/mL. Carga viral para VIH 100 034 cp/mL, CD4 76 cel/mcL (5%). El ultrasonido abdominal mostró quistes en hígado y bazo. La tomografía abdominopélvica reportó hepatoesplenomegalia, adenopatías retroperitoneales e inguinal y líquido libre en cavidad abdominal. Se realizó esplenectomía y en el estudio histopatológico se reportó Linfoma de Burkitt. Conclusión: El VIH predispone a los pacientes a cualquier tipo de cáncer. Los hallazgos intraabdominales deben hacer sospechar de linfoma y se puede presentar desde infiltración del intestino delgado, órgano sólido y tejidos blandos.

Intracranial hematopoiesis in a patient with AIDS-related central nervous system lymphoma and severe pancytopenia.

The case here reported reflects the difficulty in diagnosing meningeal extramedullary hematopoiesis (EMH), which clinically appeared concomitantly with primary cerebral lymphoma and occurred in a patient with HIV infection and severe pancytopenia. Pancytopenia secondary to HIV infection could be hypothesized as a predisposing factor for the ectopic development of hematopoietic tissue outside the bone marrow. Although rare, intracranial EMH should always be considered in the differential diagnosis of headache and other endocranial hypertension symptoms in patients with chronic bone marrow dysfunction.

AIDS-related lymphoma in a young HIV late presenter patient.

Non-Hodgkin's lymphoma (NHL) is an acquired immunodeficiency syndrome (AIDS)-indicative disease. Nowadays, NHL is rarely reported in Europe as indicative disease for human immunodeficiency virus (HIV) testing. We present the case of a 22-year-old Romanian male patient without past medical history, except the swelling of a submental lymph node 11 months ago. The excised node was histologically examined but the patient neglected to take his result. He was admitted for fever, asthenia, and weight loss over 10% of his weight, and night sweats in the last four months. The immunohistochemical analysis of the preserved lymph node samples suggested reactive hyperplasic lymphadenitis with suppuration and necrosis (lymphoid follicles CD20+, CD10+, BCL6+; germinal centers CD23+, CD68+, Ki67+; and interfollicular CD3+). Clinical, biological and imaging evaluations were performed. The diagnostic of lymphoma stage IV Ann Arbor was sustained. Severe immunosuppression and a positive HIV test were found. The patient received antiretroviral treatment, but he developed paraplegia consecutive to a vertebral metastasis, liver and kidney failure and died sooner than two months from the diagnostic time. Pathological examination confirmed NHL with diffuse lymphocyte infiltrate of multiple organs. Advanced lymphoma is a rare indicator condition of HIV diagnostic. Delayed diagnostic of lymphoma implies ethical issues on communication deficiencies between the heath providers and patients, concerning the significance of biopsy. Infectious co-morbidities with necrosis and suppurative lesions are confounder conditions in NHL histological and immunohistochemical diagnosis.

Coincidental Observation of Global Hypometabolism in the Brain on PET/CT of an AIDS Patient With High-Grade Pulmonary Non-Hodgkin Lymphoma.

AIDS-related dementia complex is the most severe form of cognitive dysfunction in a patient infected with human immunodeficiency virus. The use of FDG PET/CT to diagnose AIDS-related dementia complex has been studied previously and shows various specific metabolic patterns from striatal hypermetabolism in early asymptomatic stage to global hypometabolism in advanced stages. We present a case of a 49-year-old patient with long-standing human immunodeficiency virus infection, where global brain hypometabolism was noted coincidentally on FDG PET/CT done for initial staging of primary pulmonary non-Hodgkin lymphoma.

Dramatic treatment response of cutaneous plasmablastic lymphoma in an HIV patient: a case report.

Plasmablastic lymphoma is a variant of diffuse large B-cell lymphoma, characterized by rapid progression and is associated with a poor outcome. We report a 35-year-old male with poorly controlled HIV infection and AIDS who presented with skin lesions and swelling throughout the body. Computed tomography (CT) revealed innumerable enhancing soft tissue masses within the subcutaneous soft tissues and lymphadenopathy. Plasmablastic lymphoma was diagnosed, patient was treated with chemotherapy, and post treatment CT demonstrated complete resolution. Imaging plays a key role in the diagnosis and surveillance of this disease.

Value of combined approach with thallium-201 single-photon emission computed tomography and Epstein-Barr virus DNA polymerase chain reaction in CSF for the diagnosis of AIDS-related primary CNS lymphoma.

PURPOSE: To determine the diagnostic capability of thallium-201 (201Tl) single-photon emission computed tomography (SPECT) combined with Epstein-Barr virus DNA (EBV-DNA) in CSF for the diagnosis of AIDS-related primary CNS lymphoma (PCNSL). PATIENTS AND METHODS: All human immunodeficiency virus (HIV)-infected patients with focal brain lesions observed between June 1996 and March 1998 underwent lumbar puncture and 201Tl SPECT. Each CSF sample was tested with polymerase chain reaction (PCR) for EBV-DNA. RESULTS: Thirty-one patients were included, 13 with PCNSL and 18 with nontumor disorders. In 11 PCNSL patients, EBV-DNA was positive. Thallium-201 uptake ranged from 1.90 to 4.07 in PCNSL cases (mean, 2.77; 95% confidence interval [CI], 2.35 to 3.19) and from 0.91 to 3.38 in nontumor patients (mean, 1.62; 95% CI, 1.30 to 1.94) (P<.0002). Using a lesion/background ratio of 1.95 as cutoff, a negative SPECT was found in one PCNSL case and 16 nonneoplastic cases. A cryptococcoma and a tuberculoma showed highly increased 201Tl uptake. Epstein-Barr virus DNA was never detected in nonneoplastic patients. For PCNSL diagnosis, hyperactive lesions showed 92% sensitivity and 94% negative predictive value (NPV), whereas positive EBV-DNA had 100% specificity and 100% positive predictive value. The presence of increased uptake and/or positive EBV-DNA had 100% sensitivity and 100% NPV. CONCLUSION: Combined SPECT and EBV-DNA showed a very high diagnostic accuracy for AIDS-related PCNSL. Because PCNSL likelihood is extremely high in patients with hyperactive lesions and positive EBV-DNA, brain biopsy could be avoided, and patients could promptly undergo radiotherapy or multimodal therapy. On the contrary, in patients showing hypoactive lesions with negative EBV-DNA, empiric anti-Toxoplasma therapy is indicated. In patients with discordant SPECT/PCR results, brain biopsy seems to be advisable.

Isolated cranial nerve III palsy as the presenting manifestation of HIV-related large B-cell lymphoma: clinical, radiological and postmortem observations: report of a case and review of the literature.

Rarely can a neurologically isolated cranial nerve III palsy be the presenting manifestation of central nervous system lymphoma. We detail the clinical, radiological, and pathological features of a previously healthy 45-year-old man presenting with an isolated, pupil-involving, right cranial nerve III palsy due to human immunodefiency virus (HIV) related non-Hodgkin lymphoma. Magnetic resonance imaging demonstrated bilateral peripheral cranial nerve III enhancement with no brain parenchymal or leptomeningeal abnormalities. Cerebrospinal fluid analysis revealed a monocytic pleocytosis with an elevated protein concentration and depressed glucose level. Morphologic and flow cytometric analysis of the cerebrospinal fluid was compatible with a large B-cell lymphoma. Serologic tests for HIV were positive. Postmortem examination of the brain revealed malignant lymphomatous cell infiltration of both cranial nerve III, diffuse leptomeningeal disease and focal superficial subependymal and subpial invasion. Based on our review of the literature, we were able to find only 10 detailed cases of cranial nerve III palsy as the presenting manifestation of central nervous system lymphoma. Furthermore, none of the previously reported cases correlated the magnetic resonance imaging findings with the gross and histopathologic observations.

Laser therapy for an obstructing primary tracheal lymphoma in a patient with AIDS.

A patient with AIDS presented with progressive dyspnea leading to respiratory failure with near complete airway obstruction due to primary tracheal lymphoma. Laser therapy was used locally to debulk the tumour, which facilitated extubation and led to definitive treatment with chemotherapy. Alternatives for local airway control are discussed.

Delayed positive thallium uptake in large B-cell non-Hodgkin's malignant lymphoma.

We report an unusual finding in an AIDS patient who presented with a large mediastinal mass and multiple lymphadenopathy. A sequential thallium and gallium scan to specify the nature of the mediastinal mass was requested. The early thallium images, acquired 15 min after the intravenous injection, showed no uptake in the mass. The delayed images 2 hr later showed intense thallium uptake. A gallium scan performed 48 hr later also showed intense gallium uptake in the mediastinal mass. Biopsy from the inguinal lymph node confirmed the presence of large-cell diffuse noncleaved malignant lymphoma. This case raises questions about the optimum time of imaging for thallium in high-grade lymphoma, whether delayed imaging is essential, about previous reports of low sensitivity of thallium in undifferentiated lymphoma and about the mechanism of thallium uptake in this type of tumor.

Thallium-201 retention in focal intracranial lesions for differential diagnosis of primary lymphoma and nonmalignant lesions in AIDS patients.

UNLABELLED: The purpose of this study was to determine whether 201Tl retention in focal intracranial lesions can help distinguish central nervous system (CNS) lymphoma from toxoplasmosis and other nonmalignant CNS lesions in patients with acquired immunodeficiency syndrome. METHODS: Forty-nine patients who presented with focal lesions on CT and/or MRI had 201Tl brain SPECT studies (early and delayed image sets) performed shortly after admission. Early and delayed 201Tl uptake ratios were obtained for the positive studies, and the retention index of thallium was calculated (delayed/early target-to-background mean count ratio). RESULTS: Twenty-nine patients had foci of significantly increased 201Tl uptake on the early images in regions of corresponding CT/MRI lesions. Ten of these patients had biopsy-proven lymphomas. Another patient was found to have metastatic adenocarcinoma. Twelve additional patients had a response to radiation therapy or a clinical course consistent with lymphoma and six patients had a false-positive SPECT study. The early uptake ratio could not separate malignant from nonmalignant lesions. The 201Tl retention index in patients with lymphomas (1.18 +/- 0.16) was significantly higher than the retention index in adenocarcinoma (0.24) and in the six nonmalignant lesions (0.62 +/- 0.07). The lowest retention index in patients with lymphoma was 1.07, and the highest retention index in nonmalignant lesions was 0.70. Twenty patients showed no 201Tl uptake in the regions of CT/MRI lesions. Three of them had biopsies consistent with a benign etiology, and one patient was diagnosed with tuberculosis. Fifteen patients improved clinically on antitoxoplasmosis medications alone, and one patient had CNS lymphoma. The overall sensitivity of 201Tl brain SPECT was 96%. The specificity was 76% by counting all studies with abnormal 201Tl uptake, but it increased to 100% when the retention index was also considered. CONCLUSION: The retention index increases the specificity of 201Tl brain SPECT in human immunodeficiency virus patients. In the presence of abnormal early 201Tl uptake, it is essential to perform delayed imaging and calculate the retention index to distinguish nonmalignant lesions from lymphoma. The absence of 201Tl uptake on early images at the site of a CT/MRI abnormality excludes the diagnosis of lymphoma with a high degree of confidence and delayed imaging is unnecessary.

FDG-PET in differentiating lymphoma from nonmalignant central nervous system lesions in patients with AIDS.

Structural imaging studies such as CT or MRI are not able to accurately differentiate infectious from malignant cerebral lesions in patients with AIDS. We studied 11 individuals with AIDS and central nervous system (CNS) lesions with 18F-fluoro-2-deoxyglucose (FDG) and positron emission tomography (PET). FDG-PET was able to accurately differentiate between a malignant (lymphoma) and nonmalignant etiology for the CNS lesions. Both qualitative visual inspection of the images as well as semiquantitative analysis using count ratios was performed and revealed similar results. FDG-PET may be useful in the management of AIDS patients with CNS lesions since high FDG uptake most likely represents a malignant process which should be biopsied for confirmation rather than treated presumptively as infectious.

Evaluation of sequential thallium and gallium scans of the chest in AIDS patients.

UNLABELLED: With decreasing incidence of pneumocystis carinii pneumonia (PCP) in AIDS as a result of prophylactic regimens, there is a higher incidence of tuberculosis (TB), mycobacterium avii complex (MAC), kaposi sarcoma and malignant lymphoma. There is a need for differentiating these various pathological entities. The purpose of this study was for a retrospective evaluation of sequential thallium and gallium scans in AIDS patients for differentiating intrathoracic kaposi sarcoma from malignant lymphoma and opportunistic infections. METHODS: A total of 181 patients had both studies completed between March 1992 and May 1994. The final diagnosis was verified only in 83 patients. Results were correlated with the CD4 counts, bronchoscopic and chest radiograph findings. RESULTS: In patients with pulmonary kaposi sarcoma and no opportunistic infections (19 patients), a thallium-positive, gallium-negative pattern was detected in 17 patients with a sensitivity of 89%. In the presence of kaposi sarcoma plus opportunistic infections, this pattern was only detected in 7 of 19 patients (sensitivity dropped to 37%). In 45 patients with opportunistic infections and no kaposi sarcoma, only two false-positive findings were found in patients with cytomegalic virus pneumonia for a specificity of 96%. For the whole group of 83 patients, sensitivity was 63%; specificity 95%; positive predictive value 92%; accuracy 81%; and negative predictive value 75%. CONCLUSION: A thallium-positive, gallium-negative pattern in AIDS patients has a high specificity for the diagnosis of kaposi sarcoma, however, the sensitivity dropped from 89% to 37% in the presence of opportunistic infections.

PET scanning and the human immunodeficiency virus-positive patient.

UNLABELLED: The use of PET scanning in patients with human immunodeficiency virus infection and fever of unknown origin, confusion and/or weight loss was investigated. METHODS: Eighty patients were examined using PET. Fifty-seven patients had half-body scans with [18F]fluorodeoxyglucose (FDG), and 23 patients had brain studies performed with FDG. Fourteen patients also had [11C]methionine studies (2 chest, 1 abdomen and 11 brain) performed. RESULTS: Thirteen patients with lymphoma had the extent of the disease clearly identified in both nodal and extranodal sites. Patients with a variety of infections (Cryptococcus neoformans, Pseudomonas aeruginosa, Mycobacterium tuberculosis and Mycobacterium avium intracellulare) had disease localized for appropriate biopsy or sampling procedures. A half-body FDG-PET scan had a sensitivity of 92% and a specificity of 94% for localization of focal pathology that needed treatment. High uptake of FDG (greater than liver) had a positive predictive value for pathology needing treatment of 95%. FDG brain studies showed that 16 patients with CD4 T-lymphocyte counts less than 200 cells/ml had reduced cortical uptake compared with that in basal ganglia. FDG scans were abnormal in all 19 patients with focal space occupying lesions identified by magnetic resonance scans. The standardized uptake values (SUVs) over cerebral lesions due to toxoplasma were in the range of 0.14-3.7 (13 patients) and due to lymphoma were in the range of 3.9-8.7 (6 patients). Three more patients with progressive multifocal leukoencephalopathy had SUVs in the range of 1.0-1.5 over the lesions. Another patient had a low-grade oligodendroglioma (SUV = 2.9). Carbon-11-methionine uptake also was high in patients with cerebral lymphoma but did not add to the discrimination between toxoplasmosis and lymphoma in these patients obtained with the FDG scan. CONCLUSION: In hospitals with access to PET facilities, FDG scanning allows the rapid evaluation of the whole body, including the brain, of patients with human immunodeficiency virus infection, with a report potentially available within 4 hr of injection. Sites of infection and tumor were identified, and discrimination between cerebral pathologies was possible.

Rapid differential diagnosis of cerebral toxoplasmosis and primary central nervous system lymphoma by thallium-201 SPECT.

UNLABELLED: This study sought to assess whether 201Tl brain SPECT can significantly reduce the time required for the differential diagnosis of primary central nervous system (CNS) lymphoma and cerebral toxoplasmosis in patients with AIDS. METHODS: Eighteen patients who presented with focal lesions on CT or MRI, or both, underwent 201Tl brain SPECT shortly after admission and before a CT-guided stereotactic brain biopsy. Early and delayed 201Tl uptake ratios were obtained for patients with positive 201Tl study results, and the retention index of 201Tl was calculated. RESULTS: Ten patients had 11 foci of significantly increased 201Tl uptake in regions of corresponding CT/MRI lesions. Five of these patients had biopsy-proven lymphomas, one of them in two separate foci. Another patient was found to have metastatic adenocarcinoma. Three patients had a clinical course and response to radiation therapy consistent with lymphoma, and study results in another patient were considered falsely positive. Of nine patients with no 201Tl uptake in regions of CT/MRI lesions, two had biopsy findings consistent with a benign etiology, and the other seven improved clinically on antitoxoplasmosis medications alone. The overall sensitivity of 201Tl brain SPECT was 100%, and specificity was 90%. The 201Tl retention index in patients with lymphomas was significantly higher than that in patients with adenocarcinomas and nonmalignant lesions (1.35 +/- 0.16 versus 0.24 and 0.56, respectively). CONCLUSION: Thallium-201 brain SPECT is a sensitive and specific method for rapid differential diagnosis of CNS lymphoma and toxoplasmosis in patients with AIDS. The 201Tl retention index is useful in differentiating CNS lymphomas from other malignant and nonmalignant pathologies.

Gallium-67 imaging of pericardial lymphoma in AIDS.

A 33-yr-old homosexual man with acquired immune deficiency syndrome (AIDS) and Mycobacterium avium intracellulare (MAI) infection presented with fever, sweats, lethargy and dyspnea. A chest radiograph showed cardiomegaly and an echocardiograph revealed a large pericardial effusion. After pericardial aspiration, which confirmed T cell non-Hodgkin's lymphoma, he remained dyspneic. Gallium-67 imaging was performed to determine whether the patient's residual dyspnea was related to pulmonary MAI infection or lymphomatous infiltration of the heart. Planar 67Ga scintigraphy revealed intense tracer uptake in two areas within the mediastinum and surrounding the entire heart shadow but no evidence of pulmonary MAI infection. SPECT 67Ga scintigraphy precisely localized the two mediastinal abnormalities and demonstrated the tracer uptake around the heart to be pericardial rather than myocardial. Gallium-67 scintigraphy suggested that pericardial lymphoma was the likely basis of the patient's dyspnea.

The role of hybrid cameras in oncology.

The rapid advances in imaging technologies are a challenge for nuclear medicine physicians, radiologists, and clinicians who must integrate these technologies for optimal patient care and outcome at minimal cost. Multiple indications for functional imaging using F-18-fluorodeoxyglucose (FDG) are now well accepted in the field of oncology, including differentiation of benign from malignant lesions, staging malignant lesions, detection of malignant recurrence, and monitoring therapy. The use of FDG imaging was first shown using dedicated positron emission tomography (PET) with multiple full rings of bismuth germanate detectors. Most manufacturers now have available hybrid gamma cameras capable of imaging conventional single-photon emitters, as well as positron emitters such as FDG. This new technology was developed to make FDG imaging more widely accessible, first using single photon emission computed tomography (SPECT) with high-energy collimators, and then using dualhead coincidence (DHC) detection with multihead gamma cameras that improved spatial resolution. Most hybrid gamma cameras are now equipped with thicker NaI(TI) crystals to improve sensitivity. Technical developments are still evolving with correction for attenuation and new iterative reconstruction algorithms to improve the quality of the images. Users need to be familiar with the rapid developments of the technology as well as its limitations. Currently, one model of hybrid gamma camera is equipped with an integrated x-ray transmission system for attenuation correction, anatomic mapping, and image fusion. This powerful tool has promising clinical applications including intensity-modulated radiation therapy.