Methotrexate Polyglutamate Concentrations as a Possible Predictive Marker for Effectiveness of Methotrexate Therapy in Patients with Sarcoidosis: A Pilot Study.

INTRODUCTION: Methotrexate (MTX), a folate antagonist, is often used as second-line treatment in patients with sarcoidosis. Effectiveness of MTX has large inter-patient variability and at present therapeutic drug monitoring (TDM) of MTX is not possible. Upon administration, MTX is actively transported into cells and metabolized to its active forms by adding glutamate residues forming MTXPG(n=1-5) resulting in enhanced cellular retention. In this study we address the question whether different MTXPG(n) concentrations in red blood cells (RBC) of patients with sarcoidosis after 3 months of MTX therapy correlate with response to treatment. METHODS: We retrospectively included patients with sarcoidosis that had started on MTX therapy and from whom blood samples and FDG-PET/CT were available 3 and 6-12 months after MTX initiation, respectively. FDG-uptake was measured by SUVmax in the heart, lungs and thoracic lymph nodes. Changes in SUVmax was used to determine anti-inflammatory response after 6-12 months of MTX therapy. MTXPG(n) concentrations were measured from whole blood RBC using an LC-MS/MS method. Pearson correlation coefficients were calculated to evaluate the relationship between changes in the SUVmax and MTXPG(n) concentrations. RESULTS: We included 42 sarcoidosis patients treated with MTX (15 mg/week); 31 with cardiac sarcoidosis and 11 with pulmonary sarcoidosis. In MTXPG3 and MTXPG4 a significant negative relation between the absolute changes in SUVmax and MTXPG(n) was found r = - 0.312 (n = 42, p = 0.047) for MTXPG3 and r = - 0.336 (n = 42, p = 0.031 for MTXPG4). The other MTXPG(n) did not correlate to changes in SUVmax. CONCLUSION: These results suggest a relation between MTXPG(n) concentrations and the anti-inflammatory effect in patients with sarcoidosis. Further prospective validation is warranted, but if measuring MTXPG concentrations could predict treatment effect of MTX this would be a step in the direction of personalized medicine.

Prednisone vs methotrexate in treatment naïve cardiac sarcoidosis.

BACKGROUND: Side effects limit the long-term use of glucocorticoids in cardiac sarcoidosis (CS), and methotrexate has gained attention as steroid sparing agent although the supporting evidence is poor. This study compared prednisone monotherapy, methotrexate monotherapy or a combination of both, in the reduction of myocardial Fluorine-18 fluorodeoxyglucose (FDG) uptake and clinical stabilization of CS patients. METHODS AND RESULTS: In this retrospective cohort study, 61 newly diagnosed and treatment naïve CS patients commenced treatment with prednisone (N = 21), methotrexate (N = 30) or prednisone and methotrexate (N = 10) between January 2010 and December 2017. Primary outcome was metabolic response on FDG PET/CT and secondary outcomes were treatment patterns, major adverse cardiovascular events, left ventricular ejection fraction, biomarkers and side effects. At a median treatment duration of 6.2 [5.7-7.2] months, 71.4% of patients were FDG PET/CT responders, and the overall myocardial maximum standardized uptake value decreased from 6.9 [5.0-10.1] to 3.4 [2.1-4.7] (P < 0.001), with no significant differences between treatment groups. During 24 months of follow-up, 7 patients (33.3%; prednisone), 6 patients (20.0%; methotrexate) and 1 patient (10.0%; combination group) experienced at least one major adverse cardiovascular event (P = 0.292). Left ventricular ejection fraction was preserved in all treatment groups. CONCLUSIONS: Significant suppression of cardiac FDG uptake occurred in CS patients after 6 months of prednisone, methotrexate or combination therapy. There were no significant differences in clinical outcomes during follow-up. These results warrant further investigation of methotrexate treatment in CS patients.

Current research topics in FAPI theranostics: a bibliometric analysis.

PURPOSE: The study aimed to provide a comprehensive bibliometric overview of the current scientific publications on fibroblast activation protein inhibitor (FAPI) positron emission tomography imaging and radionuclide therapy. METHODS: A PubMed search was performed to identify all MEDLINE-indexed publications on FAPI imaging and radionuclide therapy. The last update was performed on 31 May 2022. An online database of this literature was created, and hierarchical topic-related tags were subsequently assigned to all relevant studies. Frequency analysis was used to evaluate the distribution of the following characteristics: first author's country of origin, journal of publication, study design, imaging techniques and radiopharmaceutical used, histopathological correlation, the type of cancer, and benign disease/uptake types evaluated. RESULTS: A total of 294 relevant publications on original studies were identified, consisting of 209 (71%) case reports/series and 85 cohort studies (29%). The majority of studies focused on imaging topics, predominantly comparing uptake on FAPI-PET/CT with 2-[18F]FDG-PET/CT, anatomical imaging, and/or histopathology results. 68% of studies focused on malignancies, with gastro-intestinal cancer, hepato-pancreato-biliary cancer, mixed cancers/metastases, lung cancer, sarcoma, head and neck cancer, and breast cancer being the most frequently reported. 42% of studies focused on benign disease categories, with cardiovascular, musculoskeletal, HPB, head and neck, and IgG4-related disease as most common categories. 16/294 (5%) studies focused on radionuclide therapy, with preliminary reports of acceptable toxicity profiles, tumour activity retention, and suggestion of disease control. CONCLUSION: FAPI research is rapidly expanding from diagnostic studies in malignancies and benign diseases to the first reports of salvage radionuclide therapy. The research activity needs to shift now from low-level-of-evidence case reports and series to prospectively designed studies in homogenous patient groups to provide evidence on how and in which clinical situations FAPI theranostics can be of added value to clinical care. We have provided an overview of current research topics to build upon.

Altered splenic [89Zr]Zr-rituximab uptake in patients with interstitial lung disease not responding to rituximab: could this indicate a splenic immune-mediated mechanism?

Rituximab (RTX) for immune-mediated inflammatory disease (IMID) with interstitial pneumonitis (IP) results in non-response in about a third of patients for reasons not well understood. Complete peripheral B-cell depletion in IMID-IP does not seem to correlate with successful treatment outcome. A hypothesis is that splenic B cells might play a role in B-cell recovery and attraction of naïve B cells in non-responsive patients. The aim of this post hoc analysis of clinical trial data is to search for indicators in [89Zr]Zr-rituximab PET/CT data from the spleen that might explain non-responsiveness. PET/CT data of 20 patients with IMID-IP, who were enrolled in a phase II trial and treated with RTX were analyzed. Clinical outcome was categorized into responders (RSP) and non-responders (NR) after 6 months of initial RTX by two independent pulmonologists. Patients were examined separately to search for associations between clinical outcome, splenic activity on PET/CT, lymphocyte counts and other biomarkers. Treatment failure was found in 6/20 patients (30%) while all patients exhibited B-cell depletion from the circulation. NR patients demonstrated significantly higher splenic activity than RSP patients (non-preload protocol: SUV 4.9±1.96 and SUV 2.3±1.08 respectively, P=0.025). No correlations between treatment outcome and serum lymphocyte subsets were found. Our findings suggest a potential splenic mechanism in IMID-IP patients non-responding to RTX and warrant further consideration and investigation.

In Which Patients with Sarcoidosis Is FDG PET/CT Indicated?

Sarcoidosis is a granulomatous disease of which the etiology remains unknown. The diverse clinical manifestations may challenge clinicians, particularly when conventional markers are inconclusive. From various studies, it has become clear that fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT aids in sarcoidosis care. In this article, an update on FDG PET/CT in sarcoidosis is provided. The use of FDG PET/CT in the diagnostic process of sarcoidosis is explained, especially in determining treatable inflammatory lesions in symptomatic patients with indecisive conventional tests. Furthermore, FDG PET/CT for evaluating the potential benefit of additional inflammatory treatment is described and its use in cardiac sarcoidosis is highlighted.

Quantification of pulmonary disease activity in sarcoidosis measured with 18F-FDG PET/CT: SUVmax versus total lung glycolysis.

BACKGROUND: 18F-FDG PET/CT has proven to be a reliable tool for therapy monitoring in sarcoidosis. Previous PET studies investigated the SUVmax as a marker for disease activity. Total lung glycolysis (TLuG) is a new tool, quantifying the glycolysis of the entire lung. Since SUVmax represents the maximum activity in only one pixel, we hypothesize that TLuG is a more accurate marker for active pulmonary disease and predictor of response than SUVmax. METHODS: In this retrospective cohort study, 27 patients started on infliximab for refractory pulmonary sarcoidosis. Patients received infliximab intravenously monthly at a dose of 5 mg/kg. We performed a lung function test and an 18F-FDG PET/CT before initiation of infliximab and after 6 months of treatment. SUVmax and TLuG were determined in the pre- and post-scan. Change in lung function was correlated with the change in SUVmax and TLuG and was correlated to the initial SUVmax and TLuG to evaluate the predictive value of the initial metabolic activity. RESULTS: ΔSUVmax significantly correlated with ΔFVC (r = - 0.497, p = 0.008) and with ΔFEV1 (r = - 0.467, p = 0.014). Furthermore, ΔTLuG significantly correlated with ΔFVC (r = - 0.430, p = 0.025), ΔFEV1 (r = - 0.532, p = 0.004) and ΔDLCOc (r = - 0.423, p = 0.039). Change in SUVmax and TLuG significantly correlated (r = 0.735, p < 0.001). Initial SUVmax significantly correlated with the change in FVC and DLCOc. In addition, initial TLuG significantly correlated with the change in FEV1 and DLCOc. A SUVmax > 7.5 at initiation of infliximab was predictive for 5% response in FVC, whereas SUVmax > 9.2 was predictive for 5% response in DLCOc. In addition, high TLuG > 4100 at initiation of infliximab was predictive for 5% response in FVC and FEV1 and TLuG > 4500 was predictive for response in DLCOc. CONCLUSION: SUVmax and TLuG are equal in determining the response to infliximab in pulmonary sarcoidosis patients. Furthermore, SUVmax and TLuG at initiation of infliximab can predict change in lung function after treatment. Since TLuG is a more time-consuming tool, we recommend to use SUVmax of the lung parenchyma for response monitoring in pulmonary sarcoidosis.

[89Zr]Zr-rituximab PET/CT activity in patients with therapy refractory interstitial pneumonitis: a feasibility study.

Recent studies on immune-mediated inflammatory lung diseases show encouraging treatment results with rituximab, a monoclonal antibody (mAb) against CD20-expressing B lymphocytes. The present pilot study aimed to explore the possibility to image CD20-expression in the lungs as future early predictor of treatment response. We describe a series of 10 patients with therapy refractory interstitial pneumonitis who were treated with rituximab (1000 mg at day 0 and day 14) and underwent PET/CT after the administration of [89Zr]Zr-N-suc-DFO-rituximab abbreviated as [89Zr]Zr-rituximab. [89Zr]-rituximab PET/CT of the chest was performed on day 3 and 6. [89Zr]Zr-rituximab PET/CT showed visual and quantifiable increased pulmonary activity in four patients. Other patients demonstrated no increased activity in the lungs. One patient developed a severe allergic reaction during infusion of the first 10% unlabeled rituximab after which rituximab infusion was ceased. Subsequent administration of [89Zr]Zr-rituximab, however, did not result in any adverse reaction. This patient demonstrated the highest uptake of [89Zr]Zr-rituximab in mediastinal lymph nodes and lung parenchyma compared to the other 9 patients who did receive the full dose rituximab before [89Zr]Zr-rituximab. This pilot study demonstrates that [89Zr]Zr-rituximab PET/CT imaging in patients with therapy refractory interstitial pneumonitis is feasible and shows lung-specific uptake in some patients. Further research with larger sample size should establish if the [89Zr]Zr-rituximab uptake correlates with treatment response to rituximab. The higher uptake in the absence of a full 1000 mg rituximab preload may suggest that future studies should consider [89Zr]Zr-rituximab imaging at low mAb dose before treatment with rituximab.

Efficacy and safety of infliximab biosimilar Inflectra® in severe sarcoidosis.

BACKGROUND: Infliximab, a monoclonal antibody against tumor necrosis factor alpha (TNF-α) is effective third-line therapy in severe sarcoidosis. The originator product of Infliximab, Remicade®, is expensive, limiting universal access. Recently, a less expensive biosimilar of infliximab, Inflectra®, has become available, but the efficacy and tolerability has not been studied in sarcoidosis. METHODS: In this retrospective cohort study, 29 patients treated with the infliximab biosimilar Inflectra®, were analysed. Patients received Inflectra® intravenously monthly at a dose of 5 mg/kg. We measured trough levels before every infusion. Before and after 6 months of induction therapy pulmonary function and disease activity were evaluated using Standardised Uptake Value (SUV) of the 18F-fluorodeoxyglucose by positron emission tomography (18F-FDG PET), soluble interleukin-2 receptor (sIL-2R), angiotensin converting enzyme (ACE) and health-related quality of life (HRQOL). RESULTS: In patients with pulmonary sarcoidosis as main treatment indication (n = 15) the predicted FVC improved with 8.1%, p < 0.05. Furthermore, in the whole group HRQoL improved significantly (p < 0.001), whereas SUVmax and sIL-2R significantly reduced (p < 0.001 and p = 0.001 respectively). Hospitalisation due to infections occurred in four patients. None of the patients discontinued Inflectra® due to side-effects. Furthermore, all patients had detectable trough levels indicating development of neutralizing antibodies. CONCLUSION: Infliximab biosimilar Inflectra® seems effective in the treatment of refractory sarcoidosis with a comparable safety profile to the reference product Remicade®. Inflectra® can be considered as an alternative and less expensive option for patients with refractory sarcoidosis.

Volumetric FDG PET analysis of global lung inflammation: new tool for precision medicine in pulmonary sarcoidosis?

Currently FDG PET/CT is used as a tool for detection of active sites of sarcoidosis. Routine clinical practice relies on qualitative assessment with visual interpretation. When semi quantitatively expressed, e.g. for scientific purposes, this often leads to dichotomous "positive" or "negative" results. Metabolic activity in the lungs or mediastinum can also be expressed by SUVmax, but this measure is based only on the intensity of a single voxel. Likely for this reason these parameters show poor correlation with variables such as serum biomarkers and suboptimally predict clinical response to treatment. The current study focusses on new volumetric quantification methods for FDG PET/CT. Specifically the percentage of lung volume with increased metabolic activity, "%SUV-high", and the average metabolic activity in the lung "SUVmean", shows significantly better correlation with conventional biomarkers for disease activity than PET dichotomous and SUVmax. Our proposed quantification method needs subsequent and larger studies, however it may open new possibilities for future quantitative research in lung inflammation, and improve precision medicine in sarcoidosis. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 44-54).

Cardiac sarcoidosis: challenges in clinical practice.

PURPOSE OF REVIEW: To address the current recommendations for screening, diagnosis, and treatment of cardiac sarcoidosis and the difficulties to put these recommendations into clinical practice. RECENT FINDINGS: The incidence of cardiac sarcoidosis appears to be higher than earlier reported, probably because of improved imaging techniques. Late gadolinium enhancement with cardiac MRI (LGE-CMR) and fluorodeoxyglucose positron emission tomography obtained a central role in the diagnostic algorithm and monitoring of disease activity. New techniques are being investigated: T1 and T2 mapping for early detection in CMR, a sarcoid-specific tracer in PET, integrated positron emission tomography/MRI scanners, and assessment of scar with LGE in cardiac computed tomography. Isolated cardiac sarcoidosis is an increasingly recognized phenotype, but still an enormous challenge in clinical practice. The prognostic value of (and extent of) LGE-CMR should be taken into account for risk assessment and internal cardiac defbrillator therapy, even in patients with preserved left ventricular function. Unfortunately, randomized controlled trials to guide immunosuppressive therapy are still lacking. A multidisciplinary approach to diagnose and treat cardiac sarcoidosis patients in specialized centers is strongly recommendable. SUMMARY: Cardiac sarcoidosis is increasingly recognized because of improved imaging techniques; however, treatment of cardiac sarcoidosis is still mainly based on expert opinion.

99mTc-anti-TNF-α antibody for the imaging of disease activity in pulmonary sarcoidosis.

Infliximab, a monoclonal antibody directed against tumour necrosis factor (TNF)-α, is used in the treatment of refractory sarcoidosis. However, the clinical response is variable and a tool to select responders beforehand is highly desirable. In this study we evaluated scintigraphy with technetium-99m ((99m)Tc)-labelled infliximab for the imaging of disease activity in patients with pulmonary sarcoidosis.10 patients were studied using single photon emission computed tomography/computed tomography (CT) 6 h and 20 h after intravenous administration of 370 MBq of(99m)Tc-infliximab. Correlation analysis was performed between tissue accumulation of(99m)Tc-infliximab and laboratory parameters (including soluble interleukin-2 receptor and angiotensin-converting enzyme), lung function parameters (including forced expiratory volume in 1 s and the diffusing capacity of the lung for carbon monoxide) and(18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT.Analysis showed selective and variable accumulation of(99m)Tc-infliximab in the target tissue. Accumulation correlated positively with all four laboratory parameters and negatively with all four lung function parameters, yielding better correlations than serum TNF-α levels or(18)F-FDG PET/CT.(99m)Tc-infliximab accumulation reflects thein situTNF-α expression in an individual patient and therefore provides valuable information on the presence of the biological target for anti-TNF-α therapy.

Chest Imaging.

Chest imaging has a central role in the diagnosis and monitoring of sarcoidosis. For staging of pulmonary disease on chest radiograph, Scadding stages are still widely used. High-resolution CT (HRCT), however, is more accurate in visualizing the various manifestations of pulmonary sarcoidosis as well its complications. A generally accepted HRCT scoring system is lacking. Fluorodeoxyglucose F 18 positron emission tomography can visualize disease activity better than conventional makers in a significant proportion of patients. In patients with extensive changes on HRCT but no parenchymal fluorodeoxyglucose F 18 uptake, prudence with regard to initiation or intensification of immunosuppressive treatment is warranted.

Effectiveness of infliximab in refractory FDG PET-positive sarcoidosis.

Inconclusive evidence for the efficacy of infliximab in sarcoidosis hinders the global use of this potentially beneficial drug. To study infliximab efficacy in a clinical setting, we performed a prospective open-label trial in patients refractory to conventional treatment. Patients (n=56) received eight infusions of 5 mg·kg(-1) infliximab. Pulmonary function, disease activity measured by (18)F-fluorodeoxyglucose (FDG) by positron emission tomography (PET) and quality of life were part of the clinical work-up. Infliximab levels were measured before every infusion. After 26 weeks of infliximab treatment, mean improvement in forced vital capacity (FVC) was 6.6% predicted (p=0.0007), whereas in the 6 months before start of treatment, lung function decreased. Maximum standardised uptake value (SUVmax) of pulmonary parenchyma on (18)F-FDG PET decreased by 3.93 (p<0.0001). High SUVmax of pulmonary parenchyma at baseline predicted FVC improvement (R=0.62, p=0.0004). An overall beneficial response was seen in 79% of patients and a partial response was seen in 17% of patients. No correlation between infliximab trough level (mean 18.0 µg·mL(-1)) and initial response was found. In conclusion, infliximab causes significant improvement in FVC in refractory (18)F-FDG PET positive sarcoidosis. Especially in pulmonary disease, high (18)F-FDG PET SUVmax values at treatment initiation predict clinically relevant lung function improvement. These results suggest that inclusion of (18)F-FDG PET is useful in therapeutic decision-making in complex sarcoidosis.

FDG PET for gauging of sarcoid disease activity.

Fluorodeoxyglucose (FDG), labeled with a positron emitting fluorine-18 ((18)F), is a synthesized glucose analogue and is well known for its application in a wide variety of clinical conditions such as cancer. Visualizing metabolic activity of inflammation is another application of FDG in positron emission tomography (PET). Here, active granulomas appear to have a high affinity for FDG, which is reflected in a high sensitivity of FDG PET imaging. This has led to novel applications of FDG PET in sarcoidosis diagnosis and management. Although chest radiography and high-resolution computed tomography are still the cornerstones of diagnosing pulmonary involvement, FDG PET appears to be superior to both techniques in imaging active sites of disease. FDG PET also correlates well with serum biomarkers such as soluble interleukin-2 receptor in symptomatic patients, and even visualizes active lesions in the context of normal serum biomarkers. Moreover, FDG PET activity in lung parenchyma correlates with decrease of lung function values over time. Also in cardiac involvement in sarcoidosis, FDG PET is a promising technique complementary to magnetic resonance imaging, especially in guiding treatment. New developments, such as applications for quantitative organ-specific measurement, are proceeding and will probably enhance the clinical implementation of FDG PET in sarcoidosis.

Prediction of relapse after discontinuation of infliximab therapy in severe sarcoidosis.

Infliximab is effective as a third-line therapeutic for severe sarcoidosis; however, long-term efficacy is unknown. The aim of this study was to assess the relapse rate after discontinuation of infliximab in sarcoidosis patients and predict relapse by analysis of the activity marker soluble interleukin (IL)-2 receptor (sIL-2R) and maximum standardised uptake value (SUVmax) of (18)F-fluorodeoxyglucose positron emission tomography (FDG PET). In this retrospective cohort study, the proportion of relapse was analysed using the Kaplan-Meier method and predicting factors were studied using Cox regression. 47 sarcoidosis patients who started infliximab therapy were included in the risk analysis. Kaplan-Meier analysis revealed a median time to relapse of 11.1 months and showed that 25% of the cohort relapsed within 4 months. Both mediastinal SUVmax ≥ 6.0 on FDG PET (hazard ratio 3.77, p<0.001) and serum sIL-2R ≥ 4000 pg · mL(-1) (hazard ratio 2.24, p=0.033) at start of therapy predicted relapse. In multivariate analysis, a mediastinal SUVmax ≥ 6.0 at initiation of therapy was an independent predictor of relapse (hazard ratio 4.33, p<0.001). The majority of patients that discontinued infliximab therapy relapsed. High serum sIL-2R and high SUVmax on FDG PET at initiation of therapy were significant predictors of relapse. These results suggest close monitoring of patients in this category when they discontinue infliximab treatment.

Imaging the inflammatory activity of sarcoidosis.

Accurate assessment of pulmonary and extrapulmonary organ involvement in sarcoidosis is one of the great challenges for clinicians. This assessment includes the evaluation of symptoms and of sarcoidosis activity in a specific organ and its functional consequences. In this review, radiological and nuclear techniques to image the inflammatory activity of sarcoidosis are described, in particular (18)F-FDG positron emission tomography/computed tomography. The current use of this technique in clinical practice is explained, particularly in patients with persistent symptoms, stage IV disease and cardiac sarcoidosis.

(18)F-FDG PET patterns and BAL cell profiles in pulmonary sarcoidosis.

PURPOSE: Bronchoalveolar lavage (BAL) and (18)F-fluorodeoxyglucose ((18)F-FDG) PET can both demonstrate sarcoid activity. To assess whether metabolic activity imaged by (18)F-FDG PET represents signs of disease activity as reflected by BAL, (18)F-FDG PET patterns were compared with BAL cell profiles. METHODS: In this retrospective analysis, 77 newly diagnosed pulmonary sarcoidosis patients underwent BAL and (18)F-FDG PET. Based on (18)F-FDG PET, patients were diagnosed with exclusively mediastinal/hilar activity (group A) and activity in the lung parenchyma (group B). Per group, BAL lymphocytes (%), CD4/CD8 ratio, CD103(+)CD4(+)/CD4(+) ratio and neutrophils (%) were compared with the extent of metabolic activity expressed as the maximum standardized uptake value (SUV(max)). Additionally, SUV(max) and BAL parameters per radiographic stage were analysed. RESULTS: Overall, the SUV(max) in the lung parenchyma correlated with neutrophils and SUV(max) of the mediastinum/hila correlated with the CD4/CD8 ratio. In both groups, a significant, negative correlation between the SUV(max) of the mediastinum/hila and the CD103(+)CD4(+)/CD4(+) ratio was found. In group B, the SUV(max) of the mediastinum/hila correlated with the CD4/CD8 ratio, while the SUV(max) in the lung parenchyma correlated with the CD103(+)CD4(+)/CD4(+) ratio and neutrophils. Significant differences were found in the SUV(max), CD4/CD8 ratio, CD103(+)CD4(+)/CD4(+) ratio and neutrophils between the radiographic stages. The SUV(max) of the lung parenchyma was positively related to the radiographic stage, while the SUV(max) of the mediastinum/hila and CD4/CD8 ratio were inversely related. CONCLUSION: (18)F-FDG PET correlates with the CD4/CD8 ratio and neutrophils, suggesting that (18)F-FDG PET represents this specific cell profile in BAL. High SUV(max) values of the lung parenchyma may therefore correlate with more severe parenchymal involvement, particularly when accompanied by a low SUV(max) of the mediastinum/hila.

Invasive inflammatory myofibroblastic tumor of the lung.

Inflammatory myofibroblastic tumor (IMT) of the lung is a rare tumor but it should be considered when dealing with primary lung tumors in children, adolescents, and nonsmoking adults. It is, from a pathologic point of view, a benign tumor composed of a spindle cell proliferation and inflammatory cells. Its clinical behavior, however, is variable with a benign evolution at one, and a malignant evolution with recurrent and metastatic disease at the other end of the spectrum. Diagnosis is very difficult and often only possible after resection of the tumor. We present a case of pulmonary IMT in a 15-year-old male with malignant features on radiographic and F-Fluoro-deoxyglucose positron emission tomography imaging. Pathogenesis, pathology findings, clinical behavior, and imaging of pulmonary IMT are briefly discussed.

18F-FDG PET, genotype-corrected ACE and sIL-2R in newly diagnosed sarcoidosis.

PURPOSE: Angiotensin-converting enzyme (ACE) and soluble interleukin-2 receptor (sIL-2R) are serological markers, widely used for determining sarcoidosis activity. (18)F-FDG PET has proven to be a sensitive technique in the imaging of sarcoidosis. The aim of this study was to determine sensitivity of (18)F-FDG PET, genotype-corrected ACE and sIL-2R in active sarcoidosis as well as their correlation. METHODS: This retrospective study included 36 newly diagnosed, symptomatic sarcoidosis patients. ACE and sIL-2R levels were simultaneously obtained within 4 weeks of (18)F-FDG PET. ACE was corrected for genotype and expressed as Z-score. (18)F-FDG PET was visually evaluated and scored as positive or negative. Maximum and average standardized uptake values (SUV(max) and SUV(avg)) were compared with ACE and sIL-2R. RESULTS: (18)F-FDG PET was found positive in 34 of 36 patients (94%). Thirteen patients (36%) showed an increased ACE with the highest sensitivity found in patients with the I/I genotype (67%). Seventeen patients (47%) showed an increased sIL-2R. No correlation was found between SUV and ACE or sIL-2R. Increased ACE and sIL-2R correlated with a positive (18)F-FDG PET in 12 patients (92%) and 16 patients (94%), respectively. CONCLUSION: (18)F-FDG PET is a very sensitive technique to assess active sarcoidosis, in contrast with ACE and sIL-2R, suggesting a pivotal role for (18)F-FDG PET in future sarcoidosis assessment.

Recurrent pneumonia due to an appendiceal mucinous cystadenocarcinoma: a rare presentation of a rare malignancy.

Mucinous cystadenocarcinoma of the appendix is a rare malignancy. This is a report of a 74-year-old man who presented with recurrent pneumonia which turned out to be a postobstructive pneumonia complicating a large mucinous cystadenocarcinoma of the appendix with massive retroperitoneal and intrathoracic extension. Mucinous cystadenocarcinoma of the appendix is a low-grade malignancy characterized by expansive growth due to progressive accumulation of mucinous fluid produced by the cancer cells. The tendency of this tumor to expand massively is well demonstrated by this case. The unusual retroperitoneal location of appendix in this patient probably allowed the tumor to expand massively in the retroperitoneal space and the thoracic cavity. In addition to computed tomography, [(18)F]fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) was used as an ancillary method for staging in this patient. The value of (18)F-FDG PET in the diagnosis of mucinous cystadenocarcinoma of the appendix has not been determined yet, but it might be promising. The most common presentation of this tumor is abdominal pain or a palpable ileocoecal mass. To the knowledge of the authors, this is the first report of an appendiceal mucinous cystadenocarcinoma with expansion into the thoracic cavity presenting with recurrent pneumonia.