Martha Hoffmann

Positron emission tomography with fluorine-18-2-fluoro-2-deoxy-D-glucose (F18-FDG) does not visualize extranodal B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT)-type

BACKGROUND On the basis of promising data on the use of fluorine-18-2-fluoro-2-deoxy-D-glucose (F18-FDG) whole body positron emission tomography (WB-FDG-PET) in the staging of patients with lymphoma, we initiated a pilot series to evaluate the role of WB-FDG-PET in the staging of extranodal B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) type. PATIENTS AND METHODS We examined ten consecutive patients with histologically-verified MALT-type lymphomas of various origin before initiation of therapy. Nine patients had low-grade lymphomas (five cases of gastric lymphoma, two patients with lymphoma arising in the lung, one parotid and one lacrimal gland lymphoma), while one patient had a high-grade gastric lymphoma arising from a low-grade background. Two patients had stage EI, seven had stage EII disease, and one presented with stage EIII. WB-FDG-PET scans were performed 40 min following the injection of 300-380 MBq of F18-FDG. The PET scans were correlated with extensive conventional staging including ophthalmologic investigation, otolaryngologic examination, gastroscopy, endosonography, enteroclysis, colonoscopy, CT of thorax and abdomen, and bone marrow biopsy. RESULTS WB-FDG-PET documented no lymphoma in any of the 10 patients studied, as no focal tracer uptake was demonstrated in either gastric or extragastric lesions or in involved lymph nodes, irrespective of histologic grading. In three patients the scan showed a false negative result with respect to the MALT lesions but showed focal tracer uptake indicating tumor spread, which, however, was ruled out by further follow-up and biopsy, respectively, and was thus rated false positive. Due to these results, the study was discontinued prematurely after the first ten patients. CONCLUSIONS These discouraging results indicated that WB-FDG-PET is not useful for staging and follow-up of MALT-type lymphoma, and should therefore not be included in the clinical decision making process.

Assessment of Disease Dissemination in Gastric Compared With Extragastric Mucosa-Associated Lymphoid Tissue Lymphoma Using Extensive Staging: A Single-Center Experience

PURPOSE Molecular data and preliminary clinical findings have suggested mucosa-associated lymphoid tissue (MALT) lymphoma as a multifocal disease in a high percentage of patients. We report our findings with an extensive staging routine applied in patients diagnosed with MALT lymphoma at our institution. PATIENTS AND METHODS A total of 140 consecutive patients (61 with gastric and 79 with extragastric MALT lymphoma) underwent staging according to a standardized protocol. Staging included gastroscopy with multiple biopsies, endosonography of the upper GI tract, computed tomography of thorax and abdomen, lymph node sonography, colonoscopy with multiple biopsies, otorhinolaryngologic assessment, magnetic resonance imaging of salivary and lacrimal glands, and bone marrow biopsy. All lesions suggestive of lymphoma involvement were subjected to biopsy, if accessible, and biopsies were evaluated for MALT lymphoma-specific genetic aberrations by means of reverse transcriptase polymerase chain reaction and/or fluorescent in situ hybridization. RESULTS Fifteen (25%) of 61 patients with gastric MALT lymphoma had multiorgan involvement, with dissemination beyond the GI tract in six patients. By contrast, significantly more patients with extragastric MALT lymphoma had dissemination to another MALT organ (37 of 79 patients, 46%; P = .045). Nine of these 37 patients had dissemination to the stomach. Only three (2%) of 140 patients had bone marrow involvement. Multifocality was significantly associated with t(11;18)(q21;q21) in gastric lymphomas (P = .045) and with trisomy 18 in extragastric lymphomas (P = .011). CONCLUSION Our findings suggest that MALT lymphoma frequently presents as a multifocal disease. Extragastric MALT lymphomas are significantly more prone to dissemination than gastric MALT lymphomas.

18F-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG-PET) for Staging and Follow-Up of Marginal Zone B-Cell Lymphoma

Objective: According to recent reports, nodal marginal zone lymphoma (MZL) appears to be a distinctive lymphoma entity rather than a more advanced stage of extranodal MZL of mucosa-associated lymphoid tissue (MALT). We have therefore retrospectively evaluated all patients diagnosed with nodal or extranodal MZL who have been referred to our unit for imaging using 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET). Patients and Methods: A total of 21 patients with a diagnosis of MZL upon referral for imaging with 18F-FDG-PET were identified. Histological reassessment of biopsy specimens confirmed the diagnosis of extranodal MZL of MALT in 14 patients, while a diagnosis of nodal MZL was verified in 6 patients. Lymphoma cell proliferation was assessed immunohistochemically using a Ki-67 antibody. Whole-body 18F-FDG-PET scans were performed on a GE advanced PET scanner 40 min after intravenous injection of 300–380 MBq 18F-FDG. Results: None of the patients with extranodal MZL showed focal tracer uptake within verified tumor sites. In contrast, 5 of the 6 patients with nodal MZL showed significant FDG uptake within the affected lymph nodes. These results did not simply reflect the different growth fractions of the two lymphoma entities since the proliferation indices of the two groups did not differ significantly. Conclusion:18F-FDG-PET visualizes nodal MZL in a high proportion of patients whereas FDG uptake is undetectable in extranodal MZL. Although limited by the small number of patients, this study suggests that imaging with 18F-FDG-PET might play a potential role in the diagnostic workup of patients with nodal MZL involvement.

[123I]beta-CIT SPECT distinguishes vascular parkinsonism from Parkinson's disease.

We investigated whether [123I]‐β‐CIT and single‐photon emission computed tomography (SPECT) imaging distinguishes patients with clinically suspected vascular parkinsonism (VP) from patients with idiopathic Parkinsons disease (PD). [123I]β‐CIT SPECT is a sensitive marker of dopaminergic degeneration, and the degree of striatal binding reduction in PD correlates with disease severity. Thirteen patients who fulfilled rigid clinical criteria for VP (mean ± S.D.: age, 76.5 ± 5.3 years; disease duration, 3.6 ± 2.8 years), 20 PD patients (age, 66.2 ± 9.5 years; disease duration, 4.3 ± 2.7 years), and 30 healthy persons (age, 44.6 ± 19.2 years) underwent [123I]β‐CIT SPECT imaging. Age‐corrected striatal β‐CIT binding was reduced on average by 40.8% in PD but was near normal in the VP group (mean reduction, 1.2%). This difference was statistically significant (Z = 4.68; P < 0.001). The left–right asymmetry of striatal β‐CIT binding was significantly increased in the PD group compared with normal controls and the VP group (F(2) = 17.4, P <0.001). Moreover, putamen–caudate nucleus ratios were significantly reduced in PD compared with both VP patients and healthy controls (F(2) = 65.5, P < 0.001). Whole striatal β‐CIT binding was more than one standard deviation above the mean PD values in all but one of the individual VP patients. Our findings suggest that the presynaptic dopaminergic deficits seen in PD are absent in most patients with VP. [123I]β‐CIT SPECT imaging may be useful to help distinguish between PD and VP patients during life.

Follicular thyroid carcinoma in an iodine-replete endemic goiter region: a prospectively collected, retrospectively analyzed clinical trial.

Objective:To determine risk factors for presence of lymph node or distant metastases in patients with follicular thyroid cancer (FTC) at the time of diagnosis and whether there is a relationship between the type of tumor invasion and metastases. Summary Background Data:FTC often presents distant metastases at the initial diagnosis. As distant metastases are independent prognostic factors in a patients survival, determination of clinicopathologic characteristics for patients who are at higher risk for developing metastases is of greater clinical importance. Methods:The prognostic significance of gender (male vs. female), age (≤40 years vs. <40 years), tumor size (≤40 mm vs. >40 mm), number of lesions (uni- vs. multifocality), type of invasion (minimally invasive vs. widely invasive), and oncocytic changes (with vs. without) were analyzed in 207 patients, according to presence of lymph node and distant metastases at the time of initial surgery. According to the type of invasion, the carcinoma-specific survival and the disease-free survival of minimally invasive (MI) and widely invasive (WI) FTC were estimated and compared. Results:None of the 127 patients with MI growth presented with lymph node metastases but 9.4% distant metastases. Overall risk factors for the presence of lymph node metastases at the initial diagnosis were multifocality (P = 0.02) and widely invasion (P = 0.0001) and for distant metastases age >45 years (P = 0.007), tumor size larger than 40 mm (P = 0.03) and widely invasion (P = 0.0001). WI-FTC patients show larger tumors (P = 0.0001), older age (P = 0.0001), and are presented more frequently in recurrent goiter disease (P = 0.0001). The estimated 10 years carcinoma-specific survival and disease-free survival for MI-tumors were significantly better than for WI-tumors (P = 0.0001). Conclusions:Total thyroidectomy is recommended in all patients with FTC because of early distant metastases. Patients with WI-FTC need a more aggressive surgical treatment because of higher tendency for lymph node metastases. MI-FTC has an excellent prognosis with no sign of lymph node metastases, which emphasizes a limited need for nodal surgery.

Bortezomib combined with rituximab and dexamethasone is an active regimen for patients with relapsed and chemotherapy-refractory mantle cell lymphoma

Background Bortezomib belongs to a new class of anti-cancer agents, the proteasome inhibitors, and has documented activity in multiple myeloma and mantle cell lymphoma. Preclinical studies suggest that bortezomib has synergistic activity with rituximab, which provides a rationale for the exploration of treatment combinations. Design and Methods The activity and safety of bortezomib in combination with rituximab and dexamethasone were investigated in patients with relapsed or chemotherapy-refractory mantle cell lymphoma. A treatment cycle consisted of bortezomib (1.3 mg/m2 on days 1, 4, 8, and 11; six 21-day cycles), rituximab (375 mg/m2, day 1) and dexamethasone (40 mg orally, days 1 to 4). Responding patients received four consolidating doses of rituximab. Sixteen patients with progressive mantle cell lymphoma after a median of three prior lines of therapy were enrolled. Results The overall response rate was 81.3% (13 patients), with seven patients achieving a complete response (43.8%). Six of these patients were also negative for disease activity by positron emission tomography scanning. The median progression-free survival and overall survival were 12.1 and 38.6 months, respectively. In patients achieving a complete response, the median progression-free survival and overall survival have not yet been reached. Adverse events (greater than grade II) included thrombocytopenia (37.5%), fatigue (18.8%) and peripheral neuropathy (12.5%). Two patients discontinued bortezomib because of grade III neuropathy. Conclusions Bortezomib combined with rituximab and dexamethasone has promising activity and manageable toxicity in patients with heavily pretreated mantle cell lymphoma. Achievement of complete response emerged as an important factor for sustained disease control. This trial was registered at www.clinicaltrials.gov as #NCT00261612.

High Efficacy of Concomitant Treatment of Undifferentiated (Anaplastic) Thyroid Cancer with Radiation and Docetaxel

CONTEXT Anaplastic thyroid carcinoma (ATC) is a rare but aggressive solid tumor with a very short survival time even with multimodality treatment. In view of in vitro data and the high rate of p53 mutations in ATC, we have used combined treatment with external beam radiation and docetaxel. OBJECTIVE The objective was to analyze the activity using radiation plus docetaxel. DESIGN The design was a retrospective analysis. SETTING The study was performed in a referral center of a university hospital. PATIENTS A total of six patients with ATC were treated at our institution. INTERVENTION Treatment consisted of standard external beam radiation of 60.0 Gy in 30 fractions along with docetaxel at a flat dose of 100 mg absolute every 3 wk for a total of six cycles starting within the first week of radiation. OUTCOME MEASURE The outcome measure included clinical response and survival. RESULTS Five patients completed radiochemotherapy. One patient has completed radiation but is still on treatment with docetaxel. Four patients achieved complete remission and two partial response. During radiation therapy, four patients developed severe mucositis/stomatitis and two dermatitis, necessitating hospitalization. Two patients developed pneumonia and one urinary tract infection. All patients were hospitalized for a median of 17 d (range, 4-40 d) because of toxicites. After a median follow up of 21.5 months (range, 2-40 months), five patients are alive. CONCLUSION The preliminary data suggest that the combination of radiation and concomitant docetaxel is highly effective in patients with ATC. However, a formal phase II study is needed to assess the therapeutic potential of this combination.

Evaluation of Diffusion-Weighted MRI for Pretherapeutic Assessment and Staging of Lymphoma: Results of a Prospective Study in 140 Patients

Purpose: To determine the value of diffusion-weighted MRI (DWI-MRI) for pretherapeutic imaging of fluorodeoxyglucose (FDG)-avid lymphoma and lymphoma with variable FDG avidity. Experimental Design: Treatment-naïve patients with lymphoma who were referred for whole-body staging were included in this prospective study. Group A included patients with FDG-avid lymphoma (e.g., Hodgkin, diffuse large B-cell, and follicular lymphoma), whereas Group B included patients with lymphoma of variable FDG avidity [e.g., extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT)]. All patients underwent DWI-MRI and 18F-FDG- positron emission tomography/computed tomography (PET/CT). Region-based sensitivity and agreement with Ann Arbor staging, relative to the reference standard, were calculated for DWI-MRI, and, in Group B, also 18F-FDG-PET/CT and contrast-enhanced (CE-) CT. Results: In Group A (100 patients), DWI-MRI had a region-based sensitivity of 97%, and with regard to staging, agreed with the reference standard in 94 of 100 patients (κ, 0.92). In Group B (40 patients; 38 MALT lymphomas and 2 small lymphocytic lymphomas/chronic lymphocytic leukemias), DWI-MRI, 18F-FDG-PET/CT, and CE-CT had region-based sensitivities of 94.4%, 60.9%, and 70.7%, respectively. With regard to staging in Group B, DWI-MRI, 18F-FDG-PET/CT, and CE-CT agreed with the reference standard in 37 of 40, 26 of 40, and 24 of 40 patients, with κ values of 0.89, 0.52, and 0.43, respectively. Conclusions: In patients with FDG-avid lymphoma, DWI-MRI seems to be only slightly inferior to 18F-FDG-PET/CT with regard to pretherapeutic regional assessment and staging. In patients with lymphoma subtypes that show a variable FDG avidity (e.g., MALT lymphoma), DWI-MRI seems to be superior to both 18F-FDG-PET/CT and CE-CT. Clin Cancer Res; 20(11); 2984–93. ©2014 AACR.

Dopamine transporter imaging in autopsy-confirmed Parkinson's disease and multiple system atrophy.

Dopamine transporter single‐photon emission computerized tomography can visualize dopaminergic degeneration in Parkinsons disease and multiple system atrophy. Some studies have suggested that dopamine transporter imaging can distinguish these disorders based on a more diffuse and symmetric striatal dopamine transporter binding loss in multiple system atrophy. The present study compared patterns of striatal dopamine transporter distribution in postmortem‐confirmed Parkinsons disease and multiple system atrophy. Patients with a postmortem diagnosis of multiple system atrophy (n = 6) or Parkinsons disease (n = 8) who had undergone dopamine transporter imaging were included. Imaging had been performed after a mean disease duration of 3.6 and 4.1 years in multiple system atrophy and Parkinsons disease, respectively. Visual analysis showed bilaterally reduced binding in all patients. Mean overall striatal binding was reduced by 53% in multiple system atrophy and 52% in Parkinsons disease. There was a trend for greater asymmetry of striatal binding in multiple system atrophy compared with Parkinsons disease (23% ± 15% vs 10.5% ± 7%, respectively; P = .071), with 3 multiple system atrophy patients showing more asymmetry of striatal binding than any Parkinsons disease patient. Putamen/caudate binding ratios did not differ between the groups. This is the first study comparing dopamine transporter imaging in autopsy‐confirmed multiple system atrophy and Parkinsons disease. Unexpectedly, we found a tendency for greater asymmetry of striatal binding in multiple system atrophy than in Parkinsons disease. Our findings demonstrate that these conditions cannot be differentiated by subregional analysis of striatal dopamine transporter binding.

Transformation of MALT lymphoma to pure plasma cell histology following treatment with the anti-CD20 antibody rituximab

Mucosa associated lymphoid tissue (MALT) lymphoma is a relatively common lymphoma arising from marginal-zone B-cells which are closely related to plasma cells. As opposed to the large majority of plasma cells, MALT lymphoma cells express CD20, and the anti-CD20 antibody rituximab has been reported as active treatment in patients with MALT lymphoma. We present a patient with MALT lymphoma involving stomach and lung which transformed to a pure plasma cell tumor after therapy with rituximab. This observation again supports the close association between the cell of origin of MALT lymphoma and plasma cells, suggesting that “plasmacytoma of the GI-tract” as anecdotally reported may in fact be a MALT lymphoma with extreme plasmacytic differentiation. In addition, our findings suggest that MALT lymphomas with plasmacytic differentiation might have a different 18F-FDG uptake as compared to classical MALT lymphoma.