Diffuse bone marrow involvement of Hodgkin lymphoma mimics hematopoietic cytokine-mediated FDG uptake on FDG PET imaging

Whole-body fluorine-18 fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET) has been useful in the management of a variety of malignancies. In patients with chemotherapy followed by bone marrow stimulants such as granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor, the bone marrow will have diffuse, increased FDG accumulation. Therefore, diffuse bone marrow FDG uptake is commonly attributable to the effect of hematopoietic cytokines. However, diffuse bone marrow FDG uptake can also be caused by bone marrow involvement by malignancy. The authors report a patient with diffuse bone marrow involvement of Hodgkin disease that appears indistinguishable from hematopoietic cytokine-mediated FDG bone marrow uptake.     

Evaluation of neoadjuvant therapy response of osteogenic sarcoma using FDG PET.

According to the current treatment protocol of the Cooperative Osteosarcoma Study (COSS), monitoring preoperative chemotherapy response and estimating grade of tumor regression in patients with osteosarcoma is mandatory before surgical removal of the tumor, particularly if a limb salvage procedure is intended. In addition, response to neoadjuvant chemotherapy is considered as an important prognostic indicator. The aim of this prospective study was to assess the usefulness of 2-(18F) fluoro-2-deoxy-D-glucose (FDG) PET in the noninvasive evaluation of neoadjuvant chemotherapy response in osteosarcoma. METHODS: In 27 patients with osteosarcoma, we determined tumor-to-background ratios (TBRs) of FDG uptake with PET, before and after neoadjuvant chemotherapy according to COSS 86c or COSS 96 protocols, respectively. We compared changes in glucose metabolism of osteosarcomas with the histologic grade of regression in the resected specimen, according to Salzer-Kuntschik, discriminating responders (grades I-III; n = 17) and nonresponders (grades IV-VI; n = 10). RESULTS: The decrease of FDG uptake in osteosarcomas expressed as a ratio of posttherapeutic and pretherapeutic TBRs showed a close correlation to the amount of tumor necrosis induced by polychemotherapy (P < 0.001; Spearman). With a TBR ratio cutoff level of 0.6, all responders and 8 of 10 nonresponders could be identified by PET. In addition, lung metastases of osteosarcoma were detected with FDG PET in 4 patients. CONCLUSION: FDG PET provides a promising tool for noninvasive evaluation of neoadjuvant chemotherapy response in osteosarcoma. This could imply consequences for the choice of surgical strategy, because a limb salvage procedure cannot be recommended in patients nonresponsive to preoperative chemotherapy unless wide surgical margins can safely be achieved.     

Rhabdomyosarcoma with widespread bone marrow infiltration: beneficial management role of F-18 FDG PET

Alveolar rhabdomyosarcoma (RMS) accounts for 20% to 30% of childhood RMS and is associated with a prognosis worse than embryonal RMS. Disseminated RMS can present with extensive bone marrow involvement. Assessing the extent of the tumor is critical, because therapy and prognosis depend on the degree to which the mass has spread beyond the primary site. The value of F-18 FDG PET in patients with RMS has been reported in some series but none specifically involving bone marrow. Children have a highly cellular hematopoietic bone marrow and differentiation of a highly cellular marrow from neoplastic infiltration may be difficult. Various other conditions associated with diffuse FDG uptake in the bone marrow include marrow hyperplasia resulting from hemolytic/iron-deficiency/blood-loss anemia, after chemotherapy with granulocyte/macrophage colony-stimulating factor and recombinant erythropoietin treatment, leukemia, non-Hodgkin lymphoma, and myelodysplasia. It is therefore important to consider the above differential diagnoses in mind when evaluating cases of unexpected marrow uptake in F-18 FDG PET studies. We report here a case of RMS with diffuse bone marrow involvement detected on F-18 FDG PET wherein FDG PET was useful in determining the true extent (primary and metastases) of RMS before definitive therapy and the valuable adjunct role it has with structural imaging in management.     

Brain FDG PET study of normal aging in Japanese: effect of atrophy correction

Purpose The aim of this study was to investigate the effects of atrophy correction on the results of ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG PET) in the context of normal aging.Methods Before the human study was performed, a Hoffman 3D brain phantom experiment was carried out in order to validate a newly developed correction method for partial volume effects (PVEs). Brain FDG PET was then performed in 139 healthy Japanese volunteers (71 men, 68 women; age 24–81 years). PET images were corrected for PVEs using grey matter volume, which was segmented from co-registered magnetic resonance images and convoluted with the spatial resolution of the PET scanner. We investigated the correlation between advancing age and relative regional FDG activity, which was normalised to the global activity before and after PVE correction using Statistical Parametric Mapping 99.Results The PET image, when corrected for PVEs, provided more homogeneous tracer distribution in the whole phantom than in the original PET image. The human PET study of both sexes revealed significant negative correlations between age and relative FDG activity in the bilateral perisylvian and medial frontal areas before PVE correction. However, these negative correlations were largely resolved after PVE correction.Conclusion Correction for PVEs was effective in our FDG PET study. The reduction in FDG uptake with advancing age that was detected by FDG PET without PVE correction could be accounted for largely by an age-related cerebral volume loss in the bilateral perisylvian and medial frontal areas.     

Usefulness of FDG PET for diagnosis and radiotherapy of the patient with malignant lymphoma involving bone marrow

We experienced a case of relapsed malignant lymphoma with multiple bone marrow or bone lesions. The case was diagnosed as follicular lymphoma by cytological biopsy of the right iliac bone, with ⁶⁷Ga scintigraphy showing abnormal, intense uptake in multiple bones. After about 10 months of systemic chemotherapy, a relapse was suspected because of pain in the bilateral legs and a high level of lactate dehydrogenase. Assessment of the lesions in the patient was difficult by computed tomography because the affected sites were localized mainly in the bone marrow. ¹⁸F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) was useful for detecting accurately the relapse sites in the bone marrow and enabled us to determine the field for radiotherapy. There are only a few reports of FDG-PET findings for such bone marrow malignant lymphomas. Therefore, we report the findings of FDG-PET for this case and review some of the literature about bone marrow lymphomas.     

Grading of tumors and tumorlike lesions of bone: evaluation by FDG PET.

Clinical diagnosis of skeletal tumors can be difficult, because such lesions compose a large, heterogeneous group of entities with different biologic behaviors. The aim of this prospective study was to assess the value of PET in grading tumors and tumorlike lesions of bone. METHODS: Two hundred two patients with suspected primary bone tumors were investigated using FDG PET. Uptake of FDG was evaluated semiquantitatively by determining the tumor-to-background ratio (T/B). All patients underwent biopsy, resulting in the histologic detection of 70 high-grade sarcomas, 21 low-grade sarcomas, 40 benign tumors, 47 tumorlike lesions, 6 osseous lymphomas, 6 plasmacytomas, and 12 metastases of an unknown primary tumor. RESULTS: All lesions, with the exception of 3 benign tumors, were detected by increased FDG uptake. Although sarcomas showed significantly higher T/Bs than did latent or active benign lesions (P < 0.001), aggressive benign lesions could not be distinguished from sarcomas. Using a T/B cutoff level for malignancy of 3.0, the sensitivity of FDG PET was 93.0%, the specificity was 66.7%, and the accuracy was 81.7%. CONCLUSION: FDG PET provides a promising tool for estimating the biologic activity of skeletal lesions, implicating consequences for the choice of surgical strategy.     

Biopsy versus FDG PET/CT in the initial evaluation of bone marrow involvement in pediatric lymphoma patients

Purpose  

The objective is to assess the role of ¹⁸F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)/CT versus bone marrow biopsy (BMB) in the initial evaluation of bone marrow (BM) involvement in pediatric lymphoma patients.     

FDG PET/CT for the detection of bone marrow involvement in diffuse large B-cell lymphoma: systematic review and meta-analysis

Purpose

To systematically review and meta-analyse published data on the diagnostic performance of ¹⁸F-FDG PET/CT in detecting bone marrow involvement in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL).

Methods

PubMed/MEDLINE and Embase were systematically searched for relevant studies. The methodological quality of each study was assessed. Sensitivities and specificities of FDG PET/CT in individual studies were calculated and meta-analysed with a random effects model. A summary receiver operating characteristic curve (sROC) was constructed with the Moses-Shapiro-Littenberg method. Weighted summary proportions of discrepancies between the FDG PET/CT and (blind) bone marrow biopsy (BMB) results among all patients were calculated.

Results

Seven studies, with a total of 654 patients with newly diagnosed DLBCL, were included. Overall, the quality of the included studies was moderate. The sensitivity and specificity of FDG PET/CT for detecting bone marrow involvement ranged from 70.8 % to 95.8 % and from 99.0 % to 100 %, with pooled estimates of 88.7 % (95 % confidence interval, CI, 82.5 – 93.3 %) and 99.8 % (95 % CI 98.8 – 100 %), respectively. The area under the sROC curve was 0.9983. The weighted summary proportion of FDG PET/CT-negative patients with positive BMB findings among all patients was 3.1 % (95 % CI 1.8 – 5.0 %) and the weighted summary proportion of FDG PET/CT-positive patients with negative BMB findings among all patients was 12.5 % (95 % CI 8.4 – 17.3 %).

Conclusion

FDG PET/CT is accurate and complementary to BMB for detecting bone marrow involvement in patients with newly diagnosed DLBCL. A negative FDG PET/CT scan cannot rule out the presence of bone marrow involvement, but positive FDG PET/CT findings obviate the need for BMB for the detection of bone marrow involvement in these patients.     

Long-term precision of 18F-fluoride PET skeletal kinetic studies in the assessment of bone metabolism.

(18)F-Fluoride PET allows noninvasive evaluation of regional bone metabolism and has the potential to become a useful tool for assessing patients with metabolic bone disease and evaluating novel drugs being developed for these diseases. The main PET parameter of interest, termed K(i), reflects regional bone metabolism. The aim of this study was to compare the long-term precision of (18)F-fluoride PET with that of biochemical markers of bone turnover assessed over 6 mo. METHODS: Sixteen postmenopausal women with osteoporosis or significant osteopenia and a mean age of 64 y underwent (18)F-fluoride PET of the lumbar spine and measurements of biochemical markers of bone formation (bone-specific alkaline phosphatase and osteocalcin) and bone resorption (urinary deoxypyridinoline) at baseline and 6 mo later. Four different methods for analyzing the (18)F-fluoride PET data were compared: a 4k 3-compartmental model using nonlinear regression analysis (K(i-4k)), a 3k 3-compartmental model using nonlinear regression analysis (K(i-3k)), Patlak analysis (K(i-PAT)), and standardized uptake values. RESULTS: With the exception of a small but significant decrease in K(i-3k) at 6 mo, there were no significant differences between the baseline and 6-mo values for the PET parameters or biochemical markers. The long-term precision, expressed as the coefficient of variation (with 95% confidence interval in parentheses), was 12.2% (9%-19%), 13.8% (10%-22%), 14.4% (11%-22%), and 26.6% (19%-40%) for K(i-3k), K(i-PAT), mean standardized uptake value, and K(i-4k), respectively. For comparison, the precision of the biochemical markers was 10% (7%-15%), 18% (13%-27%), and 14% (10%-21%) for bone-specific alkaline phosphatase, osteocalcin, and urinary deoxypyridinoline, respectively. Intraclass correlation between the baseline and 6-mo values ranged from 0.44 for K(i-4k) to 0.85 for K(i-3k). No significant correlation was found between the repeated mean standardized uptake value measurements. CONCLUSION: The precision and intraclass correlation observed for K(i-3k) and K(i-PAT) was equivalent to that observed for biochemical markers. This study provided initial data on the long-term precision of (18)F-fluoride PET measured at the lumbar spine, which will aid in the accurate interpretation of changes in regional bone metabolism in response to treatment.