Detection Of Bone Marrow Metastases Research Articles

Bone marrow disease in rhabdomyosarcoma visualized by 2-[18F]fluorodeoxyglucose positron emission tomography/computed tomography.

Bone marrow metastases-noted in 6% of patients with rhabdomyosarcoma-have been linked to very poor outcomes. Bilateral bone marrow sampling from iliac crests has been the gold standard for bone marrow examination in rhabdomyosarcoma, but sampling errors due to patchy bone marrow involvement may limit its sensitivity. Here, we report the case of a 6-year-old boy with embryonal rhabdomyosarcoma of the skull base and multiple 2-[18F]fluoro-2-deoxy-D-glucose (2-[18F]FDG)-avid bone marrow metastases visualized by positron emission tomography and computed tomography (2-[18F]FDG PET/CT). His bone marrow aspirates were tumor-free. This case illustrates the diagnostic value of 2-[18F]FDG PET/CT in the detection of bone marrow metastases in rhabdomyosarcoma patients, which may re-shape the definition of bone marrow disease and, ultimately, alter disease staging and risk stratification.

FDG PET/CT reveals bone marrow oligometastasis in laryngeal squamous carcinoma: a case report with favorable outcome

Laryngeal carcinoma is the most common head and neck cancer. The vast majority of laryngeal carcinomas are of squamous-cell histologic type. Metastasis of laryngeal cancer typically occurs within the cervical lymph nodes and seldom in other regions. Although a small percentage of patients experience distant metastases, bone marrow metastasis from laryngeal cancer is among the least common metastatic sites. Previous literature has suggested that bone marrow carcinomatosis is aggressive and has a poor outcome, particularly in patients with supraglottic tumors. Ante-mortem diagnosis of this metastatic pattern has been limited. To our knowledge, this case report highlights the first documented occurrence wherein the utilization of 18-fluorine fludeoxyglucose positron emission tomography/CT imaging played a pivotal role in the early detection of bone marrow metastasis in a patient diagnosed with transglottic laryngeal cancer. A solitary metastatic distant bone marrow lesion was identified early during follow-up. As a consequence, the patient exhibited a remarkable and unforeseen favorable clinical outcome.

Detection of bone marrow metastases in children and young adults with solid cancers with diffusion-weighted MRI.

To compare the diagnostic accuracy of diffusion-weighted (DW)-MRI with b-values of 50s/mm2 and 800s/mm2 for the detection of bone marrow metastases in children and young adults with solid malignancies. In an institutional review board-approved prospective study, we performed 51 whole-body DW-MRI scans in 19 children and young adults (14 males, 5 females; age range: 1-25years) with metastasized cancers before (n = 19 scans) and after (n = 32 scans) chemotherapy. Two readers determined the presence of focal bone marrow lesions in 10 anatomical areas. A third reader measured ADC and SNR of focal lesions and normal marrow. Simultaneously acquired 18F-FDG-PET scans served as the standard of reference. Data of b = 50s/mm2 and 800s/mm2 images were compared with the Wilcoxon signed-rank test. Inter-reader agreement was evaluated with weighted kappa statistics. The SNR of bone marrow metastases was significantly higher compared to normal bone marrow on b = 50s/mm2 (mean ± SD: 978.436 ± 1239.436 vs. 108.881 ± 109.813, p < 0.001) and b = 800s/mm2 DW-MRI (499.638 ± 612.721 vs. 86.280 ± 89.120; p < 0.001). On 30 out of 32 post-treatment DW-MRI scans, reconverted marrow demonstrated low signal with low ADC values (0.385 × 10-3 ± 0.168 × 10-3mm2/s). The same number of metastases (556/588; 94.6%; p > 0.99) was detected on b = 50s/mm2 and 800s/mm2 images. However, both normal marrow and metastases exhibited low signals on ADC maps, limiting the ability to delineate metastases. The inter-reader agreement was substantial, with a weighted kappa of 0.783 and 0.778, respectively. Bone marrow metastases in children and young adults can be equally well detected on b = 50s/mm2 and 800s/mm2 images, but ADC values can be misleading.

Hybrid Ga-68 prostate-specific membrane antigen PET/MRI in the detection of skeletal metastasis in patients with newly diagnosed prostate cancer: Contribution of each part to the diagnostic performance.

Bone metastasis is essential in patients with prostate cancer (PCa) as it determines prognosis and survival. Hybrid PET/MRI allows simultaneous acquisition of PET and MRI data, thus combining the strength of both technologies allows the detection of bone marrow metastases that are missed by PET/CT. In this retrospective study, we aimed to evaluate the diagnostic efficiency of hybrid PET/MRI with Ga-68 prostate-specific membrane antigen (PSMA) in detecting skeletal metastases in newly diagnosed PCa patients and compared the effectiveness of stand-alone PSMA PET reviewing versus stand-alone whole-body (WB) MRI evaluation. We also investigated the effect of the interpretation of all PET/MR data together on clinical management. We studied 74 newly diagnosed PCa patients who underwent PSMA PET/MRI for staging purposes. At first, PET and MRI were evaluated separately for bone lesions on a patient-and-lesion basis and then a further joint PSMA PET/MRI interpretation was made. Patient-based sensitivity, specificity, positive predictive value, negative predictive value and accuracy analysis for bone metastasis was, respectively, 1.0, 0.83, 0.54, 1.0, 0.86 for PET; 0.75, 0.96, 0.81, 0.95, 0.93 for WB MRI and 0.91, 0.95, 0.78, 0,98, 0.94 for PET/MRI. The combined PET/MRI evaluation changed the clinical impact in 13.5% of patients (eight correct and two wrong decisions) compared to PET stand-alone interpretation. PSMA PET imaging showed superior sensitivity to WB MRI in detecting bone metastases in newly diagnosed PCa patients, whereas WB MRI has superior specificity and PPV. Furthermore, the specificity and PPV of joint PET/MRI evaluation are better than PSMA PET alone. Despite the longer acquisition period, adding WB MRI sequences to PSMA PET imaging appears beneficial for PCa patient management.

Diagnostic Accuracy of 2-[18F]FDG-PET and whole-body DW-MRI for the detection of bone marrow metastases in children and young adults.

To compare the diagnostic accuracy of 2-[18F]fluoro-2-deoxy-D-glucose-enhanced positron emission tomography (2-[18F]FDG-PET) and diffusion-weighted magnetic resonance imaging (DW-MRI) for the detection of bone marrow metastases in children and young adults with solid malignancies. In this cross-sectional single-center institutional review board-approved study, we investigated twenty-three children and young adults (mean age, 16.8years ± 5.1 [standard deviation]; age range, 7-25years; 16 males, 7 females) with 925 bone marrow metastases who underwent 66 simultaneous 2-[18F]FDG-PET and DW-MRI scans including 23 baseline scans and 43 follow-up scans after chemotherapy between May 2015 and July 2020. Four reviewers evaluated all foci of bone marrow metastasis on 2-[18F]FDG-PET and DW-MRI to assess concordance and measured the tumor-to-bone marrow contrast. Results were assessed with a one-sample Wilcoxon test and generalized estimation equation. Bone marrow biopsies and follow-up imaging served as the standard of reference. The reviewers detected 884 (884/925, 95.5%) bone marrow metastases on 2-[18F]FDG-PET and 893 (893/925, 96.5%) bone marrow metastases on DW-MRI. We found different "blind spots" for 2-[18F]FDG-PET and MRI: 2-[18F]FDG-PET missed subcentimeter lesions while DW-MRI missed lesions in small bones. Sensitivity and specificity were 91.0% and 100% for 18F-FDG-PET, 89.1% and 100.0% for DW-MRI, and 100.0% and 100.0% for combined modalities, respectively. The diagnostic accuracy of combined 2-[18F]FDG-PET/MRI (100.0%) was significantly higher compared to either 2-[18F]FDG-PET (96.9%, p < 0.001) or DW-MRI (96.3%, p < 0.001). Both 2-[18F]FDG-PET and DW-MRI can miss bone marrow metastases. The combination of both imaging techniques detected significantly more lesions than either technique alone. • DW-MRI and 2-[18F]FDG-PET have different strengths and limitations for the detection of bone marrow metastases in children and young adults with solid tumors. • Both modalities can miss bone marrow metastases, although the "blind spot" of each modality is different. • A combined PET/MR imaging approach will achieve maximum sensitivity and specificity for the detection of bone marrow metastases in children with solid tumors.

Role of bone marrow biopsy for staging new patients with Ewing sarcoma: A systematic review.

The incidence of bone marrow metastasis (BMM) in newly diagnosed Ewing sarcoma (ES) is variable across studies. An optimal staging strategy for detecting BMM is not defined. While bone marrow (BM) biopsy and/or aspirate (BMBA) have been the gold standard, [F-18]fluorodeoxyglucose positron emission tomography (FDG-PET) to detect BMM may decrease reliance on BMBA. We conducted a systematic review to assess incidence of BMM and the role of FDG-PET. We observed a pooled incidence of BMM by BMBA of 4.8% in all newly diagnosed ES patients and 17.5% among patients with metastatic disease. Only 1.2% of patients had BMM as their sole metastatic site. FDG-PET detection of BMM compared to BMBA demonstrated pooled 100% sensitivity and 96% specificity, positive predictive value of 75%, and negative predictive value of 100%. In the era of FDG-PET imaging, omission of BMBA may be considered in patients with otherwise localized disease after initial staging studies.

Abstract 4257: Detection of bone marrow metastases: Comparison of functional magnetic resonance imaging with bone marrow biopsy and aspiration

Abstract Bone marrow metastases are frequently detected by unilateral bone marrow biopsy and aspiration (BMBA), which is invasive. In this study, the value of functional magnetic resonance imaging (MRI) of pelvis was compared with BMBA and its clinical implication was evaluated. Cancer patients with bone metastasis and CT scan of pelvis showed no bone metastasis at the site of BMBA were included. BMBA was performed after MRI scan. Apparent Diffusion Coefficient (ADC), volume transfer constant (Ktrans), Pure diffusion coefficient (D), Pseudo diffusion coefficient (D*) and Perfusion fraction (f) were detected. The sensitivity, specificity and accuracy of MRI was calculate. An internal cross-validation via bootstrap was conducted for MRI performance in terms of the area under the curve (AUC). 28 oncological patients (11 breast cancer, 8 lung cancer, 5 prostatic cancer; 4 other cancers ) were enrolled. 16 patients were confirmed bone marrow metastases by BMBA. The sensitivity, specificity and accuracy of MRI was 93%, 50% and 75%. The ROC of Ktrans was 78%, which was the best. MRI can be used as a supplement to BMBA to diagnose bone marrow metastasis. Citation Format: Hui Zhao, Zhiyu Wang, Yue Hua Li. Detection of bone marrow metastases: Comparison of functional magnetic resonance imaging with bone marrow biopsy and aspiration [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4257.

Bone Marrow Cytomorphology And Clinico-Hematological Profile of Metastatic Solid Tumors: A 5-Year Audit from A Tertiary Care Centre in Northern India

Introduction: Metastasis to bone marrow by solid malignancies is a rare event and it upgrades the tumor thereby worsening the prognosis. This is caused by an impaired response to therapy and other manifestation resulting from decreased hematopoiesis. The common malignancies to metastasize in male and female are carcinoma prostate and carcinoma breast, respectively. It is noted that metastasis from small round cell tumor (SRCT) predominates in children. Here, we present a series of cases of bone marrow metastasis by solid organ malignancies over a period of 5 years. Objectives: The aim of this study was to investigate the clinical and hematological characteristics of patients with BM metastases of solid tumors diagnosed by bone marrow (BM) aspiration. Materials & methods: In this study, we reviewed 3520 bone marrow aspirates in our hospital from January 2013 to December 2017. Patients diagnosed with solid malignancies metastasizing to bone marrow were selected. Results: We found a total of 26 cases of solid malignancies with metastasis to bone marrow. The age of the patients ranged from 2–88 years (mean age of 46 years). Most of the patients were adults (19/26), of which 77.7% were males. Seven of the 26 patients were in the pediatric age group, with an age range of 2-11 years. Various malignancies metastasizing to marrow were evaluated and clinical and hematological correlation was done. The common presenting sign & symptoms were fever, anorexia and bodyache and organomegaly. Anemia was the most common hematological finding at the time of admission. Carcinoma prostate was the most common metastatic tumor in adults and small round cell tumor in children. Conclusion: BM is one of the important and infrequent sites of metastasis of solid tumors. Detection of bone marrow metastasis has significant clinical implication with impact on therapeutic decisions and is associated with poor prognosis. Aspiration of the BM provides an easy and quick way of detecting involvement, however, biopsy with immunohistochemical and/or molecular techniques may be needed in case of microscopical tumor burden.

Detection of Bone Marrow Metastases With Magnetic Resonance Imaging

Detection of Bone Marrow Metastases With Magnetic Resonance Imaging

Detection of Lumbar Spine Osseous Metastases Using Dual-Energy CT: Phantom Results and Preliminary Clinical Validation.

The purpose of this study was to evaluate the sensitivity, tumor conspicuity, and image quality of different material decomposition images of phantoms and patients with nearly isodense bone metastases using rapid-kilovoltage-switching dual-energy CT (DECT). Fifty-one semianthropomorphic lumbar spine phantoms embedded with 75 simulated tumors were scanned without and with outer torso-attenuating encasement under the same scan settings. Two radiologists independently reviewed the 70-keV virtual monochromatic and material decomposition images (hydroxyapatite-water, water-hydroxyapatite, cortical bone-water, water-cortical bone). The sensitivity of tumor detection, tumor conspicuity (on a 3-point scale), and image quality (on a 3-point scale) were recorded by two independent readers. McNemar and Wilcoxon signed rank tests were used to compare results between the image reconstructions. Six clinical abdominopelvic DECT scans (three men, three women; mean age, 52 years) with nine nearly isodense lumbar spine tumors missed in the clinical report but confirmed on other scans were also evaluated. The hydroxyapatite-water material decomposition algorithm showed improved sensitivity for isodense lesion detection (without torso phantom encasement, 94% vs 82%, p = 0.031; with torso phantom encasement, 38% vs 18%, p = 0.013), and higher tumor conspicuity scores (p < 0.0001) compared with 70-keV virtual monoenergetic images. Artifacts were more prevalent with all material decomposition images than with 70-keV virtual monoenergetic images. Similar results were seen in the patient study. Dual-energy CT with hydroxyapatite-water material decomposition may improve the detection of bone marrow metastases, especially for subtle isodense tumors. Further study in prospective clinical scans is warranted.

Beware of Bone Marrow: Incidental Detection and Primary Diagnosis of Solid Tumours in Bone Marrow Aspiration and Biopsies; A Study of 22 Cases

Introduction: First detection of any solid tumour as metastatic deposits in bone marrow directs clinicians to start searching for the primary tumour. Detection of bone marrow metastasis determines the stage of the malignancy, prognosis, mode of treatment, chemotherapeutic response and follow-up in case of relapse. The aim of the current study was to analyse the clinico-haematological presentation and morphological pattern of infiltration of solid tumours detected first as metastatic deposits on bone marrow examination. Three-year retrospective analysis of MGG-stained bone marrow aspiration smears and touch imprints of the bone marrow biopsy and Hematoxylin and Eosin (H&E) stained histopathological sections of biopsies was performed at the Department of Pathology at a tertiary care institute (January 2014 to December 2016). The morphological pattern of metastatic deposits and haematological profiles of the patients were analysed. Exclusion criterion was the presence of hematolymphoid malignancies. In 22 cases, bone marrow was the first site of detection of metastasis. The age of the patients ranged from 3 years and 10 months to 82 years, with equal gender predilection. Overall, 16 cases had cytopenias, 9 cases each had leucocytosis and leukoerythroblastic presentation. The metastasis was from Ewing's sarcoma, prostate carcinoma, gastric adenocarcinoma invasive duct carcinoma breast, gallbladder carcinoma, lacrimal duct carcinoma and invasive papillary urothelial carcinoma. Bone marrow examination is a cheap and reliable investigation to detect metastasis in an unsuspecting case. Bilateral trephine biopsies are recommended to increase the efficacy of detecting bone marrow metastasis.

Metastasis of solid tumors into bone marrow – Single center experience

Introduction: Metastases of solid tumors to the bone marrow are rarely reported. Clinical manifestation and laboratory findings remain uncharacteristic and lead to misdiagnosis. Detection of bone marrow metastases may have an impact on therapeutic decisions and is usually associated with poor prognosis. Aim: To characterize clinical picture and hematological findings in patients with bone marrow metastasis. Material and methods: We retrospectively reviewed medical records of patients with bone marrow metastases who were primary misdiagnosed with hematological malignancies. Results: Ten patients at median age of 51 years at diagnosis were included. There were following findings on admission: duopenia (n=7), pancytopenia (n=1), anemia (n=1) and skeletal lytic lesions (n=1). The diagnosis of prior cancer was reported in 3 patients and included multiple myeloma, breast cancer and oligoastrocytoma. Clinical manifestations were hepatomegaly (n=4), lymphadenopathy (n=4), skin pallor (n=3), cachexia (n=2) and hemorrhagic diathesis (n=2). Imaging studies revealed diffuse bone lesions (n=5), pulmonary infiltrates (n=2) and liver masses (n=2). Leukoerythroblastosis was demonstrated in 4 cases. Bone marrow aspirate detected the presence of abnormal cell population in 4 patients. In all studied patients a final diagnosis was established by immunohistochemistry of bone marrow biopsy. The following malignancies were detected: prostate adenocarcinoma (n=2), anaplastic microcellular carcinoma of unknown origin (n=2), adenocarcinoma of unknown origin (n=2), Ewing's sarcoma (n=1), breast cancer (n=1), clarocellular renal cancer (n=1) and neuroendocrine tumor (n=1). Nine out of the 10 metastatic patients died shortly after chemotherapy. Conclusions: Unexplained hematological abnormalities should arise the suspicion of bone marrow metastases.

CT imaging of bone and bone marrow infiltration in malignant melanoma—Challenges and limitations for clinical staging in comparison to 18FDG-PET/CT

Rationale of this study was the evaluation of the diagnostic value of computed tomography (CT) in the detection of bone marrow infiltration in comparison to PET/CT.Fifty patients (age 61±15.12years) with metastatic malignant melanoma underwent 18F-FDG-PET/CT, including contrast-enhanced CT. 2 readers evaluated the CT images in consensus for bone and bone marrow lesions focusing on lesion location, type and size. PET/CT was used as reference standard to estimate sensitivity, specificity, negative and positive predictive value. Moreover, the bone marrow density was estimated in the long bones and the sacral bone. Serum hamoglobin, thrombocyte level and S100 protein were correlated with the presence or absence of bone and bone marrow lesions.According to PET/CT as standard of reference, of 594 bone and medullary lesions 495 were considered malignant. Of these 77.8% were medullary, 20.4% lytic, 1% sclerotic and 0.8% mixed lytic/sclerotic. Contrast-enhanced CT yielded a lesion-based sensitivity of 36.8% and a specificity of 87.9% (PPV 93.8%; NPV 21.8%). Patient-based sensitivity and specificity were 78.8% and 82.4%, respectively. Of the missed lesions, most were medullary (95.8%). A disseminated bone marrow involvement (defined as >10 bone marrow lesions or diffuse infiltration of a whole body segment) was described in 11 cases, in 6 cases the disseminated involvement was underestimated or missed on CT. In cases with disseminated bone marrow involvement the bone marrow density was significantly higher in the humerus (p=0.04), but not in the femur or sacral bone (p=0.06). Multivariate analysis revealed no isolated effect of bone metastases on S100 serum and hemoglobin level, but both were significantly altered in patients with disseminated bone marrow involvement (p<0.05).In conclusion, the diagnostic value of computed tomography for the detection of bone marrow metastases in patients with melanoma, is limited. Especially in cases with disseminated bone marrow involvement about 50% of the cases were missed or underestimated.

Detection of bone marrow metastases in prostate cancer: Role of trephine biopsy and Immunohistochemistry

Context: Bone marrow (BM) metastases are an integral part of tumor dissemination in many malignancies. Prostate carcinoma, which has high tendency to metastasize to bone, shown to have affinity for endosteal niche as well as tendency to compete with hematopoietic cells to home in BM. This marrow dissemination can be confidently proved by histopathological examination of BM. Aims: In this study, we are trying to detect the presence of metastases and micrometastases in BM of prostate carcinoma patients with the help of immunohistochemical markers prostate-specific antigen (PSA) and prostate-specific acid phosphatase and correlate the findings with American Joint Committee on Cancer Tumor, Node and Metastasis 7 th (2010) classification, serum PSA, and biopsy Gleason's score. Materials and Methods: We performed BM examination and hematological workup of 11 known prostate carcinoma patients including metastatic cases also, during our study period of 1 year. The BM biopsy sections and clot sections were used to carry out immunohistochemistry. The data were analyzed by using SPSS (Statistical Package for Social Sciences) version 15.0 statistical analysis software. Results: We found that two patients were positive for metastases in BM out of the 11. Both of these patients already had metastases to other site with very high serum PSA levels. Anemia was common hematological alteration in both of them and one of them showed increased osteoblasts in the aspirate film. Conclusion: Taking into account our small sample size and short study duration, we conclude that further large sized future studies with long-term follow-up in to this BM dissemination by prostate cancer cells could open new horizons to understand the biology of metastasis of this common malignancy and also provide more effective therapeutic options as well as prognostic implications in these patients.

Clinical Outcome of Gastric Cancer Patients with Bone Marrow Metastases

PurposeThe prognosis of gastric cancer patients with bone marrow metastases is extremely poor. The current study was conducted to evaluate the clinical outcomes of advanced gastric cancer patients with bone marrow metastases.Materials and MethodsWe retrospectively reviewed the medical records of 26 advanced gastric cancer patients with bone marrow metastases who were treated at Soonchunhyang University Hospital between September 1986 and February 2009.ResultsThe median age was 46 years (range, 24 to 61 years). All patients had poorly differentiated adenocarcinoma, including 17 signet ring cell carcinomas. The majority of the patients had thrombocytopenia, anemia, and elevated lactate dehydrogenase levels. Sixteen patients (61.5%) received palliative chemotherapy (median, 4 cycles; range, 1 to 13 cycles). The median overall survival after detection of bone marrow metastases for the cohort of patients was 37 days (95% confidence interval, 12.5 to 61.5 days). The median overall survival after detection of bone marrow involvement was 11 days in the best supportive care group (range, 2 to 34 days) and 121 days (range, 3 to 383 days) in the palliative chemotherapy group (p<0.001). The causes of death were tumor progression (11 patients, 45%), brain hemorrhage (6 patients, 25%), infection (5 patients, 21%), and disseminated intravascular coagulation (1 patient, 4%). There were no chemotherapy-related deaths.ConclusionPalliative chemotherapy could be considered in advanced gastric cancer patients with bone marrow metastases as a treatment option.

Detection of Bone Marrow Metastases of Neuroblastoma With Immunohistochemical Staining of CD56, Chromogranin A, and Synaptophysin

Neuroblastoma is one of the most common solid tumors occurring in childhood. Bone marrow evaluation is an important part of clinical staging in neuroblastoma patients. In view of the difficulty of detecting neuroblastoma cells with conventional bone marrow aspirate smears and biopsy (BMB) and specimens in cases in which metastasis is not prominent, we propose the use of immunohistochemistry (IHC) as a potential diagnostic tool. We examined 116 BMB and 115 bone marrow clot (BMC) specimens from 60 newly diagnosed neuroblastoma patients for tumor cells. Neuroendocrine IHC markers, such as CD56, chromogranin A, and synaptophysin were applied to diagnose neuroblastoma. Eighteen out of the 60 patients (25.4%) displayed BM metastasis, as observed with conventional hematoxylin and eosin staining. IHC staining of BMC sections was generally more sensitive than that of BMB sections for tumor cell detection. We detected tumors in 5 and 7 additional hematoxylin and eosin-negative BMB and BMC sections, respectively, using CD56. Overall, CD56 or a combination of CD56 and chromogranin A was effective in detecting neuroblastoma cells. IHC analysis of BMB and BMC sections is warranted as a routine component of the diagnostic work-up of neuroblastoma to overcome discrepancies between routine smears and IHC stains.

Detection of bone metastases in patients with prostate cancer by 18F fluorocholine and 18F fluoride PET–CT: a comparative study

The aim of this prospective study was to compare the potential value of (18)F fluorocholine (FCH) and (18)F fluoride positron emission tomography (PET)-CT scanning for the detection of bony metastases from prostate cancer. Thirty-eight men (mean age, 69+/-8 years) with biopsy-proven prostate cancer underwent both imaging modalities within a maximum interval of 2 weeks. Seventeen patients were evaluated preoperatively, and 21 patients were referred for post-operative evaluation of suspected recurrence or progression based on clinical algorithms. The number, sites and morphological patterns of bone lesions on (18)F FCH and (18)F fluoride PET-CT were correlated: Concordant lesions between the two modalities with corresponding changes on CT were considered to be positive for malignancy; discordant lesions were verified by follow-up examinations. The mean follow-up interval was 9.1 months. Overall, 321 lesions were evaluated in this study. In a lesion-based analysis, a relatively close agreement was found between these two imaging modalities for detection of malignant bone lesions (kappa=0.57), as well as in a patient-based analysis (kappa=0.76). Sixteen malignant sclerotic lesions with a high density were negative in both (18)F FCH and (18)F fluoride PET-CT [mean Hounsfield unit (HU), 1,148+/-364]. There was also a significant correlation between tracer intensity by SUV and density of sclerotic lesions by HU both in (18)F FCH PET-CT (r= -0.28, p < 0.006) and (18)F fluoride PET-CT (r= -0.20, p<0.05). The sensitivity, specificity and accuracy of PET-CT in the detection of bone metastases in prostate cancer was 81%, 93% and 86% for (18)F fluoride, and 74% (p=0.12), 99% (p=0.01) and 85% for FCH, respectively. (18)F FCH PET-CT led to a change in the management in two out of 38 patients due to the early detection of bone marrow metastases. (18)F fluoride PET-CT identified more lesions in some patients when compared with (18)F FCH PET-CT but did not change patient management. FCH PET-CT may be superior for the early detection (i.e. bone marrow involvement) of metastatic bone disease. In patients with FCH-negative suspicious sclerotic lesions, a second bone-seeking agent (e.g. (18)F fluoride) is recommended. (18)F fluoride PET-CT demonstrated a higher sensitivity than (18)F FCH PET-CT, but the difference was not statistically significant. Furthermore, (18)F fluoride PET could be also negative in highly dense sclerotic lesions, which presumably reflects the effect of treatment. It will be important to clarify in future studies whether these lesions are clinically relevant when compared with metabolically active bone metastases.

MR-Ganzkörperdiagnostik

The term whole-body magnetic resonance imaging (MRI) covers a whole series of different MRI techniques that can be used for detecting various diseases. Whole-body magnetic resonance angiography facilitates the visualization of the entire arterial system from head to toe with the exception of the coronary arteries. Whole-body MRA is clinically used for therapy planning in patients with multiple stenoses and may be able to be used in the future as a screening method for high risk populations, for example in patients with coronary heart disease. Whole-body MRI can replace skeletal scintigraphy in the detection of bone marrow metastases by using fluid-sensitive sequences. Fast contrast-enhanced sequences can be used as an alternative approach in the search for tumors. Whole-body MRI can even be superior to a combination of positron-emission tomography and computed tomography in the detection of distant metastases. This article presents the recent developments in whole-body MRI and its established indications, which in the future might lead to a change in the paradigm for the diagnostic work-up of many diseases.

Prognostic and predictive factors revisited

Standard prognostic factors include clinical and pathological staging, especially lymph node status and tumor size. Tumor grade and estimates of lymphatic invasion appear to be moderately strong predictive factors, but reproducibility is poor, especially for grade 2 tumors. Standard predictive factors include hormone receptor status and HER-2 amplification and/or over-expression for selection of endocrine therapy and, at least for clinical trials and in the metastatic setting, of trastuzumab, respectively. Three new markers appear particularly promising: detection of bone marrow metastases, either at baseline or after 2-4 years of follow-up; expression of UPA/PAI-1 by the primary cancer; and recognition of simultaneous multiple gene expression patterns, or "signatures." Important caveats exist for each of these. Although new technologies offer exciting and promising new approaches to determining a patient's prognosis and whether she will or will not benefit from specific therapies, few have been validated in well-designed, Level of Evidence I studies. In particular, available data are often confounded by patient selection and the effects of systemic therapy, which are often not determined prospectively, not included in analyses, and not reported adequately.

Detection of Bone Marrow Metastases by FDG-PET and Missed by Bone Scintigraphy in Widespread Melanoma

The optimal management of patients with melanoma requires accurate imaging techniques that can screen the entire body for metastases. One of the most used tests for this purpose is bone scintigraphy. PET has been reported to be more sensitive than bone scintigraphy in some malignancies. In our case, FDG-PET was also superior to bone scintigraphy in detecting the extent of skeletal disease in a patient with melanoma. This is likely the result of the fact that metastasis to bone marrow may not result in bone reaction in certain conditions and therefore bone scans may remain negative despite skeletal involvement.