Prospective Comparison of T1-SPACE and MPRAGE for the Identification of Intrinsic T1 Hyperintensity in Patients with Intracranial Melanoma Metastases.

BACKGROUND AND PURPOSE: Volumetric TSE (3D-TSE) techniques are increasingly replacing volumetric magnetization-prepared gradient recalled-echo (3D-GRE) sequences due to improved metastasis detection. In addition to providing a baseline for assessing postcontrast enhancement, precontrast T1WI also identifies intrinsic T1 hyperintensity, for example, reflecting melanin or blood products. The ability of precontrast 3D-TSE to demonstrate intrinsic T1 hyperintensity is not clear from the literature; thus, this study compares precontrast 3D-TSE and 3D-GRE sequences for identifying intrinsic T1 hyperintensity in patients with metastatic melanoma. MATERIALS AND METHODS: Patients with metastatic melanoma and previously reported intrinsic T1 hyperintensity were identified. MRIs were performed at 3T including both 3D-GRE (MPRAGE) and 3D-TSE T1 sampling perfection with application-optimized contrasts by using different flip angle evolution (T1-SPACE) sequences precontrast. Axial 1-mm slices of both T1WI sequences were independently reviewed by 2 neuroradiologists, comparing the conspicuity of each lesion between the 2 sequences according to a 5-point scale and assessing whether the intrinsic T1 hyperintensity was attributable to melanin, blood products, or both. RESULTS: Twenty examinations were performed, with a total of 214 lesions demonstrating intrinsic T1 hyperintensity. Both readers found that intrinsic T1 hyperintensity was less conspicuous with T1-SPACE compared with MPRAGE for most lesions assessed (81.8%, averaged across both readers), including for lesions with intrinsic T1 hyperintensity attributable to melanin and blood products. Intrinsic T1 hyperintensity was rarely more conspicuous on T1-SPACE (1.4%). CONCLUSIONS: Precontrast intrinsic T1 hyperintensity is more conspicuous with MPRAGE than T1-SPACE. In patients with metastatic melanoma, 3D-GRE should be preferred as the precontrast T1WI sequence when both 3D-TSE and 3D-GRE are performed postcontrast and when not administering IV contrast.

Persistent median artery on computed tomographic arteriovenous fistulograms in patients on haemodialysis.

INTRODUCTION: Cadaveric studies suggest an increasing prevalence of the persistent median artery (PMA) over a prolonged timeframe. The aim of this retrospective cross-sectional study was to evaluate the PMA prevalence in haemodialysis patients who had computed tomographic fistulograms (CTFs), and if present, their calibres and origins. METHODS: All consecutive adult patients referred for an upper limb CTFs for assessment of arteriovenous fistula (AVF) dysfunction from 2006 to 2021 were included. Patients whose CTF did not include the forearm were excluded. PMA was identified as an artery running alongside the median nerve between flexor digitorum superficialis and flexor digitorum profundus. Patient demographics, presence of PMA including size and origin were recorded. RESULTS: A PMA was found in 91/170 (53.5%) CTFs (7:3 male-to-female ratio, mean age 71-years). When stratified by age, prevalence increased with decreasing age; 51% in >70-year-olds, 54% in 50-70-year-olds and 67% in <50-year-olds. The average PMA diameter was 2.2 mm proximally and 1.8 mm distally. No stenosis was observed in the PMAs. CONCLUSION: The PMA prevalence appears to increase with decreasing age and is a frequently encountered anatomical variant. Radiologists assessing forearm vasculature need to be aware of this anatomical variant and potentially include it in their future reports. Further research into the PMA may make its potential use as arterial conduits for AVF, potential donor grafts for coronary artery bypass surgery or additional vascular access options possible. Whether the reducing prevalence with age reflects an overall increasing prevalence is yet to be determined.

Improving the diagnosis of radiation necrosis after stereotactic radiosurgery to intracranial metastases with conventional MRI features: a case series.

BACKGROUND: The distinction between true disease progression and radiation necrosis after stereotactic radiosurgery to intracranial metastases is a common, but challenging, clinical scenario. Improvements in systemic therapies are increasing the importance of this distinction. A variety of imaging techniques have been investigated, but the value of any individual technique is limited. CASE PRESENTATION: Assessment should extend beyond simply the appearances of the lesion at a given timepoint, but also consider local anatomy and lesion evolution. Firstly, enlargement of a metastasis is affected by local anatomical boundaries, such as the dural reflections or cerebrospinal fluid spaces. In contrast, the radiation dose administered with stereotactic radiosurgery does not respect these anatomical boundaries and is largely concentric around the treated lesion. Therefore, new, non-contiguous enhancement across such a boundary can be confidently attributed to radiation necrosis. Secondly, the dynamic nature of radiation necrosis may result in a change in lesion shape, with different portions of the lesion simultaneously enlarging and regressing. Regression of part of a lesion indicates radiation necrosis, even if the overall lesion enlarges. This case series describes these two features and provides illustrative clinical examples in which these features allowed a confident diagnosis of radiation necrosis. CONCLUSIONS: The distinction between true disease progression and radiation necrosis should extend beyond just the appearances of the lesion. More nuanced interpretation incorporating a relationship to anatomical boundaries and a change in shape can improve accurate diagnosis of radiation necrosis.

Error and cognitive bias in diagnostic radiology.

Errors in diagnostic radiology are not infrequent. Patient harm related to these errors is however less common and may be avoided via various preventative mechanisms within the medical system including, but not limited to, multidisciplinary meetings, second opinions, subspecialty expertise and clinician experience. Failure at a number of points in the system is often required to result in patient harm. Radiologists, and in particular departmental leaders, should proactively address the known underlying root causes of diagnostic errors and cognitive biases, ensure systems are in place to promptly discover and control unmitigated root causes as they arise and ensure an unbiased 'blameless' or 'just' culture of error investigation and proces sing including the implementation of non-punitive peer feedback and peer learning. This article provides an overview of errors in diagnostic radiology including the causes and potential ramifications and how we might reduce their frequency and impact.

Morphologic patterns of noncontrast-enhancing tumor in glioblastoma correlate with IDH1 mutation status and patient survival.

Glioblastomas with a substantial proportion of noncontrast-enhancing tumour (nCET) have a variety of imaging appearances. We aimed to determine whether glioblastomas demonstrating a substantial proportion (>33%) of nCET can be sub-classified by different morphologic pattern of nCET. We then assessed whether this improves the ability of MRI to predict isocitrate dehydrogenase-1 (IDH1) mutation status and whether this has prognostic significance independent of IDH1 mutation status. Pre-operative MRIs of patients with a new diagnosis of glioblastoma were reviewed. Tumours with >33% nCET were sub-classified by the dominant morphologic pattern of nCET: mass-like expansion, white matter dissemination, grey matter dissemination or a combination. IDH1 mutation status (by immunohistochemistry) and survival were compared for each pattern. 153 patients met the inclusion criteria, of whom 34 patients demonstrated >33% nCET. 10 patients had a significant mass-like component, either as the dominant pattern (n=4) or as part of a mixed pattern (n=6). The 10 patients with a significant mass-like component had longer survival than those without (median 387days, compared to 241days), though this was not statistically significant (p=0.242). Three patients had R132H-IDH1 mutations and >33% nCET, and all three had a mass-like component. Using the presence of a mass-like component of nCET for predicting IDH1 mutation status improved the positive predictive value, specificity and overall accuracy of MRI. Classification of nCET by morphologic pattern improves the ability of MRI to predict IDH1 mutations and may provide useful prognostic information.

Arytenoid cartilage movements are hypokinetic in Parkinson's disease: A quantitative dynamic computerised tomographic study.

BACKGROUND: Voice change is one of the earliest features of Parkinson's disease. However, quantitative studies of vocal fold dynamics which are needed to provide insight into disease biology, aid diagnosis, or track progression, are few. METHODS: We therefore quantified arytenoid cartilage movements and glottic area during repeated phonation in 15 patients with Parkinson's disease (symptom duration < 6 years) and 19 controls, with 320-slice computerised tomography (CT). We related these measures to perceptual voice evaluations and spirometry. We hypothesised that Parkinson's disease patients have a smaller inter-arytenoid distance, a preserved or larger glottic area because vocal cord bowing has previously been reported, less variability in loudness, more voice dysdiadochokinesis and breathiness and a shortened phonation time because of arytenoid hypokinesis relative to glottic area. RESULTS: Inter-arytenoid distance in Parkinson's disease patients was moderately smaller (Mdn = 0.106, IQR = 0.091-0.116) than in controls (Mdn = 0.132, IQR = 0.116-0.166) (W = 212, P = 0.015, r = -0.42), normalised for anatomical and other inter-subject variance, analysed with two-tailed Wilcoxon's rank sum test. This finding was confirmed in a linear mixed model analysis-Parkinson's disease significantly predicted a reduction in the dependent variable, inter-arytenoid distance (b = -0.87, SEb = 0.39, 95% CI [-1.66, -0.08], t(31) = -2.24, P = 0.032). There was no difference in glottic area. On perceptual voice evaluation, patients had more breathiness and dysdiadochokinesis, a shorter maximum phonation time, and less variability in loudness than controls. There was no difference in spirometry after adjustment for smoking history. CONCLUSIONS: As predicted, vocal fold adduction movements are reduced in Parkinson's disease on repeated phonation but glottic area is maintained. Some perceptual characteristics of Parkinsonian speech reflect these changes. We are the first to use 320-slice CT to study laryngeal motion. Our findings indicate how Parkinson's disease affects intrinsic laryngeal muscle position and excursion.

Reliability of noncontrast-enhancing tumor as a biomarker of IDH1 mutation status in glioblastoma.

Isocitrate dehydrogenase 1 (IDH1) mutations in gliomas have been associated with a frontal lobe location and a greater proportion of noncontrast-enhancing tumour (nCET). The purpose of our study was to validate the utility of MRI imaging features in predicting IDH1 mutations in glioblastomas. Pre-operative MRIs of new glioblastoma patients, consisting of at least FLAIR and T1-weighted post-contrast sequences, were reviewed by a neuroradiologist based primarily on the VASARI feature set. IDH1 mutation testing was performed on all patients using immunohistochemistry. 153 patients met the inclusion criteria, of whom five had IDH1 mutations (3.3%). A frontal lobe location had equivalent frequency in both the IDH1-mutated and IDH1-wildtype cohorts (p=1.000). Three (60%) of the IDH1-mutated tumours had >33% nCET, compared to 21% of IDH1-wildtype (p=0.073). 12 tumours had a frontal lobe epicentre and >33% nCET, all being IDH1-wildtype. All five IDH1-mutated tumours had either a frontal lobe epicentre or >33% nCET, but none had both these features. Our results question the strength of the association between frontal lobe glioblastomas with substantial nCET and IDH1 mutations, as these features are also relatively frequent in IDH1-wildtype tumours, which are much more common. MRI is thus more useful for ruling out an IDH1 mutation rather than strongly suggesting its presence: if a particular glioblastoma does not have a frontal lobe epicentre and has less than 33% nCET, it can be predicted to be IDH1-wildtype with a high degree of confidence.

The incidence and significance of multicentric noncontrast-enhancing lesions distant from a histologically-proven glioblastoma.

Improvements in imaging are increasing the detection of multiple lesions in the setting of glioblastoma. Occasionally distant non-enhancing lesions may be identified which have the appearances of a multicentric low-grade glioma. We aimed to determine the incidence, prognostic significance and diagnostic value of this appearance in new glioblastoma patients. Pre-operative MRIs of patients with a new diagnosis of glioblastoma were reviewed to identify multicentric non-enhancing lesions, defined as areas of FLAIR hyperintensity and mass effect, without post-contrast enhancement, separate from the histologically-proven glioblastoma. Patient survival was compared to glioblastoma patients without these appearances, and follow-up imaging was reviewed. Nine of 151 patients (6 %) had multicentric non-enhancing lesions. Their median survival of 183 days was significantly worse than the 278 days for patients without multicentric nonenhancing lesions (p = 0.025). Follow-up MRIs were performed in four patients. In one patient, there were several additional lesions, one of which developed evidence of necrosis within 22 days of presentation. In the other three patients, the multicentric lesions developed enhancement and evidence of necrosis within 1 year, and became confluent on FLAIR with the dominant lesion. The appearance of a multicentric non-enhancing lesion is an uncommon finding in glioblastoma, but a poor prognostic feature. These lesions progress faster than expected for a low-grade glioma and are thus likely to represent more advanced lesions than their appearances suggest. Confluence with the dominant lesion developing with time suggests that the tumor is more extensive than appreciated on imaging.

Multifocal and multicentric glioblastoma: Improved characterisation with FLAIR imaging and prognostic implications.

Glioblastoma usually presents on imaging as a single peripherally enhancing lesion, but multiple enhancing lesions can occur, termed multifocal if there is a connection between enhancing lesions, or multicentric when no communication is demonstrated. We aim to determine the incidence and prognostic implications of multifocal and multicentric glioblastoma in the era of modern MRI, focusing on the added benefit of T2-weighted fluid-attenuated inversion recovery (FLAIR) imaging. Patients with a new diagnosis of glioblastoma were identified. Preoperative MRI were reviewed to determine whether more than one distinct enhancing lesion was present, and whether there was communication between lesions. The findings were compared against survival data. More than one discrete contrast-enhancing lesion was present in 51 of the 151 patients (34%). Communication between lesions was identified in 47 of these, most commonly direct parenchymal spread (41 patients). The patients with multiple lesions had worse survival (median 176days, compared to 346days), but this difference was not statistically significant (p=0.253). These tumours more frequently involved deep structures (p<0.001) and the posterior fossa (p=0.045), both of which were associated with worse survival. The presence of multiple enhancing foci in glioblastoma is common, occurring in about one-third of patients, and the majority have multifocal disease. The FLAIR sequence is the crucial sequence for demonstrating a communication between lesions. The worse survival of these patients is, at least in large part related to more extensive tumour dissemination and more frequent involvement of key structures, rather than multiplicity per se.

Incidence and prognostic significance of non-enhancing cortical signal abnormality in glioblastoma.

INTRODUCTION: The presence of non-enhancing cortical signal abnormality is useful for differentiating between glioblastoma and metastatic disease, but its significance has not been studied. We aimed to determine the incidence and prognostic implications of non-enhancing cortical signal abnormality in glioblastomas. METHODS: Patients with a new diagnosis of glioblastoma between September 2007 and December 2010 were identified. Only patients with at least fluid-attenuated inversion recovery (FLAIR) and post-contrast T1-weighted sequences were included. Pre-operative MRIs were reviewed together by two readers to determine whether there was evidence of non-enhancing cortical signal abnormality, based primarily on the FLAIR sequence. The results were compared with patient survival using both univariate and multivariate analysis. RESULTS: One hundred fifty-one patients met the inclusion criteria. Seventy-seven patients (51%) had evidence of non-enhancing cortical signal abnormality. On both univariate and multivariate analysis, there was overall no significant difference in survival between patients with non-enhancing cortical signal abnormality and those without. Peripheral enhancing lesions (51 patients) were generally associated with the longest survival, but subgroup analysis suggested that non-enhancing signal abnormality was associated with worse survival in these patients (P = 0.004), conveying an intermediate prognosis. CONCLUSIONS: Non-enhancing cortical signal abnormality is a common feature of glioblastomas, occurring in about half of cases. It does not affect survival overall, but appears to be associated with worse survival in the setting of a peripherally located enhancing lesion. This has the potential to alter surgical management.

Large anterior temporal Virchow-Robin spaces: unique MR imaging features.

INTRODUCTION: Large Virchow-Robin (VR) spaces may mimic cystic tumor. The anterior temporal subcortical white matter is a recently described preferential location, with only 18 reported cases. Our aim was to identify unique MR features that could increase prospective diagnostic confidence. METHODS: Thirty-nine cases were identified between November 2003 and February 2014. Demographic, clinical data and the initial radiological report were retrospectively reviewed. Two neuroradiologists reviewed all MR imaging; a neuropathologist reviewed histological data. RESULTS: Median age was 58 years (range 24-86 years); the majority (69 %) was female. There were no clinical symptoms that could be directly referable to the lesion. Two thirds were considered to be VR spaces on the initial radiological report. Mean maximal size was 9 mm (range 5-17 mm); majority (79 %) had perilesional T2 or fluid-attenuated inversion recovery (FLAIR) hyperintensity. The following were identified as potential unique MR features: focal cortical distortion by an adjacent branch of the middle cerebral artery (92 %), smaller adjacent VR spaces (26 %), and a contiguous cerebrospinal fluid (CSF) intensity tract (21 %). Surgery was performed in three asymptomatic patients; histopathology confirmed VR spaces. Unique MR features were retrospectively identified in all three patients. CONCLUSION: Large anterior temporal lobe VR spaces commonly demonstrate perilesional T2 or FLAIR signal and can be misdiagnosed as cystic tumor. Potential unique MR features that could increase prospective diagnostic confidence include focal cortical distortion by an adjacent branch of the middle cerebral artery, smaller adjacent VR spaces, and a contiguous CSF intensity tract.

An endless line on the chest radiograph.

A 40-year-old male patient had his right femoral vein catheterised following admission with altered conscious state from polypharmacy overdose. The procedure was documented as successful and uncomplicated. A postprocedural chest radiograph demonstrated a linear metallic opacity projecting over the superior vena cava and inferior vena cava (SVC and IVC, respectively), with superior and inferior ends not visualised. This did not alert the attending radiologist and intensivist who might have assumed such a metallic object to be external to the patient. Only the central line was removed prior to patient discharge 2 days later. The patient died 2 years later from unrelated streptococcal pneumonia complicated by septicaemia and multiorgan failure. The postmortem discovered a central venous guidewire in the IVC across the right atrium into SVC.

Retroperitoneal sarcomas: a review of disease spectrum, radiological features, characterisation and management.

Retroperitoneal sarcomas are a rare disease. The overall 5-year survival rate for these lesions remains low, and surgical management offers the only option for effective treatment and potential for cure. Radiotherapy is increasingly being employed in addition to standard surgical treatment. Improvements in cross-sectional imaging have also facilitated better characterisation of lesions, preoperative planning and long-term follow-up. This article reviews the current literature and documents the various types of retroperitoneal sarcomas with a particular approach to their imaging features. We also highlight the pathology, diagnostic methods and most current management of these tumours.

Hippocampal calcification prevalence at CT: a retrospective review.

PURPOSE: To determine the prevalence of intrahippocampal calcification at brain computed tomography (CT), evaluate any association with calcification involving the intracranial arteries or lentiform nuclei, and assess the clinical importance of intrahippocampal calcification. MATERIALS AND METHODS: Study approval was obtained by the Southern Health Human Research Ethics Committee, which waived the requirement for informed consent because of the retrospective nature of the study. The presence of intrahippocampal calcification was assessed by four readers through retrospective review of 300 randomly selected nonenhanced brain CT scans. In addition, the presence of calcification involving the intracranial arteries and lentiform nuclei was assessed, and the clinical histories were reviewed in those patients with intrahippocampal calcifications and a matched control cohort without intrahippocampal calcification. Differences in proportion of patients with intrahippocampal calcifications across different age groups were assessed by using χ2 analysis. Interrater agreement and intrarater agreement were assessed by using κ analysis. RESULTS: Intrahippocampal calcification was demonstrated in 47 (15.7%) of 300 patients, and 47 (21.7%) of 217 patients older than 50 years of age. Its prevalence increased with age (P=.008). All patients with intrahippocampal calcification and the control cohort demonstrated calcification involving the intracranial arteries. Eleven (23.4%) of 47 patients with intrahippocampal calcification had calcification within the lentiform nuclei compared with 14 (29.8%) of 47 in the control cohort (P=.67). The anatomic distribution of intrahippocampal calcification was similar to that described in vascular fibrosis and calcification. CONCLUSION: The prevalence of intrahippocampal calcification appears to increase with age and is a relatively common finding in patients older than 50 years. It has a similar anatomic distribution to microscopic vascular fibrosis and calcification and likely reflects its latter stages.

Diagnostic yield of computed tomography of the brain in first episode psychosis.

INTRODUCTION: Brain computed tomography (CT) is inconsistently recommended worldwide in the investigative algorithm of patients presenting with first episode psychosis (FEP). The objective of this study is to investigate the clinical efficacy of brain CT in patients presenting with FEP without neurological signs in a major metropolitan teaching hospital. METHODS: The CT brain scan reports of 237 consecutive patients, for which the imaging requests or reports provided a history of FEP but no focal neurological signs, were retrospectively identified within a 6-year period in a 750-bed tertiary referral teaching hospital using the radiology information system text-search function (170 male, 67 female; mean age, 28.3 years). All reports were authored or approved by consultant radiologist. They were reviewed for the presence of any lesion that could cause psychosis and hence alter clinical management. Minor neuroradiological abnormalities were also noted. Hospital Ethics Committee registration and approval were obtained and patient informed consent was not required. RESULTS: No focal brain lesion potentially responsible for the psychosis or focal lesion requiring surgical intervention was identified in any patient. Findings unable to be directly linked to the psychosis such as evidence of small vessel ischaemic disease, arachnoid cysts, cerebral atrophy, and normal variants were present in 17.6% of patients (45 of 237 studies), none of which led to an alteration of clinical management. CONCLUSION: The results of this study postulate that brain CT should not be universally performed in the initial assessment of patients with first episode psychosis without neurological signs.

Susceptibility weighted imaging: a pictorial review.

Susceptibility weighted imaging (SWI) is a valuable technique in the evaluation of a wide variety of intracranial pathologies. SWI is a gradient echo sequence utilising both phase and magnitude data to achieve exquisite sensitivity to tissue magnetic susceptibility effects. Normal SWI appearances and common artefacts are illustrated. Examples of SWI in common intracranial pathologies such as subarachnoid, intraventricular and intraparenchymal haemorrhage, intra-axial and extra-axial tumours, pyogenic and non-pyogenic infections, trauma, neurodegenerative diseases and vascular disease including aneurysms, vascular malformations are illustrated and discussed. This pictorial essay will enable radiologists to recognise the normal, artefactual and common intracranial pathological appearances of SWI.

Peri-aortofemoral prosthesis urinoma: diagnosis by Tc-99m MAG3 SPECT/CT and differentiation from simultaneous hepatobiliary excretion.

A 75-year-old woman developed renal failure 1 week after elective aortobifemoral bypass surgery. Postoperative computed tomography showed right hydronephrosis. Tc-99m mercaptoacetyltriglycerine (MAG3) scintigraphy was performed to exclude renal obstruction or acute tubular necrosis. Planar MAG3 images demonstrated right hydronephrosis and unusual accumulation of tracer between the kidneys and the right upper quadrant of abdomen, with new areas of activity in the right lower quadrant on delayed images. SPECT/CT demonstrated MAG3 activity within fluid collections adjacent to the aorta and right iliac/inguinal arteries, consistent with a urine leak. The right upper quadrant activity represented MAG3 accumulation within the gallbladder.

What is the clinical and ethical importance of incidental abnormalities found by knee MRI?

INTRODUCTION: Magnetic resonance imaging (MRI) is increasingly used to examine joints for research purposes. It may detect both suspected and unsuspected abnormalities. This raises both clinical and ethical issues, especially when incidental abnormalities are detected. The prevalence of incidental, potentially clinically significant abnormalities identified by MRI and their clinical significance in a population undergoing knee MRI in research studies are unknown. METHODS: We examined the prevalence of such lesions in healthy asymptomatic adults and those with symptomatic knee osteoarthritis (OA) undergoing knee MRI with limited sequences for the purpose of research. The MRI findings in 601 asymptomatic subjects and 132 with knee OA who underwent at least one limited knee MRI scan for cartilage volume measurement were examined by an MRI radiologist for the presence of potentially clinically significant abnormalities. RESULTS: These were present in 2.3% of healthy and 2.3% of OA subjects. All required further investigation to exclude non-benign disease, including four with bone marrow expansion (0.7%), requiring further investigation and management. A single potentially life-threatening lesion, a myeloma lesion, was identified in a subject with symptomatic knee OA on their second MRI scan in a longitudinal study. CONCLUSION: As musculoskeletal MRI is increasingly used clinically and for research purposes, the potential for detecting unsuspected abnormalities that require further investigation should be recognized. Incorporating a system to detect these, to characterize unexpected findings, and to facilitate appropriate medical follow-up when designing studies using this technology should be considered ethical research practice.

MRI features of bone marrow necrosis.

OBJECTIVE: The purpose of this study was to illustrate and review the MRI appearance of histologically proven cases of bone marrow necrosis (BMN) and to review the literature on this clinicopathologic entity with emphasis on its distinction from avascular necrosis (AVN) of bone. CONCLUSION: BMN is a rare clinicopathologic entity separate from AVN and has a distinctive MRI appearance. As MRI comes to play an increasingly important role in the evaluation of bone marrow disease, BMN is likely to be more frequently encountered. Awareness of BMN and its MRI appearance and appreciation of the frequent association between BMN and underlying malignancy may assist in the early diagnosis of BMN and initiate an intensive search for occult malignancy.