Imaging of rare medullary adrenal tumours in adults.

Although adrenal medullary tumours are rare, they have important clinical implications. They form a heterogeneous group of tumours, ranging from benign, non-secretory, incidental masses to hormonally active tumours presenting acutely, or malignant tumours with disseminated disease and a poor prognosis. Increasingly, benign masses are incidentally detected due to the widespread use of imaging and routine medical check-ups. This review aims to illustrate the multimodality imaging appearances of rare adrenal medullary tumours, excluding the more common phaeochromocytomas, with clues to the diagnosis and to summarise relevant epidemiological and clinical data. Careful correlation of clinical presentation, hormone profile, and various imaging techniques narrow the differential diagnosis. Image-guided percutaneous adrenal biopsy can provide a definitive diagnosis, allowing for conservative management in selected cases. A close collaboration between the radiologist, endocrinologist, and surgeon is of the utmost importance in the management of these tumours.

Diffusion-weighted and multiphase contrast-enhanced MRI as surrogate markers of response to neoadjuvant sunitinib in metastatic renal cell carcinoma.

BACKGROUND: Current imaging criteria for categorising disease response in metastatic renal cell carcinoma (mRCC) correlate poorly with overall survival (OS) in patients on anti-angiogenic therapies. We prospectively assess diffusion-weighted and multiphase contrast-enhanced (MCE) MR imaging (MRI) as markers of outcome. METHODS: Treatment-naive mRCC patients on a phase II trial using sunitinib completed an MRI substudy. Whole-tumour apparent diffusion coefficient (ADC) maps and histograms were generated, and mean ADC and AUC(low) (proportion of the tumour with ADC values lying below the 25th percentile of the ADC histogram) recorded. On MCE-MRI, regions of interest were drawn around the most avidly enhancing components to analyse enhancement parameters. Baseline (n=26) and treatment-related changes in surviving patients (n=20) were correlated with OS. Imaged metastases were also analysed. RESULTS: Forty-seven per cent of the patients showed significant changes in whole-tumour mean ADC following therapy, but there was no correlation with outcome. Patients with a high baseline AUC(low) and greater-than-median AUC(low) increase had reduced OS (HR=3.67 (95% confidence interval (CI)=1.23-10.9), P=0.012 and HR=3.72 (95% CI=0.98-14.21), P=0.038, respectively). There was no correlation between MCE-MRI parameters and OS. Twenty-eight metastases were analysed and showed positive correlation with primary tumour mean ADC for individual patients (r=0.607; P<0.001). CONCLUSION: Primary RCC ADC histogram analysis shows dynamic changes with sunitinib. Patients in whom the tumour ADC histogram demonstrated high baseline AUC(low) or a greater-than-median increase in AUC(low) with treatment had reduced OS.

The prevalence of incidentally detected adrenal enlargement on CT.

AIM: To assess the prevalence and the department's detection rate of adrenocortical hyperplasia. MATERIALS AND METHODS: All computed tomography (CT) examinations of the adrenal glands between February and April 2011 were reviewed. The study excluded patients with known underlying cancer, abdominal trauma, or endocrine disease. The adrenal gland was deemed enlarged if its body was greater than 10 mm diameter, or a limb greater than 5 mm. RESULTS: There were a total of 564 eligible CT studies during this period. A total of 64 cases of incidental adrenal enlargement were found giving a prevalence of 11.3%. Only nine cases were reported in the contemporaneous CT report. CONCLUSION: The results of the present study show that incidental adrenal enlargement has a significant prevalence. It is often dismissed during reporting, and awareness needs to be raised in the radiological community. Equally, the clinical and biochemical significance needs to be assessed with endocrine correlation.

A prospective evaluation of VEGF-targeted treatment cessation in metastatic clear cell renal cancer.

BACKGROUND: Vascular endothelial growth factor (VEGF)-targeted therapy is administered continuously until progression in metastatic clear cell renal cancer (mRCC). The role of intermittent therapy is under investigation. Preclinical data raise concerns about this approach. MATERIALS AND METHODS: This study combined the data from three similar phase II studies investigating VEGF-targeted therapy prior to planned nephrectomy for untreated mRCC (European Union Drug Regulating Authorities Clinical Trials 2006-004511-21, 2006-006491-38 and 2009-016675-29). The significance of progression during the planned treatment break (median 4.3 weeks) was assessed. RESULTS: Sixty-two patients had a structured treatment interruption for nephrectomy after achieving clinical benefit from treatment and restarted therapy. Twenty-three of these patients (37%) progressed (Response Evaluation Criteria In Solid Tumors v1.1) on the first scan after the treatment break. Subsequent stabilisation of disease occurred in 16 of the 23 (70%) progressing patients when the same VEGF tyrosine kinase inhibitor (TKI) was reintroduced. Baseline characteristics, such as the Memorial Sloan Kettering Cancer Centre prognostic score, did not predispose to the development of this progression. Progression during the treatment break was associated with an increased risk of death on multivariate analysis {hazard ratio (HR) 5.56; [95% confidence interval 2.29-13.5], P < 0.01}. Sequential fluorodeoxyglucose positron emission tomography showed a rebound in metabolic activity during the treatment break. CONCLUSIONS: Progression during planned VEGF TKI treatment interruptions is frequent and associated with a poor prognosis. Treatment cessation should be pursued with caution.

Prostate MRI: who, when, and how? Report from a UK consensus meeting.

The current pathway for men suspected of having prostate cancer [transrectal biopsy, followed in some cases by magnetic resonance imaging (MRI) for staging] results in over-diagnosis of insignificant tumours, and systematically misses disease in the anterior prostate. Multiparametric MRI has the potential to change this pathway, and if performed before biopsy, might enable the exclusion of significant disease in some men without biopsy, targeted biopsy in others, and improvements in the performance of active surveillance. For the potential benefits to be realized, the setting of standards is vital. This article summarizes the outcome of a meeting of UK radiologists, at which a consensus was achieved on (1) the indications for MRI, (2) the conduct of the scan, (3) a method and template for reporting, and (4) minimum standards for radiologists.

MRI appearances of borderline ovarian tumours.

This review was performed to describe the range of magnetic resonance imaging (MRI) appearances of borderline ovarian tumours. The MRI findings in 26 patients with 31 borderline ovarian tumours (mean age: 40.1 years, range: 14-85 years) were retrospectively reviewed. For each tumour, site, size, MRI characteristics, and enhancement following gadolinium administration were recorded. There were 20 serous and 11 mucinous borderline ovarian subtypes. Nine of 26 patients demonstrated bilateral disease on MRI; synchronous contralateral ovarian disease included three benign, five serous borderline, and one serous invasive tumour. A history of a metachronous mucinous borderline tumour was identified in one patient. MRI appearances were classified into four morphological categories: group 1 (6/31, 19%), unilocular cysts; group 2 (6/31, 19%), minimally septate cysts with papillary projections; group 3 (14/31, 45%), markedly septate lesions with plaque-like excrescences; and group 4 (5/31, 16%), predominantly solid with exophytic papillary projections, all of serous subtype. There was a significant difference in mean volume between serous (841.5 cm(3)) and mucinous (6358.2 cm(3)) subtypes (p=0.009). All tumours demonstrated at least one MRI feature suggestive of malignancy. The present review demonstrates the variable MRI appearances of borderline ovarian tumours along with imaging features suggestive of tumour subtype. In patients in whom the clinical features are suggestive of a borderline ovarian tumour (young age and normal or minimally elevated CA125), the ability to predict a borderline disease using morphological features observed on MRI would be extremely helpful in surgical planning, with the potential to offer fertility or ovary-preserving surgery. Future studies are required to further this aim.

Computed tomography features of recurrent ovarian carcinoma according to time to relapse.

BACKGROUND: Although the sites of recurrent ovarian cancer are individually described in the literature, patterns of recurrent disease are poorly understood. PURPOSE: To describe CT patterns of disease in recurrent ovarian cancer. To emphasize common patterns, recognise subtle and unusual sites of recurrent disease. MATERIALS AND METHODS: We identified patients between 1981-2004 presenting with clinical recurrence or elevated CA 125 after complete primary clinical and radiological response. CT imaging at primary diagnosis, during and after treatment and at recurrence was retrospectively reviewed. Site, distribution, stage of disease and time to relapse was recorded. RESULTS: 400 patients were treated for ovarian cancer. 214(54%) achieved complete primary response. 161(75%) relapsed with complete imaging available in 67 patients. Of the 67 patients, 14 (21%) recurred within 1 year, 44 (66%) relapsed between 1-5 years. Therefore 87% of relapses occurred within 5 years following primary treatment. Five (8%) relapsed between 5-10 years and 4 (6%) relapsed after 10 years. Commonest pattern of relapse was pelvic mass in 35 (48%) patients, solitary in 15 (22%). 27 (45%) relapsed with peritoneal thickening, 27 (45%) had small or large bowel serosal disease, 22 (33%) had enlarged lymphadenopathy, 6 as sole manifestation of recurrence, 20 (30%) presented with unusual sites of recurrence: 6 splenic, 10 hepatic, 2 biliary, 3 brain and 2 muscle. CONCLUSION: Our study is the first to describe common patterns of recurrence in ovarian cancer. Most frequent site is pelvis, followed by peritoneum, serosal surfaces and nodal disease. 30% presented with disease at 'unusual' sites.

Clinical outcomes following unilateral adrenalectomy in patients with primary aldosteronism.

BACKGROUND: In approximately half of cases of primary aldosteronism (PA), the cause is a surgically-resectable unilateral aldosterone-producing adrenal adenoma. However, long-term data on surgical outcomes are sparse. AIM: We report on clinical outcomes post-adrenalectomy in a cohort of patients with PA who underwent surgery. DESIGN: Retrospective review of patients treated for PA in a single UK tertiary centre. METHODS: Of 120 consecutive patients investigated for PA, 52 (30 male, median age 54, range 30-74) underwent unilateral complete adrenalectomy. Blood pressure, number of antihypertensive medications, and serum potassium were recorded before adrenalectomy, and after a median follow-up period of 50 months (range 7-115). Recumbent renin and aldosterone were measured, in the absence of interfering antihypertensive medication, ≥3months after surgery, to determine if PA had been biochemically cured. RESULTS: Overall, blood pressure improved from a median (range) 160/95 mmHg (120/80-250/150) pre-operatively to 130/80 mmHg (110/70-160/93), P < 0.0001. 24/52 patients (46.2%) had cured hypertension, with a normal blood pressure post-operatively on no medication. 26/52 (50%) had improved hypertension. 2/52 patients (3.8%) showed no improvement in blood pressure post-operatively. Median (range) serum potassium level increased from 3.2 (2.3-4.7) mmol/l pre-operatively to 4.4 mmol/l (3.3-5.3) post-operatively, P < 0.0001). Median (range) number of antihypertensive medications used fell from 3 (0-6) pre- to 1 post-operatively (range 0-4), P < 0.0001. CONCLUSIONS: Unilateral adrenalectomy provides excellent long-term improvements in blood pressure control, polypharmacy and hypokalaemia in patients with lateralizing PA. These data may help inform discussions with patients contemplating surgery.

Imaging evaluation of the non-functioning indeterminate adrenal mass.

With the increasing use of abdominal cross-sectional imaging in the investigation of patient symptoms and in cancer staging, incidental adrenal masses are frequently detected. The most common clinical question is whether these masses are benign or malignant. Benign adrenal masses such as myelolipomas, lipid-rich adenomas, adrenal cysts and adrenal haemorrhage have pathognomonic imaging findings. However, there remains a significant overlap between the imaging appearances of some lipid-poor adenomas and malignant lesions, particularly metastases and small adrenal carcinomas. Our review looks at the recent advances in computed tomography, magnetic resonance imaging and positron emission tomography, which can be used to assist in the distinction between benign adenomas and malignant lesions of the adrenal gland.

Pure aldosterone-secreting adrenocortical carcinoma in a patient with refractory primary hyperaldosteronism.

UNLABELLED: We describe a young male patient with longstanding hypertension, who was diagnosed with primary hyperaldosteronism and treated by an attempted retroperitoneoscopic total unilateral adrenalectomy for a left-sided presumed aldosterone-secreting adenoma. Imaging had shown an unremarkable focal adrenal lesion with normal contralateral adrenal morphology, and histology of the resected specimen showed no adverse features. Post-operatively, his blood pressure and serum aldosterone levels fell to the normal range, but 9 months later, his hypertension recurred, primary aldosteronism was again confirmed and he was referred to our centre. Repeat imaging demonstrated an irregular left-sided adrenal lesion with normal contralateral gland appearances. Adrenal venous sampling was performed, which supported unilateral (left-sided) aldosterone hypersecretion. Redo surgery via a laparoscopically assisted transperitoneal approach was performed and multiple nodules were noted extending into the retroperitoneum. It was thought unlikely that complete resection had been achieved. His blood pressure returned to normal post-operatively, although hypokalaemia persisted. Histological examination, from this second operation, showed features of an adrenocortical carcinoma (ACC; including increased mitoses and invasion of fat) that was assessed as malignant using the scoring systems of Weiss and Aubert. Biochemical hyperaldosteronism persisted post-operatively, and detailed urine steroid profiling showed no evidence of adrenal steroid precursors or other mineralocorticoid production. He received flank radiotherapy to the left adrenal bed and continues to receive adjunctive mitotane therapy for a diagnosis of a pure aldosterone-secreting ACC. LEARNING POINTS: Pure aldosterone-secreting ACCs are exceptionally uncommon, but should be considered in the differential diagnosis of patients presenting with primary aldosteronism.Aldosterone-producing ACCs may not necessarily show typical radiological features consistent with malignancy.Patients who undergo surgical treatment for primary aldosteronism should have follow-up measurements of blood pressure to monitor for disease recurrence, even if post-operative normotension is thought to indicate a surgical 'cure'.Owing to the rarity of such conditions, a greater understanding of their natural history is likely to come from wider cooperation with, and contribution to, large multi-centre outcomes databases.

Bilateral pituitary adenomas occurring with multiple endocrine neoplasia type one.

We report a case of synchronous bilateral pituitary adenomas in a patient with multiple endocrine neoplasia type one (MEN1). The patient was previously known to have a pancreatic gastrinoma and had first-degree relatives with MEN1. Both adenomas were concurrently revealed by high-resolution MR imaging of the pituitary gland as part of the investigation of the patient's severe, persistent headaches and elevated serum prolactin level.

Use of an internal reference in semi-quantitative dynamic contrast-enhanced MRI (DCE MRI) of indeterminate adnexal masses.

OBJECTIVE: Semi-quantitative dynamic contrast-enhanced MRI (DCE MRI) has proven useful in discriminating benign from borderline/malignant adnexal lesions. Our aim was to assess if the use of a lesion-to-internal-reference ratio improved the performance in characterizing adnexal masses and which internal reference was suitable. METHODS: Semi-quantitative DCE MRI images of 71 indeterminate adnexal lesions were retrospectively reviewed. A region of interest was manually drawn onto the enhancing solid component, psoas muscle and normal outer myometrium. The DCE parameters were evaluated, and the lesion-to-internal-reference ratios were calculated. RESULTS: When the wash in rate of the lesion was higher than that of the myometrium, 97% specificity and 12% sensitivity for borderline/malignancy was reached. When the maximum relative enhancement and maximum absolute enhancement (SImax) of the lesion was less than those of the psoas, 100% specificity for benignity was achieved. The highest area under the curve (AUC) (0.807) was achieved using a SImax lesion-myometrium ratio. A slightly lower AUC (0.799) was achieved using a SImax lesion-psoas ratio, but the psoas muscle was more frequently measurable in the same slice as the lesion ROI. Although the AUC was higher, when using ratios instead of individual DCE values, this was not significantly different. CONCLUSION: DCE MRI has added diagnostic value in the assessment of adnexal lesions, and the use of internal references enables high specificity for malignancy and benignity. Lesion-internal-reference ratios have no added diagnostic value over DCE values alone. ADVANCES IN KNOWLEDGE: Both psoas muscle and myometrium are suitable internal references in the DCE assessment of adnexal lesions enabling high specificity for malignancy and benignity.

Uterine carcinosarcoma in a patient with didelphys uterus.

Background. Didelphys uterus is a noncommon finding in women. Till now, few cases with benign mesenchymal tumors in patients with didelphys uterus are described. We present a case of a patient with carcinosarcoma arising in a didelphys uterus. Case. A 73-year-old patient presented with profuse watery postmenopausal bleeding. On examination under anesthesia, left and right cervixes were identified. Tumor extended from the left cervix into the lower third of the vagina and was adherent to the right vaginal sidewall. There was no evidence of parametrial extension. Tissue was sent for biopsy which revealed high-grade uterine carcinosarcoma. Two uterine fundi and two vaginas in keeping with uterine didelphys were identified on imaging. The patient underwent vaginal excision of the protruding tumor measuring 8 × 6 cm with harmonic scalpel followed by total abdominal hysterectomy and bilateral salpingooophorectomy. Although a number of pelvic and paraaortic lymph nodes were also identified on imaging, she was not planned for lymphadenectomy after MDT (multidisciplinary team) discussion because of her comorbidities. The final histology confirmed the diagnosis. Conclusion. According to our knowledge, this is the second case of carcinosarcoma arising in didelphys uterus in the world literature.

Diffusion-weighted imaging in the assessment of tumour grade in endometrial cancer.

OBJECTIVE: Endometrial cancer is the most common gynaecological malignancy in developed countries. Histological grade and subtype are important prognostic factors obtained by pipelle biopsy. However, pipelle biopsy "samples" tissue and a high-grade component that requires more aggressive treatment may be missed. The purpose of the study was to assess the use of diffusion-weighted MRI (DW-MRI) in the assessment of tumour grade in endometrial lesions. METHOD: 42 endometrial lesions including 23 endometrial cancers and 19 benign lesions were evaluated with DW-MRI (1.5T with multiple b-values between 0 and 750 s mm(-2)). Visual evaluation and the calculation of mean and minimum apparent diffusion coefficient (ADC) value were performed and correlated with histology. RESULTS: The mean and minimum ADC values for each histological grade were 1.02 ± 0.29×10(-3) mm(2) s(-1) and 0.74 ± 0.24×10(-3) mm(2) s(-1) (grade 1), 0.88 ± 0.39×10(-3) mm(2) s(-1) and 0.64 ± 0.36×10(-3) mm(2) s(-1) (grade 2), and 0.94 ± 0.32×10(-3) mm(2) s(-1) and 0.72 ± 0.36×10(-3) mm(2) s(-1) (grade 3), respectively. There was no statistically significant difference between tumour grades. However, the mean ADC value for endometrial carcinoma was 0.97 ± 0.31, which was significantly lower (p<0.0001) than that of benign endometrial pathology (1.50 ± 0.14). Applying a cut-off mean ADC value of less than 1.28 × 10(-3) mm(2) s(-1)we obtained a sensitivity, specificity, positive predictive value and negative predictive value for malignancy of 87%, 100%, 100% and 85.7%, respectively. CONCLUSION: Tumour mean and minimum ADC values are not useful in differentiating histological tumour grade in endometrial carcinoma. However, mean ADC measurement can provide useful information in differentiating benign from malignant endometrial lesions. This information could be clinically relevant in those patients where pre-operative endometrial sampling is not possible.

Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors

By definition, an adrenal incidentaloma is an asymptomatic adrenal mass detected on imaging not performed for suspected adrenal disease. In most cases, adrenal incidentalomas are nonfunctioning adrenocortical adenomas, but may also represent conditions requiring therapeutic intervention (e.g. adrenocortical carcinoma, pheochromocytoma, hormone-producing adenoma or metastasis). The purpose of this guideline is to provide clinicians with best possible evidence-based recommendations for clinical management of patients with adrenal incidentalomas based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. We predefined four main clinical questions crucial for the management of adrenal incidentaloma patients, addressing these four with systematic literature searches: (A) How to assess risk of malignancy?; (B) How to define and manage low-level autonomous cortisol secretion, formerly called 'subclinical' Cushing's syndrome?; (C) Who should have surgical treatment and how should it be performed?; (D) What follow-up is indicated if the adrenal incidentaloma is not surgically removed? SELECTED RECOMMENDATIONS: (i) At the time of initial detection of an adrenal mass establishing whether the mass is benign or malignant is an important aim to avoid cumbersome and expensive follow-up imaging in those with benign disease. (ii) To exclude cortisol excess, a 1mg overnight dexamethasone suppression test should be performed (applying a cut-off value of serum cortisol ≤50nmol/L (1.8µg/dL)). (iii) For patients without clinical signs of overt Cushing's syndrome but serum cortisol levels post 1mg dexamethasone >138nmol/L (>5µg/dL), we propose the term 'autonomous cortisol secretion'. (iv) All patients with '(possible) autonomous cortisol' secretion should be screened for hypertension and type 2 diabetes mellitus, to ensure these are appropriately treated. (v) Surgical treatment should be considered in an individualized approach in patients with 'autonomous cortisol secretion' who also have comorbidities that are potentially related to cortisol excess. (vi) In principle, the appropriateness of surgical intervention should be guided by the likelihood of malignancy, the presence and degree of hormone excess, age, general health and patient preference. (vii) Surgery is not usually indicated in patients with an asymptomatic, nonfunctioning unilateral adrenal mass and obvious benign features on imaging studies. We provide guidance on which surgical approach should be considered for adrenal masses with radiological findings suspicious of malignancy. Furthermore, we offer recommendations for the follow-up of patients with adrenal incidentaloma who do not undergo adrenal surgery, for those with bilateral incidentalomas, for patients with extra-adrenal malignancy and adrenal masses and for young and elderly patients with adrenal incidentalomas.

The indeterminate adrenal mass in patients with cancer.

With the increasing use of abdominal cross-sectional imaging, incidental adrenal masses are frequently detected. The commonest clinical question is whether these are benign adenomas or malignant primary or secondary masses. The nature of incidentally detected adrenal masses can be determined with a high degree of accuracy using computed tomography (CT) and magnetic resonance imaging (MRI) as benign adrenal masses such as myelolipomas, lipid-rich adenomas, adrenal cysts and adrenal haemorrhage which have pathognomonic imaging findings. However, there remains a significant overlap between the imaging features of some lipid-poor adenomas and malignant lesions. We review the recent advances in CT, MRI and positron emission tomography (PET) which can be used to distinguish between benign adenomas and malignant lesions of the adrenal gland.

The performance of magnetic resonance imaging in early cervical carcinoma: a long-term experience.

We report our long-term experience of performance of magnetic resonance imaging (MRI) in localizing cervical tumor, assessing tumor size, staging, and lymph node infiltration in patients with early cervical cancer. MRI of 150 patients with early carcinoma between 1995-2005 was retrospectively reviewed. Tumor location, size, tumor distance from internal os, parametrial invasion, myometrial invasion, lymph node size, and location were documented. All patients underwent surgery, pelvic lymphadenectomy, and histological correlation of MRI findings. For staging, MRI and histopathology had kappa value of 0.89. For parametrial invasion, MRI had specificity, negative predictive value (NPV) of 97% and 100%, respectively. For tumor size, MRI and histology had mean difference of -0.9 mm with 95% limits of agreement between -12.6 to +13 mm. In tumors greater than 10 mm, mean difference was 0.3 mm and limits of agreement were -7.5 to +7.9 mm. For internal os involvement sensitivity, specificity, positive predictive value (PPV) and NPV were 90%, 98%, 86%, 98%. respectively. For myometrial invasion sensitivity, specificity, NPV, and PPV were 100%, 99%, 88%, 100%, respectively. Incidence of nodal metastases was 2.9%. On a per-patient basis, sensitivity, specificity for nodal involvement was 37% and 92% and on node-by-node basis, sensitivity and specificity of MRI was 27% and 99%, respectively. Our study confirms MRI is highly accurate in localizing cervical tumor, excluding parametrial invasion, confirming myometrial and internal os invasion. MRI is therefore useful in selecting patients for surgery and mandatory in patients for fertility-preserving surgery. Using accepted size criteria for nodal involvement, MRI is insensitive and currently will not avoid need for pelvic lymphadenectomy.

Differential diagnosis of adnexal masses: risk of malignancy index, ultrasonography, magnetic resonance imaging, and radioimmunoscintigraphy.

A risk of malignancy index (RMI), based on menopausal status, ultrasound (US) findings, and serum CA125, has previously been described and validated in the primary evaluation of women with adnexal masses and is widely used in selective referral of women from local cancer units to specialized cancer centers. Additional imaging modalities could be useful for further characterization of adnexal masses in this group of women. A prospective cohort study was conducted of 196 women with an adnexal mass referred to a teaching hospital for diagnosis and management. Follow-up data was obtained for 180 women; 119 women had benign and 61 women malignant adnexal masses. The sensitivity and specificity of specialist US, magnetic resonance imaging (MRI), radioimmunoscintigraphy (RS), and the RMI were determined. We identified a subgroup of women with RMI values of 25-1000 where the value of further specialist imaging was evaluated. Sensitivity and specificity for specialist US were 100% and 57%, for MRI 92% and 86%, and for RS 76% and 87%, respectively. Analysis of 123 patients managed sequentially, using RMI cutoff values of > or =25 and <1000 and then US and MRI provided a sensitivity of 94% and a specificity of 90%. Using this RMI cutoff followed by specialist US and MRI, as opposed to the traditional RMI cutoff value of 250, can increase the proportion of patients with cancer appropriately referred in to a cancer center, with no change in the proportion of patients with benign disease being managed in a local unit.