A prospective evaluation of postural stimulation testing, computed tomography and adrenal vein sampling in the differential diagnosis of primary aldosteronism.

CONTEXT: In primary aldosteronism (PA), discriminating unilateral from bilateral disease is crucial because adrenalectomy is frequently curative in the former case but rarely helps in the latter. Various series have reported the utility of postural stimulation testing (PST), cross-sectional imaging and adrenal vein sampling (AVS) in the assessment of PA, but most of these studies were retrospective. OBJECTIVE: To prospectively determine the diagnostic utility of PST, AVS and computed tomography (CT) using a radiological scoring system in the assessment of PA in a tertiary centre, as well as to document the incidence of autonomous cortisol cosecretion. DESIGN AND SETTING: Fifty consecutive patients with PA underwent PST, CT, AVS and a low-dose dexamethasone suppression test with measurement of serum cortisol at 48 h. For patients who underwent surgery, histological confirmation, and a normal postoperative serum aldosterone concentration and plasma renin activity were taken as evidence for unilateral disease. For other patients, results from successful adrenal vein sampling were the diagnostic evidence against which CT and PST were assessed. RESULTS: Postural stimulation testing had a sensitivity and specificity of 44-56% and 71-75%, respectively. CT had an overall sensitivity and specificity of 77% and 80%, respectively, rising to 100% sensitivity and specificity if there was a single, discrete macronodule with an unequivocally normal contralateral gland. Evidence of cosecretion of cortisol occurred in 14% of patients. CONCLUSIONS: Preliminary experience is presented of an objective radiological scoring system for selecting patients with PA for AVS. PST provides little, if any, useful additional information. A significant minority of patients with PA exhibit evidence of cortisol cosecretion, which may have implications for perioperative management.

CT, MRI and PET imaging in peritoneal malignancy.

Imaging plays a vital role in the evaluation of patients with suspected or proven peritoneal malignancy. Nevertheless, despite significant advances in imaging technology and protocols, assessment of peritoneal pathology remains challenging. The combination of complex peritoneal anatomy, an extensive surface area that may host tumour deposits and the considerable overlap of imaging appearances of various peritoneal diseases often makes interpretation difficult. Contrast-enhanced multidetector computed tomography (MDCT) remains the most versatile tool in the imaging of peritoneal malignancy. However, conventional and emerging magnetic resonance imaging (MRI) and positron emission tomography (PET)/CT techniques offer significant advantages over MDCT in detection and surveillance. This article reviews established and new techniques in CT, MRI and PET imaging in both primary and secondary peritoneal malignancies and provides an overview of peritoneal anatomy, function and modes of disease dissemination with illustration of common sites and imaging features of peritoneal malignancy.

Adrenocortical carcinoma: the range of appearances on CT and MRI.

OBJECTIVE: Adrenocortical carcinoma (ACC) is a rare, aggressive tumor arising from the adrenal cortex that typically presents late with a large mass. The increased use of cross-sectional imaging for unrelated reasons has led to a greater number of ACCs being detected incidentally at an earlier stage. Recognition of the typical clinical, biochemical, and imaging findings is imperative for rapid diagnosis, prompt intervention, and early use of the appropriate therapy. CONCLUSION: Cross-sectional imaging with CT and MRI is essential for determining the extent of local and distant tumor spread. Complete surgical resection is currently the only potentially curative treatment of ACC, and the information attained from CT and MRI is important to guide surgery and further patient management.

Ovarian Cancer Management: the role of imaging and diagnostic challenges.

Worldwide, ovarian cancer accounts for 4% of all female cancers with over 190,000 new cases diagnosed each year. The incidence rates vary considerably across the globe with the highest rates seen in Europe and the USA and low rates in Africa and Asia. Ovarian cancer has been termed a 'silent' killer with the majority of patients presenting with advanced disease due to the vague, non-specific nature of the presenting symptoms such as abdominal discomfort and bloating in 50%. The most important determinant of survival for ovarian cancer patients is the disease stage at diagnosis. Therefore there is a thrust for early detection and two large screening trials are currently underway in the UK and USA. Ovarian cancer is most commonly staged using the International Federation of Gynecology and Obstetrics (FIGO) surgical-pathological staging system. Imaging findings are not a formal component of the staging system but in clinical practice they play a significant role in the diagnosis and management of suspected ovarian cancer. Adnexal masses which are shown to have benign features on imaging can undergo simple excision at a local unit by a non-oncological gynaecologist. If a mass has malignant characteristics on imaging, then a radical surgical approach is indicated and this should be performed by a gynaecological oncological surgeon at a specialist cancer centre, as optimal cytoreductive surgery has been reported to improve outcome. This review article discusses the role of various imaging modalities in the initial assessment of an adnexal mass, the contribution to management planning and to the follow-up of patients with ovarian cancer.

MRI appearances of uterine malignant mixed müllerian tumors.

OBJECTIVE: Uterine malignant mixed müllerian tumors (MMMTs) are rare aggressive tumors with a high incidence of lymphatic, peritoneal, and pulmonary metastases. Preoperative differentiation from endometrial adenocarcinoma would be beneficial because their prognoses differ. MATERIALS AND METHODS: We retrospectively reviewed MRI examinations of 51 histologically confirmed MMMTs. Tumor size, growth pattern, and imaging characteristics were recorded. Data were compared with MRI appearances of 73 endometrial adenocarcinomas. RESULTS: On T1-weighted images, MMMTs were predominantly isointense to myometrium (76%) and endometrium (71%), with heterogeneous texture in 33% of cases and hyperintense foci in 27% of cases. On T2-weighted images, 92% of MMMTs were hyperintense to myometrium and either hypointense (55%) or isointense (41%) to endometrium. In 12% of cases, large heterogeneous MMMTs obliterated uterine architecture and were aggressive in appearance, whereas in 88% of cases, the appearances were indistinguishable from those of endometrial adenocarcinoma. Significantly more MMMTs than endometrial adenocarcinomas had cervical invasion (p = 0.008) and nodal enlargement (p = 0.00008). Dynamic contrast-enhanced images (available for 19 of 51 patients) obtained at less than 1 minute after administration of contrast agent showed MMMT enhancement to be hypointense (42%; 5/12 patients) or isointense (33%; 4/12 patients) to myometrium; between 1 and 4 minutes after administration of contrast agent, tumors were hypointense (58%; 7/12 patients); and at more than 4 minutes after administration of contrast agent (n = 18), MMMTs were isointense in 56% of cases. This finding is significantly different from that for endometrial adenocarcinoma, where enhancement is less than that of myometrium in 90% of cases (p = 4 × 10⁻8). CONCLUSION: MMMTs do not have a pathognomonic MRI appearance. However, radiologic suspicion should increase in the presence of large heterogeneous infiltrative tumors or when tumoral enhancement equals or exceeds that of myometrium.

Perforation of a malignant ovarian tumor into the recto-sigmoid colon.

Ovarian cancer often presents at an advanced stage, but tends to be an intra-peritoneal disease that respects peritoneal planes. Thus, colo-rectal perforation of the tumor is an extremely rare presentation. The surgical treatment of malignant colo-ovarian fistula should include complete cyto-reduction at the same time as the treatment of the fistula. However, prognosis remains poor, because of the advanced stage of neoplasia. We report the case of a patient with an ovarian malignant tumor perforating into the recto-sigmoid colon. CT scan was the cornerstone of the radiological diagnosis. We managed to perform a complete cyto-reduction, including an en-bloc resection of the uterus, the mass, adnexa and recto-sigmoid with removal of the associated pelvic abscess.

The indeterminate adrenal lesion.

With the increasing use of abdominal cross-sectional imaging, incidental adrenal masses are being detected more often. The important clinical question is whether these lesions are benign adenomas or malignant primary or secondary masses. Benign adrenal masses such as lipid-rich adenomas, myelolipomas, adrenal cysts and adrenal haemorrhage have pathognomonic cross-sectional imaging appearances. However, there remains a significant overlap between imaging features of some lipid-poor adenomas and malignant lesions. 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) alone. Positron emission tomography (PET) is also increasingly used in clinical practice in characterizing incidentally detected lesions. We review the performance of the established and new techniques in CT, MRI and PET that can be used to distinguish benign adenomas and malignant lesions of the adrenal gland.

Imaging of endometrial and cervical cancer.

In this article we review the ever increasing role of imaging in endometrial and cervical cancer. Magnetic resonance imaging (MRI) has emerged as the most widely used technique in the management of women with gynaecological cancer. In endometrial cancer, MRI is reliable in identifying myometrial and cervical invasion and extra-uterine disease, thereby informing preoperative surgical planning. In cervical cancer, MRI plays a crucial role in distinguishing early from advanced disease, thereby stratifying patients for surgery and chemoradiation. MRI is also valuable in assessing proximal extension of cervical tumours in young women with early stage disease for feasibility of fertility preserving surgery. In both cancers, imaging is used for diagnosing nodal metastases, detection of recurrence, and dealing with complications of both the disease and treatment.

Pearls and pitfalls of MR lymphography in gynecologic malignancy.

Dissemination of tumor to lymph nodes is one of the principal routes of metastatic disease. The presence or absence of nodal disease is an important prognostic factor in gynecologic malignancies; thus, nodal staging is an integral part of the pretreatment assessment. It is vital that pretreatment nodal staging be accurate and reliable. Current imaging techniques such as computed tomography and magnetic resonance (MR) imaging have limitations because they rely almost exclusively on size criteria. MR lymphography uses a lymph node-specific contrast agent (ferumoxtran-10) composed of ultrasmall superparamagnetic iron oxide particles. The contrast agent is taken up by macrophages within benign lymph nodes and allows differentiation from malignant nodes on the basis of alterations in signal intensity. This technique has been shown to increase the sensitivity and specificity of detection of lymph node metastases independent of nodal size. However, as with any technique, there are pitfalls that the radiologist must be aware of to avoid interpretative errors.

Fistulas in malignant gynecologic disease: etiology, imaging, and management.

A fistula that occurs in association with a malignancy of the female reproductive tract may be caused by a primary or recurrent tumor or may be a complication of surgery or radiation therapy. Identification of the cause, complexity, and location of a fistula is essential for optimal management planning. Radiologic imaging, particularly with computed tomography and magnetic resonance techniques, is invaluable for the assessment of gynecologic fistulas and may help direct the clinician toward the most appropriate management pathway. The modality and technique selected for the initial imaging evaluation depend largely on the clinical history and manifestations. However, imaging with a combination of techniques often is required for accurate diagnosis and effective treatment planning. Radiologists should be familiar with suggestive clinical signs and symptoms as well as with the characteristic appearances of rectovaginal, vesicovaginal, ureterovaginal, enterovesical, enterocutaneous, and other pelvic fistulas at multimodality imaging.

Multidetector computed tomography of the acute abdomen in the immunocompromised host: a pictorial review.

Immunocompromised patients include those receiving chemotherapy for malignant disease, post-transplant patients, patients with acquired immunodeficiency syndrome (AIDS), and those receiving steroids for autoimmune diseases. Advances in transplantation, oncology, and the treatment of AIDS have extended these patients' life expectancies and thereby increased the immunocompromised population. Classical clinical signs of abdominal sepsis may be absent in the immunocompromised host. Consequently, the radiologist is increasingly called on to diagnose specific acute intra-abdominal complications associated with immunodeficiency. This review describes the etiology of the acute abdomen in this heterogeneous group of immunocompromised patients, causes including opportunistic infections, neutropenic enterocolitis, complications of therapy, and opportunistic neoplasms. The typical radiological appearances of these conditions on multidetector computed tomography are illustrated. The challenges and limitations of multidetector computed tomography in diagnosing these conditions are discussed.

Contrasting clinical manifestations of SDHB and VHL associated chromaffin tumours.

Mutations in succinate dehydrogense-B (SDHB) and the von Hippel-Lindau (VHL) genes result in an increased risk of developing chromaffin tumours via a common aetiological pathway. The aim of the present retrospective study was to compare the clinical phenotypes of disease in subjects developing chromaffin tumours as a result of SDHB mutations or VHL disease. Thirty-one subjects with chromaffin tumours were assessed; 16 subjects had SDHB gene mutations and 15 subjects had a diagnosis of VHL. VHL-related tumours were predominantly adrenal phaeochromocytomas (22/26; 84.6%), while SDHB-related tumours were predominantly extra-adrenal paragangliomas (19/25; 76%). Median age at onset of the first chromaffin tumour was similar in the two cohorts. Tumour size was significantly larger in the SDHB cohort in comparison with the VHL cohort (P=0.002). Multifocal disease was present in 9/15 (60%) of the VHL cohort (bilateral phaeochromocytomas) and only 3/16 (19%) of the SDHB cohort, while metastatic disease was found in 5/16 (31%) of the SDHB cohort but not in the VHL cohort to date. The frequency of symptoms, hypertension and the magnitude of catecholamine secretion appeared to be greater in the SDHB cohort. Renal cell carcinomas were a feature in 5/15 (33%) of the VHL cohort and 1/16 (6%) of the SDHB cohort. These data indicate that SDHB-related tumours are predominantly extra-adrenal in location and associated with higher catecholamine secretion and more malignant disease, in subjects who appear more symptomatic. VHL-related tumours tend to be adrenal phaeochromocytomas, frequently bilateral and associated with a milder phenotype.

Imaging in covert ectopic ACTH secretion: a CT pictorial review.

The syndrome of ectopic adrenocorticotrophin secretion (EAS) is rare and is due to excess adrenocorticotrophin (ACTH) production from a nonpituitary tumour. These tumours can be covert, where the tumours are not readily apparent, and very small making them challenging to image. It is clinically and biochemically difficult to distinguish between covert EAS and Cushing's disease. The first-line investigation in locating the source of ACTH production is computed tomography (CT). The aim of this pictorial review is to illustrate the likely covert sites and related imaging findings. We review the CT appearances of tumours resulting in covert EAS and the associated literature. The most common tumours were bronchial carcinoid tumours, which appear as small, well-defined, round or ovoid pulmonary lesions. Rarer causes included thymic carcinoids, gastrointestinal carcinoids and pancreatic neuroendocrine tumours. Awareness of the imaging characteristics will aid identification of the source of ACTH production and allow potentially curative surgical resection.

Magnetic resonance imaging of endometrial and cervical cancer.

In this article we review the current and developing roles of magnetic resonance imaging (MRI) in endometrial and cervical cancer. In endometrial cancer, the purpose of MRI is to stage the primary tumor and in particular to identify myometrial and cervical invasion and extra-uterine disease, thereby informing preoperative surgical planning. MRI is also used to safely select young patients suitable for fertility-preserving medical management. In cervical cancer, MRI has an established role in local staging and in assessing proximal extension of tumors in young women for feasibility of fertility-preserving surgery. It is used to plan radiotherapy for primary tumors in cervical cancer and particularly for conformal radiotherapy to deliver optimal doses to the tumor sites, while limiting unwanted exposure of bowel and other pelvic organs. In both cancers, MRI is used for diagnosing nodal disease, surveillance, detection of recurrence, and evaluation of complications secondary to treatment.

A verification study of proposed pelvic lymph node localisation guidelines using nanoparticle-enhanced magnetic resonance imaging.

BACKGROUND AND PURPOSE: Normal sized pelvic lymph nodes are not easily identifiable on conventional imaging, but can be visualised with contrast-enhanced magnetic resonance imaging (MRI) using intravenous ultra-small particles of iron-oxide (USPIO). We have previously reported pelvic node clinical target volume (CTV) delineation guidelines for use with conventional imaging, derived from nodal mapping studies using USPIO. This study aims to verify these guidelines using an independent observer in a further patient cohort. MATERIALS AND METHODS: Ten patients with gynaecological cancer underwent MRI with and without intravenous USPIO. The guidelines were used to outline a pelvic node CTV on pre-contrast T2-weighted images. On post-contrast T2-weighted images the pelvic nodes were identified and outlined. The pre- and post-contrast images were co-registered and CTV examined for node coverage. RESULTS: By applying the guidelines, full coverage of 737 of 741 node outlines was achieved (>99%). Four nodes were not completely encompassed, two anterior external iliac nodes and two lateral external iliac nodes. CONCLUSIONS: MRI with USPIO contrast enabled the production of guidelines for localising a pelvic node CTV with conventional imaging. Application of these guidelines to a further patient cohort resulted in coverage of 99.5% node outlines demonstrating the reliability of this technique.

Adrenal phaeochromocytoma: correlation of MRI appearances with histology and function.

The purpose of this study was to describe the range of appearances of adrenal phaeochromocytomas on T2-weighted MRI, correlate appearances with histopathology, and quantify the incidence of the previously described hyperintense appearance. The appearance and MR characteristics of 44 phaeochromocytomas were reviewed retrospectively. T2-weighted appearances were grouped: (1) 'classical', homogeneous, high signal intensity, isointense to CSF; (2) homogeneous, isointense or minimally hyperintense to spleen, hypointense to CSF; (3) heterogeneous, marbled appearance; (4) heterogeneous, multiple high signal intensity pockets. All 44 adrenal phaeochromocytomas were well circumscribed, 1.2-15 cm in maximum diameter, with no visual or quantitative signal loss on chemical shift imaging. On T2-weighted MRI 5/44 (11%) had group 1 appearance; 15/44 (34%) group 2, 7/44 (16%) group 3; and 17/44 (39%) group 4. Homogeneous group 1 and 2 lesions were smaller (mean 4.5 cm) than heterogeneous group 3 and 4 lesions (mean 6.3 cm). Increasing MRI heterogeneity correlated pathologically with increasing amounts of haemorrhage, necrosis and fibrosis. No MRI features were predictive of malignancy. Non-functioning phaeochromocytomas were larger than functioning lesions. No size difference was seen between syndrome and sporadic lesions. In this large series we report a wide range of appearances of adrenal phaeochromocytomas on T2-weighted MRI. The previously described classical hyperintense phaeochromocytoma is relatively uncommon.

123I-metaiodobenzylguanidine (MIBG) scintigraphy for the detection of adrenal and extra-adrenal phaeochromocytomas: CT and MRI correlation.

CONTEXT: Evidence regarding the accuracy of [(123)I] metaiodobenzylguanidine (MIBG) imaging for phaeochromocytoma localization is currently limited to small series. OBJECTIVE: We present the largest series of primary phaeochromocytomas in which the performance of [(123)I]MIBG has been evaluated and correlated with cross-sectional imaging. DESIGN: We identified 76 patients with both preoperative [(123)I]MIBG and cross-sectional imaging for confirmed primary phaeochromocytoma between 1995 and 2005 at our institution. This comprised 60 adrenal tumours in 55 patients and 33 extra-adrenal tumours in 23 patients (2 patients had both adrenal and extra-adrenal tumours). Phaeochromocytoma metastases were not evaluated. MAIN OUTCOME MEASURE(S): [(123)I]MIBG studies were independently reviewed and correlated with CT and MRI examinations, as well as tumour functional status, to identify features that may predict a false negative [(123)I]MIBG result. RESULTS: The overall sensitivity of [(123)I]MIBG was 75%. Tumour detection was lower for extra-adrenal (58%) vs. adrenal (85%) phaeochromocytomas (P = 0.005). For extra-adrenal tumours, [(123)I]MIBG demonstrated 8 of 14 carotid body, 2 of 2 intrathoracic, 8 of 14 retroperitoneal and 2 of 3 pelvic phaeochromocytomas. Overall, MRI and CT demonstrated 68 of 68 and 72 of 74 primary phaeochromocytomas, respectively. Tumour size correlated with [(123)I]MIBG uptake for adrenal (P = 0.009) but not extra-adrenal tumours. When tumours were adjusted for size, no other imaging feature or functional status correlated with [(123)I]MIBG negativity, although two large [(123)I]MIBG negative adrenal tumours contained large areas of necrosis or haemorrhage. CONCLUSIONS: Extra-adrenal and small adrenal phaeochromocytomas are more likely to result in false negatives on [(123)I]MIBG. Tumoural necrosis or haemorrhage do not consistently relate to [(123)I]MIBG uptake, although adrenal phaeochromocytomas containing minimal solid tissue due to extensive necrosis may predict a negative [(123)I]MIBG result.

Clinical manifestations of familial paraganglioma and phaeochromocytomas in succinate dehydrogenase B (SDH-B) gene mutation carriers.

OBJECTIVE: Phaeochromocytomas and paragangliomas are familial in up to 25% of cases and can result from succinate dehydrogenase (SDH) gene mutations. The aim of this study was to describe the clinical manifestations of subjects with SDH-B gene mutations. DESIGN: Retrospective case-series. PATIENTS: Thirty-two subjects with SDH-B gene mutations followed up between 1975 and 2007. Mean follow-up of 5.8 years (SD 7.4, range 0-31). Patients seen at St Bartholomew's Hospital, London and other UK centres. MEASUREMENTS: Features of clinical presentation, genetic mutations, tumour location, catecholamine secretion, clinical course and management. RESULTS: Sixteen of 32 subjects (50%) were affected by disease. Two previously undescribed mutations in the SDH-B gene were noted. A family history of disease was apparent in only 18% of index subjects. Mean age at diagnosis was 34 years (SD 15.4, range 10-62). 50% of affected subjects had disease by the age of 26 years. 69% (11 of 16) were hypertensive and 80% (12 of 15) had elevated secretions of catecholamines/metabolites. 24% (6 of 25) of tumours were located in the adrenal and 76% (19 of 25) were extra-adrenal. 19% (3 of 16) had multifocal disease. Metastatic paragangliomas developed in 31% (5 of 16). One subject developed a metastatic type II papillary renal cell carcinoma. The cohort malignancy rate was 19% (6 of 32). Macrovascular disease was noted in two subjects without hypertension. CONCLUSION: SDH-B mutation carriers develop disease early and predominantly in extra-adrenal locations. Disease penetrance is incomplete. Metastatic disease is prominent but levels are less than previously reported. Clinical manifestations may include papillary renal cell carcinoma and macrovascular disease.

Imaging in Cushing's syndrome: [review]

Once the diagnosis of Cushing's syndrome (CS) has been established, the main step is to differentiate between ACTH dependent and independent disease. In adults, 80 percent of CS is due to ACTH-dependent causes and 20 percent due to adrenal causes. ACTH-secreting neoplasms cause ACTH-dependent CS. These are usually anterior pituitary microadenomas, which result in the classic Cushing's disease. Non-pituitary ectopic sources of ACTH, such as a small-cell lung carcinoma or carcinoid tumours, are the source of the remainder of ACTH-dependent disease. In the majority of patients presenting with clinical and biochemical evidence of CS, modern non-invasive imaging can accurately and efficiently provide the cause and the nature of the underlying pathology. Imaging is essential for determining the source of ACTH in ectopic ACTH production, locating the pituitary tumours and distinguishing adrenal adenomas, carcinomas and hyperplasias. In our chapter we review the adrenal appearances in ACTH-dependent and ACTH-independent CS. We also include a discussion on the use of MRI and CT for the detection and management of pituitary ACTH secreting adenomas. CT of the chest, abdomen and pelvis with intravenous injection of contrast medium is the most sensitive imaging modality for the identification of the ectopic ACTH source and detecting adrenal pathology. MRI is used for characterising adrenal adenomas, problem solving in difficult cases and for detecting ACTH-secreting pituitary adenomas.

Uma vez estabelecido o diagnóstico da síndrome de Cushing (SC), o passo principal é diferenciar entre a doença ACTH-dependente e a independente. Em adultos, 80 por cento da SC é devida a causas ACTH-dependentes e 20 por cento a causas adrenais. Neoplasias secretoras de ACTH causam a SC ACTH-dependente: usualmente são microadenomas da hipófise anterior que resultam na clássica doença de Cushing. Fontes ectópicas (não hipofisárias) de ACTH, como o carcinoma pulmonar de células pequenas e tumores carcinóides, são a origem do restante da doença ACTH-dependente. Na maioria dos pacientes que se apresentam com evidências clínicas e bioquímicas da SC, técnicas modernas de imagem não invasivas podem apontar acurada e eficientemente a causa e a natureza da patologia subjacente. A imagem é essencial para a determinação da fonte de ACTH na produção ectópica desse hormônio, na localização de tumores hipofisários e na distinção entre adenomas, carcinomas e hiperplasias adrenais. Nesse artigo revisaremos a imagem adrenal na SC ACTH-dependente e independente. Incluiremos, também, uma discussão sobre o uso da RM e da TC na detecção e manejo dos adenomas hipofisários secretores de ACTH. TC de tórax, abdome e pelve, com a injeção intravenosa de meio de contraste, é a modalidade de imagem mais sensível para a identificação da fonte ectópica de ACTH e na detecção da patologia adrenal. A RM é empregada para a caracterização de adenomas adrenais, para a solução de problemas em casos difíceis e para a detecção de adenomas hipofisários secretores de ACTH.