Supplementary Webappendix

Hegenscheid et al. Potentially relevant incidental findings on research whole-body MRI in the general adult population: frequencies and management. EurRadiol 2012

Supplementary webappendix

This appendix consists of online material only and includes an own reference list that is independent from the journals’ article reference list.This appendix was provided by the authors to give readers additional information on the decisions made by the advisory board for the follow-up of incidental findings.

HEAD
BRAIN TUMOUR
Heterogeneous group of intra-axial and extra-axial tumours with benign or malignant aspect. Management of incidental findings has been widely discussed for study MRI of the head [1,2].
Disclosed benign tumours were intraventricular tumours, large arachnoid cysts, large meningiomas, and a vestibular schwannoma. All of these benign tumours were disclosed due to perifocal oedema indicating space-occupying growth or location in a region with high functional priority (e.g., brain stem, eloquent brain region). Disclosed malignant tumours were suspicious for glioma or metastasis. One participant presented with an extracranial soft tissue tumour with invasive intracranial growth. All were disclosed due to their life-threatening nature[3,4].
PITUITARY MICRO-/ MACROADENOMA
Pituitary microadenoma: intrasellar lesion with a maximum diameter < 10 mm.
Pituitary macroadenoma: sellar-suprasellar mass without separately identifiable pituitary gland.Pituitary cyst: intrasellar or sellar-suprasellar cystic lesion.
All lesions suspicious for microadenoma were communicated due to a possible hormone-producing state.Macroadenomas were disclosed due to possible involvement of the optic chiasm and cavernous sinus, and affected study subjects were recommended to undergo assessment of clinical symptoms as well as ophthalmological/endocrinological evaluation[5].
ACUTE BRAIN INFARCTION
Acute cerebral infarction was diagnosed by diffusion-weighted imaging. Infarctions encountered were silent cerebral infarctions (neurologically asymptomatic).
Silent cerebral infarction was found to more than double the risk of subsequent stroke in both population- and hospital-based cohort studies, regardless of the presence of cardiovascular risk factors [6-9].This finding was communicated to allow subjects with twice the normal risk of major stroke to undergo neurological check-up for identification of potentially treatable risk factors.
SUBDURAL HAEMATOMA
Crescentic, extra-axial convexity collection, crossing sutures but not dural attachments.
One subdural haematoma was disclosed due to its space-occupying size.
NORMAL PRESSURE HYDROCEPHALUS (NPH)
NPH was suspected according to the evidence-based guidelines for the diagnosis of NPH[10].
Diagnosis of NPH required correlation with clinical symptoms. Suspected NPH was disclosed to allow neurological work-up since timely diagnosis and treatment by ventricular shunting can reverse symptoms, while natural history of NPH leads to chronic impairment [11].
NECK
CYSTIC OR SOLID PHARYNGEAL OR LARYNGEAL TUMOUR
Handling of cystic or solid oropharyngeal and laryngeal masses was difficult because their diagnosis relied on only two unenhanced MR sequences of the neck.
The advisory board decided each case of asymmetry by interdisciplinary consensus. Almost all asymmetries, excepting simple cysts, were disclosed since the incidence and mortality of oropharyngeal and laryngeal cancer is highest in the state in which the SHIP study was conducted compared to the other German states [12]. The relatively low risk of complications associated with panendoscopy of the nasopharyngeal and laryngeal cavities recommended for follow-up justified higher follow-up rates.
CYSTIC OR SOLID SALIVARY GLAND TUMOUR
Handling of cystic or solid salivary gland masses was difficult because their diagnosis relied on only two unenhanced MR sequences of the neck.
The advisory board decided by interdisciplinary consensus which masses should be followed up by assessment of clinical signs and symptoms and ultrasonography.
GOITRE WITH TRACHEAL COMPRESSION
Diffuse, multinodular enlargement of the thyroid gland with tracheal compression.
Goitres were disclosed in case of tracheal compression since significant airway compression indicates need for surgical treatment [13].
THYROID TUMOUR
Thyroid mass suspicious of malignancy: irregular demarcation from surrounding structures, invasion, metastatic cervical lymphadenopathy.
Management of incidental thyroid masses on MRI/CT has been discussed controversially [14]. Assessment required risk stratification by history, physical examination, and ancillary tests (serum TSH, ultrasonography) [13,15]. Since the SHIP study provided thyroid ultrasonography and serum TSH values for each participant in the internal branch of the study, the advisory board only disclosed masses with high propability of malignancy, whereas all nondisclosed nodules were automatically evaluated in the normal course of the SHIP study protocol.
CHEST
LUNG NODULE
Lung lesion completely surrounded by lung parenchyma < 3 cm in diameter [16].
Pulmonary nodules were reported according to the guidelines of the Fleischner Society [17,18]. Subjects with nodules 4 mm were recommended to undergo initial CT. If CT confirmed the nodule seen on MRI, further follow-up was recommended following the guidelines of the Fleischner Society.
PNEUMONIA
Segmental/lobar consolidation of the lung due to inflammatory infiltration in asymptomatic/ oligosymptomatic participants (silent infection)[19].
Asymptomatic/oligosymptomatic pneumonia was disclosed since, especially in the elderly, pneumonia can present as silent infection with atypical features (deteriorating general condition, confusion, and lethargy) but is nevertheless a major cause of morbidity and mortality [20]. Poststenotic pneumonias in central lung carcinomas are mostly subclinical infections [21]. Consequently, an underlying carcinoma should be ruled out.
PLEURAL EFFUSION
Fluid accumulation in the pleural space replacing the pulmonary volume.
Pleural effusion was disclosed if effusion was so largeof such a volume that respiratory restriction seemed likely, indicated by pulmonary dystelectasis or atelectasis.
LIVER
LIVER LESION
A benign lesion (cyst, haemangioma, adenoma, focal nodular hyperplasia (FNH)) or malignant lesion (hepatocellular carcinoma) was assumed when the respective imaging criteria were present. Lesions were classified as unclear if morphology on plain imaging was not definitively benign and criteria for malignancy (destructive or invasive growth) were not fulfilled.
(1)FNHs have few complications, and there is no evidence of malignant transformation [22]. Disclosure of FNH was based on their responsiveness to oestrogens with larger, more vascular tumours occurring in women on oral contraceptives. Therefore, FNH was communicated in premenopausal women to allow affected women and their gynaecologists to discuss discontinuation of oral contraceptives [23].
(2)Large cysts were disclosed on the basis of their higher rate of complications such as spontaneous haemorrhage, rupture, infection, or mechanical compression of adjacent structures to allow correlation with clinical symptoms [24].
(3)Most hepatic haemangioma remain stable over time and require no treatment. Treatment or follow-up is not indicated for lesions <5 cm in diameter, whereas lesions >15 cm in diameter may need resection and were therefore disclosed [25].
(4)All adenomas were communicated because of an approx. 10% risk of malignant transformation to hepatocellular carcinoma (HCC) [26].
(5)Unclear liver lesions need further imaging evaluation (MRI with liver-specific contrast medium/ ultrasonography) for reliable characterization.
(6)Liver lesions highly suspicious for hepatocellular carcinoma or metastasis were communicated due to their malignant nature.
CIRRHOSIS OR HEMOCHROMATOSIS
Cirrhosis: chronic liver disease characterized by diffuse parenchymal injury, fatty and fibrotic tissue changes, and formation of abnormal nodules.
Haemochromatosis: iron overload disorder with structural and functional impairment of involved organs. Decreased signal intensity of the liver on T1- and T2-weighted images.
Haemochromatosis and cirrhosis are severe pathologies shortening life expectancy and lowering quality of life [27,28]. These conditions were disclosed to allow evaluation of etiology and risk factors as well as to facilitate possible treatment.
BILIARYSYSTEM
CHOLESTASIS
Dilatation of the choledochal duct > 7mm/10mm or of intrahepatic bile ducts > 3mm in participants without/after cholecystectomy, respectively.
Natural history of chronic cholestasis leads to secondary biliary cirrhosis of the liver. Patients with this condition require evaluation of etiology and management of treatable causes. Recommendations included assessment of paraclinical and clinical signs as well as ultrasonographic correlation.
CHRONIC CHOLECYSTITIS
Chronic cholecystitis: diffuse gall bladder wall thickening and presence of gallstones.
Chronic cholecystitis was often seen and was only disclosed in case of acute exacerbation: pericholecystic fluid and adjacent fat signal intensity changes [29].
PANCREAS
CHRONIC PANCREATITIS
Chronic pancreatitis: pancreatic atrophy, pancreatic duct dilatation and side branch dilatation, irregularity of the pancreatic ducts, calcifications, pseudocysts, and biliary obstruction.
Chronic pancreatitis was disclosed due to a natural history with exocrine/endocrine insufficiency and chronic pain syndrome to allow evaluation and enable management of treatable causes [30]. Recommendations included assessment of paraclinical and clinical signs as well as ultrasonographic correlation.
PANCREATIC TUMOUR
Unclear pancreatic lesions disclosed were suspicious for malignancy but could also be tumour-simulating benign lesions such as inflammatory pseudotumours or complex pseudocysts.
Since unenhanced imaging with a single modality does not differentiate cancer and focal pancreatitis, disclosure allowed correlation with additional imaging findings (contrast-enhanced CT and ERCP with biopsy) [31,32]. The follow-up regimen was based on the White Paper of the ACR incidental findings committee [33].
SPLEENLYMPHATICSYSTEM
SPLENOMEGALY
Splenomegaly: craniocaudal length of the spleen exceeding 12 cm.
Splenomegaly was disclosed if suggestive of systemic diseases of the lymphatic system (e.g., generalized lymphadenopathy with concomitant splenomegaly), metastasis (e.g., abdominal lymphadenopathy in conjunction with suspicious intestinal, hepatic, or pancreatic mass), or reactive lymphadenopathy with concomitant inflammation suggested by severe tissue oedema. All of these cases were presented to the advisory board with disclosure being decided on a case-by-case basis.
SPLENIC TUMOUR
Splenic lesions were classified as lesions with a distinct MRI appearance (cyst/hemangioma, calcification, infarction) and unclear lesions.
Unclear lesions could not be reliably characterized on the basis of the available plain MR sequences. Correlation with other imaging modalities was suggested to rule out inflammatory and infectious disease, hematologic disorders, and solid malignancies [34].
INTESTINE
GASTROINTESTINAL TUMOR
Solid soft tissue mass of the intestinal wall, which reproduced in at least two different sequences to exclude peristalsis as cause of intestinal wall thickening.
Available MR images were limited, not least because no contrast agent was used. Cases in question were presented to the advisory board with disclosure being decided on a case-by-case basis.
LARGE HERNIATION
Opening or weakness in the muscular structure of the abdominal wall with protrusion of an organ or part of an organ out of the abdominal cavity.
Large herniations with protrusion of organs were disclosed due the risk of incarceration [35].
KIDNEY
RENAL CYST OR TUMOUR
We adopted the Bosniak classification system to grade cystic renal lesions [36,37]. The differential diagnosis of renal masses includes angiomyolipomaand renal cell carcinoma.
Category I cysts were disclosed > 8 cm in diameter due to the increased risk of hemorrhage especially in individuals undergoing anticoagulation therapy [38,39]. Simple category II cysts are benign, but cyst category IIF (a cystic lesion with multiple thin septa, or septa thicker than hairline, or a thick calcification) are not invariably benign [40,41]. Disclosure was implemented for cysts category ≥ IIF with follow-up according to the recommendations of the White Paper of the ACR incidental findings committee[33].Although benign, renal angiomyolipomas were always disclosed since angiomyolipoma was found to be the most frequent misdiagnosis for renal cell carcinoma [42]. Renal angiomyolipomas were also disclosed because they are associated with an increased risk of tumoural haemorrhage when their size exceeds 4 cm [43]. Kidney masses with an invasive and/or destructive growth pattern are highly suspicious for renal cell carcinoma and were disclosed due to their probably malignant nature.
ADRENAL TUMOUR
Adrenal lesion ≥ 1 cm.
All adrenal masses ≥ 1 cm were disclosed. Follow-up was recommended according to the White Paper of the ACR incidental findings committee to allow correlation with prior imaging and/or follow-up by MRI or CT[33].
CHRONIC URINARY OBSTRUCTION
We differentiated chronic urinary retention with dilatation of the calicopelvic system with concomitant atrophy of renal parenchyma from acute urinary retention with dilatation of the calicopelvic system and normal renal parenchyma.
Chronic and acute urinary retention was always disclosed since both will lead to chronic kidney disease if untreated and persisting [44,45].
URINARY BLADDER MASS
Localized circumscribed urinary bladder masses were differentiated from global thickening of the urinary bladder wall. The first is suspicious for urinary bladder malignancy, the second is a sign of chronic bladder damage.
Since the acquired MR sequences are limited regarding evaluation of the urinary bladder, among others because evaluation depends on bladder filling at the time of imaging, circumscribed or diffuse wall thickening was always disclosed to enable further diagnostic work-up (ultrasonography, cystoscopy) and correlation with possible clinical symptoms.
MALEGENITALSYSTEM
PROSTATIC HYPERPLASIA OR TUMOUR
Probably benign enlargement of the prostate due to nodular hyperplasia causing progressive urinary obstruction was distinguished from probably malignant enlargement of the prostate (asymmetric enlargement, invasive growth, lymphadenopathy) suggestive of prostatic cancer.
Volumetry of the prostate was performed in all men ([transverse diameter in cm]3x /6) [46]. Prostatic enlargement  60 ml was disclosed to allow urological risk stratification for urinary obstruction and prostate cancer (transabdominal/ transurethral ultrasound and biopsy, correlation with clinical symptoms and paraclinical parameters) [47].
INGUINAL TESTIS
Incomplete testicular descent into the scrotum with testis in the inguinal canal.
An inguinal testis has an increased risk of malignant transformation and infertility and was disclosed depending on the participant’s age [48-50].
TESTICULAR AND EPIDIDYMAL MASS
Cystic or solid testicular or epididymal mass with benign or malignant aspect.
Simple scrotal cysts (epididymal/ testicular/ tunica albuginea cyst, spermatocele] are benign and were not disclosed. Solid scrotal masses were generously disclosed with recommendation for urological clarification. For scrotal masses there are multiple differential diagnoses, and differentiation requires correlation with clinical signs and symptoms, paraclinical parameters and alternate imaging modalities, espescially ultrasonography, and ultimativley inguinal exploration[51-53].
SEMINAL VESICLE MASS
Generalized enlargement of the seminal vesicles was distinguished from focal lesions.
Diffuse enlargement was not disclosed since underlying conditions are benign (inflammation, radiotherapy-induced changes, amyloidosis). Focal lesions suggesting tumor invasion (cancer of the prostate, bladder or rectum) were disclosed [54].
FEMALEGENITALSYSTEM
UTERINE OR CERVICAL TUMOUR
Benign masses of the uterus and cervix (leiomyoma, adenomyoma/ adenomyosis, endometrial hyperplasia, polyp, Nabothian cysts) and probably malignant masses (endometrial or cervical carcinoma, endometrial sarcoma) were differentiated.
None of the definitely benign uterine lesions listed above were disclosed. For unclear uterine and cervical masses, the interdisciplinary advisory board decided on a case-by-case basis which masses to follow up. The relatively low risk of complications of colposcopy and ultrasonography recommended for follow-up justified higher follow-up rates [55,56].
COMPLEX OVARIAN CYST OR TUMOUR
Ovarian masses were differentiated into benign (functional cysts, haemorrhagic cysts), unclear, and probably malignant (solid tumours or mixed solid and cystic tumours, size > 8 cm, local invasion, peritoneal fluid, and adenopathy).
In premenopausal women, complex cysts with suspected haemorrhage and cystic tumours were disclosed, while simple cystic lesions (functional cysts) were not. In postmenopausal women, cysts were disclosed if diameter exceeded 2 cm due to the increased risk of ovarian cancer to allow correlation with ultrasound and paraclinical parameters (Ca-125)[57,58]. All unclear ovarian masses and those with signs of malignancy (solid tumour or mixed solid and cystic tumour, size > 8 cm, local invasion, peritoneal fluid, adenopathy) were disclosed [59-61].
BREAST LESION (≥ BI-RADS 3)
Breast lesions in women who underwent the contrast-enhanced MR mammography module were classified according to the Breast Imaging Reporting and Data System (BI-RADS).
Breast lesions classified  BI-RADS 3 were disclosed. For category 3 lesions, close follow-up was recommended [62,63] as well as ultrasonographic correlation[64]. For category 4 or 5 lesions, biopsy was recommended.
SPINEANDMUSCULOSKELETALSYSTEM
ABSOLUTE SPINAL CANAL STENOSIS WITH MYELOPATHY
Acquired stenosis of the cervical/lumbar spinal canal secondary to degenerative changes with intramedullary T2-hyperintensity representing myelomalacia, demyelination, or oedema.
Natural history of cervical/lumbar spinal canal stenosis is progressive and dynamic with mainly irreversible damage to the spinal cord/cauda equina. Disclosure allowed diagnostic and therapeutic interruption of the progressive disabling process [65,66].
INTRASPINAL TUMOUR
Intraspinal lesions were classified into intramedullary lesions, intradural extramedullary lesions, and extradural lesions. There are many differential diagnoses depending on many features including lesion site, signal intensities, and clinical and paraclinical parameters[67,68].
Without contrast-enhanced MR images, differentiation of benign and malignant lesions was not possible. Therefore all intraspinal lesions were disclosed to allow further diagnostic steps.
BONE LESION
Bone lesions encountered were bone cysts, chondrogenic bone tumors (with benign aspect], and unclear bone lesions not classifiable on the basis of plain MR images.
Bone cysts were disclosed if size and location suggested risk of fracture (e.g., femoral neck, case-by-case decision by the advisory board]. Most chondrogenic bone tumours were assumed to be enchondromas, which are primary benign tumours with little potential of malignant transformation. The risk of secondary malignant transformation is increased for endochondromas located in the axial skeleton and > 5 cm in diameter [69]. Enchondroma cannot reliably be differentiated from low-grade chondrosarcoma by MRI alone[70,71]. Chondrogenic bone tumours were disclosed if located in the axial skeleton and diameter > 5cm for short-time follow-up and correlation with clinical signs and other imaging modalities.
SEVERE BONE EDEMA
Differential diagnoses for bone marrow oedema vary widely depending on localization, age, clinical symptoms, and radiographic appearance (osteoarthritis, osteonecrosis, traumatic bone bruise, bone infarction, insufficiency/stress fracture, metastasis, transient bone marrow oedema syndrome, septic joint, osteomyelitis, leukaemia, and lymphoma) [72].
Bone oedema was not disclosed if it was most likely due to osteoarthritis, traumatic bone bruise, bone infarction, or early osteonecrosis. Bone oedema was communicated when it was assumed to be associated with fracture, osteomyelitis, osteonecrosis with destruction of the joint surface, and possible malignancy.
HEARTANDVESSELS
HEART FAILURE
Left ventricular ejection fraction (LVEF) was obtained for participants who underwent the cardiac MR module. If LVEF was < 35% heart failure was diagnosed.
Community-dwelling elderly persons with impaired LVEF have a substantial risk of death from congestive heart failure [73]. Therefore LVEF < 35% was disclosed.
MYOCARDIAL TUMOUR
One participant presented with a cardiac mass most likely originating from the myocardium.
The advisory board agreed upon disclosure since cardiac tumours are rare entities requiring special expertise and further diagnostic steps.
PERICARDIAL EFFUSION
One participant presented with pericardial effusion impairing diastolic ventricular filling.
The advisory board agreed upon disclosure since further increase in intrapericardial fluid volume was expected to cause decompensation.
VASCULAR STENOSIS
Arterial stenosis of the (1) renal artery and (2) aortic isthmus was identified.
(1)Renal artery stenosis causes hypertension and progressive renal failure. The need for revascularization and its benefits have been discussed controversly [74,75]. Disclosure allowed individual assessment of the need for treatment.
(2)One participant presented with aortic coarctation. The advisory board agreed upon disclosure due to the severely reduced life expectancy in untreated aortic coarctation [76].
VASCULAR ANEURYSM
Arterial aneurysms of the (1) splenic artery, (2) renal artery, (3) abdominal aorta (AAA), and (4) thoracic aorta were identified.
(1)No consensus has been reached regarding intervention in asymptomatic patients with splenic artery aneurysm. The smallest aneurysm that ruptured over a 4-year observation period at the Mayo Clinic was 2 cm [77]. It has been recommended to treat asymptomatic aneurysms greater than 2 cm in patients with a reasonable operative risk and life expectancy greater than 2 years[77,78]. Therefore all splenic aneurysms were disclosed.
(2)While the majority of renal artery aneurysms are asymptomatic, they are associated with hypertension in up to 73% of cases. A diameter greater than 1.5 cm requires repair. Aneurysm repair cures hypertension in 20-50% of cases [79]. Therefore, the single case encountered was disclosed.
(3)An AAA is a focal dilation of the abdominal aorta ≥ 1.5 times its normal diameter, by convention infrarenal aorta ≥ 3 cm [80]. The risk of rupture correlates with diameter of the aneurysm: 5-5.9 cm: 11% per year and ≥ 6 cm: 25% per year [81]. All AAAs were disclosed with recommendations:3-4 cm: yearly ultrasound examination, 4-4.5 cm: ultrasound examinationevery 6 months, ≥ 4.5 cm: referral to a vascular specialist [82].
(4)An aneurysm of the thoracic aorta is considered if diameter exceeds > 4.5 cm. All aneurysms need follow-up with regular imaging to monitor growth [83]. With regard to aneurysm size and risk of rupture or dissection, an annual rate of 2% for aneurysms5 cm, 3% for aneurysms 5 to 5.9 cm, and 7% for aneurysms > 6 cm was found [84]. Surgery is indicated for a diameter of > 5.5 cm or 6 cm in patients with an increased operative risk [83].
INTRACRANIAL ANEURYSM
Intracranial aneurysm: saccular or fusiform dilatation of an intracranial artery.
Whether incidental aneurysms should be treated preventively has been discussed controversially [85-87].All findings were disclosed after neurosurgical/neuroradiological assessment by the advisory board with individualized recommendations for diagnosis, follow-up, and treatment.
CAVERNOUS MALFORMATION
Cavernous malformations (CMs) are benign vascular hamartomas with intralesional haemorrhages of different ages.
CMs can cause seizures or intracranial haemorrhage, yet 40% of cases are asymptomatic. Asymptomatic persons need not be treated. Therefore all CMs were discussed in the advisory board. Disclosure was decided on a case-by-case basis taking into account age, localization, and size of the malformation (region with high functional priority, e.g., brain stem, eloquent brain regions).
INTERNAL CAROTID ARTERY STENOSIS
Internal carotid artery (ICA) stenosis was classified according to the NASCET method: % stenosis = (normal lumen - minimal residual lumen) / (normal lumen x 100) [88].
ICA stenosis  50% was disclosed to allow further individual assessment since in asymptomatic patients younger than 75 with carotid diameter reduction ≥ 70% carotid, endarterectomy was shown to halve the 5-year stroke risk [89].

Note–. Gray-shaded cells indicate precedents.