Differential Diagnosis of Hemoptysis in Children

Common

• Foreign-body aspiration
• Infection: Cystic fibrosis, bronchiectasis, tuberculosis
• Upper airway bleeding
• Hematemesis

Less common

• Trauma: Accidental, tracheostomy, nonaccidental
• Cardiac: Congenital heart disease, pulmonary hypertension, pulmonary embolism

Rare

• Mass: Adenoma, carcinoid, arteriovenous fistula
• Primary bleeding disorder

Very rare

• Pulmonary-renal syndromes: Goodpasture syndrome, systemic lupus erythematosus, Wegener granulomatosis, microscopic polyangiitis, Henoch-Schonlein purpura
• Idiopathic pulmonary hemosiderosis

References

Godfrey S. Pulmonary hemorrhage/hemoptysis in children. Pediatr Pulmonol. 2004 Jun;37(6):476-84.

Endometrioid Ovarian Carcinoma

Endometrioid ovarian carcinoma represents up to 15% of ovarian malignancies. Unlike serous and mucinous ovarian neoplasms, but similar to clear cell tumors, the overwhelming majority of endometrioid tumors are malignant and invasive. Thus, they constitute the second most common malignant ovarian neoplasm.

Approximately 25% of endometrioid cancers are bilateral and up to 1/3 are associated with endometrial hyperplasia or carcinoma. Despite the histologic similarity between the endometrial and ovarian lesions, they are thought to represent independent primary lesions rather than metastatic disease.

Pathologically, most endometrioid carcinomas are thought to arise from the surface epithelium and only rarely from pre-existing endometriosis.

Similar to other epithelial ovarian neoplasms, endometrioid ovarian carcinomas have variable cystic and solid components, but unlike the others, they may occasionally be completely solid. A solid ovarian tumor in a postmenopausal woman with concomitant endometrial neoplasm or hyperplasia would suggest the diagnosis of an endometrioid ovarian carcinoma.

References

• Kawamoto S, Urban BA, Fishman EK. CT of epithelial ovarian tumors. Radiographics. 1999 Oct;19 Spec No:S85-102.
• Wagner BJ, Buck JL, Seidman JD, McCabe KM. From the archives of the AFIP. Ovarian epithelial neoplasms: radiologic-pathologic correlation. Radiographics. 1994 Nov;14(6):1351-74.

DXA and Bone Mineral Density

A story on NPR on the emergence of osteopenia as a bone disease due in part to the efforts Merck inspired a closer look at dual x-ray absorptiometry (DXA) and bone mineral density (BMD) measurements.

Introduction

DXA has 3 major roles:

• Diagnosis of osteoporosis
• Monitoring response to treatment
• Assessment of fracture risk

T-scores using WHO criteria are used for patients older than 50 years of age. For patients under 50 years of age, the Z-score should be used for interpretation. Children's DXA scans should also be interpreted using Z-scores, since BMD measurements in children are affected to a greater extent by bone size.

Measurement Sites

Hip BMD is the most reliable measurement for predicting hip fracture risk, while all DXA sites are more or less equally effective at predicting an osteoporotic fracture at any site.

Spine BMD is best used for monitoring treatment response. This is because treatment changes tend to be greatest in the spine and spine BMD measurements have low precision error. However, spine DXA has limited sensitivity, and its use in monitoring patients is more controversial than its use for the diagnosis of osteoporosis and prescription of treatment. Therefore, it is recommended that follow-up scans be obtained no sooner that every 1-2 years.

For spine measurements to be diagnostic, at least 2 vertebral bodies must be used. In addition, DXA precision is decreased in obese patients and those who have large weight changes between scans.

Peripheral measurement sites (as opposed to the central hip and spine sites) can also be used, but with caution. Peripheral measurements other than "33% radius" (distal 1/3 of the radius shaft) cannot be interpreted with T-scores and WHO criteria. This is because when reference values for the different BMD measurement sites are plotted as a function of age, the hip, spine and 33% radius decline at the same rate. Reference values for other sites decline at different rates. For example, reference values for the heel decline at a much slower rate and can lead to underdiagnosis of osteoporosis if the -2.5 SD is used.

Risk Stratification

For a given hip T-score, fracture risk varies greatly according to age and other risk factors. The FRAX (Fracture Risk Assessment Xool [that's Tool with an X] initiative estimates the 10-year probability of the patient sustaining an osteoporotic fracture based on a number of risk factors. In addition, it uses "health economic criteria to set thresholds for intervention based on the costs of treatment, savings to health services, and the contribution of fracture prevention to patients' quality of life."

FRAX risk factors include:

• Country or geographic region
• Ethnic origin (US only)
• Age
• Gender
• BMI
• Previous history of fracture (after age 50)
• Parental history of hip fracture
• Current smoking habit
• Current or past use of corticosteroids
• Rheumatoid arthritis
• Secondary osteoporosis
• Alcohol intake ≥3 units daily
• Hip BMD (femoral neck was used in the development of the algorithm)

The FRAX web site can also be used without the hip BMD to determine who may benefit most from DXA.

Treatment Guidelines

Treatment Criteria from the National Osteoporosis Foundation 2008 Guidelines recommend treatment in postmenopausal women and men age 50 and older regardless of ethnicity who meet one or more of the following criteria:

• A previous hip or vertebral fracture
• T score −2.5 or less at the femoral neck, total hip, or spine
• T score between −1.0 and −2.5 at the femoral neck, total hip, or spine and one or more of the following:
  • a. Other previous fractures
  • b. A secondary cause of osteoporosis associated with a high risk of fracture
  • c. 10-year fracture risk as assessed by FRAX of 3% or more at the hip or 20% for a major osteoporosis-related fracture (humerus, forearm, hip, or clinical vertebral fracture)

References

Blake GM, Fogelman I. An update on dual-energy x-ray absorptiometry. Semin Nucl Med. 2010 Jan;40(1):62-73.

Malacoplakia of the Urinary System

Malacoplakia, Greek for "soft plaque," is a rare chronic granulomatous process that most commonly affects the urinary tract (mainly bladder), but can be seen in almost any organ.

Malacoplakia of the urinary system is predominantly found in middle aged women. Patients may present with gross hematuria and signs of urinary tract infection.

There is a high association with Escherichia coli infection and suppressed immune function (e.g., diabetes, post-transplant, etc.). The impaired immune function results in phagocytosis of bacteria with incomplete digestion. The mineralized bacterial products in phagolysosomes result in calcified intracellular inclusions called Michaelis-Gutmann bodies, which are pathognomonic.

Bladder

40% of cases of urinary system malacoplakia involve the bladder. The appearance on cross-sectional imaging is nonspecific and varied. There may be circumferential bladder wall thickening or multiple, polypoid, vascular, solid masses with or without invasion of the perivesical space. Less commonly, there may be a predominantly extravesical mass. There may also be vesicoureteric reflux and dilatation of the upper urinary tract. Calcification is not generally seen, although bladder wall adherent calculi have been described after treatment.

Biopsy is needed for definitive diagnosis, given the nonspecific appearance.

Kidney

About 15% of cases of urinary system malacoplakia involve the kidney as the primary site. Malacoplakia of the kidney, unlike that of the bladder, is progressive, nephrotoxic, and potentially lethal. The appearance is that of an infiltrative multifocal process.

On cross sectional imaging, the kidney is enlarged and contains multiple (in 75% of cases) or a solitary hypovascular mass(es). Approximately 50% of cases are bilateral. The lesions range from a few millimeters up to 4 cm and may coalesce into large masses that distort the contour of the kidney.

On ultrasound, the lesions are poorly defined and hypoehoic. On MRI, the lesions are hypointense on T1- and T2-weighted images and there is delayed enhancement of intervening fibrous stroma.

Ureters

About 10% of cases malacoplakia have ureteral involvement. Isolated involvement of ureter without renal involvement is very rare and is thought to reflect a less aggressive variant of the disease.

References

• Craig WD, Wagner BJ, Travis MD. Pyelonephritis: radiologic-pathologic review. Radiographics. 2008 Jan-Feb;28(1):255-77;
• Inoue T, Nishiyama H, Yoshimura K, Ito N, Kamoto T, Habuchi T, Ogawa O. Solitary upper ureteral malakoplakia successfully diagnosed by ureteroscopic biopsy and treated conservatively. Int J Urol. 2007 Sep;14(9):859-61.
• Long JP Jr, Althausen AF. Malacoplakia: a 25-year experience with a review of the literature. J Urol. 1989 Jun;141(6):1328-31.
• Wong-You-Cheong JJ, Woodward PJ, Manning MA, Davis CJ. From the archives of the AFIP: Inflammatory and nonneoplastic bladder masses: radiologic-pathologic correlation. Radiographics. 2006 Nov-Dec;26(6):1847-68.

Ovarian Artery Variants

The ovarian arteries most commonly (80%-90% of cases) arise anteromedially from the abdominal aorta a few centimeters inferior to the origin of the renal arteries. They may be difficult to visualize on angiography due to their small caliber (< 1 mm). If they are seen, they demonstrate a characteristic corkscrew appearance. The ovarian arteries may also arise from the renal, lumbar, adrenal, or iliac arteries.

In 40% of cases, the ovaries are supplied solely by the ovarian arteries. In about 55% of cases, both the uterine and ovarian arteries supply the ovaries, while in about 5% of cases, the uterine arteries alone supply the ovaries.

The last variant may be due congenital absence of the ovarian artery, occlusive lesions at the level of the ovarian artery or the aorta, or ovarian abnormalities (e.g., tumor or inflammatory conditions causing neovascularization). If such a case is identified on angiography, a coexistent ovarian abnormality must be excluded.

Another source of variability important in uterine fibroid embolization (UFE) is the different anastomotic connections between the uterine and ovarian arteries, which may be seen in up to 30% of cases.

• Type I: There is flow from the ovarian artery to the uterus through anastomoses with the tubal branch of the uterine artery. Following UFE, the ovarian supply is not likely to be a source of procedural failure.
  • Type Ia: Flow in the tubal artery is toward the uterus, without evidence of retrograde reflux to the ovary.
  • Type Ib: Flow in the tubal artery is toward the uterus, but there is evidence of retrograde reflux to the ovary. Injection of embolic particles into the uterine artery may cause reflux into the tubo-ovarian segment and may cause embolization of the ovary.
• Type II: There is a direct blood supply to a fibroid from the ovarian artery without prior connection to the uterine artery. Following UFE, the fibroid may continue to be supplied, and the ovarian artery can be a cause of procedural failure.
• Type III: The dominant blood supply to the ovary is from the uterine artery (see also above). This is important in UFE, as there is a high likelihood of ovarian artery embolization.

References

• Pelage JP, Cazejust J, Pluot E, Le Dref O, Laurent A, Spies JB, Chagnon S, Lacombe P. Uterine fibroid vascularization and clinical relevance to uterine fibroid embolization. Radiographics. 2005 Oct;25 Suppl 1:S99-117.
• Razavi MK, Wolanske KA, Hwang GL, Sze DY, Kee ST, Dake MD. Angiographic classification of ovarian artery-to-uterine artery anastomoses: initial observations in uterine fibroid embolization. Radiology. 2002 Sep;224(3):707-12.

Tube Management in Percutaneous Cholecystostomy

Indications for percutaneous cholecystostomy include calculous and acalculous cholecystitis, gallbladder perforation, malignant obstruction, percutaneous biliary stone removal, biliary duct drainage, and diagnostic imaging of the gallbladder and biliary ductal system. Evidence-based indications for percutaneous cholecystostomy in elderly and critically ill patients have not been established, however. (Winbladh et al, 2009).

The tube can be removed once 1) the patient has recovered from the contributory underlying illness, 2) a catheter cholangiogram has confirmed cystic and bile duct patency, and 3) the tube has drained for a minimum of 3 weeks (Wise et al, 2005).

The last requirement is to ensure maturation of a tract around the tube in order to reduce risk of bile leakage and associated peritonitis and/or sepsis. To this end, some have advocated tract imaging prior to removal. However, this may not be necessary "in patients with small-bore gallbladder catheters [e.g., 8-French] who have recovered from critical illness, show patent cystic and common ducts, and have had catheters for 3–6 weeks." (Wise et al, 2005).

In patients with calculous cholecystitis, percutaneous gallstone extraction may be performed before tube removal.

References

• Davis CA, Landercasper J, Gundersen LH, Lambert PJ. Effective use of percutaneous cholecystostomy in high-risk surgical patients: techniques, tube management, and results. Arch Surg. 1999 Jul;134(7):727-31;
• Winbladh A, Gullstrand P, Svanvik J, Sandström P. Systematic review of cholecystostomy as a treatment option in acute cholecystitis. HPB (Oxford). 2009;11(3):183-93.
• Wise JN, Gervais DA, Akman A, Harisinghani M, Hahn PF, Mueller PR. Percutaneous cholecystostomy catheter removal and incidence of clinically significant bile leaks: a clinical approach to catheter management. AJR Am J Roentgenol. 2005 May;184(5):1647-51.

Reye Tumor

Reye tumor, more properly called inclusion body fibromatosis, is also known as digital neurofibrosarcoma, infantile digital fibromatosis, infantile dermal fibromatosis, infantile digital fibroma, infantile dermal fibroma, infantile digital myofibromatosis, and digital fibrous tumor of infancy and childhood.

These dome-shaped nodules involve the extensor surfaces of the distal or middle phalanges of the fingers (more common) and toes. They have a preference for the ulnar-sided and lateral digits in the hand and foot, respectively. The majority are diagnosed in the first year of life (about 1/3 are congenital).

There may be a nonspecific soft-tissue mass on radiographs. US, CT, and MRI of inclusion body fibromatosis is also nonspecific: a heterogeneous, poorly marginated, subcutaneous soft-tissue mass similar to other superficial fibromatoses.

References

Murphey MD, Ruble CM, Tyszko SM, Zbojniewicz AM, Potter BK, Miettinen M. From the archives of the AFIP: musculoskeletal fibromatoses: radiologic-pathologic correlation. Radiographics. 2009 Nov;29(7):2143-73.

Indications for Renal Artery Angioplasty and Stent Placement

Introduction

Percutaneous angioplasty and stent placement may be performed for renal artery stenosis causing renovascular hypertension or for preserving renal function. Regarding the former indication, up to 5% of patients with hypertension have atherosclerotic renal artery stenosis. The hypertension cure and response rates following stent placement range from 60% to 80%.

Regarding ischemic nephropathy (loss of renal function caused by renal ischemia from renal artery stenosis), there is improvement in renal function in about 25% to 35% and stabilization of renal function in the same percentage of patients. However, about 1/3 of patients showed deterioration of renal function.

Indications

Class I indications (there is evidence and/or general agreement that a given procedure or treatment is beneficial, useful, and effective):

• New-onset hypertension before 30 or severe hypertension after 55
• Accelerated, resistant, or maligant hypertension
• Development of new azotemia or worsening renal function after the administration of ACE inhibitors or angiotensin receptor blockers
• Unexplained atrophic kidney or a discrepancy in size between the two kidneys of >1.5 cm.
• Sudden, unexplained pulmonary edema: Patients with severe bilateral renal artery stenosis may present with recurrent pulmonary edema with or without left ventricular systolic dysfunction. Revascularization may decrease the recurrence of angina and pulmonary edema.

Class IIa indication (weight of evidence/opinion is in favor of usefulness/efficacy):

• Unexplained renal failure, including in individuals starting renal replacement therapy.

Class IIb indications (usefulness/efficacy is less well established by evidence/opinion):

• Multivessel coronary artery disease: Significant renal artery stenosis results in activation of the renin–angiotensin–aldostenrone system resulting in renovascular hypertension and increases cardiovascular and renal morbidity.
• Unexplained heart failure or refractory angina

Importantly, there is no evidence to support revascularization of asymptomatic high-grade renal artery stenosis incidentally diagnosed while imaging for unrelated causes (e.g., "drive-by" intervention during cardiac catheterization).

An important complication of renal artery angioplasty and stenting is acute renal failure, which occurs in 10%-20% of cases.

Future Directions

The angioplasty and stent for renal artery lesions (ASTRAL) trial compared the effect of maximal medical therapy plus revascularization to medical management alone on hypertension, renal function, and cardiovascular events in patients with atherosclerotic renal artery stenosis and renal failure. Results after one year showed no statistically significant difference in the serum creatinine, cardiovascular, and cerebrovascular events, hospitalization rates for cardiovascular causes, and risk-adjusted mortality rate between the two groups.

The cardiovascular outcomes in renal atherosclerotic lesions (CORAL) is ongoing and will compare the effect of optimal medical therapy plus stent supported angioplasty to optimal medical therapy alone on multiple cardiovascular and renal end points.

References

• Hirsch AT, Haskal ZJ, Hertzer NR, et al. (2006) ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. Circulation 113(11):e463–e654.
• Martin EC, Mattern RF, Baer L, Fankuchen EI, Casarella WJ (1981) Renal angioplasty for hypertension: predictive factors for long-term success. AJR Am J Roentgenol 137(5):921–924
• Thatipelli M, Misra S. Endovascular intervention for renal artery stenosis. Abdom Imaging. 2009 Sep 29.

Mazabraud Syndrome

Mazabraud syndrome is the association of fibrous dysplasia with soft-tissue myxomas. The soft-tissue myxomas are much more common with polyostotic fibrous dysplasia but can also be seen in the monostotic form. The myxomas (which may be multiple) tend to occur close to the most severely affected bones.

Differential considerations include:

• Neurofibromatosis: There may be osseous changes in neurofibromatosis (bowing, pathologic fracture, and pseudarthrosis) in association with soft tissue masses. The osseous changes are easily differentiated from fibrous dysplasia.
• Metastases: The soft tissue mass will not generally have well-defined margins.
• Multiple myeloma: There may be extraosseous involvement in about 50% of patients. Subcutaneous nodules are common.
• Maffucci syndrome: Enchondromatosis with soft-tissue hemangiomas.
• Lymphoma: Focal muscle involvement is rare.

References

Kransdorf MJ, Murphey MD. Diagnosis please. Case 12: Mazabraud syndrome. Radiology. 1999 Jul;212(1):129-32.

The Dog Leg Sign

The dog leg sign, seen on an arteriogram of the popliteal region, refers to an acute bend in the apparent course of the popliteal artery. It is characteristically produced by a mural thrombus associated with aneurysmal dilatation of the popliteal artery.

The dog leg sign is an important secondary sign of popliteal artery aneurysms, because about 25% of popliteal artery aneurysms are not associated with angiographically visible popliteal artery dilatation. In such cases, ultrasound may be used to detect an angiographically occult aneurysm. Depending on the presence of mural thrombus, ultrasound may show a dilated, cystic structure with flow or a complex, cystic structure with flow and areas of echogenic thrombus.

The presence of this sign should also prompt investigation for other aneurysms, since 40% of popliteal aneurysms are associated with abdominal aortic aneurysms, 25% are associated with iliac arterial aneurysms, 35% are associated with femoral arterial aneurysms, and 50% are bilateral.

Other conditions may mimic the dog leg sign by causing deviation (though not typically an acute bend) of the course of the popliteal artery lumen:

• Tortuous and atherosclerotic popliteal artery
• Popliteal arterial entrapment syndrome: Passive dorsiflexion at arteriography will accentuate arterial narrowing.
• Adventitial cystic disease: There is eccentric narrowing of the popliteal artery. Ultrasound will show a cystic structure without flow in the arterial wall.
• Baker cyst.

References

Uppal A. The dog leg sign. Radiology. 2000 Feb;214(2):339-40.

Acute Vascular Insufficiency of the Limb

The differential diagnosis of acute vascular insufficiency of the limb in young people includes:

• Premature/accelerated atherosclerosis: Can be due to traditional risk factors for atherosclerosis, drugs (e.g., corticosteroids), and autoimmune and inflammatory mechanisms.
• Buerger disease (thromboangiitis obliterans): Rare disease of small and medium-sized peripheral arteries and veins. Most commonly seen in Ashkenazi Jews in Israel. Smoking is the most important risk factor.
• Adventitial cystic disease: Rare disease of young adults (mainly men) characterized by a highly viscous and mucinous cyst in the adventitia of an artery. The cyst may enlarge, causing compression. Most commonly seen in the popliteal artery.
• Adductor canal compression syndrome: Similar mechanism as popliteal artery entrapment syndrome (see below). Due to compression of the superficial femoral artery by an abnormal musculotendinous band arising from the adductor magnus muscle and lying adjacent and superior to the adductor tendon. Can occur following exercise.
• Popliteal artery entrapment syndrome: Due to anomalous anatomic relationships between the popliteal artery and surrounding musculotendinous structures. Most commonly, the popliteal artery courses through or around the medial head of the proximal gastrocnemius muscle.
• Microemboli.
• Collagen vascular disease.
• Takayasu arteritis: Vasculitis of the large vessels, usually involving the aorta and its main branches, and the upper extremities. Typically affects Asian women younger than 40 years of age.
• Coagulopathy.

References

• Małecki R, Zdrojowy K, Adamiec R. Thromboangiitis obliterans in the 21st century--a new face of disease. Atherosclerosis. 2009 Oct;206(2):328-34. Epub 2009 Feb 12.
• Papas TT, Georgiadis GS, Maltezos CK, Lazarides MK. Adventitial cystic disease of the popliteal artery: a potential cause of intermittent claudication. Wien Klin Wochenschr. 2007;119(5-6):186-8.
• Radonić V, Koplić S, Giunio L, Bozić I, Masković J, Buća A. Popliteal artery entrapment syndrome: diagnosis and management, with report of three cases. Tex Heart Inst J. 2000;27(1):3-13.
• Verta MJ Jr, Vitello J, Fuller J. Adductor canal compression syndrome. Arch Surg. 1984 Mar;119(3):345-6.

Dupuytren Disease

Superficial fibromatoses are fibroblastic proliferations that are genetically distinct from the deep fibromatoses. They tend to arise in the palmar or plantar soft tissues. Like their deep counterparts (e.g., desmoid fibromatosis) they are characterized by infiltrative growth, a tendency to locally recur, and no metastatic potential.

Dupuytren disease, or palmar fibromatosis, is the most common superficial fibromatosis, affecting about 1% of the population and 20% of people over 65 years of age. The lesions more commonly affect the ulanr-sided digits and are bilateral in about 50% of patients. These painless subcutaneous nodules may progress to cords or bands that pull on the underlying flexor tendons, causing Dupuytren contractures.

On MRI, there are multiple nodular or band-like soft tissue masses that arise from the proximal palmar aponeurosis parallel to the flexor tendons and terminate in a branching or nodular pattern at the level of the distal metacarpal. The signal intensity of the nodules and cords is variable. Lesions with higher cellular content (and less abundant collagen) tend to have higher signal intensity on T1- and T2-weighted images and more prominent enhancement. These lesions also tend to have higher rates of local recurrence after resection. It has been suggested that these lesions be allowed to "mature" more (i.e., become less cellular and more collagenous) before surgical resection is attempted in order to reduce rates of recurrence.

Ultrasound shows hypoechoic and hypervascular nodules superficial to the flexor tendons.

There is an association with other fibromatoses: Up to 20% have plantar fibromatosis (Ledderhose disease), while Peyronie disease and knuckle pad involvement can also be seen.

Surgery is the treatment of choice, and is usually reserved for symptomatic patients or those with flexion contracture greater than 20 degrees at the metacarpophalangeal joint and more than 30 degrees at the proximal interphalangeal joint.

References

• Goldblum JR, Fletcher JA. Superficial fibromatoses. in Pathology and Genetics of Tumours of Soft Tissue and Bone. Fletcher CDM, Unni KK, Mertens F (eds). IARCPress Lyon, 2002. pp 82-82.
• Montgomery E, Lee JH, Abraham SC, Wu TT. Superficial fibromatoses are genetically distinct from deep fibromatoses. Mod Pathol. 2001 Jul;14(7):695-701.
• Murphey MD, Ruble CM, Tyszko SM, Zbojniewicz AM, Potter BK, Miettinen M. From the archives of the AFIP: musculoskeletal fibromatoses: radiologic-pathologic correlation. Radiographics. 2009 Nov;29(7):2143-73.

Multiple Lucent Metaphyseal Lesions in Infants

The differential diagnosis of multiple lucent metaphyseal lesions in infants includes:

• Neurofibromatosis
• Hemangiomatosis, lymphangiomatosis
• Metastatic neuroblastoma
• Myofibromatosis (congenital generalized fibromatosis)

References

Patrick LE, O'Shea P, Simoneaux SF, Gay BB Jr, Atkinson GO. Fibromatoses of childhood: the spectrum of radiographic findings. AJR Am J Roentgenol. 1996 Jan;166(1):163-9

Rhomboid Fossa of the Clavicle

The rhomboid fossa is a normal concave lucent irregularity that may be seen along the inferomedial aspect of the clavicle. It is the insertion site of the costoclavicular ligament. The rhomboid fossa may be mistaken for an osteolytic lesion or apical pneumothorax.

References

Kumar R, Madewell JE, Swischuk LE, Lindell MM, David R. The clavicle: normal and abnormal. Radiographics. 1989 Jul;9(4):677-706.

Periosteal Reaction in Pediatrics

The differential diagnosis of periosteal reaction in pediatrics includes:

• Physiologic: Due to rapid growth
• Infection/inflammation
• Healing fracture
• Metabolic: Scurvy, vitamin A or D toxicity, Gaucher disease, etc.
• Tumor
• Prematurity: May be due to prostaglandin E, metabolic disease of prematurity, physiologic
• Melorheostosis

References

Musculoskeletal Radiology: The Requisites. Third edition. Chapter 3.

All About SUVs

The maximum (not average) activity in the region of interest (ROI) should be used, because small ROIs can result in higher average SUVs. In addition, because obese patients generally have higher SUVs in both normal and malignant tissue, lean body mass is preferred in the nominator. Finally, administered activity, the denominator of the equation, is affected by technical factors like extravasation and the amount of FDG remaining in the syringe following injection.

Specific uptake values for FDG in PET must be obtained from the attenuation corrected data. An SUV of 1 g/mL means that the FDG is uniformly distributed throughout the body.
SUV_max of Liver: 2.5 g/mL
SUV_max of Blood: 2.3 g/mL
SUV_max of Spleen: 1.9 g/mL
SUV_max of Bone marrow: 1.0 g/mL
SUV_max of Lung: 0.7 g/mL

Minor changes in scan technique can change SUVs by up to 30%. Delaying image acquisition following injection can also increase SUVs, since FDG continues to accumulate in tumors for up to two hours.

References

Mettler FA and Guiberteau MJ. Chapter 13: PET Imaging. In Essentials of Nuclear Medicine Imaging. Fifth Edition. Saunders, Philadelphia. 2006. pp 375-376.

Sequential Thallium and Gallium Scanning in AIDS Patients with Pulmonary Lesions

Pulmonary lesions in AIDS patients pose a diagnostic problem. Sequential thallium (delayed at 3 hours) and gallium imaging can help differentiate between infection, lymphoma, and Kaposi sarcoma.

	Thallium	Gallium
Kaposi	+	-
Lymphoma	+	+
Infection	-	+

Thallium scans are obtained 3 hours after injection. Gallium scans are obtained 48-72 hours after injection.

References

Lee VW, Fuller JD, O'Brien MJ, Parker DR, Cooley TP, Liebman HA. Pulmonary Kaposi sarcoma in patients with AIDS: scintigraphic diagnosis with sequential thallium and gallium scanning. Radiology. 1991 Aug;180(2):409-12.

153Sm-lexidronam (Quadramet)

Quadramet (¹⁵³Sm-lexidronam) has a physical half-life of about 46 hours and decays with emissions of both β and γ particles. The β particles have energies of 810 keV (20%), 710 keV (50%), and 640 keV (30%). The γ photon energy is 103 keV, and can be used to image the biodistribution of Quadramet with a gamma camera (see below).

Most of the injected Quadramet is rapidly taken up by osteoblastic bone metastases in proportion to the extent of metastases, causing some interpatient variability. The remainder is rapidly excreted in urine within about 6 hours, which is also subject to interpatient variability. The urinary route of excretion should be considered when prescribing Quadramet to patients with decreased renal function.

Before starting therapy, a routine bone scan must be performed to determine if there will be uptake of the radiopharmaceutical. A bone scan will also define the extent of lesion(s), since one or two lesions are best treated with external beam radiation.

Like other nuclear medicine therapies for painful osseous metastases (strontium-89 and rhenium-186 HEDP), there may be a transient increase in bone pain in the first 2-3 days that lasts for several days. Like strontium-89, approximately 10% of patients will have a painful flare response within 48 hours after initiation of therapy. Symptomatic improvement begins about 1-3 weeks after treatment and often lasts 3-6 months.

Quadramet is limited by its main side effect, bone marrow suppression. Low leukocyte (less than 2,400/μL) or platelet (less than 60,000/μL) counts are contraindications to its use. Leukocyte and platelet counts are obtained every two weeks following therapy until marrow recovery occurs. Leukocyte and platelet counts are reduced by about 50%, with the low-point occurring about a month after therapy, and with recovery occurring after about 6 weeks.

Another contraindication is an allergy to phosphates. Quadramet also should not be administered on the same day as other intravenous bisphosphonates due to competition for the same binding sites.

Finally, Quadramet therapy will not help if the patient's pain is due non-osseous metastases (e.g., an epidural lesion causing nerve root compression) or pathologic fractures.

References

• Mettler FA and Guiberteau MJ. Chapter 9: Skeletal System. In Essentials of Nuclear Medicine Imaging. Fifth Edition. Saunders, Philadelphia. 2006. p 290.
• Serafini AN. Therapy of metastatic bone pain. J Nucl Med. 2001 Jun;42(6):895-906.

Hyperglycemia and Hyperinsulinemia in FDG-PET Imaging

Acute hyperglycemia can cause decreased uptake of FDG by tumor cells, decreasing sensitivity. Hyperglycemia can also stimulates insulin release, which preferentially drives glucose and FDG into skeletal muscle. Glucose loading has been shown to have a greater effect on FDG uptake in inflammatory lesions than in tumors, which has been suggested as a way of differentiating the two. However, I haven't seen this used in practice.

Chronic hyperglycemia is a different, and more controversial issue.

On the other side of the spectrum, hyperinsulinemia can diffusely increase uptake of FDG and can lower sensitivity by decreasing the amount of FDG available to tumor cells. The Society of Nuclear Medicine recommends that if insulin is considered to normalize blood glucose, the administration of FDG be delayed for a time period depending on the type and route of administration of insulin.

References

• Delbeke D, Coleman RE, Guiberteau MJ, Brown ML, Royal HD, Siegel BA, Townsend DW, Berland LL, Parker JA, Hubner K, Stabin MG, Zubal G, Kachelriess M, Cronin V, Holbrook S. Procedure guideline for tumor imaging with 18F-FDG PET/CT 1.0. J Nucl Med. 2006 May;47(5):885-95.
• Torizuka T. Clavo AC. Wahl RL. Effect of hyperglycemia on in vitro tumor uptake of tritiated FDG, thymidine,L-methionine and L-leucine. J Nucl Med 1997; 38:382-386.
• Torizuka T, Fisher SJ, and Wahl RL. Insulin-induced hypoglycemia decreases uptake of 2-(F-18)-fluoro-2-deoxy-D-glucose into experimental mammary carcinoma. Radiology 1997; 203:169-172.
• Zhao S, Kuge Y, Tsukamoto E, Mochizuki T, Kato T, Hikosaka K, Hosokawa M, Kohanawa M, Tamaki N. Effects of insulin and glucose loading on FDG uptake in experimental malignant tumours and inflammatory lesions. Eur J Nucl Med. 2001 Jun;28(6):730-5.

Molybdenum Breakthrough

Molybdenum breakthrough refers to contamination of ^99mtechnetium obtained by elution of a molybdenum-99 column. The ^99mTc generated must be tested for molybdenum before administration to patients. The US Nuclear Regulatory Commission (NRC) allow no more than 0.15 μCi of ⁹⁹Mo per 1 mCi of ^99mTc at the time of administration. The last part is important. Because the half life of ⁹⁹Mo is longer than that of ^99mTc (66 hours vs 6 hours), if you let the eluate sit around, the relative concentration of ⁹⁹Mo will rise, making it unusable.

Testing for molybdenum breakthrough is usually done by placing the eluate in a lead shield and using a commercial dose calibrator whose energy is set to that of ⁹⁹Mo photons(740 keV and 780 keV).

References

Mettler FA and Guiberteau MJ. Chapter 3: Quality Control. In Essentials of Nuclear Medicine Imaging. Fifth Edition. Saunders, Philadelphia. 2006. p 44.

Meckel Scan

About 50% of Meckel diverticuli have gastric mucosa, which may cause bleeding by ileal mucosal ulceration from acid secretion. On the other hand, 95% of Meckel diverticula that bleed have ectopic gastric mucosa.

^99mTc-pertechnetate accumulates in mucus-secreting cells of the gastric mucosa (not the acid-secreting cells) and can be used to identify ectopic gastric mucosa in a Meckel diverticulum in a patient who is not actively bleeding (sensitivity and specificity of about 90%). Patients with active bleeding are best evaluated with radiolabeled blood cells.

Although a Meckel diverticulum may appear anywhere within the abdomen, it is classically seen in the right lower quadrant. A positive scan will show activity in the ectopic gastric mucosa at the same time as the activity in the normal gastric mucosa. A small Meckel diverticulum may seem to appear at a later time than the stomach. This can lead to a potential pitfall: Activity in the kidneys, ureter or bladder usually first appears after activity is seen in the normal gastric mucosa.

Another pitfall is pertechnetate secreted by the gastric mucosa accumulating in the small bowel. This can be differentiated from a true positive scan by the delayed appearance of an area of mildly, ill-defined increased activity. A nasogastric tube or left lateral decubitus positioning can be used to decrease the likelihood of false positive results due to passage of radiotracer from the stomach into the small bowel.

Other causes of false positive results include hyperemia due to intussusception inflammatory bowel disease or other small bowel lesions; vascular lesions, intestinal duplication cysts containing gastric mucosa.

False negative scans can occur due to ileal malrotation, small amounts of gastric mucosa, and rapid clearance of ^99mTc-pertechnetate due to localized bowel irritability.

Pre-Treatment

While pre-treatment is not necessary, some pharmacologic interventions have been used to increase sensitivity. Pentagastrin, a gastrin analog, stimulates gastric secretions and increases gastric mucosa uptake of pertechnetate. Histamine H₂ blockers (e.g., cimetidine and ranitidine) block secretion from the cells and increase gastric mucosa uptake.

Pentagastrin is administered subcutaneously 20 minutes prior to ^99mTc-pertechnetate, while oral cimetidine is given 4 times a day 2 days prior to ^99mTc-pertechnetate. Cimetidine can also be given intravenously one hour prior to imaging.

Giving an H2 blocker and pentagastrin in combination is not recommended, as H2 blockers antagonize pentagastrin.

References

• Ford PV, Bartold SP, Fink-Bennett DM, Jolles PR, Lull RJ, Maurer AH, Seabold JE. Society of Nuclear Medicine Procedure Guideline for Gastrointestinal Bleeding and Meckel’s Diverticulum Scintigraphy. February 7, 1999
• Mettler FA and Guiberteau MJ. Chapter 8: Gastrointestinal Tract. In Essentials of Nuclear Medicine Imaging. Fifth Edition. Saunders, Philadelphia. 2006. pp 216-218.

Angulation and Healing in Children's Fractures

Children's bones heal better if angulation is in the plane of motion of the adjacent joint. For example, a tibial fracture with anterior or posterior angulation (sagittal plane=plane of motion of knee) heals better than one with varus or valgus angulation (coronal plane).

References

Musculoskeletal Radiology: The Requisites. Third edition. Chapter 3, page 49.

Focal Hot Spots on Ventilation/Perfusion Scan

Focal hot spots on a V/Q scan represent areas of MAA aggregation. These may be caused by small, clinically insignificant, labeled blood clots that form if blood is introduced into the syringe during injection (e.g., for conforming intravenous location) and allowed to sit. MAA aggregates may also form if there is failure to properly suspend the MAA particles during preparation or if they are not re-suspended after sitting on the bench for a while prior to injection.

This Photoshopped image of a VQ scan simulates this appearance.

References

Mettler FA and Guiberteau MJ. Chapter 7: Respiratory System. In Essentials of Nuclear Medicine Imaging. Fifth Edition. Saunders, Philadelphia. 2006. pp 161-162.

Factors Contributing to a False Positive Result on a Renal Function Scan

The following factors may produce a false positive (i.e., suggestion of obstruction) on renal function scans:

• Poor renal diuretic response: Due to poor hydration or diminished renal function.
• Non-compliant renal pelvis: Produces increasing resistance to increasing urine flow.
• Over-compliant renal pelvis: The urine excreted during the diuretic phase may not be able to completely fill an overly compliant renal pelvis, leading to continuously increasing counts post diuretic.
• Massive hydronephrosis: Same concept as above, but instead of an overly compliant renal pelvis, we simply have too much space to fill because of massive hydronephrosis, leading to continuously increasing counts post diuretic. This is called the reservoir effect.
• Increased bladder pressure: Either due to over-distension or noncompliance, which can impair drainage from the ureters.

References

• Achong DM, Tenorio LE. Abnormal MAG3 renal scintigraphy resulting from dehydration. Clin Nucl Med. 2003 Aug;28(8):683-4.
• Mettler FA and Guiberteau MJ. Chapter 10: Genitourinary System and Adrenal Glands. In Essentials of Nuclear Medicine Imaging. Fifth Edition. Saunders, Philadelphia. 2006.

Gallbladder Visualization on MAG-3 Renal Scan

MAG3 may be visualized in the gallbladder in patients with renal failure or those in a fasting state.

Because of biliary excretion of MAG-3, it is possible for MAG-3 to accumulate in loops of bowel and mimic urinary leak in patients with renal insufficiency.

Image courtesy of Dr. Eric Rohren, M.D.

References

• Arroyo AJ, Semaan HB, Minkus KD, Patel YP. Factors affecting the hepatobiliary excretion of 99mTc-MAG3: its clinical significance in routine renography. J Nucl Med Technol. 2003 Mar;31(1):18-20.
• Dogan AS, Kirchner PT. Hepatobiliary excretion of MAG3. Simulation of a urinary leak. Clin Nucl Med. 1993 Sep;18(9):746-50.
• Taylor A Jr, Eshima D, Christian PE, Wooten WW, Hansen L, McElvany K. Technetium-99m MAG3 kit formulation: preliminary results in normal volunteers and patients with renal failure. J Nucl Med. 1988 May;29(5):616-22.

Toxic Multinodular Goiter vs Graves Disease

Toxic multinodular goiter may have a similar clinical presentation as Graves disease, and a thyroid scan can help differentiate the two.

The thyroid in a patient with Graves disease (bottom image, I-123) will be enlarged and demonstrate diffusely increased uptake without focal nodules. The thyroid in a patient with toxic multinodular goiter (top image, I-123) will demonstrate heterogeneous distribution of radiotracer with or without discrete "hot" nodules. Single toxic nodules are frequently associated with decreased uptake in the remainder of the gland. Quantitative uptake may be normal or only mildly elevated in toxic multinodular goiter.

A potential source of confusion is Graves disease in a patient with a nodular thyroid gland.

References

Sarkar SD. Benign thyroid disease: what is the role of nuclear medicine? Semin Nucl Med. 2006 Jul;36(3):185-93.

Destructive (Subacute) Thyroiditis

Destructive (subacute) thyroiditis may be caused by autoimmune disease, viral infection, or iodine overload (e.g., type II amiodarone-induced thyrotoxicosis). Viral infection is usually associated with a painful goiter, while autoimmune thyroiditis is usually painless.

The main differential consideration is iodine-induced hyperthyroidism (the Jod-Basedow effect, e.g., type I amiodarone-induced thyrotoxicosis). Scintigraphic features may mimic those of subacute thyroiditis; however, low-normal thyroid uptake (as opposed to very low) suggests Jod-Basedow effect.

The appearance of diffusely decreased thyroid uptake may also be seen with:

• Hypothyroidism:
• Medications: Amiodarone, iodinated contrast.
• Thyroid hormone therapy:
• Renal failure: Iodide excretion is diminished in advanced renal failure, leading to an increased iodide pool in the thyroid and diminished uptake of radiolabeled iodide by the thyroid.
• Ectopic thyroid hormone secretion from tumors: Struma ovarii ("ovarian goiter").

Our patient has hyperthyroidism with positive antithyroid antibodies. This image from an I-123 study shows diffusely decreased thyroid uptake. 4-hour and 24-hour uptake values were very low (1.2% and 3.5%, respectively).

References

Sarkar SD. Benign thyroid disease: what is the role of nuclear medicine? Semin Nucl Med. 2006 Jul;36(3):185-93.

Chondromyxoid Fibroma

Chondromyxoid fibromas are rare benign bone tumors composed of variable prportions of fibromyxoid tissue and cartilage tissue. They predominantly occur in adolescents and young adults and are usually found in the metaphyses of the long tubular bones, especially the tibia and femur near the knee joint. They may cross open growth plates into epiphyses or epiphyseal equivalents (e.g., the tibial tubercle, as in our case).

Chondromyxoid fibromas have a geographic pattern of bone destruction and are typically located eccentrically in the bone. Internally, the lesion is usually lucent, but ridges or septa can sometimes be seen. Calcifications, if present, can be seen on CT but not radiographs.

Peripherally, these tumors have a scalloped, sclerotic margin. The lesion can erode or balloon from the cortex, resulting in a buttress periosteal reaction.

Differential considerations on radiography include aneurysmal bone cyst, non-ossifying fibroma (cortical ballooning or destruction is rare), fibrous dysplasia (centrally located), adamantinoma (much more aggressive, older patients), and osteofibrous dysplasia (more sclerotic, younger patients).

MRI findings are nonspecific: intermediate to low signal intensity on T1-weighted images and high signal intensity on T2-weighted images.

Lateral and frontal radiographs of the proximal tibia of a 13-year-old boy show a lucent, expansile, metaphyseal lesion without a perceptable sclerotic border and with a narrow zone of transition. Axial CT image shows extension of the tumor through the anterior proximal tibial cortex with a large soft tissue component Pathologic analysis confirmed a diagnosis of chondromyxoid fibroma. Axial images show a T1-hypointense and T2-hyperintense soft tissue mass with extensive T2-hyperintensity in the surrounding marrow. Fat-saturated post-contrast sagittal image shows heterogeneous, predominantly peripheral, enhancement.

Also of interest: cartilage lesions by age and location.

References

• Greenspan A, Jundt G, Remagen W. Cartilage (Chondrogenic) Lesions. In Differential Diagnosis of Orthopaedic Oncology, 2nd Edition. 2007 Lippincott Williams & Wilkins; pp 207-212.
• Mehta S, Szklaruk J, Faria SC, Raymond AK, Whitman GJ. Radiologic-pathologic conferences of the University of Texas M. D. Anderson Cancer Center: Chondromyxoid fibroma of the sacrum and left iliac bone. AJR Am J Roentgenol. 2006 Feb;186(2):467-9.
• Wilson AJ, Kyriakos M, Ackerman LV. Chondromyxoid fibroma: radiographic appearance in 38 cases and in a review of the literature. Radiology. 1991 May;179(2):513-8.

Types of Accessory Navicular Bones

Coughlin has described 3 main types of accessory navicular bones:

• Type I ("os tibiale externum"): Up to 30% of cases. A 2–3 mm sesamoid bone in the posterior tibial tendon.
• Type II ("prehallux," shown in radiograph): 50-60% of cases. A triangular or heart-shaped ossicle that measures up to 12 mm. It arises from the secondary ossification center of the navicular bone and is connected to the navicular tuberosity by fibrocartilage or hyaline cartilage.
  
  Interestingly, the name prehallux was chosen to refer to this bone as the sixth toe seen in vertebrates such as the echidna and opossum. It is also thought that this bone may represent a reinforcement for a weakening and pronating foot arch (as a sort of kick-stand for a pes planus).
• Type III ("cornuate navicular"): The accessory navicular bone is connected to the navicular by a bony ridge.

While considered normal variants, type II and III accessory navicular bones can be associated with symptoms. Posterior tibial tendon tears can occur due to increased stress caused decreased leverage of the medial malleolus on the tendon from a more proximal insertion.

References

• Bernaerts A, Vanhoenacker FM, Van de Perre S, De Schepper AM, Parizel PM. Accessory navicular bone: not such a normal variant. JBR-BTR. 2004 Sep-Oct;87(5):250-2.
• Coughlin MJ. Sesamoid and accessory bones of the foot. In: Coughlin MJ (ed) Surgery of the foot and ankle, 8th edition. 2006. Elsevier, Amsterdam, pp 438–494
• Kidner, FC. The prehallux (accessory scaphoid) in its relation to flat foot. J. Bone Joint Surg. 1929 11(4):831–837.
• Miller TT, Staron RB, Feldman F, Parisien M, Glucksman WJ, Gandolfo LH. The symptomatic accessory tarsal navicular bone: assessment with MR imaging. Radiology. 1995 Jun;195(3):849-53.

Types of Navicular Fractures

Three types of navicular body fractures have been described by Sangeorzan et al

• Type 1: The fracture line is in the coronal plane of the foot. No angulation of the forefoot is seen.
• Type 2: The fracture line is in the dorsal-lateral to plantar-medial plane. The forefoot is displaced medially.
• Type 3: Comminuted fracture in the sagittal plane of the navicular body. There is lateral forefoot displacement.

References

Sangeorzan BJ, Benirschke SK, Mosca V, Mayo KA, Hansen ST Jr. Displaced intra-articular fractures of the tarsal navicular. J Bone Joint Surg Am. 1989 Dec;71(10):1504-10.

Solitary Pulmonary Nodules and PET

According to the American College of Chest Surgeons:
"In patients with low-to-moderate pretest probability of malignancy (5%-60%) and an indeterminate solitary pulmonary nodule (SPN) that measures at least 8 to 10 mm in diameter, we recommend that fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging should be performed to characterize the nodule.

"In patients with an SPN that has a high pretest probability of malignancy (> 60%), or patients with a subcentimeter nodule that measures < 8 to 10 mm in diameter, we suggest that FDG-PET not be performed to characterize the nodule."

References

Alberts WM; American College of Chest Physicians. Diagnosis and management of lung cancer executive summary: ACCP evidence-based clinical practice guidelines (2nd Edition). Chest. 2007 Sep;132(3 Suppl):1S-19S.