Brief Hiatus

I'll be going on a brief blog vacation to finish up a book chapter. I'll be back in about 1 week.

Bone Scan vs. FDG-PET in Pediatric Sarcomas

Walter et. al compared ¹⁸F-FDG PET/CT and ^99mTc-MDP in 29 patients with bone and soft tissue sarcomas. They found that ^99mTc-MDP did not add any diagnostic value over ¹⁸F-FDG PET/CT. The superiority of ¹⁸F-FDG PET/CT is most pronounced in patients with Ewing sarcoma family of tumors, in whom tumor tends to infiltrate the bone marrow rather than the mineralized bone, and bone destruction is dominated by osteoclastic activity, rather than osteoblastic activity.

	18F-FDG PET/CT	99mTc-MDP
Sensitivity	100%	70%
Specificity	100%	95%
Accuracy	100%	82%

The image above is from a patient with Ewing sarcoma of the distal left femur. The primary lesion (black arrow) and bony metastases are clearly seen on the MIP image from the ¹⁸F-FDG PET study, while the bone scan only shows the uptake in the area of periosteal reaction (pink arrow) and a right anterior rib lesion that likewise was associated with cortical breakthrough and a periosteal reaction. MRI shows the primary lesion (black arrow), as well as metastases in the left and right femurs (blue arrows).

References

• Völker T, Denecke T, Steffen I, Misch D, Schönberger S, Plotkin M, Ruf J, Furth C, Stöver B, Hautzel H, Henze G, Amthauer H. Positron emission tomography for staging of pediatric sarcoma patients: results of a prospective multicenter trial. J Clin Oncol. 2007 Dec 1;25(34):5435-41.
• Walter F, Czernin J, Hall T, Allen-Auerbach M, Walter MA, Dunkelmann S, Federman N. Is there a need for dedicated bone imaging in addition to 18F-FDG PET/CT imaging in pediatric sarcoma patients? J Pediatr Hematol Oncol. 2012 Mar;34(2):131-6.

Oligometastatic Disease in Breast Cancer

A subset of patients with stage IV breast cancer have limited distant metastatic disease that is often confined to a solitary lesion. This is termed oligometastatic disease (note that the term initially referred to restricted locoregional tumor load), and has been described in other malignancies, such as lung cancer, soft tissue sarcoma, osteosarcoma, renal cell carcinoma, and melanoma.

Management of the oligometastatic state is controversial. If it is thought of as the tip of the iceberg, with more widespread micrometastases escaping clinical detection, the treatment strategy would focus on systemic chemotherapy. However, several studies have shown improved survival after surgical resection of the metastasis followed by systemic therapy. Another potential benefit is an improvement in the quality of life because of discontinuation of chemotherapy.

The management of the primary tumor in this setting is also controversial, with some studies showing improved survival after resection of the primary tumor.

Definitive answers will require large, multicenter, randomized trials.

The MIP image above is from a patient with left-sided invasive ductal carcinoma with a solitary metastasis to the left T2 pedicle, who was treated with neoadjuvant chemotherapy, modified radical mastectomy, and stereotactic radiation therapy to T2. There is multicentric uptake in the left breast with multiple FDG-avid left axillary and infraclavicular lymph nodes. The lesion in the left T2 pedicle is indicated by the arrow.

References

• Pockaj BA, Wasif N, Dueck AC, Wigle DA, Boughey JC, Degnim AC, Gray RJ, McLaughlin SA, Northfelt DW, Sticca RP, Jakub JW, Perez EA. Metastasectomy and surgical resection of the primary tumor in patients with stage IV breast cancer: time for a second look? Ann Surg Oncol. 2010 Sep;17(9):2419-26.
• Tait CR, Waterworth A, Loncaster J, Horgan K, Dodwell D. The oligometastatic state in breast cancer: hypothesis or reality. Breast. 2005 Apr;14(2):87-93.

Bone Destruction and Radiography

We've often heard or read that at least 50% bone destruction must occur before it is evident on radiographs. This is often stated or written without citation and without reference to the body part or type of bone (cortical or cancellous). Some context is helpful.

The number seems to come from the work of Edelstyn et al. They used a lumbar spine specimen obtained from autopsy of a 57-year-old woman and drilled conical holes of various sizes into the cancellous bone to simulate metastatic disease. They placed the spine in a water phantom to represent the abdomen, and ensured that the holes filled with water to represent tumor tissue.

They found that somewhere between 50%-75% loss of bone thickness was needed before the lesion could be detected on a lateral radiograph of the spine. That is, at 50% bone loss, 4 radiologists were unable to detect the lesion, but at 75% (the next grade up), all 4 were able to detect the lesion. The lesions were harder to detect on the frontal view, where between 67% and 100% loss of bone thickness was needed for identification.

They noted that these findings would be easier to detect in younger patients, where bone mineral density is preserved, and harder to detect in older patients.

They then drilled a series of small holes in the cortex and noted that detection was easier when the defect was tangential to the beam.

In summary, the numbers apply to lesions in the cancellous bone of a disembodied lumbar spine of a middle-aged woman placed in a water phantom as detected on a lateral radiograph. They do not apply to the frontal view of the spine, to cortical bone, or to cancellous bone elsewhere in the body.

References

Edelstyn GA, Gillespie PJ, Grebbell FS. The radiological demonstration of osseous metastases. Experimental observations. Clin Radiol. 1967 Apr;18(2):158-62.

Intercondylar Spine Spiking and Osteoarthritis

Intercondylar spine spiking has been linked to osteophyte formation of the knee; however, it does not have a strong independent relationship with knee pain. In a study of 950 women in a general population survey, Donnelly et al. found no useful correlation between tibial spiking and pain in otherwise normal radiographs and recommended against using isolated tibial spiking as a sign of early knee osteoarthritis.

In a recent study of 35 tibial specimens from a museum collection, Hayeri et al. showed that the association between intercondylar spiking and osteoarthritis held only for the lateral intercondylar spine, and that the spine height index correlated only with osteophyte formation in the anteromedial and posteromedial quadrants of the lateral tibial plateau.

References

• Donnelly S, Hart DJ, Doyle DV, Spector TD. Spiking of the tibial tubercles--a radiological feature of osteoarthritis? Ann Rheum Dis. 1996 Feb;55(2):105-8.
• Hayeri MR, Shiehmorteza M, Trudell DJ, Heflin T, Resnick D. Proximal tibial osteophytes and their relationship with the height of the tibial spines of the intercondylar eminence: paleopathological study. Skeletal Radiol. 2010 Sep;39(9):877-81.

Radiographic Skeletal Survey and Low-Dose Whole Body CT for Multiple Myeloma

Anyone who's plugged through a radiographic skeletal survey can appreciate the subjectivity that often goes into interpreting these radiographs. Whole-body MRI is very sensitive and has been shown to demonstrate many more lesions than radiography; however, it an expensive and time consuming procedure. Low-dose whole body CT has been proposed as an alternative, with doses in the range of skeletal surveys, but with the advantage of less discomfort for the patients and quicker scan times. Using bone marrow biopsy and whole-body magnetic resonance imaging as gold standards, Gleeson et al. arrived at the following performance statistics for radiographic skeletal surveys and low-dose whole body CT.

	Skeletal Survey	CT
Sensitivity	100%	100%
Specificity	29%	56%
PPV	65%	88%
NPV	100%	100%
Accuracy	69%	90%

References

Gleeson TG, Moriarty J, Shortt CP, Gleeson JP, Fitzpatrick P, Byrne B, McHugh J, O'Connell M, O'Gorman P, Eustace SJ. Accuracy of whole-body low-dose multidetector CT (WBLDCT) versus skeletal survey in the detection of myelomatous lesions, and correlation of disease distribution with whole-body MRI (WBMRI). Skeletal Radiol. 2009 Mar;38(3):225-36.

Monoclonal Gammopathies: Multiple myeloma and Related Disorders

• Monoclonal gammopathy of undetermined significance (MGUS) : Requires the simultaneous presence of 1) A monoclonal spike < 3 g/dL on serum protein electrophoresis, 2) Bone marrow infiltration by monoclonal malignant plasma cells < 10%, and 3) Absence of end-organ damage related to multiple myeloma (CRAB: hyperCalcemia, Renal failure, Anemia, and Bone lesions). Affects ~3% of individuals older than 50 years. There is a 1%/year lifelong risk of transformation to a hematologic malignancy (mainly multiple myeloma).
• Smoldering multiple myeloma (SMM): Also known as asymptomatic myeloma. Requires a monoclonal spike ≥ 3 g/dL and/or bone marrow infiltration by monoclonal malignant plasma cells ≥ 10% in the absence of end-organ damage (CRAB: hyperCalcemia, Renal failure, Anemia, and Bone lesions). There is a 10%/year risk of progression to active multiple myeloma or related plasma cell dyscrasia in the first 5 years, 3%/year in the following 5 years, and 1%/year thereafter.
• Multiple myeloma: Requires three criteria be satisfied: 1) A monoclonal spike on serum protein electrophoresis or urine protein electrophoresis or an abnormal free light chain ratio, 2) Bone marrow infiltration by monoclonal malignant plasma cells or presence of a plasmacytoma (see below), and 3) End-organ damage related to multiple myeloma (CRAB: hyperCalcemia, Renal failure, Anemia, and Bone lesions) or hyperviscosity, amyloidosis, or recurrent infections
• Nonsecretory multiple myeloma: ~3% of all multiple myeloma. No monoclonal spike is present on serum or urine protein electrophoresis
• Solitary plasmacytoma: Variant of plasma cell dyscrasia characterized by a single area of monoclonal plasma cell proliferation in the absence of systemic disease (e.g., CRAB) and bone marrow involvement. Can be osseous or extraosseous. May have a small monoclonal component, but generally a monoclonal spike is not present on serum or urine protein electrophoresis.
• Multiple solitary plasmacytomas: Can occur in ~5% of patients with a solitary plasmacytoma. No evidence of bone marrow involvement or other skeletal lesions. May be recurrent.
• Plasma cell leukemia: Peripheral blood circulating plasma cells > 2 × 10⁹/L or 20% of leukocytes. Can either be primary (60% of cases) or secondary to leukemic transformation of preexisting multiple myeloma.

Other conditions that can present with a monoclonal spike include chronic lymphocytic leukemia, B-cell and T-cell lymphomas, chronic myeloid leukemia, and other plasma cell dyscrasias, such as amyloid light chain amyloidosis, Waldenström macroglobulinemia, and heavy chain disease.

References

• Bianchi G, Ghobrial IM. Does My Patient with a Serum Monoclonal Spike have Multiple Myeloma? Hematol Oncol Clin North Am. 2012 Apr;26(2):383-93.
• International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol. 2003 Jun;121(5):749-57.

Bisphosphonate Therapy in Children

Pediatric patients with cerebral palsy and osteogenesis imperfecta can be treated with bisphosphonates for low mineral density. In addition, third-generation bisphosphonates, such as zoledronic acid and minodronic acid have been shown to have antitumor effects in various cancers such as osteosarcoma and Ewing sarcoma. The use in children is classified as "off-label."

Radiographs reveal dense stripes parallel to the growth plate, an appearance that has been termed zebra lines. Dense metaphyseal bands tend to occur in patients treated continuously, while thin bands tend to occur in patients treated intermittently. In addition, patients treated intermittently tend to have increased bone density, increased growth, and decreased number of fractures.

The sclerotic bands correspond to decreased osteoclastic activity during drug administration, and the spaces between the bands corresponds to resumption of osteoclastic activity and linear growth of bone between treatments. With time (3-4 years), these dense bands become less distinct and eventually disappear into the diaphysis.

While similar to Harris growth arrest lines, zebra lines tend to be more widespread in epiphyseal, apophyseal, and metaphyseal regions of all growing bones. Growth arrest lines, on the other hand, are seen in the metaphyses of rapidly growing bones (e.g., distal femur, proximal and distal tibia, and proximal humerus) and may be limited to a single bone (e.g., following a major fracture).

References

• Al Muderis M, Azzopardi T, Cundy P. Zebra lines of pamidronate therapy in children. J Bone Joint Surg Am. 2007 Jul;89(7):1511-6.
• Grissom LE, Harcke HT. Radiographic features of bisphosphonate therapy in pediatric patients. Pediatr Radiol. 2003 Apr;33(4):226-9.

Breast Tissue Expanders and MRI

Tissue expanders can be inflated through a remote port or an integrated port. The injection ports can be located postoperatively either by palpation or with a device that is attracted to a small magnet in the port. These magnetic ports may become uncomfortable or cause injury during MRI. Tissue expanders with magnetic ports are contraindicated for MRI.

One such device is the Magna-Site tissue expander port (McGhan Medical Corporation, Santa Barbara, CA), which incorporates a rare-earth magnet housed in a titanium shell (arrows)in the injection port. The magnet is detected postoperatively with the Magna-Finder device.

References

• Elliott MP, Dubrul W. Magna-Site tissue expander: an innovation for injection site location. Plast Reconstr Surg. 1988 Apr;81(4):605-7.
• Liang MD, Narayanan K, Kanal E. Magnetic ports in tissue expanders--a caution for MRI. Magn Reson Imaging. 1989 Sep-Oct;7(5):541-2.

Juxta-Articular Myxoma

Juxta-articular myxomas are uncommon benign lesions that usually (~90%) occur around the knee. Patients are typically middle-aged men who present with pain and complaints of a palpable mass. The lesions are typically between 2 cm - 7 cm in size.

These myxomas most frequently occur in the subcutaneous fat of knee, but can also arise anywhere in the intra- and extracapsular spaces. While benign, a recurrence rate of ~30% has been reported.

In contrast to the more common intramuscular myxomas, which have homogenous low signal intensity on Tl-weighted images and homogeneous high signal intensity on T2-weighted images, juxta-articular myxomas are more likely to be heterogeneous and have myxoid degeneration.

The case above is a juxta-articular myxoma arising in posterior suprapatellar fat pad. The lesion is cystic on ultrasound. T1-FS images reveals a lesion that is isointense to muscle and has mild peripheral enhancement. No other sequences were available.

The main differential consideration in this case is a ganglion cyst. Ganglion cysts have myxoid tissue that is much less developed than in juxta-articular myxomas and are typically smaller.

References

• Daluiski A, Seeger LL, Doberneck SA, Finerman GA, Eckardt JJ. A case of juxta-articular myxoma of the knee. Skeletal Radiol. 1995 Jul;24(5):389-91.
• Kosty JW, Moore JG. Juxta-articular myxoma within the suprapatellar pouch masquerading as a ganglion cyst. Orthopedics. 2009 Jul;32(7):527.

Facet Anatomy of the Greater Tuberosity

The superior (anterior) facet of the greater tuberosity is horizontal on coronal oblique MR images and is the site of attachment of the supraspinatus tendon.

The middle facet of the greater tuberosity is obliquely oriented and is the site of attachment of the supraspinatus and infraspinatus tendons. The supraspinatus tendon attaches to the superior half of the middle facet, while the infraspinatus tendon attaches to the entire middle facet, covering a portion of the supraspinatus tendon.

As we move posteriorly, we see both the middle and inferior (posterior) facets. The inferior facet is vertically oriented and is the site of attachment of the teres minor tendon.

References

• Minagawa H, Itoi E, Konno N, Kido T, Sano A, Urayama M, Sato K. Humeral attachment of the supraspinatus and infraspinatus tendons: an anatomic study. Arthroscopy. 1998 Apr;14(3):302-6.

Giant Cell-Rich Osteosarcoma.

Giant cell–rich osteosarcoma makes up about 3% of all osteosarcomas. Histologically, giant cell–rich osteosarcomas are characterized by an abundance of osteoclast-like giant cells and a paucity of tumor osteoid and bone. The histologic appearance can be similar to giant cell tumor.

This paucity of tumor osteoid results in imaging features unlike those of conventional osteosarcomas. In addition, differentiation from benign lesions can sometimes be difficult. Giant cell–rich osteosarcomas are usually lytic and have poorly defined borders. Periosteal reaction is scant or absent and a soft tissue mass is usually not present.

The biological behavior is not necessarily different from that of conventional osteosarcoma.

References

• Bathurst N, Sanerkin N, Watt I. Osteoclast-rich osteosarcoma. Br J Radiol. 1986 Jul;59(703):667-73.

Radiography and MRI for Assessment of Acromial Shape

Using 3-dimensional models constructed from MR images as their gold standard, Mayerhoefer et al compared outlet view radiographs and MRI for assessment of the shape of the acromion (types 1-3). They found that MRI had good correlation (K=0.66) to the 3-dimensional model when two oblique coronal slices were used in conjunction: A slice 4 mm medial to the lateral margin of the acromion (1) and a slice lateral to the acromioclavicular joint (2). Outlet view radiographs had moderate correlation to the shape of the acromion (K=0.55), which was still better than any single MRI slice.

References

Mayerhoefer ME, Breitenseher MJ, Roposch A, Treitl C, Wurnig C. Comparison of MRI and conventional radiography for assessment of acromial shape. AJR Am J Roentgenol. 2005 Feb;184(2):671-5.

The "50% Rule"

The "50% rule" in arthroscopic and orthopaedic surgery states that tendon and ligament injuries with structural involvement of less than 50% are best treated by observation, while those with involvement of greater than 50% are best treated by surgical repair or reconstruction.

The rule appears to have come out of studies on the management of hand flexor tendon injuries and transferred over to arthroscopy in the shoulder and knee. It should be remembered that the rule is derived from expert opinion and has never been subjected to a randomized controlled clinical trial nor validated for accuracy, reliability, or reproducibility. The role of imaging in all this is as murky if not more so.

References

Pedowitz RA, Higashigawa K, Nguyen V. The "50% rule" in arthroscopic and orthopaedic surgery. Arthroscopy. 2011 Nov;27(11):1584-7.

Drugs and Cardiac FDG Uptake

Certain drugs and patient factors can affect cardiac uptake of FDG.

Drug	Effect	Comment
Insulin	↑	Similar to the effect of eating close to FDG administration. Will also cause diffuse increase in muscle uptake and a decrease in liver uptake.
Bezafibrate	↑	Fibrate drug used for hyperlipidemia.
Benzodiazepines	↑
Levothryoxine	↓
Metformin	↓	Shown above. Increases colonic FDG uptake and can result in a competitive decrease in cardiac FDG uptake.

In addition to the above, certain patient factors can increase cardiac FDG uptake: Male gender, younger patients (< 30 years), fasting duration of <5 hours, and patients with heart failure tend to have higher cardiac FDG uptake.

References

• Israel O, Weiler-Sagie M, Rispler S, Bar-Shalom R, Frenkel A, Keidar Z, Bar-Shalev A, Strauss HW. PET/CT quantitation of the effect of patient-related factors on cardiac 18F-FDG uptake. J Nucl Med. 2007 Feb;48(2):234-9.
• Maurer AH, Burshteyn M, Adler LP, Steiner RM. How to differentiate benign versus malignant cardiac and paracardiac 18F FDG uptake at oncologic PET/CT. Radiographics. 2011 Sep-Oct;31(5):1287-305.

F18-FDG PET in Neuroendocrine Tumors

Somatostatin receptor scintigraphy (e.g., octreoscan) is more sensitive than both ¹²³I-MIBG scintigraphy and ¹⁸F-FDG PET for neuroendocrine tumors. However, ¹⁸F-FDG PET is more sensitive for detection of aggressive tumors, with a sensitivity of around 90%, compared to ~70% and ~45% for somatostatin receptor and ¹²³I-MIBG scintigraphy for tumors with proliferation index above 15%.

In these aggressive tumors, somatostatin receptor and ¹²³I-MIBG scintigraphy can underestimate the extent of disease dissemination and lead to suboptimal treatment for these patients (aggressive disease is treated with systemic chemotherapy, while less aggressive disease is treated with somatostatin analogs or α-interferon).

In the example above, FDG-PET shows uptake in several areas not seen on octreoscan. One example is an enlarged retroperitoneal lymph node that is not hot on octreoscan, but light s up on FDG-PET (black arrows).

References

Binderup T, Knigge U, Loft A, Mortensen J, Pfeifer A, Federspiel B, Hansen CP, Højgaard L, Kjaer A. Functional imaging of neuroendocrine tumors: a head-to-head comparison of somatostatin receptor scintigraphy, 123I-MIBG scintigraphy, and 18F-FDG PET. J Nucl Med. 2010 May;51(5):704-12.