General Approach to Lytic Bone Lesions D. Lee Bennett, MD, MA, Georges Y. El Khoury, MD Appl Radiol. 2004;33(5)

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1 General Approach to Lytic Bone Lesions D. Lee Bennett, MD, MA, Georges Y. El Khoury, MD Appl Radiol. 2004;33(5) Abstract and Introduction Abstract When interpreting musculoskeletal radiographs, a radiologist must be able to identify a lytic lesion and provide a definitive diagnosis or a reasonable differential diagnosis for the lesion. This article addresses these issues and details a rational and systematic approach to such lesions. Introduction One of the important functions of a radiologist in interpreting musculoskeletal radiographs is to identify a lytic lesion. But once such a lesion is identified, a radiologist must also be able to provide a definitive diagnosis or a reasonable differential diagnosis for the lesion and provide appropriate recommendations to the referring clinician. We will address each of these issues in our approach to lytic bone lesions. Identifying a Lytic Lesion When a lytic lesion is suspected, the radiologist must keep in mind the possibility of a normal variant, such as a pseudocyst. [1] Two common locations for pseudocysts are the humeral head and the calcaneus. The pseudocyst of the humeral head is typically located in the region of the greater tuberosity, while the pseudocyst of the calcaneus is typically located anteriorly (Figures 1 and 2). 1/26

2 Figure 1. Proximal humeral anteroposterior (AP) pseudocyst in a 22 year old man. This AP radiograph of the shoulder shows the typical trabecular rarefaction of a humeral pseudocyst in the region of the greater tuberosity (arrows). 2/26

3 Figure 2. Anterior calcaneal pseudocyst in a 25 year old man. The typical trabecular rarefaction of a pseudocyst can be seen in the anterior calcaneus (white arrows) on this lateral radiograph. Incidental bone islands are present in the talus (black arrows). A pseudocyst is a region of relatively low stress within a bone resulting in trabecular bone formation that is not as pronounced as in higher stress areas. This area of relatively lower stress develops into an apparent lytic lesion, which is actually an area of trabecular rarefaction. When this area of trabecular rarefaction is visually compared with the surrounding bone that contains more prominent trabeculae, one sees an apparent lytic lesion or the so called pseudocyst. [1] On magnetic resonance imaging (MRI), a pseudocyst has normal marrow signal, since it is a normal variant. Another useful tool in identifying subtle lytic lesions is to compare current studies with previous radiographs or to compare them with images of the contralateral side. Comparison with prior films may help to identify subtle focal changes, which, for the less experienced radiologist, aids in the identification of a new lytic lesion. Literature has also shown that comparison with prior studies improves the diagnostic accuracy of the interpretation. [2] Comparison with the contralateral side should also be made when these radiographs are readily available. Examples of studies with readily available contralateral structures include pelvic radiographs and skeletal surveys. On radiographs of the pelvis, one hemipelvis can be readily compared with the other to more easily and confidently identify subtle lytic lesions, cortical destruction, or periosteal reaction. When interpreting skeletal surveys, a radiologist should also use available studies of the contralateral extremity for comparison purposes. Differential Diagnosis One of the most important first steps in deriving a differential diagnosis when evaluating a lytic lesion is to know the age of the patient. This is an important piece of information in musculoskel etal radiology. Typically, only certain lesions occur within any given age range; therefore, the age of the patient must be considered in order to generate a correct differential diagnosis. Some of the lytic lesions that are largely confined to certain age groups are: metastatic neuroblastoma in the infant and young child, metastasis and multiple myeloma in the middle aged and elderly, 3/26

4 Ewing's sarcoma and simple bone cyst in the long bones in children and young teenagers, and giant cell tumor in the young to middle aged adult (20 to 50 years of age). [3,4] The next step is to examine the lesion to see if it has a pathognomonic appearance and/or location. Some lytic lesions have a characteristic radiographic appearance (including matrix) and/or location that are inherently diagnostic. A few examples include: a corduroy vertebral body (hemangioma; Figure 3), a fallen fragment sign (simple bone cyst; Figure 4), intralesional gas in a juxta articular lesion (subchondral cyst, such as a degenerative cyst or intraosseous ganglion cyst; Figure 5), an enlarged bone with coarsened trabeculae and a thickened cortex (Paget's disease; Figure 6), chondroid matrix in a geographic lytic lesion in the hand (enchondroma; Figure 7), vertebra plana in an otherwise healthy child (Langerhan's cell histiocytosis; Figure 8), and the cockade sign in the calcaneus (intraosseous lipoma; Figure 9). One must become familiar with characteristic pathognomonic radiographic signs and appearances of lytic lesions. Figure 3. Vertebral body hemangioma in a 48 year old woman. (A) The vertically oriented, thickened trabeculae (corduroy sign) of a vertebral body hemangioma can be seen on this lateral view, which is coned down to the L2 vertebral body. (B) T1 weighted and (C) T2 weighted MR images show the typical increased signal intensity of a vertebral body hemangioma (arrows). (D) This axial CT image of the L2 vertebral body illustrates the classic dot appearance to the trabecular bone found in vertebral body hemangiomas. 4/26

5 Figure 3. Vertebral body hemangioma in a 48 year old woman. (A) The vertically oriented, thickened trabeculae (corduroy sign) of a vertebral body hemangioma can be seen on this lateral view, which is coned down to the L2 vertebral body. (B) T1 weighted and (C) T2 weighted MR images show the typical increased signal intensity of a vertebral body hemangioma (arrows). (D) This axial CT image of the L2 vertebral body illustrates the classic dot appearance to the trabecular bone found in vertebral body hemangiomas. Figure 3. Vertebral body hemangioma in a 48 year old woman. (A) The vertically oriented, thickened trabeculae (corduroy sign) of a vertebral body hemangioma can be seen on this lateral view, which is coned down to the L2 vertebral body. (B) T1 weighted and (C) T2 weighted MR images show the typical increased signal intensity of a vertebral body hemangioma (arrows). (D) This axial CT image of the L2 vertebral body illustrates the classic dot appearance to the 5/26

6 trabecular bone found in vertebral body hemangiomas. Figure 3. Vertebral body hemangioma in a 48 year old woman. (A) The vertically oriented, thickened trabeculae (corduroy sign) of a vertebral body hemangioma can be seen on this lateral view, which is coned down to the L2 vertebral body. (B) T1 weighted and (C) T2 weighted MR images show the typical increased signal intensity of a vertebral body hemangioma (arrows). (D) This axial CT image of the L2 vertebral body illustrates the classic dot appearance to the trabecular bone found in vertebral body hemangiomas. 6/26

7 Figure 3. Vertebral body hemangioma in a 48 year old woman. (A) The vertically oriented, thickened trabeculae (corduroy sign) of a vertebral body hemangioma can be seen on this lateral view, which is coned down to the L2 vertebral body. (B) T1 weighted and (C) T2 weighted MR images show the typical increased signal intensity of a vertebral body hemangioma (arrows). (D) This axial CT image of the L2 vertebral body illustrates the classic dot appearance to the trabecular bone found in vertebral body hemangiomas. 7/26

8 Figure 3. Vertebral body hemangioma in a 48 year old woman. (A) The vertically oriented, thickened trabeculae (corduroy sign) of a vertebral body hemangioma can be seen on this lateral view, which is coned down to the L2 vertebral body. (B) T1 weighted and (C) T2 weighted MR images show the typical increased signal intensity of a vertebral body hemangioma (arrows). (D) This axial CT image of the L2 vertebral body illustrates the classic dot appearance to the trabecular bone found in vertebral body hemangiomas. 8/26

9 Figure 3. Vertebral body hemangioma in a 48 year old woman. (A) The vertically oriented, thickened trabeculae (corduroy sign) of a vertebral body hemangioma can be seen on this lateral view, which is coned down to the L2 vertebral body. (B) T1 weighted and (C) T2 weighted MR images show the typical increased signal intensity of a vertebral body hemangioma (arrows). (D) This axial CT image of the L2 vertebral body illustrates the classic dot appearance to the trabecular bone found in vertebral body hemangiomas. Figure 3. Vertebral body hemangioma in a 48 year old woman. (A) The vertically oriented, thickened trabeculae (corduroy sign) of a vertebral body hemangioma can be seen on this lateral view, which is coned down to the L2 vertebral body. (B) T1 weighted and (C) T2 weighted MR images show the typical increased signal intensity of a vertebral body 9/26

10 hemangioma (arrows). (D) This axial CT image of the L2 vertebral body illustrates the classic dot appearance to the trabecular bone found in vertebral body hemangiomas. Figure 4. Simple bone cyst in an 8 year old child. This anteroposterior radiograph of the proximal humerus shows the fallen fragment sign (arrow) of a simple bone cyst. 10/26

11 Figure 5. Intraosseous ganglion cyst in a 16 year old. This axial CT image shows intralesional gas (arrow), which confirms the diagnosis of an intraosseous ganglion cyst in this otherwise healthy patient. Figure /26

12 Paget's disease involving the calcaneus in a 50 year old man. (A) This lateral radiograph of the ankle readily shows the classic Paget's disease findings of an enlarged bone, coarsened trabeculae (arrows), and thickened cortex (arrowheads). (B) This coronal T1 weighted MR image of the calcaneus also shows the coarsened trabeculae (arrow) and thickened cortex (arrowheads) of Paget's disease. In the peripheral skeleton, bone involved with Paget's disease should have normal marrow signal interspersed between the coarsened trabeculae. Figure 6. Paget's disease involving the calcaneus in a 50 year old man. (A) This lateral radiograph of the ankle readily shows the classic Paget's disease findings of an enlarged bone, coarsened trabeculae (arrows), and thickened cortex (arrowheads). (B) This coronal T1 weighted MR image of the calcaneus also shows the coarsened trabeculae (arrow) and thickened cortex (arrowheads) of Paget's disease. In the peripheral skeleton, bone involved with Paget's disease should have normal marrow signal interspersed between the coarsened trabeculae. In regard to matrix, mineralization of both chondroid and osteoid matrix can be visible on radiographs. Mineralization of chondroid matrix is seen as dot like, popcorn like, arcs and rings of calcifications within the bone tumor, while osteoid matrix has a cloud like, wispy appearance (Figures 10 and 11). Some lesions that can have radiographically visible chondroid matrix include enchondroma, chondroblastoma, and chondrosarcoma. Osteoid matrix can be seen in osteosarcoma and osteoid osteoma/osteoblastoma. [5] 12/26

13 Figure 6. Paget's disease involving the calcaneus in a 50 year old man. (A) This lateral radiograph of the ankle readily shows the classic Paget's disease findings of an enlarged bone, coarsened trabeculae (arrows), and thickened cortex (arrowheads). (B) This coronal T1 weighted MR image of the calcaneus also shows the coarsened trabeculae (arrow) and thickened cortex (arrowheads) of Paget's disease. In the peripheral skeleton, bone involved with Paget's disease should have normal marrow signal interspersed between the coarsened trabeculae. 13/26

14 Figure 7. Enchondroma of the proximal phalanx in a 57 yearold woman. The pathognomonic findings of a lytic geographic lesion with expansion and chondroid matrix (arrows) are seen on this radiograph of the proximal phalanx of the index finger. If the appearance of the lytic lesion is not pathognomonic, such that one cannot give a definitive diagnosis or a succinct differential diagnosis, then the radiologist must determine the aggressiveness of the lesion. Generally speaking, benign lesions can have a quiescent or aggressive appearance, while malignant lesions have an aggressive appearance. Two radiographic characteristics we have found useful in determining the aggressiveness of a lytic lesion are the appearance of the lesion based on the Lodwick classification system and the type of periosteal reaction present. The authors use the revised Lodwick classification system when evaluating the appearance of a lytic lesion because this has been shown to be a reliable and accurate method of determining that certain lesions have a very high likelihood of not being malignant based on their radiographic appearance. [6,7] This is a fairly versatile classification system in that multiple factors important in evaluating lytic bone tumors can be incorporated into a single grading system. The factors incorporated into the revised Lodwick classification system include soft tissue involvement, pattern of bone destruction, size of lesion, zone of transition, margin sclerosis, and host response. The revised Lodwick classification system consists of five grades labeled IA, IB, IC, II, and III. The grading of a 14/26

15 lesion is performed in a sequential four step manner. The first step is to determine the type of bone destruction present in the lesion. A lesion with geographic destruction would be defined as a lesion having a sharp, clearly defined margin (grade I; Figure 12). Moth eaten destruction is similar to moth eaten clothes with holes of destroyed bone. Permeative destruction is an ill defined, diffuse, somewhat subtle destructive process of bone. Those lytic lesions that are entirely moth eaten and/or permeative are grade III (Figure 13). Any lytic lesion that is a combination of geographic with moth eaten and/or permeative destruction is a grade II lesion (Figure 14). If the lesion is grade II or III, then that lesion is classified and is considered malignant until proven otherwise. If the lesion is grade I, then classification proceeds to the second step. Lodwick often found it difficult to differentiate between grade II and III lesions, but it does not really matter because both grades indicate an aggressive lesion that needs further evaluation and/or treatment. Figure 8. Langerhan's cell histiocytosis involving the spine in an 8 year old boy. In this otherwise healthy child, vertebra plana can be seen (arrow) in the thoracic spine, which is consistent with Langerhan's cell histiocytosis. 15/26

16 Figure 9. Intraosseous lipoma of the calcaneus in a 35 year old man. (A) This lateral radiograph of the ankle shows a geographic lytic lesion in the calcaneus. Dystrophic calcifications, known as the cockade sign, can be seen within the lesion (arrow). This is a classic pathognomonic appearance and location of an intraosseous lipoma. Parasagittal (B) T1 weighted and (C) Short tau inversion recovery (STIR) MR images, respectively, show signal characteristics (hyperintense on T1 and hypointense on STIR) that are consistent with a fatcontaining lesion (intraosseous lipoma). Signal arising from the dystrophic calcifications can also be seen within the lesion (arrows). 16/26

17 Figure 9. Intraosseous lipoma of the calcaneus in a 35 year old man. (A) This lateral radiograph of the ankle shows a geographic lytic lesion in the calcaneus. Dystrophic calcifications, known as the cockade sign, can be seen within the lesion (arrow). This is a classic pathognomonic appearance and location of an intraosseous lipoma. Parasagittal (B) T1 weighted and (C) Short tau inversion recovery (STIR) MR images, respectively, show signal characteristics (hyperintense on T1 and hypointense on STIR) that are consistent with a fatcontaining lesion (intraosseous lipoma). Signal arising from the dystrophic calcifications can also be seen within the lesion (arrows). 17/26

18 Figure 9. Intraosseous lipoma of the calcaneus in a 35 year old man. (A) This lateral radiograph of the ankle shows a geographic lytic lesion in the calcaneus. Dystrophic calcifications, known as the cockade sign, can be seen within the lesion (arrow). This is a classic pathognomonic appearance and location of an intraosseous lipoma. Parasagittal (B) T1 weighted and (C) Short tau inversion recovery (STIR) MR images, respectively, show signal characteristics (hyperintense on T1 and hypointense on STIR) that are consistent with a fatcontaining lesion (intraosseous lipoma). Signal arising from the dystrophic calcifications can also be seen within the lesion (arrows). The second step is to re evaluate the margin of the lesion, including any cortex that the lesion abuts. If any of the margins are indistinct, then the lesion is classified as grade IC (Figure 15). Margins that are indistinct should not be confused with moth eaten/permeative destruction (grade II or III). If the lesion cannot be classified as grade IC, then classification proceeds to the third step. 18/26

19 Figure 9. Intraosseous lipoma of the calcaneus in a 35 year old man. (A) This lateral radiograph of the ankle shows a geographic lytic lesion in the calcaneus. Dystrophic calcifications, known as the cockade sign, can be seen within the lesion (arrow). This is a classic pathognomonic appearance and location of an intraosseous lipoma. Parasagittal (B) T1 weighted and (C) Short tau inversion recovery (STIR) MR images, respectively, show signal characteristics (hyperintense on T1 and hypointense on STIR) that are consistent with a fatcontaining lesion (intraosseous lipoma). Signal arising from the dystrophic calcifications can also be seen within the lesion (arrows). In the third step, the lesion is evaluated for expansion. If an expanded cortical shell is present and it exceeds 1 cm, then the lesion is classified as grade IB (Figure 16). The fourth step consists of evaluating the lesion for the presence of a circumferential sclerotic margin. If the lesion has a sclerotic margin, it is classified as grade IA (Figure 12). Those with a nonsclerotic margin are classified as grade IB. 19/26

20 Figure 10. Enchondroma of the distal femur in a 45 year old woman. This anteroposterior radiograph of the distal femur readily shows the coarse dot like, popcorn like mineralization of chondroid matrix. Usually, the authors recommend follow up imaging for lytic lesions that are asymptomatic, have a grade IA appearance, and are found in an otherwise healthy patient. Nonspecific and nonpathognomonic lytic lesions that are grade IB, IC, II, III, or are symptomatic warrant further work up at the time of discovery. Based on previous studies, the likelihood of malignancy using the revised Lodwick classification (disregarding patient symptoms and whether the lesion is pathognomonic in appearance) is as follows: grade IA is 6%, grade IB is 48%, grade IC is 36%, grade II is 97%, and grade III is 100%. [6,7] If pathognomonic lesions are excluded from the results of these studies, the likelihood of malignancy of grade IA lesions falls to 2% to 4%. If periosteal reaction is present, we classify it as either solid or interrupted ( ). [8] Solid periosteal reaction is described as a single layer of new bone thicker than 1 mm and uninterrupted throughout its extent. Interrupted periosteal reaction is simply the laying down of new bone that is interrupted that is, not continuous or solid. Some examples include sunburst and Codman's triangle. Interrupted periosteal reaction indicates that the associated lesion is aggressive. [8] Those lesions that are not pathognomonic in appearance and have an interrupted periosteal reaction also warrant further work up because of their higher likelihood of malignancy. [8] It is important to remember that interrupted periosteal reaction is sometimes seen with osteomyelitis. 20/26

21 Further work up recommendations for the aggressive, nonspecific lytic lesion typically consist of MRI and/or computed tomography (CT), a whole body nuclear medicine bone scan, or even a biopsy. Further work up is also performed on those lesions that are aggressive and pathognomonic in appearance for malignancy, such as osteosarcoma (osteoid matrix) and chondrosarcoma (chondroid matrix). It should be remembered that further work up with MRI and nuclear medicine studies is primarily used for lesion staging and/or prebiopsy work up. In the vast majority of cases, the key to the diagnosis is in the plain radiographic appearance of the lesion. At our institution, we obtain an MRI of an aggressive, nonspecific lytic lesion to evaluate its full extent, to aid in prebiopsy/preoperative planning, and, occasionally, to aid in diagnosis. If there is any concern that the lesion might be an osteosarcoma or Ewing's sarcoma, then the entire length of the involved bone must be imaged, including any joints with which the involved bone articulates. The reason the entire length is imaged is to detect any skip lesions, which can be seen with osteosarcoma and Ewing's sarcoma. [9] A skip lesion is a separate area of disease involvement from the originally discovered lesion. The separate area of involvement will have intervening normal marrow between it and the original lesion (Figure 17). Identification of a skip lesion changes the treatment and, possibly, the prognosis. When evaluating the extent of marrow involvement, T1 weighted sequence images should be used, as these have been shown to most accurately reflect the true extent of involvement. [10,11,12] Figure 11. Osteosarcoma of the proximal tibia in a 14 year old girl. The wispy, cloudlike mineralization (arrows) of osteoid matrix can be seen on this anteroposterior radiograph of the proximal tibia. 21/26

22 Figure 11. Osteosarcoma of the proximal tibia in a 14 year old girl. The wispy, cloudlike mineralization (arrows) of osteoid matrix can be seen on this anteroposterior radiograph of the proximal tibia. 22/26

23 Figure 11. Osteosarcoma of the proximal tibia in a 14 year old girl. The wispy, cloudlike mineralization (arrows) of osteoid matrix can be seen on this anteroposterior radiograph of the proximal tibia. MRI will also aid in establishing which compartments and structures are involved. [3] The determination of which compartments are involved is important in the decision of the type of treatment or surgery necessary, as well as to determine a biopsy path. In general, a biopsy path should avoid any compartments that are not grossly involved by the neoplasm. Occasionally, an MRI or a CT examination of a nonspecific lytic lesion will narrow the differential diagnosis. An example of this would be the presence of fluid fluid levels, which are most commonly found in an aneurysmal bone cyst. [13] Another example would be a fatty tumor seen on MRI in the anterior calcaneus, which is consistent with an intraosseous lipoma (Figure 9). In patients who are claustrophobic or who have a contraindication for MRI, a CT examination is used to evaluate the extent of the lesion. CT is also useful in the evaluation of lesions located in anatomically complex osseous structures, such as the pelvis, scapula, or spine (Figure 3). CT is also useful in identifying mineralization of a matrix. For example, CT would be used to identify chondroid matrix in a suspected chondroblastoma (Figure 18). 23/26

24 Figure 12. Nonossifying fibroma of the distal tibia in a 9 year old girl. The classic circumscribed edge of a geographic lesion is seen on this anteroposterior radiograph of the distal tibia. The lesion has sclerotic margins with minimal cortical expansion, making this a grade IA lesion. 24/26

25 Figure 12. Nonossifying fibroma of the distal tibia in a 9 year old girl. The classic circumscribed edge of a geographic lesion is seen on this anteroposterior radiograph of the distal tibia. The lesion has sclerotic margins with minimal cortical expansion, making this a grade IA lesion. A nuclear medicine bone scan is performed to look for a polyostotic process. If the process is polyostotic, then the differential diagnosis of a nonspecific lytic lesion can be narrowed. For example, the vast majority of polyostotic lytic processes in the elderly would represent either metastasis or multiple myeloma. [3] A bone scan may also identify other lesions that may be more appropriate to biopsy; therefore, the bone scan also plays a role in prebiopsy evaluation. If the lesion is still nonspecific after thorough imaging, image guided biopsy of the lesion can be performed. The biopsy pathway should be selected in conjunction with the surgeon so that any uninvolved compartments can be avoided and any seeding along the biopsy path can be easily resected during surgery without worsening the patient's outcome or prognosis if the lesion is a primary bone malignancy. Finally, percutaneous needle biopsy of a chondrosarcoma should be avoided. Lytic bone lesions are frequently encountered in a general radiology practice. A rational and systematic approach can often result in a specific diagnosis or a short differential diagnosis. Based on this, a reasonable diagnostic work up can be prescribed. References 25/26

26 1. Resnick D, Cone RO III. The nature of humeral pseudocysts. Radiology.1984;150: Berbaum K, Franken EAJr, Smith WL. The effect of comparison films upon resident interpretation of pediatric chest radiographs. Invest Radiol.1985;20: Manaster BJ. Tumors. In: Manaster BJ, Disler DG, May DA, eds. Musculoskeletal Imaging: The Requisites.2nd ed. St. Louis, MO: Mosby; 2002: Resnick D. Tumors and tumor like lesions of bone: Imaging and pathology of specific lesions. In: Resnick D, ed. Bone and Joint Imaging.2nd ed. Philadelphia, PA: W.B. Saunders; 1996: El Khoury GY, Sundaram M. Logical approach to the evaluation of solitary bone lesions. In: El Khoury GY, ed. Essentials of Musculoskeletal Imaging.Philadelphia, PA: Churchill Livingston; 2003: Lodwick GS, Wilson AJ, Farrell C, et al. Determining growth rates of focal lesions of bone from radiographs. Radiology.1980;134: Lodwick GS, Wilson AJ, Farrell C, et al. Estimating rate of growth in bone lesions: Observer performance and error. Radiology.1980;134: Edeiken J, Hodes PJ, Caplan LH. New bone production and periosteal reaction. Am J Roentgenol Radium Ther Nucl Med.1966;97: Khoury NJ, El Khoury GY, Bennett DL: Primary malignant bone forming tumors. In: El Khoury GY, ed. Essentials of Musculoskeletal Imaging.Philadelphia, PA: Churchill Livingston; 2003: Sundaram M, McGuire MH, Herbold DR, et al. Magnetic resonance imaging in planning limb salvage surgery for primary malignant tumors of bone. J Bone Joint Surg Am. 1986;68: Onikul E, Fletcher BD, Parham DM, Chen G. Accuracy of MR imaging for estimating intraosseous extent of osteosarcoma. Am J Roentgenol.1996;167: Hoffer FA, Nikanorov AY, Reddick WE, et al. Accuracy of MR imaging for detecting epiphyseal extension of osteosarcoma. Pediatr Radiol. 2000;30: Davies AM, Cassar Pullicino VN, Grimer RJ. The incidence and significance of fluid fluid levels on CT of osseous lesions. Br J Radiol. 1992;65: Appl Radiol. 2004;33(5) 2004 Anderson Publishing, Ltd. 26/26

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