Secondary aneurysmal bone cysts and associated primary lesions: imaging features of 49 cases

Clinical Imaging 62 (2020) 23–32

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Musculoskeletal and Emergency Imaging

Secondary aneurysmal bone cysts and associated primary lesions: imaging features of 49 cases

T

Luis B. Gutierreza,1, , Thomas M. Linka, Andrew E. Horvaib, Gabby B. Josepha, Richard J. O'Donnellc, Daria Motamedia ⁎

a

Department of Radiology and Biomedical Imaging, University of California, San Francisco, 505 Parnassus Ave, San Francisco, CA 94143, United States of America Department of Pathology, University of California, San Francisco, 505 Parnassus Ave, San Francisco, CA 94143, United States of America c Department of Orthopaedic Surgery, University of California, San Francisco, 505 Parnassus Ave, San Francisco, CA 94143, United States of America b

ARTICLE INFO

ABSTRACT

Keywords: Aneurysmal bone cyst Musculoskeletal imaging Bone tumor Giant cell tumor Chondroblastoma Fibrous dysplasia Osteoblastoma Osteosarcoma

Purpose: To describe the imaging, anatomic, and clinical features of a series of secondary aneurysmal bone cysts (ABC) and to ascertain their most commonly associated primary bone lesions. Methods: Forty-nine cases of histopathologically proven secondary ABCs were retrospectively reviewed. Demographic data and clinical history were obtained. Radiographic, computed tomographic, magnetic resonance, and nuclear medicine imaging were analyzed. Lesion location, imaging characteristics, and associated primary lesions were documented. Linear regression analysis and Chi-squared testing was performed for statistical analysis. Results: Twenty-four males and 25 females were included, with an age range of 8—79 years (mean 29.7 + − 4.5 years). Eleven types of primary bone lesion were identified, with giant-cell tumor (n = 17, 35%), chondroblastoma (n = 11, 22%), fibrous dysplasia (n = 6, 12%), osteoblastoma (n = 4, 8%) and osteosarcoma (n = 4, 8%) being the most frequent. The lesions involved chiefly the long bone epiphyses (n = 25, 51%). Secondary ABC imaging findings and locations most closely approximated those of their primary counterparts, although fluid-fluid levels were seen at a higher frequency than previously reported in primary chondroblastoma (9/11, 82%), fibrous dysplasia (2/6, 33%), osteoblastoma (4/4, 100%), osteosarcoma (3/4, 75%), and chondromyxoid fibroma (1/2, 50%). Conclusion: The most common primary lesions associated with secondary ABC were giant cell tumor and chondroblastoma, located in the long bone epiphyses. The majority of the secondary ABCs demonstrate predominant imaging characteristics typical of the primary bone lesions, but with a higher presence of fluid-fluid levels.

1. Introduction Aneurysmal bone cyst (ABC), first described in the literature by Jaffe and Lichenstein in 1942 [1], is a benign, expansile, osteolytic lesion composed of blood-filled spaces segregated by connective-tissue septa, mostly involving the long bones and spines of children and young adults [2–10]. The lesion develops either de novo as a true mesenchymal neoplasm, termed a primary ABC, or secondary to a pre-existing bone lesion, termed a secondary ABC [9,11–14]. Secondary ABCs can be morphologic mimics of primary ABCs, but lack the USP6 and CDH11 gene abnormalities frequently seen in primary ABCs and likely develop as a common pathophysiologic endpoint of various types of non-ABC

primary bone lesions [11]. Secondary ABC demonstrates similar pathologic characteristics as a primary ABC, but has further histologic findings indicating the presence of an additional coexisting lesion [2]. Approximately 70% of ABC cases are primary, and 30% are secondary [2–4,10]. Secondary ABCs have previously been associated with a variety of benign, borderline and malignant primary bone lesions including giant cell tumor, chondroblastoma, osteoblastoma, fibrous dysplasia, Langerhans cell histiocytosis, hemangioma, nonossifying fibroma, and osteosarcoma [2–5,10,11]. Although several studies have described the radiologic, pathologic, and clinical characteristics of primary ABCs, there is a paucity of this information in the literature regarding secondary ABCs [2,5,10,11,15].

Corresponding author at: Department of Radiology and Biomedical Imaging, University of California, San Francisco, 505 Parnassus Ave., Room M391, Box 0628, San Francisco, CA 94143, United States of America. E-mail address: [email protected] (L.B. Gutierrez). 1 Present address: 100 West California Blvd, Pasadena, CA 91105. ⁎

https://doi.org/10.1016/j.clinimag.2020.01.022 Received 28 October 2019; Received in revised form 13 January 2020; Accepted 27 January 2020 0899-7071/ © 2020 Elsevier Inc. All rights reserved.

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Fig. 1. 14-year-old girl with a history of shoulder pain secondary to a humeral head chondroblastoma with secondary ABC. The lesion was treated with curettage. Low magnification photomicrograph of the surgical specimen demonstrates chondroblastoma component (arrow) composed of plaquelike fibrochondroid stroma, ovoid mononuclear cells with eccentric cytoplasm and stippled calcifications. Secondary ABC component (arrowhead) is composed of collagenous fibrous septae containing spindle cells, foam cells, hemosiderin and osteoclast-type giant cells.

As a result, diagnosis of secondary ABC may still be challenging and biopsy misleading [16,17]. One potential diagnostic pitfall is the misinterpretation of a secondary ABC as a primary lesion potentially missing an underlying malignancy. In particular, small biopsy specimens and inadequate imaging increase the potential for misdiagnosis. In this situation, the role of a radiologist with expertise in musculoskeletal imaging is crucial in ensuring that there is optimal radiologicpathologic correlation and accurate diagnosis. The purpose of this study is to describe the imaging, anatomic, and clinical features of a series of pathologically proven secondary ABCs, to ascertain their most common associated primary bone lesions, and to highlight typical imaging features, facilitating radiologic-pathologic correlation efforts.

2.2. Imaging and image analysis Using our institution's picture archiving and communication system (PACS), each patient's radiologic images were reviewed in consensus by two fellowship trained musculoskeletal radiologists (25 years and 7 years of experience in musculoskeletal radiology). Because of the long time period over which cases were retrospectively collected, a wide range of radiographs (in 39/49 cases), computed tomographies (CT) (in 22/49 cases), magnetic resonance (MR) imaging studies (in 39/49 cases), and nuclear medicine studies (in 17/49 cases) were available for pre-operative analysis. Specific imaging characteristics were documented for each lesion systematically, including lesion location, size, margin definition, margin sclerosis, expansile nature, cortical thinning, fracture, periosteal reaction, bone marrow edema, internal architecture including internal matrix, septations, or trabeculations, soft-tissue mass, fluid-fluid level on cross-sectional imaging, contrast enhancement, radiopharmaceutical uptake, and T1/T2/proton density signal intensity on MR imaging. The signal intensities on MR were classified as hypo-, iso-, and hyperintense in comparison with muscular signal intensity. In cases of heterogeneous signal intensities, the predominant signal intensity of the lesion, defined as signal intensity of more than 50% of the lesion, was recorded.

2. Materials and methods 2.1. Patient cohort This retrospective study is in compliance with the Health Insurance Portability and Accounting Act and was approved by our institutional review board. Our institution's pathology database was retrospectively analyzed and all reviewable cases of pathologically proven secondary ABCs were compiled since 1988. Exclusion criteria included lack of diagnostic radiologic imaging prior to tissue diagnosis, more definitive follow-up pathology demonstrating a diagnosis other than secondary ABC, or final pathologic diagnosis rendered at another institution. Patient age at time of diagnosis, gender, relevant medical comorbidities, presenting symptoms, and available pre-biopsy radiologic imaging were recorded, as detailed in the electronic medical record. A total of 49 subjects fulfilled all of the inclusion and exclusion criteria of this study.

2.3. Pathological diagnosis The pathologic diagnoses of the primary bone lesions and of secondary ABC, respectively, were established histologically based on standard criteria [18]. The diagnoses were confirmed by a pathologist with expertise in bone pathology. Cases were classified histologically by their primary tissue diagnosis, anatomically by the main bone involved (e.g., proximal humerus, distal femur), and further anatomically by the

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Table 1 Secondary aneurysmal bone cyst, summary table. Case

Histology

Main bone, sub-location center

Gender

Age (years)

Size (cm)

Imaging

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49

Giant-cell tumor Giant-cell tumor Giant-cell tumor Giant-cell tumor Giant-cell tumor^ Giant-cell tumor Giant-cell tumor Giant-cell tumor Giant-cell tumor Giant-cell tumor Giant-cell tumor Giant-cell tumor Giant-cell tumor Giant-cell tumor Giant-cell tumor Giant-cell tumor Giant-cell tumor Chondroblastoma Chondroblastoma Chondroblastoma Chondroblastoma Chondroblastoma Chondroblastoma Chondroblastoma Chondroblastoma Chondroblastoma Chondroblastoma Chondroblastoma Fibrous dysplasia Fibrous dysplasia Fibrous dysplasia Fibrous dysplasia Fibrous dysplasia Fibrous dysplasia~ Osteoblastoma Osteoblastoma Osteoblastoma` Osteoblastoma Osteosarcoma Osteosarcoma Osteosarcoma Osteosarcoma* Chondromyxoid fibroma Chondromyxoid fibroma Ossifying fibroma Hemangioma Epithelioid hemangioma LCH Osteonecrosis

Femur, distal epiphysis Femur, distal epiphysis Femur, distal epiphysis Femur, distal epiphysis Femur, distal epiphysis Tibia, proximal epiphysis Tibia, proximal epiphysis Tibia, proximal epiphysis Tibia, proximal epiphysis Tibia, proximal epiphysis Tibia, proximal epiphysis Humerus, proximal epiphysis Humerus, proximal epiphysis Radius, distal epiphysis Ulna, distal epiphysis Pelvis, sacrum Patella, entire bone Femur, epiphysis Femur, greater trochanter Femur, greater trochanter Tibia, proximal epiphysis Tibia, distal epiphysis Humerus, greater tuberosity Humerus, distal epiphysis Pelvis, ischiopubic synchondrosis Talus, medial aspect Talus, medial aspect Metacarpal, proximal epiphysis Femur, mid diaphysis Rib, anterior 1st and 2nd Rib, lateral 4th and 5th Metacarpal, proximal diaphysis Pelvis, ilium Cranium, parietal bone Metatarsal, entire diaphysis Talus, anterosuperior aspect Cranium, sphenoid bone Thoracic spine, posterior elements Femur, distal metaphysis Pelvis, ilium Cranium, temporal bone Femur, distal metaphysis Tibia, proximal metaphysis Cranium, occipital bone Mandible, ramus Calcaneus, anterolateral aspect Fibula, distal epiphysis Femur, proximal diaphysis Femur, proximal epiphysis

M M M F F F F M F F M M M M M M M M F F F F F M F M M M F F M F M M F F F M F F M F M M F M F M M

29 57 25 31 35 37 23 53 21 29 56 25 22 31 39 24 27 18 26 16 13 29 14 27 16 26 28 18 24 38 37 13 31 21 11 24 25 15 20 79 43 32 65 8 67 23 8 11 63

6×8×5 8×5x7 4×3×4 6×6×8 2×4×7 5×4×6 4×4×5 5×5×5 4×4×5 5×6×8 6×5×5 5×5×6 4×4×6 3×3×4 3×3×5 4×3×2 2×4×4 3×3×4 8×4×4 4×2×2 3×4×3 5×5×6 3×2×2 2×3×2 4×2×1 3×3×3 4×3×2 4×4×5 2 × 2 × 17 9 × 5 × 10 6×2×6 2×2×2 3×2×3 6×6×6 5×2×2 3×2×3 7×4×6 3×4×3 13 × 7 × 4 13 × 20 6×4×7 9 × 7 × 10 56 × 5 1×1×1 4×5×5 4×4×3 2×1×2 2×2×5 4 × 6 × 17

XR XR, CT, MR, PET XR XR, CT, PET XR, MR XR, MR XR, MR, BS XR, CT, MR, BS XR, CT, MR XR, CT, MR, BS XR, MR XR, MR, BS XR, MR XR XR, MR, BS CT, MR XR, MR XR, CT, MR, BS XR, MR, BS XR, MR XR, MR XR, CT, MR XR, MR XR, MR, BS XR, CT, MR XR, CT, MR CT, MR XR XR, MR, BS XR, CT CT XR, MR, BS XR, CT, MR CT, MR XR, MR XR, CT, MR CT, MR CT, MR, BS XR, CT, MR, PET, BS XR MR XR, MR XR, MR, BS CT, MR CT XR, MR, PET MR XR XR, CT, MR, PET

Note. — M = Male, F = Female, ^ABC in lesion recurrence, measured largest of multiple lesions, ~McCune-Albright syndrome, ` Aggressive osteoblastoma subtype, *ABC in lesion recurrence, LCH = Langerhans cell histiocytosis, XR = Radiograph, CT = Computed tomography, MR = Magnetic resonance, BS = Bone scan, PET = Positron emission tomography.

sub-location center (e.g., epiphyseal, diaphyseal, metaphyseal). Mean radiologic lesion size was calculated for each type of primary bone lesion by first obtaining the largest measured diameter for each of the 49 cases, then using these diameters to obtain a mean diameter for each of

the 11 lesion types; if only one case example was available for a type of primary lesion, the largest measured diameter was used.

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Table 2 Secondary ABC case and demographics summary. Mean lesion size

Age range

Mean age

Histology

Cases

Male

Female

(cm), ± SD

(years)

(years)

Giant-cell tumor Chondroblastoma Fibrous dysplasia Osteoblastoma Osteosarcoma Chondromyxoid fibroma Ossifying fibroma Hemangioma Epithelioid hemangioma Langerhans cell histiocytosis Osteonecrosis Total

17 (35%) 11 (22%) 6 (12%) 4 (8%) 4 (8%) 2 (4%) 1 (2%) 1 (2%) 1 (2%) 1 (2%) 1 (2%) 49

9 (18%) 5 (10%) 3 (6%) 1 (2%) 1 (2%) 2 (4%) 0 1 (2%) 0 1 (2%) 1 (2%) 24

8 (16%) 6 (12%) 3 (6%) 3 (6%) 3 (6%) 0 1 (2%) 0 1 (2%) 0 0 25

5.8 ± 1.5 4.4 ± 1.4 7.3 ± 5.0 4.8 ± 1.5 12.5 ± 4.8 3.5 ± 2.5 5 4 2 5 17 6.1

21–57 13–29 13–37 11–25 20–79 8–65 67 23 8 11 63 8–79

33.2 21 27.3 18.3 43.5 36.5 – – – – – 29.7

Note.—Mean lesion sizes were calculated for each type of primary bone lesion by averaging the largest measured diameters for each primary lesion type. If only one case example was available, the largest measured diameter was provided. SD = Standard deviation. Fig. 2. 57-year-old man presented with a history of progressive knee pain due to giant-cell tumor with secondary ABC. Frontal radiograph of the distal femur (a) demonstrates a well-defined lytic lesion centered at the medial aspect of the distal femoral epiphysis, lacking a sclerotic border. Axial positron emission tomography image through the distal femurs (b) demonstrates relative radiopharmaceutical uptake in the left distal femur at the site of the giantcell tumor. Axial CT image of the distal femur on bone window (c) demonstrates a well-defined, lytic lesion. Coronal proton density weighted fat saturated MR image of the distal femur (d) demonstrates a well-defined hyperintense lesion centered in the epiphysis and extending to the subchondral region, containing internal septations, and surrounded by moderate periosteal reaction and bone marrow edema. Axial proton density weighted fat saturated MR image of the distal femur (e) demonstrates fluidfluid levels within the lesion (arrow).

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Fig. 3. 16-year-old female patient presented with a 9-month history of left hip pain due to chondroblastoma with secondary ABC. Frontal radiograph of the proximal femur (a) demonstrates a well-defined lytic lesion centered at the greater trochanter (an epiphyseal equivalent), with a mildly sclerotic border. Sagittal (b) and axial (c) proton density weighted fat saturated MR images of the proximal femurs demonstrate a well-defined lesion centered in the left greater trochanter, containing internal septations, surrounded by mild periosteal edema and bone marrow edema compared to the contralateral side, and containing fluid-fluid levels (arrows).

3. Statistical analysis

secondary ABC. A total of 32 of these patients were excluded either because of a lack of diagnostic radiologic imaging prior to pathologic diagnosis of secondary ABC (n = 24), more definitive follow-up pathology demonstrating a diagnosis of primary rather than secondary ABC (n = 4), more definitive follow-up pathology demonstrating a lack of secondary ABC (n = 2), or because final histologic diagnosis was performed at an outside institution (n = 2). The final study population comprised of 25 females (age range 8—79 years; mean 27.2 ± 15.8 years) and 24 males (age range 8—65 years; mean 32.2 ± 15.9years), with an overall age range of 8—79 years and mean age of 29.7 ± 16 years. Of note, one patient had a previous history of McCune-Albright syndrome manifesting as polyostotic fibrous dysplasia, one patient developed secondary ABC with recurrent osteosarcoma, and one patient developed secondary ABC with recurrent giant-cell tumor. There were no additional relevant patient histories, metabolic disorders, or other significant medical co-morbidities identified. Several of the pathology specimens consisted of curettage specimens, which histologically appeared as a mixture of primary tumor and discrete fragments of secondary ABC (Fig. 1). Patients underwent various combinations of radiographic, CT, MR, and/or nuclear medicine imaging prior to histologic diagnosis, as

Statistical analysis was performed using STATA version 14 software (StataCorp LP, College Station, TX). The statistical significance threshold was set at a p value less than 0.05. Lesion volumes were calculated by multiplying transverse, anteroposterior, and craniocaudal lengths of the lesions. Linear regression analysis was used to quantify the associations between lesion type and (a) age at diagnosis and (b) lesion volumes, as well as to quantify the associations between patient ages and lesion volumes. Chi-squared tests were used to assess differences in the distribution between lesion type and (a) gender (b) lesion location (c) presence of a well-defined margin (d) presence of margin sclerosis (e) presence an expansile lesion (f) presence of cortical thinning (g) presence of a fracture (h) presence of periosteal reaction (i) presence of bone marrow edema (j) presence of internal architecture (k) presence of a soft tissue mass and (l) presence of fluid-fluid levels. 4. Results Between August 1988 and July 2016 (28 year time period), 81 patients underwent bone tissue sampling with an initial diagnosis of

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The tumors associated with secondary ABCs, as well as the tumor sizes, gender distributions, and patient ages associated with each type of primary lesion are summarized in Table 2. Eleven primary bone lesions were associated with secondary ABC with the most frequent being giant-cell tumor (Fig. 2), chondroblastoma (Fig. 3), fibrous dysplasia (Fig. 4), osteoblastoma (Fig. 5), and osteosarcoma (Fig. 6). Interestingly one case of secondary ABC was associated with osteonecrosis, a nonneoplastic lesion. Cases occurred in ten anatomic locations as summarized in Table 3, with the most frequent location being long bone epiphyses. Specific imaging characteristics for the six most frequent primary bone lesions are summarized in Table 4. Specific imaging characteristics for the five primary bone lesions with single case examples are summarized in Table 5. Linear regression analysis demonstrated that there was a significant difference in age at diagnosis between lesion types (p = 0.004), in lesion volume between lesion types (p = 0.003) (Fig. 7), and in lesion volume between patient ages (p = 0.004) (Fig. 8). Chi-squared tests also demonstrated that there was a significant difference in lesion location between lesion types (p = 0.001). These results are unsurprising as several of the identified primary lesions have very well established predilections for certain age groups and anatomic locations. For example, chondroblastomas with secondary ABCs in our study occurred in younger, less skeletally mature individuals, as well as in epiphyseal or epiphyseal-equivalent locations, similar to previously reported cases of primary chondroblastomas [3,4,7,9–11]. Chi squared testes demonstrated that there was a significant difference in the presence of a well-defined margin (p = 0.004), in the presence of cortical thinning (p = 0.001), and in the presence of a soft tissue mass between lesion types (p = 0.003), reflecting a difference in lesion aggressiveness. In particular, none of the osteosarcoma cases had well-defined margins, and all had associated soft tissue masses. Chi squared tests demonstrated that there was a significant difference in the presence of internal architecture (p = 0.032) and in the presence of fluid-fluid levels between lesion types (p = 0.024). The cases of Langerhans cell histiocytosis and osteonecrosis, as well as few of the giant cell tumor and fibrous dysplasia cases, had no internal architecture. All of the osteoblastoma and osteosarcoma cases demonstrated fluid-fluid levels, while the remaining primary lesion types variably demonstrated them. Fluid-fluid levels have previously been reported in 16.2% of giant cell tumors, 16% of chondroblastomas, 18.8% of fibrous dysplasias, 22.6% of conventional osteosarcomas, and 5% of chondromyxoid fibromas [19,20]; although osteoblastomas have traditionally been associated with fluid-fluid levels, only few case reports are available in the literature [19,21]. All of the primary lesion types containing fluid-fluid levels in our study demonstrated them at a higher percentage than previously reported in the literature (Table 4). Of note, the proportion of the fluid-fluid component relative to the primary bone lesion component, although difficult to objectively quantify for each lesion, greatly varied between each lesion by visual inspection, even within the different histologic sub-groups. Some lesions only had few scattered fluid-fluid levels (Fig. 1E), while others where almost completely replaced by fluid-fluid levels (Fig. 3B).

Fig. 4. 13-year-old female patient presented with a 6-month history of a rapidly enlarging “bump” in her hand due to fibrous dysplasia with secondary ABC. Frontal radiograph of the wrist (a) demonstrates a well-defined lytic and expansile lesion with mixed density centered at the fifth proximal metacarpal diaphysis. Bone scan image of the bilateral hands (b) demonstrates significant radiopharmaceutical uptake at the lesion site in the hand (arrowhead). Axial T2 weighted MR image through the metacarpals (c) demonstrates a well-defined lesion centered in the fifth proximal metacarpal diaphysis, containing internal septations and fluid-fluid levels (arrows).

detailed in Table 1; the table also lists every patient's gender, age, lesion location, and lesion size. Lesions were discovered either due to imaging for workup of pain (n = 35), unrelated trauma (n = 3), or an enlarging mass (n = 6); five referral cases did not have the patients' presenting clinical symptoms documented in our institution's electronic medical record.

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Fig. 5. 24-year-old female patient presented with a 3-year history of ankle pain due to aggressive osteoblastoma with secondary ABC. Lateral ankle radiograph (a) demonstrates a well-defined lytic, expansile, exophytic lesion with soft tissue extension and internal mineralization, centered at the anterosuperior aspect of the talus. Axial contrast enhanced CT image of the left talus on bone window (b) demonstrates a focus of internal nodular enhancement (asterisk), marginal irregularity, and osseous erosion at the anterolateral aspect of the lesion (arrowhead). Sagittal T1 weighted MR image of the talus (c) demonstrates a well defined, and exophytic talar lesion with predominant T1 isointensity, as well as periosteal reaction (arrowheads) and bone marrow edema. Sagittal short tau inversion recovery (STIR) weighted MR image of the talus (d) demonstrates a fluid-fluid level (arrow).

Chi-squared tests demonstrated that there was no significant difference in gender distribution between lesion types (p = .405), in presence of margin sclerosis between lesion types (p = .113), in the presence of an expansile lesion between lesion types (p = .098), in the presence of a fracture between lesion types (p = .814), in the presence of periosteal reaction between lesion types (p = .406), and in the presence of bone marrow edema between lesion types (p = .147), implying that these demographic and imaging characteristics are less helpful in distinguishing between the primary lesion types. Except for cases of recurrent osteosarcoma, chondromyxoid fibroma, and osteonecrosis, most primary lesions evaluated with intravenous contrast demonstrated enhancement (30/32). Except for one chondroblastoma case, all lesions that were evaluated with nuclear medicine exams demonstrated radiopharmaceutical uptake (16/17). Most lesions that were evaluated with MR imaging demonstrated predominant T1 isointensity and T2/proton density hyperintensity when compared to muscle signal intensity; no lesion demonstrated predominant signal hypointensity on any sequence. One osteosarcoma case did demonstrate T1 hyperintensity along with T2 hyperintensity, possibly reflective of blood products.

5. Discussion Our study confirms that secondary ABCs are associated with a wide variety of primary bone lesions, most frequently giant cell tumor, chondroblastoma, fibrous dysplasia, and osteoblastoma, as well as malignant tumors, such as osteosarcoma. One case of osteonecrosis, a non-neoplastic lesion, was also associated with secondary ABC. The imaging, anatomic, and clinical characteristics of each of the eleven primary bone lesions associated with secondary ABCs in our study, aside from the higher presence of fluid-fluid levels, were overall equivalent to the expected findings of the primary bone lesions independent of secondary ABC, which is in concordance with previous findings reported in the literature [2–5,7,9–11,15,21–53]. Our study also revealed that several of the imaging characteristics were not helpful in differentiating one primary bone lesion from another. For example, there was no significant difference in margin sclerosis, presence of an expansile lesion, presence of a fracture, presence of periosteal reaction, or presence of bone marrow edema between lesion types. Also, most lesions demonstrated radiopharmaceutical uptake, enhancement, T1 isointensity, and T2 hyperintensity.

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Table 3 Secondary ABC location summary. Location

Cases

Long bone, epiphysis Long bone, metaphysis Long bone, diaphysis Pelvis Tarsal Cranium Rib Mandible Spine Patella Total

25 (51%) 3 (6%) 4 (8%) 4 (8%) 4 (8%) 4 (8%) 2 (4%) 1 (2%) 1 (2%) 1 (2%) 49

levels are not pathognomonic for ABCs and can occur in several other tumor entities, they can be more suggestive of their presence in the appropriate clinical setting [13,54,55]. Still, in clinical practice, the presence of a fluid-fluid level within a bone lesion by imaging does not definitively establish the presence of a secondary bone cyst. Our study is limited in that it is largely descriptive in nature and is retrospective. Radiologic analyses of the 49 patient images were done in consensus by two musculoskeletal radiologists with knowledge of the lesion diagnoses, which introduces the possibility of observer bias. Some primary lesion types in our study only had one or few case examples available, possibly weakening statistical power. In conclusion, the cases of secondary ABC included in our study had imaging, anatomic, and clinical features most consistent with the expected characteristics of their primary bone lesions independent of the presence of a secondary ABC, with the most common primary lesions associated with secondary ABC being giant cell tumor and chondroblastoma, located in the long bone epiphyses. Several of the primary bone lesions containing secondary ABCs more frequently demonstrated fluid-fluid levels than previously reported in the literature, however the presence of a fluid-fluid level is not diagnostic of the presence of a secondary bone cyst. Ultimately, the true value of radiologic correlation in these cases is not to confirm the presence of a secondary ABC, but rather to suggest the presence of the most likely primary bone lesion based on lesion location, lesion imaging characteristics, and patient demographics. This is particularly important in guiding tissue sampling and appropriate treatment, as secondary ABCs are typically treated based on the histology of the underlying primary bone lesion. Any disparity in the expected clinical, imaging, and pathologic characteristics identified in the workup of a bone tumor should raise suspicion of a misdiagnosis, and necessitates further joint review of the findings by the clinician, pathologist, and radiologist.

Fig. 6. 20-year-old female patient presented with a 3-month history of knee pain and swelling with associated 10-pound weight loss due to osteosarcoma with secondary ABC. Frontal distal femur radiograph (a) demonstrates an illdefined lytic lesion with internal fluffy osteoid matrix and diffuse periosteal reaction, centered at the distal femoral metaphysis and extending proximally into the diaphysis. Frontal bone scan of the lower extremities (b) demonstrates intense radiopharmaceutical uptake in the left distal femur, as well as proximal skip lesions in the left femur (black arrows). Axial T2 weighted fat saturated MR image of the distal femur (c) demonstrates fluid-fluid levels with thin septal walls (white arrow). Axial contrast enhanced CT image of the distal femur (d) demonstrates cortical breakthrough with associated soft tissue mass (arrowhead), and internal dense osteoid matrix.

Interestingly, the giant cell tumor, chondroblastoma, fibrous dysplasia, osteoblastoma, osteosarcoma, and chondromyxoid fibroma cases with secondary ABC demonstrated a higher percentage of lesions associated with fluid-fluid levels when compared to primary lesions without secondary ABCs, supporting the idea that although fluid-fluid

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Table 4 Secondary ABC imaging characteristics (six lesions with multiple cases each). Primary

Lesion OB

Image characteristic

GCT

CB

FD

Well-defined margin Margin sclerosis Expansile Cortical thinning Fracture Periosteal reaction Bone marrow edema Internal architecture Soft-tissue mass Fluid-fluid level Contrast enhancement Radiopharmaceutical uptake T1 signal hyperintensea T1 signal isointensea T2 signal hyperintensea T2 signal isointensea PD signal hyperintensea PD signal isointensea

16/17 (94%) 2/17 (12%) 17/17 (100%) 17/17 (100%) 3/17 (18%) 11/17 (65%) 8/13 (62%) 15/17 (88%) 3/17 (18%) 4/13 (31%) 8/8 (100%) 6/6 (100%) 1/10 (10%) 9/10 (90%) 11/11 (100%) 0 10/10 (100%) 0

11/11 (100%) 6/11 (55%) 9/11 (82%) 10/11 (91%) 0 9/11 (82%) 7/10 (70%) 11/11 (100%) 0 9/10 (90%) 6/6 (100%) 2/3 (67%) 2/9 (22%) 7/9 (78%) 8/8 (100%) 0 6/6 (100%) 0

5/6 1/6 5/6 6/6 0 3/6 1/4 4/6 0 2/4 5/5 2/2 0 4/4 4/4 0 1/1 0

(83%) (17%) (83%) (100%) (50%) (25%) (67%) (50%) (100%) (100%) (100%) (100%) (100%)

4/4 2/4 4/4 4/4 0 3/4 1/4 4/4 2/4 4/4 4/4 1/1 0 4/4 2/4 2/4 1/1 0

OS (100%) (50%) (100%) (100%) (75%) (25%) (100%) (50%) (100%) (100%) (100%) (100%) (50%) (50%) (100%)

0 1/4 4/4 2/3 0 3/3 3/3 3/3 3/3 3/3 2/3 1/1 1/3 2/3 3/3 0 n/a n/a

CF (25%) (100%) (67%) (100%) (100%) (100%) (100%) (100%) (67%) (100%) (63%) (100%)

2/2 0 2/2 2/2 0 2/2 0 2/2 2/2 1/2 2/2 1/1 0 1/1 2/2 0 n/a n/a

(100%) (100%) (100%) (100%) (100%) (100%) (50%) (100%) (100%) (100%) (100%)

Note.—Ratio of cases with the listed imaging characteristic to the total cases analyzed for the imaging characteristics provided, as well as percentage. n/ a = Parameter not available for analysis. GCT = Giant-cell tumor, CB = Chondroblastoma, FD = Fibrous dysplasia, OB = Osteoblastoma. OS = Osteosarcoma, CF = Chondromyxoid fibroma, PD = Proton density. a Magnetic resonance signal intensity compared to muscle; no tumor had hypointense signal. Table 5 Secondary ABC imaging characteristics (six lesions with single case each). Primary

Lesion

Image characteristic

OF

HA

EH

LCH

ON

Well-defined margin Margin sclerosis Expansile Cortical thinning Fracture Periosteal reaction Bone marrow edema Internal architecture Soft-tissue mass Fluid-fluid level Contrast enhancement Radiopharmaceutical uptake T1 signal hyperintensea T1 signal isointensea T2 signal hyperintensea T2 signal isointensea PD signal hyperintensea PD signal isointensea

+ + + − + − n/a + − n/a − n/a n/a n/a n/a n/a n/a n/a

+ − + + − + + + − − + + − + − + − +

+ n/a + − − + + + − − + n/a − + + − n/a n/a

+ − + + − − n/a − − n/a n/a n/a n/a n/a n/a n/a n/a n/a

− − − − − + + − − − − + − + + − n/a n/a

Fig. 7. Bar graph demonstrating differences in lesion volume by primary lesion type.

Note.— n/a = Parameter not available for analysis, + = Present, − = Absent. OF = Ossifying fibroma, HA = Hemangioma, EH = Epithelioid hemangioma. LCH = Langerhans cell histiocytosis, ON = Osteonecrosis, PD = Proton density. a Magnetic resonance signal intensity compared to muscle; no tumor had hypointense signal.

Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Declaration of competing interest None. Fig. 8. Linear regression analysis, demonstrating differences in lesion volume by patient age at diagnosis. 31

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L.B. Gutierrez, et al.

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