Utility of Repeat Core Needle Biopsy of Musculoskeletal Lesions With Initially Nondiagnostic Findings

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1 Musculoskeletal Imaging Original Research Repeat Core Needle Biopsy of Initially Nondiagnostic Musculoskeletal Lesions Musculoskeletal Imaging Original Research JOURNAL CLUB Jim S. Wu 1 Colm J. McMahon 1 Santiago Lozano-Calderon 2 Justin W. Kung 1 Wu JS, McMahon CJ, Lozano-Calderon S, Kung JW Keywords: core needle biopsy, diagnostic yield, musculoskeletal lesions, repeat biopsy DOI: /AJR Received February 11, 2016; accepted after revision September 7, Department of Radiology, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA Address correspondence to J. S. Wu (jswu@bidmc.harvard.edu). 2 Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center, Boston, MA. AJR 2017; 208: X/17/ American Roentgen Ray Society JOURNAL CLUB: Utility of Repeat Core Needle Biopsy of Musculoskeletal Lesions With Initially Nondiagnostic Findings OBJECTIVE. The purpose of the present study is to assess the utility of repeat imageguided core needle biopsy (CNB) of musculoskeletal lesions in the setting of initially nondiagnostic CNB findings. MATERIALS AND METHODS. A retrospective review was conducted of 1302 consecutive CNBs performed on bone or soft-tissue lesions at a single institution. Pediatric cases and spine lesions were not included. All cases for which a repeat biopsy of the same lesion was performed because biopsy results were nondiagnostic were included in the study. Tumor characteristics, such as lesion size and type (i.e., bone vs soft tissue), were correlated with the diagnostic yield on repeat biopsy. Technical factors, including the modality used, the number of passes performed, the gauge of the biopsy device, the time between biopsies, the radiologist performing the procedure, and the portion of the lesion biopsied, were also correlated. RESULTS. Twenty-six of the 1302 CNBs (2.0%) performed had been referred for repeat biopsy. A diagnosis was obtained for 10 of these 26 cases (38.5%) after repeat CNB. For five of the cases (19.2%), repeat CNB yielded a diagnosis of malignancy. Overall, 11 cases ultimately had histologic findings indicating malignancy, and five of these cases (45.4%) had diagnostic findings after rebiopsy. Of the 14 cases that were found to be benign, five (35.7%) had diagnostic findings after rebiopsy. One case was lost to follow-up. A statistically significant difference in the diagnostic yield was found in association with an increase in the number of passes (p = 0.047) and an increase in time (p = 0.020) between biopsies. CONCLUSION. Repeat CNB of musculoskeletal lesions with initially nondiagnostic biopsy findings can be useful. Increasing the number of passes on the second biopsy attempt is recommended. B iopsy of musculoskeletal lesions allows histologic diagnosis and guides medical and surgical management. Open surgical biopsy is considered to be the reference standard for diagnosis; however, image-guided core needle biopsy (CNB) is often performed first because of its minimally invasive nature, decreased recovery time, lower cost, and lower complication rate [1 5]. The reported diagnostic accuracy of CNB is well established and ranges from 66% to 98% [1, 2, 6 19]. Cases for which a nondiagnostic finding is obtained can lead to a clinical conundrum because a nondiagnostic finding may result in delayed or incorrect treatment and patient and physician anxiety. Nondiagnostic CNB results are noted more often in association with benign and low-grade neoplasms as opposed to malignant neoplasms [15]. Moreover, the diagnos- tic yield is lower for sclerotic bone lesions than for lytic lesions [20]. Furthermore, certain diagnoses, such as ganglia or subchondral cysts due to osteoarthritis, cannot be conclusively made on the basis of histologic findings because of the small amount of tissue obtained during a CNB [21]. These factors lead to a higher rate of nondiagnostic results with CNB [21] versus surgical biopsy. Although nondiagnostic CNB results can be useful [21], in cases for which malignancy is suspected, a definitive histologic diagnosis is often still needed. This can be accomplished by surgical biopsy or a repeat CNB. Repeat CNB has been shown to be useful for analysis of other body parts, including the breast [22] and kidney [23]. It is unclear whether this is true for musculoskeletal lesions. This information could be important to guide diagnostic management, because a repeat CNB with diagnostic findings may AJR:208, March

2 spare the patient the morbidity and cost associated with an open surgical biopsy; however, another nondiagnostic CNB result could delay patient care and create more anxiety. Therefore, the purpose of the present study is to assess the utility of repeat CNB after an initial nondiagnostic CNB result. Materials and Methods This study was approved by the institutional review board at Beth Israel Deaconess Medical Center. The requirement for informed patient consent was waived. A retrospective review was conducted of 1302 consecutive CNB examinations of bone or soft-tissue lesions performed at a tertiary academic center between June 2004 and September The CNBs were performed on indeterminate or suspicious musculoskeletal lesions requiring a pathologic tissue diagnosis. A total of 26 cases for which a repeat biopsy of the same lesion was requested by the referring physician because initial nondiagnostic biopsy results were included in the study. Among the cases that were excluded were those for which an alternative lesion was biopsied at the time of the second image-guided biopsy procedure, pediatric cases, and lesions in the vertebral body, because these types of cases are not evaluated by our musculoskeletal radiology service. Biopsy Technique In all cases, CNBs were performed under ultrasound or CT fluoroscopy guidance by musculoskeletal fellowship trained radiologists with 5 12 years of experience. Ultrasound was generally used for soft-tissue lesions, whereas CT fluoroscopy was used for osseous lesions. The biopsy approach was determined after consultation with the orthopedic surgeon, to ensure that the biopsy track would correlate with the surgical approach, minimize intercompartmental contamination, and avoid neurovascular structures. In most cases, samples were obtained by musculoskeletal fellows under the supervision of an attending musculoskeletal radiologist. A cytopathologist was present if there was high concern for sampling error, and fine-needle aspirations were performed if there was a high suspicion for lymphoma or if poor CNB samples were obtained. A 14- or 16-gauge coaxial automated biopsy system (Achieve, Cardinal Health) was used for soft-tissue lesions or osseous lesions with softtissue components. For intraosseous lesions, a 13- or 15-gauge bone biopsy system (Bonopty, Apriomed) or a coaxial (11-gauge access needle and 13-gauge biopsy needle) battery-powered bone access system (OnControl, Vidacare) was used. For each biopsy, a minimum of three cores and a maximum of six cores were obtained. For Nondiagnostic (n = 282) Repeat CNBs (n = 26) Nondiagnostic (n = 16) Surgical biopsy (n = 7) 1 benign 6 malignant sclerotic bone lesions, the least sclerotic region was targeted, if possible. All CNB samples were placed in formalin. Images showing the biopsy needle within the lesion were obtained in all cases. In cases of suspected osteomyelitis, additional samples were placed in a sterile container and delivered directly to the microbiology department for placement in growth medium. A diagnostic biopsy sample was one for which culture results were positive for a causative organism, even if the pathologic findings for the specimen were unhelpful. The pathologic samples and the pathology reports were reviewed by experienced musculoskeletal pathologists at the same institution. Data Analysis Two board-certified musculoskeletal radiologists with 11 and 6 years of experience reviewed images of the rebiopsied lesions in consensus on an independent workstation (Centricity, GE Healthcare). Medical records were also reviewed. Images were evaluated for lesion size (categorized as < 2 cm, 2 5 cm, or > 5 cm) and lesion subtype (categorized as soft tissue, sclerotic bone, or mixed or lytic bone), to determine whether any of these factors correlated with a higher diagnostic yield on repeat biopsy. Medical records and procedure reports were retrospectively reviewed to determine the number of passes performed, the gauge of the biopsy device, the time between biopsies, the radiologist performing the procedure, Total CNBs (n = 1302) Surgical biopsy (n = 110) 95 benign 15 malignant Diagnostic (n = 10) Diagnostic yield = 38.5% 5 benign 5 malignant Clinical follow-up (n = 9) 9 benign Diagnostic (n = 1020) Diagnostic yield = 78.3% 428 benign 592 malignant Clinical follow-up (n = 146) 143 benign 3 malignant Fig. 1 Flowchart of findings for 1302 core needle biopsies (CNBs) of musculoskeletal lesions. and the pathologic findings for the specimen. A biopsy sample was considered to be nondiagnostic if a distinct pathologic diagnosis could not be rendered from analysis of the biopsy tissue that explained the lesion clinically and from imaging. The final diagnosis for each lesion was based on the type of surgery performed (i.e., biopsy or excision) or the findings from clinical follow-up (mean, 50.1 months; range, months). For nondiagnostic lesions with clinical follow-up only, we would not be able to arrive at a specific diagnosis for many cases because of the lack of tissue. However, we would conclude that the lesion was likely benign if there was no change either in symptoms or in the appearance of the lesion on imaging after 12 months. Statistical Analysis The overall diagnostic rate associated with repeat CNB was determined. Moreover, subgroup analyses were performed on the final diagnosis (benign vs malignant). soft-tissue versus bone tumors, and lesion size. Analysis of differences in technical factors (i.e., the number of passes, the gauge of the biopsy needle, the time between biopsies, the radiologist performing the procedure, and the pathologic findings for the specimen) between repeat CNB and the initial biopsy was performed, and each factor was correlated with the diagnostic rate by use of the chi-square test. All statistical calculations were performed using statistical software (Stata, version 13.1, StataCorp). 610 AJR:208, March 2017

3 Repeat Core Needle Biopsy of Initially Nondiagnostic Musculoskeletal Lesions TABLE 1: Summary of Findings for Malignant and Benign Lesions That Underwent Repeat Core Needle Biopsy Malignant Lesion Type No. of Lesions No. (%) of Lesions With Diagnostic Findings on Rebiopsy Metastatic carcinoma 3 2 (66.7) Lymphoma 2 1 (50.0) Ewing sarcoma 2 1 (50.0) High-grade sarcoma 2 1 (50.0) Malignant peripheral nerve sheath tumor 1 0 Chondrosarcoma 1 0 Benign Osteomyelitis or sacroiliitis 3 1 (33.3) Paget disease 2 2 (100.0) Stress fracture 2 0 Ossifying fibroxanthoma 1 1 (100.0) Solitary fibrous tumor 1 1 (100.0) Eosinophilic granulomatosis 1 0 Atypical histiocytoid 1 0 Unknown 3 0 A Results During a 10 year and 4 month period, 1302 CNBs of musculoskeletal lesions were performed (Fig. 1). Of these biopsies, 282 (21.7%) had nondiagnostic findings, and 26 lesions in 26 patients (12 men and 14 women; mean age, 55.3 years; range, years) ultimately were rebiopsied with CNB at the request of the referring physician. Thus, only 9.2% of cases with nondiagnostic findings underwent repeat biopsy. The biopsy needle sizes used were as follows: 13-gauge needles were used for 10 patients; 14-gauge needles, for two patients; 15-gauge needles, for five patients; and 16-gauge needles, for nine patients. Of the lesions that were biopsied, 11 ultimately were found to be malignant, and 14 were found to be benign, with one patient who had a history of colon cancer eventually being lost to follow-up after undergoing two biopsies for which findings were nondiagnostic. A diagnosis was obtained for 10 of 26 cases (38.5%) after a second biopsy was performed. For five of the 26 cases (19.2%), a repeat CNB indicated malignancy. Of the 11 malignant cases, five cases (45.4%) had diagnostic findings after rebiopsy. Five of the 14 benign cases (35.7%) had diagnostic findings after rebiopsy. When malignant and benign cases were compared, the difference in the proportion of repeat biopsies for which results were positive was not statistically significant (p = 0.623, two-sample proportion test). A summary of findings for the lesions is provided in Table 1. Characteristics of the lesions were analyzed to determine whether they affected the rate of rebiopsy. The lesions were subdivided into the following three subtypes: soft-tissue, sclerotic bone, and mixed or lytic bone lesions. Of the six soft-tissue tumors that were rebiopsied, two (33.3%) had diagnostic findings after the repeat procedure. Of the osseous lesions, 11 were sclerotic, and four of these 11 lesions (36.4%) had diagnostic findings on rebiopsy. The remaining osseous lesions were lytic or mixed. Of these nine lesions, four (44.4%) had diagnostic findings (Table 2). There was no significant difference among these subgroups Fig year-old man with lytic left acetabular Ewing sarcoma. A, Coronal T1-weighted fat-saturated contrast-enhanced MR image shows heterogeneously peripherally enhancing left acetabular mass (arrows) with central necrosis. B, CT fluoroscopic image from initial nondiagnostic core needle biopsy shows biopsy needle (arrow) in inferior portion of lesion but likely in area of necrosis. C, CT fluoroscopic image obtained at rebiopsy shows biopsy needle (arrow) in left acetabular lesion in different and more superior portion of lesion, which revealed Ewing sarcoma. Six core biopsy samples were obtained at rebiopsy versus four samples obtained during initial biopsy. B C AJR:208, March

4 TABLE 2: Characteristics of Rebiopsied Lesions Lesion Type and Patient Lesion Description Patient Age (y) Patient Sex History of Cancer Suspicious Biopsy Findings Aggressive Appearance Suspicious for Infection Size (mm) Malignant Diagnostic Findings on Rebiopsy Diagnosis Follow-Up Soft tissue 1 Soft-tissue mass in left pectoral region 2 Soft-tissue mass in left thigh 3 History of myxofibrosarcoma with thigh mass 4 Enlarging mass in right posterior thigh 5 History of malignant schwannoma with thigh mass 6 Soft-tissue mass in left thigh Osseous Sclerotic 7 Sacroiliac joint erosion and sclerosis 8 Desmoid tumor with multiple bone lesions 9 Colon and lung cancer with iliac bone lesion 10 Sclerotic lesion in distal femur 11 History of breast cancer with iliac bone lesions 12 History of breast cancer with iliac bone lesions 13 Lymphoma with lesion in proximal femur 63 M High-grade liposarcoma 68 F Atypical hystiocytoid neoplasm 82 M Unknown Resolved on follow-up 73 F Pleiomorphic sarcoma 59 F Malignant nerve sheath 47 M Solitary fibrous tumor 31 F Infectious sacroiliitis Treated for septic arthritis 50 F Unknown Stable at follow-up 82 F Ossifying fibroxanthoma Stable at follow-up 60 F Lymphoma Surgical biopsy 57 F Breast carcinoma Treated 72 F Breast carcinoma Treated 39 M Lymphoma Treated 14 Sclerotic lesion in femur 37 M Osteomyelitis Surgery and antibiotics 15 History of breast cancer with left iliac bone lesion 16 Hodgkin lymphoma with acetabular lesion 61 F Breast cancer Treated for carcinoma 71 M Stress fracture Resolved at follow-up 17 Acetabular lesion 37 M Ewing sarcoma (Table 2 continues on next page) 612 AJR:208, March 2017

5 Repeat Core Needle Biopsy of Initially Nondiagnostic Musculoskeletal Lesions TABLE 2: Characteristics of Rebiopsied Lesions (continued) Diagnostic Findings on Rebiopsy Diagnosis Follow-Up Size (mm) Malignant Suspicious for Infection Aggressive Appearance Suspicious Biopsy Findings History of Cancer Patient Sex Patient Age (y) Lesion Type and Patient Lesion Description Mixed or lytic 18 Mixed tibial lesion 55 F Paget disease Stable at follow-up 19 Lytic left acetabular lesion 34 M Ewing sarcoma Transferred care 20 Periprosthetic soft-tissue 78 M Unknown Stable at follow-up and lytic lesion 34 F Low-grade chondrosarcoma 21 Sclerotic and lytic lesion in right femur 64 M Unknown Lost to follow-up 22 Colon cancer and lytic lesion in acetabulum 31 M Chronic osteomyelitis Surgery and antibiotics 23 Lytic bone and soft-tissue lesion in femur 76 F Stress fracture Resolved at follow-up 24 Metastatic breast cancer with mixed sacral lesions 57 F Paget disease Stable at follow-up 25 Lytic and sclerotic left iliac lesion Treated and resolved 26 Lytic right ischial lesion 19 M Eosinophilic granulomatosis Note Plus sign (+) denotes presence of finding. F = female, M = male. in terms of the diagnostic yield at repeat biopsy (p = 0.950, by Fisher exact test). Lesions were also grouped by size (< 2 cm, 2 5 cm, or > 5 cm). Six lesions were smaller than 2 cm, and one of these six lesions (16.6%) had diagnostic findings. Of the 10 lesions that were between 2 and 5 cm, four (40.0%) had diagnostic findings on rebiopsy. Finally, 10 lesions were larger than 5 cm; of these, five (50.0%) had diagnostic findings on rebiopsy. There was no statistically significant correlation between lesion size and the diagnostic rate at repeat CNB (p = 0.235, Kendall tau b test). Follow-up was performed for all cases. Of the 16 cases with nondiagnostic findings after rebiopsy, one case was lost to follow-up. Seven of the 16 cases (43.8%) underwent surgical biopsy; for five of these cases, tumors were found to be malignant, and for the remaining two cases, tumors were found to be benign. The remaining cases were followed for an average of 50.1 months (range, months). One of these cases was treated presumptively for metastatic breast carcinoma. The remaining cases were stable or had resolved on follow-up. Of the 10 cases for which findings were diagnostic after rebiopsy, three (30%) underwent surgery. There were no discrepancies between the pathologic findings from CNB versus surgery. Two of these cases were benign and included one case of solitary fibrous tumor, which was resected, and one case of chronic osteomyelitis, which was débrided. One case of malignant liposarcoma was treated surgically. Care for a case of Ewing sarcoma was transferred to another institution. Repeat biopsy obviated open biopsy and allowed treatment of one case of lymphoma and two cases of breast carcinoma. Overall, 10 of 26 cases underwent surgical biopsy or excision, so CNB potentially spared 61.5% of the patients from having to undergo surgery. We evaluated factors that might result in rebiopsy of a lesion (Table 2). Eleven of the 26 patients had a known preexisting malignancy. For 10 of the 26 patients, the initial biopsy finding was suspicious for malignancy, but a definitive diagnosis could not be made. For three patients, either the sample did not survive processing or extensive crush artifact was present. One lesion had a floater artifact. Nineteen of the 26 lesions had an aggressive imaging appearance, whereas four of 26 lesions had an imaging appearance that was suspicious for infection. Finally, in the setting of a nondiagnostic initial result, we evaluated which factors were modified on the repeat biopsy, in an attempt to increase the diagnostic yield. These factors included an increased number of biopsy needle passes (13 patients [50.0%]), biopsy performed with the use of a different imaging modality as guidance (three patients [11.5%]), biopsy performed with a larger-gauge device (four patients [15.4%]), biopsy performed by different radiologists (18 patients [69.2%]), and biopsy of a different region of the target lesion (13 patients [50.0%]) (Fig. 2). A statistically significant difference in the diagnostic yield was noted for cases for which an increased number of passes was made, for which the rate of diagnosis was 61.5% (Table 3). When an increased number of passes was not made, the diagnostic rate was 23.1%. There was also a statistically significant difference in the mean time between the initial and repeat biopsy for the diagnostic group versus the nondiagnostic group (p = 0.020). The mean number of days between biopsies was 18.3 days for the group with nondiagnostic findings and 75.4 days for the group with diagnostic findings. AJR:208, March

6 Discussion We evaluated the musculoskeletal CNB database of a large academic universitybased medical center over a 10-year period, to determine the utility of repeat CNB of musculoskeletal lesions for which initial findings were nondiagnostic. Our results revealed that the rate of rebiopsy of such lesions is low but can result in a biopsy with diagnostic findings in 38.5% of cases. Thus, rebiopsy may be underutilized. Repeat biopsies were requested for only 26 of 282 biopsies with initial nondiagnostic results. This finding is similar to those published by other tertiary care orthopedic oncology referral centers. In a study by Yang et al. [19] from John Hopkins University that investigated the specific factors and diagnoses most likely to yield nondiagnostic results, 16 of 508 lesions (3.2%) underwent a repeat CNB. Hwang et al. [11] from Memorial Sloan Kettering Cancer Center evaluated the proportion of bone lesions with indeterminate results after CNB that were ultimately found to be malignant. In their study, eight of 800 lesions (1.0%) underwent repeat CNB. The low percentage of cases that underwent repeat CNB was somewhat surprising given that the alternative to CNB is open surgical biopsy and given that uncertainty is associated with clinical follow-up. It is recognized that a significant percentage of CNB results (range, 5 29%) are nondiagnostic [1, 19, 24 26]. The study by Hwang et al. [11] revealed that, of the 249 of 800 lesions (31.1%) with indeterminate findings after initial CNB, 40 (16.1%) underwent subsequent surgical biopsy. Our rate of nondiagnostic results (21.7%) is within the reported range. Requests for repeat CNB of lesions with initial nondiagnostic results potentially may be underutilized by referring physicians. A study by Rimondi et al. [16] at a single institution in Italy evaluated CT-guided musculoskeletal biopsies and performed repeat biopsy with CNB TABLE 3: Effect of Changes in Technical Factors on the Diagnostic Yield at Rebiopsy of 26 Lesions Technical Factor No. (%) of Lesions Diagnostic Yield (%) p a Increased number of passes 13 (50.0) b Modality change 3 (11.5) Biopsy needle upsize 4 (15.4) Different radiologist 18 (69.2) Different area of lesion biopsied 13 (50.0) a According to chi-square test. Statistically significant. or open surgical biopsy for all lesions with nondiagnostic results. In that study, 408 of 2027 lesions (20.1%) underwent repeat CNB, with 340 of these cases (83.3%) having diagnostic findings on repeat biopsy. The study by Rimondi and colleagues differed from the present study because it did not include soft-tissue lesions, included CT-guided biopsies only, and contained a large number of spinal lesions. Moreover, their practice of performing repeat biopsy for all cases with nondiagnostic findings is not routine at many centers. Although their diagnostic rate on repeat biopsy was higher than that noted in the present study and in previously published papers, these findings do suggest that rebiopsy of musculoskeletal lesions can have utility. In our series, rebiopsy of lesions with initially nondiagnostic findings resulted in 15 of 26 patients avoiding potential surgical biopsy. Repeat biopsy of lesions with initially nondiagnostic findings has been studied for lesions in other organs, including kidney [23], thyroid [27], and breast [22] lesions. Repeat biopsy has been shown to be successful in these studies. Leveridge et al. [23] evaluated the feasibility of repeat biopsy of small renal lesions in the setting of an initially nondiagnostic biopsy result and determined that diagnosis was possible for 83.3% of cases. In their series of 345 biopsies, Leveridge and colleagues found that 67 biopsies (19.4%) had nondiagnostic results, and 12 were rebiopsied, with 10 ultimately having diagnostic results. Dershaw et al. [22] evaluated repeat stereotactic CNB of the breast for patients with initial nondiagnostic results. In their series of 314 patients, they found that 22 of 50 patients who underwent repeat biopsy had carcinoma. After repeat biopsy was performed in the present study, a higher percentage of cases had diagnostic findings of malignancy (50.0%) than benignancy (35.7%). It is well established that benign lesions have a significantly lower diagnostic yield than do malignant lesions [15, 21]. Therefore, it is not surprising that malignant lesions trended toward having higher diagnostic yields on rebiopsy. However, this trend may also have been influenced by the fact that lesions that were more suspicious for malignancy on the basis of clinical findings and imaging findings would undergo repeat biopsy. Percutaneous CNB has limitations because the diagnostic yield can be affected by specific factors, such as the number of samples obtained, the length of the sample obtained, the size of the lesion, the percentage of necrosis, and the degree of sclerosis [21], and thus are subject to operator variability. Undersampling or incorrect sampling of lesions may occur. Furthermore, nonspecific histologic features, necrosis, crush artifact, or floater artifact (as seen in some of our cases) may be present. Thus, a nondiagnostic biopsy result cannot be assumed to be a surrogate for the absence of malignancy. Repeat sampling may be useful, especially for those cases in which malignancy is strongly suspected. This may be particularly helpful for those malignancies for which treatment consists of systemic chemotherapy or radiation. Knowledge of the accuracy of diagnosis and the expected diagnostic yields of lesions may be helpful in selecting which cases to rebiopsy. In our series, the malignant lesions that were rebiopsied included metastatic disease, lymphoma, Ewing sarcoma, high-grade sarcoma, malignant peripheral nerve sheath tumor, and low-grade chondrosarcoma. In a study by Dupuy et al. [9], diagnostic accuracy rates were 87%, 75%, 94%, and 100% for primary malignancy, round cell lesions, local recurrence, and metastatic carcinoma, respectively. The diagnostic accuracy for malignancies was reported to be lower for low-grade neoplasms and lymphoma [15, 19]. In these suspected cases, sampling error must be considered. When presented with a nondiagnostic biopsy result for a case with a high suspicion for a lesion for which diagnostic accuracy and diagnostic rates are known to be high, such as metastatic disease, one should consider repeat CNB. Benign lesions are known to have a lower diagnostic rate than malignant lesions [19, 21]. However, a nondiagnostic CNB result may have utility because it can support benign processes and can help avert unnecessary surgery [21]. In the present study, benign lesions underwent rebiopsy secondary to a known underlying malignancy, an imaging appearance suspicious for malignancy or infection, or suspicious initial biopsy results. Thus, clinical suspicion again plays an important role in selecting which patients should undergo rebiopsy. When a repeat CNB is performed, it may be important to vary the technique used. In the cohort in the present study, there was a significant 614 AJR:208, March 2017

7 increase in diagnostic yield when the number can be useful when the initial biopsy result nosis of primary bone tumors with image-guided of passes was increased, compared with the initial approach. However, for small lesions (i.e., lized. Less than 10.0% of lesions with initially Radiology 2002; 223: is nondiagnostic and that it may be underuti- percutaneous biopsy: experience with 110 tumors. Repeat Core Needle Biopsy of Initially Nondiagnostic Musculoskeletal Lesions lesions < 2 cm), sampling a different portion of nondiagnostic biopsy results underwent a repeat 14. Lis E, Bilsky MH, Pisinski L, et al. Percutaneous the lesion may not be possible. Furthermore, it biopsy; however, the diagnostic yield at CT-guided biopsy of osseous lesion of the spine in is well established that the size of the lesion directly rebiopsy was nearly 40.0%. 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Acta skew the results. Moreover, because cases involving needle biopsy of musculoskeletal neoplasms. AJR Orthop Scand 1985; 56: the spine are evaluated by the inter- 1998; 171: Nagira K, Yamamoto T, Akisue T, et al. Reliabil- ventional radiology service at our institution 10. Espinosa LA, Jamadar DA, Jacobson JA, et al. ity of fine-needle aspiration biopsy in the initial with the use of different biopsy techniques, this CT-guided biopsy of bone: a radiologist s perspective. diagnosis of soft-tissue lesions. Diagn Cytopathol would affect the consistency of the methods AJR 2008; 190:[web]W283 W ; 27: used. Moreover, despite the large number of biopsies 11. Hwang S, Lefkowitz RA, Landa J, et al. Percutane- 26. Ogilvie CM, Torbert JT, Finstein JL, Fox EJ, performed at our institution, there was ous CT-guided bone biopsy: diagnosis of malig- Lackman RD. Clinical utility of percutaneous bi- a relatively small number of cases for which nancy in lesions with initially indeterminate biopsy opsies of musculoskeletal tumors. Clin Orthop CNB of an initially nondiagnostic result was results and CT features associated with diagnostic Relat Res 2006; 450: requested; therefore, robust statistical analysis or indeterminate results. AJR 2011; 197: Na DG, Kim JH, Sung JY, et al. Core-needle biopsy could not be performed. Finally, some of the lesions 12. Issakov J, Flusser G, Kollender Y, Merimsky O, is more useful than repeat fine-needle aspira- were followed clinically only, which lim- Lifschitz-Mercer B, Meller I. Computed tomogration in thyroid nodules read as nondiagnostic or ited the accuracy of the final diagnosis. phy-guided core needle biopsy for bone and soft atypia of undetermined significance by the In conclusion, the present study suggests tissue tumors. Isr Med Assoc J 2003; 5:28 30 Bethesda system for reporting thyroid cytopathology. that repeat biopsy of musculoskeletal lesions 13. Jelinek JS, Murphey MD, Welker JA, et al. Diag- Thyroid 2012; 22: FOR YOUR INFORMATION This article has been selected for AJR Journal Club activity. The accompanying Journal Club Study Guide can be found on the following page. AJR:208, March

8 AJR Journal Club Study Guide Utility of Repeat Core Needle Biopsy of Musculoskeletal Lesions With Initially Nondiagnostic Findings Alan Mautz 1, Margaret Mulligan 2, Joseph J. Budovec 2 1 The Aroostook Medical Center, Presque Isle, ME. 2 Medical College of Wisconsin, Milwaukee, WI. amautz@emhs.org, mmulliga@mcw.edu, jbudovec@mcw.edu* Introduction 1. What clinical question did the study aim to address? 2. What rationale was provided for undertaking the analysis presented in this study? Methods 3. What type of study was performed? How were cases selected for inclusion in this study? 4. What were the exclusion criteria for this study? Were the exclusion criteria appropriate? 5. Did the study adequately describe the biopsy technique and the handling of the biopsy specimen? What measures were taken to improve the likelihood of the biopsy results being diagnostic? 6. What were the limitations of this study? Were these limitations adequately addressed? 7. What data points were considered for analysis? What statistical methods were used in this study? Results 8. How often were repeat biopsies performed in this series? How likely was it that repeat biopsy results would be diagnostic, compared with initial biopsy results? 9. What factors had statistical significance in determining whether repeat biopsy was likely to be successful? Discussion 10. The study cited another study with significantly better success rates for rebiopsy. Why might the results of these studies be disparate? 11. What reason was suggested to explain why the interval between the initial unsuccessful biopsy and the subsequent diagnostic biopsy should be increased? Should this influence the way rebiopsy is planned? Did the study adequately address why the longer intervals between biopsies occurred? 12. The study acknowledged the limitation of its relatively small sample size. In the practice of evidence-based medicine, how should one incorporate data from a study such as this? 13. At your institution, how is the decision to biopsy a musculoskeletal lesion made? If the initial biopsy is unsuccessful, how involved would you be in making the decision to rebiopsy, move to open biopsy, or undertake clinical follow-up alone? Would you be willing to participate in a multidisciplinary patient visit during which these options would be discussed with the patient? Background Reading 1. Hwang S, Lefkowitz RA, Landa J, et al. Percutaneous CT-guided bone biopsy: diagnosis of malignancy in lesions with initially indeterminate biopsy results and CT features associated with diagnostic or indeterminate results. AJR 2011; 197: Wu JS, Goldsmith JD, Horwich PJ, Shetty SK, Hochman MG. Bone and soft-tissue lesions: what factors affect diagnostic yield of image-guided core-needle biopsy? Radiology 2008; 248: *Please note that the authors of the Study Guide are distinct from those of the companion article. 616 AJR:208, March 2017