Sampling Modality Influences the Predictive Value of Grading in Adult Soft Tissue Extremity Sarcomas Hatim Khoja, MD; Anthony Griffin, MSc; Brendan Dickson, MD, FRCPC; Jay Wunder, MD, FRCSC; Peter Ferguson, MD, FRCSC; David Howarth, MD, FRCPC; Rita Kandel, MD, FRCPC
Context.—Histologic grade is one of the best predictors of outcome in adult soft tissue sarcomas. Current grading systems were validated on resection specimens; however, there has been a trend toward the use of biopsies to diagnosis these tumors. Objectives.—To determine whether the grade of an extremity soft tissue sarcoma determined on tissue obtained by either core needle biopsy or incisional biopsy is predictive of metastasis- or disease-free survival, and whether either sampling modality is superior. Design.—One hundred three core needle biopsies and 107 incisional biopsies of nonmetastatic spindle cell sarcomas of the extremities were retrieved from the archives. All cases had a minimum 2-year follow-up. Patient data and outcome and tumor characteristics were recorded. Tumors were reviewed and evaluated using the French Federation of Cancer Centers Sarcoma Group grading system. Kaplan-Meier survival curves were gener-
ated to correlate tumor grade with metastasis- and diseasefree survival for both groups. Results.—Patient and tumor characteristics were similar between groups except that more tumors were grade 3 and superficial in the incisional biopsy group. Grade determined on core needle biopsy was not predictive of either metastasis-free survival (P ¼ .59) or disease-free survival (P ¼ .50). In contrast, grade determined on incisional biopsy was predictive of both metastasis-free survival (P , .001) and disease-free survival (P ¼ .001). Conclusions.—Biopsy, particularly core needle biopsy, represents a convenient diagnostic tool, particularly in the context of neoadjuvant therapy. However, based on these results incisional biopsy is recommended if grading is to be used to predict prognosis in spindle cell soft tissue sarcomas of the extremities. (Arch Pathol Lab Med. 2013;137:1774–1779; doi: 10.5858/arpa.2012-0427-OA)
S
per 10 high-power fields (1 high-power field at 3400 magnification ¼ 0.1734 mm2) (0–9, 10–19, and 20), and 1 to 3 according to the degree to which tumor cells resemble the normal counterpart. The 3 scores are totaled to give a final grade. Validation of the ability of the FNCLCC grading system to predict patient outcome was evaluated on resection specimens only.1,14 However, there has been an increasing trend toward the use of biopsies to diagnose these tumors. Depending on several criteria, one of which is histologic grade, these tumors following diagnosis may be treated with radiation or chemotherapy before resection, which precludes grading of the resection specimen. Two sampling modalities are currently used: core needle biopsy (CNB) and incisional/open biopsy (IB). Core needle biopsies have become increasingly popular in the diagnosis of STS because of the minimal morbidity and the lower cost and time required in comparison with IB.16–19 Accurate grading requires an adequate sample of tissue, which may not always be available with CNB.20 Previous studies have reported good concordance between CNB and IB in terms of tumor type,16–30 with most of these studies emphasizing that CNB is an accurate alternative to IB. Only one of these studies demonstrated that tumor grade determined using the FNCLCC system on CNB correlated with the resection specimen. Correlation with outcome was not performed.26 The objectives of this retrospective study were to determine (1) if tumor grading performed on biopsy specimens (CNB and IB) of extremity STS is predictive of
oft tissue sarcomas (STSs) are relatively rare malignant neoplasms requiring a multidisciplinary approach to diagnosis and treatment. Multiple prognostic factors have been evaluated for STS. At present, histologic grade has been shown to be one of the best predictors of outcome, including both metastatic risk and disease-free survival, in adult STS.1–8 Although multiple grading systems for STS have been proposed since the 1980s,9–13 the French Federation of Cancer Centers Sarcoma Group (FNCLCC) grading system is currently favored for the grading of STSs.14,15 This is a 3tier system based on 3 histologic features: necrosis, mitotic activity, and degree of differentiation. Points are assigned for each category: 0 to 2 depending on the amount of necrosis (0%, ,50%, 50%), 1 to 3 for the number of mitotic figures Accepted for publication March 7, 2013. From the Departments of Pathology and Laboratory Medicine (Drs Khoja, Dickson, Howarth, and Kandel) and Orthopaedic Surgery (Mr Griffin and Drs Wunder and Ferguson), Mount Sinai Hospital, Toronto, Ontario, Canada; and the Departments of Laboratory Medicine and Pathobiology (Drs Dickson, Howarth, and Kandel) and Surgery (Drs Wunder and Ferguson), University of Toronto, Toronto, Ontario, Canada. The authors have no relevant financial interest in the products or companies described in this article. Reprints: Rita Kandel, MD, FRCPC, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Ave, 6th Floor, Toronto, ON M5G 1X5, Canada (e-mail: [email protected]). 1774 Arch Pathol Lab Med—Vol 137, December 2013
Sampling Modality in Extremity Soft Tissue Sarcoma—Khoja et al
Table 1.
Clinical Data and Tumor Characteristics Sampling Modality
Clinical Features
Core Needle Biopsy (n ¼ 103)
Sex Male Female Age, mean (range), y Tumor size, mean (range), cm Tumor depth Superficial Deep Unknown Treatment Surgery alone Surgery and radiation Surgery and chemotherapy Surgery, radiation, and chemotherapy
Incisional Biopsy (n ¼ 107)
61 42 58 (16–97) 10.5 (1.8–36)
52 55 56 (18–85) 8.1 cm (1.2–25)
17 81 5
46 61 0
19 74 0 10
28 72 3 4
RESULTS Initial analysis of the 238 cases resulted in the exclusion of 28 patients (22 patients from the CNB group and 6 patients from the IB group) for multiple reasons, including unavailability of slides and insufficient amount of tissue for proper grading (insufficient tissue to count mitoses in 1.7 mm2). This resulted in 210 cases for analysis (103 CNBs and 107 IBs). The median follow-up was 63 months for those who underwent IB and 57 months for CNB. The clinical data and
tumor characteristics are summarized in Table 1. There were 61 male and 42 female patients in the CNB group, and 52 male and 55 female patients in the IB group. The mean patient age was similar in both CNB and IB groups: 58 years (range, 16–97 years) in the CNB group, and 56 years (range, 18–85 years) in the IB group. The average tumor size was also similar in both groups: 10.5 cm (range, 1.8–36 cm) in the CNB group, and 8.1 cm (range, 1.2–25 cm) in the IB group. As shown in Table 1, there were more superficial tumors in the IB group (43% versus only 16% in the CNB group). Patients were treated with different modalities including surgery alone, surgery with preoperative or postoperative radiation, surgery and chemotherapy, or a combination of all 3 modalities. The majority of patients in both groups were treated with combined surgery and preoperative or postoperative radiation therapy (74 of 103 patients [71%] in the CNB group, and 72 of 107 patients [67%] in the IB group). Ten patients in the CNB group and 7 in the IB group received chemotherapy with or without radiation therapy. The majority of these patients (14 of 17) had synovial sarcomas. The remaining 3 tumors that received chemotherapy were sarcoma not otherwise specified, fibrosarcoma, and undifferentiated pleomorphic sarcoma. The range of diagnoses was similar in both the CNB and IB groups. The most common diagnosis was undifferentiated pleomorphic sarcoma in both groups followed by myxofibrosarcoma and synovial sarcoma (Figure 1, A through C). More cases diagnosed as sarcoma not otherwise specified were present in the CNB group (CNB, n ¼ 13; IB, n ¼ 8) (Table 2). Five cases of myxoinflammatory fibroblastic sarcoma were present in the IB group. The number of grade 1 tumors was similar in the CNB and IB groups: 10 and 11 cases, respectively (Figure 2). However, there were more grade 3 tumors sampled by IB compared with CNB (CNB, n ¼ 37; IB, n ¼ 52). Grade determined on CNB was not predictive of either metastasis-free survival (P ¼ .59) (Figure 3, A) or diseasefree survival (P ¼ .50) (Figure 3, B) by Kaplan-Meier analysis. The estimated 5-year metastasis-free survival in the CNB group was 56.3%, 53.6%, and 50.4% for grade 1, 2, and 3 tumors, respectively (Table 3). The estimated 5-year diseasefree survival in the CNB group was 56.3%, 53.6%, and 48.8% for grade 1, 2, and 3 tumors, respectively (Table 3). Grade determined on IB was predictive of metastasis-free survival (P , .001) (Figure 4, A) and disease-free survival (P
Arch Pathol Lab Med—Vol 137, December 2013
Sampling Modality in Extremity Soft Tissue Sarcoma—Khoja et al 1775
patient outcome and (2) if either sampling modality is superior in predicting patient outcome. DESIGN The histologic slides of 238 adult patients with spindle cell sarcomas of the extremities diagnosed between December 1989 and December 2008 were retrieved from the archives of our institution (Mount Sinai Hospital, Toronto, Ontario, Canada) following research ethics board approval. Inclusion criteria included (1) extremity spindle cell sarcoma (excluding small round cell tumors such as Ewing sarcoma, malignant peripheral nerve sheath tumor, osteosarcoma/ chondrosarcoma, or liposarcoma); (2) absence of metastases at the time of presentation; (3) diagnosis made by either CNB or IB; and, (4) at least 2 years of follow-up (patients who died of causes other than sarcoma were censored at their last follow-up). No case had received any therapy before the biopsy was taken. Round cell sarcomas such as Ewing and rhabdomyosarcoma and malignant peripheral nerve sheath tumor were excluded to fulfill the FNCLCC criteria. Liposarcomas were excluded, as these tumors usually demonstrate type-specific behavior (eg, well-differentiated liposarcoma/atypical lipomatous tumor does not metastasize if it occurs in the extremities) and are often hard to diagnose on CNB and thus could bias the assessment of grading. Patient age and sex, tumor size and depth, treatment modality, and patient outcome were recorded. All tumors were reviewed histologically by 2 soft tissue pathologists blinded to oncologic outcome and evaluated using the FNCLCC grading system.14 The clinical course of each patient was reviewed. Metastasis-free survival and disease-free survival based on grade for both CNB and IB groups were estimated using the method of Kaplan and Meier, and differences were compared with the log-rank test.
Table 2.
Soft Tissue Sarcoma Diagnosis Distribution by Sampling Modality Sampling Modality
Tumor Type Synovial sarcoma Leiomyosarcoma Myxofibrosarcoma Fibrosarcoma Undifferentiated pleomorphic sarcoma Pleomorphic sarcoma with myogenic features Myofibrosarcoma Sarcoma not otherwise specified Myxoinflammatory fibroblastic sarcoma
Core Needle Incisional Biopsy Biopsy (n ¼ 103) (n ¼ 107) 18 10 14 4 33
20 13 20 2 33
11
5
0 13 0
1 8 5
Interestingly, grade 1 and 2 tumors showed overlap in disease-free survival curves, suggesting that for low-grade tumors the FNCLCC grading system may not be sufficient to predict outcome for IB specimens (Figure 4, B). COMMENT In this study, the predictive value of histologic grade using the FNCLCC grading system in biopsy specimens of extremity spindle cell STS obtained by different sampling modalities (CNB versus IB) was evaluated. Grading performed on CNB did not predict patient outcome for either metastasis-free or disease-free survival. This is likely a result of the limited tumor sampling. Grading performed on tumor obtained from IB was predictive of patient outcome for both metastasis-free and disease-free survival. Interestingly, there was some overlap of survival curves for low-grade (grade 1 or 2) tumors; however, further study is required to confirm this finding. There have been several studies that have compared both sampling modalities and in some studies fine-needle aspiration16–30 for accuracy in identifying the presence of malignancy and classifying the tumor subtype and/or grade. One of these studies also looked at the effect on eventual treatment.20 None of these studies determined whether grading performed on biopsy samples (CNB or IB) can accurately predict patient outcome as has been shown for specimen resection samples. To our knowledge, the current study is the first to evaluate this topic.
Figure 1. Photomicrographs of representative soft tissue sarcomas exhibiting features of (A) grade 1 myxofibrosarcoma, French Federation of Cancer Centers Sarcoma Group (FNCLCC) score ¼ 3; (B), grade 2 myxofibrosarcoma, FNCLCC score ¼ 4; and (C), grade 3 undifferentiated pleomorphic sarcoma, FNCLCC score ¼ 7 (hematoxylin and eosin, original magnifications 3200).
¼ .001) (Figure 4, B). The estimated 5-year metastasis-free survival in the IB group was 100%, 84%, and 50.1% for grade 1, 2, and 3 tumors, respectively. The estimated 5-year disease-free survival in the IB group was 100%, 81.8%, and 49.1% for grade 1, 2, and 3 tumors, respectively (Table 3). 1776 Arch Pathol Lab Med—Vol 137, December 2013
Figure 2. Sampling modality according to tumor grade. Sampling Modality in Extremity Soft Tissue Sarcoma—Khoja et al
Figure 3. Metastasis-free (A) and disease-free survival (B) according to grade as determined on core needle biopsies. Figure 4. Metastasis-free (A) and disease-free survival (B) according to grade as determined on incisional biopsies.
There are some features of the study that may have influenced the results. First, the total number of patients evaluated is small, approximately 100 cases per biopsy type, possibly skewing the results. More than 400 cases were used to validate the FNCLCC grading system.14 However, the sample size of our study is not considered a major limitation, as it did confirm, when sufficient tissue was available (IB), that grade as determined using the FNCLCC system is prognostic. Second, more tumors were deep to fascia in the CNB group than in the IB group, possibly because of ease of access. Third, patients were treated with different modalities, including surgery alone, surgery with preoperative or postoperative radiation, surgery and chemotherapy, and a combination of all 3 modalities, which may influence patient outcome. Although IB has long been considered the gold standard for diagnosis of extremity-based STS,20,31 several studies have reported good concordance between CNB and the final resection for malignancy, tumor type, and/or tumor grade, Arch Pathol Lab Med—Vol 137, December 2013
suggesting that it may be an alternative approach to IB for tissue sampling.16–30 These studies are summarized in Table 4. In 6 studies the diagnosis, not grade, obtained from CNB was correlated to that of the final resection specimen, but none of these compared the 2 biopsy techniques.18,20,21,23,25,29 Nine studies correlated the tumor grade determined on the CNB to that of the final resection, and these showed concordance ranging from 45.6% to 100%.* These studies differ from the current study in several aspects. Studies either had small numbers of patients (eg, 16), did not state the grading system used, included bone tumors and/or other STS that were excluded in the current study (eg, liposarcoma, Ewing sarcoma), or used a different grading system so are not directly comparable. Only 4 studies compared both sampling techniques (CNB versus IB) and tumor grade and correlated them with the grade of the final resection specimen.17,24,27,30 For example, Heslin et al27 described that * References 16, 17, 19, 22, 24, 26–28, 30. Sampling Modality in Extremity Soft Tissue Sarcoma—Khoja et al 1777
Table 3.
Estimated 5-Year Metastasis-Free and Disease-Free Survival According to Sampling Modality Core Needle Biopsy Estimated 5-y Metastasis-Free Survival, %
Tumor Grade 1 2 3
Incisional Biopsy
Estimated 5-y Disease-Free Survival, %
Estimated 5-y Metastasis-Free Survival, %
Estimated 5-y Disease-Free Survival, %
56.3 53.6 48.8
100 84 50.1
100 81.8 49.1
56.3 53.6 50.4
for adequate CNB specimens, 95%, 88% and 75% correlated with the final resection diagnosis for malignancy, grade, and histologic subtype, respectively, but with IB specimens the correlation was better: 100%, 96%, and 84% respectively. However, the study population was small and the grading system used was not described. Of these 4 studies, only that by Strauss et al26 stated the grading system used (FNCLCC). However, in that report the tumors were subdivided into low-grade (grade 1) and high-grade (grades 2 and 3) tumors, which differs from the current study. The CNB accuracy was shown to be 86.3%, with a negative predictive value of 66.2%. Interestingly, CNB misgraded 24 of 71 lowgrade tumors. As a result of their findings, the authors concluded that CNB can be used as an alternative to IB in the diagnosis of soft tissue tumors, which differs from the conclusion of the current study. There are several possible reasons why sarcomas sampled by CNB were accurately graded in that study in contrast to the current study. First, the design of our study was somewhat different, as we did not compare grade in the CNB with the resection specimen but with the IB and then with outcome. This approach prevented the bias that could result from eliminating cases as a result of preoperative radiotherapy. Strauss et al26 did not correlate grade with outcome, so there was no gold standard to confirm their ability to grade tumors. This is important as the FNCLCC reproducibility study showed only 75% concordance in grade among pathologists.32 Table 4.
Source, y 16
a
Ball et al, 1990 Barth et al,28 1992 Skrzynski et al,29 1996a Heslin et al,27 1997b Welker et al,17 2000c Yao et al,21 1999 Hoeber et al,24 2001d Ray-Coquard et al,23 2003e Yang and Damron,22 2004f Mitsuyoshi et al,25 2006 Woon and Serpell,30 2008 Kasraeian et al,20 2010 Strauss et al,26 2010 Verheijen et al,18 2010 Adams et al,19 2010c
Second, they had 4 CNBs in each case (size of biopsy not mentioned), whereas we had anywhere from 1 to greater than 4 biopsies per case. It has been suggested that 4 to 6 cores are necessary for accurate sarcoma diagnosis and grading.33,34 In our study, approximately 75% of cases had 3 or more core biopsies, and it may be that if we had considered the cases with fewer than 3 biopsies to be insufficient we might have had similar results. Third, cases in the study of Strauss et al26 were not restricted to extremity sarcomas. It is not clear whether the prognostic ability of core biopsies could be improved. Recommending the number/ size of cores for which accurate grading might be accomplished is problematic for several reasons. First, high-grade tumors or tumors with a characteristic translocation (eg, synovial sarcoma) would likely require fewer cores; second, histologic heterogeneity is more prevalent in some tumor types, for example myxoid tumors; and third, if the biopsies are mostly necrotic more biopsies will be required. In summary, the data suggest that IB may be a more reliable sampling technique in extremity STS for prognostication, likely because it provides an adequate amount of tissue for grading. Core needle biopsy specimens are prone to sampling error with the risk to underestimate tumor grade, perhaps because histologic features such as necrosis are underrepresented. Furthermore, IB appears to give a
Summary of Previous Studies
No. of Samples of STS CNB
No. of Samples of STS IB
40 16 43 (19 STT) 60 155 105 (42 STT) 182 85 (63 STT) 23 26 35 19 175 90 212
ND ND 37 45 12 25 44 ND ND ND ND 19 ND 195 ND
Grading System
Correlation of CNB Grade to Final Resection, %
Correlation of IB Grade to Final Resection, %
NS NS NS Low and high grade NS NS NS NS NS NS NS AJCC (FNCLCC) FNCLCC NS NS
88 100 ND 88 88.6 ND 84.9 ND 83 ND 45.6 ND 86.3 ND 80.7
ND ND ND 96 66.7 ND 64.9 ND ND ND 100 ND ND ND ND
Abbreviations: AJCC, American Joint Committee on Cancer; CNB, core needle biopsy; FNCLCC, French Federation of Cancer Centers Sarcoma Group grading system; IB, incisional biopsy; ND, not done, only accuracy of diagnosis determined; NS, not stated; STS, soft tissue sarcoma; STT, soft tissue tumor. a Malignant tumors include malignant peripheral nerve sheath tumor, non–spindle cell sarcomas, and liposarcoma. b Large number of liposarcomas; includes benign and malignant tumors. c Includes both bone and soft tissue tumors and cases that were not sarcoma. d Includes non–spindle cell sarcomas. e Includes cases that were not sarcomas; not always compared with surgical resection specimen. f Includes both bone and soft tissue tumors; not all samples correlated with resection specimen. 1778 Arch Pathol Lab Med—Vol 137, December 2013
Sampling Modality in Extremity Soft Tissue Sarcoma—Khoja et al
better estimate of prognosis based on grade as compared with CNB. This would suggest that IB is the sampling modality of choice for extremity STSs for prognostic purposes, although it is possible that, as imaging methods improve and can accurately quantify necrosis, directed core needle biopsies, when combined with imaging features or other assessments such as molecular analyses, may be sufficient for accurate grading.35 The authors would like to acknowledge Marcus Wong for retrieving slides and Marie Maguire and Chriselle Solante for secretarial assistance. References 1. Coindre JM, Terrier P, Guillou L, et al. Predictive value of grade for metastasis development in the main histologic types of adult soft tissue sarcomas: a study of 1240 patients from the French Federation of Cancer Centers Sarcoma Group. Cancer. 2001;91(10):1914–1926. 2. Coindre JM. Grading of soft tissue sarcomas: review and update. Arch Pathol Lab Med. 2006;130(10):1448–1453. 3. Markhede G, Angervall L, Stener B. A multivariate analysis of the prognosis after surgical treatment of malignant soft-tissue tumors. Cancer. 1982;49(8): 1721–1733. 4. Gaynor JJ, Tan CC, Casper ES, et al. Refinement of clinicopathologic staging for localized soft tissue sarcoma of the extremity: a study of 423 adults. J Clin Oncol. 1992;10(8):1317–1329. 5. Saddegh MK, Lindholm J, Lundberg A, Nilsonne U, Kreicbergs A. Staging of soft-tissue sarcomas: prognostic analysis of clinical and pathological features. J Bone Joint Surg Br. 1992;74(4):495–500. 6. Pisters PW, Leung DH, Woodruff J, Shi W, Brennan MF. Analysis of prognostic factors in 1,041 patients with localized soft tissue sarcomas of the extremities. J Clin Oncol. 1996;14(5):1679–1689. 7. Heise HW, Myers MH, Russell WO, et al. Recurrence-free survival time for surgically treated soft tissue sarcoma patients: multivariate analysis of five prognostic factors. Cancer. 1986;57(1):172–177. 8. Zagars GK, Ballo MT, Pisters PW, et al. Prognostic factors for patients with localized soft-tissue sarcoma treated with conservation surgery and radiation therapy: an analysis of 1225 patients. Cancer. 2003;97(10):2530–2543. 9. Costa J, Wesley RA, Glatstein E, Rosenberg SA. The grading of soft tissue sarcomas: results of a clinicohistopathologic correlation in a series of 163 cases. Cancer. 1984;53(3):530–541. 10. Trojani M, Contesso G, Coindre JM, et al. Soft-tissue sarcomas of adults; study of pathological prognostic variables and definition of a histopathological grading system. Int J Cancer. 1984;33(1):37–42. 11. van Unnik JA, Coindre JM, Contesso C, et al. Grading of soft tissue sarcomas: experience of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer. 1993;29A(15):2089–2093. 12. Hashimoto H, Daimaru Y, Takeshita S, Tsuneyoshi M, Enjoji M. Prognostic significance of histologic parameters of soft tissue sarcomas. Cancer. 1992; 70(12):2816–2822. 13. Gustafson P. Soft tissue sarcoma: epidemiology and prognosis in 508 patients. Acta Orthop Scand Suppl. 1994;2591–2531. 14. Guillou L, Coindre JM, Bonichon F, et al. Comparative study of the National Cancer Institute and French Federation of Cancer Centers Sarcoma Group grading systems in a population of 410 adult patients with soft tissue sarcoma. J Clin Oncol. 1997;15(1):350–362.
Arch Pathol Lab Med—Vol 137, December 2013
15. Fletcher CDM, Unni KK, Mertens F; World Health Organization; International Academy of Pathology. Pathology and Genetics of Tumours of Soft Tissue and Bone. Lyon, France: IARC Press; 2002. 16. Ball AB, Fisher C, Pittam M, Watkins RM, Westbury G. Diagnosis of soft tissue tumours by Tru-Cut biopsy. Br J Surg. 1990;77(7):756–758. 17. Welker JA, Henshaw RM, Jelinek J, Shmookler BM, Malawer MM. The percutaneous needle biopsy is safe and recommended in the diagnosis of musculoskeletal masses. Cancer. 2000;89(12):2677–2686. 18. Verheijen P, Witjes H, van Gorp J, Hennipman A, van Dalen T. Current pathology work-up of extremity soft tissue sarcomas, evaluation of the validity of different techniques. Eur J Surg Oncol. 2010;36(1):95–99. 19. Adams SC, Potter BK, Pitcher DJ, Temple HT. Office-based core needle biopsy of bone and soft tissue malignancies: an accurate alternative to open biopsy with infrequent complications. Clin Orthop Relat Res. 2010;468(10): 2774–2780. 20. Kasraeian S, Allison DC, Ahlmann ER, Fedenko AN, Menendez LR. A comparison of fine-needle aspiration, core biopsy, and surgical biopsy in the diagnosis of extremity soft tissue masses. Clin Orthop Relat Res. 2010;468(11): 2992–3002. 21. Yao L, Nelson SD, Seeger LL, Eckardt JJ, Eilber FR. Primary musculoskeletal neoplasms: effectiveness of core-needle biopsy. Radiology. 1999;212(3):682– 686. 22. Yang YJ, Damron TA. Comparison of needle core biopsy and fine-needle aspiration for diagnostic accuracy in musculoskeletal lesions. Arch Pathol Lab Med. 2004;128(7):759–764. 23. Ray-Coquard I, Ranchere-Vince D, Thiesse P, et al. Evaluation of core needle biopsy as a substitute to open biopsy in the diagnosis of soft-tissue masses. Eur J Cancer. 2003;39(14):2021–2025. 24. Hoeber I, Spillane AJ, Fisher C, Thomas JM. Accuracy of biopsy techniques for limb and limb girdle soft tissue tumors. Ann Surg Oncol. 2001;8(1):80–87. 25. Mitsuyoshi G, Naito N, Kawai A, et al. Accurate diagnosis of musculoskeletal lesions by core needle biopsy. J Surg Oncol. 2006;94(1):21–27. 26. Strauss DC, Qureshi YA, Hayes AJ, et al. The role of core needle biopsy in the diagnosis of suspected soft tissue tumours. J Surg Oncol. 2010;102(5):523– 529. 27. Heslin MJ, Lewis JJ, Woodruff JM, Brennan MF. Core needle biopsy for diagnosis of extremity soft tissue sarcoma. Ann Surg Oncol. 1997;4(5):425–431. 28. Barth RJ Jr, Merino MJ, Solomon D, Yang JC, Baker AR. A prospective study of the value of core needle biopsy and fine needle aspiration in the diagnosis of soft tissue masses. Surgery. 1992;112(3):536–543. 29. Skrzynski MC, Biermann JS, Montag A, Simon MA. Diagnostic accuracy and charge-savings of outpatient core needle biopsy compared with open biopsy of musculoskeletal tumors. J Bone Joint Surg Am. 1996;78(5):644–649. 30. Woon DT, Serpell JW. Preoperative core biopsy of soft tissue tumours facilitates their surgical management: a 10-year update. ANZ J Surg. 2008;78(11): 977–981. 31. Huvos AG. The importance of the open surgical biopsy in the diagnosis and treatment of bone and soft-tissue tumors. Hematol Oncol Clin North Am. 1995;9(3):541–544. 32. Coindre JM, Trojani M, Contesso G, et al. Reproducibility of a histopathologic grading system for adult soft tissue sarcoma. Cancer. 1986; 58(2):306–309. 33. Wu JS, Goldsmith JD, Horwich PJ, Shetty SK, Hochman MG. Bone and soft-tissue lesions: what factors affect diagnostic yield of image-guided coreneedle biopsy? Radiology. 2008;248(3):962–970. 34. Clayer M. Pre-operative core biopsy of soft-tissue tumours facilitates their surgical management: comment. Aust N Z J Surg. 1998;68(12):864. 35. De Marchi A, Brach del Prever EM, Linari A, et al. Accuracy of core-needle biopsy after contrast-enhanced ultrasound in soft-tissue tumours. Eur Radiol. 2010;20(11):2740–2748.
Sampling Modality in Extremity Soft Tissue Sarcoma—Khoja et al 1779
Copyright of Archives of Pathology & Laboratory Medicine is the property of College of American Pathologists and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Context.—Histologic grade is one of the best predictors of outcome in adult soft tissue sarcomas. Current grading systems were validated on resection specimens; however, there has been a trend toward the use of biopsies to diagnosis these tumors. Objectives.—To determine whether the grade of an extremity soft tissue sarcoma determined on tissue obtained by either core needle biopsy or incisional biopsy is predictive of metastasis- or disease-free survival, and whether either sampling modality is superior. Design.—One hundred three core needle biopsies and 107 incisional biopsies of nonmetastatic spindle cell sarcomas of the extremities were retrieved from the archives. All cases had a minimum 2-year follow-up. Patient data and outcome and tumor characteristics were recorded. Tumors were reviewed and evaluated using the French Federation of Cancer Centers Sarcoma Group grading system. Kaplan-Meier survival curves were gener-
ated to correlate tumor grade with metastasis- and diseasefree survival for both groups. Results.—Patient and tumor characteristics were similar between groups except that more tumors were grade 3 and superficial in the incisional biopsy group. Grade determined on core needle biopsy was not predictive of either metastasis-free survival (P ¼ .59) or disease-free survival (P ¼ .50). In contrast, grade determined on incisional biopsy was predictive of both metastasis-free survival (P , .001) and disease-free survival (P ¼ .001). Conclusions.—Biopsy, particularly core needle biopsy, represents a convenient diagnostic tool, particularly in the context of neoadjuvant therapy. However, based on these results incisional biopsy is recommended if grading is to be used to predict prognosis in spindle cell soft tissue sarcomas of the extremities. (Arch Pathol Lab Med. 2013;137:1774–1779; doi: 10.5858/arpa.2012-0427-OA)
S
per 10 high-power fields (1 high-power field at 3400 magnification ¼ 0.1734 mm2) (0–9, 10–19, and 20), and 1 to 3 according to the degree to which tumor cells resemble the normal counterpart. The 3 scores are totaled to give a final grade. Validation of the ability of the FNCLCC grading system to predict patient outcome was evaluated on resection specimens only.1,14 However, there has been an increasing trend toward the use of biopsies to diagnose these tumors. Depending on several criteria, one of which is histologic grade, these tumors following diagnosis may be treated with radiation or chemotherapy before resection, which precludes grading of the resection specimen. Two sampling modalities are currently used: core needle biopsy (CNB) and incisional/open biopsy (IB). Core needle biopsies have become increasingly popular in the diagnosis of STS because of the minimal morbidity and the lower cost and time required in comparison with IB.16–19 Accurate grading requires an adequate sample of tissue, which may not always be available with CNB.20 Previous studies have reported good concordance between CNB and IB in terms of tumor type,16–30 with most of these studies emphasizing that CNB is an accurate alternative to IB. Only one of these studies demonstrated that tumor grade determined using the FNCLCC system on CNB correlated with the resection specimen. Correlation with outcome was not performed.26 The objectives of this retrospective study were to determine (1) if tumor grading performed on biopsy specimens (CNB and IB) of extremity STS is predictive of
oft tissue sarcomas (STSs) are relatively rare malignant neoplasms requiring a multidisciplinary approach to diagnosis and treatment. Multiple prognostic factors have been evaluated for STS. At present, histologic grade has been shown to be one of the best predictors of outcome, including both metastatic risk and disease-free survival, in adult STS.1–8 Although multiple grading systems for STS have been proposed since the 1980s,9–13 the French Federation of Cancer Centers Sarcoma Group (FNCLCC) grading system is currently favored for the grading of STSs.14,15 This is a 3tier system based on 3 histologic features: necrosis, mitotic activity, and degree of differentiation. Points are assigned for each category: 0 to 2 depending on the amount of necrosis (0%, ,50%, 50%), 1 to 3 for the number of mitotic figures Accepted for publication March 7, 2013. From the Departments of Pathology and Laboratory Medicine (Drs Khoja, Dickson, Howarth, and Kandel) and Orthopaedic Surgery (Mr Griffin and Drs Wunder and Ferguson), Mount Sinai Hospital, Toronto, Ontario, Canada; and the Departments of Laboratory Medicine and Pathobiology (Drs Dickson, Howarth, and Kandel) and Surgery (Drs Wunder and Ferguson), University of Toronto, Toronto, Ontario, Canada. The authors have no relevant financial interest in the products or companies described in this article. Reprints: Rita Kandel, MD, FRCPC, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Ave, 6th Floor, Toronto, ON M5G 1X5, Canada (e-mail: [email protected]). 1774 Arch Pathol Lab Med—Vol 137, December 2013
Sampling Modality in Extremity Soft Tissue Sarcoma—Khoja et al
Table 1.
Clinical Data and Tumor Characteristics Sampling Modality
Clinical Features
Core Needle Biopsy (n ¼ 103)
Sex Male Female Age, mean (range), y Tumor size, mean (range), cm Tumor depth Superficial Deep Unknown Treatment Surgery alone Surgery and radiation Surgery and chemotherapy Surgery, radiation, and chemotherapy
Incisional Biopsy (n ¼ 107)
61 42 58 (16–97) 10.5 (1.8–36)
52 55 56 (18–85) 8.1 cm (1.2–25)
17 81 5
46 61 0
19 74 0 10
28 72 3 4
RESULTS Initial analysis of the 238 cases resulted in the exclusion of 28 patients (22 patients from the CNB group and 6 patients from the IB group) for multiple reasons, including unavailability of slides and insufficient amount of tissue for proper grading (insufficient tissue to count mitoses in 1.7 mm2). This resulted in 210 cases for analysis (103 CNBs and 107 IBs). The median follow-up was 63 months for those who underwent IB and 57 months for CNB. The clinical data and
tumor characteristics are summarized in Table 1. There were 61 male and 42 female patients in the CNB group, and 52 male and 55 female patients in the IB group. The mean patient age was similar in both CNB and IB groups: 58 years (range, 16–97 years) in the CNB group, and 56 years (range, 18–85 years) in the IB group. The average tumor size was also similar in both groups: 10.5 cm (range, 1.8–36 cm) in the CNB group, and 8.1 cm (range, 1.2–25 cm) in the IB group. As shown in Table 1, there were more superficial tumors in the IB group (43% versus only 16% in the CNB group). Patients were treated with different modalities including surgery alone, surgery with preoperative or postoperative radiation, surgery and chemotherapy, or a combination of all 3 modalities. The majority of patients in both groups were treated with combined surgery and preoperative or postoperative radiation therapy (74 of 103 patients [71%] in the CNB group, and 72 of 107 patients [67%] in the IB group). Ten patients in the CNB group and 7 in the IB group received chemotherapy with or without radiation therapy. The majority of these patients (14 of 17) had synovial sarcomas. The remaining 3 tumors that received chemotherapy were sarcoma not otherwise specified, fibrosarcoma, and undifferentiated pleomorphic sarcoma. The range of diagnoses was similar in both the CNB and IB groups. The most common diagnosis was undifferentiated pleomorphic sarcoma in both groups followed by myxofibrosarcoma and synovial sarcoma (Figure 1, A through C). More cases diagnosed as sarcoma not otherwise specified were present in the CNB group (CNB, n ¼ 13; IB, n ¼ 8) (Table 2). Five cases of myxoinflammatory fibroblastic sarcoma were present in the IB group. The number of grade 1 tumors was similar in the CNB and IB groups: 10 and 11 cases, respectively (Figure 2). However, there were more grade 3 tumors sampled by IB compared with CNB (CNB, n ¼ 37; IB, n ¼ 52). Grade determined on CNB was not predictive of either metastasis-free survival (P ¼ .59) (Figure 3, A) or diseasefree survival (P ¼ .50) (Figure 3, B) by Kaplan-Meier analysis. The estimated 5-year metastasis-free survival in the CNB group was 56.3%, 53.6%, and 50.4% for grade 1, 2, and 3 tumors, respectively (Table 3). The estimated 5-year diseasefree survival in the CNB group was 56.3%, 53.6%, and 48.8% for grade 1, 2, and 3 tumors, respectively (Table 3). Grade determined on IB was predictive of metastasis-free survival (P , .001) (Figure 4, A) and disease-free survival (P
Arch Pathol Lab Med—Vol 137, December 2013
Sampling Modality in Extremity Soft Tissue Sarcoma—Khoja et al 1775
patient outcome and (2) if either sampling modality is superior in predicting patient outcome. DESIGN The histologic slides of 238 adult patients with spindle cell sarcomas of the extremities diagnosed between December 1989 and December 2008 were retrieved from the archives of our institution (Mount Sinai Hospital, Toronto, Ontario, Canada) following research ethics board approval. Inclusion criteria included (1) extremity spindle cell sarcoma (excluding small round cell tumors such as Ewing sarcoma, malignant peripheral nerve sheath tumor, osteosarcoma/ chondrosarcoma, or liposarcoma); (2) absence of metastases at the time of presentation; (3) diagnosis made by either CNB or IB; and, (4) at least 2 years of follow-up (patients who died of causes other than sarcoma were censored at their last follow-up). No case had received any therapy before the biopsy was taken. Round cell sarcomas such as Ewing and rhabdomyosarcoma and malignant peripheral nerve sheath tumor were excluded to fulfill the FNCLCC criteria. Liposarcomas were excluded, as these tumors usually demonstrate type-specific behavior (eg, well-differentiated liposarcoma/atypical lipomatous tumor does not metastasize if it occurs in the extremities) and are often hard to diagnose on CNB and thus could bias the assessment of grading. Patient age and sex, tumor size and depth, treatment modality, and patient outcome were recorded. All tumors were reviewed histologically by 2 soft tissue pathologists blinded to oncologic outcome and evaluated using the FNCLCC grading system.14 The clinical course of each patient was reviewed. Metastasis-free survival and disease-free survival based on grade for both CNB and IB groups were estimated using the method of Kaplan and Meier, and differences were compared with the log-rank test.
Table 2.
Soft Tissue Sarcoma Diagnosis Distribution by Sampling Modality Sampling Modality
Tumor Type Synovial sarcoma Leiomyosarcoma Myxofibrosarcoma Fibrosarcoma Undifferentiated pleomorphic sarcoma Pleomorphic sarcoma with myogenic features Myofibrosarcoma Sarcoma not otherwise specified Myxoinflammatory fibroblastic sarcoma
Core Needle Incisional Biopsy Biopsy (n ¼ 103) (n ¼ 107) 18 10 14 4 33
20 13 20 2 33
11
5
0 13 0
1 8 5
Interestingly, grade 1 and 2 tumors showed overlap in disease-free survival curves, suggesting that for low-grade tumors the FNCLCC grading system may not be sufficient to predict outcome for IB specimens (Figure 4, B). COMMENT In this study, the predictive value of histologic grade using the FNCLCC grading system in biopsy specimens of extremity spindle cell STS obtained by different sampling modalities (CNB versus IB) was evaluated. Grading performed on CNB did not predict patient outcome for either metastasis-free or disease-free survival. This is likely a result of the limited tumor sampling. Grading performed on tumor obtained from IB was predictive of patient outcome for both metastasis-free and disease-free survival. Interestingly, there was some overlap of survival curves for low-grade (grade 1 or 2) tumors; however, further study is required to confirm this finding. There have been several studies that have compared both sampling modalities and in some studies fine-needle aspiration16–30 for accuracy in identifying the presence of malignancy and classifying the tumor subtype and/or grade. One of these studies also looked at the effect on eventual treatment.20 None of these studies determined whether grading performed on biopsy samples (CNB or IB) can accurately predict patient outcome as has been shown for specimen resection samples. To our knowledge, the current study is the first to evaluate this topic.
Figure 1. Photomicrographs of representative soft tissue sarcomas exhibiting features of (A) grade 1 myxofibrosarcoma, French Federation of Cancer Centers Sarcoma Group (FNCLCC) score ¼ 3; (B), grade 2 myxofibrosarcoma, FNCLCC score ¼ 4; and (C), grade 3 undifferentiated pleomorphic sarcoma, FNCLCC score ¼ 7 (hematoxylin and eosin, original magnifications 3200).
¼ .001) (Figure 4, B). The estimated 5-year metastasis-free survival in the IB group was 100%, 84%, and 50.1% for grade 1, 2, and 3 tumors, respectively. The estimated 5-year disease-free survival in the IB group was 100%, 81.8%, and 49.1% for grade 1, 2, and 3 tumors, respectively (Table 3). 1776 Arch Pathol Lab Med—Vol 137, December 2013
Figure 2. Sampling modality according to tumor grade. Sampling Modality in Extremity Soft Tissue Sarcoma—Khoja et al
Figure 3. Metastasis-free (A) and disease-free survival (B) according to grade as determined on core needle biopsies. Figure 4. Metastasis-free (A) and disease-free survival (B) according to grade as determined on incisional biopsies.
There are some features of the study that may have influenced the results. First, the total number of patients evaluated is small, approximately 100 cases per biopsy type, possibly skewing the results. More than 400 cases were used to validate the FNCLCC grading system.14 However, the sample size of our study is not considered a major limitation, as it did confirm, when sufficient tissue was available (IB), that grade as determined using the FNCLCC system is prognostic. Second, more tumors were deep to fascia in the CNB group than in the IB group, possibly because of ease of access. Third, patients were treated with different modalities, including surgery alone, surgery with preoperative or postoperative radiation, surgery and chemotherapy, and a combination of all 3 modalities, which may influence patient outcome. Although IB has long been considered the gold standard for diagnosis of extremity-based STS,20,31 several studies have reported good concordance between CNB and the final resection for malignancy, tumor type, and/or tumor grade, Arch Pathol Lab Med—Vol 137, December 2013
suggesting that it may be an alternative approach to IB for tissue sampling.16–30 These studies are summarized in Table 4. In 6 studies the diagnosis, not grade, obtained from CNB was correlated to that of the final resection specimen, but none of these compared the 2 biopsy techniques.18,20,21,23,25,29 Nine studies correlated the tumor grade determined on the CNB to that of the final resection, and these showed concordance ranging from 45.6% to 100%.* These studies differ from the current study in several aspects. Studies either had small numbers of patients (eg, 16), did not state the grading system used, included bone tumors and/or other STS that were excluded in the current study (eg, liposarcoma, Ewing sarcoma), or used a different grading system so are not directly comparable. Only 4 studies compared both sampling techniques (CNB versus IB) and tumor grade and correlated them with the grade of the final resection specimen.17,24,27,30 For example, Heslin et al27 described that * References 16, 17, 19, 22, 24, 26–28, 30. Sampling Modality in Extremity Soft Tissue Sarcoma—Khoja et al 1777
Table 3.
Estimated 5-Year Metastasis-Free and Disease-Free Survival According to Sampling Modality Core Needle Biopsy Estimated 5-y Metastasis-Free Survival, %
Tumor Grade 1 2 3
Incisional Biopsy
Estimated 5-y Disease-Free Survival, %
Estimated 5-y Metastasis-Free Survival, %
Estimated 5-y Disease-Free Survival, %
56.3 53.6 48.8
100 84 50.1
100 81.8 49.1
56.3 53.6 50.4
for adequate CNB specimens, 95%, 88% and 75% correlated with the final resection diagnosis for malignancy, grade, and histologic subtype, respectively, but with IB specimens the correlation was better: 100%, 96%, and 84% respectively. However, the study population was small and the grading system used was not described. Of these 4 studies, only that by Strauss et al26 stated the grading system used (FNCLCC). However, in that report the tumors were subdivided into low-grade (grade 1) and high-grade (grades 2 and 3) tumors, which differs from the current study. The CNB accuracy was shown to be 86.3%, with a negative predictive value of 66.2%. Interestingly, CNB misgraded 24 of 71 lowgrade tumors. As a result of their findings, the authors concluded that CNB can be used as an alternative to IB in the diagnosis of soft tissue tumors, which differs from the conclusion of the current study. There are several possible reasons why sarcomas sampled by CNB were accurately graded in that study in contrast to the current study. First, the design of our study was somewhat different, as we did not compare grade in the CNB with the resection specimen but with the IB and then with outcome. This approach prevented the bias that could result from eliminating cases as a result of preoperative radiotherapy. Strauss et al26 did not correlate grade with outcome, so there was no gold standard to confirm their ability to grade tumors. This is important as the FNCLCC reproducibility study showed only 75% concordance in grade among pathologists.32 Table 4.
Source, y 16
a
Ball et al, 1990 Barth et al,28 1992 Skrzynski et al,29 1996a Heslin et al,27 1997b Welker et al,17 2000c Yao et al,21 1999 Hoeber et al,24 2001d Ray-Coquard et al,23 2003e Yang and Damron,22 2004f Mitsuyoshi et al,25 2006 Woon and Serpell,30 2008 Kasraeian et al,20 2010 Strauss et al,26 2010 Verheijen et al,18 2010 Adams et al,19 2010c
Second, they had 4 CNBs in each case (size of biopsy not mentioned), whereas we had anywhere from 1 to greater than 4 biopsies per case. It has been suggested that 4 to 6 cores are necessary for accurate sarcoma diagnosis and grading.33,34 In our study, approximately 75% of cases had 3 or more core biopsies, and it may be that if we had considered the cases with fewer than 3 biopsies to be insufficient we might have had similar results. Third, cases in the study of Strauss et al26 were not restricted to extremity sarcomas. It is not clear whether the prognostic ability of core biopsies could be improved. Recommending the number/ size of cores for which accurate grading might be accomplished is problematic for several reasons. First, high-grade tumors or tumors with a characteristic translocation (eg, synovial sarcoma) would likely require fewer cores; second, histologic heterogeneity is more prevalent in some tumor types, for example myxoid tumors; and third, if the biopsies are mostly necrotic more biopsies will be required. In summary, the data suggest that IB may be a more reliable sampling technique in extremity STS for prognostication, likely because it provides an adequate amount of tissue for grading. Core needle biopsy specimens are prone to sampling error with the risk to underestimate tumor grade, perhaps because histologic features such as necrosis are underrepresented. Furthermore, IB appears to give a
Summary of Previous Studies
No. of Samples of STS CNB
No. of Samples of STS IB
40 16 43 (19 STT) 60 155 105 (42 STT) 182 85 (63 STT) 23 26 35 19 175 90 212
ND ND 37 45 12 25 44 ND ND ND ND 19 ND 195 ND
Grading System
Correlation of CNB Grade to Final Resection, %
Correlation of IB Grade to Final Resection, %
NS NS NS Low and high grade NS NS NS NS NS NS NS AJCC (FNCLCC) FNCLCC NS NS
88 100 ND 88 88.6 ND 84.9 ND 83 ND 45.6 ND 86.3 ND 80.7
ND ND ND 96 66.7 ND 64.9 ND ND ND 100 ND ND ND ND
Abbreviations: AJCC, American Joint Committee on Cancer; CNB, core needle biopsy; FNCLCC, French Federation of Cancer Centers Sarcoma Group grading system; IB, incisional biopsy; ND, not done, only accuracy of diagnosis determined; NS, not stated; STS, soft tissue sarcoma; STT, soft tissue tumor. a Malignant tumors include malignant peripheral nerve sheath tumor, non–spindle cell sarcomas, and liposarcoma. b Large number of liposarcomas; includes benign and malignant tumors. c Includes both bone and soft tissue tumors and cases that were not sarcoma. d Includes non–spindle cell sarcomas. e Includes cases that were not sarcomas; not always compared with surgical resection specimen. f Includes both bone and soft tissue tumors; not all samples correlated with resection specimen. 1778 Arch Pathol Lab Med—Vol 137, December 2013
Sampling Modality in Extremity Soft Tissue Sarcoma—Khoja et al
better estimate of prognosis based on grade as compared with CNB. This would suggest that IB is the sampling modality of choice for extremity STSs for prognostic purposes, although it is possible that, as imaging methods improve and can accurately quantify necrosis, directed core needle biopsies, when combined with imaging features or other assessments such as molecular analyses, may be sufficient for accurate grading.35 The authors would like to acknowledge Marcus Wong for retrieving slides and Marie Maguire and Chriselle Solante for secretarial assistance. References 1. Coindre JM, Terrier P, Guillou L, et al. Predictive value of grade for metastasis development in the main histologic types of adult soft tissue sarcomas: a study of 1240 patients from the French Federation of Cancer Centers Sarcoma Group. Cancer. 2001;91(10):1914–1926. 2. Coindre JM. Grading of soft tissue sarcomas: review and update. Arch Pathol Lab Med. 2006;130(10):1448–1453. 3. Markhede G, Angervall L, Stener B. A multivariate analysis of the prognosis after surgical treatment of malignant soft-tissue tumors. Cancer. 1982;49(8): 1721–1733. 4. Gaynor JJ, Tan CC, Casper ES, et al. Refinement of clinicopathologic staging for localized soft tissue sarcoma of the extremity: a study of 423 adults. J Clin Oncol. 1992;10(8):1317–1329. 5. Saddegh MK, Lindholm J, Lundberg A, Nilsonne U, Kreicbergs A. Staging of soft-tissue sarcomas: prognostic analysis of clinical and pathological features. J Bone Joint Surg Br. 1992;74(4):495–500. 6. Pisters PW, Leung DH, Woodruff J, Shi W, Brennan MF. Analysis of prognostic factors in 1,041 patients with localized soft tissue sarcomas of the extremities. J Clin Oncol. 1996;14(5):1679–1689. 7. Heise HW, Myers MH, Russell WO, et al. Recurrence-free survival time for surgically treated soft tissue sarcoma patients: multivariate analysis of five prognostic factors. Cancer. 1986;57(1):172–177. 8. Zagars GK, Ballo MT, Pisters PW, et al. Prognostic factors for patients with localized soft-tissue sarcoma treated with conservation surgery and radiation therapy: an analysis of 1225 patients. Cancer. 2003;97(10):2530–2543. 9. Costa J, Wesley RA, Glatstein E, Rosenberg SA. The grading of soft tissue sarcomas: results of a clinicohistopathologic correlation in a series of 163 cases. Cancer. 1984;53(3):530–541. 10. Trojani M, Contesso G, Coindre JM, et al. Soft-tissue sarcomas of adults; study of pathological prognostic variables and definition of a histopathological grading system. Int J Cancer. 1984;33(1):37–42. 11. van Unnik JA, Coindre JM, Contesso C, et al. Grading of soft tissue sarcomas: experience of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer. 1993;29A(15):2089–2093. 12. Hashimoto H, Daimaru Y, Takeshita S, Tsuneyoshi M, Enjoji M. Prognostic significance of histologic parameters of soft tissue sarcomas. Cancer. 1992; 70(12):2816–2822. 13. Gustafson P. Soft tissue sarcoma: epidemiology and prognosis in 508 patients. Acta Orthop Scand Suppl. 1994;2591–2531. 14. Guillou L, Coindre JM, Bonichon F, et al. Comparative study of the National Cancer Institute and French Federation of Cancer Centers Sarcoma Group grading systems in a population of 410 adult patients with soft tissue sarcoma. J Clin Oncol. 1997;15(1):350–362.
Arch Pathol Lab Med—Vol 137, December 2013
15. Fletcher CDM, Unni KK, Mertens F; World Health Organization; International Academy of Pathology. Pathology and Genetics of Tumours of Soft Tissue and Bone. Lyon, France: IARC Press; 2002. 16. Ball AB, Fisher C, Pittam M, Watkins RM, Westbury G. Diagnosis of soft tissue tumours by Tru-Cut biopsy. Br J Surg. 1990;77(7):756–758. 17. Welker JA, Henshaw RM, Jelinek J, Shmookler BM, Malawer MM. The percutaneous needle biopsy is safe and recommended in the diagnosis of musculoskeletal masses. Cancer. 2000;89(12):2677–2686. 18. Verheijen P, Witjes H, van Gorp J, Hennipman A, van Dalen T. Current pathology work-up of extremity soft tissue sarcomas, evaluation of the validity of different techniques. Eur J Surg Oncol. 2010;36(1):95–99. 19. Adams SC, Potter BK, Pitcher DJ, Temple HT. Office-based core needle biopsy of bone and soft tissue malignancies: an accurate alternative to open biopsy with infrequent complications. Clin Orthop Relat Res. 2010;468(10): 2774–2780. 20. Kasraeian S, Allison DC, Ahlmann ER, Fedenko AN, Menendez LR. A comparison of fine-needle aspiration, core biopsy, and surgical biopsy in the diagnosis of extremity soft tissue masses. Clin Orthop Relat Res. 2010;468(11): 2992–3002. 21. Yao L, Nelson SD, Seeger LL, Eckardt JJ, Eilber FR. Primary musculoskeletal neoplasms: effectiveness of core-needle biopsy. Radiology. 1999;212(3):682– 686. 22. Yang YJ, Damron TA. Comparison of needle core biopsy and fine-needle aspiration for diagnostic accuracy in musculoskeletal lesions. Arch Pathol Lab Med. 2004;128(7):759–764. 23. Ray-Coquard I, Ranchere-Vince D, Thiesse P, et al. Evaluation of core needle biopsy as a substitute to open biopsy in the diagnosis of soft-tissue masses. Eur J Cancer. 2003;39(14):2021–2025. 24. Hoeber I, Spillane AJ, Fisher C, Thomas JM. Accuracy of biopsy techniques for limb and limb girdle soft tissue tumors. Ann Surg Oncol. 2001;8(1):80–87. 25. Mitsuyoshi G, Naito N, Kawai A, et al. Accurate diagnosis of musculoskeletal lesions by core needle biopsy. J Surg Oncol. 2006;94(1):21–27. 26. Strauss DC, Qureshi YA, Hayes AJ, et al. The role of core needle biopsy in the diagnosis of suspected soft tissue tumours. J Surg Oncol. 2010;102(5):523– 529. 27. Heslin MJ, Lewis JJ, Woodruff JM, Brennan MF. Core needle biopsy for diagnosis of extremity soft tissue sarcoma. Ann Surg Oncol. 1997;4(5):425–431. 28. Barth RJ Jr, Merino MJ, Solomon D, Yang JC, Baker AR. A prospective study of the value of core needle biopsy and fine needle aspiration in the diagnosis of soft tissue masses. Surgery. 1992;112(3):536–543. 29. Skrzynski MC, Biermann JS, Montag A, Simon MA. Diagnostic accuracy and charge-savings of outpatient core needle biopsy compared with open biopsy of musculoskeletal tumors. J Bone Joint Surg Am. 1996;78(5):644–649. 30. Woon DT, Serpell JW. Preoperative core biopsy of soft tissue tumours facilitates their surgical management: a 10-year update. ANZ J Surg. 2008;78(11): 977–981. 31. Huvos AG. The importance of the open surgical biopsy in the diagnosis and treatment of bone and soft-tissue tumors. Hematol Oncol Clin North Am. 1995;9(3):541–544. 32. Coindre JM, Trojani M, Contesso G, et al. Reproducibility of a histopathologic grading system for adult soft tissue sarcoma. Cancer. 1986; 58(2):306–309. 33. Wu JS, Goldsmith JD, Horwich PJ, Shetty SK, Hochman MG. Bone and soft-tissue lesions: what factors affect diagnostic yield of image-guided coreneedle biopsy? Radiology. 2008;248(3):962–970. 34. Clayer M. Pre-operative core biopsy of soft-tissue tumours facilitates their surgical management: comment. Aust N Z J Surg. 1998;68(12):864. 35. De Marchi A, Brach del Prever EM, Linari A, et al. Accuracy of core-needle biopsy after contrast-enhanced ultrasound in soft-tissue tumours. Eur Radiol. 2010;20(11):2740–2748.
Sampling Modality in Extremity Soft Tissue Sarcoma—Khoja et al 1779
Copyright of Archives of Pathology & Laboratory Medicine is the property of College of American Pathologists and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
