Biopsy of Soft Tissue Masses: Evidence-based Medicine for the Musculoskeletal Tumor Society

Abstract

The literature contains a number of controversies regarding key questions: (1) When is a biopsy indicated? (2) How should the biopsy be placed? (3) How should the biopsy be performed and which has the greatest diagnostic accuracy? (4) Who should perform the biopsy? (5) What clinical parameters present the greatest diagnostic difficulty? Using PubMed and Google Scholar we performed English-language literature searches of clinical studies reporting biopsy of soft tissue masses. Thirty-two studies met the inclusion criteria but were only able to address three of the five questions the authors had hoped to evaluate. Available evidence suggests open biopsy has the highest diagnostic accuracy over core needle biopsy, which was higher than fine needle aspiration. There was no evidence to address who is best suited to perform the biopsy (general surgeon, orthopaedic surgeon, radiologist, pathologist) in terms of accuracy of diagnosis. Frozen section at the time of biopsy may improve diagnostic accuracy. Diagnostic difficulty was associated with myxoid and round cell neoplasms, infections, and tumors located in the paraspinal region. The limited number of references addressing these issues demonstrated the need for more Level I research in the area of biopsy of soft tissue masses.

Level of Evidence: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Appendix 1. Annotated References

Accuracy and Comparison of Biopsy Techniques

1. Altuntas AO, Slavin J, Smith PJ, Schlict SM, Powell GJ, Ngan S, Toner G, Choong PF. Accuracy of computed tomography guided core needle biopsy of musculoskeletal tumors. ANZ J Surg. 2005;75:187–191.

EBM Level IV: This is a retrospective study on a series of 127 patients with musculoskeletal tumor. Computed tomography-guided core needle biopsy in the present series has an overall accuracy of 80.3%. The effective accuracy as determined by a malignant versus benign lesion was 89%. There were 86 malignant tumors with a biopsy accuracy of 81.4% and there were 41 benign tumors with a biopsy accuracy of 78%. The positive predictive value (PPV) of a malignant tumor is 98.9% and the PPV of benign tumor 90.2%. There were no reported complications arising from the biopsy.

2. Ball AB, Fisher C, Pittam M, Watkins RM, Westbury G. Diagnosis of soft tissue tumors by Tru-Cut biopsy. Br J Surg. 1990;77:756–758.

EBM Level IV: Sarcoma surgeon performed core biopsy with 94% accuracy (includes 4% inadequate tissue) for malignancy, 85% accuracy for subtype, and 88% accuracy for grade. Tru-Cut biopsies were obtained from 52 consecutive patients referred with soft tissue tumors. Of the biopsies, 96% provided adequate material for diagnosis. The accuracy of Tru-Cut biopsy was 98% for the diagnosis of malignancy and 94% for the diagnosis of sarcoma. Tumor subtype was correctly specified in 85% of sarcomas and tumor grade in 88%.

3. Barth RJ Jr, Merino MJ, Solomon D, Yang YC, 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;112:536–543.

EBM Level III: Core accuracy 96%, FNA 64%.

4. Carrino JA, Khurana B, Ready JE, Silverman SG, Winalski CS. Magnetic resonance imaging-guided percutaneous biopsy of musculoskeletal lesions. J Bone Joint Surg Am. 2007;89:2179–2187.

EBM Level IV: In a retrospective case series, 45 consecutive biopsies were performed in an open midfield 0.5-T interventional MRI unit. Samples were obtained with FNA, core needle biopsy, or a combination of these techniques. The diagnostic yield was 91% (41 of 45 biopsies yielded sufficient material for a diagnosis) overall, 95% (19 of 20) for the bone lesions, 94% (17 of 18) for the extra-articular soft tissue lesions, and 71% (five of seven) for the intra-articular soft tissue lesions. With regard to the diagnostic accuracy, the sensitivity was 0.86, the specificity was 1.00, the PPV was 1.00, and the negative predictive value was 0.76 in the overall group. The respective values were 0.92, 1.00, 1.00, and 0.86 for the bone lesions; 0.77, 1.00, 1.00, and 0.57 for the extra-articular soft tissue lesions; and 1.00, 1.00, 1.00, and 1.00 for the intra-articular soft tissue lesions. There was one complication: exacerbation of neuropathic pain related to a biopsy of a peripheral nerve sheath tumor.

5. Costa MJ, Campman SC, Davis RL, Howell LP. Fine-needle aspiration cytology of sarcoma. Retrospective review of diagnostic utility and specificity. Diagn Cytopathol. 1996;15:23–32.

EBM Level IV: The pathologist obtained tissue with FNA with 20.9% diagnostic accuracy; suspicion of malignancy was 88% accurate.

6. Das K, Hameed M, Heller D, Mirani N, Doty N, Benevenia J, Patterson F, Aisner S. Liquid-based vs conventional smears in fine needle aspiration of bone and soft tissue tumors. Acta Cytol. 2003;47:197–201.

EBM Level III: Pathologists obtained tissue using FNA with 64% diagnostic accuracy.

7. Domanski HA, Akerman M, Carlen B. Core-needle biopsy performed by the cytopathologist: a complement to FNA of soft tissue and bone lesions. Cancer. 2005;105:229–239.

EBM Level IV: Combined core needle biopsy with FNA resulted in 77% accuracy and grade accuracy of 90%.

8. Dupuy DE, Rosenberg AE, Punyaratabadhu T, Tan MH, Mankin HJ. Accuracy of CT-guided needle biopsy of musculoskeletal neoplasms. AJR Am J Roentgenol. 1998;171:759–762.

EBM Level IV: A radiologist performed the biopsy with core needle biopsy and had diagnostic accuracy of 93% (includes nondiagnostic biopsies) and 80% FNA (includes nondiagnostic biopsies). Using frozen section increased diagnostic accuracy from 88% to 94%. Higher diagnostic error occurred with paravertebral lesions and round cell histology.

9. Hau A, Kim I, Kattapuram S, Hornicek FJ, Rosenberg AE, Gebhardt MC, Mankin HJ. Accuracy of CT-guided biopsies in 359 patients with musculoskeletal lesions. Skeletal Radiol. 2002;31:349–353.

EBM Level IV: Computed tomography-guided core needle biopsies and fine needle aspirates were performed on 359 musculoskeletal lesions. The overall accuracy was determined to be 71%. The accuracy for 101 FNAs was 63% and for 258 computed tomography-guided core biopsies was 74%. It is of note that the biopsies of 81 pelvic lesions had higher rates of diagnostic accuracy (81%) than those of 278 nonpelvic sites (68%), and especially 94 lesions of the spine (61%). The lowest success rates occurred in 26 patients with infectious diseases (50%).

10. Hodge JC. Percutaneous biopsy of the musculoskeletal system: a review of 77 cases. Can Assoc Radiol J. 1999;50:121–125.

EBM Level IV: A total of 77 percutaneous biopsies were performed under computed tomographic or fluoroscopic guidance of 63 bone and 14 soft tissue biopsies. No followup information was available for eight patients, and one patient died before an accurate diagnosis could be made. There were 44 true-positive, 17 true-negative, eight false-negative, and no false-positive results. The correct diagnosis was obtained in 57 of 68 cases (83.8%). For bone biopsies, the accurate diagnosis was obtained in 47 of 55 cases (85.5%). For soft tissue biopsies, the correct diagnosis was obtained in 10 of the 13 cases (76.9%). Diagnostic accuracy was slightly better for osteolytic than for osteosclerotic lesions. Accuracy also varied with lesion site and needle type. Cytology and pathology specimens were almost equally useful in contributing to the correct diagnosis.

11. Hoeber I, Spillane AJ, Fisher C, Thomas JM. Accuracy of biopsy techniques for limb and limb girdle soft tissue tumors. Ann Surg Oncol. 2001;8:80–87.

EBM Level III: Core needle biopsy was 80% accuracy, defined malignancy from benign lesion 98.7%, and outside needle biopsies had similar diagnostic accuracy.

12. Issakov J, Flusser G, Kollender Y, Merimsky O, Lifschitz-Mercer B, Meller I. Computed tomography-guided core needle biopsy for bone and soft tissue tumors. Isr Med Assoc J. 2003;5:28–30.

EBM Level IV: There were 80 soft tissue and 135 bony lesions. All biopsies were performed by the same radiologist and the histologic examination by the same pathologist. Of the 80 soft tissue biopsies, 35 were malignant (25 soft tissue sarcomas, six lymphomas, four metastatic carcinomas); 40 were benign (myositis ossificans, neurofibroma, desmoid tumor, schwannoma, hematoma, and others), and five were inconclusive and followed by an open incisional biopsy. The core needle biopsy histologic diagnosis was compared with that of the definitive surgery and the diagnostic accuracy was 90%. Only three samples initially diagnosed as benign turned out to be malignant. No significant complications occurred during the procedures.

13. Kissin MW, Fisher C, Carter RL, Horton LW, Westbury G. Value of Tru-Cut biopsy in the diagnosis of soft tissue tumors. Br J Surg. 1986;73:742–744.

EBM Level IV: Tru-Cut needle biopsies from 50 consecutive soft tissue tumors were assessed by three pathologists and compared with the definitive histologic diagnosis. A correct predictive diagnosis of sarcoma was made on 87% to 98% of adequate Tru-Cut specimens, the accuracy varying between pathologists. Three sources of diagnostic error were recognized: false-positive cores (8%), false-negative cores (8%), and cores inadequate for diagnosis (16%).

14. Maitra A, Ashfaq R, Saboorian MH, Lindberg G, Gokasian ST. The role of FNA biopsy in the primary diagnosis of mesenchymal lesions. A community hospital-based experience. Cancer. 200;90:178–185.

EBM Level IV: Pathologists using FNA were able to determine malignancy 88% of the time in a nonsarcoma center.

15. Mitsuyoshi G, Naito N, Kawai A, Kunisada T, Yoshida A, Yanai H, Dendo S, Yoshino T, Kanazawa S, Ozaki T. Accurate diagnosis of musculoskeletal lesions by core needle biopsy. J Surg Oncol. 2006;94:21–27.

EBM Level IV: The diagnoses were determined on 163 core needle biopsies (bone, 91; soft tissue, 72) performed on 157 consecutive patients. One hundred forty-three specimens (88%) were determined to be adequate for histologic examination. A pathologist with experience in musculoskeletal lesions was able to differentiate malignant tumors from benign lesions in 97% of the cases (bone, 100%; soft tissue, 94%) and arrive at a specific diagnosis in 88% (bone, 96%; soft tissue, 78%) when adequate cores were obtained. The overall accuracy was 77% (bone, 85%; soft tissue, 68%). There was no morbidity related to the procedure.

16. Madhavan VP, Smile SR, Chandra SS, Ratnakar C. Value of core needle biopsy in the diagnosis of soft tissue tumors. Indian J Pathol Microbiol. 2002;45:165–168.

EBM Level IV: This was a prospective study to determine the accuracy of core needle biopsy in the diagnosis and grading of soft tissue tumors and to study the morbidity of core needle biopsy. Forty-one cases with 85.3% of core biopsies yielded an adequate sample. Core needle biopsy had a sensitivity of 90%, specificity of 100%, PPV of 100%, and a negative predictive value of 88.23%. Overall accuracy for diagnosis of malignancy was 94.28%, 77.7% of tumors were correctly subtyped, and none of them were histologically graded.

17. Moore TM, Meyers MH, Patzakis MJ, Terry R, Harvey JP Jr. Closed biopsy of musculoskeletal lesions. J Bone Joint Surg Am. 1979;61:375–380.

EBM Level IV: Pathologists using core biopsy had 76% diagnostic accuracy.

18. Moulton JS, Blebea JS, Dunco DM, Braley SE, Bisset GS 3rd, Emery KH. MR imaging of soft-tissue masses: diagnostic efficacy and value of distinguishing between benign and malignant lesions. AJR Am J Roentgenol. 1995;164:1191–1199.

EBM Level IV: The imaging features of 225 soft tissue tumors (179 benign, 46 malignant) in 222 patients were analyzed. By quantitative analysis, no single imaging feature or combination of features could reliably be used to distinguish benign from malignant lesions. For the subjective analysis, a correct and specific benign diagnosis could be made on the basis of MRI findings in 100 (44%) of the 225 tumors. For the entire cohort, the sensitivity was 78%, the specificity was 89%, the PPV was 65%, and the negative predictive value was 94% for a malignant diagnosis. When the diagnostic benign tumors were excluded, the specificity and negative predictive value decreased to 76% and 86%, respectively, whereas the sensitivity and PPV remained the same.

19. Nagira K, Yamamoto T, Akisue T, Marui T, Hitora T, Nakatani T, Kurosaka M, Ohbayashi C. Reliability of FNA biopsy in the initial diagnosis of soft tissue lesions. Diagn Cytopathol. 2002;27:354–361.

EBM Level IV: A sarcoma surgeon performed FNA with 92% accuracy in predicting malignancy and 54% diagnostic accuracy.

20. Ogilvie CM, Torbert JT, Finstein JL, Fox EJ, Lackman RD. Clinical utility of percutaneous biopsies of musculoskeletal tumors. Clin Orthop Relat Res. 2006;450:95–100.

EBM Level IV: FNA by radiologists were predictive of malignancy 75% and increased to 81% if included core biopsy. Twenty-five percent required open biopsy by a sarcoma surgeon. Myxoid histology was more often associated with diagnostic error.

21. Parkkola RK, Mattila KT, Heikkila JT, Ekfors TO, Komu ME, Vaara T, Aro HT. MR-guided core biopsies of soft tissue tumors on an open 0.23 T imager. Acta Radiol. 2001;42:302–305.

EBM Level IV: Twenty-nine consecutive patients with known or suspected benign or malignant soft tissue tumors underwent MRI. MR-guided core biopsy of the tumor was performed on an open 0.23-T magnet. The MR-guided core biopsy specimens were sufficient for histopathologic diagnosis in 27 of 29 cases.

22. Puri A, Shingade VU, Agarwal MG, Anchan C, Juvekar S, Desai S, Jambhekar NA. CT-guided percutaneous core needle biopsy in deep seated musculoskeletal lesions: a prospective study of 128 cases. Skeletal Radiol. 2006;35:138–143.

EBM Level IV: One hundred thirty-six consecutive computed tomography-guided biopsy sessions were undertaken for musculoskeletal lesions in 128 patients. In 121 patients, a single session was sufficient to obtain representative material, whereas for six patients, two sessions and for one patient three sessions were necessary. One hundred eight biopsy sessions yielded a diagnosis, whereas 28 were inconclusive (diagnostic yield of 79.41%). Of 108 diagnostic biopsies, five were considered inaccurate (accuracy rate of 95.37%). The overall diagnostic yield and accuracy rate for soft tissue lesions were 70% and 92.85%. There were two complications with no permanent sequelae.

23. Ray-Coquard I, Ranchère-Vince D, Thiesse P, Ghesquières H, Biron P, Sunyach MP, Rivoire M, Lancry L, Méeus P, Sebban C, Blay JY. Evaluation of core needle biopsy as a substitute to open biopsy in the diagnosis of soft-tissue masses. Eur J Cancer. 2003;39:2021–2025.

EBM Level IV: Its diagnostic usefulness was investigated retrospectively in 110 patients with soft tissue masses (s-t-M) undergoing core needle biopsy between September 1994 and September 2000. One hundred three of 110 core needle biopsies were suitable for analysis. Core needle biopsy specificity and PPV were 100%; sensitivity was 95%, 99%, and 92%; and negative predictive value 85%, 95%, and 88% for diagnosing malignancy, soft tissue tumor, and sarcoma, respectively. Core needle biopsy sensitivity and negative predictive value were 100% for malignancy, connective tumor and sarcoma in lymphomas, high-grade sarcomas, and desmoid tumors. In low-grade sarcomas, sensitivity was 94% and 85% and negative predictive value 84% and 77% for malignancy and sarcoma, respectively.

24. Rydholm A, Akerman M, Idvall I, Persson BM. Aspiration cytology of soft tissue tumors. A prospective study of its influence on choice of surgical procedure. Int Orthop. 1982;6:209–214.

EBM Level IV: The pathologist at a sarcoma center using FNA was 83% accurate in predicting malignancy.

25. Serpell JW, Pitcher ME. Pre-operative core biopsy of soft-tissue tumors facilitates their surgical management. Aust N Z J Surg. 1998;68:345–349.

EBM Level IV: All patients with primary soft tissue tumors managed by two surgeons with a special interest in soft tissue sarcomas since 1991 were reviewed. The overall accuracy of core biopsy was 84%. The sensitivity was 94% with 100% specificity.

26. 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;78:644–649.

EBM Level II: A sarcoma surgeon using core biopsy had 84% diagnostic accuracy versus 94% open biopsy. Core biopsy had 78% grade accuracy. Core needle biopsy was less expensive than open biopsy.

27. Smith TJ, Safail H, Foster EA, Reinhold RB. Accuracy and cost-effectiveness of fine needle aspiration biopsy. Am J Surg. 1985;149:540-545.

EBM Level IV: Pathologists were able to predict malignancy 86% of the cases using FNA.

28. Soudack M, Nachtigal A, Vladovski E, Brook O, Gaitini D. Sonographically guided percutaneous needle biopsy of soft tissue masses with histopathologic correlation. J Ultrasound Med. 2006;25:1271–1277.

EBM Level IV: Retrospective review of the medical records of patients who underwent sonographically guided core biopsy of 183 soft tissue masses at our institution during a 50-month period. Biopsy results were diagnostically accurate in 174 (91%) cases. Thirteen biopsies were inconclusive. No complications occurred. The overall sensitivity, specificity, PPV, and accuracy in separating malignant from benign lesions were 97%, 99%, 99%, and 98%, respectively.

29. Torriani M, Etchebehere M, Amstalden E. Sonographically guided core needle biopsy of bone and soft tissue tumors. J Ultrasound Med. 2002;21:275–281.

EBM Level IV: A prospective study was performed in 74 patients referred for image-guided core needle biopsy of primary or recurrent musculoskeletal neoplasms and suspected solitary metastasis. An accurate diagnosis was obtained in 47 (97%) of 48 biopsies; sensitivity was 96%, and specificity was 100%. The method did not yield sufficient tissue to establish a diagnosis in one case. Considering all 65 biopsies, high-quality specimens were obtained in 96%. There were no complications.

30. Wakely PE, Kneisl JS. Soft tissue aspiration cytopathology. Diagnostic accuracy and limitations. Cancer. 2000;90:292–298.

EBM Level IV: Pathologists using FNA predicted accurately malignancy 97% and 83% grade.

31. Yang YJ, Damron TA. Comparison of needle core biopsy and fine-needle aspiration for diagnostic accuracy in musculoskeletal lesions. Arch Pathol Lab Med. 2004;128:759–764.

EBM Level I: Pathologist using both FNA and core biopsy in all patients found core needle biopsy was associated with a higher diagnostic accuracy of malignancy than FNA (93% versus 88%) and prediction of specific diagnosis (83% versus 64%).

32. Yeow KM, Tan CF, Chen JS, Hsueh C. Diagnostic sensitivity of ultrasound-guided needle biopsy in soft tissue masses about superficial bone lesions. J Ultrasound Med. 2000;19:849–855.

EBM Level IV: Authors evaluated the value of ultrasound-guided needle biopsy in 20 soft tissues masses. A diagnostic sensitivity of 95% and specificity of 100% in separating a benign or a malignant lesion was obtained. Fine needle aspiration cytology allowed the specific cell type of malignancy to be diagnosed in 80% of cases, whereas core needle biopsy allowed it in 91%.

EBM = evidence-based medicine; FNA = fine needle aspiration.