Biopsy of Musculoskeletal Tumors

2

Biopsy of MusculoskeletalTumors

Jacob Bickels, James Jelinek, Barry Shmookler and Martin Malawer

OVERVIEW

Biopsy is a key step in the diagnosis of bone and soft-tissue tumors. An inadequately performed biopsy may failto allow proper diagnosis, have a negative impact on survival, and ultimately necessitate an amputation toaccomplish adequate margins of resection. Poorly performed biopsy remains a common finding in patients withmusculoskeletal tumors who are referred to orthopedic oncology centers. The principles by which an adequateand safe biopsy of musculoskeletal tumors should be planned and executed are reviewed and a surgical approachto different anatomic locations is emphasized.

Malawer Chapter 02 21/02/2001 15:03 Page 37

INTRODUCTION

Biopsy is a key step in the diagnosis of a musculo-skeletal tumor. In a book published in 1958, Jaffe statedthat a biopsy should be regarded as the final diagnosticprocedure, not as a mere short cut to diagnosis.1 Biopsymust be preceded by careful clinical evaluation andanalysis of the imaging studies. The diagnosis of amusculoskeletal lesion is based on these three para-meters; all three have to fit and the diagnosis must bequestioned when they do not match.1 In the past,biopsies were performed routinely through a largeincision with significant contamination of thesurrounding soft tissues with tumor cells. Thecontamination, however, had minimal significancebecause most malignant tumors of the extremities andpelvis were treated with amputation. Today, limb-sparing procedures are performed in 90–95% ofpatients with musculoskeletal tumors of the extrem-ities, and indications and surgical technique ofmusculoskeletal biopsy had to be changed to allowthese procedures to be performed.2,3

The presence of a bone or soft-tissue lesion does notnecessarily merit a biopsy. The combination of medicalhistory, thorough physical examination, laboratorydata when indicated, and appropriate imaging studiesallows accurate diagnosis of most musculoskeletallesions. Clinically and radiologically benign-appearinglesions do not have to have a biopsy. In contrast, biopsyis indicated in benign aggressive, malignant, andquestionable lesions to confirm the clinical diagnosisand accurately classify the lesion before initiation ofdefinitive treatment.

Technically, most biopsies are simple. Decisionsregarding the indication for biopsy, the specific regionof the lesion that has to have a biopsy, and the anatomicapproach and biopsy technique can make thedifference between a successful biopsy and a cata-strophe. A poorly performed biopsy could become anobstacle to proper diagnosis and may have a negativeimpact on survival. Furthermore, patients who haveundergone poorly performed biopsies subsequentlymay require an amputation to achieve an adequatesurgical resection.

In 1982, Mankin et al.4 evaluated 329 patients whounderwent biopsy for bone or soft-tissue sarcomas. Therate of major errors in diagnosis was 18.2%, and the rateof complications was 17.3%. Unnecessary amputationswere performed in 4.5% of these patients.4 Theseevents were found to occur with far greater frequencywhen the biopsy was performed in a referringinstitution rather than in a specialized oncology center.In addition to technical recommendations (most ofwhich will be discussed in this chapter), it was

recommended that if a surgeon or an institution is notequipped to perform accurate diagnostic studies ordefinitive surgery and adjunctive treatment ofmusculoskeletal tumors, the patient should be referredto a specialized treating center before the biopsy isperformed.4 In 1996, Mankin et al.5 performed a secondstudy on 597 patients. They documented major errorsin diagnosis in 13.5% of the patients, a complicationrate of 15.9%, and unnecessary amputations in 3%. Thedifferences in outcome between referring and oncologycenters were unchanged and their recommendationwas identical.5

The current chapter reviews the principles accordingto which a safe and adequate biopsy of bone and soft-tissue tumors should be planned and performed.

BIOLOGY OF MUSCULOSKELETAL TUMORS

Because of the common origin from the mesenchymalelements of the musculoskeletal system, bone and soft-tissue sarcomas share certain unique biologic charac-teristics. Sarcomas grow in a centripetal fashion withthe most immature part of the lesion at the growingedge. A reactive zone is formed between the tumor andthe compressed surrounding normal tissues. Thereactive zone is composed of induced proliferation ofmesenchymal cells, neovasculature, and inflammatoryprocess.6 The type of mesenchymal proliferation isdetermined by the anatomic location of the tumor: soft-tissue tumors stimulate a fibrous reaction, andintraosseous lesions stimulate a bone-forming reaction.Furthermore, the same lesion in different areas willstimulate different mesenchymal responses. Thereactive region around an intraosseous lesion maturesinto reactive bone, whereas if the lesion penetrates thesoft tissues, the mesenchymal response is fibrous.6,7

Unlike sarcomas, carcinomas usually infiltrate, ratherthan push, the surrounding tissues and usually do notinduce the formation of a reactive zone.8

The reactive zone may be invaded by tumor nodulesthat represent microextensions of tumor. These nodulesare termed satellites and are not a metastatic pheno-menon. High-grade sarcomas may present with tumornodules that grow outside the reactive rim but withinthe same anatomic compartment in which the lesion islocated. These nodules are termed skip lesions (Figures2.1, 2.2).2,7 Low-grade sarcomas rarely manifest withskip lesions.6 Metastatic disease from bone and soft-tissue sarcomas is site-specific; it is manifested by lunginvolvement in its early stage and secondarily by boneinvolvement.2,9

Musculoskeletal Cancer Surgery38


DIAGNOSTIC STUDIES AND BIOPSYCONSIDERATIONS

Biopsy of a musculoskeletal lesion should be performedonly at the conclusion of staging, which is the processthat entails performing the imaging studies required todetermine the characteristics and local extent of thetumor and the presence of metastatic disease. Staging

Biopsy of Musculoskeletal Tumors 39

Figure 2.1 Growth pattern of bone and soft-tissuesarcomas. Sarcomas grow in a centripetal fashion, with themost immature part of the lesion at the growing edge. Areactive zone is formed between the tumor and thecompressed surrounding normal tissues and may beinvaded by tumor nodules that represent microextensions oftumor (satellites) and are not a metastatic phenomenon.High-grade sarcomas may present with tumor nodules thatgrow outside the reactive zone (skip lesions) but within thesame anatomic compartment in which the lesion is located.

Figure 2.2 A 40-year-old woman presented with a rapidlyenlarging mass that had developed in her calf. Physicalexamination revealed a deep-seated, firm mass, 10 cm indiameter, located at the proximal aspect of the calf. (A)Magnetic resonance imaging revealed the primary lesionand additional skip metastasis in the substance of the soleusmuscle. Core needle biopsy of the primary lesion establishedthe diagnosis of a high-grade leiomyosarcoma. (B) The skipmetastasis is shown clearly in an angiogram performedbefore radical excision of the tumors.

A

B

Skip lesion

Satellite lesion

BONE SARCOMA

Reactive zone

Skip lesion

SOFT TISSUESARCOMA

Reactive zone


helps determine the exact anatomic approach to thetumor and specifies the region of the tumor thatrepresents the underlying disease. A final reason fordeferring biopsy until staging is complete is that biopsysuperimposes real and artificial radiologic changes atthe biopsy site, and therefore can alter the inter-pretation of the imaging studies.

Anatomic Location of the Biopsy Tract

The position of the biopsy site within the lesion has amajor significance because bone and soft-tissue tumorsmay have regional morphologic variations.2,6,7 As aresult of that heterogeneity, multiple samples arerequired to establish a diagnosis. Carcinomas, bycontrast, are commonly homogeneous and a singletissue core or aspirate is sufficient for diagnosis. Theterm “sampling error” refers to an incorrect orinconclusive diagnosis that occurs because the biopsyspecimen was taken from a region that does notrepresent the underlying primary disease. The clinicalfindings and imaging studies must be evaluated beforebiopsy by the surgeon and the radiologist, who must befamiliar with the biologic and radiologic findings ofmusculoskeletal tumors. The questions that must beanswered before biopsy are: (1) What part of the lesionhas to have a biopsy? and (2) What is the safestanatomic route to that location?

Despite serious concerns regarding the potential ofaccelerated growth or metastatic dissemination of amalignant tumor after biopsy, there is no well-founded,objective evidence that biopsy promotes either adverseevent. The real risk of open and needle biopsies is thatthey may spread tumor cells locally and facilitate localtumor recurrence (Figure 2.3).10–13 The actual risk oflocal recurrence after biopsy is not well documented,but it is reasonable to assume that it is higher in openbiopsy than in needle biopsy, and that it is related to thewidth of the biopsy tract and adequacy of homeostasis.In planning the definitive surgery it must be assumedthat the biopsy tract is contaminated with tumor cellsand, therefore, it should be resected with the samesafety margins as the primary tumor (i.e., wide margins– Figure 2.4).

For these reasons the surgeon performing the biopsymust be familiar with the technique of the potentialdefinitive procedure, whether it is limb-sparing surgeryor amputation. The biopsy incision or the needle punc-ture hole, and the tract to the tumor, must be made withthe planned surgical incision site so that they will beincluded within the surgical specimen. Preferably, thesurgeon performing the biopsy will be the same personwho will perform the definitive procedure.

General guidelines regarding positioning of thebiopsy tract are applicable to biopsies of bone and soft-

tissue lesion and are independent of the technique(open versus needle biopsy) and anatomic location.These guidelines can be summarized as follows: (1)Decide, before biopsy, what part of the lesion is mostrepresentative of the underlying disease and will needto have a biopsy. As a rule the extraosseous componentof a malignant bone tumor is as representative of thetumor as is the bony component, and should havebiopsy, if present. Violating the cortex of a bone thatharbors a malignant tumor, predisposes the patient to apathologic fracture, and is recommended only if thereis no extraosseous extension of the tumor. (2) Positionthe point of entry along the planned incision of thedefinitive surgery. (3) The biopsy tract must be theshortest way to the lesion; however, it must not violatemore than one compartment and must be as remote aspossible from the main neurovascular bundle of theextremity. Figures 2.5–2.7 show the recommendedsurgical approach to the four most common locations ofprimary bone sarcomas (proximal femur, distal femur,proximal tibia, and proximal humerus).

Biopsy Technique

A closed biopsy does not involve an incision. Thespecimen is obtained after skin puncture by a needle ortrephine. An open biopsy, in contrast, requires anincision. It can either by incisional, in which case only arepresentative specimen is removed from the lesion, orexcisional, in which the lesion is excised en-bloc. Anysurgical procedure, even the most minor, is accom-panied by a risk of complications that may includeiatrogenic injury to blood vessels or nerves, com-plicated wound healing, wound infection, and tumorcell contamination along the biopsy tract andsubsequent local recurrence.

Open incisional biopsy is a reliable diagnostic methodbecause it allows the pathologist to evaluate cellularmorphologic features and tissue architecture fromdifferent sites of the lesion. Furthermore, it providesmaterial for performing ancillary studies such asimmunohistochemistry, cytogenetics, molecular gene-tics, flow cytometry, and electron microscopy. Thesestudies may help in the diagnosis and subclassificationof bone and soft-tissue tumors, and therefore guide thedefinitive treatment.

Needle biopsy of mesenchymal tumors initially wascriticized because the quantity of biopsy material wasoften insufficient for routine histopathologic evaluationand ancillary studies that require tissue. Fine-needleaspiration (FNA) using a 22-gauge needle, has beenshown to be a reliable technique for the diagnosis ofsoft-tissue tumors that also provides sufficient materialfor additional studies.14–20 Diagnostic accuracy of FNA ishighest when the cell type of the tumor is homogeneous,



as in the case of multiple myeloma or metastaticcarcinomas. Tissue architecture and matrix formationhave a major significance in the histologic evaluationand diagnosis of bone tumors. An important limitationof FNA stems from its inability to sample tissue matrixadequately and to show tumor structure.16 Because ofthese considerations, with the exception of fewspecialized centers,14,21,22 FNA is not commonly used todiagnose primary bone tumors.23

Core needle biopsy (CNB), using a 14-gauge needlethat provides a core of tissue with a maximum length of20 mm, was shown to be more than 90% accurate indifferentiating malignant from benign lesions.24 In mostpatients with suspected bone or soft-tissue sarcomas itis the biopsy performed before initiation of treatment.Core needle biopsy is commonly practiced as the first

biopsy modality.24 Open biopsy is performed when thepathologic diagnosis either is inconclusive or does notcorrelate with the clinical presentation and radiologicfindings. Bone biopsies, using a CNB, should beperformed under CT or fluoroscopy guidance, andmultiple cores should be obtained. Biopsy of a deep-


Figure 2.3 (A) Computed tomography guided core needlebiopsy of a lytic lesion of the distal humerus, suspected ofbeing a metastatic malignant melanoma. (B) That patientunderwent resection–curettage and cryosurgery, followedby radiation therapy. The biopsy tract was resected en-blocand its pathological evaluation revealed a tumor deposit.

A

B

Figure 2.4 (A) Biopsy site over an osteosarcoma of thedistal femur. The definitive surgical incision is planned toinclude the biopsy skin incision and the biopsy tract. (B) Thetumor is resected en-bloc with the biopsy tract and thebiopsy skin incision.

A

B



Figure 2.5 Biopsy tract, proximal and distal femur. A distinction is made between lateral and medial lesions. Because themajority of primary bone sarcomas have an extraosseous extension, the muscle underlying the tumor has to be resected withthe specimen. This principle applies to all anatomic locations.

Figure 2.6 Biopsy tract, proximal tibia.


seated or pelvic soft-tissue tumors is performed underCT guidance. If a soft-tissue tumor is palpable and isremote from the neurovascular bundle, a biopsy can beperformed in a clinic setting.

After adequate planning of the biopsy tract, biopsyshould be executed according to the following guide-lines: (1) Use the smallest longitudinal incision that iscompatible with obtaining an adequate specimen.Transverse incisions are contraindicated because theyrequire a wider soft-tissue resection at the time ofdefinitive surgery (Figure 2.8). (2) Use a knife or curetteto avoid crushing or distorting the specimen’s texture.When a purely intraosseous bone lesion is havingbiopsy, make a cortical window and pay attention to itsshape. Clark et al.25 evaluated the impact of three typesof hole shape (rectangular hole with square corners,rectangular hole with rounded corners, and oblonghole with rounded ends) on the breaking strength ofhuman femora. They found that an oblong hole withrounded ends afforded the greatest residual strength.25

They also found that increasing the width of the holecaused a significant reduction in strength, butincreasing the length did not.25 Therefore, when thebiopsy must be taken from the bone, a small circularhole should be made so that only minimal stress-risersare created. If a larger window is needed, an oblongwindow should be made (Figure 2.9). (3) Obtain

enough tissue. Always send a specimen for frozensection or touch-prep to verify the presence ofrepresentative tumor material in the specimen. Forneedle biopsies, cytopathologic evaluation has toconfirm the presence of viable tumor cells. If pathologicevaluation is negative or questionable, repeat thebiopsy. (4) As a general rule, culture what you biopsyand biopsy what you culture. (5) Use meticuloushemostasis. Any hematoma around a tumor should beconsidered contaminated. Large hematoma maydissect the soft and subcutaneous tissues andcontaminate the entire extremity, making limb-sparingsurgery impossible. A tourniquet is rarely indicated foran open biopsy, because bleeding vessels cannot beobserved and adequate hemostasis is hard to achieve. Ifa tourniquet is used, the limb should not be exsan-guinated by wrapping with an Esmarch bandage,because this may force tumor cells to the proximalaspect of the extremity and into the bloodstream. Toallow hemostasis, the tourniquet must be removedbefore wound closure. (6) Use drains if necessary. Theport of entry has to be in proximity and continuationwith the skin incision, not to its sides (Figure 2.10). Thedrain path is considered contaminated and has to beexcised with the surgical specimen. Guidelines regard-ing the excision of the draining tract therefore aresimilar to those that apply to the biopsy tract.


Figure 2.7 Biopsy tract, proximal humerus. The deltoid muscle has to be resected with most primary bone sarcomas of theproximal humerus. A transdeltoid approach through the anterior third of the muscle is used. The traditional deltopectoralapproach will necessitate wider resection of the pectoralis major muscle, compromise its use for soft-tissue reconstruction, andmay contaminate the main neurovascular bundle of the upper extremity.



Figure 2.8 (A) The smallest longitudinal incision thatallows an adequate specimen to be obtained should be used.A transverse biopsy incision requires a wider resection ofsoft tissues at the time of the definitive surgery. (B)Horizontal biopsy incision over a high-grade soft-tissuesarcoma of the thigh. Definitive surgery had to be modifiedto include the biopsy incision.

A

B

Figure 2.9 An oblong cortical window with rounded endsaffords the greatest residual strength and is recommendedfor biopsy of purely intraosseous lesions.

Figure 2.10 A drain has to be positioned in proximity toand along the site for planned incision of the definitiveprocedure.


SUMMARY

Accurate diagnosis of a musculoskeletal tumor is basedon these factors: clinical presentation, results ofradiologic studies, and pathologic evaluation. Theimportance of careful planning and performance of a

biopsy cannot be overemphasized because an errormay have a negative impact on survival, impede aproper diagnosis, and compromise the ability toperform limb-sparing surgery. Core needle biopsies,performed under CT guidance when indicated, arerecommended.


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10. Davies NM, Livesly PJ, Cannon SR. Recurrence of anosteosarcoma in a needle biopsy tract. J Bone Joint Surg.1993;75B;977–8.

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References



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Biopsy of Musculoskeletal Tumors