NEOPLASMS OF THE MUSCULOSKELETAL TISSUES

Oleh
Dr. HARI TJAHJONO WAHONO, FICS, SpOT, FWPOA
(Ahli Bedah Orthopaedi dan Traumatologi)
RSD SIDOARJO

Neoplasms of the musculoskeletal tissues meliputi :

1. Primary Neoplasms of bone
2. True Primary Neoplasms of bone
3. Mertaststic Neoplasms in Bone
4. Specific Primary Neoplasms and neoplasms- Like Lesions of Synovial Joint,
Bursae and Tendon Sheaths
5. Non – neoplastic Lesion of Synovial Membrane

Definition of Terms
The term tumor (which is often loosely used to describe any localized swelling, or
lump) seems less precise than the term neoplasms or new growth, which refers to a new
and abnormal formation of cell, a process that progresses and continues to progress,
throughout the life of the patient, unless some type of therapy intervenes.
Thus, succeeding generations of neoplasms cells continue to devide by mitosis more
rapidly than do normal cells of the particular tissue and consequently produce a
progressive lesion; this explains the presence of excessive numbers of mitotic figure in
rapidly growing neoplasms. Neoplastic cells demonstrate ability to initiate independent
growth in distant sites (metastases), the neoplasms is malignant and referred to as
cancer.
Primary neoplasms of a given structure arise from cells that are normally “local
inhabitants” of that structure, whereas secondary neoplasms arise from cells that are “
outside invaders” from elsewhere.
The primary lesions may be divided into the following groups : osteogenic,
chondrogenic, collagenic and myelogenic. Turthermore, in each group there may be
reactive lesions (which are not neoplasms), hamartomas (which many consider to be
“benign neoplasms”) and true neoplasms (some of which wre potentially malignant
and others of which are frankly malignant).

Classification (Aegerter, 1968)

I. Reactive Bone Lesions :
A. Osteogenic : 1. Osteoid Osteoma
2. Benign osteoblastoma
B. Collagenic : 1. Subperiosteal cortical defect
2. Non-osteogenic fibroma
II. Hamartomas Affecting Bone
A. Osteogenic : 1. Osteoma
: 2. Osteochodroma
B. Chondrogenic : Enchodroma
C. Collagenic : 1. Angioma
2. Aneurysmal bone cyst
III. True Neoplasms of Bone
A. Osteogenic : 1. Osteosarcoma
2. Parosteal sarcoma
3. Osteoclastoma (Giant Cell Tumor)
B. Chondrogenic : 1. Benign chondroblastoma
2. Chondromyxoid fibroma
3. Chondrosarcoma
C. Collagenic : 1. Fibrosarcoma
2. Angiosarcoma
D. Myelogenic : 1. Plasma cell myeloma (multiple Myeloma)
2. Ewing’s tumor
3. Reticulum cell sarcoma
4. Hodgkin’s disease

OSTEOID OSTEOMA
Merupakan reactive bone lesion, klinis terdapat persistent pain, biasanya pada children
dan adolescent, khususnya pada laki-laki, pendeteksinya pada lower limb, femur, tibia.
Jarang tumbuh dan biasanya ukuran diameternya kurang dari 1 cm, kadang besar.
Nyerinya hilang dengan pemberian analgesic, bila dekat sendi bisa terjadi effusion,
atropi atau sekitarnya.
Harus dibedakan dengan chronic osteomyelitis, walaupun ini self limiting, tapi bila nyeri
terus mungkin perlu di operasi.

Osteoid
Figure 1
Osteoma pada Femur

BENIGN OSTEOBLASTOMA (Giant Osteoid osteoma)

Biasanya terdapat di vertebra atau tulang lain, lebih besar dari osteoid osteoma, rasa nyeri
hilang dengan di operasi.
 Benign osteoblastoma
pada humerus

OSTEOCHODROMA (Osteocartilaginous
Exostoses)
Merupakan tumor jinak, suatu pertumbuhan yang
abnormal pada daerah metaphyse di tulang panjang
dari anak yang sedang tumbuh, disini terjadi
kegagalan remodeling dari tulang. Terdapat
pertumbuhan yang abnormal dari tulang dan cartilage, gejala klinis terdapat tumor
dengan local sweeling atau lump. Biasanya terdapat pada daerah metaphyse dari lower
end of femur, upper end of tibia, upper end of humerus, kebanyakan pada actively
growing ends of long bone, bila terjadi di banyak tempat disebut diaphyseal aclasis
(multiple osteocartilaginous exostoses). Dengan tumbuh panjangnya tulang maka tangkai
tumor ini dekat epiphyseal plate sedang ujungnya didaerah diaphyse. Bisa berubah jadi
malignant kira-kira pada 1% dari kasus osteochondroma dan angka lebih tinggi pada
yang multiple gejala klinis biasanya terdapat benjolan tampan rasa nyeri didaerah
metaphyse tulang panjang. Tidak semua osteochondroma memerlukan terapi, kecuali bila
menimbulkan keluhan maka perlu dilakukan operasi excise.

Osteochodroma pada Tibia proximal dan Femur distal

ENCHODROMA
Terdapat banyak pada phalanges, metacarpal, metatarsal bila terjadi di banyak tempat
disebutenchondromatosis (Ollier’s dyschondroplasia), terdapat pertumbuhan lesi absorsi
bagian dalam dari cortek dan terdapat subperiosteal reavtive bone ke outer surface. Bisa
berubah jadi chondrosarcoma. Terapi dengan curretase dan bone graft.

Enchondroma pada phalanx medius digiti

OSTEOSARCOMA
Adalah tumor ganas, timbul dari primitive cell (poorly differentiated) didaerah
metaphyse tulang panjang pada dewasa muda, merupakan tumor primer tulang,
merupakan tumor ganas terbanyak kedua setelah multiple myeloma. Secara genesis
berasal dari osteoblastic primitive mesenchimal cells
Terbanyak terletak pada femur distal, tibia proximal atau fibula, humerus proximal.
Tumbuh dengan cepat terjadi destruksi, bisa terjadi fraktur patologi. Terdapat
Codman’s triangle (elevasi dari periosteum pada foto rontgen). Kombinasi antara
reactive bone dan neoplastik bone pada sepanjang pembuluh darah terlihat sebagai
“sunburst” appearance. Pada 50% dari kasus bisa metastase ke paru, gejala klinis tumor
tumbuh dengan cepat, mula – mula terdapat rasa nyeri ringan kemudian sedang
selanjutnya nyeri sekali dan menetap. Kulit terasa hangat, banyak pembuluh darah vena
yang dilatasi. Diagnosa dengan biopsi, prognosa jelek karena kebanyakan sudah
metastase ke paru pada stadium awal.
 Osteosarcoma Femur distal dan fraktur patologis

OSTEOCLASTOMA (Giant Cell Tumor of Bone)

Tumbuh didaerah epiphysis tulang panjang, setelah epiphyseal plate menutup, terdapat
pada radius distal, tibia proximal, femur distal, biasanya exten ke articular cartilage.
Tulang destruksi, cancellous dan cortical bone diresorbsi dari dalam, terdapat expanded
periosteum deposit bone cenderung jadi gabas, pada mikroskopis terlihat a vascular
network of stromal cells dan sejumlah banyak multinucleated giant cells. Gejala klinis
penderita mengeluh local pain, kadang ada gangguan sendi Radiology terdapat local
destruksi daerah epiphyse seperti gelembung sabun. Prognosa jelek.
 Giant cell tumor pada radius distal

MULTIPLE MYELOMA
Tumbuh dari bone marrow tulang, biasanya pada usia diatas 40 tahun, terdapat pada
spine, pelvis, skull, terasa nyeri, terdapat destruksi tulang bisa terjadi fraktur patologis
tulang, Terdapat banyak gamma globulin protein di excresi lewat urine, protein ini di
produksi oleh plasma cell. Dan ini disebut Bence-Jone protein yang terdapat sekitar 50%
dari kasus. Diagnosa dengan needle aspiration bipsi dari marrow crista illiaca atau
sternum. Prognosa jelek

EWING’S SARCOMA (EWING’S TUMOR)

Merupakan tumor ganas tumbuh cepat dari primitive cell bone marrow, terjadi pada
umur muda, biasanya pada medullary cavity tulang panjang. Ini merupakan tumor
ganas terbanyak ketiga setelah multiple myeloma dan osteosarcoma terdapat banyak pada
anak dewasa muda di tulang femur, tibia, ulna, metatarsals. Tumbuh dari medullary
cavity kemudian perforasi ke cortex dari shaft dan elevasi dari periosteum, repeated
elevasi dari periosteum timbullah “Union Skin”. Metastase ke paru dan tulang tulang
lain. Mikroskopis terdapat poorly differentiated round cells of marrow origin.
Metastase lewat blood stream dan menimbulkan gejala sistemik seperti slight fever,
moderate leucocitosis dan peningkatan laju endap darah, dan pada tumor terdapat
avascular necrosis dari tulang. Juga terdapat keluhan nyeri progresif dari penderita.
Deferential diagnose dengan chronic osteomyelitis dan eosinophylic granuloma,
diagnose pasti dengan biopsy. Prognose jelek, angka kematian 95% dari kasus dan
terjadi beberapa tahunpertama setelah diagnose
dibuat.
 Ewing’s sarc oma pada
femur

METASTATIC CARCINOMA
Menyebar dari primer carcinoma lewat aliran darah, limfe atau secara langsung,
biasanya terdapat pada vertebra, pelvis, ribs dan proximal tulang panjang dari limbs.
Pada umumnya tumor primer berasal dari breast, prostate, lung dan ginjal.
Biasanya gambaran tulang terlihat destruktif, dan osteolytic metastase, kadang
osteoslerotic metastases. Keluhan penderita terdapat rasa nyeri dan kadang terdapat
fraktur patologis dari tulang. Juga bisa terdapat kenaikan dari serum alkaline
phosphatase.

PRINSIP PENGOBATAN DARI SEMUA TUMOR

Pertama perlu diagnose yang akurat
Benign neoplasma dan no malignant lain (jinak) biasanya dengan excise curettement
dan bone grafting.
Sedangkan yang malignant biasanya dilakukan perbaikan keadaan umum, amputasi,
radiasi cytotoxic drugs dan obat paliatip yang lain.
Prinsip pembedahan bisa dilakukan menurut Surgical Staging dari Enneking

Overview
The prognosis of patients with musculoskeletal tumors has improved markedly because
of the advent of new chemotherapeutic drugs and regimens and as a result of advances in
imaging and surgical techniques. Limb-salvage operations can currently be performed
with better outcomes, while in the past, limbs with tumors were treated only with
amputation. (See the images below.)
 Frontal radiograph in a 9-year-old with trauma to the left knee
shows a well-defined, cortically-based lesion with sclerotic margins, situated on the
lateral aspect of the left upper tibial metaphysis. The lesion has the typical appearance of

a fibrous cortical defect. Enneking stage 0. Frontal radiograph in a 10-year-

old boy with pain of the left upper limb shows a well-defined, loculated, centrally located
lesion in the left humeral metaphysis. Overlying cortical thinning is noted. The lesion has
the typical appearance of a unicameral bone cyst. Enneking stage II.

Computed tomography (CT) scan of the lungs shows

multiple lung metastases (white arrows) and bilateral pleural effusions (black arrows) in a
patient with osteosarcoma of the humerus. Enneking stage III.

Accurate preoperative surgical staging of musculoskeletal tumors is currently possible

because of advanced imaging techniques, which is important because the images provide
prognostic information and aid clinicians in choosing the most appropriate treatment
option for the patient

Surgical Staging of Bone Tumors

The aims of surgical staging are to determine the surgical margins of resection and to
facilitate interinstitutional and interdisciplinary communication regarding treatment data
and results

The Enneking system for the surgical staging of bone and soft-tissue tumors is based on
grade (G), site (T), and metastasis (M) and uses histologic, radiologic, and clinical
criteria. It is the most widely used staging system and has been adopted by the
Musculoskeletal Tumor SocietyThe system should be reserved for staging mesenchymal
lesions rather than nonmesenchymal ones (such as the lesions of Ewing sarcoma,
lymphoma, and leukemia), because the biologic behavior of nonmesenchymal tumors
differs from that of mesenchymal lesions. For example, studies have shown that the site
of occurrence of Ewing sarcoma is not a significant factor when tumor size is considered.

Grade

In the Enneking system, bone tumors are graded as follows:

  G0 - Benign lesionA
 G1 - Low-grade malignant lesion
 G2 - High-grade malignant lesion

Surgical grade generally follows histologic grade; however, a higher surgical grade may
be applied if the radiographic features and clinical behavior of a lesion indicate an
aggressiveness that is incompatible with its benign histologic features.

Site

In the Enneking system, the site and local extent of bone tumors are classified as follows:

 T0 - A benign tumor that is confined within a true capsule and the lesion's
anatomic compartment of origin (ie, a benign intracapsular, intracompartmental
lesion)
 T1- An aggressive benign or malignant tumor that is still confined within its
anatomic compartment (ie, an intracompartmental lesion)
 T2 - A lesion that has spread beyond its anatomic compartment of origin (ie, an
extracompartmental lesion)

Metastasis

Metastatic classification in the Enneking system is as follows:

 M0 - No regional or distant metastasis

 M1 - Regional or distant metastasis

Staging

Under the Enneking system, malignant tumors are classified into stages I-III, with further
subdivisions into A and B. Grade 1 and grade 2 tumors are stage I and stage II,
respectively. T1 and T2 tumors are stage A and stage B, respectively. Tumors with
distant metastasis are stage III (see Table 1 below).

Table 1. Enneking System for the Surgical Staging of Malignant Bone and Soft-Tissue
Tumors

Stage Grade Site Metastasis

IA G1 T1 M0
IB G1 T2 M0
IIA G2 T1 M0
IIB G2 T2 M0
III G1 or G2 T1 or T2 M1

Staging of Benign Tumors

The Enneking staging system divides benign tumors into latent, active, or aggressive
tumors (see Table 2 below). Latent tumors are asymptomatic and are usually discovered
incidentally. They reach a stage of nongrowth after a period of slow growth. Active
tumors are mildly symptomatic and may be discovered if pathologic fracture occurs or if
the tumor is associated with mechanical dysfunction. Active tumors usually grow
steadily. Aggressive benign lesions grow rapidly and usually are symptomatic and tender
on palpation. Table 2. Enneking System for the Surgical Staging of Benign Lesions

Stage Description Grade Site Metastasis

1 Latent G0 T0 M0
2 Active G0 T0 M0
3 Aggressive G0 T1 or T2 M0 or M1
Limb Salvage Surgery and Staging
The aims of limb salvage surgery are to cure disease and to preserve limb function for the
patient. The aims are usually achieved by using a combination of limb salvage surgery
and adjuvant therapy.

Limb salvage operations are indicated if the following conditions are satisfied:

 The tumor is situated in the extremities and/or the axial skeleton.

 The tumor margins are amenable to surgery.
 Only moderate soft-tissue extension is present.
 The neurovascular bundles are intact.
 Metastases are absent or amenable to curative treatment.
 The patient is in good general health.

Regarding resection margins, optimal surgical margins are 6 cm of healthy bone around
the bone margins and 2 cm of healthy soft tissue around the soft-tissue extent of the
tumor. If a malignant tumor is responsive to chemotherapy, smaller resection margins
may be acceptable.

The Enneking classification correlates the tumor stage with the excision margins as
follows:

Benign tumors

 Stage 1 tumors - Intracapsular excision (or curettage) is adequate.

 Stage 2 tumors - Extracapsular excision passing through the reactive zone is
needed.
 Stage 3 tumors - Wide margins of resection are required in stage 3 lesions
(aggressive benign tumors). In areas that are not amenable to wide excision,
marginal excision together with adjuvant treatment (eg, radiation therapy) may be
acceptable.

Malignant tumors

 Stage IA - These tumors are treated with wide excision and are usually amenable
to limb salvage procedures.
 Stage IB - Such tumors may be treated with wide excision, but the choice between
amputation and limb salvage depends on the estimated amount of residual tumor
left behind after a limb salvage procedure.
 Stage II - These tumors are high grade, are usually extracompartmental, and have
a significant risk for skip metastases. They usually are not amenable to limb
salvage operations and require radical amputation or disarticulation in most
patients. However, bone tumors responsive to chemotherapy may be treated
successfully using wide excision and adjuvant therapy.
 Stage III - Tumors at this stage are responsive to chemotherapy and may be
treated with aggressive resection. Those that are not responsive to adjuvant
therapy should be treated with palliative resection.

Radiograph
Radiography is the initial imaging modality in the evaluation of bone tumors. Some
benign lesions have characteristic radiographic features that make biopsy unnecessary.
Examples include fibrous cortical defects, bone islands, simple bone cysts, bone infarcts,
and typical variants, such as pseudocysts of the humerus and calcaneus. (See the images
below.)
 Frontal radiograph in a 9-year-old with trauma to the left knee
shows a well-defined, cortically-based lesion with sclerotic margins, situated on the
lateral aspect of the left upper tibial metaphysis. The lesion has the typical appearance of

a fibrous cortical defect. Enneking stage 0. Frontal radiograph in a 10-year-

old boy with pain of the left upper limb shows a well-defined, loculated, centrally located
lesion in the left humeral metaphysis. Overlying cortical thinning is noted. The lesion has

the typical appearance of a unicameral bone cyst. Enneking stage II. Frontal
radiograph in a 16-year-old girl with pain in the right upper limb shows a metaphyseal
lesion with ill-defined, permeative destruction. Cortical erosion and a Codman triangle
are seen (arrow). These are the radiographic features of an aggressive lesion that was
proven subsequently to be osteosarcoma. Enneking stage IIB.

Radiographic features can also help in distinguishing malignant from benign bone lesions
in many patientsLodwick and colleagues established a radiographic grading system based
on the analysis of the radiographic features of a bony lesion.[ The important radiographic
signs for grading bone tumors is listed as follows, in order of priority:

 Pattern of destruction - Geographic or not geographic, appearance of marginal

interface zone
 Penetration of the cortex by the lesion
 Absence or presence of a sclerotic rim
 Absence or presence of the expanded cortical shell, as well as its extent

The grading system developed by Lodwick and coauthors groups lesions into 3 grades.

 Grade 1A, 1B, and 1C - Benign lesions with edge characteristics ranging from
well defined to poorly defined
 Grade 2 - Low-grade malignant lesions with invasive features; applies particularly
to lesions demonstrating total penetration of the cortex
 Grade 3 - High-grade malignant lesions with invasive, permeative, and destructive
features
Another grading system divides bone lesions into 4 groups, each with individual
management algorithms.[

 Group 1 - Radiographically benign lesions that do not require further investigation

or treatment
 Group 2 - Lesions with a high likelihood of being benign but that should be
confirmed as benign by means of clinical or radiographic follow-up examination
 Group 3 - Benign lesions that require surgical resection because of aggressive
behavior or a risk of pathologic fracture
 Group 4 - Aggressive-appearing lesions that should be considered malignant but
on which a biopsy should be performed to confirm the diagnosis and histologic
grade

CT Scan
In the staging of bone tumors, computed tomography (CT) scanning has a role in the
detailed evaluation of local disease and in assessing the lungs for pulmonary metastases.

In evaluating local disease, CT scanning complements radiography because it can be used

to assess disease in areas that are not easily visualized with radiography, such as the spine
and pelvis. In addition, CT scanning is better for use in determining the type of cortical
destruction that has occurred and in assessing whether matrix mineralization is present.
CT scanning is also helpful in determining the internal contents of some lesions. (See the
images below.)

Frontal radiograph in an 11-year-old girl with back pain

shows an ill-defined, lytic lesion in the right iliac bone, just above the acetabulum
(arrowheads). The lesion was proven to be a Ewing sarcoma. The Enneking staging
system is not used for nonmesenchymal lesions such as Ewing sarcoma.

Computed tomography (CT) scan demonstrates the

characteristics of a lytic lesion, such as destruction of the thin, overlying cortex (arrow)

of the right iliac bone. Computed tomography (CT) scan

of the lungs shows multiple lung metastases (white arrows) and bilateral pleural effusions
(black arrows) in a patient with osteosarcoma of the humerus. Enneking stage III.

Although magnetic resonance imaging (MRI) is generally accepted to be superior to CT

scanning in the evaluation of local tumor spread, Panicek and colleagues have shown that
CT scanning and MRI are equally accurate in the staging of local disease in bone tumors.
CT scans have been shown to be more accurate than chest radiographs in evaluating the
lungs for the presence of metastases. However, CT scans may produce false-positive
results when small lung nodules are detected. Follow-up CT scans are useful in
monitoring the nodules.

Apostolova et al studied the use of single-photon emission computed tomography

(SPECT), compared with planar bone scanning, in 271 patients with tumors of the spine
and pelvis, and they suggested that SPECT be used in patients with equivocal findings on
planar imaging. Retrospective image interpretation was performed independently for
planar and SPECT scans. SPECT changed definite staging on planar images in fewer than
4% of patients, but in patients with planar equivocal staging, SPECT provided a definite
diagnosis in more than 80%

MRI
MRI has several advantages compared with other imaging modalities in visualizing and
staging bone tumors. In particular, accurate depiction of the soft tissues allows sensitive
detection of soft-tissue extension of and medullary involvement by a tumor. MRI can be
performed in several orthogonal planes. The absence of ionizing radiation and beam-
hardening artifacts are advantages of MRI compared with CT scanning. MRI is the
modality of choice for the imaging and staging of bone tumors.

Technical considerations for MRI

 Obtain magnetic resonance images before performing a biopsy.

 Position the patient comfortably to minimize motion artifacts.
 Sedation is often required in children.
 Place a vitamin E or cod liver oil capsule over the site of interest.
 Use the appropriate coils.
 Perform the imaging in at least 2 planes.

Sequences

 Perform conventional T1-weighted and T2-weighted, spin-echo sequences

because they provide reproducible images. Typically, pathology appears as areas
of low signal intensity on T1-weighted images and as areas of high signal
intensity on T2-weighted images.
 Fast spin-echo sequences with fat suppression also are popular imaging
sequences, and they are used in many centers because of the time-saving

advantages (see the image below). Osteosarcoma of the right

humerus. Fast spin-echo, T2-weighted, coronal magnetic resonance image shows
a large, metaphyseal-based lesion of mixed signal intensity with a large, soft-
tissue component (arrows). Enneking stage IIB.
 Short T1 inversion recovery (STIR) sequences provide fat-suppressed images
with T1- and T2-additive effects (see the image below). STIR sequences are
particularly useful for the detection of small lesions and bone marrow
 abnormalities Short T1 inversion recovery (STIR), coronal magnetic
resonance image shows the lesion's extent and a large, soft-tissue component.
Enneking stage IIB.

MRI contrast agents

The intravenous administration of gadolinium diethylenetriamine penta-acetic acid (Gd-

DTPA) increases the signal intensity on T1-weighted images by reducing the T1
relaxation time (see the images below). This feature is useful in distinguishing necrosis
from an active tumor and in differentiating cystic lesions from solid lesions. Although
some authors have indicated that MRI contrast agents do not improve tumor detection or
staging accuracy, most authors have found that the administration of MRI contrast agents
is useful in making difficult diagnoses.

T1-weighted, fat-saturated, axial magnetic resonance

image demonstrates the lesion and its soft-tissue component (arrowheads). Enneking

stage IIB. T1-weighted, fat-saturated, axial magnetic

resonance image acquired after the intravenous administration of gadolinium
diethylenetriamine penta-acetic acid shows marked enhancement and increased signal
intensity in the lesion and its soft-tissue component (arrowheads). Enneking stage IIB.

Gadolinium-based contrast agents have been linked to the development of nephrogenic

systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). The disease has
occurred in patients with moderate to end-stage renal disease after being given a
gadolinium-based contrast agent to enhance MRI or magnetic resonance angiography
(MRA) scans. NSF/NFD is a debilitating and sometimes fatal disease. Characteristics
include red or dark patches on the skin; burning, itching, swelling, hardening, and
tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble
moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs;
and muscle weakness.

Role of MRI in diagnosis

In many cases, MRI cannot provide a histologic diagnosis of soft-tissue lesionsHowever,
some lesions have appearances that are usually characteristic enough for a histologic
diagnosis based on the MRI findings. Examples of such lesions include lipomas,
superficial and skeletal muscle hemangiomas, benign neural tumors, periarticular cysts,
hematomas, and pigmented villonodular synovitis.

The most common soft-tissue lesions diagnosed with MRI are lipomas. They appear well
circumscribed, homogeneous, and isointense relative to subcutaneous fat on images
obtained with all pulse sequences. Thin, low-intensity septa also are sometimes seen in
lipomas.

Some general guidelines regarding the relationship between MRI signals and histologic
tissue types can be made, as follows:

 Tumor tissue is usually low in signal intensity on T1-weighted images and high in
signal intensity on T2-weighted images.
 The mineralized matrix is seen as areas of low signal intensity on T1-weighted
and T2-weighted images.
 Areas of hemorrhage are seen as areas of high signal intensity on T1-weighted
and T2-weighted images.
 The measurement of T1 and T2 relaxation times are useful in determining the
histologic features.

The imaging criteria that are used in differentiating benign from malignant lesions on
radiographs and CT scans have been applied to MRITypically, benign lesions are well
defined and sharply demarcated from the surrounding healthy tissue. Malignant lesions
are typically more extensive and involve surrounding tissue to a greater extent than do
benign lesions. However, MRI signal intensity alone is not reliable in distinguishing
between benign and malignant tumors.

Erlemann and colleagues reported that dynamic imaging after contrast enhancement is
approximately 80% accurate in differentiating benign tumors from malignant ones. MRI
may be useful in distinguishing benign from malignant cartilaginous tumors.[ Low-grade
chondrosarcomas have enhancing areas of fibrovascular septa with high signal intensity
on T2-weighted images, between lobules of hyaline cartilage. Janzen and coauthors
reported that the presence of abnormal marrow or soft tissue around a chondroid tumor is
suggestive of chondrosarcoma, especially if bony destruction or aggressive radiographic
features are lackingOther benign lesions with characteristic MRI findings include
osteochondromas, chondromas, aneurysmal bone cysts, and nonossifying fibromas

Role of MRI in staging

MRI is the modality of choice in assessing local spread of tumor (Enneking sites T1 and
T2). MRI can help in accurately detecting tumor involvement of neurovascular structures,
muscle compartments, growth plates, and joints.

MRI is accurate in determining involvement of the neurovascular bundle (see the image
below). MRA may provide additional information regarding neurovascular bundle
involvement. MRA can help in assessing peripheral vascular branches and tumor
neovascularity. By demonstrating treatment-induced changes in tumor neovascularity,
MRI may also help in assessing a tumor's response to treatment.

Fast spin-echo, T1-weighted, axial magnetic resonance

image obtained with fat saturation and the administration of gadolinium
diethylenetriamine penta-acetic acid, in a 13-year-old boy with osteosarcoma of the left
distal femur. The image shows enhancing tumor tissue that extends circumferentially into
the surrounding soft tissues. The distal femoral vessels are almost involved (arrowheads).
Enneking stage IIB.
Although MRI usually accurately depicts the intramedullary spread and soft-tissue
extension of a tumor (see the image below), differentiating tumor edema from true tumor
spread may occasionally be difficult. Typically, edema is seen as an ill-defined,
homogeneous, hyperintense area with a featherlike appearance. Edema tends to follow
the tissue planes; it has no mass effect, and unlike the distinct pseudocapsule of tumor
tissue, it possesses a fading margin. The administration of Gd-DTPA also aids in the
distinction of tumor tissue from tumor edema, because tumor tissue enhances and edema
does not. Intramedullary spread and soft-tissue extension of a tumor are more accurately
assessed with MRI than with CT scanning.

Fast spin-echo, T2-weighted, coronal magnetic resonance image with fat

saturation demonstrates the presence of a tumor within the medullary cavity (small
arrow) and extending to the midshaft of the femur (large arrow). Soft-tissue tumor
extension is shown (arrowheads). Enneking stage IIB.

The accuracy of MRI in the evaluation of joint involvement is controversial (see the
image below). Some authors have found MRI to be more accurate than CT scanning in
demonstrating joint involvement, although Bloem and colleagues found that CT scanning
and MRI provided similar results in their study. Enhancement of joint synovium after Gd-
DTPA administration may mimic tumor involvement. Joint effusion alone is not
diagnostic of tumor involvement.

Fat-saturated, T1-weighted, contrast-enhanced, coronal

magnetic resonance image in an 8-year-old boy with osteosarcoma of the right upper
humerus shows an enhancing tumor involving the shoulder joint. Enneking stage IIB.

Role of MRI in assessing the response to treatment

MRI is increasingly used to assess tumor response to preoperative chemotherapy (see the
images below). This assessment is achieved by evaluating changes in a tumor's size,
margins, signal intensity, and enhancement patterns.

Prechemotherapeutic, T1-weighted, axial magnetic

resonance image in a 19-year-old man with B-cell lymphoma of the left humeral head
shows a low–signal-intensity tumor involving the left humeral head (H). A soft-tissue
mass surrounds the humeral head (arrowheads), with involvement of the glenohumeral

joint (arrow). Enneking stage IIB. Postchemotherapeutic,

T1-weighted, axial magnetic resonance image shows that the humeral head has regained
normal signal intensity (H). Resolution of the soft-tissue mass is almost complete. No
glenohumeral joint involvement is present at this time. Enneking stage IIA.

After chemotherapy, a poor tumor response with no reduction in tumor size usually
indicates a poor histologic response; however, a substantial reduction in tumor size does
not necessarily indicate a good prognosis. In most patients with Ewing sarcoma, a marked
decrease in tumor size is an expected finding MRI findings of residual soft-tissue
components and tumor volume are usually correlated with the histologic response of the
tumor to chemotherapy. Tumors that decreased in size by 25% and 75% after
chemotherapy have a substantial overlap between good responses and poor responses.

Postchemotherapeutic MRI signal–intensity changes

MRI patterns are often unpredictable because tumors undergo necrosis, hemorrhage,
edema accumulation, granulation-tissue formation, and fibrosis after chemotherapy.
{Ref37}Some general indicators of a good response to chemotherapy include the
following:

 Decreasing signal intensity on T2-weighted images

 A circumferential hypointense rim combined with a decrease in size of the soft-
tissue component in patients with Ewing sarcoma
 Increased homogeneous signal intensity on T2-weighted images in Ewing
sarcoma (indicating tumor replacement by a hypocellular mucomyxoid matrix)

Contrast-enhanced MRI

The intravenous administration of Gd-DTPA helps in differentiating remnant tumor from

nontumorous tissue. Because of its greater vascularization, tumor tissue enhances more
than does nontumorous tissue. However, the presence of vascularized granulation tissue,
neovascularity in necrotic areas, or reactive hyperemia also may cause Gd-DTPA
enhancement on static MRIs, making tumor-free tissue difficult to differentiate from
tumor tissue.

Dynamic, contrast-enhanced magnetic resonance images are better than static images for
determining a tumor's response to chemotherapy (see the images below). Images in
patients who respond well to chemotherapy show a reduction in enhancement, whereas
those of patients who respond poorly show little or no reduction. Images should be
acquired by using short time intervals because reactive changes may show contrast
enhancement indistinguishable from that of tumor in the later phases of enhancement.
 Osteosarcoma of the left upper humerus. Contrast-enhanced,
dynamic, coronal, color magnetic resonance image shows the degrees of enhancement of
the tumor at different regions of interest (1-4). Enneking stage IIB.

Dynamic time-intensity curves show a steep uptake of

contrast material in the region of the viable tumor. A nonviable tumor shows a gradual
gradient of contrast agent uptake.

Parametric first-pass imaging and subtraction MRI have been used to increase the
detection of early arterial enhancement of residual viable tumor.

The use of magnetic resonance spectroscopy with phosphorus-31 in assessing changes in

tumor metabolism and in monitoring changes in spectra has been evaluated. There are
still limitations to this technique because of the difficulty of obtaining representative
spectra in all locations in the tumor, the contamination of tumor spectra with phosphorus
in adjacent soft tissues, and the technique's insensitivity to tumor heterogeneity.

Role of MRI in detecting recurrence

The differentiation between tumor recurrence and chronic posttherapeutic changes

remains a difficult challenge. In general, recurrence is suggested when T1-weighted
imaging demonstrates a hypointense lesion, which then enhances after Gd-DTPA
administration and appears hyperintense on T2-weighted images. Chronic,
posttherapeutic changes in a nonnodular lesion have low to intermediate signal intensity
on T1-weighted images and lack high signal intensity on T2-weighted images.

Static, contrast-enhanced MRI may not always be helpful in distinguishing recurrent

tumors from posttherapeutic changes because the latter may also show enhancement after
the administration of Gd-DTPA. Dynamic, contrast-enhanced MRI may be beneficial by
demonstrating early enhancement in tumor tissue that is not seen in posttherapeutic
changes.

Fatty marrow may reconvert to hemopoietic marrow in children with osteosarcoma who
have been treated with chemotherapy and granulocytic colony-stimulating factor. When
such reconversion occurs in a patient, the marrow's appearance on magnetic resonance
images may resemble that of a recurrent tumor, although reconverted marrow usually
appears bilateral and symmetric. The reconverted marrow's signal intensity is similar to
that of skeletal muscle, unlike the signal-intensity characteristics of a recurrent tumor.

Tumor recurrence may be hard to detect when orthopedic implants are in close proximity
to tumor sites. Orthopedic implants may cause susceptibility artifacts, making evaluation
of the surrounding tissues difficult. Susceptibility artifacts occur at interfaces of
structures with markedly different magnetic susceptibilities. Pure titanium orthopedic
implants are nonferromagnetic, whereas some alloys are ferromagnetic. Susceptibility
artifacts may be decreased by optimally positioning patients with orthopedic implants, by
switching the orientation of the frequency- and phase-encoding gradients, by using the
smallest voxel size, and by choosing fast spin-echo sequences. Susceptibility artifacts are
more severe in gradient-echo sequences and in sequences with a long echo time.

Radiologic Studies and Intervention

Nuclear medicine studies

Radionuclide bone scans are commonly obtained by using technetium-99m (99m Tc)–
labeled diphosphonate to stage bone tumors.

Radionuclide bone scanning has a role in detecting metastases, skip lesions, lesion
multiplicity, and postoperative tumor recurrence. Bone-forming, metastatic lesions in the
lungs (eg, osteosarcoma) are occasionally detected with bone scintigraphy (see the image
below).

Disarticulation of the right shoulder was performed in this patient with right
humeral osteosarcoma. A radionuclide bone scan obtained 5 months after surgery shows
abnormal focal areas of increased tracer uptake in the right scapula, left upper humerus,
and right distal femur (arrows). These uptake areas correspond to bony metastases.
Abnormal areas of increased tracer uptake are seen in the lungs, corresponding to
pulmonary metastases (arrowheads). Enneking stage III.

Areas showing increased tracer uptake in the skeleton should be evaluated by using
radiography. Further evaluation with CT scanning or MRI may be necessary if plain
radiographic findings are negative. Biopsy may be necessary if a positive result might
change the patient's treatment.

Ultrasonography

Soft-tissue masses and the soft-tissue components of bony tumors may be visualized by
using ultrasonography (US) The histologic diagnosis of the lesions usually cannot be
made by using US. The aim of US in the evaluation of musculoskeletal lesions is to
confirm the presence of a lesion, to determine if the lesion is cystic or solid, to assess the
relationship of the mass to the surrounding structures (eg, neurovascular bundle), to
evaluate the vascularity of the mass, and to guide interventional procedures if indicated.

Although color Doppler ultrasonographic evaluation of the mass is unreliable in

determining the histologic diagnosis of the lesion and whether the lesion is benign or
malignant, color Doppler US is a useful tool for monitoring the regression of tumor
neovascularity induced by therapy in patients with musculoskeletal sarcoma. When the
clinical findings suggest the recurrence of a soft-tissue sarcoma, US can be used as the
initial imaging technique for evaluation. US can also be used in addition to MRI when
susceptibility artifacts secondary to orthopedic hardware (including prostheses) prevent
the evaluation of specific areas.

Angiography
Currently, angiography is used only occasionally to evaluate neurovascular bundle
involvement. Its role has largely been replaced by cross-sectional imaging modalities.
Angiography still has a postoperative role in decreasing hemorrhage through the
embolization of tumor-supplying vessels (see the images below).

Pre-embolization, bilateral iliac angiogram in a 51-year-

old man with sacral chordoma shows tumor hypervascularity (arrows). Image courtesy of

Austin MM Htoo, FRCP, FRCR. Postembolization

angiogram shows a reduction of tumor vascularity. The embolization was performed
using Gelfoam and coils. Image courtesy of Austin MM Htoo, FRCP, FRCR.

Positron emission tomography scanning

Positron emission tomography (PET) scanning was developed in the 1960s and has
increasingly been used in some centers for detecting and staging malignancy. PET
scanning can be used to image tumor metabolism because of the detection of photons
emitted from tissue after the intravenous injection of a pharmaceutical, such as 2-
[fluorine 18]-fluoro-2-deoxy-D-glucose (FDG).

These photons are detected by the PET scanner and reconstructed into a 3-dimensional
image. Tumor metabolism is higher than that of normal tissue and shows higher FDG
uptake. In bone tumors, the degree of FDG uptake is related to the histologic grade of the
tumor. However, increased FDG uptake in a tumor does not necessarily indicate
malignancy, because increased uptake can also be seen in benign bone lesions, such as
nonossifying fibromas, fibrous dysplasia, giant cell tumors, eosinophilic granulomas, and
aneurysmal bone cysts.

According to Bischoff et al, combined FDG-PET-CT reliably differentiates soft tissue

and bone tumors from benign lesions. The authors performed a retrospective study to
determine whether integrated FDG-PET and CT (FDG-PET-CT) is more accurate than
the 2 modalities interpreted separately. Sensitivity, specificity, and accuracy for CT alone
was 81%, 84%, and 83%. Sensitivity, specificity, and accuracy for PET was 71%, 82%,
and 76%. Sensitivity, specificity, and accuracy for FDG-PET-CT was 80%, 83%, and
86%.

PET has been shown to have a sensitivity similar to that of serial CT scanning and MRI
for detecting lesions and for distinguishing postsurgical scarring from recurrent tumors.
However, the specificity of PET is higher than that of serial CT scanning or MRI.

In evaluating musculoskeletal sarcomas, when it comes to detecting recurrent tumor,

FDG-PET scanning has higher sensitivity and specificity, as well as a greater positive and
negative predictive value, than does iodine-131-meta-iodobenzylguanidine (MIBG)
scanning.
In summary, PET scanning appears to be better than CT scanning and MRI in depicting
residual or recurrent tumor after treatment. The main disadvantage of PET scanning is the
high cost of the equipment, which limits the modality's availability.

Radiologic intervention

Image-guided biopsy is less expensive and safer than open biopsy. The biopsy site should
be located where the needle tract will be excised in future surgery, because of possible
tumor seeding along the needle tract. Fluoroscopy with C-arm guidance, CT scanning,
and MRI can be used to locate the most appropriate biopsy site. The primary advantage to
fluoroscopy is its ability to create dynamic images.

CT-guided biopsy is usually employed if the lesion is located in a complicated part of the
anatomy, such as the upper thoracic spine or pelvis (see the image below).

Biopsy of a vertebral body tumor. A 17-gauge bone-

cutting needle is inserted through the left T11 pedicle (arrow).

For aspiration cytology, a fine-gauge needle is used. For a lesion that predominantly
consists of soft-tissue components, a cutting needle is usually chosen. For bone tumors, a
combined trephine and cutting needle is utilized. The needle tract should pass through the
bony and soft-tissue components of the tumor, allowing for complete histologic
examination. Hemorrhage, infection, and trauma to surrounding tissues are complications
of biopsy.

Conclusion
Imaging plays a crucial role in staging bone tumors. Radiography, occasionally with the
aid of CT scanning, is required for the detection and diagnosis of bone tumors. CT
scanning and bone scintigraphy are useful in depicting pulmonary metastases and the
multiplicity of lesions, respectively. MRI is the modality of choice in staging bone tumors
because it can accurately depict the local spread of tumor to surrounding tissues.
Contrast-enhanced MRI may be helpful in detecting viable posttreatment tumors.