BONE TUMORS : DIAGNOSIS AND

BIOPSY TECHNIQUES
dr. Muhammad Phetrus Johan, M.Kes, Ph.D, Sp.OT (K)
Introduction
• Most bone tumors are benign, although the true incidence of benign bone tumors
is unknown because most are asymptomatic and are usually discovered as an
incidental lesion.
• Primary malignant bone tumors are uncommon but are a significant cause of
cancer morbidity and mortality, especially among young people.
• Primary malignant bone tumors are classified according to the morphologic
features of the tumor cells and, partially, by the type of matrix produced by the
tumor.
• The initial work-up and staging evaluation of a patient with a suspected primary
bone tumor, particularly the diagnostic biopsy, is a critical component of
successful management.
CLINICAL PRESENTATION
• Patients with a bone tumor (primary malignant or metastatic) typically come to
medical attention because of localized pain or swelling of a few weeks' or months'
duration.
• Trauma, often minor, may be the initiating event that calls attention to a benign or
malignant bone tumor.
• Benign bone tumors are most often asymptomatic.
• The pain associated with malignant tumors, which may be mild at first, may be
aggravated by exercise and is often worse at night.
• A distinct soft tissue mass can sometimes be appreciated.
DIAGNOSTIC AND STAGING WORK-UP
• The goals of the diagnostic evaluation are to establish the tissue diagnosis,
evaluate disease extent, and assess the feasibility of surgical resection using the
principles of limb-sparing surgery.
• Imaging — A suspected bone tumor can be imaged using plain film radiographs,
magnetic resonance imaging (MRI), and/or computed tomography (CT); each
imaging modality has different benefits.
Differential Diagnosis
Differential diagnosis depends on
recognition of the tissue type and the
degree of aggressiveness.
• Osteosarcoma
• Chondrosarcoma
• Ewing sarcoma
• Other tumors
Osteosarcoma
• Osteosarcoma is by far the most common primary
malignant tumor arising in bone (myeloma excluded).
• Osteosarcoma, which is most common in the second
and third decades of life, is usually a high-grade
malignancy, although the low-grade central
osteosarcoma and parosteal osteosarcoma are
notable exceptions.
• Most often, osteosarcoma is located in the
metaphysis of a long bone
• Characteristic features of conventional
osteosarcomas (which account for the majority of
cases) include destruction of the normal trabecular
bone pattern, indistinct margins, and lack of
endosteal bone response.
Radiograph shows mixed lytic and sclerotic lesion
with osteoid matrix associated with malignant tumor
cells (arrow) and Codman triangle (arrowhead)
involving the proximal tibia.
Chondrosarcoma
• a condition of middle aged and older adults, can be
low, intermediate, or high grade.
• Cartilage can be recognized on imaging because it
tends to grow in nodules, has a very high water
content (making it bright on T2 weighted MRI and
dark on CT scan), and deposits mineral in dense "rings
and arcs," whose density can focally exceed cortical
The large tumor contains extensive areas
bone. of matrix mineralization. Aggressive lytic
destruction of the posterior part of the rib
and the thoracic vertebral body is noted
(arrow). Histology of these lytic areas
shows undifferentiated small round cells.
Ewing sarcoma
• Ewing sarcoma of the bone (as well as
the other members of the Ewing family
of tumors and all of the small round blue
cell tumors) has a "permeative" or
"moth-eaten" pattern on imaging with
very poorly defined margins.
• The tumors can be large and frequently
involve the diaphysis
"Onion skin" periosteal reaction AP (A) and lateral (B) view
• The characteristic periosteal reaction of the distal femur (arrows) in a 15-year-old female child
produces layers of reactive bone, with Ewing sarcoma. Multiple layers of periosteal reaction
deposited in an "onion peel" appearance simulate the appearance of the layers of an onion's skin.
Note the disruption of the outermost layer and the soft
tissue mass, suggestive of a malignant process.
Other tumors
World Health Organization (WHO) classification of tumors of bone
Other tumors
World Health Organization (WHO) classification of tumors of bone
Evaluation of the rest of the skeleton 
• Radionuclide bone scans or total body 18-fluorodeoxyglucose positron emission
tomography (FDG-PET) can evaluate the entire skeleton for the presence of
multiple lesions
• Bone scans are also limited by a lack of specificity, with most false-positive results
due to trauma, whether recalled by the patient or not.
• There is growing consensus that PET scans represent an excellent approach to the
clinical evaluation of bone metastases and possibly the evaluation of a primary
bone tumor.
• PET scans are more specific than bone scans for detection of bone metastases,
although they are possibly less sensitive (especially for osteoblastic foci) and
clearly more expensive.
Evaluation of the rest of the skeleton 
• Guidelines from the National Comprehensive Cancer
Network (NCCN) suggest either PET or bone scan in
the staging work-up of a primary bone tumor, and
imaging guidelines from the Children's Oncology
Group Bone Tumor Committee for both
osteosarcoma and Ewing sarcoma recommend
radionuclide bone scan and/or PET scan for whole-
body staging.
• Whole-body MRI has the potential to detect more
lesions in the axial skeleton (particularly the spine)
than bone scan, but it is generally not feasible in
most centers due to time constraints.
• Low-dose whole-body CT can also be used to assess
lytic lesions in patients with multiple myeloma,
which is discussed separately.
The images are from different patients and show different patterns of osseous metastases in radiographs. Arrowheads indicate lytic disease and arrows indicate blastic
disease. Image A is a lateral skull radiograph from a patient with prostate carcinoma and shows two well defined blastic metastases. Image B is a lateral skull radiograph
from a patient with lytic metastases and show irregularity of the zone of transition between the lytic lesion and normal surrounding bone (arrowheads). Image C is a
lateral skull radiograph from a patient with multiple myeloma and also shows lytic disease. Image D is a lateral radiograph of the thoracic spine in a patient with blastic
metastases (single arrow). Image E is an AP radiograph of the pelvis of a patient with lung carcinoma which shows a lytic metastasis in the right greater trochanter
(arrowhead). The metallic T-shaped structure in the pelvis is an IUD. Image F is an AP radiograph of the pelvis in a patient with treated breast carcinoma which shows
both lytic (arrowhead) and blastic disease (arrow) in the left femoral neck.
The reconstructed CT images are from three different patients and reflect different patterns of metastatic bone disease. The bone windows of the spine are projected as
sagittal reconstructions. The first (A) is a patient with breast carcinoma complicated by blastic metastatic disease of the thoracolumbar spine (arrow). The second (B) is a
patient with multiple myeloma and multiple lytic lesions in the thoracolumbar spine (arrowheads). The third (C) is a patient with breast carcinoma with both blastic
(arrows) and lytic (arrowheads) disease.
Staging system
• The staging system used by the Musculoskeletal Tumor Society for primary bone
sarcomas was developed by Enneking
• This system characterizes nonmetastatic malignant bone tumors by grade (low-grade
[stage I] versus high-grade [stage II]) and further subdivides these stages according to
the local anatomic extent (intracompartmental [A] versus extracompartmental [B]).
• The American Joint Committee on Cancer (AJCC) adopted a tumor, node, metastasis
(TNM) staging system in its 1997 fifth edition, and despite several modifications, it has
not been in widespread use for bone sarcomas.
• Compared with earlier versions, the latest 2017 revision of the joint AJCC/Union for
International Cancer Control (UICC) staging criteria has separate and distinct TNM
classifications for primary tumors arising in the appendicular skeleton/trunk/skull/facial
bones and those arising in the pelvis and spine
Bone sarcomas TNM staging AJCC UICC 8th edition
Bone sarcomas TNM staging AJCC UICC 8th edition
Bone sarcomas TNM staging AJCC UICC 8th edition
INDICATION FOR BIOPSY
Bone biopsy is indicated in the following circumstances:
• Whenever there is significant doubt as to the diagnosis of a benign or malignant
lesion
• When the histologic distinction among possible diagnoses could alter the planned
course of treatment
• When definitive confirmation of the diagnosis is required before undertaking a
hazardous, costly, or potentially disfiguring treatment
Doubtful diagnosis
• A symptomatic lesion with demonstrable
anatomical abnormality requires tissue
diagnosis unless a specific entity can be
confidently identified from the radiographic
imaging studies.
• As an example, a radiographic diagnosis of
"nonossifying fibroma" does not require a
definitive tissue biopsy, while a nonspecific
"benign-appearing bone lesion" may
warrant biopsy confirmation. A non-ossifying fibroma can usually be diagnosed with
confidence from imaging studies alone, and seldom
requires either biopsy or operative intervention. The lesion
(arrows) is recognized by its eccentric (cortical) origin,
"polycyclic" outline, well-formed thin sclerotic wall, and
progressive ossification, beginning with the portion of the
lesion furthest from the growth plate.
Metastatic disease
A bone biopsy may sometimes be indicated to confirm the diagnosis of
metastatic disease prior to definitive treatment with radiation or chemotherapy
Planning the biopsy 
• The biopsy must be performed such that the entire
biopsy tract can be easily excised during later definitive
surgery.
• The length of the biopsy incision should be kept to a
minimum so that the final resection does not sacrifice
excessive normal tissue and the wound is easily closed
• Open biopsies that are performed with a transverse
rather than longitudinal incision may compromise more
than one compartment, and the neurovascular bundle
may also be contaminated. A properly performed
incision (arrow) is small
• Many bone tumors are hypervascular and can bleed and longitudinal.
profusely after even a small incisional biopsy.
 The CT-guided needle biopsy of this
osteosarcoma was performed using a posterior
approach. Although targeting the lytic soft
tissue component (arrow) for sampling was
appropriate, the posterior needle track would
have been difficult to excise with the specimen
and could theoretically have compromised the
surgery. In this case, however, amputation was
performed.
 CT-guided needle biopsy of this posterior soft
tissue mass (arrows) was accomplished using an
anterior approach, which would not have
compromised a planned limb-sparing
procedure because the needle track could be
entirely excised with the resection specimen.
BIOPSY TECHNIQUES
Needle biopsy — Progress in imaging technology and needle guidance has made it
possible to biopsy virtually all parts of the body safely and effectively.
• Fine needle aspiration biopsy — The fine needle aspiration (FNA) biopsy can be
performed with or without image guidance.
• Core biopsy — Core biopsies without image guidance can be performed in the clinic
setting if the mass is large and easily palpable, and this may result in considerable cost
savings when compared with either image-guided or open biopsy
Operative biopsy — An operative or open biopsy is performed following standard skin
preparation and draping. Antibiotics are not typically administered prior to the biopsy;
they are not necessary as long as the standard sterile technique is used. Furthermore,
since infection (osteomyelitis) can sometimes masquerade as a neoplastic process, the
use of antibiotics may compromise the utility of cultures taken at the time of biopsy.
Technique
• Fine needle aspiration technique — Material for cytological preparations can be obtained using any of the fine-
caliber cutting needles (eg, the Chiba needle). Placing the needle into the tumor and moving it rapidly in and out in
a piston-like movement while maintaining suction with a small amount of saline in a syringe will usually exfoliate a
sufficient number of cells. The sample should be immediately spread on a slide and fixed to prevent air-drying.
• Core biopsy technique — Side-cutting needles (eg, the Tru-Cut needle) result in well-preserved soft tissue
samples. Newer automated spring-loaded biopsy devices (eg, the TEMNO device) come in a variety of gauges and
have calibrated sheaths that allow them to be accurately placed at the appropriate depth. The length of the core
sample can be adjusted on several of these devices to suit the size of the lesion.
• Anesthesia — Most needle biopsies of bone can be performed with local anesthetic, either with or without
conscious sedation. In general, malignant lesions, particularly metastatic foci, result in less procedural pain than
benign lesions
• Accuracy of needle biopsy — The "success" of bone biopsy ranges from 90 to 95 percent for metastatic lesions,
with lower rates (70 to 80 percent) reported for primary bone tumors and infectious lesions in most series. Sclerotic
lesions are more difficult to biopsy than lytic lesions, and accuracy rates for such lesions tend to be lower in many,
but not all, series
• Complications — Complications are rare with image-guided needle biopsy. Some
complications may occur with any procedure that breaks the skin (eg, infection,
bleeding), while others are anatomically specific (eg, pneumothorax, nerve injury,
airway compromise, damage to the great vessels).
• Although it was previously thought that spinal biopsies have a higher risk of
complications than biopsies of appendicular lesions, in two series with a combined
150 spinal biopsies, there was only one complication
SPECIMEN HANDLING
• Fine needle aspiration — FNA biopsy yields cells or cell clusters that are suitable
for cytological preparation, which can be done rapidly. Although the specific tissue
diagnosis may require additional time and special processing, the presence of
diagnostic material in the specimen can often be confirmed during the biopsy
procedure. This permits additional "passes" to be performed as required and
decreases the need for repeat procedures.
• Frozen section preparation — Frozen section preparation of large core samples
can be performed as for an operative specimen. However, analysis of tissue
prepared in this way is less accurate than standard permanent fixation, and if the
sample is small, it is preferable not to attempt a frozen section.
SPECIMEN HANDLING
Special specimen handling requirements — The extensive pathologic evaluation that is often required to ascertain the
correct diagnosis may require special handling for all or part of the specimen:
• "Touch preparations" stained with Wright's stain for certain hematologic malignancies.
• Decalcification to adequately process the biopsy.
• Cytogenetic (karyotyping), flow cytometric studies, and establishment of cell lines (in tissue culture media).
• Specialized immunocytochemical studies for diagnosis.
• Molecular analysis on formalin fixed paraffin embedded (FFPE) or frozen tissue (cryopreserved at -70°).
• Cytologic imprinting for fluorescence in situ hybridization (FISH) studies (alcohol-fixed and air-dried).
• A sample of tissue, aspiration of fluid, or swab should be sent for microbial culture if osteomyelitis is in the differential diagnosis.
• Ultrastructural examination by electron microscopy (in glutaraldehyde buffered solution) is seldom used as a diagnostic tool.
• If lymphoma is suspected, the hematopathologist should be alerted ahead of time for proper tissue handling. Samples should be
collected in saline and sent to the laboratory where they can be triaged to flow cytometry, cytogenetic and molecular studies. It
can be difficult to obtain diagnostic tissue from a lymphoma due to its susceptibility to severe "crush artifact." Multiple biopsies
are often needed and even then may not yield a definitive diagnosis.
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