BONE & JOINT TUMORS

New tissue growth can have a three-way evolution:

1. Exceeding repair will be interpreted as reactive tumor
(keloid scars or keloma).
2. Benign tumors present spontaneous proliferation with no
invasion or metastasis.
3. Malignant tumors with uncontrolled proliferation and
capable of metastasis.

The involved terms should be explained:

- Hyperplasia means the accumulation of normal cells
due to exceeding proliferation (e.g. callous tissue, synovial
chondromatosis, etc.)
- Hamartroma and dysplasia originate in unused
embryonic tissue; such tissue can have a parallel,
autonomous and pointless development; their maturity is
reached at skeletal maturity. They have coherent structure
and prevail in one half of the body (exostosis, some
fibromas)
- Tumors are neo-formations originating in various
tissues. They can be benign, low – malignant or malignant.

They can have multiple ways of evolution:

A) Benign

They are characterized by:

- slow autonomous growth ;
- pointless evolution
- differentiated cells preserving typical features and
functions;
- expansible growth with clear limitation towards
surrounding tissues; often encapsulated;
- no relapse following complete resection; no metastasis.

236
According to their evolution they can be:
1. Inactive (static or slow)(stage I)
They are sealed within a mature fibrous capsule or bone
cortical; they remain localized and do not cross the
compartment limit. Reactive area is minimal. Histology shows:
well-differentiated matrix, no hyper-chromatism, differentiated
cells, no anaplasia (modified cell components like nucleus), no
pleomorphysm (various altered shapes), clinically symptom-
less.

2. Active (stage II)

They have no limited growth - they keep on growing, inducing
deformity to bone or cartilage. They remain encapsulated, with
possible lobular aspect. Minimal marginal reactive area.
Clinically, medium intensity symptoms may occur, along with
pathological fractures or other malfunctions.

3. Aggressive (stage III)

They have some invasive power. There is low penetration
within normal tissues; capsular or capsule-like limitation may
be observed, even if it does not limit growth. This capsule like
formation still has the power to prevent skip-metastasis. It can
invade neighboring compartment. Histology will show
different degrees of maturation and high division potential.
Clinically, they may show tumor compression signs and
possibly fractures.

B) Low malignancy tumors

- slow but more obvious progressive growth than in benign

ones;
- unclear border with invasive aspect;
- incomplete resection leads to local relapse;
- some of them may produce late metastasis;
- can switch to malignant (egg. Chondroma 1-2nd degree);

237
C) Malignant tumors

- rapid and pointless growth; no coherent border or limitation;

invasive and infiltrating;
- atypical cells; nuclear mutations and invasive tendency;
- anarchic architecture
- frequently, local relapse and with constant metastasis;

Biological behavior of tumors

This defines their possibilities of growing beyond natural

limits. Anatomical limits will include: capsule, bone or fibrous
layer around the lesion and the reaction area consisting of
mesenchyma, neo-vascular and inflammatory tissues,
bordering the capsule outside. Compartment limits include
bone cortical, periosteum and joint cartilage.
Breaking these limits makes tumors become extra-
compartmental. If the capsule is not broken, then the
development is intra-capsular.

Diagnosis

Diagnose is set upon the following:

1. Clinical and anamnestic features;
2. Radiological criteria;
3. Biological criteria;
4. Pathological anatomy criteria;

1. Clinical and anamnesis criteria

a) Frequency - bone malignant tumors account for 1,2% of

the tumors (genital, digestive, respiratory and systemic).
b) Etiology – is unknown but numerous favoring factors have
been described: degeneration of pre-malignancy
238
 (chondroma, Paget’s disease, chronic festering in
osteomyelitis, etc.), nuclear or x-ray exposure.
c) Age of the subject can help identification of tumor. For
instance lythic (melting) osteosarcoma will occur mostly at
14-19 years, ossifying sarcoma occurs at 20 -25 years,
chondrosarcoma after 35, “Giant cell” sarcoma between 20-
30, Ewing tumor between 15-20, multiple myeloma after
50 years, etc.
d) Gender - most of the bone malignancies will prevail in
males, with the exception of “Giant cell” tumors, affecting
mostly women.
e) Symptoms will occur late and with poor significance; they
will merely determine the initiation of additional tests on
the subject:
- Pain- has variable intensity (from weak to maximal,
which is enhanced at night time). Location can be at tumor
site, irradiated or diffuse; strong pain (because of periosteal
pressure) can be consistent with rapid and invading
evolution of an aggressive tumor.
- tumefaction (swelling) has variable location and late
occurrence;
- muscle hypotrophy is a late determination of antialgic
self-induced immobilization;
- local and regional adenopathy;
- inflammatory response in some cases (Ewing tumor);
- variable functional disability of joints;
- pathological fractures following minor trauma;

f) Rapid development
One of the most interesting (but also disturbing)
characteristic features of malignancy is rapid growth.
Growth speed of malignant tumors is considerably higher
than the one of normal cells, due to their hyperactive
behavior. The pointless growth and multiplication of such
tumor cells is consistently induced by their lack of contact
receptors, which in normal tissue wounds will inform cells

239
 of their neighbor presence and consequently prevent
overgrowth.

g) Tumor site – may be characteristic.

- Giant cell tumor is currently located in metaphyseal area,
occurring after epiphyseal plate involution. Giant cell
tumor cannot co-exist with epiphyseal plate.
- chondroblastoma will develop mostly in epiphyseal
areas and upon apophysis, over-riding the epiphyseal plate.
- Adamantinoma will develop upon tibia or ulna;
- Chondroma may develop within skull base, sacrum or
spine;
- Periosteal tumors are less malignant than those inside
bone;

h) Local hyperthermia as indicated by thermograph

2. Radiological criteria

There are several types of imagery available for adequate

tumor exploration and monitoring.

a) Bone radiograph (x-ray) will indicate the site and the

spreading of the tumor. Biopsy will be radiologically
guided; x-ray check up is needed every 30-40 days. Two
types of tumors will be found on x-ray:
- aggressive type – massive ostheolysis with unclear
border, destroyed cortical, low osteogenetic reaction;
- low malignancy type – slow growth and non-infiltration;
clear border ostheolysis ; peri-tumoral orthogenesis and
preserved cortical.

b) CT scan is complementary to regular x-ray; it will enhance

the visibility of tumor limits by using contrast substances. It
will display tumor extension within medullary channel, its
relationship with blood vessels, nerves and viscera. It also
240
 enables us to monitor the result of specific treatment
(chemical and radiation therapy).

c) Arteriography, lymphography and phlebography will show

tumor extension, its relationship with blood and lymph
vessels; may witness the treatment effectiveness.
In benign tumors, modifications are related to neighboring
compression; in malignancies, rich, anarchic, atypical
newly formed blood vessel network will be observed.
d) Scintigraphy information will indicate the activity index
and by exploring the whole skeleton, it may even reveal
tumors, which are invisible to x-ray. It will also show the
real extent of the tumor and the skip metastasis and the
response to adequate treatment. Its alleged dangerous effect
upon patient is largely mystified and should be regarded as
negligible.
e) MRI - or NMR. (Nuclear Magnetic Resonance) allows
better resolution, as it is based on a totally different system.
Strong magnetic field is able to reveal the slightest
modification of tissues by scanning the area in various
directions and allowing a 3-D visual approach. The use of
MRI is only limited by the presence of metallic implants,
but only those made out of iron alloys.

3. Lab tests

Biological assessment can be extremely relevant. There are

some very significant alterations:
- ESR is increased over 50 mm/h
- increased potassium rate
- low calcium rate
- low protein rate; low albumin rate;
- increased fibrinogen and gamma globulin
- increased APH (Alkaline Phosphatase) in sarcoma; can
be used as treatment referential, as it follows tumor
evolution;
241
- LDH. (Lactic Dehydrogenase) is increased in Ewing
tumor, leukemia and lymphoma.
Immune histo-chemical tests will indicate tumor cell markers.
Flow cytometry will show the content of DNA. Histo –
chemical tests may also reveal increased MPZ
(mucopolysaccharide) content, conversely proportional to the
differentiation degree.

4. Pathological anatomy and histology

Macroscopic examination can be performed during surgery.

Histo-pathological examination of the biopsy samples, which
can be harvested with special needles or devices, will allow
observation of cell type, malignancy features and indicate the
precise type of tumor.
Biopsy can be done by:
- small fine needles – with the disadvantage of harvesting
tiny amount of tissue;
- trocar needle – allowing 2-3 mm large samples of tumor
tissue;
- offhand biopsy – indicated in case of other types of
biopsy not being useful. It has to be performed by avoiding
exceeding laceration and it allows a minimal 1 cm³ sample;
- removal biopsy – main sample is the removed tumor
itself. It is indicated when there is evidence of malignancy.
Variable shape and dimension, atypical mitosis and a modified
nucleus – cytoplasm ratio, characterize tumor cell. There are

Classification

a) Anatomical and clinical (Lichtenstein)

This classification allows us to understand the origin of

tumors, regardless of their type. The best way to assess them is
within a comparative table:

242
 Hystogen Benign Low malignancy High malignancy
esis
I. Fibrous 1. Histiocyte 1. Grade 1 and 2 fibro 1. Fibro
& fibroma sarcoma sarcoma (3rd
histiocyte 2. Benign fibrous 2. Malignant fibrous and 4th
histiocytoma histiocytoma (1st and degree)
3. Giant cell tumor 2nd degree)
4. Desmoid fibroma
2. Malignant
fibrous
histiocytoma
(3rd and 4th )
II. 1. Exostosis 1. Central 1. Central
Cartilage 2. Epiphyseal chondrosarcoma (1st chondrosarco
dysplasia and 2nd degree) ma (3rd
3. Chondroma 2. Peripheral degree)
4. Chondroblastom chondrosarcoma (1st 2. Peripheral
a and 2nd degree) chondrosarco
5. Chondromyxoid 3. Periosteal ma (3rd
fibroma chondrosarcoma (2nd degree)
degree) 3. Periosteal
4. Clear cell chondrosarco
chondrosarcoma ma (3rd
degree)
4. Mesenchyma
chondrosarco
ma
III. Bone 1. Osteoma 1. Cortical linked 1. Classic
2. Osteoid osteoma osteosarcoma osteosarcoma
3. Osteoblastoma 2. Periosteal 2. Hemorrhage
4. Fibrous dysplasia osteosarcoma osteosarcoma
5. Osteo-fibrous 3. Low malignancy 3. Small cell
dysplasia central osteosarcoma osteosarcoma
4. Osteosarcoma
tosis
IV. ----- ----- 1. Lymphoma
Marrow 2. Plasmocytom
mesenchy a
ma 3. Leukemia;
Hodgkin;
V. 1. Hemangioma 1. Hemangio- 1. Angiosarcom
Vascular 2. Lymphangioma epithelioma a
2. Hemangio- 2. Hemangio-
pericytoma pericytoma
VI. 1. Neurinoma -----
Nervous 2. Neurofibroma
VII. 1. Lipoma ----- Liposarcoma
Adipose
VIII. ----- Adamantinoma Malignant
Mixed mesenchynoma
IX. ----- Chordoma ------

243
Notocorda
l

This classification was considered by WHO in 1972.

c) Therapeutical classification of Hennequin;

This classification represents the complex assessment of three

important factors:
- Malignancy degree (G);
- tumor extension (T);
- presence of metastasis (M);

Malignancy degree (G)

This parameter is a marker for biological aggressiveness.
There are two G degrees, G1 and G2.
G1 characterizes the low malignancy (1st or 2nd degree
Brothers). Its main features are:
- histology – low mitosis rate with moderate
differentiation;
- radiology – cortical destruction, endosteal irregularities,
periosteal reaction (Codmann triangle);
- clinical aspect – painless and slow growth, seldom
remote metastasis;

G2 is the marker of high malignancy (3rd and 4th Brothers

degree). Main features are:
- histology – frequent mitosis, immature and less
differentiated matrix, anaplasia and hyper-chromatic nuclei;
- radiology – more destructive and also invasive lesions;
- clinical aspect – painful and rapid growth, neighboring
invasion, regional or / and remote metastasis;

The T (or extension) factor

244
This factor is important for assessing prognosis and
establishing a surgical strategy.
T1 - means intra-compartmental tumor or tumor inside the
original compartment;
T2 - means extra-compartmental tumor (beyond the origin
compartment);
The compartment notion involves a well-defined anatomical
space able to oppose tumor extension, such as: cartilage, joint
capsule, aponeurosis, periosteum.

The M (or metastasis) factor

The risk or the presence of metastasis is an important factor

that can help prediction and treatment strategy.

Mo - lack of obvious metastasis;

M1 - obvious metastasis;

All three elements can help us describe the evolution stages.

Stage I - low malignancy tumors –

I A - G1 T1 Mo
I B - G1 T1 Mo

Stage II - increased malignancy tumors

II A - G2 T1 Mo
II B – G2 T2 Mo

Stage III - low or high malignancy tumors, but with the

presence of metastasis:
III A – G1-2 T1 M1
III B - G1-2 T2 M1

There is a classification of Ennequin for malignant tumors

(1980).

245
 Stage IA IB II A II B III A III B
G grade G1 G1 G2 G2 G 1-2 G 1-2
T factor T1 T2 T1 T2 T1 T2
M factor Mo Mo Mo Mo M1 M1
Clinical Slow Slow Fast Fast ---- ----
evolution
scintigraph + + + + ---- ----
y beyond beyond X-ray
X-ray limit
limit
X-ray grade 1 2 3 3 2 3
Angiograph Light peri- Light Clear Clear peri- High reaction of
y tumoral peri- peri- tumoral vascular
vascular tumoral tumoral vascular lymph-
reaction vascular vascular reaction nodes
reaction reaction
MRI Unclear Extra- Unclear Extra- Presence of metastasis in
border, but compart border, compartmenta lung, bone, lymph-nodes,
inside mental but inside l origin or etc.
compartme origin or compart expansion
nt expansio ment
n

There is also a similar Ennequin classification for benign

tumors.

Stage 1 (non-active) 2 (active) 3 (aggressive)

G grade Go Go Go
T factor To To T 1-2
M factor Mo Mo M 0-1
Clinical aspect Symptom- less; Symptomatic Aggressive;
no growth; growth; spreading invading
healing; toward neighboring neighboring
tissues; tissues;
X-ray grade 1 2 3
Scintigraphy Negative Positive inside Positive even for
lesion peripheral line
Angiography No vascular Modest vascular Important neo-
reaction reaction vascular reaction
MRI Clear border; Clear but large Unclear margins;
thick capsule; borders; thin lack of capsule;
homogenous capsule; lack of
content; homogenous homogenous
content; content;

Treatment principles

246
It is obvious that the treatment of tumors has to rely upon
several means of therapy, mostly applied simultaneously.
There is a complex approach involving surgery, radiotherapy
and chemical therapy.

1. Surgical approach

This type of treatment is depending on tumor type, stage and

location. Given the oncology-based principles, there are
several types of surgical approach:
a) intra-capsular / intra-lesion approach;
b) marginal – allowing the entire tumor removal by using the
cleavage space between tumor and the neighboring tissues;
skip metastasis may be present in malignant tumors;
c) large approach – meaning the overall removal of tumor
together with surrounding assumed healthy tissues (without
touching the capsule or capsule – like formation); there can
be skip metastasis in high malignancy tumors;
d) radical or compartmental – tumor is removed together with
originating anatomical compartment; no resting skip
metastasis;

The approach is defined more by the quality of the resected

neighboring tissue than its pure quantity.

2. Radio-therapy

There is a certified effect upon bone, soft tissues and tumor

itself.
In soft tissues, radiation may determine early radiation
dermatitis, radiation-induced fibrosis.
Bone exposure to radiation will induce necrosis and increased
fragility.
Tumor will be subject to necrosis and permanent healing in
sensitive ones (like reticulo-sarcoma) or may undergo
palliative transformation, according to dosage and amount of
exposure.
247
3. Chemical therapy

Chemical therapy is currently using cytotoxic anti-blastic

substances. This type of effect is also present upon normal
cells, but cyclic administration in coordination with other
drugs will decrease action in normal cells and energize action
upon malignant ones.
These drugs belong to several chemical groups:

1. alkylant
2. anti-metabolic
3. alkaloid
4. anti-blastic antibiotic

1. Alkylant agents act by their alkyl groups able to penetrate

the DNA and compromise its function, leading to mutation
and death of the cell. Most used are: CPM (cyclo-
phosphamide) , iso-phosphamide (IPM), cis-DDP, BCNU;

2. Anti-metabolic agents act within protein synthesis function.

Methotrexat (MTX) is most used in this group.

3. Alkaloid acts upon synthesis of micro-tubes for mitosis

trails, thus interrupting the mitosis cycle. Most used are:
Vinblastine , Vincristine (VCR), etoposide (VP 16);

4. Anti - blastic antibiotic inhibits cell growth. By joining the

nucleotides, they block transcription within DNA and
RNA. Most used are: D(ACD) actinomycin, DBN
(doxorubicin), adriamycin (ADM), bleomycin (BLM) and
mitomycin (Mit.C).

Here are some examples of anti-blastic use:

- for osteosarcoma, most useful are: MTX, Doxorubicin,
Aphosphamide. Association of these drugs can render some
50-75% survival rate.
248
- For Ewing tumor, most efficient are: CPM, Vincristine,
ETP, Actinomycin.
Chemical therapy can be indicated with two clear options:
- pre-operative (neo-adjuvant) , which is given as infusion
or intra-artery for 2-3 months. Positive evolution means
necrosis of tumor and obvious regression of aggressiveness.
A good answer means a 90% necrosis. Capsular limitation
grows thicker and differentiation becomes more clear.
Amputation can be avoided in some cases by using such
approach.
- Post-operative (adjuvant or complementary), useful in
metastasis creating tumors. Immunity depression is one of
the main problems when such approach is used.

Interferon is acting at cell level: delays growth, delays mitosis

and cell differentiation, with results similar to chemical
therapy.

Therapeutical approach in malignant tumors

These therapeutical means can and will be employed in a

coherent manner, according to carefully planned programs.
The programs contain a detailed planning of action by each
and every therapeutical approach. They are assembled in
simultaneous or subsequent proceedings. Biological tests are
frequently run according to a pre-programmed time- table or
whenever there is a need for them.
The therapy program is designed according to the stage of the
tumor, as type of treatment, dosage of drugs, radiation dose or
surgical proceeding also depend on it.

Stage I A

- large but conservative resection (tumor is still inside

originating compartment, but skip metastasis may be
present inside cover tissue); Used in chondrosarcoma grade
I-II, cortical osteosarcoma, chordoma or adamantinoma.
249
Stage I B ( G1 T2 M0 )

- large resection is required; amputation is recommended

in case of relapse or if the main blood supply of the limb
segment has to be sacrificed.

Stage II A ( G2 T1 M0 )

– large, compartmental resection if no malfunction is resting.

Amputation and additional therapy (chemical and radiation)
required in Ewing tumor.

Stage II B ( G2 T2 M0 )

- amputation or dis-articulation of the limb is required.

Additional treatment due in some cases for preventing
relapse.

Stage III ( G1-2 T 1-2 M1 )

- adequate approach on primitive tumor is required.

Metastasis control by chemical therapy and pin-point
surgery , as indicated in
chondroblastoma, giant cell tumor
or less malignant tumors.

107. Local, regional or segmental

approach on a benign tumor

Patient check-up

Clinical and x-ray check-up at tumor

site and thorax is due every 2-3
months. After 2 years, the interval can
250
be extended to 4-5 months. Within the 5th year the check-up is
performed twice and later on yearly.
The biological check-up consists of:
- alkaline phosphatase; LDH; creatinine; urea; ESR;
- blood cell count and rate assessment;

Therapeutical approach in benign tumors

Therapeutical approach is also consistent with a number of

factors, tumor stage / grade to begin with.
Grade I – non active
Dysplasia (bone cyst;
chondroma; exostosis; etc.) will
require simple removal of the
lesion.
Grade II – active (Osteoid
osteoma; chondroblastoma;
osteoblastoma; aneurysm cyst;
etc.)
In these cases, tumor should be
removed by cutting off its
margins. If this is difficult to do,
removal of the lesion should be
followed by local cauterisation
with substances like: phenol, 90°
alcohol or liquid Nitrogen.

108. Surgical approach in malignant tumor

Grade III - aggressive (giant cell tumor and some others)

Large resection should be performed in such cases. If there is a

T2 type and / or repeated relapse, amputation should be
considered.

251
The following chapter is dedicated to the brief description of
some of the most significant tumor types.

Fibrous origin tumors

1. NOG (non-osteogenetic) Fibroma

It is a dysplasia affecting children aged 4 – 10. Commonly

placed on the extremities of femur and tibia / fibula, with
metaphyseal and diaphysary development. Generally lacking
symptoms, except for slightly painful occasionally palpable
“bump”. The x-ray image is classic: longer cavities, bubble-
like shaped and with clear sclerotic contour.
The cavity is filled with yellowish, compact and elastic tissue,
consisting of long, fibrous cells. Smaller tumors heal
spontaneously within 2 years. Emptying the content and filling
it with bone graft may surgically treat larger ones.
Spontaneous fractures are commonly treated conservatively.

2. Giant cell tumor (GCT)

This is a multiple-nuclei cell formation developing inside

bone. It will occur mostly in women aged 20-30 and in
metaphyseal areas of femur and tibia, less frequent in radius
and pelvis.
Symptoms include rheumatism-like pain, palpable non-
adherent tumor, and limited joint movement range when
located near joint and sometimes spontaneous fracture.
The x-ray assessment will unveil a quite characteristic
ostheolysis area; this proves to be eccentric, homogenous, with
the aspect of “blown” and sometimes thinned cortical. There is
little, if any, osteogenetic reaction and sometimes it may
display a multiple chamber pattern.
Pathology shows a soft, red-brown content of the tumor,
with clear separation from bone marrow channel; cortical bone
may be thinned, but with no additional fibrous or bone
formation. Fibrous stripes may divide inside little chambers
252
filled with clotted blood. Aggressive tumors will affect the
surrounding muscle and other soft tissues.
Histology will display two main elements: giant cells (10-
100 micron wide) with some 50-100 nuclei gathered in the
middle; weak, single-nucleus cell fibrous tissue but with very
rich vascular network. The histology looks the same for the 2nd
or 3rd degree and even for relapse tumor.
The clinical stage classification is as expected: a fade
symptom list for the 1st degree, clear and specific
characteristics for stage 2 (active) and rapid growth with soft
tissue invasion for stage 3.
Evolution and prognosis is rather difficult to assess. The
tumor is generally having a slow, benign evolution;
sometimes, after a long quiet evolution it turns aggressive.
Relapse is more frequent in tumors treated within the first 3
years of evolution and less until 10 years. This benign tumor
can exceptionally give
metastasis (lung), but
they have a slow
evolution, with very
good survival rate.

109. Giant cell tumor -

microscopy

Giant cell sarcoma may occur in very special

circumstances. Untreated GCT may exceptionally turn
malignant. It is also a rare possibility that sarcomas develop
upon relapse of treated GCT. Conversely, it is quite often to
encounter sarcomas developing upon irradiated GCT (more
than 400 rad) within 10 years. It should be clear that radiation
exposure is not an option for GCT treatment.
The presence of the epiphyseal plate excludes GCT. Bone
cyst, local bone dystrophy, chondrosarcoma and osteosarcoma
should be differentiated in adults.

253
 Treatment is according to stage: common type will benefit
from total excision, local cauterisation with adequate agents
(phenol, alcohol) and cavity bone substitution (bone-graft,
mineral substitution or even cement). Extensive type requires
segmental resection. Spine, pelvis or sacrum localization may
require selective artery obstruction. Relapse should be
considered for amputation. There is some 10% relapse in usual
approach and practically none after large resection. Adequate
monitoring is needed within the first five years.

3. Fibrosarcoma (FS)

FS is a tumor originating in the fibroblasts of the Havers

systems, mostly in the femoral or tibial extremities. It is a rare
tumor, accounting for 2% of all bone malignancies.
Symptoms include ever growing pain, firm swelling,
decrease in neighboring joint performance and ultimately
pathological fracture.
X-ray reveals massive ostheolysis with irregular contour
and neighboring tissue invasion. There is weak periosteal
reaction. Pathology will describe central or peripheral types.
Tumor will display irregular content, with cyst-like and fibrous
formations. Microscopy shows abnormal cells, deployed in
fish-scale like collagen formations and with modified
fundamental substance. FS displays 4 Broders degrees, with a
more differentiated first degree. It has to be differentiated from
other malignant
tumors. Evolution is
slower for lower
degrees; more rapid
growth and metastasis
will characterize 3rd
and 4th degree.
110. Perforated
(gunshot) aspect of
skull bones in
multiple myeloma
254
 Treatment consists of large resection for grade 1 and 2 and
radical one for 3 and 4. Post-operative chemotherapy is
compulsory in highly malignant FS.
Prognosis is rather poor as only 30-40% of the patient may
expect a 5-year survival.

Cartilage origin tumors

Solitary exostosis (SE)

It originates in a sub-periosteal overgrowth of the

epiphyseal plate. It will grow with the skeleton and become
mature when bone growth stops.
It accounts for almost 39% of benign tumors of the bone
and males are affected twice more often.
Location is mostly represented by long bones, in their
metaphyseal area, but shoulder blade, pelvis, ribs and spine
can also be affected. SE never touches epiphysis, tarsal or
carpal bones (short of calcaneus). Distal femur covers for 24%,
proximal tibia for 17%, same as proximal humerus, the rest of
the skeleton shares the remaining 42%.
Symptoms are scarce: solid, non-painful tumor,
apparently attached to bone. It may grow painful because of
local inflammation triggered by movement (friction bursitis).
This may also render the “growing” aspect. Joint discomfort /
pain is to be expected when close to articulation. Accidental
fracture may also trigger pain.
X-ray will display the common image of “the tip of a
glove finger”, with rounded, sometimes bubbled sound cortical
and widely implanted base into the metaphysis. MRI can
reveal the cartilage part.
Pathology will show a bone-like aspect; the covering
cartilage is the same to the epiphyseal plate in growing kids
and turns hyaline in adults.
255
 Clinical and x-ray examination proves to be satisfactory
for a correct diagnosis.
Overgrowth of the covering cartilage at adult age (over
2 cm by MRI measurement) may signify evolution towards
sarcoma.
Treatment is extra-periosteal resection when symptoms
intensify or as prophylaxis when SE is located on body.

Chondrosarcoma (CS)

Chondrosarcoma is a malignant tumor derived from cartilage.

It may display a primitive development or it can derive from
benign cartilage tumors.
It can vary as location within bone; central, peripheral,
periosteal, mesenchyma linked and the so-called clear cell
chondrosarcoma.
The central chondrosarcoma accounts for some 10% of all
malignant bone tumors and develops mostly between 30 and
60 years of age. Never encountered before puberty.
Most affected bones are femur, pelvis, humerus, scapula, tibia,
sternum, spine or even ribs. Longer bones are affected towards
extremities and the pelvis within acetabular area.
Symptoms are scarce and late. There is a common
development, with pain and slow growth over 10-20 years, but
there can be a much faster evolution, with rapid destruction
and metastasis within 1-2 years.
X-ray visible structure is configured as large ostheolysis, with
cortical attack and some possible densified areas within.
Invasion aims for the medullary channel and surrounding soft
tissues.
Pathology displays a lobular structure, with mixoid, liquefied
or calcified areas. Histology may display 3 degrees of staging:
- 1st degree – extremely rare and looking like chondroma,
only with some nuclear irregularities.
- 2nd degree – a more frequent situation, with visible and
typical nuclear anomalies (multiple bigger nuclei, with
more intense staining).
256
- 3rd degree – accounts for 25% of the cases. Nuclear
anomalies are increased, as well as mythosis and the degree
of differentiation is decreased.
Malignancy progress is slow and uncertain towards the 1st and
2nd degree, but more obvious and rapid from the 2nd towards
the 3rd degree.
Treatment is relying on large surgical resection, that can be
satisfactory in lower degrees, but it should be more aggressive
in 3rd degree. Metastases are more characteristic for the 3rd
degree and they are quite well defined (allowing for instance,
clear surgical resection within lungs).
The peripheral CS may develop upon exostosis. Pelvic,
femur, spine, sacrum, humerus are among its preferred targets.
Invasion of exostosis
X-ray displays an extra-osseous tumor with variable density
bone-like matter, but with uncertain contour. A transparent and
invasive cartilage cover of exostosis exceeding 2 cm in
thickness in an adult can be held as proof for malignancy.
Peripheral CS has a superior differentiation and it can seldom
turn highly malignant, in relapse only. Evolution is slow, with
possible relapse within 10 years. Life expectancy may cover
20 years after first symptom registration.
The periosteal CS is a more rare possibility of evolution,
mostly on the limb area. Its malignancy is lower than that of
the central CS, metastasis at low risk and large resection may
grant healing. The mesenchyma CS is also rare, affecting
mostly the body skeleton, but with a more aggressive and
invasive behavior. Evolution is swifter and only 28% of the
patients make it in the first decade.
Some CS with slow evolution may suddenly turn hot as rapid
and vivid malignancy occurs, often because of the
development of another type of malignant tumor, with very
poor prognosis.

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Bone originating tumors

Osteoma

This is a benign tumor that occurs mostly on flat bones

(periosteal ossification) like within skull or face area. It has no
symptom unless important deformity affects sensitive areas
like the orbit or sinuses.
X-ray displays a tumor formation with appearing bone
structure. Scintigraphy turns positive. Histology will disclose
the aspect of a normal bone tissue, but with elements of
intense turnover and remodeling.
Differential diagnosis should exclude sarcoma and post-trauma
ossification.
Surgical excision is bound to heal the tumor.

Osteoid osteoma

It is a small but painful benign tumor consisting of osteoid

tissue, surrounded by condensed bone matter. Mostly
occurring between 5 and 30, it prefers locations as the upper
extremity of the femur, tibia, talus, spine and phalanx.
Clinically it becomes obvious due to almost continuous pain,
enhanced by night-time and palpation, which does not depend
on activity status and responds to aspirin treatment.

111. Osteoid
osteoma within
calcaneus

The x-ray
reveals the
ostheolysis characterized core of the tumor, called nidus,
enveloped in a condensation hallo. Vivid hyper-fixation is
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visible on scintigraphy, which can reveal otherwise invisible
formations. CT scan allows depiction of precise location pre-
operatively. There is also local osteoporosis triggered by pain
and local inflammation.
Histology shows a central core, made out of osteoid
tissue and charged with rich cell content (osteoblast,
osteoclast, fibroblast and capillary). Condensed bone clearly
envelops the tumor and there is a visible inflammatory reaction
in the synovia and surrounding soft tissues.
Differential diagnosis has to be done with solitary
(Brodie) abscess or chronic bone infection (osteomyelitis).
The osteoid osteoma will never disappear by itself. It
also doesn’t grow and it almost never turns malignant. If
correctly excised, relapse is seldom. Finding the accurate
location of the nidus is compulsory for adequate surgical
approach.

Osteosarcoma (OS)

The OS is a malignant tumor emerging from mesenchyma,

with cells that assume the osteoblast role of creating osteoid
tissue (newly formed bone). There are various types of
classifications, according to the originating cell.

Common (classic) OS

It accounts for 0,2% of the bone malignancies. It will

prevail in male population between 10-20, and no later than
30.
Most frequent locations are lower femur, proximal tibia
and humerus; in fact, about 2/3 of all being located within the
knee and shoulder. Pelvis, proximal femur, lower tibia are
rarely affected and other locations are exceptional.
It currently originates in the metaphysis and less in other
areas and the epiphyseal plate will block its articular invasion.
Clinical aspect is quite characteristic:

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- Ever increasing severe pain, that can get to excruciating
level, mostly nocturnal; it will precede tumor occurrence by
6-12 months;
- Progressive tumoral growth, covered by thinned,
inflammation flushed tegument displaying collateral
venous circulation;
- Increased local temperature, local muscular atrophy and
neighboring joint response;
- Increase of serum AP
(Alkaline Phosphatase);
- Decrease of general
condition and anemia (may witness
already spreading metastasis);

112. Osteosarcoma – microscopy

The x-ray assessment displays a rapidly growing and invading

tumor. For advanced stages, there is a classic aspect:
- the osteolitic development betrayed by inside cavity
with uncertain contour;
- osteoblastic ( bone formatting) development displays
bone condensation;
- merging images, combining the two tendencies, in
mixed type;
The sun rays disposal of some bone trabeculae, perpendicular
to the cortical, represent a specific malignant aspect. The
peripheral activity of the lifted periosteum creates triangular
shaped bone areas (named by Codmann).
Adequate imaging includes scintigraphy, CT and MRI
scan, allowing close monitoring of tumor development and
local impact.
Pathology assessment will reveal a macroscopic aspect
of mixed tissue: osteoid, condroid and fibrous. The non-
osteoid areas have a distinctive cerebral-like aspect. These
softer tissue areas may alternatively mix with dense, osteoid
ones.
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 Tumors will invade medullary channel, neighboring
tissues and even joints. The epiphyseal plate may delay
expansion, as it will oppose tumor invasion for some time.
Eventually, invasion may include blood vessels (deep veins).
Histology reveals the most important features of the two
types of tumor tissue:
- Soft tissue areas: atypical large cells, with multiple
nuclei under frequent mythosis and monstrous alterations;
immature, anarchic osteoid substance;
- Osteogenetic areas: more abundant and calcified bone
tumor substance, disorderly invading spaces around it like
melting lava; cells are rare and shrink, showing small and
modified nuclei;
- Tumor blood vessels are tortuous, dilated or have the
aspect of fragile caverns inside tissue, without walls of their
own.
These tumors have a high degree of malignancy (3-4).
Positive diagnosis is based on clinical, biological and imagery
proof, certified by biopsy.
Differential diagnosis must set this
tumor apart from other malignant
or benign tumors.

113. Bone sarcoma on x-ray

Evolution is very rapid, although a bit slower in bone

generating types. Blood spreading metastasis will affect first
the lungs and then other organs. Death follows in 1-2 years in
untreated cases and fatality covers a great number of treated
cases, also.

Treatment of osteosarcoma is complex and comprises

chemical-therapy and surgery.
Chemical therapy uses Methotrexat, Cisplastine, Adriamycin,
Bleomycin – CPM – Dactynomicin, etc. The adequate

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proceeding can be given pre-operatively and clinical response
is evaluated 2 months after:
- pain cease or decrease;
- tumor decrease;
- decrease of AP (alkaline phosphatase);
- osseous maturation of the tumor (positive imaging);
- diminished vascular network of the tumor and its
neighboring tissues visible on arteriography;
- reduced hyper-fixation on scintigraphy;

114. Distal femoral location for

osteosarcoma

Given such positive evolution

landmarks, surgery can be
performed and tumor removed.
Evaluation of tumoral cell necrosis
is then necessary. Such tumor cell
necrosis has been described by
Huvos as having four degrees:
st
- 1 degree – 0 – 50%
- 2nd degree – 50-90%
- 3rd degree – over 90%
- 4th degree – 100%
3rd and 4th degree will be regarded as good response, justifying
continuation of the already initiated chemical therapy. A weak
response (1st or 2nd degree) may be reason for therapy change.
The post-operative (added) can be sustained in cycles for over
6-12 months, with therapy change if necrosis degree drops
below 90%.
Surgical treatment is commonly employed as enlarged
conservatory resection, upon cases with previous pre-operative
chemical therapy. Since over 90% of the cases of classic OS
are being diagnosed when expanded beyond cortical (stage 2B,

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extra-compartmental), they will undergo this type of treatment,
with some exceptions:
- extension of tumor in the medullary channel and skip-
metastasis;
- neighboring joint invasion
- presence tumoral cell cluster within deep veins;
Prognosis depends on a number of factors:
- tumor extension;
- location (the more central on the body, the more lethal);
- tumor necrosis response under chemical therapy; 80%
of the patients with tumor necrosis exceeding 90% have the
chance of survival beyond the 5 year limit;

There are various types of OS that worth mentioning:

- the hemorrhaging type (osteolitic with rapid destruction,
but with good response to chemical therapy, at least in
some of the cases);
- the small cell OS – a less differentiated version which is
osteolitic and with poor response to treatment;
- central OS – unfortunately a very rare type with low
malignancy and good response to treatment;
- multiple OS – very rare and lethal; unfortunately
developing at age below 15;
- maxillary OS – with enhanced chondroblast structure
and affecting mostly aging people; it has a better prognosis;
- secondary OS upon Paget disease or other secondary
bone conditions ( necrosis, radiation, giant cell tumor,
chondrosarcoma, etc.);
- periosteal OS – with diaphysary determination on larger
bones and less malignant;
- next-to-cortical OS – with slower evolution of both
tumor and metastasis (they may cover for the next 20 years
following treatment);

Ewing sarcoma

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It is a malignant tumor originating in undifferentiated
mesenchyma and there is still a debate over its true origin. It
accounts for 10% of the bone malignancies and affects mostly
males between 10 – 20 (exceptionally under 5 and beyond 25).
It will affect mostly long bones: 23% femur, 9% tibia, 19%
pelvis; 11% ribs and some 5% for scapula.

There are vivid clinical signs that characterize the tumor: pain,
tumor growth, fever 38˚ C, increased ESR rate and LDH rate;
X-ray image displays the typical aspect of onion. Histology
displays the aspect of non-differentiated tissue. It is extremely
invasive and highly metastatic.
Treatment includes chemical therapy, irradiation and surgery.
Surgery employs large resection or amputation, prepared by
proper chemical therapy and / or
radiation. Relapse is frequent and
resistant to radiation.

115. Ewing tumor on tibial

shaft

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