CLASSIFICATION OF BONE TUMORS

Moderator Dr Bellad S H
Presenter Dr Syed Wahaj
Date
27-6-2016

AGE DISTRIBUTION
2nd ,3rd decades

Benign bone
tumors
Osteosarcoma
Ewings
sarcoma

3rd,4th decades

GCT

Older Ages

Multiple
myeloma
Chondrosarco
ma
Fibrosarcoma
Metastatic
bone tumors

SEX DISTRIBUTION

MALES
Most benign
and
malignant
tumors are
more
common in
males

FEMALES
GCT is more
common in
females

CLASSIFICATION OF BONE TUMORS

BONE TUMORS

PRIMARY

BENIGN

SECONDARY/METASTA
TIC

MALIGNA
NT

Most common malignancy of bone =

metastatic disease
Most common primary malignancy of bone =
myeloma>osteosarcoma
Most common primary sarcoma of bone
=intramedullary
osteosarcom(35.1%)>chondrosarcoma(25.8%
)>Ewings Sarcoma(16%)
Most common benign tumor of bone =
osteochondroma,fibrous cortical defect

METASTATIC BONE DISEASE

MC skeletal malignancy
Skeleton=third most common site of
mets in the body after lung and liver
MC site=axial skeleton > lower
extremity
Vertebral
column(69%)>pelvis(41%)>hip(25%)
Cause=red marrow is rich in capillary
network,has slow blood flow,this
facilitates implantation and growth of

METASTATIC BONE DISEASE

Incidence of bony
mets

Diagnosis

Myeloma
Breast
Prostate
Lung
Kidney
Thyroid
Melanoma

95-100%
65-75%
65-75%
3040%
20-25%
60%
14-45%

METASTATIC BONE DISEASE

Commonly Lytic

Commonly Blastic

Lung
Kidney
Thyroid
Adrenal
Uterus
GIT
Malignant melanoma

Prostate(adenocarcin
oma)
Bladder with prostrate
Bronchial carcinoid

Mixed lytic,blastic

Breast
Lung
Ovary
Testis
Cervix

METASTATIC BONE DISEASE

Skeletal
mets
Are
typically
MULTIFOC
AL

Solitary
lesions=
-Kidney
-Thyroid

CLASSIFICATION OF PRIMARY BONE TUMORS

Primary bone tumors are uncommon

Overall, bone sarcomas account for 0.2% of all malignancies
They represent a difficult category of tumors for appropriate
recognition, classification and treatment
Although the occurrence of bone sarcomas is low, they affect
particularly children and adolescents, which implies that they
have a major impact on the life of patients and their families
In recent years, advances in medical and surgical treatment
modalities have resulted in an improvement of the outcome
and survival of primary malignant bone tumors
This has been paralleled by significant developments in the
molecular and cytogenetic characterization, which in
combination with light/electron microscopy and
immunohistochemical techniques, has contributed to a better
understanding of this group of tumors

WHO CLASSIFICATION OF PRIMARY BONE

TUMORS

The first edition of the WHO (World Health Organization)

Histologic Classification of Bone Tumors was published in
1972.
Having been adopted widely, it has promoted uniformity in
diagnosis and provided the basis for a number of clinical,
pathologic, and epidemiologic studies
In 1993,it was reviewed by an international panel of
pathologists from 9 countries
Latest review= in 2013
The revised and expanded classification reflects advances in
our knowledge, but is similar in concept and framework to
the original version to allow comparisons between data
collected in the past and future.

WHO CLASSIFICATION OF PRIMARY BONE

TUMORS

Framework of WHO classification=

Primary bone tumors are classified based on
histologic criteria
-the type of differentiation shown by tumor
cells (via conventional light microscopy)
-type of intercellular matrix produced(via
conventional light microscopy)
It is recognized that electron microscopy and
especially immunohistochemistry may be
relevant for precise classification and diagnosis

CLASSIFICATION OF PRIMARY BONE TUMORS

Reasons for wide acceptance of a

histopathological classification=

it provides reproducible diagnostic criteria and

categories
it helps us to understand the intrinsic biology of
the tumor and to identify specific phenotypes
and genetic alterations to help in diagnosis of
the tumor
it allows us to predict the biological potential of
a tumor and help build a guide for treatment

WHO CLASSIFICATION OF PRIMARY BONE TUMORS

WHO CLASSIFICATION OF PRIMARY BONE TUMORS

WHO CLASSIFICATION OF PRIMARY BONE TUMORS

EVOLUTION OF CLASSIFICATION

Bone tumors are classified based on the line of

differentiation of neoplastic cells and their
resemblance to normal counterparts
Advantage-These criteria can be easily applied to
cartilage-forming or bone-forming tumors
Disadvantage
-certain tumors lack a recognizable
differentiation that can link them to a normal
tissue eg= Ewings sarcoma
-mesenchymal tumors-cell of origin is unknown.
also, no precursor lesions have been identified

EVOLUTION OF CLASSIFICATION

On these bases, the current WHO

classification of primary bone tumors has
abandoned the concepts of histogenesis
and cell of origin of the tumor, to focus on
a combination of parameters that include
morphology, phenotype and genotype

(Fletcher CDM, Unni KK, Mertens F.World Health Organization Classification of

Tumours Pathology and Genetics of Tumours of Soft Tissue and Bone.Lyon:
IARC Press; 2002

EVOLVING CONCEPTS AND NEW ENTITIES

advances in the characterization of the

molecular phenotype of tumor cells

Has led to relevant changes in the classification

schemes

disappearance of some entities and the

inclusion of new ones

EVOLVING CONCEPTS AND NEW ENTITIES

Hemangiopericytoma of bone is no longer

recognized as a true separate entity, but rather as
a morphological growth pattern which is common
to different tumor types, including infantile
myofibromatosis, phosphaturic mesenchymal
tumor, synovial sarcoma, solitary fibrous tumor
among primary tumors, and metastatic
meningioma among secondary ones

(A reappraisal of hemangiopericytoma of bone; analysis of cases

reclassified as synovial sarcoma and solitary fibrous tumor of
bone.Verbeke SL, Fletcher CD, Alberghini M, Daugaard S, Flanagan AM,
Parratt T, Kroon HM, Hogendoorn PC, Bove JV ,Am J Surg Pathol. 2010 Jun;
34(6):777-83 )

EVOLVING CONCEPTS AND NEW ENTITIES

Another tumor type whose existence as a separate true

diagnostic category has been deeply reconsidered in the
past decades is malignant fibrous histiocytoma (MFH).
Since fibroblast and its variants are the predominant cell
types found in these tumors, it has been suggested that the
diagnostic entity MFH should be rather classified as a
pleomorphic fibrosarcoma
Moreover, the use of ancillary techniques, including
immunohistochemistry and electron microscopy, may help to
more precisely classify high grade pleomorphic sarcomas in
specific categories, such as for example leiomyosarcoma or
myofibrosarcoma, or to recognize metastatic tumors, such
as melanoma or sarcomatoid carcinoma
(Primary fibrosarcoma and malignant fibrous histiocytoma of bone--a
comparative ultrastructural study: evidence of a spectrum of fibroblastic
differentiation.Antonescu CR, Erlandson RA, Huvos AG
Ultrastruct Pathol. 2000 Mar-Apr; 24(2):83-91)

EVOLVING CONCEPTS AND NEW ENTITIES

Another recent advance in the field of bone and soft tissue

tumors, has been the recognition that myoepithelial neoplasms
may occur primarily at these sites, which are otherwise entirely
devoid of myoepithelial cells
This further underlines the concept of a non-feasibility of a
histogenetic approach to the classification of bone and soft tissue
tumors
these tumors show the same morphological spectrum as their
salivary gland counterparts, including the presence of an
epithelial component, in which case they are better regarded as
mixed tumors
primary myoepitheliomas of bone frequently present with EWSR1
gene rearrangement, a feature that could be useful in the
diagnosis
(Primary mixed tumor of bone.de Pinieux G, Beabout JW, Unni KK, Sim FH
Skeletal Radiol. 2001 Sep; 30(9):534-6
Primary malignant myoepithelioma of the distal femur.Alberghini M, Pasquinelli G, Zanella L, Pignatti G, Benini S, Bacchini
P, Bertoni F
APMIS. 2007 Apr; 115(4):376-80
EWSR1-POU5F1 fusion in soft tissue myoepithelial tumors. A molecular analysis of sixty-six cases, including soft tissue,
bone, and visceral lesions, showing common involvement of the EWSR1 gene.Antonescu CR, Zhang L, Chang NE, Pawel BR,
Travis W, Katabi N, Edelman M, Rosenberg AE, Nielsen GP, Dal Cin P, Fletcher CD
Genes Chromosomes Cancer. 2010 Dec; 49(12):1114-24.)

EVOLVING CONCEPTS AND NEW ENTITIES

The WHO classification currently recognizes

chordoma, which is defined as a low to
intermediate grade malignant tumor that
recapitulates notochord, as the only member of the
group of tumors of the notochord
However, several reports support the existence of
notochord-type lesions of the axial skeleton that
are radiologically and histologically distinct from
chordoma and which appear to be benign but may
undergo malignant transformation into classic
chordomas
(Benign notochordal lesions of the axial skeleton: a review and current appraisal.Kyriakos
M
Skeletal Radiol. 2011 Sep; 40(9):1141-52)
(Benign notochordal cell tumors: A comparative histological study of benign notochordal
cell tumors, classic chordomas, and notochordal vestiges of fetal intervertebral
discs.Yamaguchi T, Suzuki S, Ishiiwa H, Shimizu K, Ueda Y
Am J Surg Pathol. 2004 Jun; 28(6):756-61)

EVOLVING CONCEPTS AND NEW ENTITIES

Oncogenic osteomalacia is an unusual variant of

osteomalacia
It is associated with soft tissue and bone tumors of
various types
The term phosphaturic mesenchymal tumor,
mixed connective tissue variant (PMTMCT) has
been coined to describe these unique lesions
These tumors overexpress fibroblast growth factor23 (FGF-23)
Importance = The correct diagnosis of PMTMCT is
critical, as complete resection cures intractable
oncogenic osteomalacia
(RT-PCR analysis for FGF23 using paraffin sections in the diagnosis of phosphaturic
mesenchymal tumors with and without known tumor induced osteomalacia.Bahrami
A, Weiss SW, Montgomery E, Horvai AE, Jin L, Inwards CY, Folpe AL
Am J Surg Pathol. 2009 Sep; 33(9):1348-54)

CONTRIBUTION OF GENETICS TO THE DIAGNOSIS AND CLASSIFICATION

OF BONE TUMORS

majority of primary malignant bone tumors carry

nonspecific genetic changes within a background of a
complex karyotype
Ewings sarcoma presents with tumor-specific
chromosomal translocation mainly t (11;22)(q24;q12)
Advantage =

major impact in understanding the pathogenesis of this

tumor, and furnished the basis for its classification as tumor
with neuroectodermal differentiation
tumor specific translocations such as those identified in
Ewings sarcoma represent a molecular diagnostic tool to
assist the pathologist in the diagnosis and in detecting
minimal residual disease

CONTRIBUTION OF GENETICS TO THE DIAGNOSIS AND CLASSIFICATION

OF BONE TUMORS

ABC=a benign bone lesion described in 1942 by Jaffe and Lichtenstein

until recently considered as a reactive process with the potential for local
recurrence
The term secondary ABC has been used to designate those lesions
occurring in association with other processes, mainly fibrous dysplasia,
chondroblastoma, osteoblastoma and giant cell tumor of bone
The identification of a recurrent chromosomal translocation t (16;17)
(q22; p13) has supported the notion that at least a subset of ABC have a
neoplastic nature
this translocation is present only in the spindle cell component of
primary ABC, and it is not detected in secondary ABC
Recent observations indicate that the cells affected are immature
osteoblasts and the translocation appears to simultaneously inhibit
osteoblast maturation and stimulate osteoclast activity, thus favoring
the growth of ABC
these findings support the notion that primary ABC is a mesenchymal
neoplasm possibly of the osteoblastic lineage, whereas secondary ABC
most likely represents a common endpoint of differentiation in various
non-ABC bone tumors

GRADING OF BONE TUMORS

Histological grading is an attempt to predict the

biological behaviour of a malignant tumour based on
histological features
In bone tumours, cellularity, i.e., the relative amount of
cells compared to matrix, and nuclear features of the
tumour cells are the most important criteria used for
grading
Generally, the higher the grade, the more cellular the
tumour
Irregularity of the nuclear contours, enlargement and
hyperchromasia of the nuclei are correlated with grade.
Mitotic figures and necrosis are additional features

GRADING OF BONE TUMORS

Spindle cell sarcomas such as osteosarcoma and

fibrosarcoma need to be graded
histological grading correlates with prognosis in
chondrosarcoma and malignant vascular tumours
Tumours which are monomorphic, such as small cell
malignancies (Ewing sarcoma, malignant lymphoma and
myeloma), do not lend themselves to histological
grading
Mesenchymal chondrosarcomas and dedifferentiated
chondrosarcomas are always high grade
clear cell chondrosarcomas are low grade
grading is not useful in predicting prognosis in
adamantinoma and chordoma

STAGING OF BONE TUMORS

staging incorporates the degree of differentiation as well as local and

distant spread, in order to estimate the prognosis of the patient
As defined by the International Union Against Cancer, the objectives
of cancer staging are
(1) to aid in planning the course of treatment,
(2) to provide insight into the prognosis,
(3) to assist in evaluating the results of treatment, (4) to facilitate
effective interinstitutional communication
(5) to contribute to continuing investigation of human malignancies
the most useful staging system
-would guide the nature of the surgical procedure
-organize the most significant prognostic factors into a system
describing progressive degrees of risk to which a patient is subjected
-outline progressive stages of the disease having specific
implications for surgical management
-provide guidelines for use of adjunctive therapy

TGNM SYSTEM OF THE AMERICAN JOINT COMMITTEE

FOR CANCER FOR STAGING OF SOFT TISSUE SARCOMAS

Since its establishment in 1959, the

American Joint Committee for Cancer
(AJCC) has undertaken the
responsibility for developing clinically
useful staging systems for various
types of cancer

(Copeland MM, Robbins GF, Myers MH. Developing of a clinical staging

system for primary malignant tumors of bone: a progress
report.Management of Primary Bone and Soft Tissue Tumors. Chicago, IL:
Year Book Medical Publishers, Inc; 1977;35)

TGNM SYSTEM OF THE AMERICAN JOINT COMMITTEE

FOR CANCER FOR STAGING OF SOFT TISSUE SARCOMAS

ENNEKING STAGING SYSTEM

In 1980, a system for surgical staging of

musculoskeletal sarcoma was proposed, studied,
and adopted by the Musculoskeletal Tumor
Society and subsequently by the AJCC
(A system for the surgical staging of musculoskeletal sarcoma.Enneking WF, Spanier SS, Goodman MA
Clin Orthop Relat Res. 1980 Nov-Dec; (153):106-20.)

This system was established initially at the

University of Florida in 1977 based on the data
collected from 1968 through 1976 by Dr. William
Enneking
There are separate staging systems for benign
and malignant mesenchymal tumors

ENNEKING STAGING FOR BENIGN MUSCULOSKELETAL

TUMORS

based on radiographic characteristics

of the tumor host margin

Well demarcated borders,

grows slowly and then stops
remains static /heals spontaneous
eg=osteoid osteoma
Indistinct borders
Progressive growth limited by natural
barriers
not self limiting/tendency to recur
eg=ABC
Indistinct borders
growth not limited by
natural barriers
eg=GCT

ENNEKING STAGING FOR MALIGNANT

MUSCULOSKELETAL TUMORS

based on surgical grade, local extent,

and presence or absence of metastasis

ENNEKING SURGICAL STAGING-CONFIRMATION/VALIDATION

has been validated in two distinct

situations: (1) intramurally by the
University of Florida musculoskeletal
oncology service (258 patients
(2) extramurally by a multicentric study
(13 institutions) conducted by the
Musculoskeletal Tumor Society (139
patients)

LIMITATIONS

The Enneking surgical staging system is based on

the natural evolution of mesenchymal tumors and
thus is not applicable to tumors originating in
either the marrow or reticuloendothelial system
These include lymphomas, multiple myeloma,
plasmacytoma, Ewings sarcoma, other round cell
neoplasms, and metastatic carcinomas
Lesions originating in the skull also behave
differently and thus cannot be staged or classified
using this system.

MUSCULOSKELETAL TUMOUR SOCIETY STAGING.

SURGICAL MARGINS

MUSCULOSKELETAL TUMOUR SOCIETY STAGING.

SURGICAL MARGINS