Phase II 3rd year (2010 intake)

Musculoskeletal System Module

PATHOLOGY OF SOFT TISSUE &

BONE TUMORS
ID#480

By Dr. Rola Ali

Pathology Department
Sunday, 5 th May 2013 , 1-2.50
 OB JEC TIVES
1. Soft tissue tumors:

Classification

Microscopic findings

Clinicopathologic correlation

2. Bone tumors:

Classification

Microscopic findings

Clinicopathologic correlation and radiologic findings

Metastatic tumors to bone

 BONE & SOFT TISSUE TUMORS:
ROLE OF PATHOLOGIST

Surgical specimen (or small Pathologist examines Pathologist takes small

biopsy) is sent to pathology specimen grossly samples from specimen
lab

Pathologist
establishes Glass slide
diagnosis
microscopically
SOFT TISSUE
TUMORS
 WHAT I S SO FT TI SSUE?
Non-epithelial tissues that
connect, support, or surround
other structures and organs of
the body

Include:
Fat

Muscles

Nerves

Blood vessels

Fibrous tissues
 SOFT TISSUE TUMORS:
TERMINOLOGY
Adipose tissue Skeletal muscle Smooth muscle Blood vessels

Lipo- Rhabdomyo- Leiomyo- (Hem)angio-

Benign: -oma Malignant: -sarcoma

Lipoma Rhabdomyoma Leiomyoma Hemangioma
Liposarcoma Rhabdomyosarcoma Leiomyosarcoma Angiosarcoma
 SOFT TI SSUE TUMORS:
C L ASSI FI CATI ON
TUMORS OF ADIPOSE TISSUE TUMORS OF SMOOTH MUSCLE
Lipoma Leiomyoma
Liposarcoma Leiomyosarcoma

TUMORS OF FIBROUS TISSUE VASCULAR TUMORS

Nodular fasciitis Hemangioma
Fibromatosis Angiosarcoma
Fibrosarcoma
PERIPHERAL NERVE TUMORS
FIBROHISTIOCYTIC TUMORS Neurofibroma
Benign fibrous histiocytoma Schwannoma
Malignant fibrous histiocytoma Malignant peripheral nerve sheath tumor

TUMORS OF SKELETAL MUSCLE TUMORS OF UNCERTAIN HISTOGENESIS

Rhabdomyoma Synovial sarcoma
Rhabdomyosarcoma Alveolar soft-part sarcoma
Epithelioid sarcoma
 SOFT TISSUE TUMORS:
LOCATION

Common locations:
Lower extremity (40%) especially thigh
Upper extremities
Trunk
Head and neck
Retroperitoneum

In extremities and trunk soft tissue tumors can be

either:
Superficial: in subcutaneous fat
Deep: within muscular compartment
 SOFT TISSUE TUMORS:
LOCATION
Soft tissue tumors arising in superficial locations (skin and
subcutaneous fat) have a better prognosis than deep-seated tumors.

Deep-seated
within the
muscle

Superficial within the

subcutaneous fat
 SOFT TISSUE TUMORS:
AGE
Incidence generally increases with age

Specific sarcomas tend to appear in certain age

groups:
Rhabdomyosarcoma in children
Synovial sarcoma in young adulthood
Liposarcoma in middle to late adult life

Sarcomas constitute the 4 t h most common

malignancy in children following brain tumors,
hematopoietic tumors, and Wilms tumor
 SOFT TISSUE TUMORS:
PROGNOSIS
Several features influence prognosis:

Histologic type

Histologic grade (degree of differentiation) :

Mitoses
Pleomorphism
Necrosis

Stage (extent of tumor):

Size
Location
Depth
Presence or absence of metastases
 SOFT TISSUE TUMORS:
PATHOGENESIS
Etiology is unknown

Contributing factors: radiation therapy, trauma, HHV-8 in

Kaposi sarcoma

Some predisposing hereditary syndromes:

Neurofibromatosis type 1 neurofibroma, malignant peripheral
nerve sheath tumor
Gardner syndrome fibromatosis
Li-Fraumeni syndrome several soft-tissue sarcomas

Some soft tissue tumors are associated with specific

chromosomal translocations
 SOFT TISSUE TUMORS:
PATHOGENESIS- TRANSLOCATIONS

Translocation: part of a chromosome is transferred to

another chromosome
 SOFT TISSUE TUMORS:
PATHOGENESIS- TRANSLOCATIONS
Cytogenetic
Tumor Genetic Abnormality
Abnormality
Ewing sarcoma t(11;22) FLI1-EWS fusion gene
t(21;22) ERG-EWS fusion gene
t(7;22) ETV1-EWS fusion gene
Liposarcomamyxoid t(12;16) CHOP/TLS fusion gene
Synovial sarcoma
Rhabdomyosarcomaalveolar type The list is
t(x;18)
t(2;13)
SYT-SSX fusion gene
PAX3-FKHR fusion gene

continuously
t(1;13)
Extraskeletal myxoid chondrosarcoma
t(9;22)
PAX7-FKHR fusion gene
CHN-EWS fusion gene

Clear-cell sarcoma
expanding!
Desmoplastic small round-cell tumor
t(11;22)
t(12;22)
EWS-WT1 fusion gene
EWS-ATF1 fusion gene
Dermatofibrosarcoma protuberans t(17;22) COLA1-PDGFB fusion gene
Alveolar soft-part sarcoma t(X;17) TFE3-ASPL fusion gene
Congenital fibrosarcoma t(12;15) ETV6-NTRK3 fusion gene
EXAMPLES OF SOFT
TISSUE TUMORS
 SOFT TISSUE TUMORS:
FATTY TUMORS
Lipoma L i p o s a r c o ma

The most common soft- One of the most common

sarcomas of adulthood
tissue tumor of adulthood
Usually in deep soft
Usually superficial in the tissues & retroperitoneum
subcutaneous tissue Larger than lipoma
Recur if inadequately
Small, mobile, painless excised
Benign Some variants can
metastasize
 SOFT TISSUE TUMORS:
FATTY TUMORS- GROSS
Lipoma L i p o s a r c o ma

Well-circumscribed Irregular outline

mass (regular outline) No capsule
Encapsulated Larger than lipoma
 SOFT TISSUE TUMORS:
FATTY TUMORS- HISTOLOGY
Lipoma L i p o s a r c o ma
Composed of mature Disorganized adipose tissue
adipocytes Lipoblasts: immature fat
cells that contain vacuoles of
lipid and scalloped nucleus
 SOFT TISSUE TUMORS:
VASCULAR TUMORS
Hemangioma An g i os a r c o m a
Common in infancy and
Older adults

childhood; most are present at Location: scalp of elderly, deep soft

tissue, breast, liver
birth
Risk factors:
Can regress spontaneously

Polyvinyl chloride Hepatic

angiosarcoma
Location:

Lymphedema after radical

Superficial often in the head or
neck
Internal organs especially liver
mastectomy & lymph node resection
Radiation for breast cancer
Aggressive (5-year survival rates
30%).
 SOFT TISSUE TUMORS:
V A S C U L A R TU M O R S - G R O S S
Hemangioma An g i os a r c o m a
Red-blue in color Red-blue in color
Usually small & well-defined Large
Rare giant forms can affect Irregular outline
large areas of the face, or Central areas of necrosis and
extremities hemorrhage
 SOFT TISSUE TUMORS:
VASCULAR TUMORS- HISTOLOGY
Hemangioma An g i os a r c o m a
Well-circumscribed ill-defined & infiltrative
Round vascular spaces filled with Dissecting anastomosing
blood vascular channels
Spaces lined by benign
Vascular channels are lined by
endothelial cells
atypical endothelial cells
Variants: capillary hemangioma
and cavernous hemangioma

Cavernous-type hemangioma
 SOFT TISSUE TUMORS:
EXAMPLES OF ANGIOSARCOMA
Angiosarcoma due
to lymphedema
after radical
mastectomy &
lymph node
resection

Angiosarcoma of liver

Angiosarcoma
Angiosarcoma
arising after
on scalp of an
radiation for
elderly
breast cancer
 SOFT TISSUE TUMORS:
SMOOTH MUSCLE TUMORS
Leiomyoma L e i o myo s a r c o m a
Often arise in the uterus Women > men
(fibroid) Seen in the uterus, skin and
Uterine leiomyomas are the deep soft tissues of the
most common neoplasm in extremities and retroperitoneum.
women Can cause death by both local
Also seen in skin, nipples, extension and metastatic spread.
genital areas
In the skin may be multiple
and painful.
 SOFT TISSUE TUMORS:
SMOOTH MUSCLE TUMORS- GROSS
Leiomyoma L e i o myo s a r c o m a
Well-circumscribed May be large and bulky
Firm Irregular outline
Whorled cut surface Hemorrhage & necrosis
 SOFT TISSUE TUMORS:
SMOOTH MUSCLE TUMORS-
HISTOLOGY
Leiomyoma L e i o myo s a r c o m a
Non-invasive Invasive
Bundles of spindle cells Bundles of spindle cells
Cigar-shaped nuclei Cigar-shaped nuclei but large
No nuclear atypia and no & atypical
mitosis Numerous mitoses & necrosis
BONE TUMORS
 BO NE TUMORS

Radiologists play an important role in diagnosing bone tumors

and in deciding which lesions need to be biopsied for
histological assessment.

Benign bone tumors greatly outnumber their malignant

counterparts

A lot of the benign bone tumors occur in the first three

decades of life

In the elderly a bone tumor is likely to be malignant

 BO NE TUMORS:
CLASSIFICATION
Histologic Type Benign Malignant
Hematopoietic Myeloma
Lymphoma
Chondrogenic Osteochondroma Chondrosarcoma
Chondroma
Chondroblastoma
Chondromyxoid fibroma

Osteogenic Osteoid osteoma Osteosarcoma

Osteoblastoma
Fibrogenic Non-ossifying fibroma Fibrosarcoma
Fibrous histiocytoma
Unknown origin Giant cell tumor
Aneurysmal bone cyst
Neuroectodermal Ewing sarcoma
Notochordal Benign notochordal cell tumor Chordoma
 BO NE TUMORS:
LOCATION

Location within the bone itself is an important diagnostic clue.

Diaphysis Ewing sarcoma

Lymphoma
Myeloma
Metastasis

Metaphysis Osteosarcoma
Osteochondroma
Metastasis

Epiphysis Giant cell tumor

Chondroblastoma
 BO NE TUMORS:
PRESENTATION

Bone tumors can present in different ways:

Asymptomatic: incidental finding on imaging

Pain

Mass

Sudden pathologic fracture

 BO NE TUMORS:
RADIOLOGIC-PATHOLOGIC CORRELATION

Role of radiology:
location of tumor

extent of tumor

detect features that help limit the differential diagnosis

give clues to the aggressiveness of the tumor

Ultimately, in most instances, biopsy and histologic study are

necessary.
EXAMPLES OF BONE
TUMORS
 BO NE TUMORS:
OSTEOSARCOMA
The most common primary sarcoma of bone

Osteo- means a tumor producing neoplastic bone

Age:
Adolescents (75%, usually idiopathic)
Elderly (usually there is a pre-existing bone disease)

Clinical presentation:
pain, swelling, pathological fracture

Location:
Metaphysis of long bones
 BO NE TUMORS:
OSTEOSARCOMA- ETIOLOGY
For the majority of cases the cause is unknown

Syndromes predisposing to osteosarcoma:

Li-Fraumeni syndrome p53 mutation
Hereditary retinoblastoma syndrome RB mutation

Pre-existing bone disease may predispose to OS:

Bone infarcts
Chronic osteomyelitis
Paget disease
Radiation
Metal prostheses
 BO NE TUMORS:
OSTEOSARCOMA- RADIOLOGY
Mass with
Codman cloud-like Humerus
triangle mineralization
Large indicative of
osteoid matrix
mass
production

Distal femur
 BO NE TUMORS:
OSTEOSARCOMA- RADIOLOGY
 BO NE TUMORS:
OSTEOSARCOMA- GROSS
Distal femur
Tumor affects
metaphysis

Tumor
destroys bone
extending into
soft tissue
 BO NE TUMORS:
OSTEOSARCOMA- GROSS
Distal femur

Codman triangle
seen radiologically
This example
arises in
metaphysis &
also extends to
epiphysis
 BO NE TUMORS:
OSTEOSARCOMA- HISTOLOGY
The lace-like pink
material is
neoplastic bone
(neoplastic
osteoid)

Atypical
osteoblasts
 BO NE TUMORS:
OSTEOSARCOMA- CLINICAL BEHAVIOR

Osteosarcoma is a malignant tumor

It is an aggressive neoplasm that can metastasize

and spread hematogenously especially to lungs

Treated with chemotherapy followed by surgery

 BO NE TUMORS:
CHONDROSARCOMA
The second most common primary sarcoma of bone

Chondro- means a tumor producing neoplastic

cartilage

Age:
Middle age- elderly (40s or older)

Location:
Axial skeleton (central portions of skeleton) more than long
bones
Most common: pelvis, shoulder, ribs
 BO NE TUMORS:
CHONDROSARCOMA- RADIOLOGY
Popcorn
calcification

Large mass arising in a rib

destroying the bone and
extending into soft tissues
 BO NE TUMORS:
CHONDROSARCOMA- GROSS
Gray-white glistening
tissue that looks like
hyaline cartilage

Tumor destroying
the bone &
extending outside
 BO NE TUMORS:
CHONDROSARCOMA- HISTOLOGY
Normal cartilage Chondrosarcoma
Atypical dark
Small pale nucleus
nucleus

2 chondrocytes
1 chondrocyte
in 1 lacuna
in 1 lacuna
 BO NE TUMORS:
CHONDROSARCOMA- CLINICAL
BEHAVIOR
Chondrosarcoma is a malignant tumor

Metastatic potential is related to tumor grade:

Grade 1: only locally aggressive and rarely metastasize

Grade 2: intermediate behavior

Grade 3: usually metastasize

 BO NE TUMORS:
EWING SARCOMA
A malignant small round-cell tumor

Age:
Children particularly between 10-15 years old

Characterized by the translocation t(11;22) resulting in

EWS-FLI-1 gene fusion

Clinical presentation:
Systemic symptoms: fever, ESR, anemia, leukocytosis mimicking
infection

Location:
Diaphysis of long bones especially femur
Also flat bones e.g. pelvis and ribs
 BO NE TUMORS:
EWING SARCOMA- RADIOLOGY

1. Diaphysis of the bone

2. Destructive lytic tumor
3. Periosteal reaction seen as
onionskin or sun-ray
appearances

sun-ray
 BO NE TUMORS:
EWING SARCOMA- RADIOLOGY

Onion-skin Sun-ray
(parallel to bone) (perpendicular to bone)
 BO NE TUMORS:
EWING SARCOMA- GROSS

Mass arising in the

diaphysis (shaft) of
femur
 BO NE TUMORS:
EWING SARCOMA- HISTOLOGY

Small round cells Homer-wright rosette

 BO NE TUMORS:
EWING SARCOMA- CLINICAL BEHAVIOR

Ewing sarcoma is a malignant tumor

Treated with chemotherapy followed by surgery

 BO NE TUMORS:
METASTATIC TUMORS TO BONE
Metastatic tumors are the most common form of bone
malignancy in adults!

Most common tumors that metastasize to bone in adults:

Prostate cancer
Breast cancer
Renal cancer
Lung cancer

Most common tumors that metastasize to bone in

children:
Neuroblastoma
Wilms tumor
Rhabdomyosarcoma
 BO NE TUMORS:
METASTATIC TUMORS TO BONE
Location: axial bones (spine,
Sagittal CT of thoracic spine
pelvis, ribs, skull) more than
long bones

Radiologically:
Lytic: decreased opacity on x-ray
and CT scan
Sclerotic: increased opacity on x-ray
and CT scan
lytic Mixed

sclerotic Many cancers give rise to lytic

metastases but prostate
cancer can also give rise to
sclerotic metastases
THANK YOU!