Malignant connective tissue

tumors

PATHOLOGY II

3/12/2024 First 2024 /2025

Dr KHALID SOBHI MOWAQET Lecture number 16
 • By the end of this Lecture the student should Know
and understand the following
• Malignant connective tissue tumors
• Fibrous tissue: Fibrosarcoma
• Bone: Osteosarcoma
• Cartilage: Chondrosarcoma
• Adipose tissue: Liposarcoma
• Muscular tissue: Leiomyosarcoma.
Rhabdomyosarcoma
• Joints : Synovial Sarcoma (SS)

2
 Malignant tumors of Fibrous tissue
Fibrosarcoma Definition;
A malignant neoplasm of fibroblastic cells

Etiopathogenesis
The cause of fibrosarcoma is not known.
Predisposing factors such as
1. Previously irradiated sites,
2. Preexisting connective tissue tumors such as liposarcoma
3. Mutation of TP53 gene

3
Clinical Features
Fibrosarcoma is a tumor results from proliferation of malignant mesenchymal cells at the site of
origin. Secondary ulceration may be seen as the lesion enlarges. Young adults are most
commonly affected.
This is an infiltrative neoplasm that is more of a locally destructive problem than a metastatic
problem.
Histopathology
 Fibrosarcoma is a highly cellular
tumor composed of anaplastic
spindle-shaped nuclei with an
eosinophilic cytoplasm that
blends with delicate collagen
fibers.
 Mitotic figures are numerous,
and many are atypical.
 The cells are arranged in
fascicles, often with a
4 “herringbone” pattern.
 OSTEOGENIC SARCOMA
Definition
Osteosarcoma is defined as a malignant tumor of bone cells, that forms bone or osteoid.
Etiology and Pathogenesis:
The age distribution of osteosarcoma is bimodal, with 75% occurring before 20 years of age.
A smaller peak occurs in older adults, in whom it is frequently associated with predisposing
conditions such as Paget disease, bone infarction and prior radiation.
The tumor occurs most frequently in the growth plate of rapidly growing bones, where increased
proliferation may predispose to mutations of several tumor suppressor genes.
Most important are:
• RB mutations are present in up to 70% of sporadic osteosarcomas; Osteosarcoma could
• TP53 is mutated in the germline of individuals with Li-Fraumeni be
syndrome, who have a greatly increased incidence of osteosarcoma Primary from the
• CDKN2A which encodes two tumor suppressors, p16 and p14, is bone cells or
inactivated in many osteosarcomas. Secondary (most
common from Prostate
in old male)
5
Location of Osteosarcoma Clinically;
Although any bone can be The usual osteosarcoma presents with pain, tenderness and an
involved, tumors usually obvious swelling of affected extremity.
arise in the metaphyseal Serum alkaline phosphatase level is generally raised but calcium
region of the long bones; and phosphorus levels are normal.
almost 60% are near the The tumor metastasizes rapidly and widely to distant sites by
knee in the distal femur or haematogenous route and disseminates commonly to the lungs,
proximal tibia. other bones, and brain.

Depending upon their locations within the bone, osteosarcomas

are classified into 2 main categories: 2. Surface (periosteal).
1. Central (medullary) juxtacortical
conventional type

6
 The radiographic appearance is quite distinctive: characteristic
‘1. Sunburst pattern’ due to osteogenesis within the tumor and
CENTRAL MEDULLARY OSTEOSARCOMA presence of
This is the more common and classic type and is 2. Codman’s triangle

generally referred to as ‘osteosarcoma’ if not

specified.
The tumor occurs in young patients between the
age of 10 and 20 years.
Males are affected more frequently than females.
tumor arises in the metaphysis of long bones.
Most common sites are: the lower end of femur
and upper end of tibia (i.e. around knee joint
about 60%); and the upper end of humerus.
The tumor arises centrally in the metaphysis,
extends into the medullary cavity, expands
laterally on either side breaking through the
cortex and lifting the periosteum

7
SURFACE OSTEOSARCOMA
About 5% of osteosarcomas occur on the surface of bone and are slow-growing tumors compared
to medullary osteosarcomas. Surface osteosarcoma includes 2 variants:

Parosteal or Periosteal
juxtacortical osteosarcoma
osteosarcoma is a rare form of
is an uncommon form osteosarcoma that
of osteosarcoma having arises between
its origin from the the cortex and the
metaphysis on the overlying
external surface of the periosteum.
bone (parosteal or Its common
juxtacortical means location is the
outer to cortex). diaphysis of the
tibia or the femur
8
HISTOPATHOLOGY:
Osteogenic sarcoma lesions must contain normal
or abnormal osteoid or bone that is closely
associated with the malignant connective tissue
cells to distinguish them from other forms of
sarcoma.

9
 CHONDROSARCOMA
Definition
Chondrosarcoma is a malignant tumor of chondroblasts (Cartilage).
It has much better prognosis than that of osteosarcoma.
Chondrosarcoma is the third most common bone malignancy after
myeloma and osteosarcoma, most occur in the 30 to 60 year age
group with 75% arising in men.

Etiology & Pathogenesis of CS

CS most commonly arises de novo
(primary), or (secondary) in a preexisting
benign cartilaginous lesion such as
enchondroma or osteochondroma).
Lesions have been associated with Paget
disease, and Ollier disease (multiple
enchondromatosis), CS exhibit mutations
of EXT genes
10
 Two types of chondrosarcoma are distinguished

1.Central
Chondrosarcoma is 2.Peripheral
more common and arises Chondrosarcoma arises
within the medullary in the cortex or
cavity of diaphysis or periosteum of
metaphysis. metaphysis.
This type of It may be primary or
chondrosarcoma is secondary occurring on a
generally primary pre-existing benign
cartilaginous tumor such
as (osteochondromas),
majority of chondrosarcomas are found and chondroblastoma
more often in the central skeleton (in the
pelvis,
11
ribs and shoulders).
 Chondrosarcoma

Histopathology
Grade I (well differentiated) CS often have a proliferations similar to benign
cartilage to those with increased numbers of chondrocytes Grade II tumors often
have a myxoid stroma with enlarged chondrocyte nuclei showing mitotic figures
and increased cellularity
Grade III (poorly differentiated) CS are markedly cellular, often with a spindle
cell component. Mitotic figures may be numerous.
So, The grading of chondrosarcoma depends mainly upon the number of tumor Normal cartilage histology
12
cells (Cellularity).
 Bone Tumors of Unknown Origin

EWING’S SARCOMA
Definition:
Ewing’s sarcoma (ES) is a highly malignant small round cell tumor occurring in patients
between the age of 5 and 20 years with predilection for occurrence in females.

PNEC consists of cells derived from the ectoderm.

It is confirmed now that the origin cells are primitive Formation of the neuroectoderm is the first step in
neuroectodermal cells (PNEC) the development of the nervous system
The diaphyses of the femur are the most common
sites, followed by the tibia and the humerus
Ewing’s sarcoma includes 3 variants:
i) Classic (skeletal) Ewing’s sarcoma;
ii) Soft tissue Ewing’s sarcoma;
iii) Primitive neuroectodermal tumor (PNET)
The three variants are linked together by a
1. Common neuroectodermal origin and by a
2. Common cytogenetic translocation abnormality
t(11; 22)

13
 Histology
Ewing sarcoma is a small-blue-round-cell tumor that
typically has a clear cytoplasm on H&E staining, due
to glycogen.

Signs and symptoms include:

intermittent fevers, anemia, leukocytosis,
increased sedimentation rate, and other
symptoms of inflammatory systemic illness.
the most common symptoms are localized
pain,
14 swelling, and sporadic bone pain
 Synovial Sarcoma (SS)
SS, Is a distinctive soft tissue sarcoma arising from synovial tissues close to
the large joints, tendon sheaths, bursa and joint capsule
Most common locations are the large joints mainly the knee
However, SS is also found in regions such as in the anterior abdominal wall,
parapharyngeal region and the pelvis.
The tumor occurs in young adults, usually under 40 years of age.
The tumor grows slowly as a painful mass but may metastasise via blood
stream, chiefly to the lungs.

15
Grossly,
the tumor is of variable size, round to multilobulated and
encapsulated.
Cut surface shows foci of calcification, cystic spaces and areas of
hemorrhages and necrosis
Microscopically,
classic synovial sarcoma shows a characteristic biphasic cellular
pattern composed of clefts or gland-like structures lined by cuboidal
to columnar epithelial-like cells and plump to oval spindle cells

16
 LIPOSARCOMA

• Is one of the most common soft tissue sarcomas in adults, Unlike lipoma which originates from mature adipose cells,
liposarcoma arises from primitive mesenchymal cells, the lipoblasts.
• The peak incidence is in 5th to 7th decades of life.
• In contrast to lipomas which are more frequently subcutaneous in location, liposarcomas often occur in the deep tissues.
• Most frequent sites are intermuscular regions in the thigh, buttocks and retroperitoneum.

Four major histologic varieties of liposarcomas are distinguished: 1. Well-differentiated liposarcoma resembles lipoma
but contains vacuolated lipoblasts
2. Myxoid liposarcoma is the most
common histologic type. 3. Pleomorphic liposarcoma 4. Round cell liposarcoma
It is composed of monomorphic, is highly undifferentiated and is composed of uniform, round
fusiform cells lying in myxoid-rich the most anaplastic type. to oval cells having fine
ground substance. There are numerous large multivacuolated cytoplasm with
Occasional tumor giant cells may be tumor giant cells and bizarre central hyperchromatic nuclei.
present. lipoblasts Round cell liposarcoma may resemble
Prominent capillaries forming chicken-
a signet-ring carcinoma but mucin
wire pattern is a conspicuous feature.
stains help in distinguishing the two.

17
 The prognosis of liposarcoma depends upon the
location
and histologic type.
In general, well-differentiated and myxoid
varieties have excellent prognosis, while
pleomorphic liposarcoma has significantly poorer
prognosis.
Round cell and pleomorphic variants metastasize
frequently
to the lungs and other visceral organs.
18
 RHABDOMYOSARCOMA
Is a much more common soft tissue tumor than rhabdomyoma, and is the commonest soft tissue sarcoma in children and
young adults. It is a highly malignant tumor arising from rhabdomyoblasts in varying stages of differentiation
Depending upon the histology, 4 types
3. ALVEOLAR (RMS) 4. PLEOMORPHIC (RMS)
1. EMBRYONAL (RMS) 2. BOTRYOID (RMS) Alveolar type is more This less frequent variety of
The embryonal form is the Botryoid variety is common in older children rhabdomyosarcoma occurs
most common pattern regarded as a variant of and young adults under the predominantly in older adults
It occurs predominantly in embryonal (RMS) age of 20 years. above the age of 40 years.
children under 12 years of age. occurring in children The most common They are most common in the
The common locations are in under 10 years of age. locations, are the lower limbs.
the head and neck region, most It is seen most frequently extremities
frequently in the orbit, in the vagina, urinary
Histologically,
urogenital tract and the bladder and nose
The tumor consists of a
retroperitoneal.
mixture of small, round to
oval cells and spindle-
shaped strap cells having
tapering bipolar
cytoplasmic processes in
which cross-striations may
be evident.
19
 Leiomyosarcoma
Leiomyosarcoma (LMS) is a malignant mesenchymal
tumor showing smooth muscle differentiation

20
 Epidemiology
LMS is one of the most common subtypes of malignant mesenchymal neoplasms
Overall incidence of LMS increases with age and peaks at the seventh decade of life
Sex predilection greatly depends on tumor location, with women comprising a clear majority of
patients with retroperitoneal and inferior vena cava LMS and men showing a slight predominance
in soft tissue sites
Sites
Most commonly arise in the extremities, retroperitoneal, abdomen / pelvis and trunk
Pathophysiology
Some of the most common changes in LMS occur in the form of loss in chromosomes 10 (PTEN)
and 13 (RB1)

Histology
Fascicles of eosinophilic
spindled cells with blunt
ended nuclei showing
variable pleomorphism
21