Transcript SOFT TISSUE TUMOURS By Dr. Fahd Al-Mulla •Understand the classification and types of soft tissue tumours •Understand the necessity for a team-approach •Correlate Pathological.

SOFT TISSUE TUMOURS
By Dr. Fahd Al-Mulla
•Understand the classification and types of soft tissue tumours
•Understand the necessity for a team-approach
•Correlate Pathological findings with clinical presentation
(Clinico-pathological correlation)
•Know the most relevant information and know it well
•ALL INFORMATION IS ON WEBSIT:
http://www.tumours.com
Soft Tissue Tumours: Definition
Mesenchymal proliferations that occur in the extraskeletal, nonepithelial
tissues of the body, excluding the viscera, coverings of the brain, and
lymphoreticular system.
Histologic type
Benign
Malignant
Adipose Tissue
Lipoma
Liposarcoma
Fibrous tissue
Fibromatosis
Nodular fasciitis
Fibrosarcoma
Fibrohistiocytic tumours
Fibrous histiocytoma
Dermatofibroma
Malignant Fibrous
Histiocytoma?????
Skeletal Muscle
Rhabdomyoma
Rhabdomyosarcoma
Smooth Muscle
Leiomyoma
Leiomyosarcoma
Vascular
Haemangioma
Lymphangioma
Angiosarcoma
Peripheral nerve
Neurofibroma
Schwannoma
Malignant peripheral
nerve sheath tumour
Uncertain histogenesis
Granular cell tumour
Synovial Sarcoma
Alveolar soft part
sarcoma
Epithelioid sarcoma
The cause of most soft tissue tumors is unknown. There are documented
associations, however, between radiation therapy and rare instances in
which chemical burns, heat burns, or trauma were associated with
subsequent development of a sarcoma. Exposure to phenoxyherbicides
and chlorophenols has also been implicated in some cases. Kaposi
sarcoma in patients with AIDS and in immunosuppressed patients is
related to viruses and defective immunocompetence. Most soft tissue
tumors occur sporadically, but a small minority are associated with
genetic syndromes, the most notable of which are neurofibromatosis
type 1 (neurofibroma, malignant schwannoma), Gardner syndrome
(fibromatosis), Li-Fraumeni syndrome (soft tissue sarcoma), and
Osler-Weber-Rendu syndrome (telangiectasia).
More recently, Enzinger and Weiss proposed a classification system
based on histogenic origin.
Problems:
1) It is very difficult for competent pathologists to agree on the
histogenesis of these tumors. Some sarcomas have multiple cell types
present in different areas of the tumor.
2) Many tumors are so undifferentiated that to subclassify them into
their histogenic type is close to impossible, even with specialized
techniques such as electron microscopy and immunohistochemistry
However, the major drawback of this classification system is that it
does not really take into account the grade of the tumor and its
implications for prognosis.
After the histologic type of soft-tissue sarcoma has been determined, the
tumor is graded 1 to 4, depending on its degree of differentiation
(How similar it is to the original tissue)
The majority of histologic types can be low-, intermediate-, or highgrade (grade 1, 2, or 3, respectively). However, some soft-tissue
sarcomas such as well-differentiated liposarcomas and myxoid
liposarcomas are always low-grade, whereas others such as
rhabdomyosarcoma, synovial sarcoma, mesenchymal
chondrosarcoma, and extraskeletal Ewing’s and osteosarcomas are
always high-grade
The American Joint Committee on Cancer (AJCC) has developed a
clinicopathologic staging system that depends primarily on the grade
and size of soft-tissue sarcomas
Primary tumor (T)
T0
T1
T2
No evidence of primary tumor
Tumor <5 cm
Tumor >5 cm
Lymph nodes (N)
N0
N1
No regional metastasis
Regional node metastasis
Distant metastasis (M)
M0
M1
No distinct metastasis
Distant metastasis
Histopathalogic grading (G)
G1
G2
G3
G4
Well differentiated (low grade)
Moderately differentiated (intermediate grade)
Poorly differentiated (high grade)
Undifferentiated
American Joint Committee on
Cancer
AJCC of soft tissue sarcomas
classification
Stage
IA
IB
IIA
IIB
IIIA
IIIB
IVA
IVB
G1
G1
G2
G2
G3
G4
G3
G4
Any G
Any G
T1
T2
T1
T2
T1
T1
T2
T2
Any T
Any T
N0
N0
N0
N0
N0
N0
N0
N0
N1
Any N
M0
M0
M0
M0
M0
M0
M0
M0
M0
M1
FATTY TUMOURS
Benign tumors of fat, known as lipomas, are the most common soft
tissue tumor of adulthood.
MORPHOLOGY.
The conventional lipoma, the most common subtype, is a wellencapsulated mass of mature adipocytes that varies considerably in size.
It arises in the subcutis of the proximal extremities and trunk, most
frequently during mid-adulthood. Infrequently, lipomas are large,
intramuscular, and circumscribed. Histologically, they consist of mature
fat cells with no evidence of pleomorphism or abnormal growth.
Lipomas are soft, mobile, and painless (except angiolipoma) and are
usually cured by simple excision.
conventional lipomas often show rearrangements of 12q14-15, 6p, and
13q, and spindle cell and pleomorphic lipomas have rearrangements of
16q and 13q .
Liposarcoma
Liposarcomas are one of the most common sarcomas of adulthood and
appear in the forties to sixties; they are uncommon in children. They
usually arise in the deep soft tissues of the proximal extremities and
retroperitoneum and are notorious for developing into large tumors.
MORPHOLOGY.
Histologically, liposarcomas can be divided into well-differentiated,
myxoid, round cell, and pleomorphic variants. The cells liposarcomas are
readily recognized as lipoblasts, which mimic fetal fat cells
Fibrous tumours and Fibrohistiocytic tumours
Fibromatoses
SUPERFICIAL FIBROMATOSIS (PALMAR, PLANTAR, AND PENILE
FIBROMATOSES)
Palmar, plantar, and penile fibromatoses, more bothersome than serious lesions,
constitute a small group of superficial fibromatoses. They are characterized by nodular
or poorly defined fascicles of mature-appearing fibroblasts surrounded by abundant
dense collagen. Immunohistochemical and ultrastructural studies indicate that many of
these cells are myofibroblasts
Examples: Dupuytren contracture, plantar fibromatosis
DEEP-SEATED FIBROMATOSIS (DESMOID TUMORS)
Biologically, deep-seated fibromatoses lie in the interface between exuberant fibrous
proliferations and low-grade fibrosarcomas. On the one hand, they present frequently as
large, infiltrative masses that may recur after incomplete excision, and on the other, they
are composed of banal well-differentiated fibroblasts that do not metastasize.
Fibrosarcoma
Fibrosarcomas are rare but may occur anywhere in the body, most
commonly in the retroperitoneum, the thigh, the knee, and the distal
extremities.
MORPHOLOGY.
Typically, these neoplasms are unencapsulated, infiltrative, soft, fishflesh masses often having areas of hemorrhage and necrosis. Betterdifferentiated lesions may appear deceptively encapsulated. Histologic
examination discloses all degrees of differentiation, from slowly
growing tumors that closely resemble cellular fibromas sometimes
having spindled cells growing in a herringbone fashion to highly cellular
neoplasms dominated by architectural disarray, pleomorphism, frequent
mitoses, and areas of necrosis.
TUMORS OF SKELETAL MUSCLE
Skeletal muscle neoplasms, in contrast to other groups of tumors, are
almost all malignant. The benign variant, rhabdomyoma, is distinctly
rare.
Rhabdomyosarcoma
Rhabdomyosarcomas, the most common soft tissue sarcomas of
childhood and adolescence, usually appear before age 20. They may arise
in any anatomic location, but most occur in the head and neck or
genitourinary tract.
MORPHOLOGY.
Rhabdomyosarcoma is histologically subclassified into the embryonal,
alveolar, and pleomorphic variants. The rhabdomyoblast--the diagnostic
cell in all types--contains eccentric eosinophilic granular cytoplasm rich
in thick and thin filaments. The rhabdomyoblasts may be round or
elongate; the latter are known as tadpole or strap cells
Cytogenetics play an important role in confirming the diagnosis rhabdomyosarcoma. Alveolar
rhabdomyosarcoma is associated with a specific translocation, t(2;13)(q37;q14) or its variant
t(1;13)(p36;q14). Embryonal rhabdomyosarcoma often shows loss of heterozygosity for 11p, but there is no
specific cytogenetic or molecular marker comparable to those for alveolar RMS.
TUMORS OF SMOOTH MUSCLE
Leiomyomas
Leiomyomas, the benign smooth muscle tumors, often arise in the uterus
where they represent the most common neoplasm in women. Leiomyomas
may also arise in the skin and subcutis from the arrector pili muscles found
in the skin, nipples, scrotum, and labia (genital leiomyomas) and less
frequently develop in the deep soft tissues.
They are usually not larger than 1 to 2 cm in greatest dimension and are
composed of fascicles of spindle cells that tend to intersect each other at
right angles. The tumor cells have blunt-ended elongated nuclei and show
minimal atypia and few mitotic figures.
Leiomyosarcoma
Leiomyosarcomas account for 10% to 20% of soft tissue sarcomas. Most
develop in the skin and deep soft tissues of the extremities and
retroperitoneum. Microscopically, the lesion is composed of interlacing
fascicles of mildly pleomorphic, spindle cells with blunt-ended nuclei and
eosinophilic cytoplasm. Average mitotic rate was 3 per 10 hpf. Geographic
areas of necrosis is present
SYNOVIAL SARCOMA
Synovial sarcoma is so named because it was once believed to
recapitulate synovium, but the cell of origin is still unclear. In addition,
although the term synovial sarcoma implies an origin from the joint
linings, less than 10% are intra-articular. Synovial sarcomas account for
approximately 10% of all soft tissue sarcomas and rank as the fourth
most common sarcoma.
MORPHOLOGY.
The histologic hallmark of synovial sarcoma is the biphasic
morphology of the tumor cells (i.e., epithelial-like and spindle cells).
Immunohistochemistry is helpful in identifying these tumors, since the
epithelioid and spindle cell portions yield positive reactions for keratin
and epithelial membrane antigen, differentiating these tumors from most
other sarcomas.
In Summary:
-Soft tissue benign tumours outnumber malignant
Tumours 100:1
-They are aggressive if malignant
-Be a good clinician and always correlate clinical
with pathological findings.
-Work together as a multi-disciplinary team
Any Questions??
Bone Tumours
WHAT SHOULD YOU KNOW
•Understand the clinical algorithm
•Correlate clinical presentation with radiological features
•Understand the classification and types of bone tumours
•Comprehend the management of bone tumours
•Understand the necessity for a team-approach
•Correlate Pathological findings with clinical presentation
(Clinico-pathological correlation)
CLASSIFICATIONS OF PRIMARY TUMOURS
INVOLVING BONES
Metastatic cancers are the most frequent malignant tumors found in bone
Histological Types
Benign
Hematopoietic (40%)
Malignant
Myeloma
Malignant lymphoma
Chondrogenic (22%)
Osteochondroma
Chondroma
Chondroblastoma
Chondromyxoid fibroma
Chondrosarcoma
Dedifferentiated
chondrosarcoma
Osteogenic (19%)
Osteoid osteoma
Osteoblastoma
Osteosarcoma
Unknown origin (10%)
Giant cell tumour
Ewing tumour
Giant cell tumour
Adamantinoma
Histiocytic origin
Fibrogenic
Notochordal
Vascular, Cystic, lipogenic
neurogenic
Fibrous histiocytoma
Fibroma
MFH
Fibrosarcoma
Chordoma
AGE(probably the most important clinical clue).
Age group
Most common benign lesions
Most common malignant tumors
0 - 10
simple bone cyst
eosinophilic granuloma
Ewing's sarcoma
leukemic involvement
metastatic neuroblastoma
10 - 20
non-ossifying fibroma
fibrous dysplasia
simple bone cyst
aneurysmal bone cyst
osteochondroma (exostosis)
osteoid osteoma
osteoblastoma
chondroblastoma
chondromyxoid fibroma
osteosarcoma,
Ewing's sarcoma,
adamantinoma
20 - 40
enchondroma
giant cell tumor
chondrosarcoma
osteoma
metastatic tumors
myeloma
leukemic involvement
chondrosarcoma
osteosarcoma (Paget's associated)
MFH
chordoma
40 & above
SITE OF LONG BONE INVOLVEMENT
(most primary bone tumors have favored sites within long bones; this may provide a clue to
diagnosis).
Diaphyseal lesions centered in
the cortex:
Adamantinoma, osteoid
osteoma
Metaphyseal intramedullary lesions:
Osteosarcoma is usually centered in the
metaphysis. Chondrosarcoma and
fibrosarcoma often present as metaphyseal
lesions. Osteoblastoma, enchondroma,
fibrous dysplasia, simple bone cyst, and
aneurysmal bone cyst are common in this
location.
Metaphyseal exostosis:
Osteochondroma
Diaphyseal intramedullary lesions:
Favored location for Ewing's sarcoma,
lymphoma, myeloma. Common for
fibrous dysplasia and enchondroma
Metaphyseal lesions centered in the
cortex:
Classic location for a non-ossifying
fibroma (NOF). Also, a common site for
osteoid osteoma.
Epiphyseal lesions:
Chondroblastoma (Ch) and Giant
Cell Tumor (GCT) are almost
invariably centered in the
epiphysis. Chondroblastoma is a rare
tumor seen in children and
adolescents with open growth plates.
GCT is the most common tumor of
epiphyses in skeletally mature
individuals with closed growth
plates. GCT often shows
metaphyseal extension.
General Histologic Assessment of the Lesion
The following are the most important histologic features to consider:
•Pattern of growth (eg., sheets of cells vs. lobular architecture)
•Cytologic characteristics of the cells
•Presence of necrosis and/or hemorrhage and/or cystic change
•Matrix production
•Relationship between the lesional tissue and the surrounding bone (eg., sharp
border vs. infiltrative growth)
But remember:
1. Listen to your patients (Is the lesion painful, What is the age of the patient)
2. Listen to the Radiologist (patterns of growth and ask to see the films)
3. Listen to the surgeons (rapid growth, involve the periosteum, soft tissue)
An 11-year-old male was seen in consultation for an increasingly painful distal femoral lesion associated with a soft tissue mass.
Plain radiograph shows an ill-defined
destructive tumor in the distal femur. Fluffy
radiodense infiltrates represent malignant
tumor osteoid.
Biopsy material shows two major
components of this neoplasm: highly
pleomorphic cells and haphazard
deposits of osteoid. Note that the
malignant cells fill the spaces between
osteoid deposits. Lace-like osteoid
deposition is very characteristic of this
neoplasm.
The tan-white tumor fills most of
the medullary cavity of the
metaphysis and proximal
diaphysis. It has infiltrated
through the cortex, lifted the
periosteum, and formed soft
tissue masses on both sides of the
bone.
A 17-year-old male presented with increasing pain in the left upper arm of approximately 3 months' duration and a recent onset of low-grade
fever. On physical examination, there was some local tenderness and soft tissue swelling over the proximal and mid thirds of the left humerus.
Most important here is the patient's age and short duration of symptoms.
Plain radiograph shows a large ill-defined, destructive,
diaphyseal intramedullary lesion with permeative
pattern of bone destruction and periosteal reaction of a
"hair-on-end" type. The lesion is associated with a soft
tissue mass.
Biopsy material showed a highly cellular,
infiltrative neoplasm consisting of sheets of
tightly packed, round cells with very scant
cytoplasm ("round blue cell tumor"). Occasional
Homer-Wright rosettes were identified. Other
fields showed extensive necrosis.
The cell population consisted of two distinct cell
types: the larger round cells with a high N/C
ratio, fine chromatin pattern and occasional
small, inconspicuous nucleoli, and the smaller
and darker cells with eosinophilic cytoplasm and
hyperchromatic, "shrunken" nuclei (degenerated
cells, a typical finding in this entity). Mitotic rate
averaged 2 per 10 hpf.
The following studies are required to support the diagnosis of ES and PNET:
Demonstration of t(11;22) or EWS-FLI-1 fusion transcript (present in both ES and PNET)
Immunostains(both ES and PNET are positive for CD99/O13. In addition, PNET shows positive staining with
neural markers)
EM (ES cells are undifferentiated and show prominent glycogen deposits; PNET shows neural
differentiation)
A 16-year-old boy was seen in consultation for increasing pain in the mid upper arm. Characteristically, the pain intensified at night and subsided
with aspirin.
Plain film shows a small, intracortical,
radiolucent focus (nidus), surrounded by dense
reactive periosteal bone. The lesion is located
in the mid portion of the humeral shaft.
If the nidus is removed intact, it
appears as a circumscribed
portion of red, trabecular bone,
usually less than 1cm in size.
Low-power view shows the lesional tissue ("nidus"), well demarcated
from the surrounding sclerotic bone.
The lesion is composed of thin, often interconnected spicules of
osteoid and woven bone rimmed by osteoblasts. Osteoclast-like
giant cells can be seen. Intervening fibrous stroma shows
prominent vascularity.
A 39-year-old female gave a 2-month history of increasing pain in her knee. There was no evidence of
joint effusion. Laboratory work-up showed normal serum levels of calcium, phosphate and alkaline
phosphatase
Plain radiograph demonstrated a well
defined, lytic lesion eccentrically located in
the distal femoral epiphysis with
subchondral and metaphyseal extension.
There was associated focal thinning of the
cortex
Curettage specimen consisted of fragments of soft,
hemorrhagic, tan-brown tissue with some firm areas and
yellowish speckles. Microscopic examination showed a
cellular lesion composed of numerous multinucleated
giant cells in a background of small, ovoid, mononuclear
stromal cells
Stromal cells had poorly defined
cytoplasmic borders and bland nuclei
resembling those of giant cells. Mitoses
were easily found averaging 4 per 10 hpf.
However, no atypical mitoses were
identified.
A 45-year old female presented with increasing pain and swelling around the knee. She mentioned that the symptoms had progressed over a 4month period.
Age of the patient is an important diagnostic clue. If a pathologic fracture is excluded, pain and swelling imply active growth of the lesion.
Plain film demonstrates a large, lobulated, illdefined lesion centered in the distal femoral
metaphysis. There is endosteal scalloping and
periosteal thickening. Central stippled and
"ring and arc" calcifications are apparent and
are typical of cartilaginous matrix. Small
radiolucent areas are seen at the periphery of
the lesion.
Low magnification shows a moderately
cellular, lobulated cartilaginous tumor.
High-power view shows scattered
plump, moderately pleomorphic
chondrocytes. Binucleated cells are
present. Mitotic rate averaged 1 per
10 hpf.
The aggressiveness of chondrosarcomas can be predicted by their histologic grade. Grading system is based on three parameters: cellularity,
degree of nuclear atypia and mitotic activity.
Grade 1 (low-grade)
Very similar to enchondroma. However, the cellularity is
higher, and there is mild cellular pleomorphism. The nuclei are
small but often show open chromatin pattern and small
nucleoli. Binucleated cells are frequent. Mitoses are very rare.
Grade 1 chondrosarcomas are locally aggressive and prone to
recurrences, but usually do not metastasize.
Grade 2 (low-grade)
The cellularity is higher than in Grade 1 tumors. Characteristic
findings are moderate cellular pleomorphism, plump nuclei,
frequent bi-nucleated cells, and occasional bizarre cells.
Mitoses are rare. Foci of myxoid change may be seen. Unlike
Grade 1 tumors, about 10% to 15% of Grade 2
chondrosarcomas produce metastases.
Grade 3 (high-grade)
Characteristic findings are high cellularity,
marked cellular pleomorphism, high N/C
ratio, many bizarre cells and frequent
mitoses (more than 1 per hpf). These are
high grade tumors with significant
metastatic potential.
A 14-year-old female was seen in consultation for an increasingly painful left humeral lesion associated with mild joint effusion.
Pay attention to the patient's age, skeletal location, and the presence of joint effusion, which may complicate epiphyseal lesions.
Plain radiograph showed an irregular, but
circumscribed, lytic epiphyseal lesion
surrounded by reactive bone sclerosis.
There was no evidence of bone expansion,
and the cortex was intact. The growth plates
were open.
The cytoplasmic borders were very
distinct with multiple foci of
"chicken-wire" calcification
(calcified reticulin network around
individual tumor cells).
A 20-year-old male presented with a painless, hard subcutaneous mass in the popliteal fossa. He stated that the mass had been present for several
years and did not change in size.
Two words, "painless" and "non-growing" (or very slow growing), suggest that the lesion described here is probably benign.
Plain radiograph demonstrated a
pedunculated bony outgrowth at the
proximal tibial metaphysis. The
lesion had a uniform, cartilagenous
cap with stippled calcifications. The
tibial cortex and medulla were
continuous with those of the lesion.
The specimen consisted of a
pedunculated lesion, 3 x 3 x
2cm, with a lobulated
cartilage cap measuring up to
0.9cm in thickness
Osteochondroma, the most common benign bone tumor, is not a
neoplasm but a hamartoma. It is thought to arise from a portion of
growth plate cartilage entrapped beneath the periosteum during skeletal
growth. These entrapped pieces continue to grow and ossify at the same
rate as the adjacent bone. When skeletal maturity is reached,
osteochondromas usually stop growing.
An incidental finding of a bone lesion in the distal femur of a 38-year old female. The lesion was completely asymptomatic.
Plain radiograph showed an intarmedullary zone
of stippled and ring-shaped calcifications in
the distal femoral metaphysis. This
mineralization pattern with radiodense stipples
and rings is characteristic of mature hyaline
cartilage.
Low-power microscopic examination of
the biopsy specimen shows three
characteristic features of this lesion: a)
vague lobularity; b) abundant cartilaginous
matrix, which can be focally calcified; c)
low cellularity.
High-power view shows clustered and
scattered chondrocytes with small,
uniform, darkly stained nuclei.
Occasional bi-nucleated chondrocytes are
present. Importantly, there were no
mitotic figures.
A 17-year-old male presented with a slowly enlarging, painful lesion of the right clavicle.
Plain radiograph reveals a
circumscribed, loculated,
radiolucent lesion producing
blowout expansion of the bone.
Gross photograph shows a spongy, expansile lesion
containing multiple, blood-filled cavities of varying sizes.
Low-power view demonstrates blood-filled
cystic spaces without recognizable
epithelial lining.
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