soft & bone tumours 2006

7/31/2019 Soft & Bone Tumours 2006

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Soft Tissue Tumours: Definition

Mesenchymal proliferations that occur in the extraskeletal, nonepithelialtissues of the body, excluding the viscera, coverings of the brain, and

lymphoreticular system.


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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 peripheralnerve sheath tumour

Uncertain histogenesis Granular cell tumour Synovial Sarcoma

Alveolar soft part

sarcoma

Epithelioid sarcoma


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The cause of most soft tissue tumors is unknown. There are documented

associations, however, between radiation therapy and rare instances inwhich 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 isrelated 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), andOsler-Weber-Rendu syndrome (telangiectasia).


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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 drawbackof this classification system is that itdoes not really take into account the grade of the tumor and its

implications for prognosis.


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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 high-

grade (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 Ewings and osteosarcomas are

always high-grade

The American Joint Committee on Cancer (AJCC) has developed aclinicopathologic staging system that depends primarily on the grade

and size of soft-tissue sarcomas


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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 well-

encapsulated mass ofmature adipocytes that varies considerably in size.

It arises in the subcutis of the proximal extremities and trunk, mostfrequently during mid-adulthood. Infrequently, lipomas are large,

intramuscular, and circumscribed. Histologically, they consist ofmature

fat cells with no evidence of pleomorphism or abnormal growth.

Lipomas are soft, mobile, and painless (except angiolipoma) and areusually 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 .


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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


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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 superficialfibromatoses. They are characterized by nodularor poorly defined fascicles ofmature-appearing fibroblasts surrounded by abundant

dense collagen. Immunohistochemical and ultrastructural studies indicate that many of

these cells aremyofibroblasts

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.


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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, fish-

flesh masses often having areas of hemorrhage and necrosis. Better-

differentiated 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, frequentmitoses, and areas of necrosis.


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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 orgenitourinary tract.

MORPHOLOGY.

Rhabdomyosarcoma is histologically subclassified into the embryonal,

alveolar, and pleomorphic variants. The rhabdomyoblast--the diagnosticcell 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


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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


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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. Leiomyomasmay 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. Mostdevelop 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 ofnecrosis is present


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SYNOVIAL SARCOMA
http://www.microscopyu.com/galleries/pathology/leiomyosarcoma.html


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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 forapproximately 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.


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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??


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Bone TumoursWHAT 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-approachCorrelate Pathological findings with clinical presentation

(Clinico-pathological correlation)

CLASSIFICATIONS OF PRIMARY TUMOURS


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CLASSIFICATIONS OF PRIMARY TUMOURS

INVOLVING BONESMetastatic cancers are the most frequent malignant tumors found in bone

Histological Types Benign Malignant

Hematopoietic (40%) 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

AdamantinomaHistiocytic origin

Fibrogenic

Notochordal

Vascular, Cystic, lipogenic

neurogenic

Fibrous histiocytoma

Fibroma

MFH

Fibrosarcoma

Chordoma


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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 involvementmetastatic neuroblastoma

10 - 20

non-ossifying fibroma

fibrous dysplasia

simple bone cyst

aneurysmal bone cyst

osteochondroma (exostosis)

osteoid osteomaosteoblastoma

chondroblastoma

chondromyxoid fibroma

osteosarcoma,

Ewing's sarcoma,

adamantinoma

20 - 40enchondroma

giant cell tumorchondrosarcoma

40 & above osteoma

metastatic tumors

myeloma

leukemic involvement

chondrosarcoma

osteosarcoma (Paget's associated)

MFH

chordoma


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SITE OF LONG BONE INVOLVEMENT

(most primary bone tumors have favored sites within long bones; this may provide a clue to

diagnosis).

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 theepiphysis. 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.

Metaphyseal exostosis:

Osteochondroma

Metaphyseal intramedullary lesions:

Osteosarcoma is usually centered in the

metaphysis. Chondrosarcoma and

fibrosarcoma often present as metaphyseallesions. Osteoblastoma, enchondroma,

fibrous dysplasia, simple bone cyst, and

aneurysmal bone cyst are common in this

location.

Diaphyseal lesions centered inthe cortex:

Adamantinoma, osteoid

osteoma

General Histologic Assessment of the Lesion


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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)


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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 malignanttumor osteoid.

Biopsy material shows two major

components of this neoplasm: highly

pleomorphic cells and haphazarddeposits of osteoid. Note that the

malignant cells fill the spaces between

osteoid deposits. Lace-like osteoid

deposition is very characteristic of this

neoplasm.


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The tan-white tumor fills most of

the medullary cavity of the

metaphysis and proximal

diaphysis. It has infiltratedthrough the cortex, lifted the

periosteum, and formed soft

tissue masses on both sides of the

bone.


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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


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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 softtissue 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.


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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)


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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

j i t ff i L b t k h d l l l f l i h h t d lk li


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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.


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A 45-year old female presented with increasing pain and swelling around the knee. She mentioned that the symptoms had progressed over a 4-

month 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, ill-

defined 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.


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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 ld f l i l i f i i l i f l l f h l l i i d i h ild j i ff i


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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 ld l d i h i l h d b i h li l f H d h h h d b f l


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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. Thelesion 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 x2cm, 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.


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An incidental finding of a bone lesion in the distal femur of a 38-year old female. The lesion was completely asymptomatic.


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Plain radiograph showed an intarmedullary zone

ofstippled 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


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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 recognizableepithelial lining.


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OncologistBoneTumours

DiagnosisTreatment

Radiologist

Cytopathologist

Surgeon

HistopathologistMolecular

PathologistGeneticist

psychiatrist

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Support staff

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soft & bone tumours 2006

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