Bones And Muscles

1. BONES AND MUSCLES ROBERTO D. PADUA JR., MD, FPSP DEPARTMENT OF PATHOLOGY FATIMA COLLEGE OF MEDICINE

OSTEOGENESIS IMPERFECTA

Brittle bone disease

Hereditary disorder involving defects in the synthesis or structure of collagen type I

Cardinal features : osteopenia associated with recurrent fracture and skeletal deformity

Biochemical findings : increased AP, increased level of hydroxyproline, hypercalciuria

Histology : abnormal skeletal matrix; cartilaginous bars formed by vascular invasion of the metaphyses do not become envelop by bones; cortical bone is almost non-existent

1. OSTEOPOROSIS

Loss of normally mineralized bone

Diagnosed clinically with non-invasive radiographic techniques that measures bone density

Changes in the bone :

Structurally weak

Loss of trabecular bone

Enlargement of the medullary space

Cortical porosity

Reduction in cortical thickness

2. RENAL OSTEODYSTROPHY

Seen in patients with advanced renal failure

Clinical presentations :

Bone pain (most common), spontaneous fractures, aseptic necrosis of hip, myopathy

Laboratory findings :

Low levels of 1;25(OH)2D3,hyperphosphatemia, hypocalcemia, alterations in the secretion or activity of PTH

X-ray :

Subperiosteal erosions, patchy osteosclerosis (rugger jersey appearance of thoracic vertebral spine on lateral views, salt and pepper appearance of skull, slipped epiphyses

3. OSTEOMALACIA

Defective mineralization of the trabecular and cortical bone matrix

Associated with decreased serum calcium phosphate product

A common complication of chronic renal failure in adults

Secondary to Vitamin D deficiency

Histologically characterized by excessive quantities of osteoid because of the failed matrix calcification despite continued matrix synthesis by the osteoblasts

4. RICKETS

Defective mineralization of the epiphyseal growth plate cartilage

Clinical features : craniotabes, frontal bossing, rachitic rosary, pectus excavatum, Harrisons groove, thoracic kyphosis, rachitic potbelly, genu varum/genu valgum

Histologic appearance :

Rachitic growth plate is wide and irregular

Columnar rearrangement of the hypertrophic chondrocyts is lost

Zone of provisional calcification disappears

Cartilage extends deep into the metaphyses

5. Hyperparathyroidism

Skeletal manifestations are caused by unabated osteoclastic bone resorption

Entire skeleton is affected

Anatomic changes of osteitis fibrosa cystica are now rarely encountered

Skeletal abnormalities in secondary hyperparathyroidism tends to be milder

Morphology

Increased osteoclast activity affects cortical bone more severely than cancellous bone

X-ray involves the radial aspect of the middle phalanges of the index and middle fingers

Dissecting osteitis osteoclasts tunnel into and dissect centrally along the length of the trabeculae creating the railroad appearance of railroad tracks

Brown tumor bone loss predispose to microfractures and secondary hemorrhages that elicit an influx of multinucleated macrophages and an ingrowth of reparative fibrous tissue, creating a mass of reactive tissue

Generalized osteitis fibrosa cystica (von Recklinghausen disease of bone)

Hallmark of severe hyperparathyroidism

Composed of increased bone cell activity, peritrabecular fibrosis, and cystic bone tumors

FRACTURE REPAIR

Blastemawound closurescar formation

Initial repair tissue formed is called a CALLUS which is composed of fibrous tissue, woven bone and cartilage

3 phases of fracture healing :

A) inflammatory phase

B) reparative phase = orderly removal and replacement of immature woven bone by cartilage differentiation

C) modeling phase = realignment & mechanical shaping of the bone and callus; restoration of the medullary cavity and bone marrow

Complications of fracture healing :

A) nonunions

B) fibrous union

OSTEOMYELITIS

Classified according to several factors

1. its duration = acute, subacute or chronic

2. nature of the exudate = hemorrhagic, purulent, or nonsuppurative

3. its location = bone, periosteum, or epiphyses

4. etiologic agent = Staphylococcus, Tb, etc.

Histologically, inflammatory cells are seen

Loss of normal marrow architecture

Hematopoietic elements and fat are replaced by leukocytic infiltrates

OSTEOMYELITIS..

Causes:

Coagulase (+) Staph. Aureus (60-90%)

Streptococcus

Pneumococcus

E.coli

Klebsiella

Salmonella

Bacteroides

OSTEOMYELITIS..

Causes :

Tuberculosis

Spread hematogenously

Characteristic lesion : Chronic caseating granulomatous inflammation which often involves the subchondral part of the joint. Sequestrum forms in the subchondral bone and articular cartilage resulting in a kissing sequestrum.

Potts disease Tb of the spine

SARCOIDOSIS

Noncaseating granulomatous process

Manifest as small lytic and sclerotic foci in the bones of the hand

Large areas of destruction are not typically found

PAGETS DISEASE OF BONE (OSTEITIS DEFORMANS)

A chronic osteolytic and osteosclerotic disease of uncertain cause

May involve one or more bones

Presents with pain, skeletal deformities, and occasionally sarcomatous transformation

Usually affects 3% of white population over 40 y/o

Incidence increases with age; men>women

Most patients are asymptomatic (80-90%)

PAGETS DISEASE OF BONE..

Common skeletal sites of involvement are the sacrum, spine, pelvis, skull, femur, clavicle, tibia, ribs, and humerus

Histopathology:

Normal marrow is replaced by a richly vascular, loose fibrous connective tissue

Isolated clusters of inflammatory cells may be seen

Osteoclasts aggregate on the existing bone trabeculae and within the cortex

Innumerable small, irregularly shaped bone fragments (mosaic pattern)

Grossly resembles the gritty but brittle texture of pumice or lava rock

PAGETS DISEASE OF BONE.

X-RAY : flocculant, radiopaque deposit likened to cotton wool. Pelvis is the most common site of involvement.

Elevated AP and osteocalcin level

Elevated urinary excretion of hydroxyproline, pyridinoline and deoxypyridinoline

Malignant transformation are also observed

Osteosarcomas

Fibrosarcomas

Giant cell malignant fibrous histiocytoma

OSTEONECROSIS

Infarction of bone typically involving the femoral head

3 generic categories = post-fracture, idiopathic, and renal transplant associated

Also known as avascular necrosis of bone

Earliest histologic changes are death of the bone and the surrounding hematopoietic & fatty marrow

X-ray : Crescent sign , a separation of fracture cleft forms between the impacted fragments and the overlying sub-chondral plate. Increased density within the necrotic bone.

Most malignant tumors arise de novo

Benign bone lesions that predispose to the development of skeletal malignancies

Pagets disease, chondromatosis, osteochondromatosis, fibrous dysplasia, and osteofibrous dysplasia

Five basic parameters in the diagnosis of bone tumors

Age of the patient

Bone involved

Specific area within the bone

Radiographic appearance

Microscopic appearance

1. OSTEOMA

Seen almost exclusively in the flat bones of skull and face

Microscopically: composed of dense, mature, predominantly lamellar bone

Benign

Associated with Gardners syndrome

2. OSTEOID OSTEOMA

Benign neoplasm seen in patients between 10 and 30 y/o

2:1 male-female ratio

Intense pain is the most prominent symptom

Reported in practically every bone, most are centered in the cortex (85%), spongiosa (13%), or subperiosteal region (2%)

X-ray: typical finding is a radiolucent nidus that is seldom larger than 1.5 cm and may or may not contain a dense center. This nidus is surrounded by a peripheral sclerotic reaction.

Microscopic: sharply delineated central nidus composed of more or less calcified osteoid lined by plump osteoblast and growing within vascularized connective tissue, without evidence of inflammation.

2. OSTEOBLASTOMA

Benign osteoblastoma, giant osteoid osteoma

Closely related to osteoid osteoma both microscopically and ultrastructurally

It has a larger size of the nidus, absence of surrounding area of reactive bone formation, and the lack of intense pain

A cartilaginous matrix is present in some cases

Most cases arise in the spongiosa of the bone involving the spine or major bones of the lower extremity

Osteomalacia can be seen as a complication

3. OSTEOSARCOMA

The most frequent primary malignant tumor, exclusive of hematopoietic malignancy

Usually occurs in patients between 10 and 25 years of age and is rare in pre-school children

Another peak age incidence occurs after the age of 40, in association with other disorders

Most osteosarcomas arise de novo, but others arise within the context of a preexisting condition

Pagets disease, radiation exposure, chemotherapy, preexisting benign bone lesions, foreign bodies, trauma

OSTEOSARCOMA..

Located in the metaphyseal area of long bones, particularly the lower end of femur, upper end of the tibia, and the upper end of the humerus

Large majority arise within the medullary cavity from which they extend into the cortex

Gross appearance varies depending on the relative amounts of bone, cartilage, cellular stroma and vesselsbony hard to cystic, friable, and hemorrhagic

From its usual origin in the metaphysis of a long bone, the tumor may spread along the marrow cavity, invade the adjacent cortex, or elevate or perforate the periosteum (Codmans triangle)

OSTEOSARCOMA..

Extend into the soft tissues, extend into the epiphysis, extend into the joint space, form satellite nodules independent from the main tumor mass proximal to the primary lesion (skip metastases), metastasize through the blood stream to distant sites particularly the lung.

OSTEOSARCOMA..

Microscopic features

May destroy preexisting bone trabeculae or grow around them in an appositional fashion

Key feature is the presence of osteoid and or bone produced directly by tumor cells without interposition of cartilage

Osteoblastic areas are often mixed with fibroblastic and chondroblastic foci

Tumor cells may grow in diffuse, nesting or pseudopapillary arrangements

OSTEOSARCOMA..

OS cells usually exhibit strong AP activity, regardless of their appearance

Ultrastructurally, tumor cells resemble normal osteoblasts

Consistently expresses Vimentin

In some cases, they are positive for smooth muscle actin, desmin, EMA, S-100 protein

Osteonectin, osteocalcin, osteopontin bone morphogenetic protein and bone GLA protein have been identified immunohistochemically

OSTEOSARCOMA..

Microscopic variants

Telangiectatic

Small cell

Fibrohistiocytic

Anaplastic

Well-differentiated intramedullary

Others = parosteal (juxtacortical), periosteal

OSTEOSARCOMA..

Diagnosis: characteristic radiographic appearance, open biopsy, needle biopsy, FNAB, frozen section.

Therapy: amputation or disarticulation. At present, limb-sparing procedures coupled with other therapeutic modalities.

Prognosis:

Poor : presence of Pagets disease, multifocal OS, chondroblastic type, Telangiectatic variant, elevated AP, low postchemotherapy tumor necrosis, loss of heterozygosity of the RB gene, HER2/neu expression, expression of P-glycoprotein

1. CHONDROMA

A common benign cartilaginous tumor that occurs most frequently in the small bones of the hands and feet, particularly the proximal phalanges

30% are multiple

Microscopically, they are composed of mature hyaline cartilage. Foci of myxoid degeneration, calcification, and endochondral ossification are common

Enchondromas begins in the spongiosa of the diaphysis from which they expand and thin out the cortex

Lesions with predominantly unilateral distribution are referred to as Olliers disease

Its association with soft tissue hemangiomas is known as Maffuccis syndrome

2. OSTEOCHONDROMA

Most frequent benign tumor

Usually asymptomatic, but may lead to deformity or interfere with the function of adjacent structures such as tendons and blood vessels

Most common locations are metaphyses of the lower femur, upper tibia, upper humerus and pelvis

Average age of onset is 10 y/o, majority appears before the age of 20

Average greatest diameter is 4 cm but may reach 10 cm or more

A cap of cartilage covered by fibrous membrane continous with the periosteum of the adjacent bone

Microscopically, the cells resemble those of normal hyaline cartilage. Eosinophilic, PAS-(+) inclusions may be seen in the cytoplasm. The bulk of the lesion is composed of mature bone trabeculae located beneath the cartilaginous cap and containing normal bone marrow.

3. CHONDROBLASTOMA

Occurs predominantly in males under 20 y/o

Usually arises in the epiphyseal end of long bones before the epiphyseal cartilage has disappeared, particularly in the distal end of femur, proximal end of humerus, and proximal end of tibia

X-ray: tumor is fairly well delimited and contains areas of rarefaction

Microscopic:

the basic tumor cell is an embryonic chondroblast with only a limited capacity for the production of cartilaginous matrix.

Presence of occasional scattered giant cells

CHONDROBLASTOMA..

Microscopic:

Cells are usually polyhedral with round to indented nuclei. Reticulin fibers surround each individual cell.

Presence of small zones of focal calcification (chicken wire)

Diagnosis can be made by fine needle aspiration which will show neoplastic chondroblast, multinucleated osteoclast-like giant cells, and chondroid myxoid fragments

Treatment is by curettement with bone grafting

4. CHONDROMYXOID FIBROMA

An unusual benign tumor

Usually occurs in long bones of young adults

Radiographically, it is sharply defined and may attain a large size

Grossly, it is solid and yellowish white or tan, replaces bone and thins the cortex.

Microscopically, shows hypocellular lobules with a chondromyxoid appearance separated by intersecting bands of fibroblast-like spindle cells and osteoclasts

Strong positivity to S-100 protein

Treatment is by curettage with a recurrence rate of 25%

5. CHONDROSARCOMA

A malignant tumor of cartilage-forming tissues

Divided into conventional and variants

Conventional chondrosarcoma can be

Central = located in the medullary cavity, usually of flat or long bone. X-ray show osteolytic lesion with splotchy calcification with ill-defined margins, fusiform thickening of the shaft, and perforation of the cortex

Peripheral = may arise de novo or from the cartilaginous cap of a preexisting osteochondroma

Juxtacortical (periosteal) = involves the shaft of a long bonecharacterized by a cartilaginous lobular pattern with areas of splotchy calcification and endochondral ossification

CHONDROSARCOMA..

Microscopically, there is production of cartilaginous matrix and the lack of direct bone formation by the tumor cells

Soft tissue implantation following biopsy is a well known complication

Chondrosarcoma variants

Clear cell chondrosarcoma

Myxoid chondrosarcoma

Dedifferentiated chondrosarcoma

Mesenchymal chondrosarcoma

Osteoclastoma

Patients are over 20 years of age

More common in women then men

More frequently in Oriental than Western countries

Classic location is epiphysis of long bone

Affects more commonly the lower end of femur, upper end of tibia, and lower end of the radius. It also occurs in the humerus, fibula, and skull particularly the sphenoid bone.

Multicentricity has been reported particularly in young patients and in the small bones of hands and feet

X-ray:

The typical appearance is that of an entirely lytic, expansile lesion in the epiphysis, usually without peripheral bone sclerosis, or periosteal reaction

Gross:

The size of the tumor varies; when large, it may be associated with a pathologic fracture

The cut surface is solid and tan or light brown, traversed by fibrous trabeculae, and often contains hemorrhagic areas

The cortex is thinned, but periosteal new bone formation is rare

Microscopic:

Two main components are stromal cells and giant cells

The giant cells are usually large and have over twenty or thirty nuclei, most of then are arranged toward the center.

They resemble osteoclasts at all levels: ultrastructurally, enzyme histochemically and immunohistochemical

Result of fusion of circulating monocytes that have been recruited into the lesion

Possible mechanisms:

Autocrine or paracrine loop mediated by transforming growth factor beta

Microscopic..

Possible mechanisms.

2. Production of osteoprotegerin ligand (a factor essential for osteoclastogenesis)

3. Expression of the ligand for RANK (receptor activator of nuclear factor Kappa B)

Mononuclear stromal cells is the only proliferating element in the lesion and the one exhibiting atypia in the rare cytologically malignant examples of this tumor

These changes may be focal, hence a thorough sampling is required

Produces type I & III collagen and has receptors for PTH

Frequent positivity for S-100 protein

Many benign lesions with giant cells have been diagnosed as giant cell tumor in the past

A diagnosis of a lesion other than GCT should be favored if:

1. patient is a child

2. lesion is located in the metaphysis or diaphysis of a long bone

3. lesion is multiple

4. lesion is located in the vertebrae, jaw, or bones of the hands or feet

1. EWINGS SARCOMA/PRIMITIVE NEUROECTODERMAL TUMOR (PNET)

Undifferentiated type of bone sarcoma in children

Related to the neoplasm originally described in the soft tissues as primitive (peripheral) neuroectodermal tumor

Usually seen in patients between the ages of 5 and 20 years

Clinically, the tumor may simulate OM because of pain, fever, and leukocytosis

Occurs most often in long bones (femur, tibia, humerus, and fibula) and in the bones of the pelvis, rib, vertebrae, mandible and clavicle

It generally arises in the medullary canal of the shaft, from which it permeates the cortex and invade the tissues

Can present clinically as a soft tissue neoplasm with a normal appearance of the underlying bone on plain x-ray films

X-ray : cortical thickening and widening of the medullary canal. With progression of the lesion, reactive periosteal bone may be deposited in layers parallel to the cortex (onion-skin appearance) or at right angle to it (sun-ray appearance)

Microscopic :

Consists of solid sheets of cells divided into irregular masses by fibrous bands

Individual cells are small and uniform

The cells outline are indistinct, resulting in a syncitial appearance

The nuclei are round, with frequent indentations, small nucleoli and variable but usually brisk mitotic activity

There is well developed vascular network

Pseudorosettes and rosettes arrangement of cells may be seen

Cells contains large amounts of cytoplasmic glycogen --- (+) PAS

Ultrastructurally shows few dense core granules

Immunohistochemically, positive for vimentin, LMW keratin, NSE, protein gene product 9.5, Leu7, and neurofilaments

Over 95% of cases show a reciprocal translocation 11;22 (q24;q12)

Metastatic spread is to the lungs and pleura, other bones (particularly the skull), CNS, and (rarely) regional LN

About 25% of the patients have multiple bone and/or visceral lesions at the time of presentation

Treatment:

Combination of high-dose irradiation and multidrug chemotherapy sometimes combined with limited surgery

2. MALIGNANT LYMPHOMA

Can involve the skeletal system primarily or as a manifestation of a systemic disease

LARGE CELL LYMPHOMA

More common in adults than in children

60% of cases occurring in patients over 30 y/o

No sex predilection

Most cases involve the diaphysis or metaphysis og long bones or vertebrae producing patchy cortical and medullary destruction associated with minimal to moderate periosteal reaction

The tumor is pinkish gray and granular, frequently extends into the soft tissues and invades the muscle

LARGE CELL LYMPHOMA..

Radiographically, a combination of bone production and bone destruction often involves a wide area of a long bone

Microscopically, the appearance is similar to that of the large cell lymphoma in nodal and other extranodal sites, some cases are accompanied by prominent fibrosis

The 5-year survival rate for localized B-cell lymphoma of bone has ranged from 30-60%

The stage of the disease is the single most important prognostic determinator

HODGKINS LYMPHOMA

Produces radiographically detectable bone lesions in approximately 15% of the patients

Involvement is multifocal in about 60% of cases, most frequent sites being vertebrae, pelvis, ribs, sternum, and femur

Osseous lesions are often asymptomatic and in half of the cases are not demonstrable radiographically

Anaplastic large cell lymphoma

Burkitts lymphoma

Lymphoblastic lymphoma

Associated with radiographic abnormalities in the skeletal system in 70-90% of cases

Destructive bone lesions are extremely rare in the chronic leukemias

1. HEMANGIOMA

Often seen in the vertebrae as an incidental post-mortem finding

The most common locations are the skull, vertebrae, and jaw

Cut section has a currant jelly appearnce

Microscopically, there is a thick-walled lattice-like pattern of endothelial lined cavernous spaces filled with blood

Multiple hemangiomas are mainly seen in children and are associated in about half of the cases with cutaneous, soft tissue, or visceral hemangiomas

2. MASSIVE OSTEOLYSIS

Gorhams disease

Not a vascular neoplasm

Has microscopic similarities with skeletal angiomatosis

It has a destructive character

It results in reabsorption of a whole bone or several bones and the filling of the residual spaces by a heavy vascularized fibrous tissue

3. LYMPHANGIOMAS

Most cases are multiple and associated with soft tissue tumors of similar appearance

4. GLOMUS TUMOR

May erode the underlying bone

5. HEMANGIOPERICYTOMA

Can present as a primary bone lesion, most common location is the pelvis

6. EPITHELIOID HEMANGIOENDOTHELIOMA

A borderline type of vascular neoplasm characterized microscopically by the presence epithelial- or histiocyte-like endothelial cells with abundant acidophilic and often vacuolated cytoplasm, large vesicular nucleus, modest atypia, scanty mitotic activity, inconspicous or absent anastomosing channels, recent and old hemorrhage and an inconstant but sometimes prominent inflammatory component rich in eosinophils

7. ANGIOSARCOMA

Malignant hemangioendothelioma, hemangioendothelial sarcoma

Exhibits obvious atypia of the tumor cells, formation of solid areas alternating with others with anastomosingvascular channels, and foci of necrosis and hemorrhage

Multicentricity is common

Distant metastasis are common, particularly lungs

In most cases the lesions are multiple

More than 80% arises from the breast, lung, prostate, thyroid, or kidney

These metastases can be accompanied by visceral deposits or represent the only apparent site of dissemination

Soft tissue sarcomas rarely metastasize to the bones except embryonal rhabdomyosarcoma in children

They are usually osteolytic but maybe osteoblastic or mixed

The mechanism is thought to be the production of bone growth factors by tumor cells, such as TGF-beta, fibroblast growth factor, and bone morphogenetic proteins

Symptoms is usually pain

Treatment is relief of pain and to prevent fracture of weight-bearing bones

1. SOLITARY BONE CYST

Unicameral bone cyst

Usually occur in long bones, most often in the upper portion of the shaft of the humerus and femur

Also seen in the short bones, calcaneus

Mostly affects males and are seen in patients under 20 years

Usually are advanced when first seen, most are centered in the metaphysis and they migrate away from the epiphyseal line

SOLITARY BONE CYST.

The cysts contains a clear or yellow fluid that is lined by a smooth fibrous membrane

Maybe hemorrhagic if previous fracture occurred

Microscopic: well-vascularized connective tissue, hemosiderin and cholesterol clefts are frequent

Treatment of choice is curettement and replacement of the cyst with bone chips

2. ANEURYSMAL BONE CYST

Usually seen in patients between 10 and 20 years of age

More common in females

Occurs mainly in the vertebrae and flat bones but can also arise in the shaft of long bones

Multiple involvement is common in the vertebral lesions

X-ray: shows eccentric expansion of the bone with erosion and destruction of the cortex and a small area of periosteal new bone formation

ANEURYSMAL BONE CYST.

GROSS: it forms a spongy hemorrhagic mass covered by a thin shell of reactive bone, which may extend into the soft tissue

Microscopic:

show large spaces filled with blood

They do not contain endothelial lining but are rather delimited by cells with similar features to fibroblast, myofibroblasts, and histiocytes

A row of osteoclasts is often seen immediately beneath the surface

There is significant deposition of generated calcifying fibromyxoid tissue.

ANEURYSMAL BONE CYST.

Pathogenesis is still unknown

In a few cases, the lesion is preceded by trauma with fracture or subperiosteal hematoma

It may also arise in some preexisting bone lesion as a result of changed hemodynamics

Insulin-like growth factor-I may play in its pathogenesis

Ddx: chondroblastoma, GCT, fibrous dysplasia, nonossifying fibroma, osteoblastoma, chondrosarcoma

Treatment : en bloc resection or curettage with bone grafting

RHABDOMYOSARCOMA

Most common soft tissue sarcoma of childhood and adolescence

Usually appears before the age of 20

Commonly occurs in the head and neck or genitourinary tract, extremities

Cytogenic abnormalities

t(2;13)(q35;q14)

t(1;13)(q36;14)

RHABDOMYOSARCOMA

In the more common translocation, t(2;13), the PAX3 gene on chromosome 2 fuses with the FKHR gene on chromosome 13

PAX3 gene functions upstream of genes that control muscle differentiation

Pathogenesis of tumor involves dysregulation of muscle differentiation by the chimeric PAX3-FKHR protein

RHABDOMYOSARCOMA MORPHOLOGY

EMBRYONAL

ALVEOLAR

PLEOMORPHIC

*** Diagnostic cell is the RHABDOMYOBLAST

= contains eccentric eosinophilic granularcytoplasm rich in thick and thin filaments

= may be round or elongated (tadpole or strap cells

= Ultrastructurally, contain sarcomeres

= Immunohistochemically, they stain withantibodies to the myogenic markers desmin,MYOD1 and myogenin

EMBRYONAL RHABDOMYOSARCOMA

Most common type, accounting to 60%

Includes Sarcoma Botryoides

Occurs in children under 10 years of age

Typicallyarises in the nasal cavity, orbit, middle ear, prostate and paratesticular region

Allelic loss of chromosome 11p15.5 as its major genomic abnormality

EMBRYONAL RHABDOMYOSARCOMA

Grossly, they present as a soft gray infiltrative mass

Microscopically, the tumor cells mimic skeletal muscle cells at various stages of embryogenesis and consist of sheets of both malignant round and spindled cells in a variably myxoid stroma

Sarcoma botryoides grows in a polypoid fashion, producing the appearance of a cluster of grapes protruding into a hollow structure such as the bladder or vagina

ALVEOLAR RHABDOMYOSARCOMA

Most common in the early and mid-adolescence and usually arises in the deep musculature of the extremities

Histologically, the tumor is traversed by a network of fibrous septae that divide the cells into clusters or aggregates; as the central cells degenerate and drop out, resembles pulmonary alveolae

Tumor cells are moderate in size and have little cytoplasm

ALVEOLAR RHABDOMYOSARCOMA

Cells with cross-striations are identified in about 25% of cases

Cytogenetic studies show a t(2;13) or t(1;13) chromosomal translocations

PLEOMORPHIC RHABDOMYOSARCOMA

Characterized by numerous large, sometimes multinucleated, bizarre eosinophilic tumor cells

This variant is rare

Arises in the deep soft tissue of adults

Resemble malignant fibrous histiocytoma histologically

RHABDOMYOSARCOMA

Usually treated with a combination of surgey and chemotherapy with or without radiation

Histologic variant and location of the tumor influence survival

Sarcoma botryoides have the best prognosis, followed by embryonal, pleomorphic, and alveolar variants

Overall prognosis for children is good = 65%;less for adults

LEIOMYOMA

Benign smooth muscle tumor, commonly arises in the uterus

May also arise in the erector pili muscles found in the skin, nipples, scrotum and labia and less in the deep soft tissues

Multiple lesions is thought to be hereditary and transmitted as an autosomal dominant trait

Occur in adolescence and early adult life

LEIOMYOMA

Tumors are usually not larger than 1 to 2 cm in greatest dimension

Composed of fascicles of spindle cells that tend to intersect each other at right angles

Tumor cells have blunt-ended, elongated nuclei and show minimal atypia and few mitotic figures

Treatment is surgical

LEIOMYOSARCOMA

Account for 10 to 20% of soft tissue sarcomas

Occurs in adults, women>men

Most develop in the skin and deep soft tissues of the extremities and retroperitoneum

Present as painful, firm masses

Retroperitoneal tumors may be large and bulky and cause abdominal symptoms

LEIOMYOSARCOMA

Histologically, characterized by malignant spindle cells that have cigar-shaped nuclei arranged in interweaving fascicles

Immunologically, they stain with antibodies to vimentin, actin, smooth muscle actin and desmin

Treatment depends on the size, location and grade of the tumor

Bones And Muscles

Health & Medicine

Transcript of Bones And Muscles