Musculo-skeletal system
2016Objectives
Defining and mentioning pathogenesis of inherited bone development disorders including osteogenesis imperfecta and achondroplsiaDefining and mentioning the pathogenesis of acquired bone development disorders (osteoporosis, Paget’s disease, rickets and osteomalasia)Features of bone infectionFeatures of bone neoplasmsDefining, listing the pathological features and mentioning the pathogenesis of OA. Defining, listing the pathological features and mentioning the pathogenesis of Gout disease. Defining infectious arithritis Mentioning two examples on joint tumors Defining muscle atrophy and dystrophy Mentioning examples on muscle tumors Examples of soft tissue tumors
Congenital anomalies of bone
Osteogenesis Imperfecta (OI) defective synthesis of and thus premature degradation of type I collagen There is too little bone that show marked cortical thinning and attenuation of trabeculae resulting in extreme susceptibility to fracturesAchondroplasia
mutation in the fibroblast growth factor receptor, which causes inhibition of chondrocyte proliferationAchondroplasia is an autosomal dominant disorder
Un affectedAchondroplasia
Intrauterine death
ACQUIRED DISEASES OF BONE DEVELOPMENT
osteoporosisincreased porosity of the skeleton resulting from reduced bone mass that can be Primary: (most common) Postmenapausal Senile Secondary Endocrine disorders Neoplasia Gastrointestinal diseases Drugs Miscellaneous
Obvious increase in porosity of the bone
thinning of the trabeculae and widening of Haversian canals no alteration in the ratio of minerals to protein matrix.osteoporosis
imbalance of bone formation that favors more bone resorption. It is caused by imbalance in RANK RANK receptors OPG It causes: Pathological fractures Kyphoscoliosis Various deformities
Paget’s disease repetitive episodes of exaggerated, regional osteoclastic activity (osteolytic stage), followed by exuberant bone formation (mixed osteoclastic-osteoblastic stage), and then exhaustion of cellular activity (osteosclerotic stage) There is net gain of bone mass that lack strength
Paget’s disease Occurs in mid-adulthood then become more common Axial skeleton and femur are more commonly affected Complications include: Congestive heart failure Cranial nerve injury osteosarcoma
Rickets and Osteomalacia
an excess of unmineralized matrix. Rickets in growing children and osteomalacia in adults result from: Diets deficient in calcium and vitamin D Limited exposure to sunlight. Renal disorders causing decreased synthesis of 1,25 (OH)2-D or phosphate depletion Malabsorption disorders.Pathogenesis
Decrease bone mineralization
In rickets
derangement of endochondral bone growth
Overgrowth of epiphyseal cartilage Deposition of osteoid matrix Disruption of the orderly replacement of cartilage by osteoid matrix Microfractures and Deformation of the skeleton
Features of rickets and osteomalasia
In infancy: Frontal bossing Rachitic rosary in the chest pigeon breast deformity In ambulating child : lumbar lordosis bowing of the legs In adult Although the contours of the bone are not affected, the bone is weak and vulnerable to gross fractures or microfractures, which are most likely to affect vertebral bodies and femoral necksHyperparathyroidism
Primary by parathyroid gland adenomaSecondary in renal failure: increased PTH secretion induced by hypocalcemia that result from:inadequate 1,25-(OH)2-D synthesis hyperphosphatemia that suppresses renal α1-hydroxylaseBone changes include: (ostieitis fibrosa cystica)Replacement of cortical bone by loose connective tissueSubperiosteal bone resorption more in distal phalangies reduced bone massostieitis fibrosa cystica
OsteonecrosisIschemic necrosis with resultant bone infarction occurs mostly due to fracture or after corticosteroid use that lead to subchondral infarcts Then osteoclasts can resorb many of the necrotic bony trabeculae Subchondral infarcts often collapse and can lead to severe osteoarthritis
Osteomyelitis
Acute or chronic inflammation of the bone and related marrow cavity almost always due to infection (pyogenic or tuberculous).Pyogenic osteomyelitis
Hematogenous dissemination, extension from a nearby infection or traumatic implantation Staphylococcus aureus is the most frequent cause Mixed bacterial infections, occur in osteomyelitis complicating bone trauma. In as many as 50% of cases, no organisms can be isolated
Pathological features
Acute inflammatory reaction with formation of sequestrum. Extension of infection to the subperiosteal space that in children results in sizable subperiosteal abscesses segmental bone necrosis. cutaneous draining sinus suppurative arthritis in infants Viable organisms can persist in the sequestrum for yearsosteomyelitis
Complications of chronic OM1. A source of acute exacerbations 2. Pathologic fracture 3. Secondary amyloidosis 4. Endocarditis 5. Development of squamous cell carcinoma in the sinus tract (rarely osteosarcoma).
Tuberculous Osteomyelitis
complicates up to 3% of those with pulmonary tuberculosisThe long bones and vertebrae are favored sitesgranulomatous inflammation with caseous necrosis and extensive bone destructionPott’s disease is a TB of vertebral bodies that may lead to vertebral collapse and neurological deficitpsoas muscle abscesses is fairly common in Pott diseaseBONE TUMORS
classified according to their normal cell of origin or line of differentiation Most bone tumors develop during the first few decades of life and tend to originate in the long bones of the extremities clinical information is often critical for the appropriate diagnosis Occasionally, a sudden pathologic fracture is the first manifestation.
Bone-Forming Tumors
Osteoma is a benign lesion of bone most common in the head, including the paranasal sinuses Microscopically, there is a mixture of woven and lamellar bone. may cause local mechanical problems (e.g., obstruction of a sinus cavity) and cosmetic deformitiesOsteoid osteoma and osteoblastoma
Both lesions typically arise during the 2nd & 3rd decades They are well-circumscribed lesions, usually involving the cortex The nidus (central part) is radiolucent Osteoid osteoma is smaller, arising in long bones and causes pain relived by aspirin Osteoblastomas arise most often in the vertebral column; they also cause pain, which is not responsive to aspirin Malignant transformation is rare when the lesion is treated by radiationOsteoid osteoma
Osteosarcomais “a bone-producing malignant mesenchymal tumorExcluding myeloma and lymphoma, osteosarcoma is the most common primary malignant tumor of bone (20%)The peak age of incidence is 10-25 years with 75% of the affected patients are younger than age 20 years; there is a second peak that occurs in the elderly, usually secondary to other conditions, e.g. Paget disease, bone infarcts, and prior irradiation
60% occurring about the knee, 15% around the hip, & 10% at the shoulder arising in the metaphysis. RB , P53 and cyclin D3 are implicated in pathogenesis Osteosarcomas typically spread hematogenously; 10% to 20% of patients have demonstrable pulmonary metastases at the time of diagnosis
Gross and radiological features
gritty, gray-white, often with foci of hemorrhage and cystic degeneration. destroys the surrounding cortex to extend into the soft tissue penetration of the epiphyseal plate or the joint space is infrequent. Radiographs usually show a large, destructive, mixed lytic and blastic mass with infiltrating margins (Codman triangle) is characteristic but not specific of osteosarcomaMicroscopic features
Tumor cells are pleomorphic with large hyperchromatic nuclei; bizarre tumor giant cells are common, as are mitoses Formation of osteoid by malignant cells is essential for diagnosis of osteosarcoma. Cartilage can be present in varying amounts RB , P53 and cyclin D3 are implicated in pathogenesis
osteosarcoma
Cartilage-Forming TumorsOsteochondroma common benign cartilage-capped outgrowth attached by a bony stalk to the underlying skeleton Solitary are usually in late adolescence and early adulthood (male-to-female ratio of 3:1) Multiple become apparent during childhood, occurring as multiple hereditary exostosis, an autosomal dominant disorder the EXT gene (a tumor suppressor gene) is implicated in pathogenesis Arise in long bone and only rarely in short tubular bones.
Osteochondromas vary from 1-20cm in size Newly formed bone form the inner part that is covered by bengin cartilage may be painful multiple hereditary exostoses are at increased risk of malignant transformation
Chondroma (benign)
When it arises within the medullary cavity, it is termed enchondroma when on the bone surface it is called juxtacortical chondroma the favored sites being the short tubular bones of the hands and feet. Ollier disease is characterized by multiple chondromas Enchondromatosis are at increased risk of malignant transformationEnchondromas are gray-blue, translucent nodules usually smaller than 3 cm
Chondrosarcomas (malignant)production of a cartilaginous matrix and the lack of direct bone formation by the tumor cells Either conventional or variant (location or microscopic appearance) most patients age 40 years or more, with men affected twice as frequently as women. central (medullary), peripheral (cortical), and juxtacortical (periosteal).
Conventional chondrosarcomas : arise within the medullary cavity of the bone to form an expansile glistening mass that often erodes the cortex . Spotty calcifications are typically present
Higher grade lesions contain pleomorphic chondrocytes with frequent mitotic figures with multinucleate cells and lacunae containing two or more chondrocytes
Other variants include myxoid, clear-cell and mesenchymal chondrosarcomas Dedifferentiated chondrosarcoma indicate presence of high grade sarcomatous elements in otherwise low grade tumor. There is also a direct correlation between grade and biologic behavior tumors larger than 10 cm being significantly more aggressive than smaller tumors
Fibrous and Fibro-Osseous Tumors
Fibrous Cortical Defect and Nonossifying FibromaFibrous cortical defect found in 30% to 50% of children older than 2 years found in 30% to 50% of children older than 2 years may enlarge in size (5-6 cm) to form nonossifying fibromas sharply demarcated radiolucencies surrounded by a thin zone of sclerosis
Fibrous cortical defects are asymptomatic and are usually only detected as incidental radiographic lesions Most undergo spontaneous differentiation into normal cortical bone Fibrous cortical defects are asymptomatic and are usually only detected as incidental radiographic lesions benign fibroblasts (arranged in stroriforms) and macrophages, including multinucleated forms
Fibrous Dysplasia
Microscopic features There are curved trabeculae of woven bone (mimicking Chinese characters), without osteoblastic rimming The above are set within fibroblastic proliferation Rarely, polyostotic disease can transform into osteosarcoma, especially following radiotherapyOther Bone Tumors
Ewing Sarcoma & Primitive Neuroectodermal Tumor (PNET)
primary malignant small round-cell tumors of bone and soft tissue viewed as the same tumor because they share an identical chromosome translocation PNETs demonstrate neural differentiation whereas Ewing sarcomas are undifferentiated the second most common pediatric bone sarcomas.Most patients are 10 to 15 years old The common chromosomal abnormality is a translocation that causes fusion of the EWS gene with a member of the ETS family of transcription factors. almost all patients with Ewing tumor have t(11;22). The resulting protein functions as an active transcription factor to stimulate cell proliferation
arise in the medullary cavity but eventually invade the cortex and periosteum to produce a soft tissue mass that is tan-white, frequently with foci of hemorrhage and necrosis.
sheets of uniform small, round cells The cells have scant glycogen-rich cytoplasm The presence of Homer-Wright rosettes (tumor cells circled about a central fibrillary space) indicates neural differentiation, and hence indicates by definition PNET.
painful enlarging masses in the diaphyses of long tubular bones X-rays show a destructive lytic tumor with infiltrative margins and extension into surrounding soft tissues. There is a characteristic periosteal reaction depositing bone in an onionskin fashion
Giant-Cell Tumor of Bone (GCT):
is dominated by multinucleated osteoclast-type giant cells, hence the synonym osteoclastoma GCT is locally aggressive, usually arising in individuals in their 20s to 40s Current opinion suggests that the giant cell component is likely a reactive macrophage population and the mononuclear cells are neoplastic.Tumors are large and red-brown with frequent cystic degeneration composed of uniform oval mononuclear cells with frequent mitoses, with scattered osteoclast-type giant cells that may contain 30 or more nuclei. The majority of GCTs arise in the epiphysis of long bones around the knee Radiographically, GCTs are large, purely lytic, and eccentric; the overlying cortex is frequently destroyed
Although GCTs are benign, roughly 50% recur after simple curettage; some malignant examples (5%) metastasize to the lungs.
osteoarthritis
is the most common joint disorder It is degeneration of the articular cartilage. It can be primary or secondary Gender has some influence on affected sitePathological features
Reduction of elasticity Vertical and horizontal fibrillation and cracking Bone eburnation. Formation of loose bodies (joint mice) Formation of fibrous walled cysts. Osteophytes (bony outgrowths) formation. A fibrous synovial pannus covers the peripheral portions of the articular surface.OA
Pathogenesis
Degenerating cartilage containing more water and less proteoglycan, The collagen network is also diminished and chondrocyte apoptosis is increased. Cartilage tensile strength and resilience are reduced, chondrocytes in the deeper layers proliferate matrix changes and chondrocyte loss eventually predominate. Inciting stimulus may be wear & tear of aging, estrogens in females, and genetic susceptibilityGOUT
tissue accumulation of excessive amounts of uric acid It is marked by recurrent episodes of acute arthritis result of precipitation of monosodium urate crystals from supersaturated body fluids influences besides hyperuricemia contribute to the pathogenesis primary (90%) and secondary forms (10%).Pathologic features
1. Acute arthritis: needle shape monosodium urate crystals are frequently found 2. Chronic tophaceous arthritis: visible deposits seen in the synovium that becomes hyperplastic, fibrotic. In severe cases, fibrous or bony ankylosis occurs. 3. Tophi in various sites: are the pathognomonic hallmarks of gout. 4. Gouty nephropathy3. Tophi in various sites: are the pathognomonic hallmarks of gout. Can occur in the joint or soft tissue and can cause skin ulceration. Composed of aggregates of crystals surrounded by inflammatory cells and foreign body reaction. 4. Gouty nephropathy: medullary tophi, intratubular precipitations and renal calculi
Pathogenesis
Most of primary cases the cause is unknown rare patients have identifiable enzymatic defects In secondary gout, hyperuricemia can be caused by increased urate production or decreased excretion, or both. increased levels of uric acid in the blood and other body fluids (e.g., synovium) lead to the precipitation of monosodium urate crystals.precipitated crystals are chemotactic to neutrophils & macrophages. cytokines can also directly activate synovial cells and cartilage cells to release proteases Repeated bouts of acute arthritis, however, can lead to the permanent damage seen in chronic tophaceous arthritis.
Pseudogout (chondrocalcinosis)
accumulation and eventual crystallization of pyrophosphate with calcium Approximately 50% of patients experience significant joint damage.Infectious Arthritis:
Suppurative Arthritis is a subtype of infectious arthritis in which the bacteria seed the joint during episodes of bacteremia Haemophilus influenzae predominates in children under age 2 years, S. aureus is the main causative agent in older children and adults, and gonococcus is prevalent during late adolescence and young adulthoodJOINT TUMORS AND TUMOR-LIKE LESIONS
A ganglionSynovial cyst
Pigmented Villonodular Tenosynovitis (PVNS) & Giant-Cell Tumor (GCT) of Tendon Sheath
PVNS tends to involve joints diffusely, whereas GCT usually occurs as a single tendon sheath nodule PVNS usually affects the knee (80% of cases). Patients typically complain of pain, locking, and recurrent swelling GCT manifests as a solitary, slowly growing mass frequently involving wrist and finger tendon sheaths. GCT is the most common soft tissue tumor of the hand.
This lesion was excised from the finger. The tumor is lobulated and the brown color is due to the deposition of haemosiderin.
Giant cell tumour of tendon sheath (benign synovioma)
Pigmented villonodular synovitis (PVNS).
The joint synovium is diffusely converted into red-brown finger-like projections.Sheets of proliferating cells in PVNS bulging the synovial lining.
LP view showing there is villous appearance of the proliferation and hyperplastic synovium. Hemosiderine deposition is also present.Skeletal Muscle Pathology
Muscular DystrophyThe muscular dystrophies are “a heterogeneous group of inherited disorders, often presenting in childhood, characterized by progressive degeneration of muscle fibers leading to muscle weakness and wasting.” In advanced cases muscle fibers are replaced by fibrofatty tissue. This histologic feature distinguishes dystrophies from myopathies, which also present with muscle weakness.
X-Linked Muscular Dystrophy: Duchenne Muscular Dystrophy (DMD)
This X-linked inherited disease is the most common & the most severe form of muscular dystrophy. It becomes clinically evident by age 5, with progressive weakness leading to wheelchair dependence by age 10 to 12 years, and death by the early 20s. The same gene is involved in a related but milder form designated Becker muscular dystrophyA boy with Duchenne muscular dystrophy (DMD) demonstrating pseudohypertrophy of his calves
Duchenne muscular dystrophy (DMD)
Microscopical features
Marked variation in muscle fiber size, caused by hypertrophy and atrophy. The residual muscle fibers show degenerative & regenerative changes (the former is evidenced by fiber splitting and necrosis & the latter by sarcoplasmic basophilia & nuclear enlargement). Connective tissue is increased throughout the muscle. In the late stages of the disease, extensive fiber loss and adipose tissue infiltration are present. The definitive diagnosis is based on the demonstration of abnormal staining for dystrophin in immunohistochemical preparations.There is variation in muscle fiber size, increased endomysial connective tissue, and regenerating fibers (blue hue).
Duchenne muscular dystrophy (DMD)
DMD is caused by abnormalities in the dystrophin gene located on the short arm of the X chromosome. In affected families, females are carriers; they are clinically asymptomatic. Boys with DMD show delayed walking. There is enlargement of the calf muscles associated with weakness, a phenomenon termed pseudohypertrophy; this is an important clinical finding.
The increased muscle bulk is caused initially by an increase in the size of the muscle fibers and then, as the muscle atrophies, by an increase in fat and connective tissue. Pathologic changes are also found in the heart, and patients may develop heart failure or arrhythmias. Serum creatine kinase is elevated during the first decade of life. Death results from respiratory insufficiency, pulmonary infection, and heart failure.
Skeletal Muscle Tumors
RhabdomyosarcomaRhabdomyosarcoma is the most common soft tissue sarcoma of childhood and adolescence, usually appearing before age 20. They occur most commonly in the head and neck or genitourinary tract. Chromosomal translocations are found in most cases; the more common t(2;13) translocation fuses the PAX3 gene (controls skeletal muscle differentiation & development) on chromosome 2 with the FKHR gene on chromosome 13. The hybrid PAX3-FKHR protein probably involves dysregulation of muscle differentiation.
Gross features
Tumors arising near the mucosal surfaces of the bladder or vagina, can present as soft, gelatinous, grapelike masses, designated sarcoma botryoides. In other cases they are deceptively demarcated or infiltrative grayish-white to brownish masses.The grape-like configuration of this lesion is characteristic.
Sarcoma botrryoides (embryonal rhabdomyosarcoma) of vagina
Embryonal Rhabdomyosarcoma (sarcoma botryoides) Urinary bladder
A huge glistening tumor mass is seen filling the lumen of the organ.This tumor was removed from the forearm with a good margin of muscle around it. The tumor is brown, with a central area of haemorrhage. Wide local resection, wherever possible, is currently accepted as the treatment of choice for malignant soft tissue tumors.
Rhabdomyosarcoma
Gross appearance of alveolar rhabdomyosarcoma. The tumor is embedded within skeletal muscle.
Alveolar rhabdomyosarcoma
Microscopical features
Rhabdomyosarcoma is histologically subclassified into the embryonal, alveolar, and pleomorphic variants. The rhabdomyoblast is the diagnostic cell in all types; it exhibits granular eosinophilic cytoplasm, and may be round or elongated; the latter are known as tadpole or strap cells and may contain cross-striations visible by light microscopy. The diagnosis of rhabdomyosarcoma is based on the demonstration of skeletal muscle differentiation, either in the form of sarcomeres under the electron microscope or by immunohistochemical demonstration of muscle-associated antigens such as desmin and muscle-specific actin.Nests of small round cells with scant cytoplasm grouped in nests that are separated by thick fibrous trabeculae. Cells in centers of nests are poorly cohesive & fall away from sides to produce a pattern reminiscent of lung alveoli. See higher power next
Alveolar rhabdomyosarcoma
Note the eosinophilic cytoplasm & the presence of rhabdomyoblasts (malignant giant cells).
Pleomorphic rhabdomyosarcoma with tumor giant cells and tapering cytoplasmic processes (rhabdomyoblasts).Pleomorphic-type rhabdomyosarcoma
Soft Tissue Tumors
Fatty Tissue Tumors Benign MalignantLipoma
Pathological features Conventional lipomas (the most common subtype) are soft, yellow, well-encapsulated masses They can vary considerably in size. Microscopically, they consist of mature fat cells with no pleomorphismExternal surface of (benign) lipoma. The bright yellow color is typical of fat. Note the lobulated appearance, which is also typical of this lesion. This particular tumor arose in the subcutaneous fat (note the small strip of skin denoted by the black arrows).
Subcutaneous lipoma
Conventional Lipoma
Except for the circumscription, the appearance is indistinguishable from that of normal fat. lipomas consist of bright yellow fat separated by fine fibrous trabeculae.
The entire lesion is composed of typical large adipocytes
Subcutaneous lipomaLiposarcoma
is a malignant neoplasm of adipocytes. These tumors occur most commonly in the 40 to 60 years of age & mostly in the deep soft tissues (cf. lipoma) or in visceral sites. The prognosis of liposarcomas is greatly influenced by the histologic subtype; well-differentiated and myxoid variants tend to grow in a fairly indolent fashion and have a more favorable outlook than do the more aggressive round cell and pleomorphic variants, which tend to recur after excision and metastasize to lungs. A t(12;16) chromosomal translocation is associated with myxoid liposarcomas; the rearrangement affects a transcription factor that plays a role in normal adipocyte differentiationPathological features
Usually they are relatively well-circumscribed large masses. Several different histologic subtypes are recognized, including two low-grade variants, the well-differentiated liposarcoma and the myxoid liposarcoma, the latter characterized by abundant, mucoid extracellular matrix. Some well-differentiated lesions can be difficult to distinguish histologically from lipomas, whereas very poorly differentiated tumors can resemble various other high-grade malignancies. In most cases, cells indicative of fatty differentiation are present. Such cells are known as lipoblasts; they recapitulate fetal fat cells with cytoplasmic lipid vacuoles that scallop the nucleus.Photograph of sectioned gross specimen reveals the solid but gelatinous myxoid liposarcoma.
Myxoid liposarcoma thigh
Well demarcated lipoma-like tumor in the mesocolon. Liposarcomas are generally large tumors
Liposarcoma of mesocolon
Lipoblast: relatively specific for liposarcoma
These are relatively specific for liposarcoma; the cell contains multiple cytoplasmic lipid vacuoles that scallop the nucleus.Adult-appearing fat cells and more primitive cells, with lipid vacuoles (lipoblasts) are scattered in abundant myxoid matrix with compressed & branched capillaries
Myxoid liposarcoma thigh
The cell nuclei of Lipoblasts show, in contrast to mature fat cells much larger nuclei with Atypia. They are typical, but not specific for the liposarcoma.
Myxoid liposarcoma signet ring lipoblasts
Pleomorphic liposarcoma
The very poorly differentiated tumors can resemble various other high-grade malignancies.Fibrous Tumors and Tumor-Like Lesions
Fibrosarcomais a malignant neoplasm composed of fibroblasts. Most occur in adults, typically in the deep tissues of the thigh and retroperitoneal area. As with other sarcomas, fibrosarcomas often recur locally after excision (>50% of cases) and can metastasize hematogenously (>25% of cases), usually to the lungs.
Pathological features These unecapsulated, infiltrative sarcomas show frequently areas of hemorrhage and necrosis. Microscopically, the low-grade tumors may closely resemble fibromatosis; less differentiated examples show densely packed spindled cells growing in a herringbone fashion, there are frequent mitoses, and necrosis.
Well-circumscribed fibrosarcoma growing within skeletal muscle.
FibrosarcomaMalignant spindle cells arranged in a herringbone pattern.
Fibrosarcoma
Fibrohistiocytic Tumors
These are composed of a mixture of fibroblasts and phagocytic, lipid-laden cells resembling activated macrophages. The neoplastic cells are most likely fibroblasts. These tumors are divided into benign, of intermediate malignant potential, frankly malignant.Benign Fibrous Histiocytoma (Dermatofibroma)
are relatively common benign lesions in adults presenting as small (<1 cm) mobile nodules in the dermis or subcutaneous tissue. Microscopically, the lesion consists of bland, interlacing spindle cells admixed with foamy, lipid-rich histiocyte-like cells. The borders of the lesions tend to be infiltrative. The pathogenesis of these lesions is uncertainMalignant Fibrous Histiocytoma (MFH)
is a term rather loosely applied to a variety of soft tissue sarcomas characterized by considerable cytologic pleomorphism, the presence of bizarre multinucleate cells, and storiform architecture. Despite the name, the phenotype of many such tumors is fibroblastic and not histiocytic. Nevertheless, it is also important to note that several tumors diagnosed as MFH actually exhibit markers for cells of other origin (e.g., smooth muscle cells, adipocytes, skeletal muscle cells) and are therefore more appropriately classified as leiomyosarcomas, liposarcomas, etc. MFH exhibiting fibroblastic differentiation are usually large (5-20 cm), gray-white unencapsulated masses that often appear deceptively circumscribed. They usually arise in the musculature of the proximal extremities or in the retroperitoneum. Most of these tumors are extremely aggressive, recur unless widely excised, and have a metastatic rate of 30% to 50%.Soft tissue MFH: most cases occur in deep soft tissues of extremities in adults (reported in children). Often quite large at time of excision
Malignant fibrous histiocytoma
MFH of storiform/pleomorphic type. The two most important microscopic features of MFH are 1. Presence of highly pleomorphic tumor cells 2. Storiform pattern of growth i.e. bundles of spindle cells radiating from a central focus in a cart wheel-like fashion (arrows)
There is marked pleomorphism, with numerous multinucleated giant cells.
Smooth Muscle Tumors
Leiomyoma are common, well-circumscribed neoplasms that can arise from smooth muscle cells anywhere in the body, but are encountered most commonly in the uterus.leiomyosarcoma
(15% of soft tissue sarcomas). They occur in adults, more commonly females. Deep soft tissues of the extremities and retroperitoneum are common sites. Microscopically, they show spindle cells with cigar-shaped nuclei arranged in interweaving fascicles. Superficial leiomyosarcomas are usually small and have a good prognosis, whereas retroperitoneal tumors are large, cannot be entirely excised, and cause death by both local extension and metastatic spread.. The fusiform shape of the tumor is due to the fact that the tumor is following the course of the large blood vessels from which it arose.
Leiomyosarcoma of soft tissues of arm
Leiomyosarcoma Retroperitoneum
Gross appearance of retroperitoneal leiomyosarcoma, removed in continuity with the spleen. The whorling appearance of the cut surface is characteristic.Leiomyosarcoma metastatic to the liver
As with sarcomas in general, leiomyosarcomas have spindle cells but with cigar-shaped nuclei. Several mitoses are seen here, just in this one high power field.Leiomyosarcoma
Synovial Sarcoma
(10% of all soft tissue sarcomas) The cell of origin is unclear and is most certainly not a synoviocyte. Reflecting a non-joint origin, 90% of synovial sarcomas are not intra-articular but rather paraarticular. They are typically seen in the 20-40 years of age. Most develop in deep soft tissues around the large joints of the extremities, especially around the knee. Most synovial sarcomas show a characteristic t(X;18) translocation, which relates to prognosis.Microscopically, synovial sarcomas may be biphasic or monophasic. Classic biphasic synovial sarcoma exhibits differentiation of tumor cells into both epithelial-like cells and spindle cells. The epithelial cells are cuboidal to columnar and form glands or grow in solid cords or aggregates. The spindle cells are arranged in densely cellular fascicles that surround the epithelial cells.
Immunohistochemistry is helpful, because the tumor cells are positive for keratin and epithelial membrane antigen. Common metastatic sites are lung, bone, and regional lymph nodes. Only 10% to 30% live for more than 10 years.