What are the hereditary syndromes associated with soft tissue tumors?
- neurofibromatosis type 1 (neurofibroma, malignant peripheral nerve sheath tumor)
- Gardner syndrome (fibromatosis)
- Li-Fraumeni syndrome (soft-tissue sarcoma)
- Osler-Weber-Rendu syndrome (telangiectasia)
What is the most commonly involved chromosome in ES and PNET?
What are the mc translocations in soft tissue tumors?
- Ewing sarcoma/Primitive neuroectodermal tumor--> t(11:22)
- Liposarcoma—myxoid and round-cell type-->t(12:16)
- Synovial sarcoma--> t(x:18)
- Rhabdomyosarcoma—alveolar type --> t(2:13), t(1:13)
- Desmoplastic small round-cell tumor--> t(11:22)
- Dermatofibrosarcoma protuberans--> t(17:22)
What is the mc place for soft tissue sarcoma?
lower extremity, especially the thigh
What is the association of age with soft tissue tumors?
- As age increases the incidence increases
- Fourth mc malignancy in children after CNS, hematopoietic, and WT
- rhabdomyosarcoma in children
- synovial sarcoma in young adulthood
- liposarcoma and fibrosarcoma in middle to late adult life
What is the prognosis of soft tissue sarcoma based on the site?
Superficial better than deep
What determines prognosis in most soft tissue tumor?
Histologic subtype, grade, stage
What are spindle cell tumors?
- Rod-shaped, long axis twice as great as short axis
- Fibrous, fibrohistiocytic, smooth muscle, Schwann cell
What are Small round cell soft tissue tumors?
- Size of a lymphocyte with little cytoplasm
- Rhabdomyosarcoma, primitive neuroectodermal tumor
What are Epithelioid cell tumors?
- Polyhedral with abundant cytoplasm, nucleus is centrally located
- Smooth muscle, Schwann cell endothelial, epithelioid sarcoma
What are the soft tissue tumors based on cell type?
- Spindle cell--> Fibrous, fibrohistiocytic, smooth muscle, Schwann cell
- Small round cell--> Rhabdomyosarcoma, primitive neuroectodermal tumor
- Epithelioid--> Smooth muscle, Schwann cell endothelial, epithelioid sarcoma
In which tumor Fascicles of eosinophilic spindle cells intersecting at right angles are seen?
In which tumor Short fascicles of spindle cells radiating from a central point like spokes on a wheel—storiform are seen?
In which tumor Nuclei arranged in columns—palisading are seen?
In which tumor Herringbone are seen?
In which tumor Mixture of fascicles of spindle cells and groups of epithelioid cells—biphasic are seen?
What is the histology hallmark of Smooth muscle tumors?
Fascicles of eosinophilic spindle cells intersecting at right angles
What is the histological hallmark of Schwann cell tumor?
Nuclei arranged in columns—palisading
What is the histology of Fibrohistiocytic tumor?
Short fascicles of spindle cells radiating from a central point like spokes on a wheel—storiform
What is the histology hallmark of Fibrosarcoma?
What is the histology hallmark of synovial sarcoma?
Mixture of fascicles of spindle cells and groups of epithelioid cells—biphasic
What is the mc soft tissue, benign soft tissue and malignant soft tissue tumor in adults?
Lipoma/ Lipoma/ Liposarcoma
What are the features of lipoma?
- well-encapsulated mass of mature adipocytes
- Proximal extremity and trunk
- Soft, painless, mobile
- conventional lipomas often show rearrangements of 12q, 6p, and 13q
Which variant of lipoma is painful?
What is the clinical characteristics of liposarcoma?
- most common sarcomas of adulthood
- deep soft tissues of the proximal extremities and retroperitoneum
- Can become very large
- High recurrence rate
What is the histology of liposarcoma?
- Divided into well-differentiated, myxoid/round cell, and pleomorphic variants
- The cells in well-differentiated liposarcomas are readily recognized as lipocytes, and the tumor cells frequently contain supernumerary rings and giant rod chromosomes due to amplification of the 12q14–q15 region containing the MDM2 oncogene (inhibit P53)
- In the other variants, most of the tumor cells are not obviously adipogenic, but some cells indicative of fatty differentiation are almost always present. These cells are known as lipoblasts; they mimic fetal fat cells and contain round clear cytoplasmic vacuoles of lipid that scallop the nucleus . The myxoid/round cell variant of liposarcoma has a t(12;16)
What is the major chromosomal abnormality in well-diff liposarcoma?
supernumerary rings and giant rod chromosomes due to amplification of the 12q14–q15 region containing the MDM2 oncogene (that inhibit P53)
What is the major translocation in Mixoid liposarcoma?
What are Reactive pseudosarcomatous proliferations?
- Nonneoplastic lesions that either develop in response to some form of local trauma (physical or ischemic) or are idiopathic.
- Composed of plump reactive fibroblasts and related mesenchymal cells.
- Clinically they are alarming, because they develop suddenly and grow rapidly. Histologically they cause concern, because their hypercellularity, mitotic activity, and primitive appearance mimic sarcoma.
- Nodular fasciitis and myositis ossificans.
What is the mc reactive pseudosarcomas?
What is the usual presentation of nodular fasciitis?
- Volar aspect of the forearm
- Several-week history of a solitary, rapidly growing, and sometimes painful mass.
- Preceding trauma is reported in only 10% to 15% of cases.
What is the histologic feature of nodular fasciitis?
- Deep subcutaneous
- Poorly defined margins
- Richly cellular and contains plump, immature-appearing fibroblasts and myofibroblasts arranged randomly or in short intersecting fascicles
- Abundant mitosis
- Mixoid stroma with extravasated RBC and lymph
What is the hallmark of myositis ossificans?
What is the clinical feature of MO?
- Develops in athletic adolescents and young adults and follows an episode of trauma in more than 50% of cases.
- Musculature of the proximal extremities.
- Early phase -->swollen and painful
- During the subsequent several weeks it becomes more circumscribed and firm. Eventually--> painless, hard, well-demarcated mass.
What is the histological feature of MO?
- Initially, the lesion is cellular and consists of plump, elongated fibroblast and myofibroblast-like cells simulating nodular fasciitis.
- In due course these cells are surrounded by an intermediate zone that contains osteoblasts, which deposit ill-defined trabeculae of woven bone.
- The most peripheral zone contains well-formed, mineralized trabeculae that closely resemble cancellous bone. Eventually the entire lesion ossifies, and the intertrabecular spaces become filled with bone marrow.
- The mature lesion is completely ossified.
What is the radiology of MO?
- Initially, X-rays may show only soft-tissue fullness, but at about 3 weeks patchy flocculent radiodensities form in the periphery. The radiodensities become more extensive with time and slowly encroach on the radiolucent center
How can MO distinguished from extraskeletal osteosarcoma?
- Osteosarcoma usually occurs in elderly patients,
- the proliferating cells are cytologically malignant,
- and the tumor lacks the zonation of myositis ossificans
What are superficial fibromatosis?
- Broad fascicles of fibroblasts and myofibroblasts surrounded by abundant dense collagen.
- Include palmar (Dupuytren), plantar, and Penile (Peyronie)
What are the features of superficial fibromatosis?
- Palmar: nodular thickening of the palmar fascia either unilaterally or bilaterally (50%) Plus skin dimpling. Slowly progressive flexion contracture develops that mainly affects the fourth and fifth fingers of the hand.
- Plantar: similar to palmar except that flexion contractures are uncommon and bilateral involvement is infrequent.
- Penile: on the dorsolateral aspect of the penis. Eventually, it may cause abnormal curvature of the shaft, constriction of the urethra.
What is the hallmark of deep-seated fibromatosis (desmoid tumor)?
- Deep-seated fibromatoses lie in a gray zone between benign fibrous tumors and low-grade fibrosarcomas.
- On the one hand, they often present as large, infiltrative masses that frequently recur after incomplete excision;
- on the other, they are composed of banal well-differentiated fibroblasts that do not metastasize.
What are the subtypes of desmoid tumor?
- Extra-abdominal, abdominal, and intra-abdominal
- Extra-abdominal M=F/musculature.
- Abdominal : musculoaponeurotic structures of the anterior abdominal wall in women during or after pregnancy.
- Intra-abdominal :mesentery or pelvic walls, FAP (Gardner syndrome)
What is the major kind of desmoid in Gardner syndrome?
Intraabdominal (mesentery or pelvic wall)
What is the genetic hallmark of most desmoid tumors?
APC or β-catenin mutation
What are the histological features of desmoid tumors?
- Plump banal fibroblasts arranged in broad sweeping fascicles that infiltrate the adjacent tissue.
- Mitoses may be frequent.
- Regenerative muscle cells when trapped within these lesions may take on the appearance of multinucleated giant cells.
What are the features of fibrosarcoma?
- deep soft tissues of the extremities
- herringbone pattern
What is the mc soft tissue sarcoma in children and adolescent?
What is the most common location for Rhabdomyosarcoma?
GU, H and N
What are the histological subtypes of rhabdomyosarcoma?
embryonal, alveolar, and pleomorphic
What are the features of major cells involved in rhabdomyosarcoma?
- Rhabdomyoblast contains eccentric eosinophilic granular cytoplasm rich in thick and thin filaments.
- Rhabdomyoblasts may be round or elongate; the latter are known as tadpole or strap cells, and may contain cross-striations visible by light microscopy.
- Contain sarcomeres,
- Positive IHC for desmin, MYOD1, and myogenin.
What is the mc subtype of rhabdomyosarcoma?
What are the features of Embryonal rhabdomyosarcoma?
It includes the sarcoma botryoides, spindle cell and anaplastic variants. < 10 years of age Nasal cavity, orbit, middle ear, prostate, and paratesticular region. This variant of rhabdomyosarcoma commonly has parental isodisomy of chromosome 11p15.5, which leads to overexpression of the imprinted IGFII gene. The sarcoma botryoides subtype develops in the walls of hollow, mucosal-lined structures, such as the nasopharynx, common bile duct, bladder, and vagina. Where the tumors abut the mucosa of an organ, they form a submucosal zone of hypercellularity called the cambium layer.
What are the features of Alveolar rhabdomyosarcoma?
- Early to middle adolescence
- Deep musculature of the extremities
- Traversed by a network of fibrous septae that divide the cells into clusters or aggregates that creates a crude resemblance to pulmonary alveolae
- Those in the center of the aggregates are dyscohesive, while those at the periphery adhere to the septae.
- Translocation that either fuses the PAX3 to the FOXO1a gene, t(2,13) or the PAX7to the FOXO1a gene, t(1;13).
- Tumors with the PAX3-FOXO1a fusion gene are more aggressive and associated with a worse prognosis.
What are the features of pleomorphic rhabdomyosarcoma?
- Large multinucleated, bizarre eosinophilic tumor cells
Sarcoma commonly metastasize to .......
Bone and lung
What is the mc neoplasm in women?
Which tumor can arise in also arise from the arrector pili muscles found in the skin, nipples, scrotum, and labia?
Leiomyomas: Those arising in the arrector muscles (pilar leiomyomas) may be multiple and painful
How is the phenotype of multiple cutaneous leiomyomas, in some individuals transmitted?
- associated with uterine leiomyomas and a predisposition to develop RCC.
- This disorder is associated with a germline loss-of-function mutation in the fumarate hydratase gene located on chromosome 1q.
What are the histological features of leiomyoma?
- 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
What are the features of leiomyosarcoma?
- skin and deep soft tissues of the extremities and retroperitoneum
- Painless firm masses.
- Malignant spindle cells with cigar-shaped nuclei arranged in interweaving fascicles. Thin filaments with dense bodies and pinocytic vesicles, and individual cells are surrounded by basal lamina. Immunohistochemically, they stain with antibodies to smooth muscle actin and desmin.
What is the origin of synovial sarcoma?
What is the mc place for synovial sarcoma?
deep soft tissue of the lower extremity, especially around the knee and thigh.
What are four diagnostic features of synovial sarcoma?
- 1) monophasic or biphasic
- 2)calcified concretion
- 4)positive reactions for keratin and epithelial membrane antigen
What is unique to synovial sarcoma relative to other sarcoma?
positive reactions for keratin and epithelial membrane antigen
What are the histological characteristics of synovial sarcoma (biphasic)?
- Dual lines of differentiation (i.e., epithelial-like and mesenchymal-like).
- 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
What is the mc pathologic condition of bones?
What are simple and compound fractures?
closed (simple) when the overlying tissue is intact; compound when the fracture site communicates with the skin surface
What are pathologic and stress fracture?
- If the break occurs in bone already altered by a disease process, it is described as a pathologic fracture.
- A stress fracture is a slowly developing fracture that follows a period of increased physical activity in which the bone is subjected to new repetitive loads—as in sports training or marching in military boot camp.
How is bone unique in its repair?
By reactivating processes that normally occur during embryogenesis
What is the earliest change in the fractured bone?
What are the stages of bone repair after fracture?
- Immediately after fracture, rupture of blood vessels results in a hematoma. Fibrin mesh, seal off the fracture site and creates a framework for the influx of inflammatory cells and ingrowth of fibroblasts and new capillary vessels.
- Simultaneously, degranulated platelets and migrating inflammatory cells release mediators, which activate the osteoprogenitor, osteoclastic and osteoblastic activity.
- By the end of the first week the hematoma is organizingSoft-tissue callus or procallus—provides some anchorage between the ends of the fractured bones but offers no structural rigidity for weight bearing
- Subsequently, the activated osteoprogenitor cells deposit subperiosteal trabeculae of woven bone that are oriented perpendicular to the cortical axis and within the medullary cavity.
- In some cases the activated mesenchymal cells in the soft tissues and bone surrounding the fracture line also differentiate into chondroblasts that make cartilage.
- In an uncomplicated fracture, the repair tissue reaches its maximal girth at the end of the second or third week, which helps stabilize the fracture site.
- The newly formed cartilage along the fracture line undergoes enchondral ossification(Bony callus--> tolerate weight)
- As the callus matures and is subjected to weight-bearing forces, the portions that are not physically stressed are resorbed, and in this manner the callus is reduced in size until the shape and outline of the fractured bone have been re-established.
What is a pseudoarthrosis?
If a nonunion allows too much motion along the fracture gap, the central portion of the callus undergoes cystic degeneration, and the luminal surface can actually become lined by synovial-like cells, creating a false joint or pseudoarthrosis
What is an important obstacle to normal bone healing?