Soft Tissue and Skeletal Muscle

eaton lambert syndrome

Antibodies inhibit a presynaptic calcium channel which block acetyocholine release associated with neuroendocrine carcinoma of the lung and other underlying malignancies initial weakness, rapid repetitive stimulation that improves with muscle strength treatment is immunosuppressive agents

Are malignant ST tumors or benign ST tumors more common?

Benign! (100:1) excewp tofr skeletal muscle neoplasms

tumor grade

Degree of cellular differentiation based on histologic appearance of tumor

how does well-differentiated liposarcoma appear on histology?

adipocytes are abundant, blood vessels, lipoblasts, fibrosis, few atypical spindle cells good prognosis! note picture is of liposarcoma with amplification of 12q13-q15

What does soft tissue include?

adipose, blood vessels, lymph vessels , smooth muscle, skeletal muscle, fibrous connective tissue, and PNS

complex karyotypes

aneuploidy genetics are not recurrent reproducible for diagnostic purposes found in older patients higher grade tumors, heterogenous

myasthenia gravis

autoantibodies against acetylcholine receptor associated with thyomoma and thymus hyperplasia painless weakness that worsens with exertion treatment is acetylcholinesterase inhibitors, plasmapheriesis, immunosuppressive drugs (because of complement fixation) and thymectomy

Types of rhabdomyosarcoma

botryoid (best) embryonal (good) alveolar (intermediate) pleomorphic (poor)

fibromatosis

can be superficial or deep appears malignant but is benign superficial is more common than deep deep is more common among females than males superficial sites: plantar, palmar, penile deep sites: abdominal cavity, limb girdle treatment is excision for both, but deep is difficult to treat

myopathic muscle injury

damaging muscle fibers directly segmental myofiber degeneration and regeneration myofiber hypertrophy cytoplasmic inclusions

biphasic synovial sarcoma

includes gland structures, lungs and lN mets

dermatomyositis labs

increased CK, + ANA, +Jo-1

fibrosarcoma

infantile or adult infantile has a better prognosis gross: infantile >30 cm, adult varigated appearance treatment is with surgery, chemo, radiation

infantile fibrosarcoma vs adult fibrosarcoma on histology

infantile= high mitotic rate with hemorrhage/necrosis (above) adult= herringbone pattern (below)

MDM2

inhibits p53 amplified in liposarcomas

alveolar rhabdomyosarcoma

intermediate prognosis <20 y.o has fibrous septae dividing cells into clusters analogous to normal pulmonary alveoli

dedifferentiated

it started out as a well differentiated tumor but has not accumulated abnormalities and is now poorly differentiated

how does myxoid liposarcoma appear on histology?

less normal adipocytes, more hyperchromatic nuclei, brown fat-like, myxoid appearance, more blood vessels looks "mucinous" intermediate prognosis associated with translocation 12;16

How does lipoma appear on histology?

lipoma histology: close to normal fat, small nuclei and very few vessels. low mitoses

two types of muscle injury

neurogenic or myopathic

fibromatosis histology

no atypia with low mitotic activity superficial has subcutis fibrosis, deep is infiltrative the picture is an example of a deep, infiltrative fibromatosis

dermatomyositis histology

perimysial inflammation (CD$ T cells, B cells, and complement MAC) perifascicular SKM atrophy from inflammation mononuclear infiltrate and atrophy from inflammation

Embryonal rhabdomyosarcoma (sarcoma botryoides)

prognosis is best age: <20 year olds tumor of hollow organs (ex. female genital tract) primitive appearing tumor (cells do not tell you who they are) appear round blue to eosinphic (tadpole cells) cells condensed below a hypercellular "cambium layer" followed by a hypocellular area cells will be positive for skeletal muscle markers

Pleomorphic Rhabdomyosarcoma

prognosis is poor more common in adults poorly circumscribed large, multi nucleated bizarre tumor cells mitotic figures and necrosis is common Immunohistochemical is positive for myogenin complex cytogenetics

nodular fasciitis

rapid fibroplastic and myofibroblastic proliferation mimics malignancy, tells you it feels like it arose in a day superficial more common in young adults, or with trauma patients gross: usually well circumscribed micro: variable zonal patterns, cellular, loos/myxoid fibrous, red blood cells and lymphs, lacks atypia treatment: spontaneously regresses, or excision

inclusion body myositis histology

rimmed vacuoles like PM with endomysial CD8 t cells infiltrates, cytoplasmic inclusions containing, proteins typical of neurodegenerative diagnosis, endomysial fibrosis, and fatty replacement

undifferentiated pleomorphic sarcoma histology

sheets of large, anaplastic cells with bizarre nuclei and a high mitotic rate

rhabdomyoma

skeletal muscle lesion general: in cardiac tissue in patients with tuberous sclerosis gross: circumscribed micro: eosinphilic spider cells with low mitosis treatment: excision

rhabdomyosarcoma

skeletal muscle tumors that are malignant (more common than benign skeletal muscle tumor) more common in children than adults micro: based on subtype, variable mitotic activity treatment: excision

leiomyoma

smooth muscle tumor common in uterus gross: well circumscribed, usually less than 2 cm, usually negative for hemorrhagic/necrotic tissue (if larger we are more concerned) micro: fascicles of eosinophilic spindled cells with blunt nuclei, low mitotic activity, no necrosis SMA+ (smooth muscle actin) treatment: excision

How does rhabdomyoma appear on histology?

star shaped cells "eosinophilic spider cells" no necrosis, no mitosis "bizarre appearance"

leiomyosarcoma

superficial skin= good prognosis deep= poor prognosis gross: usually hemorrahgic and necrotic; mets to lungs, LN's micro: blunt to round hyperchromatic nuclei; infiltrative; high mitotic activity, SMA+ (smooth muscle actin) treatment: wide excision and radiation

polymyositis

symmetric proximal weakness WITHOUT skin changes adult onset can involve heart and lungs treatment is glucocorticoids

dermatomyositis

symmetric proximal weakness and skin changes juvenile- good prognosis, adult- associated with malignancies sites: eyelids (heliotrope), knees, kncules, and elbows (gottron papules), esophagus, lung treatment is glucocorticoids

cytogenetics associated with nodular fasciitis

t(17,22) MYH9-USP6 fusion gene

Alveolar rhabdomyosarcoma translocation

t(2;13) PAX3-FOX01 and t(1;13) PAX7-FOX01 fusion

genetics associated with synovial sarcoma

t(x;18) SS18-SSX1, X2, X4 fusion genes

synovial sarcoma

tumors of uncertain origin general: 10% of sarcomas epid/clin: older adults sites: H and N, chest wall gross: well circumscribed micro: monophasic or biphasic treatment: limb sparing surgery, chemo, stage and age determines prognosis

monophasic synovial sarcoma

uniform spindle cells with scant cytoplasm in short fascicles

how does pleomorphic liposarcoma appear on histology?

unrecognizable normal adipocytes, anaplastic cells, bizarre nuclei all different sized cells poor prognosis complex karyotype

Genetics of liposarcomas

well differentiated- amplification myxoid- transloaction pleomorphic- complex karyotypes

fibromatosis gross

white cut surface, nodules if superficial, large and infiltrative if deep

lipoma

general: most common benign soft tissue tumor site: superficial, soft, mobile, usually painless gross: well circumscribed, yellow cut surface treatment: excision

liposarcoma

general: most common soft tissue sarcoma sites: deep tissue, fixed gross: large, not well circumscribed micro: well-differentiated, myxoid, or pleomorphic treatment: excision, post op radiation

inclusion body myositis

has characteristics of inflammation and immunology myositis >50 year olds myopathy >65 year olds responds poorly to glucocorticoids

how does leiomyosarcoma appear on histology?

hemorrhage, abnormal mitotic figures, necrosis lack of nice spindled uniformness

undifferentiated pleomorphic sarcoma

high grade sarcomas with pleomorphic cells lacking differentiation, cannot be molecularly, histologically, or IHC categorized largest category of adult sarcomas deep within extremities treatment: surgery, chemo and radiation, prognosis is poor

how to diagnose ST tumors

histology, immunohistochemistry, molecular diagnostics (single lesions/simple karyotypes)

neurogenic muscle injury

disrupting muscle innervation leads to fiber type grouping and grouped atrophy

tadpole or strap cells

elongated spindle cells seen in embryonal RMS and positive for skeletal muscle markers

polymyositis histology

endomysial inflammation (CD8 cells)

simple karyotypes

euploid with a single/limited number of chromosome changes ; diagnostic marker for disease found in younger patients tumors that look the same from beginning to end

post synaptic Ach receptors antibodies

fix complement and lead to damage more common autoantibody in myasthenia gravis

muscle specific receptor tyrosine kinase antibodies

focal muscles involved dont fix complement but interfere with trafficking