soft tissue tumors

diseases of skeletal muscle

neurogenic disease, myasthenic syndromes, & dystrophies

• may all cause muscular weakness & fatigability

denervation atrophy

a peripheral neuropathy in which there is axial degeneration that leads to secondary muscle atrophy

• atrophic muscles consists of small angulated fiber

  • muscle fiber is usually reinnervated by collateral sprouting from an adjacent nerve fiber

  • muscle fiber type determined by innervation → regenerated fibers will be the same as adjacent fibers

  • type grouping & group atrophy

• ATPase stains differentiate type I & II fibers

clinical presentations

• weakness & fasciculations → lower motor neuron deficit

type grouping

repeated denervation & reinnervation by collateral sprouts produces clusters of fibers of a single type

group atrophy

with damage of the innervating axon, the muscle fibers that undergo atrophy will be in groups

Duchenne muscular dystrophy

most commonly occurring dystrophy with an X-linked defect causing deficiency in dystrophin

morphology

• ongoing damage in the form of segmental myofiber degeneration & regeneration associated with an admixture of atrophic myofibers

• muscle tissue is replaced by collagen & fat cells (“fatty replacement” or “fatty infiltration“) leading to pseudohypertrophy of the calves

clinical presentations

• first indications of muscle weakness are clumsiness & inability to keep with with peers around age 5

• weakness begins in the pelvic girdle muscles & then extends to the shoulder girdle (proximal muscles)

• mean age of wheelchair dependence is around 9.5 years

• mean age of death is 25 - 30 years of age (from respiratory insufficiency, pulmonary infection, or heart failure)

Becker muscular dystrophy

X-linked defect causing insufficiency in dystrophin

• milder type of Duchenne dystrophy

• later onset of disease

inflammatory myopathies

non-infectious, immunologically mediated injury & inflammation of skeletal muscles

examples

• dermatomyositis

• polymyositis

• inclusion body myositis

• acanthosis nigricans

• Bower’s disease

dermatomyositis

inflammatory myopathy associated with damage to small blood vessels

clinical presentations

• heliotrope skin rash & proximal muscle disease

• infiltrates of mononuclear inflammatory cells in the perimysial connective tissue & around blood vessels

• risk of developing visceral cancers

polymyositis

inflammatory myopathy associated with proximal muscle weakness

• CD8+ cytotoxic T cells are prominent part of the inflammatory infiltrate in affected muscle

inclusion body myositis

inflammatory myopathy associated with distal muscle weakness in the elderly

• patchy often endomysial mononuclear inflammatory cell infiltrates rich in CD8+ T cells

• abnormal cytoplasmic inclusions described as “rimmed vacuoles“

myasthenia gravis

an autoimmune disease with antibody production to the acetylcholine receptor (AchR) of the neuromuscular junction

• type II hypersensitivity

• antibodies to the AchR present in the serum of 85 - 90% of patients

clinical presentations

• female-to-male ratio 2:1 in the young adults but male predominance in older adults

• fluctuating weakness that worsens with exertion & often over the course of the day

• ocular muscle weakness common

• later involves muscles producing dysphagia & dysarthria

• trunk & limb muscles affected in late stages

• 10% of the patients have a thymoma & 30% have thymic hyperplasia

treatments

• < 5% mortality rate now

• thymectomy usually beneficial in patients with thymoma

• response to anticholinesterase drugs seen in some patients

• plasmapheresis & immunosuppressive drugs

soft tissue tumors

tumors of non-epithelial tissue excluding the skeleton, joints, CNS, hematopoietic & lymphoid tissues

• benign — outnumber malignant sarcoma by 100x

• arise in the extremities, especially the thigh

• vimentin positive

superficial tumors are usually benign

deep (& retroperitoneal) tumors are usually malignant

majority of sarcomas are sporadic & have no known predisposing cause

• origins unknown

lipoma

most frequent soft tissue tumor, usually arising in the subcutis of the proximal extremities & trunk

clinical presentation

• during middle adulthood

• superficial lesion which is well-circumscribed & partially encapsulated

• soft & doughy to touch; rubbery & moves easily when touched

• histologically looks likes normal adipose tissue

liposarcoma

one of the most common adult sarcomas that are derived from primitive mesenchymal cells & arise deep in the proximal extremities or retroperitoneum of people in their 50s & 60s

• well-differentiated & pleomorphic types

well-differentiated liposarcoma

liposarcoma that has adipocytes & atypical spindle cells & indolent course

pleomorphic liposarcoma

consists of sheets of anaplastic cells, bizarre nuclei & variable amounts of immature adipocytes (lipoblasts)

nodular (pseudosarcomatous) fasciitis

subcutaneous growth involving the extremities & has rapid growth

• richly cellular & contains plump, immature-appearing fibroblasts & myofibroblasts arranged randomly or in short fascicles reminiscent of tissue culture fibroblasts

• often mistaken for sarcoma

• spontaneously regresses & rarely recurs if excised

myositis ossificans

ossification of injured muscles usually caused by trauma

• may be mistaken for malignancy

• feels hard/firm

fibromatoses

benign superficial proliferations of fibrous tissue

• make be palmar, plantar, or penile

  • palmer = Dupuytren's contracture (digit 4 & 5)

  • penile = Peyronie’s disease (may constrict urethra & cause painful erections)

desmoid tumor

aggressive fibromatoses commonly found in the abdominal wall of women

• associated with pregnancy & has estrogen receptors

• mutations in APC or β-catenin genes

• intraabdominal lesions seen with Gardner syndrome

fibrosarcoma

rare soft tissue tumor that occurs mostly in the retroperitoneum, thigh, knee, & distal extremities

• encapsulated, infiltrative, soft, fish flesh masses with areas of hemorrhage & necrosis

• highly cellular neoplasm of spindle cells growing in a herringbone (or basket-weave) fashion which nuclear pleomorphism & frequent mitosis

benign fibrous histiocytoma

a tumor consisting of fibroblasts and histiocyte-like cells, typically found in the skin of the lower extremities (95%)

• also known as dermatofibroma

malignant fibrous histiocytoma

undifferentiated pleomorphic sarcoma (UPS); most common adult sarcoma that may invade bone & is osteolytic

• storiform-pleomorphic type is the most common - sheets of large anaplastic spindled to polygonal cells with hyperchromatic irregular, sometimes bizarre nuclei

• treated with surgery & adjuvant chemotherapy, and/or radiation

• most are aneuploid & prognosis is generally poor

rhabdomyosarcoma

most common soft tissue sarcoma in children & adolescents (alveolar & embryonal) that often arise in the sinuses, head, neck, & genitourinary tract

• only 20 - 25% arise in skeletal muscles

• desmin & myoglobin usually present in all types

  • actin ,myosin, & glycogen also seen

• overall average survival ~ 3 - 5 years

  • ~ 20% already have metastases @ diagnosis

  • pleomorphic type = worse prognosis

embryonal rhabdomyosarcoma

rhabdomyosarcoma that include cambium layer with primitive around cells, oval cells, strap cells, & racquet-shaped cells

• sarcoma botryoides - variant which presents as grape-like mass

synovial sarcoma

rare soft tissue tumor that occurs near joints but not usually in joints

• associated with gene fusions SS18-SSX1, -SSX2, or -SSX4 (chimeric transcription factors)

• probably arises from multipotential mesenchyme

clinical presentations

• can present in locations that lack synovium (chest wall, head, neck)

• most occur in people in their 20s - 40s

• microscopically has a biphasic pattern of spindle cells & glands