MS Disorders

• - Selective depigmentation of hair/eyebrows w/ white streaks
• - Hypertelorism
• - Pear-shaped nose
• - Normal intelligence
• - Hearing loss

• - Mutation 5q21
• - Jaw osteomas
• - Intraabdominal desmoid (fibromatosis)
• - Familial adenomatosis polyposis with hundreds of colonic tubular adenomas and 100% risk of colonic carcinoma recommend resect colon by age 39 years

• - FGFR2 mutation
• - Autosomal dominant inheritance
• - Early closure of cranial sutures
• - Brachycephaly
• - Spacious forehead
• - Hypertelorism
• - Proptosis
• - Strabismus (“walleye”)
• - Nystagmus
• - Beak-like nose
• - Maxillary hypoplasia

• - Multiple enchondromas involving hands & feet
• - Multiple hemangiomas (spindle cell hemangiomas) of extremities
• - Extremities w/ calcified thrombi on x-ray
• - Increased risk of chondrsarcoma (15%) after age 40

• - Mucopolysaccharidosis (MPS) I
• - Alder Reilly Anomaly granules in neutrophils in peripheral blood smear
• - Cloudy corneas
• - Coarse facial features (gargoylism)
• - Depressed nasal bridge
• - Mental retardation
• - Abnormal heart valves
• -Knock-knees
• - Stiff joints
• - Autosomal recessive inheritance
• - Alpha L-iduronidase deficiency
• - Death in first decade due to respiratory insufficiency

• Multiple enchondromas of hands & feet
• Increased risk (30-50%) of chondrosarcomas after age 40

• - Polyostotic fibrous dysplasia with bony trabeculae having a Chinese letter arrangement w/o osteoblastic rimming & fibrous stroma
• - Often hip/femur involvement w/ shepherd’s crook deformity
• - Widened cortex w/ ground-glass appearance
• - Isosexual precocious puberty in females w/ early menarche
• - Café-au-lait macules w/ irregular coast of Maine periphery
• - Slightly increased risk of osteosarcoma

• - Linked to Chlamydia trachomatis infection
• - Classic triad of:
• 1) arthritis
• 2) Nongonococcal
• urethritis (NGU)
• 3) Conjunctivitis

• MPS II
• Similar to Hurler except no cloudy corneas
• X-linked recessive inheritance
• Different enzyme deficiency
• Sulfoiduronate sulfatase deficiency

• Hypoxanthine guanine phosphoribosyl transferase (HGPRT) enzyme deficiency
• Mental retardation
• Choreoathetosis
• Hyperreflexia
• ClonusLeg scissoring
• Self-mutilation w/ biting of lips, cheeks, & fingertips
• Early death in 2nd or 3rd decade due to infection or renal failure secondary to sodium urate deposits

• - Point mutation in FGFR3 on 4p16.3
• - Short extremities due to premature deposition of bony struts at growth plate
• - Overgrowth of disorganized chondrocytes not in columns
• - Large head w/ prominent forehead & depressednasal root
• - Normal intelligence
• - Normal reproductivity
• - Sporadic mutations
• - Autosomal dominant

• - Open neural tube defect w/ meningomyelocele or encephalocele
• - Repeatedly elevated alpha-fetoprotein in maternal serum & amniotic fluid
• - Linked to folic acid deficiency

• - Fatal in infancy or stillborn
• - Short flipperlike limbs
• - Small chest & bell-shaped abdomen
• - Death due to respiratory insufficiency
• - FGFR3 receptor missense or point mutation

• - Type II lethal in infancy
• - Deforming type III
• - Majority autosomal dominant generalized osteopenia w/ multiple bone fractures
• - Short stature
• - Abnormalities in synthesis of type 1 collagen
• - Blue sclera
• - Gray opalescent teeth w/ fractures due to dentinogenesis imperfecta

• Vitamin D deficiency in children
• Causes malnutrition, liver disease, renal insufficiency, lack of sunlight exposure
• Bowing of legs
• Knobbiness rachitic rosary at Costochondral junctions
• Flattened occiput if infant
• Disorderly arrangement of chondrocytes w/ lack of columns
• Excess unmineralized osteoid
• Generalized osteopenia
• Increased Parathyroid Hormone (PTH)
• Hypocalcemia

• - Infantile fatal
• - Autosomal recessive childhood form
• - Autosomal dominant adult form
• - Bone fractures
• - Cranial nerve palsies
• - Hearing loss
• - Vision problems
• - No marrow signal by MRI in infancy
• - Carbonic anhydrase II deficiency
• - Loss of osteoclastic activity
• - Primitive bone & primary spongiosa
• - Loss of medullary bone so pancytopenia w/ bleeding & infections
• - Increased bone density on x-ray w/ striped appearance
• - Loss of corticomedullary demarcation

• - Vitamin D deficiency in adults
• - Excess unmineralized osteoid w/ widened osteoidseams
• - Generalized osteopenia
• - Fractures, deformities w/ kyphoscoliosis

• - Primary senile postmenopausal due to decreased estrogen & increased osteoclastic activity
• - Secondary causes include endocrine E.g. Cushing’s disease or syndrome
• - Drugs
• - Thinning/loss of horizontal trabeculae w/ normal mineralization
• - Compression fractures in cervical and thoracic/lumbar spine

• Primary or secondary w/ bone pain involving metaphysic of radius, ulna, fibula, femur, humerus in decreasing order of freq.
• Clubbing of digits
• Periosteal new bone
• Secondary causes include bronchogenic lung carcinoma
• Cystic fibrosis
• Pulmonary metastases

• - Dead bone w/ empty lacunae plus
• - Fat necrosis in medullary cavity
• - No neutrophils
• - Causes include corticosteroids
• - Pancreatitis
• - Hemoglobinopathies including sickle cell anemia,polycythemia vera
• - Dysbarism (bends)
• - Often involves hip(s)
• - Found in 20% of cases of Gaucher’s disease

• - Dissecting osteitis w/ increased osteoclasticactivity
• - Often mixed w/ osteomalacia & osteosclerosis

• - Usually type I
• - Splenomegaly
• - Pancytopenia, first thrombocytopenia
• - Bone pain in long bones or spine
• - Present in 30s-40s
• - Autosomal recessive inheritance
• - Mineralized infarct
• - Widened metadiaphysis w/ Erlenmeyer flask appearance
• - Replacement of marrow by sheets of histiocytes w/ abundant PAS+ cytoplasm resembling wrinkled tissue paper

• - Avascular necrosis of femoral head (hips) in pediatric age
• - Limp, Abnormal gate
• - Pain referred to thigh
• - Must maintain range of motion

• - Caucasian, Northern European, US
• - M>F, older males 50 plus
• - Thickened skull bones so tight hat
• - Bowing of long bones
• - Classic osteosclerotic phase w/ prominent cement lines resembling jigsaw puzzle piece or mosaic
• - Coarse trabeculae on x-ray w/ widened cortex flame or blade of grass sign
• - Fatal secondary osteosarcoma
• - Increased serum alkaline phosphatase and urinary hydroxyproline; normal serum calcium & phosphorus

• - Associated w/ increased serum calcium due to increased parathyroid hormone
• - Pituitary adenoma
• - Dissecting osteitis w/ tunneling
• - Increased osteoclastic activity w/ bone resorption
• - Fibroblastic replacement

• - < 2cm, young, 1st 2 decades
• - Nocturnal pain relieved w/ aspirin
• - Long bones
• - Classic x-ray w/ mineralized nidus
• - Lytic zone & peripheral osteosclerosis
• - Central woven bone
• - Next loose connective tissues w/ vascular proliferation
• - Peripheral osteosclerosis
• - Zonation

• - Middle to old age
• - Axial skeleton
• -Pelvic or shoulder girdle
• - Multiple pleomorphic nuclei in a single lacuna
• - Mitoses
• - Pleomorphism
• - Conventional
• - Low grade w/ favorable prognosis
• - High grade III 70% mets usually to lung
• - Increased risk of chondrosarcoma:
• Maffucci syndrome
• Ollier’s disease
• Familial multiple osteochondromas EXT1 gene

• - Benign intramedullary tumor of hyaline cartilage
• - Lobules of cartilage w/ one nucleus in a lacunar space
• - X-ray showing rings & arcs
• - Stippled or flocculent densities
• - If multiple & involve hands & feet think Maffucci syndrome or Ollier’s disease

• - 2nd– 3rd decade,
• - Diaphysisof long bones
• - Small blue round cell tumor w/ islands of hyaline cartilage
• - Poor prognosis 28% at 5 years

• - Teens-20s
• - Metaphysis of long tubular bones
• - Oval bubbly w/ sclerotic rim on x-ray
• - Nodulesof hyaline cartilage w/ myxoid change
• - Proliferation of stellate and spindle cells w/ increased cellularity at periphery in fibrous septa

• - 30s-40s, MIDLINE lesion so sacrococcygeal or spheno-occipital
• - Rectal pain &constipation if sacrococcygeal
• - Visual field defects if spheno-occipital
• - Cords/nests of cells w/ clear bubbly cytoplasm (physaliferous cells)
• - EMA+, cytokeratin+, S100 protein+

• - Teens-20s,epiphyseal location
• - End of long bone
• - Distal femur
• - Proximal humerus
• - Sheets of polyhedral cells w/ eosinophilic cytoplasm
• -Mineralized matrix w/ a “chicken wire” appearance
• - Eccentric lytic lesion w/ sclerotic rim

• - Dev. defect so stop growing at puberty
• - Lateral displacement of growth plate
• - Cartilaginous cap, often pedunculated
• - Communication of medulla of osteochondroma & medullary cavity of long bone

• - Involve bones of skull or maxilla
• - Thickened bony trabeculae w/ woven & lamellar bone, often bones of skull
• - If multiple think of Gardner syndrome (tori)

• - Most common primary matrix producing malignancy of bone
• - Malignant ostoblasts
• - More common in males
• - 2 peaks w/ largest in 2nd-3rd decade and seconda peak in elderly as secondary osteosarcoma
• - early hematogenous spread to lungs
• - 20% w/ primary osteosarcoma have lung mets at presentation
• - Painless or painful mass most often around knee (distal femur, proximal tibia)

• found in eldery
• associated with radiation therapy
• paget's disease
• infarct

• - Classic low grade w/ favorable prognosis
• - Popliteal fossa mass
• - 2nd-3rd decade
• - Broad-based mass attached but not penetrating cortex of distal femur
• - Fibroblastic stroma w/ cartilaginous cap
• - Rare mitosis
• Rare“lacy” osteoid

• High grade
• Distal femur or proximal tibia
• Grossly resemble “bag of blood”
• Malignant osteoblasts in stroma
• Dilated vascular spaces

• Bloom, Li Fraumeni, McCune Albright Retinoblastoma, Rothman-Thomson, Werner elevation
• Lamellated onionskin appearance
• Spiculated or “sunburst” appearance characteristic of high sarcomas esp. high grade osteosarcoma & Ewing sarcoma
• [LiFraumeni, assoc w/ p53 mutation]

• Mono-ostotic or polyostotic
• Pediatric lesion
• Widened cortex w/ ground-glass appearance
• Irregular bony trabeculae w/ Chinese letter appearance w/o osteoblastic rimming & fibrous stroma
• Facial bones, ribs
• Femur/hip w/ shepherd’s crook deformity
• Polyostotic form w/ café-au-lait spots see w/ McCune Albright syndrome (3%)

• (called fibrous cortical defect if small lesion 0.5 cm in toddler)
• NOF in adolescent
• 5-6 cm in diameter
• Distal femur, proximal tibia
• Eccentric lytic intracortical w/ scalloped edges
• Metaphysis
• Fibroblastic proliferation w/ a storiform (“pinwheel”) pattern & clusters of foamy/xanthomatous histiocytes

• Codman triangle
• Abnormal periosteal reaction including Codman triangle (discontinuous periosteal reaction)
• Ivory-like density on x-ray,
• Extension of ivory-like density into soft tissue indicative of cortical destruction w/ soft tissue extension
• - Pathognomonic “lacy” or lacelike osteoid
• - Many mitoses
• - Some atypical, pleomorphic osteoblasts
• - Osteoblastic type has ivory-like density
• - Amount of necrosis inversely related to prognosis
• - Poor survival w/ increased necrosis

• Unifocal Langerhans cell histiocytosis
• Teens-20s
• Single lytic lesion in skull, rib, or metaphysic of femur
• CD1a+
• S100 protein+
• Langerhans cells w/ bluish gray cytoplasm & nuclear groove
• Accompanied by numerous eosinophils

• 2nd decade
• Metadiaphyseal
• Femur, tibia, radius
• Blown out eccentric lytic lesion
• Recurs if only curetted
• Dilated thin-walled vascular spaces
• Fibrous stroma w/ osteoclastic giant cells
• May be seen w/ other bone tumors including giant cell tumor of bone

• More common in females
• Unusual among bone tumors
• Eccentric lytic epiphyseal lesion w/ sclerotic rim
• Proliferating mononuclear type cell growing insyncytium & osteoclastic type giant cells
• Benign
• Recurs if incompletely excised

• Hypercalcemia w/ constipation & lethargy
• Low back pain, [anemia]
• 50-80 years
• Multiple lytic bone lesions or generalized osteopenia
• “spike” in gamma globulin region of SPEP
• Bence Jones protein in urine w/ “spike” and free monoclonal light chains
• IgG>IgA
• Light chain types
• In marrow sheets of plasma cells w/ eccentric nuclei, nucleoli, & multinucleation
• Most Common primary malignancy in bone

• T(11;22)
• Small, blue round cell tumor
• 1st – 2nd decades
• Permeative moth-eaten diaphyseal lesion w/ cortical destruction & soft tissue extension
• Abnormal lamellated periosteal reaction
• Many mitoses
• Necrosis
• PAS+ cytoplasm due to glycogen
• CD99+
• Vimentin+
• Aggressive tumor
• Requires chemotherapy, radiation

• Monoclonal gammopathy of IgM type
• More often presents w/ enlarged lymph nodes due to lymphoplasmacytic lymphoma
• Plasma cells w/ Dutcher bodies (intranuclear eosinophilic inclusions due to monoclonal protein)
• Small mature lymphocytes
• Plasmacytoid lymphocytes in bone marrow
• Headaches
• Blurred vision due to hyperviscosity syndrome
• Rouleaux formation with RBCs in periph. blood smear resembling stacks of coins
• Rouleaux can occur w/ any type of monoclonal gammopathy including plasma cell myeloma

• MOST COMMON malignancy in bone
• Remember eponym:
• Bacon Lettuce Tomato w/ Kosher Pickle
• Mets from: B= breast L = lung T = thyroid K = kidney P= prostate
• Lytic bone lesions in patient > 40 yrs is a METASTASIS, all lytic except prostate which is osteoblastic w/ woven new bone formation so x-ray of prostate mets shows increased bone density

• Also known as degenerative joint disease
• Increasing incidence at >50+ years
• Principally due to mech. wear & tear injury
• Increased TNFalpha & IL-1
• Fibrillation of articular cartilage w/ formation of joint mouse/mice (loose bodies) in synovial fluid
• Complete loss of articular cartilage called eburnation
• Subchondral cysts
• Subchondral osteosclerosis
• Involvement of major weight-bearing joints including hips, knees, spine
• Osteophyte formation
• Asymmetric, osteophytes at DIP joints in hands called Heberden’s nodes
• Stiffness in morning w/o decrease in symptoms w/ activity

• Necrotic bone w/ empty lacunae & neutrophils
• MOST COMMON cause is Staph aureus so see Gram positive cocci in clusters

• Other causes if IVDU or urinary tract infection include

• Klebsiella species, E. coli, or Pseudomonas aeruginosa

• Salmonella

• species in sickle cell anemia pts

• Hemophilus influenzae or Streptococcus agalactiae

• (Group B strep) in pediatric cases

• Lytic lesion w/ periosteal reaction in x-ray

• Hematogenous or direct spread

• Autoimmune condition
• HLADR4+
• Activated T lymphocytes, cytokines
• FEMALE predominance
• Relapsing/remitting
• Present in 20s-30s
• Systemic condition so can have fever
• Proliferative synovitis w/ classic finding of lymphoid nodules & also plasma cells
• Proliferating synovium forms pannus which grows over & destroys articular cartilage and extends to involve supporting tendinoligamentous structures w/ joint instability
• Mainly involves small joints of hands/feet
• Symmetric
• Stiffness in morning abates w/ activity
• Positive rheumatoid factor of IgM type
• PIP & MCP principally involved
• Ulnar deviation
• Swan neck deformity
• Subluxation at MCP joints
• Rheumatoid nodule w/ central fibrinoid necrosis & periph. palisading of histiocytes & lymphocytes over flexer surfaces
• Elbows or visceral organs

• Chronic inflammation w/ plasma cells
• Fibroblastic proliferation
• Necrotic bone w/ empty lacunae called sequestrum,
• Overlying woven bone on necrotic bone is called involucrum

• If involve spine, called Pott’s disease
• Granulomas w/ central caseation & periph. Langhans giant cells & T lymphocytes
• [Periph =peripheral]

• Seen in 5% of pts w/ psoriasis
• 35-45 yrs of age
• Silvery scales in flexural areas
• Most often asymmetric oligoarticular
• DIP of hands/feet > ankles > knees & hips
• Sausage-shaped fingers (dactylitis) w/ pitting of nails
• Onycholysis of nails

• Caused by deposits of sodium urate crystals which arethin, needle-shaped showing strong negative birefringence (blue perpendicular to axis of compensation & yellow parallel)

Large aggregates of sodium urate called tophi seen w/

• recurrent disease usually after history of 12+ yrs

• Treat w/ allopurinol

• Abort attack w/ colchicines

• & NSAIDs

• Exacerbate symptoms w/ alcohol & obesity

• Classic pain in first MTP joint of great toe > insteps

• > ankles > heels

• Later hands

• Asymmetric

• Can have renal stones or renal failure

• Classic crystals identified in synovial fluid

• Also know as chondrocalcinosis
• Deposits of calcium pyrophosphate crystals which are short w/ blunt ends showing weak positive birefringence (blue parallel to axis of compensation & blue perpendicular)

• Increasing symptom

• s

• Starts in adolescence & progresses
• Males w/ spinal immobility (“bamboo spine”)
• Involvement of sacroiliac joints
• HLAB27+
• Inflammation of tendinoligamentous insertion w/ bony outgrowths

• Classic triad of arthritis
• Nongonococcal urethritis (usually due to Chlamydiatrachomatis) & conjunctivitis
• HLAB27+
• Males in 20s-30s
• Some have hx of GI infectionsArthritis may have similar distribution w/ involvementof sacroiliac joints as seen in ankylosing spondylitis

• Joint most often involved is knee
• Causative agents include Staph aureus, Hemophilus influenzae, N. gonorrhoeae

• Gram

• negative bacilli (E. coli, Salmonella sp., Pseudomonas sp.)

• < 2 yr Hemophilus influenzae

• Older

• children & adults Staph aureus

• 15-25 year Neisseria gonorrhoeae w/ neutrophils as well

• as intracellular and extracellular Gram negative cocci in pairs (diplococci)

• Inborn error of metabolism w/ autosomal recessive inheritance
• Homogentisic oxidase deficiency
• Early diagnosis if mother notices black color in diaper
• Brown-black conjuctiva
• Early onset of crippling osteoarthritis w/ brown-black pigment deposits in articular cartilage w/ erosion
• Low back pain initially due to spine involvement
• Later hips & knees
• Many loose bodies
• Renal stones & renal failure
• Early onset of angina and atherosclerosis

• Caused by Borrelia burgdorferi with reservoir white-footed mouse
• Hard tick vector lxodes dammini or lxodes scapularis
• Erythema chronicum migrans papule surrounded by erythematous ring
• Follows few weeks to 2 years after untreated Lyme disease
• Asymmetric
• Can be destructive like rheumatoid arthritis
• involves knees, shoulders, elbows, ankles

• Clonal proliferation
• Knee and ankle most often involved
• Bony erosion/destruction
• Proliferating mononuclear cells
• Hemosiderin deposits
• Fibrosis & osteoclast-like giant cells

• Common mass lesion involving fingers
• Identical histology to pigmented villonodular synovitis

• p53 mutation on 17p13
• Increased risk of osteosarcoma or chondrosarcoma
• Soft tissue sarcoma including: Rhabdomyosarcoma, Breast Carcinoma, Brain tumors, Adrenal cortical carcinoma

• Port wine stain w/ ipsilateral venous angiomatosis of leptomeninges
• Seizures
• Mental retardation

• Hemangiomas
• Dysplastic arteriopathy
• Pain & hypertrophy of involved extremity
• Risk of infection

• Adenoma sebaceum (angiofibroma of nasolabial region)
• Shagreen patches
• Bilateral multiple angiomyolipomas of kidneys
• Subependymal giant cell astrocytoma/hamartoma
• Lymphangioleiomyomatosis
• Mentalretardation
• Epilepsy/seizures
• Cardiac rhabdomyoma w/ large “spider” cells having clear cytoplasm
• PAS+ due to glycogen

• Chronic lymphedema due to axillary dissection w/ breast carcinoma & radical mastectomy
• Violaceous tumor mass due to angiosarcoma w/ anastomosing vascular channels lined w/ CD31+ pleomorphic endo cells w/ hobnail appearance plus solid growth pattern of pleomorphic CD31+ cells

• Hemihypertrophy
• Wilms tumor
• Increased risk of soft tissue sarcoma including rhabdomyosarcoma
• Mutation of 11p15

• Mutation of 17q11.2 involve neurofibromin
• Multiple neurofibromas usually plexiform w/ gross appearance of “bag of worms”
• Mixture of neuritis, collagen, S100 protein+ Schwann cells
• Numerous café-au-lait macules (large, >6)
• Lisch nodules of irides
• Autosomal dominant inheritance
• 5% risk of developing malignant peripheral nerve sheath tumor in deep plexiform neurofibromas

• Mutation of 22q12 involving merlin
• Acoustic “neuromas” actually schwannomas
• Cellular Antoni A w/ Verocay bodies
• Myxoid hypocellular Antoni B
• Hyalinized vessel walls
• Cafe-au-lait macules
• No Lisch nodules
• Nodular Fascitis
• Children & young adults
• Volar forearm
• Reaction to repetitive trauma (chest wall of weight lifter)
• Rapid growth
• Central myxoid change w/ “tissue culture” like appearance
• Proliferating mitotically active fibroblasts
• Well circumscribed
• Benign

• Slightly older than population affected by nodular fascitis
• Most often shoulder/upper extremity
• Ganglion cell-like appearance to proliferating cells
• Not as common as nodular fascitis
• Less well circumscribed
• Benign

• 2nd-3rd decade
• Athlete
• 50% associated w/ trauma
• Proximal extremity
• Rapidly growing mass w/ ossification occurring over 3 weeks
• Central lesion resembles nodular fascitis w/ myxoid “tissue culture” appearance
• Surrounding granulation tissue & woven bone
• Peripheral lamellar bone formation
• ZONATION
• Benign

• S100 protein+, diagnostic cell is lipoblast which is pleomorphic cells w/ varying sized fat vacuoles which indent central enlarged hyperchromatic nucleus or
• Signet-ring like lipoblast w/ single cytoplasmic fat vacuole pushing an enlarged hyperchromatic nucleus to side
• Well differentiated lipoma-like liposarcoma
• Also called Atypical lipoma
• GOOD prognosis
• 10% have dedifferentiated component w/ worse prognosis
• Marker ring & giant chromosomes derived from 12q13-15

• t(12;16)
• Typical lipoblasts mainly of which resemble signet ring cells
• Myxoid/mucoid background
• Delicate plexiform vascular network
• Middle age
• Deep soft tissue mass involving extremities or retroperitoneum
• Also popliteal mass

• Also t(12;16)
• Less favorable prognosis than myxoid LPS
• Much more cellular, Resembles lymphoma
• Look for diagnostic lipoblasts,

• Middle age, Deep soft tissue mass involving extremities

• or retroperitoneum

• Benign proliferation of fibroblasts w/ long sweeping fascicles of bland spindle cells
• Focal keloidal type collagen
• Widely infiltrative difficult to completely excise
• Involves abdominal wall after pregnancy
• Classic intraabdominal fibromatosis called desmoid found in Gardner syndrome

• [Aka Dermatofibroma]
• Middle age, mobile tan skin nodule
• Tumor of dermis
• Overlying epidermal hyperplasia
• No Grenz zone
• Heterogenous population of proliferating factor XIIIa+ fibroblasts in a storiform pattern demonstrating collagen trapping
• Hemosiderin deposits
• Clusters of foamy histiocytes
• Pushing border w/ subcutaneous tissue
• Benign

• Cardiac lesion often involving left ventricle
• Remember in conjxn w/ tuberous sclerosis
• Benign tumor of skeletal muscle
• Classic “spider”cells w/ central nucleus & tendrils of cytoplasm extending from nucleus & clear PAS+ cyto due to glycogen
• [cyto = cytoplasm]

• Malignancy of skeletal muscle
• Classic nuclear stain w/ myogenin & MYOD1

• 1st decade median age 7 years
• Usually of spindle cell type w/ superior prognosis
• Small blue round cell tumor
• Scattered tadpole cell
• Cells w/ eosinophilic cytoplasm having cross striations
• Myxoid change
• Nuclear myogenin and MYOD1 positive
• Also found in head & neck, orbit

• Superior prognosis
• Arise in a hollow viscus
• Most often urinary bladder or vagina
• Less often head & neck in nasal cavity
• Toddler-6 years
• Grossly has grape-like polypoid appearance
• Submucosal cambium layer w/ increased cellularity
• Underlying myxoid change w/ scattered cc & cc w/ eosinophilic cyto & cross striations
• Nuclear myogenin & MYOD1 positive

• 1st decade
• Intermediate prognosis
• Most often head & neck area

• 1st – 2nd decade
• Deep soft tissue of extremities
• WORST prognosis
• Nested appearance
• Clusters of small to medium sized cells, some w/ eosinophilic cytoplasm
• Central necrosis causing dropout leading to an alveolar appearance
• Fibrous stroma around nests w/ giant cells having a wreathlike arrangement of nuclei
• Nuclear MYOD1+
• Nuclear myogenin+

• Malignant tumor of smooth muscle
• > 3 mitoses per 10 HPF suspicious for malignancy outside uterus
• Pleomorphic nuclei
• Hemorrhage and necrosis seen grossly
• Also larger size
• Deep soft tissues of extremities or retroperitoneum
• Middle age or older

• Der(17) t(X;17), TFE3 positive
• POOR prognosis
• 15-35 years
• Deep soft tissues of thigh or less often buttocks
• Hematogenous spread mets to lung
• Vascular invasion seen at presentation
• Nested pattern
• Large polygonal cells w/ vesicular nuclear chromatin
• Prominent nucleoli
• Granular eosinophilic cytoplasm & cytoplasmic PAS+ crystalline inclusions
• Cell of origin unknown TFE3 pos

• Classic t(X;18), TLE3 positive
• 15-35 years
• Popliteal mass w/ calcification
• Most often biphasic tumor w BCL2+ CD99+ short spindle cells having overlapping nuclei & clusters of EMA+ cytokeratin+ epitheloid cells which may form gland-like spaces
• Relatively poor prognosis w/ late fatal lung metastases
• Poorly differentiated variant resembling small blue round cell tumors does worse
• Neurofibroma & schwannoma already discussed w/ NF1 & NF2, can be solitary independent lesions, both S100 protein+

• Prototype small blue round cell tumor
• Adrenal mass or paravertebral
• abdominal pain, palpable mass
• 90% <5 years
• Favorable <1 year at presentation
• Low stage favorable
• Ovoid small blue cells, stippled nuclei
• Homer-Wright pseudorosettes around pink neuropil
• Unfavorable N-myc amplification HSR homogenous staining regions, double minutes