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227 Cards in this Set
- Front
- Back
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Common congenital malformations
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p. 224
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Name 7 common congenital malformations
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(1) Heart Defects (congenital rubella) (2) Hypospadias (3) Cleft lip with or without cleft palate (4) congenital hip dislocation (5) spina bifida (6)anencephaly (7) pyloric stenosis (associated with polyhydramnios & projectile vomiting)
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Name 2 neural tube defects (NTDs)
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Spina bifida and anencephaly
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Name 2 diagnostic associations with NTDs during gestation
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increased serum and amniotic fluid levels of a-fetoprotein
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How can the incidence of NTDs be reduced?
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Folate ingestion during pregnancy
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Congenital Heart Disease
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p. 224
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What kind of shunts cause early cyanosis?
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R-to-L "blue babies"
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What kind of shunts cause late cyanosis?
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L-to-R "blue kids"
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Name 3 common R-to-L shunts.
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The 3 T's: Tetralogy of Fallot (most common cause of early cyanosis), Transposition of the great vessels, truncus arteriosus
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What might you see children with a R-to-L shunt do to relieve discomfort?
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Squat to increase venous return
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Name 3 common L-to-R shunts.
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VSD, ASD, PDA
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Rank them in order of frequency
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VSD > ASD > PDA
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What are the auscultatory signs of an Atrial Septal Defect?
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Loud S1; wide, fixed split S2
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How do you treat PDA?
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Indomethacin
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Name 3 sequelae of L-to-R shunts.
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1) Increased pulmonary resistance due to arteriolar thickening. 2) Progressive pulmonary HTN 3) R-to-L shunt (Eisenmenger's)
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Eisenmenger's Syndrome
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p. 224
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What are signs/symptoms of Eisenmenger's?
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Late cyanosis, clubbing, polycythemia
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Tetrology of Fallot
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p. 224
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What is the Tetrology?
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(1) Pulmonary Stenosis (2) RVH (3) Overriding aorta (4) VSD (mnemonic: PROVe)
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What is the direction of the shunt in the tetralogy?
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right-to-left across the VSD
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What is the x-ray finding on the tetralogy?
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Boot-shaped heart due to RVH
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What is the embryological cause of the tetralogy?
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Anterosuperior displacement of the infundibular septum.
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Transposition of great vessels
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p. 225
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The transposition occurs because of a failure of the --------------- --------- to -------
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failure of the aorticopulmonary septum to spiral
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In transposition of the great vessels, the aorta leaves ------------ and the pulmonary trunk leaves the ------------
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aorta leaves the RV (anterior) and the pulmonary trunk leaves the LV (posterior)
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How might transposition of the great vessels, be compatible with life?
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If a shunt (e.g. VSD, PDA or patent foramen ovale) exists, blood from the systemic and pulmonary circulations can mix. Clinicians use PGE to keep PDA open.
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Transposition of the great vessels is a common congenital heart disease in offspring of mothers with what disease?
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Diabetes
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Coarctation of aorta
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p. 225
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Where is the aortic stenosis in the infantile type of coarctation?
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Preductal (proximal to insertion of ductus arteriosus) - INfantile (in close to heart)
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Where is the aortic stenosis in the adult type of coarctation?
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Postductal (distal to ductus arteriosus). - ADult (Distal to Ductus)
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Name 3 symptoms in adult type coarctation?
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(1) Notching of the ribs (2) HTN in upper extremities (3) Weak pulses in upper extremities
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What is the Male-to-Female ratio in coarctation?
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3-to-1
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What pulses should you check on physical exam?
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Femoral
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Patent ductus arteriosus
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p. 225
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Which direction is the shunt in a neonate with PDA?
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Left-to-right
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What change occurs to the heart in PDA?
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RVH and failure
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What is the auscultatory finding in PDA?
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Continuous, "machine-like" murmur.
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How is patency maintained in PDA?
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PGE synthesis and low Oxygen tension.
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What drug is used to close a PDA?
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Indomethacin
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How is a PDA kept open?
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PGE
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Why would you want to keep a PDA open?
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To sustain life in conditions such as transposition of the great vessels.
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Autosomal trisomies
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p. 226
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What is the most common chromosomal disorder and cause of congenital mental retardation?
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Down Syndrome (trisomy 21), 1:700
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In Down syndrome, 4% of cases are due to ------- translocation, and 1% are due to -------- mosaicism
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Robertsonian; Down
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95% of Down syndrome cases occur because of --------- --------- of homologous chromosomes
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meiotic nondisjunction
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What is the type and cause of the most common congenital heart malformation in Down syndrome?
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Septum-primum-type ASD due to endocardial cushion defects
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Name 8 findings in trisomy 21
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(1) mental retardation (2) flat facial profile(3) prominent epicanthal folds (4) simian crease (5) duodenal atresia (6) congenital heart disease (7) Alzheimer's in affected >35 yrs old (8) Increased risk of ALL
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Name a risk factor for Down Syndrome
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Advanced maternal age (1:500 < 20 yo; 1:25 > 45 yo)
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What is the name of the syndrome associated with trisomy 18?
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Edwards' syndrome (Election age = 18)
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Name 7 findings in trisomy 18
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(1) severe mental retardation (2) rocker bottom feet (3) low-set ears (4) microngathia(5) congenital heart dz (6) clenched hands (flexion of fingers) (7) prominent occiput
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What is the life expectancy in trisomy 18?
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Death usually w/in 1 year of birth
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What chromosomal anomaly is found in Patau's syndrome?
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trisomy 13 (1:6000)
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Name 7 findings in Patau's
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"(1) severe mental retardation (2) microphthamlia
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What is the life expectancy in Patau's?
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Death usually w/in 1 year of birth
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Genetic gender disorders
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p. 226
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What is the chromosomal anomaly in Klinefelter's syndrome?
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XXY (1:850) - male
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Name 5 characteristics of Klinefelter's syndrome
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"(1) Testicular atrophy (2) Enuchoid body shape
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What is a Barr body and is it found kin Klinefelter's syndrome?
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It is the inactivated X chromosome. Yes.
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What is the chromosomal anomaly in Turner's syndrome?
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Female XO; (1:3000)
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Name 4 characteristics of Turner's syndrome
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(1) Short stature (2) Ovarian dysgenesis (streak ovary) (3) Webbing of next (4) Coarctation of the aorta
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Turner's syndrome is the most common cause of primary ------------
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amenorrhea
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Is there a Barr body in Turner's syndrome?
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No
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Double Y males have what genotype?
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XYY (1:1000) - male
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What is the double Y phenotype?
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Normal phenotype, very tall, severe acne, antisocial behavior (seein in 1-2% of XYY males; seen increasingly among prison inmates)
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Muscular dystrophies
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p. 226
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How are muscular dystrophies diagnosed?
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Elevated CPK and muscle biopsy
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What is the gene involved in muscular dystrophy?
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Dystrophin
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What is the mutation in Duchenne's MD?
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Frame-shift mutation - deletion of dystrophin gene - accelerated muscle breakdown.
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What is the age of onset in Duchenne's MD?
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Before 5 years
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In what muscles does weakness begin with Duchenne's MD?
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Pelvic girdle muscles and progresses superiorly
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Name 3 diagnostic characteristics of Duchenne MD.
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(1) Pseduohypertrophy of calf muscles due to fibrofatty replacement of muscle (2) Cardiac myopathy (3) Use of Gowers' maneuver, requiring assistance of upper extremities to stand up - indicates proximal lower limb weakness
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What distinguishes Becker's from Duchenne's MD?
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Less severe mutation in Becker's. Less debilitating.
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Pseudohermaphroditism
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p. 227
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What is pseudohermaphroditism?
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Disagreement between the phenotypic (external genitalia) and gonadal (testes vs. ovaries) sex.
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A female pseudohermaphrodite has ------- present, but external genitalia are -------- or -----------.
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ovaries; virilized or ambiguous
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What causes female pseudohermaphroditism?
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Excessive and inappropraite exposure to androgenic steroids during early gestation (i.e.,congenital adrenal hyperplasia or exogenous administration of androgens suring pregnancy).
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What are the phenotypes in female and male pseudohermaphroditism?
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"female - XX;
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A male pseudohermaphrodite has ------- present, but external genitalia are --------- or ---------.
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testes; female or ambiguous
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What is the most common form of male pseudohermaphroditism?
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Testicular feminization (androgen insensitivity), which results from a mutation in the androgen receptor gene (x-linked); blind-end vagina
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What determines gender identity?
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External genitalia and sex of upbringing.
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True Hermaphrodite (46,XX or 47, XXY)
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p. 227
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What is a true hermaphrodite?
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Both ovary and testicular tissue present; ambiguous genitalia.
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What are the genotypic possibilities for a true hermaphrodite?
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46,XX or 47,XXY
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Testicular Feminization syndrome (46, XY)
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p. 227
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What is the molecular defect in testicular feminization syndrome?
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Defect in DHT receptor resulting in normal-appearing female
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What genitalia are present in testicular feminization syndrome?
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female genitalia with rudimentary vagina; uterus and uterine tubes generally absent; develop testes (often found in labia majora; surgically removed to prevent malignancy)
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What are the genotype and horomone levels in testicular feminization syndrome?
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46, XY; levels of testosterone, estrogen and LH are all high
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5a-reductase deficiency
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p. 227
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What is the biochemical consequence of 5a-reductase deficiency
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Unable to convert testosterone to DHT.
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Describe genital development in 5a-reductase deficiency.
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Ambiguous genitalia until puberty, when increased testosterone causes masculinization of genitalia.
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What are the hormone levels in 5a-reductase deficiency.
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Testosterone/estrogen levels are normal; LH is normal or elevated.
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Cri-du-chat syndrome
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p. 227
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What is the mutation in Cri-du-chat syndrome?
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Congenital deletion of short arm of chromosome 5 (46,XX or XY, 5p-)
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What are the findings in Cri-du-chat
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Microcephaly, severe mental retardation, high-pitched crying/mewing, epicanthal folds, cardiac abnormalities.
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What does Cri-du-chat mean in english, which might help remember the symptoms?
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Cry of the cat.
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Fragile X syndrome
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p. 227
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What is the 2nd most common cause of genetic mental retardation?
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Fragile X syndrome
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What genetic change is involved in Fragile X syndrome?
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x-linked defect affecting the methylation and expression of the FMR1 gene.
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Name 4 physical features associated with Fragile X syndrome?
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(1) macro-orchidism (enlarged testes) (2) Long face with a large jaw (3) large everted ears (4) autism
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Cystic Fibrosis (CF)
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p. 228
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What is the genetic defect in cystic fibrosis?
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Autosomal-recessive defect in CFTR gene on chromosome 7
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What is the molecular defect in CF?
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Defective Cl- channel
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What are the consequences of the defect in CF?
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The defective chloride channel causes secretion of abnormally thick mucus that plugs lungs, pancreas and liver, which leads to recurrent pulmonary infections (pseudomonas species and S. aureus), chronic bronchitis, bronchiectasis, pancreatic insufficiency (malabsorption and steatorrhea), meconium ileus in newborns.
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Name a diagnostic test for CF.
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Increased concentration of Cl- ions in sweat test.
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Why does CF cause infertility in males?
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Absent vas deferens.
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What vitamins are often deficient in CF?
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Fat-soluble - A,D,E,K
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Name an epidemiologic characteristic of CF.
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Most common lethal genetic disease of Caucasians.
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What is the treatment for CF?
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N-acetylcysteine to loosen mucous plugs.
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Autosomal-dominant diseases
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p. 228
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A patient presents with flank pain, hematuria, hypertension, progressive renal failure and has a mutation in one of his copies of APKD1 (chromosome 16); what is the diagnosis?
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Adult polycystic kidney disease. N.B. the juvenile form is recessive.
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Name 2 other characteristics of adult polycystic kidney disease.
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(1) always bilateral, (2) massive enlargement of the kidneys due to multiple large cysts.
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What sequelae are associated with adult polycystic kidney disease?
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(1) polycystic liver disease (2) berry aneurysms (3) mitral valve prolapse
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What disease involves elevated LDL owing to defective or absent LDL receptor?
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Familial hypercholesterolemia (type IIA)
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What are the average cholesterol levels in heterozygotes and homozygotes with familial hypercholesterolemia (tyype IIA)?
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"heterozygotes (1:500) - 300 mg/dL
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What are 3 sequelae of familial hypercholesterolemia (type IIA)?
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(1) severe atherosclerotic disease early in life (2). tendon xanthomas (classically in the Achilles tendon) (3) MI may develop before age 20
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What is the genetic defect in Marfan's syndrome?
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Fibrillin gene mutation leads to connective tissue disorders.
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What are the skeletal abnormalities in Marfan's?
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tall with long exteremities, hyperextensive joints, and long, tapering fingers and toes.
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What are the cardiovascular risks in Marfan's?
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cystic medial necrosis of aorta leads to aortic incompetence and dissecting aortic aneurysms; floppy mitral valve.
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What are the ocular risks in Marfan's?
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Subluxation of lenses.
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What is another name for Neurofibromatosis type 1?
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von Recklinghausen's disease
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What chromosome is affected in NF type 1?
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Long arm of chromosome 17 (17 letters in von Recklinghasen's)
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What are 5 classic characteristics of people with NF type 1?
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(1) café-au-lait spots (2) neural tumors (3) Lisch nodules (pigmented iris hamartomas) (4) skeletal disorders (e.g., scoliosis) (5) Increased tumor susceptibility
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What disease is associated with bilateral acoustic neuroma?
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Neurofibromatosis type 2
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What gene is affected in neurofibromatosis type 2?
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NF2 gene on chromosome 22; (type 2 = 22)
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What is the genetic mutation in Von-Hippel-Lindau disease?
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Deletion of VHL gene (tumor suppressor) on chromosome 3p. (Von Hippel-Lindau = 3 words for chromosome 3)
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What are the clinical findings in Von-Hippel-Lindau disease?
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hemiangioblastomas of retina/cerebellum/medulla; about half of affected individuals develop multiple bilateral renal cell carcinomas and other tumors.
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What is the diagnosis in a 20-50 year old person who presents with depression, progressive dementia, choreiform movements, caudate atrophy, and decreased levels of GABA and Ach in the brain?
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Huntington's disease
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What chromosome holds the gene involved in that disease?
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Chromosome 4; triplet repeat disorder ("Hunting 4 food")
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What disease is responsible for a colon that ecomes covered with adenomatous polyps after puberty?
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Familial adenomatous polyposis (FAP)
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What is the progression in that disease if colon not resected?
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Colon cancer
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What is the genetic defect in this disease?
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deletion on chromosome 5 - 5 letters in polyp
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What are 3 characteristics of hereditary spherocytosis?
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(1) spheroid erythrocytes (2) hemolytic anemia (3) increased MCHC
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What is the cure for hereditary spherocytosis?
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splenectomy
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What is the genetic defect in achondroplasia?
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Autosomal dominant cell-signaling defect of fibroblast growth factor (FGF) receptor 3.
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What are the physical characteristics of achondroplasia?
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Dwarfism, short limbs, but head and trunk are normal size.
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Autosomal-recessive diseases & X-linked recessive diseases
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p. 229
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For the following diseases, recognize as X-linked or AR: (continue - no answer)
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p229
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Cystic fibrosis
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AR
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albinism
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AR
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Fragile X
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X-linked
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Duchenne's muscular dystrophy
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X-linked
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hemophilia A and B
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X-linked
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a1-antitrypsin deficiency
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AR
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Fabry's
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X-linked
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G6PD deficiency
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X-linked
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Hunter's syndrome
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X-linked
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Phenylketonuria (PKU)
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AR
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thalassemias
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AR
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sickle cell anemias
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AR
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ocular albinism
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X-linked
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glycogen storage diseases
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AR
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mucopolysaccharidoses (except Hunter's)
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AR
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sphingolipidoses (except Fabry's)
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AR
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infant polycystic kidney
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AR
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Lesch-Nyhan syndrome
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X-linked
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Bruton's agammaglobulinemia
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X-linked
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hemochromatosis
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AR
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Wiskott-Aldrich syndrome
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X-linked
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What are femal carriers of x-linked recessive disorders rarely affected?
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Inactivation of X chromosomes in each cell
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Neural Tube Defects (NTD)
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p. 229
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Name two associations with neural tube defects during pregnancy.
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(1) Low folic acid intake (2) Elevated a-fetoprotein in amniotic fluid
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What NTD is associated with failure of bony spinal canal to close, but no structural herniation?
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Spina bifida occulta
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Which NTD is involved with herniation of meninges through spinal canal defect?
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Meningocele
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What is the NTD that involves herniation of meninges AND spinal cord through spinal canal defect?
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Meningomyelocele
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Which NTD is usually seen at lower vertebral levels?
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Spina bifida occulta
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Take a look at the figures in the book for good visualization of the NTDs.
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Fetal Alcohol Syndrome
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p. 229
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Who is at greatest risk of FAS?
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Newborns of mothers who consumed significant amounts of alcohol (teratogen) during pregnancy (highest risk at 3-8 weeks).
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Name 5 congenital abnormalities in FAS?
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(1) pre and postnatal developmental retardation (2) microcephaly (3) facial abnormalities (4) limb dislocation (5) heart and lung fistulas
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How does FAS rank among congenital malformations in the U.S.?
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It's number 1
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What is the presumed mechanism of FAS?
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Inhibition of cell migration?
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NEOPLASTIC PROGRESSION
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P. 230
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when cells increase in number it is called?
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hyperplasia
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what are two enzymes that allow neoplastic cells to invade th ebasement membrane?
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collagenase and hydrolase
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when cells have an increased nulear to cytoplasmic ratio but have not invaded the basement membrane, it is called?
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carcinoma in situ
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_ -PLASIA DEFINITIONS
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P. 231
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squamous _________ occurs in the trachea and bronchi of smokers
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metaplasia
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what is it called when a cell has reversible preneoplastic changes with abnormal shape and size?
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dysplasia
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abnormal cells that lack differentiation are called?
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anaplastic cells
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TUMOR STAGE VS. GRADE
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P. 231
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staging of a tumor takes into account what factors?
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"TMN" size of tumor, node involvment, metastases
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histolgy of a tumor is used to determine?
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grade
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what has more prognostic value? Grade or stage?
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stage
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TUMOR NOMENCLATURE
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P. 231
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the term _________ implies epithelial origin, whereas _________ implies mesenchymal origin
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carcinoma, sarcoma
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a tumor of blood vessels is called what when it is benign? When it is malignant?
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hemangioma, angiosarcoma
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what is a benign tumor of skeletal muscle called?
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rhabdomyoma
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DISEASES ASSOCIATED WITH NEOPLASMS
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p. 232
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Kaposi's sarcoma and aggressive malignant lymphomas are associated with what disease
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AIDS
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Actinic Keratosis predispose to what disease?
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squamous cell carcinoma of skin
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down syndrome is associated with what neoplasm?
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ALL
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ONCOGENES
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P. 232
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c-myc oncogenes are associated with what neoplasm?
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burkitt's lymphoma
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breast, ovarian, and gastic carcinomas all have this oncogene mutation in common?
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erb B2
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MEN II and III are associated with what oncogenic mutation?
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ret
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TUMOR SUPRESSOR GENES
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P. 233
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Name the associated tumor witht the following tumor supressor gene mutations: Rb, APC, WT1
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retinoma blastoma, colorectal cancer, wilms tumor
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p53 is on what chromosome
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17p
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osteosarcoma is associated with what tumor supressor gene mutation
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Rb
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TUMOR MARKERS
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P. 233
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TRAP is a tumor marker for what neoplasm
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hairy cell leukemia
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what tumor marker is elevated in hyatidiform moles
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beta-HCG
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ovarian tumors are associated with what tumor marker
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CA-125
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ONCOGENIC VIRUSES
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P. 233
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the virus associated with burkitts and nasopharyngeal cancer is?
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ebv
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hpv is responsible for what cancers?
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cervical, penile, and anal carcinoma
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what virus is responsible for kaposis sarcoma?
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hhv8
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CHEMICAL CARCINOGENS
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P. 233
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aflatoxin, vinyl chloride and ccl4 damage what organ?
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liver
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nitrosamines cause cancer in what organs?
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esophagus or stomach
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asbestos causes what types of cancer?
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bronchogenic and mesothelioma
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LOCAL EFFECTS OF TUMORS
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P. 234
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When the following are obstructed, what can occur: bronchus? Biliary tree? Left colon?
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pneumonia, jaundice, constipation
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tumor mass in the brain can cause the following
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seizure, increased intracranial pressure, mass effect and herniation
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compression of the recurrent laryngeal nerve can cause what?
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hoarseness
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PROSTATIC ADENOCARCINOMA
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P. 234
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what lobe/zone is most often involved in prostatic cancer?
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posterior lobe, peripheral zone
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what is a common site of metastases for prostate cancer?
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bone
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what are useful tumor markers for prostate CA
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psa, and prostatic acid phosphatase
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SKIN CANCER
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P. 234
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this type of skin cancer has palisading nuclei
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basal cell carcinoma
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dyplastic nevi are a precursor fot this type of cancer
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melanoma
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this type of skin cancer is associated with keratin pearls
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squamous cell carcinoma of skin
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PRIMARY BONE TUMORS
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P. 235
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the translocation 11;22 is associated with this cancer of the bone that occurs most commonly in young boys
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ewing's sarcoma
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this tumor is characterized by a "double bubble" or "soap bubble" appearance
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benign giant cell tumor
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this is the most common benign bone tumor, usually in men younger than 25, with a rare transformation to malignancy
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osteochondroma
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