What are more common: Malignant or Benign tumors?
Benign- can still cause problems due to location
What % of all cancers occur in infancy/childhood?
What % of infantile deaths in US infants/children?
2%
9%
What is heterotopia (choristoma)
benign/normal tissue in abnormal location. can cause mass effect , local destruction, can cause carcinoma
What is the term for overgrowth of benign tissue in its TYPICAL location?
Hamartoma
What are 3 common mesenchymal benign tumors?
Tumors of germ cell origin?
hemangiomas, lymphangiomas, fibrous tumors
teratomas
Most common tumor of infancy?
Most located where?
hemangioma
in the skin
What are the 2 growth phases of hemangiomas?
What can this indicate?
What can it cause (2)
Rapid proliferative phase (0-3 months)
Involution phase: often regresses completely by age 7
von Hippel-Lindau disease
can cause low platelets or cardiac stress
What are the 2 histological types of hemangiomas?
capillary and cavernous hemangiomas
picture shows capillary, cavernous more like mass
What is another term for lymphatic hamartomas?
lymphangioma-lymphatic spaces
What is the condition involving abnormal dilation of lymphatics often resulting in swollen extremity?
lymphangiectasia
enjoy a picture of a baby with lymphangioma
What fibrous tumor has low cellularity, has superficial and deep types, and is infiltratiec/ locally aggressive?
Fibromatosis
What fibrous tumor is typically in the extremities of children under 5 years of age, highly cellular, has >80% 5-year survival, and associated with a translocation?
Congenital-infantile fibrosarcoma
What fibrous tumor is present at infancy or birth and usually appears with multiples, recurrent if excised, grow rapidly for 1 year then involute over 10 years, can cause discomfort, and is located at fingers and toes?
Infantile Digital Fibromatosis
What percent of teratomas are benign? what are the characteristics of these type? (3)
Mature- 75% well-differentiated, cystic, majority seen in young infants
What are immature teratomas?
Indeterminate in malignant potential
What type of teratomas are 12% of cases?
What are the 2 types
Malignant- 2 types
mixed with another germ cell tumor
malignant transformation of one germ cell layer (non-germ cell tumor)
What are the 2 peaks of incidence of teratomas?
What are 4 common sites of teratomas?
Less than age 2 and late adolescence
sacrococcygeal, testis, ovary, MIDLINE locations (mediastinum, retroperitoneum, Head/neck)
What is the most common of teratoma of childhood?
Are these associated with anything?
Sacrococcygeal teratomas
M:F = 1:4
10% associated with congenital anomalies (spina bifida, meningocele)
What is the most common of teratoma of childhood?
Are these associated with anything?
Sacrococcygeal teratomas
M:F = 1:4
10% associated with congenital anomalies (spina bifida, meningocele)
What condition accounts for more deaths in children less than age 15 than all other tumors combined?
Leukemia
T/F teratogenesis- congenital malformations are associated with tumors?
True
Enjoy a pic of aniridia
What malignancies are associated with Down syndrome? (2)
Acute myeloid leukemia
Transient Abnormal myelopoiesis
What are the top 3 pediatric and adult tumor location by incidence?
Peds: bone marrow, central/sympathetic NS, kidney
Adult: Skin, Lung, Colorectal
What are 3 important tumors with embryonal cells of origin?
Think small round blue cell tumors
nephroblastoma, retinoblastoma, Ewing sarcoma/PNET
Whats the most common intraocular childhood cancer?
Whats its origin?
retinoblastoma
neuronal
What percent of Retinoblastoma inherit germline mutation of RB allele?
Can it be bilateral
40%
Yes and even trilateral
What are 2 key histological characteristics of retinoblastoma?
undifferentiated cells
Flexner-Wintersteiner rosettes/fleurettes
What is the term for tumors of sympathetic ganglia and adrenal medulla?
neuroblastic tumors
What are neuroblastic tumors derived from?
primordial neural crest cells
What are special characteristics of neuroblastic tumors? (3)
spontaneous or therapy induced differention into mature elements
Spontaneous tumor regression
Variable clinical behavior/prognosis
THE SPONTANEOUS TUMOR
Most cases of neuroblastoma are generally sporadic or heritable?
What gene is mutated in heritable cases?
Sporadic
1-2% familial
ALK- clinical trials aimed at kinase targeted therapy
In childhood, what percent of neuroblastomas occur at adrenal medulla? paravertebral? Posterior mediastinum?
What are the other 3 sites?
40% adrenal medulla
25% paravertebral
15% posterior mediastinum
Other sites: neck, pelvis, brain
How does neuroblastomas typically present under 2 years of age?
greater than 2 years?
under 2 years of age:
large abdominal mass, fever, weight loss, (rare) multiple cutaneous metastases
older than 2 years of age: may present with metastatic disease: pains and resp symptoms
Neonates presenting as Blue-berry muffin baby is indicative of _______?
neuroblastoma- multiple cutaneous metastases
Neuroblastoma: do metastases occur early or later in development?
early
What percent of neuroblastomas produce catecholamines in the serum?
What are 2 catabolites of these molecules that are found in urine?
90%
Vanillylmandelic acid (VMA)
Homovanillic acid (HVA)
Vanillas
Also produce a neuron-specific enolase
What are 3 morphological characteristics of neuroblastoma?(macro)
What are 3 micro morphologies of neuroblastoma?
necrosis, cystic softening, hemorrhage
Fibrillary neuritic processes(neruopil) , Homer-Wright pseuforosettes (neuropil core), mitotic activity/karyorrhexis
picture shows homer wright pseudorosettes
What molecule from neuroblastomas can be IDed via immunohistochemistry?
neuron specific enolase
What are 2 other ancillary tests for neuroblastoma identificaton?
EM of cytoplasmic catecholamine vesicles
FISH
Is maturation of neuroblastoma favorable or not?
What is required to mature neuroblasts? (2)
Yes favorable
Schwannian stroma and Ganglion cells
neuroblastomas can either regress or spontaneously differentiate
Ganglioneuroblastoma is a_________ while ganglioneuroma is essentially no________?
maturational mix
neuroblasts
What are 2 important characteristics at time of diagnoses for determining neuroblastoma outcome?
Age and stage
If patient is under 18 months of age when diagnosed with neuroblastoma, prognosis is_____?
excellent even if at stage 4S
f patient is over 18 months of age when diagnosed with neuroblastoma, prognosis is_____?
intermediate to high risk of death
What is the most important prognostic indicator for neuroblastoma?
How often does it occur and what risk?
N-MYC oncogene amplification by FISH
20-30% of cases--> high risk
What is favorable histology for neuroblastoma? (2)
Schwannian stroma and gangliocytic differentiation
How does ploidy in children <2 years of age predict prognosis with neuroblastoma?
IF hyper-diploid--> better prognosis
IF near-diploid--> unfavorable prognosis
What. 3 chromosomal deletions and additions are bad prognosis for neuroblastoma
1p36 deletion
11q deletion
add (17q)
What is the overall survival rate between ages 0-19 for neuroblastoma?
74.1%
What is the most common renal tumor of childhood and 4th among pediatric cancer?
What age?
nephroblastoma: WILMS Tumor
Usually occurs age 2-5 years
What percent of Wilms tumors are bilateral
(5-10%) associated with early age of onset
What 3 syndromes are associated with Wilms' tumor?
What % syndromic?
WAGR syndrome
Denys-Drash syndrome
Beckwith-Wiedemann
10%
What is WT1 and its fxn?
gene for transcription factor expressed in fetal kidney and gonads-->acts as tumor suppressor gene
10% abnormal in sporadic WT
What signaling pathway is B-catenin involved?
How can it be altered in subset of sporadic WT
WNT
gain of fxn
may be synergistic to WT1 mutations
What is WAGR syndrome?
what incidence of WT?
What was the first and second hits in this syndrome?
W-WT
A-Aniridia
G-Genital anomalies
R-retardation
33% incidence of WT
germline deletion of WT1 on 11p13 is first hit
second hit is acquired (somatic) mutation of 2nd WT1 allele
Deletion of auto dominant gene for aniridia
pic of hypospadias
What is Denys-Drash syndrome?
What does bi-allelic inactivation of WT1 result in?
90% incidence of WT
Dominant germ mutation of WT1 causes gonadal dysgenesis
Bi-allelic inactivation of WT1 occurs in Denys-Drash w/ cases Wilm's Tumor
What are 5 characteristics of Beckwith-Wiedemann Syndrome?
What is needed for normal fxn of 11p15.5 WT2 gene
What are 2 causes of overexpression?
organomegaly, macroglossia, hemihypertrophy, ompalocele, adrenal cytomegaly
imprinting- methylation of promoter to silence an allele
overexpression of the allele cause Beckwith- Wiedemann Syndrome
1.loss of imprinting
2. uniparental disomy
What 5 conditions are at increased risk for patients with Beckwith-Wiedemann Syndrome?
Wilms Tumor
Hepatoblastoma
Pancreatoblastoma
Adrenocortical tumors
Rhabdomyosarcomas
WHARP
What are 4 clinical features presented with Wilms' tumor?
What percent are bilateral/multicentric?
What may be present at diagnosis of Wilms' Tumor
Hematuria
Abdominal pain
Intestinal obstruction
Hypertension
pulmonary metastases may be present at diagnosis
What process does Wilms' Tumor mimic?
Nephrogenesis
What are nephrogenic rests?
Where are they found?
How are they similiar to WT?
Immature nephrogenic elements commonly found adjacent to WT
They are precursor lesions- genetic changes similiar to WT
What do nephrogenic rests imply?
risk of contralateral WT-routine surveillance required
What percent of Wilms' Tumor contain foci of anaplasia?
What do these look like?
5%
large, hymperchromatic pleomorphic nuclei and abnormal mitoses
What is the most predictive characteristic of WT for an adverse prognosis?
Anaplastic histology
What are the 5 treatment strategies for Wilms' Tumor?
- primary surgical resection
-primary chemo
-combo
-radiotherapy for high stages or LN involvment
-High dose chemo with autologous stem cell rescue
What is the approximate long term survival rate for WT?
prognosis for recurrences?
90%
recurrences are often successfully treated