Langerhans cell histiocytosis
Proliferative disorder of monocytes
Variants include:
Hand-Schuller-Christian disease
-Skull lesions
-Exophthalmos
-Diabetes insipidus
-Mostly in patients older than 2
Letterer-Siwe syndrome
-Hepatosplenomegaly
-Anemia/hemorrhage
-Patients usually under 2
Histiocytosis X
-solitary eosinophilic granuloma
-bone lesions
-older children (over 2)
-may be observed if asymptomatic
-RT given for lesions recurrent after surgery or refractory to steroids/chemo
-10Gy gives good local control, over 80%
Saturday, September 4, 2010
Retinoblastoma
Epidemiology
300 cases/year
Almost all patients are under 5
60 - 70% sporadic
30 - 40% hereditary (younger patients, more likely to be bilateral, 5 - 10% develop osteosarcoma later in life)
Trilateral RB (Bilateral RB with pineal PNET)
5 to 10% of hereditary RB cases
Biology
Two-hit hypothesis
Rb is tumor suppressor gene located on chromosome 13
If a mutated copy of Rb is inherited, patients are at higher risk of losing the second copy and developing RB
Clinical
Leukocoria, strabismus, decreased visual acuity
Biopsy is contraindicated as it can seed the rest of the eye
Treatment
Primarily laser/surgical
Plaque brachy can be performed
300 cases/year
Almost all patients are under 5
60 - 70% sporadic
30 - 40% hereditary (younger patients, more likely to be bilateral, 5 - 10% develop osteosarcoma later in life)
Trilateral RB (Bilateral RB with pineal PNET)
5 to 10% of hereditary RB cases
Biology
Two-hit hypothesis
Rb is tumor suppressor gene located on chromosome 13
If a mutated copy of Rb is inherited, patients are at higher risk of losing the second copy and developing RB
Clinical
Leukocoria, strabismus, decreased visual acuity
Biopsy is contraindicated as it can seed the rest of the eye
Treatment
Primarily laser/surgical
Plaque brachy can be performed
Neuroblastoma
Epidemiology
Most common cancer in infants
700 cases per year
Median age at diagnosis is 2 years
Screening programs have been tested (famously in Japan) without affecting the mortality rate
No screening is currently offered
Prognostic factors
Unfavorable
-n-myc amplification
-unfavorable Shimada classification
-diploid DNA
-LOH at 1p
-Age older than one year
-Higher stage
Clinical
Most common site adrenal glands, then paraspinal
70% have mets at diagnosis
Skin mets: "Blueberry muffin" sign; blanch when pressed
85% of masses are calcified
Tumor markers: urinary and serum catecholamines (VMA, HVA)
Paraneoplastic syndromes: opsoclonus/myoclonus syndrome, fever, weight loss, hyper-VIP-ism
Staging: should include MIBG scan, bone marrow biopsy
Therapy
Low risk = stage I - II or IVS with favorable histology, normal n-myc, aneuploid
-Surgery only for stage I (gross total resection)
-Surgery + chemo for stage IIA (subtotal resection, node negative)
-Observation for IVS patients
Intermediate risk = stage IIA - IIB with any histology; III (unresectable) with favorable histology, infants with stage IV
-Induction chemo
-Surgery
-RT (24Gy) for residual disease)
High risk = Older than one year with mets; any age or stage with unfavorable pathology
-High intensity chemo with BMT
-Adjuvant cis-retinoic acid
-RT to primary and sites of bulky disease (24-30Gy)
Most common cancer in infants
700 cases per year
Median age at diagnosis is 2 years
Screening programs have been tested (famously in Japan) without affecting the mortality rate
No screening is currently offered
Prognostic factors
Unfavorable
-n-myc amplification
-unfavorable Shimada classification
-diploid DNA
-LOH at 1p
-Age older than one year
-Higher stage
Clinical
Most common site adrenal glands, then paraspinal
70% have mets at diagnosis
Skin mets: "Blueberry muffin" sign; blanch when pressed
85% of masses are calcified
Tumor markers: urinary and serum catecholamines (VMA, HVA)
Paraneoplastic syndromes: opsoclonus/myoclonus syndrome, fever, weight loss, hyper-VIP-ism
Staging: should include MIBG scan, bone marrow biopsy
Therapy
Low risk = stage I - II or IVS with favorable histology, normal n-myc, aneuploid
-Surgery only for stage I (gross total resection)
-Surgery + chemo for stage IIA (subtotal resection, node negative)
-Observation for IVS patients
Intermediate risk = stage IIA - IIB with any histology; III (unresectable) with favorable histology, infants with stage IV
-Induction chemo
-Surgery
-RT (24Gy) for residual disease)
High risk = Older than one year with mets; any age or stage with unfavorable pathology
-High intensity chemo with BMT
-Adjuvant cis-retinoic acid
-RT to primary and sites of bulky disease (24-30Gy)
Wilms tumor
Epidemiology
Most common pediatric renal tumor
450 cases per year
Age: 3 to 4 years
Risk factors
WAGR syndrome (Wilms tumor, aniridia, GU abnormalities, mental retardation)
Denys-Drash syndrome (Wilms tumor, pseudohermaphroditism, renal failure)
Beckwith-Wiedemann syndrome (hemihyperptrophy)
Pathology
WT1: tumor suppressor gene (located at 11p13)
-abnormal in 82% of Wilms patients with a congenital syndrome
-WT1 mutations are more rare in sporadic cases
WT2: mutated in Beckwith-Wiedemann syndrome
Clear cell sarcoma and rhabdoid tumor of the kidney are pediatric tumors that do not represent true Wilm's: rhabdoid tumor of the kidney may be related to ATRT
Prognostic factors
Stage
Histology: anaplastic Wilms (diffuse anaplasia is worse than focal)
LOH @ 1p or 16q
Clinical
Flank mass, hypertension, hematuria
Only 5-10% of tumors are calcified (calcified flank masses are much more likely to be neuroblastoma)
Therapy
Surgery only if:
-Patient less than 2 years old
-Stage I (confined to kidney and completely resected without spillage or biopsy)
-Tumor weighs less than 550g
-Favorable histology
Surgery + chemo if:
-Stage I, any of above criteria not fulfilled
-Any Stage II (extends beyond kidney with complete resection)
Surgery + chemo + RT if:
-Stage II, unfavorable histology (flank gets 10.8Gy)
-Stage III (residual disease), favorable histology (flank gets 10.8Gy)
-Stage III with diffuse anaplasia/RTK (flank gets 19.8Gy)
-Spillage or intra-abdominal tumor implants (whole abdomen gets 19.8Gy)
-Lung mets (12Gy whole lung irradiation, current COG protocol eliminates WLI if pt obtains a rapid complete response to chemo)
-Liver mets (19.8Gy to whole liver)
-Bone mets (25.2Gy)
Bilateral (stage V):
Induction chemo
Nephron sparing surgery if at all possible
Most common pediatric renal tumor
450 cases per year
Age: 3 to 4 years
Risk factors
WAGR syndrome (Wilms tumor, aniridia, GU abnormalities, mental retardation)
Denys-Drash syndrome (Wilms tumor, pseudohermaphroditism, renal failure)
Beckwith-Wiedemann syndrome (hemihyperptrophy)
Pathology
WT1: tumor suppressor gene (located at 11p13)
-abnormal in 82% of Wilms patients with a congenital syndrome
-WT1 mutations are more rare in sporadic cases
WT2: mutated in Beckwith-Wiedemann syndrome
Clear cell sarcoma and rhabdoid tumor of the kidney are pediatric tumors that do not represent true Wilm's: rhabdoid tumor of the kidney may be related to ATRT
Prognostic factors
Stage
Histology: anaplastic Wilms (diffuse anaplasia is worse than focal)
LOH @ 1p or 16q
Clinical
Flank mass, hypertension, hematuria
Only 5-10% of tumors are calcified (calcified flank masses are much more likely to be neuroblastoma)
Therapy
Surgery only if:
-Patient less than 2 years old
-Stage I (confined to kidney and completely resected without spillage or biopsy)
-Tumor weighs less than 550g
-Favorable histology
Surgery + chemo if:
-Stage I, any of above criteria not fulfilled
-Any Stage II (extends beyond kidney with complete resection)
Surgery + chemo + RT if:
-Stage II, unfavorable histology (flank gets 10.8Gy)
-Stage III (residual disease), favorable histology (flank gets 10.8Gy)
-Stage III with diffuse anaplasia/RTK (flank gets 19.8Gy)
-Spillage or intra-abdominal tumor implants (whole abdomen gets 19.8Gy)
-Lung mets (12Gy whole lung irradiation, current COG protocol eliminates WLI if pt obtains a rapid complete response to chemo)
-Liver mets (19.8Gy to whole liver)
-Bone mets (25.2Gy)
Bilateral (stage V):
Induction chemo
Nephron sparing surgery if at all possible
Osteosarcoma
Epidemiology
Most common primary bone tumor of children
700 cases per year
Slightly more common in boys
No racial differences
Adolescents
Risk factors
Prior RT
Hereditary retinoblastoma
Li-Fraumeni syndrome
Paget's disease (adults)
Pathology
Classic: higher grade
Periosteal: variant of classic
Parosteal: indolent, few mets
Clinical
Metaphysis of long bones
40% occur in the femur
90% of tumors are in the extremities
Codman's triangle = periosteal elevation
15% have mets at diagnosis, most common site is lung
Head and neck osteosarcoma seen more frequently in adult patients (mandible/maxilla); poor control with surgery alone and patients should receive chemotherapy
Pelvic and spine tumors are also more difficult to control (but rare)
Prognostic factors
Stage
Extent of necrosis after chemo
Therapy
1) Induction chemo: methotrexate, cisplatin, adriamycin, ifosfamide
2) Resection
3) More chemo
RT: Only for unresectable tumors, positive margin after surgery, palliation
Cade technique: RT with delayed amputation
Most common primary bone tumor of children
700 cases per year
Slightly more common in boys
No racial differences
Adolescents
Risk factors
Prior RT
Hereditary retinoblastoma
Li-Fraumeni syndrome
Paget's disease (adults)
Pathology
Classic: higher grade
Periosteal: variant of classic
Parosteal: indolent, few mets
Clinical
Metaphysis of long bones
40% occur in the femur
90% of tumors are in the extremities
Codman's triangle = periosteal elevation
15% have mets at diagnosis, most common site is lung
Head and neck osteosarcoma seen more frequently in adult patients (mandible/maxilla); poor control with surgery alone and patients should receive chemotherapy
Pelvic and spine tumors are also more difficult to control (but rare)
Prognostic factors
Stage
Extent of necrosis after chemo
Therapy
1) Induction chemo: methotrexate, cisplatin, adriamycin, ifosfamide
2) Resection
3) More chemo
RT: Only for unresectable tumors, positive margin after surgery, palliation
Cade technique: RT with delayed amputation
Ewing sarcoma
Epidemiology
2nd most common pediatric bone tumor (after osteosarcoma)
200 cases per year
Risk factors
57% males
Ages 8 - 25
Rare in blacks
Pathology
t11;22 (EWS gene) or t11;21 (ERG gene)
c-myc amplified
Staining: PAS+, S-100+, vimentin+, neuron specific enolase-, cytokeratin-
Clinical
Most common sites are pelvis (25%) and lower extremity (30%)
Diaphysis of the bone
On imaging: Onion-skinning = subperiosteal involvement; moth eaten bone
25% have mets at diagnosis
Prognostic factors
Unfavorable: tumor in pelvis or trunk, large mass, older age, poor chemo response, mets, unresectable tumor, VEGF+, p53, p16, p14 mutations
Therapy
1) Induction chemo: cyclophosphamide, adriamycin, vincristine, dactinomycin, ifosfamide, etoposide
Response to chemo is highly predictive of the ultimate outcome
2) Surgery: if at all possible
3) RT indications (always given with concurrent chemo)
-Unresectable tumor (55.8Gy)
-Positive or close margins
-Incomplete histologic response
RT technique:
-Whole bone RT is not necessary
-Typical field encompasses the pre-chemo volume + 2-4cm to 36-45Gy then boost residual disease/tumor bed to 50.4Gy or 55.8Gy (residual/unresectable tumor)
-Whole lung RT to 18Gy can be given for mets
2nd most common pediatric bone tumor (after osteosarcoma)
200 cases per year
Risk factors
57% males
Ages 8 - 25
Rare in blacks
Pathology
t11;22 (EWS gene) or t11;21 (ERG gene)
c-myc amplified
Staining: PAS+, S-100+, vimentin+, neuron specific enolase-, cytokeratin-
Clinical
Most common sites are pelvis (25%) and lower extremity (30%)
Diaphysis of the bone
On imaging: Onion-skinning = subperiosteal involvement; moth eaten bone
25% have mets at diagnosis
Prognostic factors
Unfavorable: tumor in pelvis or trunk, large mass, older age, poor chemo response, mets, unresectable tumor, VEGF+, p53, p16, p14 mutations
Therapy
1) Induction chemo: cyclophosphamide, adriamycin, vincristine, dactinomycin, ifosfamide, etoposide
Response to chemo is highly predictive of the ultimate outcome
2) Surgery: if at all possible
3) RT indications (always given with concurrent chemo)
-Unresectable tumor (55.8Gy)
-Positive or close margins
-Incomplete histologic response
RT technique:
-Whole bone RT is not necessary
-Typical field encompasses the pre-chemo volume + 2-4cm to 36-45Gy then boost residual disease/tumor bed to 50.4Gy or 55.8Gy (residual/unresectable tumor)
-Whole lung RT to 18Gy can be given for mets
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