Lymphoma Rhabdomyosarcoma Neuroblastoma

definition Embryonal ca of
peripheral SNS
Spontaneous regression
or aggressive
epidemiology 3rd most common ca (</_14 y/o) Most common pedia Most common
Most common in adolescents soft tissue sarcoma extracranial solid tumor
in children

Most common CA in
infants
HL NHL
incidence 60% of lymphoma whites
age 15-35 y/o and >50 y/o 2nd most common 22 mos., 90% dx at 5 yrs
15-35 y/o
Most common ca in
adolescents and young
adults

3rd Most common in

<15 y/o
M:F M>F in young M>F
Infectious agent HHV6, EBV (4x) Mostly de novo

2dary to
immunodef, HIV,
EBV, genetic
syndromes
Pathology From primordial neural
crest cells
Spectrum:
Undifferentiated small
round cells
(neuroblastoma)
Mature and maturing
Schwannian stroma w/
ganglion cells
(ganglioneuroblastoma
or ganlioneuroma)

Small round blue cells:

rhabdom ewing sarc,
NHL
Pathogenesis From same embryonic Amplification of MYCN
mesenchyme as (N-myc) protooncogene
striated skeletal (adv or poor) and tumor
muscle cell DNA content or
ploidy (better in <1 yr)
PAX-FOXO1
Pathognomonic Reed-sternberg cell 4 subtypes: 3 subtypes:
feature (RS)
-large, Lymphoblastic Embryonal (60%) –
multiple/multilobulate lymphoma (LBL) intermediate
 d nuclei Burkitt lymphoma prognosis
-hallmark of HL (BL) Botryoid type var. –
-also in IM, NHL, etc Diffuse-large B cell edematous stroma
-from germinal center lymphoma project into body
B cells (DLBCL) cavity like a bunch of
-surrounded by: Anaplastic large grapes in vagina,
lymphocytes, plasma cell lymphoma uterus, bladder,
cells, eo cells (ALCL) nasopharynx, middle
*Next table* ear

Alveolar (25-40%)
PAXFOX01 fusion
transcript

Tumor in nests w/
cleft-like spaces
resembling alveoli

Trunk and extremities

Poorest prognosis

Pleomorphic type
-adult form
Prognosis Poor:
Eo and CD68+
macrophages,
increased cytokine (IL1
and IL6, TNF)
Spread From lymphoid tissue Common in >1yr, local
to adjacent LN, invasion or distant
hematogenous: liver, hematogenous or
spleen, bone, BM lympathic

Regional or distant LN,

long bones, skull, BM,
liver, skin
Clin. Lymphadenopathy: Head and neck, GUT, At any site of SNS,
Manifestations Painless, nontender, extremities, orbit, adrenal glands,
firm, rubbery, cervical retroperitoneal paraspinal sympathetic
or supraclavicular, ganglia
mediastinal S: mass not painful. Sx
involvement are due to Local may be
displacement or asymptomatic
Systemic: obstruction of normal
B symptoms structures Superior cervical
Unexplained fever ganglion -> Horner
>38C, weight loss syndrome
>10% TBW over 6
mos., night sweats Spinal and Nerve root
compression in
paraspinal
neuroblastoma
 Opsoclonus-myoclonus-
ataxia syndrome

Catecholamine:
Sweating, HTN

TLS, DIC

<1 yr stage 4S
Dx Lymphadenopathy Main: surgery Immunohistochemistr Mass o multiple masses
-persistent, y (desmin, muscle- RT, CT, MRI
unexplained CBC, electrolytes, specific actin,
LDH, uric acid, myogenin) Mass has calcification
CXR, CT neck chest, calcium, and haemorrhage on RT
abdomen, pelvis, PET phosphorus, BUN, RTPCR or CT
creatinine,
CBC, ESR, serum bilirubin, ALT, Fluorescent in situ US prenatal dx
ferritin (baseline eval AST, BM hybridization for
for tx too) aspiration and PAXFOX01 transcript Tumor markers
biopsy, CSF alveolar tumor
BM asp and biopsy cytology, count, Catecholamine
protein HP: small roun blue metabolites
cell Homovanillic acid and
CXR, CT neck Vanillylmandelic acid
chest, abdomen, Definitive dx: increase in urine
pelvis microscopic and
immunohistochemical Patho dx on biopsy:
Flow cytometry and PAXFOX01 small round blue tumor
immunophenotyp expression cells
e and cytogenetis
(karyotyping) LN sampling dse Metastasis CT, MRI of
spread and boys .10 chest and abdomen
Fluorescent in situ yrs for paratesticular
hybridization, tumors Bone scans: cortical
quanti RT PCR for bone involvement
translocations, T
and B cell At least 2 BM aspirations
rearrangement and biopsies
studies, molecular
profiling by Iodine-123
oligonucleotide metaiodobenzylgunaidin
microarray e (123I-MIBG) for extent

MRI of spine for

suspected or potential
compression
RT -Before biopsy (Formal Tumor mass and
excisional > needle) indication of bony
-Id large mediastinal erosion
mass
-determines “bulk” ds
CT Extent of mediastinal eval of primary tumor
 mass, hilar nodes and site
pulmonary abdominal and pelvic
parenchymal tumors
involvement
MRI eval of primary tumor
site
intracranial extension
or meningeal
involvement
bony involvement or
erosion at base of
skull
BM asp and biopsy Rule out advacement
Bone scans Due to Bone
pain/increased ALP
Gallium scan Id areas of increased
uptake
Fluorodeoxyglucos 1 day, High resolution, Enhance staging
e PET better dosimetry, less
intestinal act,
quantification
Staging Ann Arbor St. Jude/Murphy Favourable site: International
I – single LN, or eLN classification female genital, Neuroblastoma Staging
(IE) paratesticular, head 1 – localized, complete
I – 1eLN or 1 LN, and neck gross excision, (+/-)
II - >/_2 LN regions (-) mediastinum (nonparameningeal) microscopic residual, (-)
Or or abdomen ipsilateral LN
1 E, 1LN region All T stage does not
same side diaphragm II - 1eLN regional affect staging 2A – localized,
>/_2 LN same side incomplete gross
III – LN both sides of of diaphragm 1 – favourable site excision, (-) ipsilateral
diaphragm Primary GIT tumor nonadherent LN
-w/ spleen (IIIS), eLN (-) mesenteric 2 – unfavourable site,
(IIIE), or IIISE nodes, grossly size a (<5 cm), N0/Nx 2B – localized, w/ or w/o
resected complete gross excision,
IV – diffuse or 3 – unfavourable site, (+) ipsilateral
disseminated >/_1 E III - 2eLN or LN size a (<5cm) w/ N1 nonadherent LN, (-)
w/ or w/o LN opposite sides of b (>/= 5cm) any nodal enlarged contralateral
A-asymptomatic diaphragm status LN
B-B symptoms Primary
intrathoracic 4 – as long as there is 3 – unresectable
tumor metastasis unilateral across
(mediastinal, midline, w/ or w/o
pleuralm thymic) regional LN involvement
Localized unilateral w/
IV – any of the contralateral regional
above (+) CNS or LN, midline tumor w/
BM involvement bilateral extension by
infiltration
Mostly III or IV
4 – any primary tumor
w/ dissemination to
distant LN, bone, BM,
 skin, liver

4S – localised primary
tumor, w/
dissemination limited to
skin, liver, and BM
(<1yr)
Complete Complete resolution
response on clin exam and
imaging studies OR 70-
80% reduction of dse,
from (+) to (-) PET or
gallium
Residual fibrosis is
common
Tx Chemo, RT (w/o low- Primary: Low risk Low risk
dose in pedia) multiagent Vincristine and -surgery
systemic chemo actinomcyin w/ or Intermediate risk
Chemo: w/ intrathecal w/o lower dose -mod intensity chemo:
Cyclophosphamide, chemo cyclophosphamide, RT cisplatin, carboplatin,
procarbazine, for residual dse cyclophosphamide,
vincristine or RT for CNS hepatic irradiation,
vinblastine, involvement in Intermediate surgery
prednisone or LBL, acute Vincristine,
dexamethasone, superior actinomycin, High risk
doxorubicin, mediastinal cyclophosphamide, RT Dose-intenstive chemo,
bleomycin, syndrome or surgery, external beam
dacarbazine, paraplegias High risk RT, myeloablative
etoposide, Intensive multiagent chemo w/ autologous
methotrexate, TLS: chemotherapy along hematopoietic stem cell
cytosine arabinoside Vigorous w/ biological agents rescue, isotretinoin w/
hydration, investigated ganglioside GD2
COPP electrolyte immunotherapy
(cyclophosphamide, monitoring,
vincristine [Oncovine], xanthine oxidase Frequent relapse
procarbazine, inhibitor or
prednisone) recombinant 4s
urate oxidase in Supportive care
ABVD (doxorubicin high risk TLS Favourable prognosis,
[Adriamycin], may regress
bleomycin, vinblastine, spontaneously
dacarbazine)
Compression – chemo,
ABVE-PC and BEACOPP surgery, radiation
(ABVD + prednisone,
cyclophosphamide,
etoposide)

BAVD (brentuximab
vedotin, doxorubicin
[Adriamycin],
vincristine, daarbazine
)
 Localized/low stage
ABVD +-IFRT

Intermediate
COPP or dose-intense
multiagent CT + low
dose RT

Advanced
Dose-intense
multiagent CT + low-
dose RT
Dose-intense
BEACOPP+- IFRT
Single-agent therapy in
refractory HL:
Brentuximab vedotin
Ab-drug conjugate
anti-CD30 Ab
brentuximab-
monomethyl auristatin
E
Relapse 1st 3 yrs, late as 10 yrs Reinductoin
Poor prognosis: tumor chemo
bulk, stage, eLN, B sx Allogeneic or
autologous
Myeloablative stemm cell
Chemotherapy and transplantation
autologous stem cell
transplantation w/ or Prognostic
w/o RT marker:
If relapse or progress measurement of
<12 mo minimal residual
dse (esp ALCL and
LBL)
Prognosis Best: Excellent Good: resectable
relapse >12mo after tumor and favourable
CT or combined histo
modality Unresectable,
favourable site

Poor:
disseminated
complication Multiagent chemo
for adv at risk for
mucositis,
infections,
cytopenias
Electrolyte
imbalance, poor
nutri
 Long term:
Growth
retardation,
cardiac toxicity,
gonadal toxicity
w/ infertility,
2dary
malignancies
others Indolent in adult
Aggressive and
high grade in
pedia

NHL 4 subtypes

LBL BL DLCBL ALCL

Arises from Immature T or B cell Mature B or T cell
subtypes Germinal center
B-cell-like
-favorable
prognosis
-most common
DLCBL

Activated B cell-
like
Primary
mediastinal B-
cell
-poor prognosis
Cell origin 90% T cell 70% T cell CD30
10% B cell CD19, 20, 22 20% null cell
10% B cell
Genetic mutation T(8;14) T(8;14) complex T(2;5) fusion gene
T(2;8) T(8;22) or aneuploid encoding
13q deletion karyotype nucelophosmin-
poor prognosis anaplastic
lymphoma kinase
tyrosine kinase
Clin Tumor lysis Tumor lysis B sx, not
Manifestation syndrome (TLS) rapid syndrome (TLS) prognostic
cell turnover -> rapid cell Capillary leak
severe metabolic turnover -> syndrome
abnormalities severe metabolic (ALK+ALCL)
abnormalities
Primary site Intrathoracic or Abdominal Abdominal or Systemic (90%)
mediastinal (sporadic) head mediastinal Cutaneous (10%)
supdradiaphragmatic and neck
(endemic)
spread BM or CNS BM, CNS Rarely BM, CNS Liver, spleen,
lung,
mediastinum
Rare BM, CNS
Tx Localized or Similar for mature B-NHL Localized: surgical
advanced: 12-24 resection
mos. Chemp, Localized: multiagent, prog excellent Adv: multiagent
intrathecal therapy, Advanced: 4-6 mos multiagent
cranial RT rituximab CNS prophylaxis:
intrathecal
Induction, chemo or
consolidation, methotrexate
interim
maintenance, and CNS tx:
reinduction (adv) Intrathecal
phases + 1 yr long chemo and
maintenance phase cranial RT
w/ 6-
mercaptopurine and
methotrexate

Poor prognosis for

relapse