PART 22. Neoplstic Diseases and Tumors.
Chapter 445. Epidemiology
#
incidence rate of malignant tumor
; 14/100,000 in children under
15yr. (1986-1987)
#
the precise cause of childhood cancer is unknown
#
specific genetic event
; retinoblastoma
-
Rb tumor-suppressor gene
; Li-fraumeni-syndrome
-
p53 tumor-suppressor gene
#
*childhood cancer는 environmental factors보다 host
factors가 더
중요하다.
Environmental Factors
★Table
445-1
Ionizing Radiation
.radiation dose & frequency of
leukemia were related in a linear fashion.
.type & latency of leukemia
were related to age at exposure
.leukemia는
radiation exposure후 5년이 peak incidence time이다.
.breast cancer; 10세 이전에 노출된 중년의 여성에서 빈도 증가
.thyroid tumor
.brain tumor
Ultraviolet Radiation
.exposure of sunlight-skin cancer
.genetic predisposition(eg,
xeroderma pigmentosa,other congenital defect in DNAS repair)
있는 경우
ultraviolet에 neoplasm의 risk 더 높다.
Drug
.DES-clear cell adeno ca. of the vagina
only proven transplacental carcinogen
.Neuroblastoma-fetal hydantoin synd.
.fetal alcohol synd.
.immunosuppressive
agent; eg, NHL
.anabolic
androgenic steroid; liver tumor
.alkylating
agent & epipodophyllotoxins
; can cause second neoplasm
Diet
.high
fat intake, obesity-breast
colon ca
uterus
Viruses
1)RNA
viruses; lymphatic leukemia & lymphoma
-type C RNA
virus in animal
leukemia/lymphoma-retrovirus
Kaposi sarcoma AIDS
CNS lymphoma
2)DNA
viruses; EBV IM(미국), Burkitts' lymphoma(아프리카)
Lymphepithelioma
Hodgkin's dz.
HBV-H.C.C
3)papova
viruses; warts, papilloma
type 6 & 11-laryngeal papilloma
condyloma acuminatum
carcinoma of the uterine Cx.
(sub type 16, 18)
Chapter 446. Molecular Pathogenesis
Oncogenesis
#
oncogene
; endogenous human DNA
sequence arising from protooncogene
; develope to tumorigenesis
#
Rhabdomyosarcoma
; activating ras oncogene
point mutation
#
Burkitts lymphoma
; chr. translocation t(8:14)(q24q32)
in protooncogens(C-myc) on chromosome 8
★Table
446-1
★Table
446-2
Tumor Suppressor Genes
.cancer발생을 억제하는
tumor suppressor gene(antioncogene)의 down regulation은
malignant growth를 자극시킨다.
.retinoblastoma;
submicroscopic deletion in chr 13
.Rb
gene 1)nuclear phosphoprotein with DNA biredig activity(cell cycle regulation
에 중요하다.
2)정상인에 존재하며, cell growth를 관장하는 데
retinoblastoma환아에서는 없다.
Li-fraumeri
synd.; 가족적으로 다양한 childhood solid tumor가 발생.(bone
, breast, lung
cancer)하는 임상증후군으로, p-53 tumor suppressor
gene의 germline
mutation이 나타난다.
-p53 tumor suppressor gene의 product는
apoptosis(programmed natural
cell death)를 관장하는 데, 이것의 결여로 인해
excessive tumor cell
growth
가 생긴다.
Other Mechanisms And Implications
.underlying
genetic disorder와 malignancy와 연관되어 있는 경우가 많은 데,
이것은 oncogenesis 의 다른
mechanism을 암시한다.
.ex1)xeroderma
pigmentosa, ataxia-telangiectasia,Bloom synd. Fanconi anemia는
malignancy의 risk가 높다.
.ex2)immmunodeficiency
state인 Wiskott-Aldrich synd, congenital
X-linked immunodeficiency경우 lymphoid malignancy의 확률이 높다.
.malignancy
환아의 evaluation시
, familial association과 congenital synd.을 확인해야 한다.
Chapter 447. Principles Of Diagnosis
.most
childhood cancers are curable
.Px
relates most strongly to tumor type, extent at diagnosis, effectiveness of tx.
.대부분의
physician이 환자를 처음 대할 때, cancer를 떠올리지 않기에,
놓치는 수가 있는
데, atypical course를 기억해야 한다.
★Table
447-1
osteosarcoma,
Ewing's sarcoma는 10대에 잘 생기고, 이 나이가
physical activity가 왕성하므
로, bone pain시기와
trauma시기가 중복되는 수가 많다.
-radiologic exam이 도움을 줄 수 있다.
.nasopharynx
or middle ear tumor는 inf.과 유사하다.
지속되는 이통, 이루,
retropharyngeal swelling시는 malignancy를 의심해야 한다.
.cervical
lymph node enlargement시는 inf.과
lymphoma를 구분해야 한다.
(Sx. 지속시 LN.bx. 시행한다.)
.leukemia의 초기 증세가
low grade fever, bone pain, joint pain에 국한될 수 있으며, PB에서
blast가 안 보일 수도 있다. anemia, neutropenia,
mild thrombocytopenia 있을 시 BMA를
해야 한다.
.bx에 앞서
metastasis유무 보기 위한 stage work up을 잘 해야 한다.
->surgeon이
operation시, resection범위를 결정하게 된다.
.Dx.의 중심은
histologic type이다.
Chapter 448. Principles Of Treatment
#
the gene of all forms of tx.
-to remove or destroy as much tumor as
possible
-with least damage to normal cells.
448.1 Chemotherapy
★Table
448-1
<phase
I study>; low dose에서 start해서
max. tolerate dose까지 측정
<phase
II study>; specific tumor type의 tx. efficacy를 측정
<phase
III study>; protocol의 기존의 약과 같이 schedule에 입력시켜 효과측정한다.
Acute Complications & Supportive Care
#
Early complications
; metabolic disorders
;
bone marrow suppressions
;
immunosuppressions
#
★Tumor Lysis Syndrome
; substantial breakdown of
tumor cells
-->
tubular precipitates of uric acids crystals
-->
impaired renal functions
; *symptomatic hyperphosphatemia, hypocalcemia, hyperkalemia
; *▲often in hematologic
malignancy
; large solid tumor도 가능하다.
-
e.g.) Burkitt's lymphoma, germ cell tumor, neuroblastoma
; Treatment
-
adequate hydration & allopurinol before chemotherapy
#
bone marrow suppression
; Granulocytopenia(500/mm3이하)
; life threatening inf.이 생길 수 있다.
=>febrile
granulocytopenic pt.는 broad spectrum antibiotics를 사용해야 하며,
1주 이상
지속시는 antifungal agent도 고려해야 한다,.
.특히,
candida 혹은 aspergillus species가 흔하다.
.opportunistic
inf.; pneumocystitis carinii
->그래서,
bactrim을 예방적으로 사용
.
항암치료 환아에서, varicella에 노출되면
varicella zoster immunoglobulin을 맞고, 임상증세 생기면 입원해서,
iv로 acyclovir를 투여한다.
3)항암 치료후
pt.의 대부분의 평소 B.Wd의
10%를 소실한다.( tx associated
nausea, vomiting)
-intensive CTx, total body irradiation,
abd. head, neck의 irradiation tx환아는
malnutrition이 위험하며 TPN이 필요하다.
Late Sequelae
;
radiation-related problems
- *not obvious until patients is fully grown
- e.g.)
/
marked asymmetry of irradiated & non irradiated area & extremity
/
hypothyroidism or sterility
/
*growth retardation from pituitary
hormone deficiency
/
neurological & intellectual dysfunction
;
★chemotherapy can cause severe organ damage
-
high-dose MTX : leukoencephalopathy
- anthracyclin : myocardial
damage
-
bleomycin : pul. fibrosis
- asparaginase : pancreatitis
- cisplatin : hearing loss
- irreversible change
;
baseline test후, adequate monitoring이 필요
;
*▲serious
late effect
- second cancer
- the risk is cumulative
/
*0.5% per yr to 12% at 25yr
448.2 Bone Marrow Transplantation
.in
general, the younger the patient, the more favorable the response.
.Autologous
BMT; BM에 치명적인 용량의 radiation tx 혹은
chemotherapy시행할 때,
먼저 환아의 BM을 따로 보관한 후,
tx후 다시 autologous marrow를
reinfusion
->ALL, AML, neuroblastoma, Hodgkin's
dz, Non Hodgkin's dz, Ewing's sarcoma,
brain tumor
.문제점;
이식한 BM의 residual malignant
cell이 relapse할 수 있다는 점.
.allogenic
BMT-환자의 HLA와 "match"되는
donor로부터 골수룰 이식받음.
-the best donor is major MHC가 같은
sibling(확률 ; 20-30%)
-morbidity; GVHD, marrow rejection
-matched sibling donor라서,
어느 정도의 alloreactivity는 있다.(
minor HLA typing은
틀리므로 )
-serious post transplantation problems;
.graft
versus host disease
;어린 환아일수록 덜 발생하고, 최근에는
cyclosporin의 투여로 그 발생이 감소되고 있으나,
GVHD의 발생이 감소할수록 cancer relapse가 증가
1)acute
GVHD(1st & 2nd Mo. after transplantation
;target organ-skin, GI tract, liver
tx)steroid or anti T-cell monoclonal
antibody
2)chronic
GVHD(3-4Mo. after transplantation)
; resembles autoimmune dz.
(ex; scleroderma, MG)
.all
patients are at risk for life-threatening infection until recovery of immune
function
<application
of BMT>
.In
congenital immunodeficiency, BMT is the only curative option
.In
hematopoietic malignancies, the role of BMT is more difficult to define
(Randomazied clinical trials are lacking)
.tx.
decision are based on Pt's history, condition, prognosis, donor availability
Chapter 449. The Leukemias
;
▲ common childhood cancer
;
33% of pediatric malignancy
;
*ALL-75% of leukemia, peak
incidence-4yr
;
*AML-20% of leukemia, increasing
incidence from adolescent
;
anual incidence
- 42/만명
(백인)
-
24/만명 (흑인)
-->
due to lower incidence of ALL in black
449.1 ALL
;
first curable disseminted cancer with chemotherapy & irradiation
;
♥Asso. with diseases
- immunodeficiency ;
congenital hypogammaglobulinemia, ataxia-telangiectasia
- consititutional chromosomal
defect ; trisomy 21
Pathology
;
subclassed according to morphologic, immunologic, genetic feature of leukemic
blast.
;
definite diagnosis-BMA
;
★FAB system(morphologic subtypes)
1) L1 - predominantly small
with little cytoplasm
2) L2
-
larger & pleomorphic with increased cytoplasm
- irregular nuclear shape, prominent nucleoli
3) L3
-
*finely stippled and homogenous
nuclear chromatin
-
prominent nucleoli
-
*deep blue cytoplasm with prominent
vacuolization
;
chromosomal abnormalities
- 80-90% in childhood ALL
Clinical Manifestation
;
*signs and symptoms of their disease
for less than 4wk at the time of diagnosis
- 66% of children
;
first Sx
- usually nonspecific
- anorexia, irritability, and
lethargy
;
progressive bone marrow failure
- pallor(anemia),
bleeding(thrombocytopenia), fever(neutropenia, malignancy)
;
petechiae or mucous membrane bleeding - 50%
;
fever - 25%
;
occasionally prominent lymphadenopathy
;
splenomegaly
- usually extending less than
6cm below the costal margin
- 66%
;
*less common hepatomegaly
;
*significant bone pain and arthralgia
- 25%
;
rarely, signs of increased intracranial pressure
- headache and vomiting
- indicate leukemic meningeal
involvement.
#
★Children With T-Cell ALL
; older and more often male
; 66% anterior mediastinal
mass
★Table 449-1
Diagnosis
-on
initial exam, most have anemia, about 25% have Hb levels below 6g/g이하
-thrombocytopenia, 25% have platelet counts greater than
100,000/mm3
-diagnosis
of leukemia is suggested by the presence of blast cells on a peripheral blood
smear but is conformed by examination of
bone marrow
-If
the marrow cannot be asperated or specimen is hypocellular, bone marrow bx. is
required
-a
chest radiograph is necessary to determine whether there is a mediastinal mass
-bone
radiograph
-CSF
should be examined for leukemic cells
Differential Diagnosis
#
aplastic anemia, myelofibrosis, infectious mononucleosis
#
♥Pediatric Tumors That Can Infiltrate Marrow
1) neuroblastoma
2) *rhabdomyosarcoma
3)
Ewing sarcoma
4)
rarely retinoblastoma
Treatment
#
★Average Risk Of Relapse (=standard group)
; between the ages of 1 &
10 yr
; under 100,000/mm3
; lack evidence of
mediastinal mass or of CNS leukemia
; B-progenitor cell
immunophenotype
★Table
449-2
-a
combination of prednisone, vincristine(oncovin), and asparginase should produce
remission in about 98% of children with
standard-risk ALL.
-in
the absence of prophylactic treatment, the CNS is the initial site of relapse
in more
than 50% of patients.
-Most
patients with T-cell ALL relapse within 3-4yr if treated with a standard-risk
regimen.
-With
more intensive multidrug regimen
-B-cell
cases with L3 morphology and surface immunoglobulin expression once had a
poor prognosis.
Relapse
; ★bone
marrow
-
*▲common
site of relapse
; experience bone marrow
relapse during treatment, intensive chemotherapy followed by
bone marrow transplantation
; ★CNS
and the testes
-
*▲important
extramedullary sites of relapse
-the
common early manifestations of CNS leukemia increased intracranial pressure
and
include vomiting, headache, papilledema, and lethargy.
-convulsions
and isolated cranial nerve palsies may occur with CNS leukemia or as side effects of
vincristine.
#
CNS relapse
; should be given intrathecal
chemotherapy weekly for 4-6wk until
lymphoblasts have disappeared from the CSF
; cranial irradiation
; intrathecal TX.
#
Testicular relapse
; generally produces painless
swelling of one or both testicles
; conformed by bx
; Treatment
-
*include irradiation of the gonads
Prognosis
#
★Treatment
; *▲important prognostic
factors
#
clinical features
; initial WBC counts
; age
-
older than 10yr, younger than 12mo : poor
#
★Chromosomal Rearrangement
; 11q23 region : poor
; hyperdiploidy with more
than 50 chromosomes : favorable
; *two poor chromosomal translocations
-
t(9;22) or Philadelphia chromosome
-
t(4;11)
; *B-progenitor cell ALL with the t(1;19) : favorable
449.2 Acute Myeloid Leukemia
-annual
incidence of five to six cases per million in children younger than 15 yr.
-AML
constitutes 15-20% of all childhood leukemias.
-there
are no clear racial or gender differences.
-the
distribution of cases by age is consistent throughout childhood.
-the
incidence of AML exceeds 1)trisomy 21, 2)fanconi anemia, 3)Diamond -Blackfan
anemia, 4)Kostmann syndrome, and
5)Bloom syndrome.
-children
previously treated for another malignancy are also at increased risk;
-the
incidence of secondary AML approaches 5% after tx. of some malignancies.
-incidence
of secondary AML pe만 within 10 yr of the initial
malignancy
-associated
with specific therapies(alkylating drugs such as cyclophosphamide, agents
that inhibit DNA repair such as
etoposide).
Clinical Manifestations
;
typically signs and symptoms attributable to bone marrow failure
;
*less common bone pain
;
*common liver and spleen enlargement
;
*less common lymphadenopathy
;
unexplained gingival hypertrophy or parotid gland swelling
;
★chloroma
- localized mass of leukemic
cells
- *retro-orbital, epidural location
/
*▲common
- maybe precede leukemic cell
infiltration of bone marrow
;
initially with only anemia, leukopenia, or thrombocytopenia
- ★MDS
Diagnosis
-the
presence of at least 30% leukemic blast cells in the bone marrow
-morphology
and cytochemical analysis(histochemical stain positive for myeloperoxidase,
Sudan black, or nonspecific esterase)
#
FAB system divides AML into eight subtypes, M0 to M7
Table 449-3
-the
number of patients with the M0, M1, and M2 subtypes approximates the number
of M4 and M5 cases.
-FAB
types accounts for 80% of childhood.
-The
M3 and M7 subtypes are less common, and M6 is rare.
-Hemorrhagic
diathesis(disseminated intravascular coagulation at presentation or later);
acute promyelocytic leukemia(M3)
-Translocation
between chromosomes 8 and 21, typically present in the M2 subtype,
is closely associated with chloroma.
#
Myelodysplastic syndrome
; some resemblance to AML,
but the bone marrow contains a lower percentage of blast cells and has
characteristic dysplastic features, including megaloblastosis
; ★chromosomal
changes
-
*trisomy 8 and complete or partial
deletion of chromosome 5 or 7
/
common in secondary myelodysplastic syndromes and secondary AML
#
juvenile chronic myelogenous leukemia(JCML)
; unlike adult type CML
; similar to those of AML and
myelodysplastic syndrome
; *Philadelphia chromosome is not present in JCML
Treatment
-chemotherapeutical
regimens; anthracyclin (daunorubicin, idarubicin) and cytarabine.
-Retinoic
acid as initial treatment for acute promyelocytic leukemia may reduce
the risk of the hemorrhage but is not
curative.
-autologous
or allgenetic bone marrow transplantation
-intrathecal
chemotherapy is necessary to prevent CNS relapse.
Prognosis
-poor
-with
aggressive therapy, 40-50% of patients who achieve remission(3-40%overall cure
rate.)
449.3 Chronic Myelogenous Leukemia(CML)
-CML
is a clonal malignancy of the hematopoietic stem cell characterized by a
specific translocation, the
t(9;22)(q34;q1), Philadelphia chromosome.
-CML
is more common in adults and
accounts for only 3%of cases of childhood leukemia.
-progression
to a myeloid or lymphoid blast crisis
*Pathology
-characterized
by myeloid hyperplasia with increased numbers of differentiating
myeloid cells in blood and bone marrow.
-the
pathognomonic Philadelphia chromosome is easily detectable in more than 95% of
cases
-Southern
blot analysis or polymerase chain reaction technique reveal the bcr-abl
rearrangement.
Clinical Features
-Sxs
of hypermetabolism, including wt. loss, anorexia, and night sweats.
-Sxs
of leukostasis, such as visual disturbance or priapism, occur rarely.
Diagnosis
-elevated
white blood cell counts exceed 100,000/mm3, with all forms of
myeloid cells
seen in the blood smear.
-PLT
counts may also be abnormally high.
-elevated
serum levels of vitamin B12 and uric acid and reduced or absent leukocyte
alkaline phosphatase activity.
-the
bone marrow is hypercellular, with normal myeloid cellsin all stages of
differrentiation.
-megakaryocytes
may be more numerous.
-cytogenetic
or molecular studies showing the Philadelphia chromosome.
Treatment
-chemotherapy
with busulfan(Myleran), or hydroxyurea.
449.4 Congenital Leukemia
-extremely
rare disease, diagnosed within the 1st mo
life at a rate of 4.7 per million
live birth.
-Myeloid
leukemia appears marked leukocytosis, petechiae, ecchymoses, and
extramedullary involvement massive
hepatosplenomegaly, cutaneous nodule, and CNS
leukemia.
-occurs
primarily in neonates with trisomy 21 or chromosome 21 mosaicism.
-Most
transient myeloproliperative disorders undergo spontaneous remission within a
few wks.
-poor
prognosis,especially, leukemic cell chromosomal rearrangement affecting the
q23region
of chromosoe 11
Chapter 450. Lymphoma
;
the third most common cancer in children
450.1 Hodgkin Disease
Epidemiology
#
peak age
; *the middle to late 20s
;
age of 50yrs
#
*whites male
#
*EB virus may be involved in the
pathogenesis
Pathology
#
4 histologic subtypes
1) lymphocytic predominance
;
mature lymphocytes or a mixture of lymphocytes and benign histiocytes
-
occasionally Reed-Sternberg cells
;
10-20%
;
*clinically localized disease
;
more common in male & younger patients
;
*▲best
prognosis
2) nodular sclerosing type
;
*▲common
type
;
50% of younger patients, 70% of adolescents
;
special cytologic feature
-
*clear space surrounding “lacunar
cell”: variants of the R-S
cell
3)
mixed cellularity
; second common
;
40-50%
; *inflammatory bacground
of lymphocytes, plasma cells, eosinophils, histiocytes, malignant reticular
cells
-
*abundant R-S cells
;
more likely advanced disease & extranodal extension
4) lymphocyte depletion
;
*least common and least favorable
form
;
fewer than 10% of patients
; numerous bizarre malignant reticular cells along with R-S cells
-
relatively few lymphocytes
- various degree of partly hyalinized
fibrosis
- arises in lymph nodes in allmost all
cases
extranodal primary sites : fewer
than 1% of patients
-> spleen, lever, lung,bone,and BM
- the manner of spread : direct anatomic
extension
-> adjacent lymphnode : the first site of spread in most patients
along
adjacent lymphoid channels
- systemic Sx (B-sx) : night sweat,
fever, recent wt loss of more than 10% of BW
Clinical Manifestations
; painless enlarged cervical
or supraclacicular lymph node, occasionally nodes of the axillary or inguinal
areas
-
▲common presenting finding
-
firm, nontender, usually discrete
- mediastinal LN enlargement ->
produce a cough, usually non-productive
- pruritus : an unusual early complaint
if pruritus occurs alone -> no B category
- if pulmonary involvement ->
establishment of stage Ⅳ
;
BM involvement
-
neutropenia, thrombocytopenia and anemia
; ★immune
disorders
-
immunohemolytic anemia
- immunothrombocytopenia
- nephrotic syndrome
; *impaired cellular immunity
-
*varicella-zoster infection
- fungal infection
/
cryptococcosis, histoplasmosis, candidiasis
; transiently depressed
humonral immunity
Diagnosis
;
suspected in the patient with persistent unexplained lymphadenopathy
;
in a significant percentage of patients
-> a history of relatively
recent antecedent serologically proven infectious
mononucleosis(+)
-> 따라서
infectious mononucleosis를 앓은 후 enlarged LN가 줄어들지 않은 경우
Bx를 시행하여야
한다.
;
chest X-ray
- *performed before biopsy
- explore possibility of
mediastinal involvements & examine airway potency
#
blood counts
; not helpful but
characteristic changes in WBC counts
-
neutrophilic leukocytosis, lymphopenia, and sometimes eosinophilia and
monocytosis
#
increased acute phase reactant
;
ESR, serum copper, and serum ferritin ; nonspecific but markers of disease
activity
#
★Staging Procedure After Confirmed Diagnosis
; roentgenogram of the chest
;
CT scan of the chest
; CT or MRI of abdomen
; lymphangiography
-
lymph node involvement
/
not be filled with contrast materials
; staging laparotomy
-
determine with certainty the presence or absence of infradiaphragmatic disease
-
*현재는
findings이 치료
방향을 좌우할
경우에만 시행
; ★BM
biopsies
♥Table
450-1
Treatment
; localized disease (stage I
or IIa)
-
radiation alone to standard fields with doses of 3500-4406 rad
-
radiation + combination chemotherapy
; advanced disease
-
MOPP
/
nitrogen mustard, vincristine(oncovin), procarbazine, prednisone
-
ABVD
/
doxorubicin(adriamycin), bleomycin(blenoxane), binblastine(vleban), dacarbazine
-
MOPP/AVDG alternating with low-dose (2000-2500cGy) radiotherapy
/
more useful
/
cure rate 70-90%
/
♥why?
:
potential growth defects and risk of second solid tumor are reduced by limiting
the radiotherapy
:
risk of infertility and leukemogenesis is decreased by reduced exposure to
alkylating agents
:
exposure to drugs with potential cardiopulmonary toxicity is limited
Prognosis
- more than 90% of patients : complete
initial clinical remission
- most patients with disease in stages Ⅰ
and Ⅱ will be crued
- in stages Ⅲ
; 75% cured
- in stage Ⅳ : at least 50% cured
#
complications of treatment
- the complications of irradiation
; irradiation of upper body node :
restriction of lung capacity
cardiac involvement
late hypothyroidism
; in younger child, disturbance of
the growth of the vertebra, the clavicle, breast bud
; 따라서 성장문제 때문에 children에게서는
standard dose radiation을 주지 않는다.
-irradiation of the ovaries->
sterility or premature menopause or both.
- complication of chemotherapy ; late
pulmonary toxicity : bleomycin
late cardiac toxicity : doxorubicin
MOPP : sterility in male
- staging laparotomy : splenectomy ;
sepsis with pneumococcus or H.influenza
abdominal adhesion
#
secondary malignancy
; *5-10yr after treatment
; 1.2-13% at 10yr
; ★acute
myeloid leukemia
-
*▲frequently
450.2 Non-Hodgkin Lymphoma
;
malignant clonal proliferations of primarily T or B lymphocytes
#
♥High Risk Diseases
; ataxia-telangiectasia
; Wiskott-Aldrich syndrome
; combined immune
deficiencies
; X-linked lymphoproliferative(XLP)
syndrome
-
marked sensitivity to EBV-induced disease
-
fatal infectious mononucleosis case 57%
Pathology
#
Difference from adults
; diffuse, extranodal,
high-grade tumors type
#
high-grade NHL subtype
①
small noncleaved cell (Burkitt and non-Burkitt subtypes)
;
B cell tumor
;
express surface immunoglobulin
;
★contain one of three chromosomal translocations
-
*t(8;14), t(2;8), t(8;22)
;
★involved c-myc oncogene, immunoglobulin gene (mu heavy chain,
kappa light chain, lambda light chain)
②
Lymphoblastic lymphoma
;
T-cell origin
;
*contain a translocation involving a
T-cell receptor gene
③
Large cell NHL
;
T-cell, B-cell, non-B, non-T cell phenotypes
;
t(2;5)(p23;q35) asso. with CD30
Clinical Manifestations
; ★▲common
primary site
-
*abdomen(31.4%), mediastinum(26%),
head/neck region including Waldeyer ring and/or cervical lymph nodes (29%), non
cervical LN(6.5%)
; ★striking
association between histologic subtype and disease sites
-
lymphoblastic type
/
head and neck region or ant. mediastinum
-
SNCC
/
abdomen and/or head and neck
-
large cell type
/
any anatomic location
; mediastinal mass
-
pleural effusions,respratory distess,superior vena cava syndrome,
; Abdominal mass( ileocecal
region)
-
abdominal distension, nausea, vomiting change in bowel habits
;
BM involvement
-
anemia or thrombocytopenia
; central nervous system
disease
-
headache, ICP 증가, cranial nerve palsies
Diagnosis
★Table
450-2
Treatment
; common TLS
; ※CNS prophylaxis
; multiagent chemotherapy
-
cyclophosphamide-based COMP regimen
/
SNCC type
-
intensive multiagent LSA2L2 regimen
/
Lymphoblastic type
-
★CHOP regimen (cyclophosphamide, doxorubicin, vincristine,
predisone)
/
*▲effective
protocols for large cell type
Prognosis
·2-yr event-free
survival (EFS) : 90% for children with limited-stage disease
70% for those with stage Ⅲ and Ⅳ
·improvement in the
treatment of advanced-stage SNCC NHL ; 90% 2-yr EFS
(70% for those with central nervous system disease)
CHAP. 451. Neuroblastoma
;
*▲
extracranial solid tumor of childhood (8-10% of all children cancer)
;
*▲frequently
diagnosed neoplasm in infants
;
median age
- *2 yrs (90% : before 5yr)
;
8.7/million children (new case 500-600 /yr U.S.A)
;
*spontaneous regresstion - 10%(주로 1세이하, stage I or IVs)
;
higher in males and in whites
;
*some familial
- asso. /c *neurofibromatosis, nesidioblastosis,
hirschsprung disease
;
microscopic clusters in adrenal gland of fetuses
- 1 of 200 neonates at
autopsy
- normal
;
mass screening programs
- urinary catecholamine
metabolites(VMA)
- at 6 mo in japan
Pathology
;
originate in neural crest cells of sympathetic nervous system
- anywhere from post. fossa
to coccyx
;
site
- *abdomen (70% : adrenal gland 50%), thorax(20%)
;
*hematogenous spread - bone marrow,
skeleton, liver
;
*tumor cells in peripheral blood -
more than 50% at diagnosis or relapse
#
histological features
; small round cells with
abundant granules
; forming *Homer-Wright rosettes
; calcification and necrosis
with extensive hemorrhage
; EM
-
peripheral dendritic processes
-
containing longitudinally oriented microtubules,
- small, spherical membrane-bound granules with electron-dense cores
-->
representing cytoplasmic neurosecretory granules(catecholamines)
-->
secretes catecholamines, neuron-specific enolase(NSE), ferritin
;
catecholamines metabolites in urine
- vanillylmandelic acid,
homovanillic acid
;
monoclonal Ab to cell surface antigen*(glycosphingolipid,
diganglioside, synaptophysin, NSE, neurofilament)
;
♥Cytogenetic Abnormality
; 80%
1)
partial deletion of the short arm of chromosome 1, chromosome 17
2) genomic amplification of
the ★N-myc oncogene ; indiator of poor prognosis
Clinical manifestations and Diagnosis
;
hard, painless mass in the neck
- localized intrathoracic
mass on chest radiograph
; large palpable mass in flank or abdomen
;
*metastasis in 65-70% at diagnosis
#
Direct invasion Sx
; proptosis and ecchymosis -
orbit involve
; lower limb paresis -
paraspinal tumor -> epidural extension
; *horner syndrome - lesion in cervical or upper thoracic sympathetic
ganglia
; unilateral epistaxis or
occlusion of nasal passage - tumor in nasopharynx
; *firm, blue-tinged subcutaneous nodules resembling blueberry muffins
in neonates & infants
; *anemia, thrombocytopenia - bone marrow infiltration
#
Indirect Sx due to substances
; ★acute
cerebellar encephalopathy
-
*cerebellar ataxia, rapid and random
eye movement, myoclonic jerks
-
4%
; *severe diarrhea with extreme hypokalemia & achlorhydria
-
due to VIP
; *hypertension due to catecholamine
#
Physical Examination
; LN enlargement,
hepatomegaly, abdominal or flank mass
; periorbital ecchymoses,
scalp nodules
#
Lab. finding
; anemia, thrombocytopenia
; DIC
; elevated LDH, ferritin,
NSE, BUN, creatinine
; *increased homovanillic acid & vanillymandelic acid in urine
-
*▲useful
markers of neuroblastoma
#
Imaging study
; chest radiograph
; CT of chest, abdomen-pelvis
; bone scan
-
detecting the primary tumor
-
defining the extent fo skeletal metastasis
; MRI
-
detecting intraspinl extension, vessel encasement or displacement, bone marrow
involvement
;
MIBG(meta-iodobenzylguanidine)
#
Confirm Diagnosis
; tissue biopsy
; *any surgical procedure을 하기전에
반드시 BM aspiration &
biopsy을 시행하여
전이여부를 확인해야
한다.
#
♥Definite Diagnosis
; histologic studies of tumor
tissue
; documentation of bone
marrow involvement plus increased urine or serum catecholamine level
#
★DNA Determination Of Tumor Materials
; DNA content(tumor cell ploidy)
; presence of N-myc amplication
; cytogenetic analysis
Staging
#
Pediatric Oncology Group (POG) system
stage A ; grossly resected
tumor
stage B ; localized
unresectable tumor
stage C ; metastasis to
noncontiguous intracavitary lymph nodes
stage D ; metastasis beyond
lymph nodes
stage Ds ; infants with
small adrenal primary with metastatic disease limited to skin
liver or bone marrow
Table 31-6 by PO
★Bone involvement of
neonatal neuroblastoma
--> poor prognostic factor
Treatment
;
main modalities
- surgery(localized tumor),
chemotherapy, radiotherapy
#
Primary surgical resection Ix
; abdominal tumors localized
to one side of the midline
; abdominal tumors crossing
the midline without encasement of major blood vessels
; tumor in chest
; to determine status of
intracavitary LN that not attached to primary tumor
-
★liver biopsy should be in infant
;
★second-look or delayed surgery
#
Chemotherapy
; infants with disseminated
disease or children with localized unresectable disease
-
cyclophosphamide, doxorubicin
; older children with locally
advanced & disseminated neuroblastoma
-
combination
-
*cyclophosphamide, doxorubicin,
cisplatin, etoposide, ifosfamide, melphalan, vincristine, carboplatin
#
Experimental approaches
; extensive chemotherapy with
or without BMT
; Radioactive MIBG
; Monoclonal Ab directed
against neuroblastoma cell surface proteins
#
Radiotherapy
; *most neuroblastomas are radiosensitive
Prognosis
;
age and stage
- *▲ significant predictors
of outcome
;
*younger than 1yr : good prognosis
than same stage children
- low stage infants - more
than 90%
- infant with metastatic
disease - more than 50%
;
★Biologic And Genetic Markers
- DNA content(ploidy)
/hyperdiploid(DNA
index more than 1)
:
80% survival expectancy compared with 20% for diploid tumors
- ㉿N-myc
amplication
/
*poor outcome in all age/stage tumors
※96 Table 31-11 by PO
Chapter 452. Neoplasms Of The Kidney
452-1 Wilms' Tumor
.
accounts for almost all neoplasms in childhood.
.
equal frequency in both sexes.
.
annual incidence ; 7.8 million children under the age of 15yr.
#
association with congenital anomalies
; *genitourinary anomalies(4.4%) : ▲common
;
hemihypertrophy(2.9%)
;
sporadic aniridia(1.1%).
#
★deletion one of two loci in chromosome 11
; *33% of Wilms' tumors
1) hemizygous constitutional
deletions of one loci, *11p13
-
asso. with two syndrome
/
*WAGR syndrome
:
Wilms' tumor, aniridia, G-U malfomations, mental retardation
/ *Denys-Drash
syndrome
:
Wilms' tumor, nephropathy, genital abnormalities
2) deletion of one loci, *11p15
- association of Wilms' tumor with Beckwith-Wiedemann syndrome,
congenital syndrome (several types of embryonal neoplasms, hemihypertrophy,
macroglassia, visceromegaly)
3) Third locus
-involved in familial Wilms' tumor
Pathology
#
the classic Wilms' tumor
; solitary growth in any part
of either kidney
; sharply demarcated and
variably encapsulated
; common small areas of
hemorrhage
;
usually distort the renal outline.
#
favorable-histologic
; *triphasic, epithelial, blastemal
; *presence of stromal elements
; resemble abortive glomeruli
#
unfavorable histologic
; occur in older, nonwhite
; 3 times the normal size
; hypochromatic nuclei,
abnormal mitoses
; ★2
subtype
-
Rhabdoid tumor
/
composed of cells with fibrillar eosinophilic inclusions
/
*▲often
in very young patients
-
Clear cell sarcoma
/
spindle cell patterns with striking vasocentric arrangements
/
male predominance
/
*tendency to metastasize to bone
#
staging system (NWTS group)
stage 1 ; limited to kidney,
completely excised with capsular surface intact.
stage
2 ; extends beyond the kidney,
but can be completely excised.
stage
3 ; non hematogenous extension of tumor,
confined to abdomen
stage
4 ; hematogenous metastases,
which most commonly involve the lung.
*stage 5 ; bilateral renal involvement,
5-10%
Clinical Manifestations
;
median age at Dx ; 3yr (Wilms tumor)
;
*asymptomatic abdominal or flank mass
- *▲frequent sign
;
smooth and firm and rarely crosses the midline
.
mean diameter ; ll cm
.
50% - abdominal pain, vomiting, or both
.
신경아 세포종에 비해 연령이 높고 less ill 하게 보임
.
Hypertension (60%)
-owing to pressure of the tumor on
the renal a.
Diagnosis
. microscopic 혹은
gross hematuria (10∼25%)
. ultrasonography ; the mass is
intrarenal. (신경아 세포종과의 감별이 중요)
. CT scan ; most helpful.
-CT without enhancement ; arise from kidney as inhomogeneous masses
with areas of low density indicating necrosis.
. areas of hemorrhage and small
focal calcifications ;
->generally less common and less prominent than in neuroblastoma.
-CT with enhancement ;
. slight enhancement of tumor is
noted.
. often a sharp demarcation
between the tumor and normal parenchyma.
- primary usefulness of CT in Wilms tumor ;
. establish the intrarenal origin of the tumor->rule out
neuroblastoma.
. detect multile masses
. determine the extent of tumor.
. evaluate the opposite kidney.
#
differential diagnosis
; hydronephrosis
; renal cysts
; mesoblastic nephroma
; other renal malignancies ;
renal cell carcinoma
sarcoma
lymphoma
; Neuroblastoma (가장 중요)
#
pulmonary metastases ;
.evident on roentgenogram in 10∼15%
of patients at time
of diagnosis.
.more common in neuroblastoma.
.CT scan of chest ; plain
radiograph로 발견하기 어려운
the dome of the diaphragm
아래쪽의 metastatic lung lesions을
발견하는데 도움이 된다.
hepatic
metastasis 의심시
-CT of abdomen
evaluation
of bone and BM.고려.
-persistent bone pain
-unfavorable histologic subtype
paraneoplastic
syndrome
-1.produce
erythropoietin->polycythemia
2.secondary hypercalcemia
-임상적으로
von Willebrand disease와 유사한 양상 보임.
Treatment
#
surgical removal of the kidney
; usual immediate treatment
; pulmonary metastases가 존재하더라도
시행
#
*Wilms tumor is sensitive both
chemotherapy and to radiotherapy
#
radiotherapy
; *술후 모든
환자에게 시행
#
chemotherapy
; NWTS groups에서
combination therapy가 single agent therapy보다 효과적으로
인정
; *vincristine+dactinomycin : patients with localized disease
; *vincristine+dactinomycin+doxorubicin : advanced disease
; stage 1
-
a short postoperative course(6mo or less) of combination chemotherapy
postoperative radiotherapy is not necessary.
; stage 2 and 3
-
postoperative radiation with chemotherapy.
; stage 4
-
radiotherapy+ combination chemotherapy with 3 or 4 drugs for 15mo.
#
preoperative therapy
; not recommended for
patients with unilateral disease.
; treatments of choice for
pt. with bilateral disease.
Prognosis
#
★▲significant prognostic variables
; Histologic subtype and
stage
#
재발시 poor prognosis
452.2 Other Renal Neoplasms
Nephroblastomatosis
.
immature renal elements (nephrogenic rests)
-33%
of unilateral Wilms tumor에서 발생
-대개
bilateral
.
precursor lesions
-unifocal and deep within renal parenchyma (intralobar rest)
-multifocal (perilobar rest)
*
Mesoblastic Nephroma
.
grossly and microscopically resembling
-leiomyoma
-low-grade leiomyosarcoma
with trapped nephrons.
.
EM상 fibroblasts 혹은
myofibroblasts 보임.
.
남아
.
renin production
Renal Cell Carcinoma
.
10대에 발생
.
abdominal mass and hematuria
-initial finding
.
어른의 renal cell ca,와 비슷한 현미경 소견과 임상 경과를 가짐.
Chapter 453. Soft Tissue Sarcomas
.
50%이상이 rhabdomyosarcoma
453.1 Rhabdomyosarcoma
Epidemiology
;
*▲common
soft tissue sarcoma
.
male (많이 발생)
#
site
; head and neck (40%)
;
genitourinary tract (20%)
;
extremities (20%)
;
trunk (10%)
; retroperitoneal
#
risk patients
; neurofibromatosis
; maternal breast cancer in
the Li-Fraumeni syndrome.
Pathology
#
"small round cell tumors" on light microscopy.
; ※96 DDx
-
*Ewing sarcoma, neuroblastoma,
neuroectodermal tumor, non-hodgkin lymphoma
#
histologic subtypes ( 4 가지 )
1.embryonal; about 60% of the tumors,
intermediate prognosis.
2.botroid; 6%
commonly seen in the vagina, uterus, bladder, nasopharynx, middle ear.
3.alveolar; about 15%
most often trunk and extremities, in older children.
the most poor prognosis, 특징; t(2;13) chromosomal
translocation.
4.pleomorphic; adult form, 1% of cases.
-undifferentiated tumor; about 20%.
Clinical Manifestation
;
*painful or not painful mass
- *▲common presenting
feature
.
nasopharynx tumor; nasal congestion, mouth breathing, epistaxis, difficult
swallowing and chewing.
.
extension into the cranium; cranial nerve paralysis, blindness, IICP sign
#
orbit
; *proptosis, periorbital edema, change in visual acuity, local pain
#
middle ear
; pain, loss of hearing,
chronic otorrhea, tumor mass in ear canal.
.
larynx; unremitting croupy cough and progressive stridor.
.
trunk or extremities; 처음 한동안은 hematoma로 오인하기 쉽다.
.
genitourinary tract; hematuria, obstruction of the lower urinary tr,
recurrent UTI, incontinence
.
paratesticular tissues; a rapidly growing mass in the scrotum.
.
vagina; a grape like mass, vaginal bleeding, obstruction of the urethra or
rectum.
.
tumor가 어느 위치에 있든지 상관없이 early dissemination이 발생하며
pulmonary metastasis때 발생하는 the presenting symptom은
pain or
respiratory distress
Diagnosis
.
in head and neck;
-roentgenogram
-CT scan; check for intracranial
extension.
look for bony involvement at the base of skull.
.
for abdominal tumor; ultrasound and CT scanning.
.
in the bladder; cystourethrogram.
.
before surgery;
-a
full skeletal metastatic survey.
-radionuclide scans of the skeleton
-a chest roentgenogram and CT.
-BM exam.
.
the most essential element of the diagnostic workup;
-the exam of tumor tissue.
Treatment
.
based on the primary tumor location and disease stage("clinical
group")
.group 1
tumor; complete local excision+chemotherapy.
.group 2
and 3; local irradiation+systemic chemotherapy+surgery
.group 4;
systemic chemotherapy+irradiation
.intrathecal
chemotherapy시행
-primary disease in parameningeal
sites(nasopharynx, paranasal sinuses etc)
-with intracranial extension.
Prognosis
.
resectable tumor; prolonged tumor free survival in 80-90%
.
unresectable tumor라도 orbit와 같은 favorable site에 발생하는 경우 high likelihood of
cure를 가진다.
.
disseminated disease; a poor prognosis.
.
older children;
-a worse prognosis
-greater frequency of
lesions of the extremities and of alveolar histology.
453.2 Other Soft Tissue Sarcomas
*NRSTS ( nonrhabdomyosarcoma soft tissue
sarcomas )
-3%
childhood malignancy
.
median age at Dx; 12세
.
M:F=2.3:1
.
histologic types
-synovial sarcoma(42%)
-fibrosarcoma(13%)
-malignant fibrous
histiocytoma(12%)
-neurogenic tumors(10%)
호발부위
-trunk or lower extremities
Chapter 454. Neoplasms Of Bone
;
2nd decade of life
;
male (우세)
㉿Table 454-1
454.1 Osteosarcoma
#
호발부위
; metaphyseal region of
rapidly growing bones
-
distal femur, proximal tibia, proximal humerus
#
Genetic And Hereditary Conditions
; *increased risk among children with bilateral retinoblastoma
-
*loss of normal Rb tumor-suppressor gene
; *increased risk of Li-Fraumeni syndrome
-
*germline mutations of p53
#
★Others Risk Conditions
; Paget disease
;
enchondromatosis
;
multiple hereditary exostoses
;
osteogenesis imperfecta
;
local irradiation for Ewing sarcoma
Pathology
.
highly malignant spindle cell neoplasm
.
arises in the cortical/medullary region of long bones
- break through bone cortex and
invade surrounding soft tissues
.
skip lesion
- may occur at some distance
from the primary tumor mass
.
high-grade osteosarcoma의 분류
; 1. osteoblastic
2. chondroblastic
3. fibroblastic
.
rare subtype
- parosteal;
a well differentiated, extramedullary tumor,
low metastatic potential
surgical resection alone is often adequate therapy
- periosteal;
histologically,more pleomorphic.
more aggressively clinically.
- telangiectatic;
bloody, cystic lesion.
radiographically, no new bone formation
--> confused with aneurysmal bone cyst.
poor prognosis.
.
multifocal sclerosing osteosarcoma;
- 동시에 여러 장소에서
tumor가 발병하는 형태를 말하며,
주로 osteoblastic pattern을 나타낸다.
Clinical Manifestations
;
*localized pain and swelling
- *▲common presenting
symptom
;
P/Ex
- local
swelling, tenderness, warmth
- limited range
of motion
.
CBC, Chemistry; 대개 Nl
.
metastases occur most often
-lungs and other
bones
Diagnosis
.
persistent unexplained bone pain,
particularly when associated with
a palpable mass
->
suspection->roentgenographic exam of that bone.
.
typical findings on X-ray;
-broken through the cortex,
calcification in the surrounding soft tissues.
-sclerosis of bone and
periosteal new bone formation.
.
stage를 결정하기 위한 최소한의 검사;
-a radionuclide scan
and a roentgenographic study
-CT scan of the chest.
.
CT scan with contrast enhancement of the affected extremity;
-define the extent of
medullary involvement.
-assist in surgical
planning.
.
serum alkaline phosphatase activity;
-increased.
-a marker to follow
the effect of therapy.
.
conformation; by histologic exam.
Treatment
#
surgery
; mainstay
#
radiotherapy
; *not useful due to radioresistance tumor
#
combined CTx
; due to micrometastasis at
diagnosis
; *수술자체만으로는 5년
생존율이 20%미만
#
※97 Advantage of adunvant chemotherapy
; immediate treatment for
ocult metastatic disease
; tumor response
; limb-sparing surgery
Prognosis
.
best with low-grade tumors, such as parosteal osteosarcoma.
.
high-grade osteosarcoma and no evidence of metastasis.
-66% cured
454.2 Ewing Sarcoma/Peripheral Neuroepithelioma
;
a family of highly malignant small round cell undifferentiated neoplasms
;
more common in male
;
*▲often
in 2nd decade of life
;
★▲often sites
- *flat bones(pelvis, chest walls, vertebrae)
- diaphyseal region of long
bones
;
soft tissues tumors
-most often in the trunk.
-50%이상이 chest주위에서 발생함.
.Ewing
sarcoma
-전형적으로 extensive soft tissue
component가짐.
-lung과 bone이 가장 전이가 잘 되는 부위
Pathology
#
special histochemical staining for DDx from rhabdomyosarcoma, neuroblastoma,
lymphoma
; *specific staining for cell-surface glycoprotein p30/32MIC2(HBA
71)
#
specific chromosomal translocation
;
t(11;22)(q24;q12)
-->
results in a *chimeric EWS and FLi1 gene product
Clinical Manifestation
;
pain, swelling, tenderness in involved sites
;
fever
;
the two conditions most often mistaken clinically for Ewing sarcoma
- eosinophilic granuloma
-
osteomyelitis
;
때때로 항생제를 쓰면 Ewing sarcoma의 증상이 좋아지는 경우도 있으므로
bacterial culture 에서 음성으로 나타나는 osteomyelitis를 대하면 반드시
Ewing sarcoma를 고려해야 한다.
Diagnosis
.clinical
history and radiologic features
.확진; surgical biopsy
.CT
scan
.Bone
scan
.BM;
전이가 의심될 때.
.MRI;
primary lesion의 extent를 평가하는 데 가장 좋다.
특히
, 치료에 대한 반응을 평가하는 데 유용하다.
Treatment
#
response to both radiotherapy and chemotherapy.
; *amputation is rarely indicated
#
Multiagent chemotherapy
; 4
drug CTx
-
cyclophosphamide, doxorubicin, vincristine, dactinomycin
- 추가 약제; ifosfamide and etoposide
.
local RTx
-효과적이긴
하지만 high-dose radiotherapy시행이 부작용
1)failure of bone growth
2)soft tissue fibrosis
3)secondary malignancy(특히, osteosarcoma)
.long-term
F/U이 필요
-진단
10년 혹은 이상에서도 재발이 있을 수 있기 때문.
Prognosis
454.3 Rare Bone Tumors
*
Chondrosarcoma
.rare
in children, usually seen during the second decade.
.most
common in the pelvis.
.lung
and bone으로 metastasis가 가능하지만
대개는 local extension.
.histologic
exam; osteosarcoma도 chondrosarcomatous component를 많이 가지고 있기
때문에 주의를 요한다.
.Tx;
-surgical removal
-relatively radioresistant.
*
Fibrosarcoma
.rare
.soft
tissue에서 발생
.주치료 방법;
surgical resection
Chapter 455. Retinoblastoma
#
★Average Age At The Time Of Diagnosis
; 11 mo for bilateral tumor
; *23 mo for unilateral tumor
#
bilateral involvement
;
30%
;
dominantly inherited predisposition to retinoblastoma
-
20% of patients with unilateral disease
#
★Genetic Predispostion
; retinoblastoma occurred
with *“13q-syndrome”
-->
suggesting the retinoblastoma locus on chromosome 13
; Rb gene
-
increased risk of other tumors
/
osteosarcoma developed by 10yr of age in about of 1% of survivors
-
secondary malignancy
/
30% witin 30yr
;
trilateral retinoblastoma syndrome
-
bilateral ocular disease + pineal tumors
Pathology
usually
develops in the posterior portion of the retina
consists
of small, round, closely packed
malignant cells with scanty cytoplasm
endopytic
growth:
-arises in the internal nuclear
layers of the retina
-> growing into the vitreous
cavity
-easily seen with the
ophthalmoscope
exophytic
growth
-arising in the external nuclear
layers and growing into the sub retinal space
-> diagnosis is more
difficult, because the tumor is hidden
endophytic
tumor로부터 떨어져 나온 tumor fragment가
vitreous 내에서 떠돌다가
다른 retina로
seeding 되는 경우 large tumor를 형성하고
poor prognosis를 나타낸다.
choroid로
extension 되어 있는 경우 hematogenous
metastasis 의 경향을 보인다.
retinoblastoma는 대개
metastasis 가 드물기 때문에 진단 당시 주관 심은 useful vision
을 보존하는 것이다
Clinical Manifestation
;
presenting Sx
-*leukokoria
: yellowish white reflex in the pupil (due to tumor behind the lens)
;
diminished or absent vision, strabismus
;
more advanced tumor
- pupillary irregularity,
hyphema, pain
;
very advanced tumor
- proptosis, IICP sign, bone
pain
;
*both eye involvement at diagnosis
- *more than 80%
Diagnosis
#
leukocoria
--> ★a careful fundoscopic examination in general anesthesia
#
CT scans
; *evaluate the intra orbital extent of tumor
; *see whether optic nerve or bony
structures are involved
; intratumoral calcification
#
MRI
; define optic nerve invasion
#
★DDx Of Leukokoria
; retinal detachment
;
persistent hyperplastic primary vitreous
;
nematode endophthalmitis
;
bacterial panendophthlmitis
;
cataract
;
coloboma of the choroid
;
the retinopathy of prematurity
#
Radionuclide bone scan
#
bonemarrow exam
#
CSF study
#
carcinoembryonic antigen
; rarely found at diagnosis
; recur시 다시 상승
Treatment
-standard
tx. for unilateral disease: enucleation of the eye
-bilateral:
salvage useful vision in at least one eye by using radiotherapy
and / or cryotherapy
-심하게 침범된 쪽이 보다 더
dramatic response를 보일 수 있기
때문에 radiation therapy는
both eye에 시행한다.
-한쪽 눈이
useful vision이 남아 있지 않을 정도로 심하게 침범되거나
complication으로
painful glaucoma가 발생하면 그 쪽 눈을 enuculation한다.
-enuculation후 gross or microscopic residual
disease 가 남아 있으면
radiation therapy와 더불어
chemotherapy(cytoxan+doxorubicin)가 고려된다.
Prognosis
;
overall survival rate: 90%이상
Chapter 456. Gonadal And Germ Cell Neoplasms
Epidemiology
3%
of childhood cancer
but ,sacrococcygeal teratoma is the most
common solid tumor in newborns
childhood
& early adolescence :sacrococcygeal & ovarian tumor의 빈도 수가
많으므로 female predominance
14세 이후
testicular tumor가 많으므로 male predominance
risk
for gonadal or germ cell tumor: gonadal dysgenesis & cryptorchidism
Pathology
Figure 456-1
most germ cell tumor : benign lesion
(cystic teratoma: most common)
malignancy 경향은 primary site 와
age 에 따라 다름
ovarian germ cell tumor : 10 세 이하에서 대개
benign
adolescence에서는
30%에서 malignant
sacrococcygeal tumor :malignancy 빈도가
10% at birth
50% at age 2 mon
Choriocarcinoma
; highly malignant
;
occurs after puberty in the testicle
-
but both before and after puberty in the ovary
; *high β-HCG level
Yolk Cell Carcinoma(Endodermal Sinus Tumor)
; schiller-duval bodies
; *elevated AFP
Embryonal Carcinoma
; poorly differentiated cells
with epithelial appearance
Seminoma Of Testicle
; during or after adolescence
;
clear cells aggregated in lobles & separated by fibrous stroma
; ★no
associated with biologic markers
Dysgerminoma Of Ovary
; counterpart of seminoma
Teratoma
; usually benign
; *consist of at least two, &
sometimes three germ cell layers
Clinical Manifestation & Diagnosis
testicular
germ cell: intact-painless mass in scrotum, no signs of
inflammation
older boy-swelling, pain ,tenderness
ovarian
germ cell tumor: acute or chronic pain & enlarged abdomen
abdominal mass or fullness
sacrococcygeal
germ cell tumor: most have external pelvic component
involving buttocks or sacrum
D.Dx : meningocele, chordoma, duplication of
the rectum, neurogenic tumor,
lipoma, rhabdomyosarcoma, hemangioma
signs & sx.:constipation and/ or
anuria
Dx:
plain radiographs, chest CT scans, radionuclide bone scans
MRI: identifying local
tumor extension into the adjacent bone or
intra spinal canal
surgical excision or
biopsy
serum level of AFP
& B-HCG
Treatment
Whenever
possible, surgical excision
dysgerminoma
& seminoma -traditionally Radiotherapy
Most
patients with malignant germ cell tumors :combination chemotherapy
(likelihood of subclinical dissemination
at the time of diagnosis)
-cisplatin, bleomycin,
etoposide
Prognosis
-depend
on disease extent at Dx. & primary site
malignant germ cell
tumor- 70-80% : alive without disease 5 yr after Dx
advanced disease -40-70% 5-yr survival rate
* Other tumors of the gonad
-sertoli tumor: benign
before the age of 6 mo.
columnar cells with tubular formation
-leydig cell tumor: benign
the ages of 4-9 yr
sexual precocity
surgical
resection
-benign ovarian cyst: 50% of ovarian tumors
torsion-mimic an acute abdomen
-granulosa-theca cell tumor: benign
ovarian stromal
origin
precocious puberty
-cystadenocarcinoma
-hemangioma
-lymphoma: ovarian enlargement
is the first manifestation
in small cases
-gonadoblastoma-occur only with gonadal dysgenesis
victimization, cryptorchidism, hypospadias
and / or female internal or secondary sex organs
Chapter 457. Neoplasm Of The Liver
457.1 Hepatoblastoma
;
*▲common
primary malignant liver neoplasm
;
mostly younger than 3yr
;
male > female
;
★associated with congenital anomaly
- *hemihypertrophy, Beckwith-Wiedemann syndrome, diaphragmatic &
umbilical hernias, Meckel diverticulum, renal anomaly
;
composed immature hepatic epithelial tissues
four
histologic subtype: fetal ,embryonal,macrotrabecular,anaplastic
Clinical & Laboratory Characteristics
;
*enlarging, asymptomatic abdominal
mass
;
pain, fever, weight loss, and/ or vomiting
- 소수에서 나타난다.
;
*jaundice - rare
;
*isosexual precocious puberty due to β-hCG
;
severe osteoporosis with pathologic fractures
;
*elevated a-fetoprotein - 66%
;
significant thrombocytosis, mild anemia, moderate leukocytosis
;
X-ray
- hepatic enlargement with
tumor calcification(30%)
Treatment And Outcome
surgical
excision of primary tumor is necessary to achieve a cure
-initially
feasible in only 50%
highly chemosensitive (cisplatinum
with either vincristine and 5-FU or
doxorubicin)
3-yr
survival rate:90% with initially resected tumor
457.2 Hepatocellular Carcinoma
;
*▲often
in older children 12-15yr
- peak incidence *before age 4 yr
;
33%
- *cirrhosis secondary to metabolic abnormality(galactosemia,
tyrosinosis), glycogen storage disease, malnutrition, biliary atresia, giant
cell hepatitis
Clinical Manifestation And Laboratory Data
: abdominal distention, RUQ mass
50%:abdominal pain;
nausea, vomiting
fever, weight loss,
anorexia
thrombocytosis is less
common & elevated transaminase levels are
more common in
HCC
serum-a-fetoprotein is
elevated in about 50%
Rt. lobe is the most
common primary site
Lung & L.N are the
most common metastatic site
Treatment
complete surgical excision is the only
effective Tx
respond to CTx
are in 30-40%
457.3 Benign tumors
-cavernous hemangioma
-hemangioendothelioma
-mesenchymal harmatoma
-focal nodular hyperplasia
-liver cell adenoma
Chapter 458. Gastrointestinal Neoplasm
458.1 Salivary Gland Tumor
458.2 Nasopharyngeal Carcinoma
.high degree of association
with EB virus
.the histologic appearance :
undifferentiated carcinoma.
.the most early finding :
cervical lymphadenopathy(usually unilateral)
.early Sx and Sg : trismus,
epistaxis, sorethroat, swallowing difficulty
.Dx : Bx of cervical node
.local extension : the base
of the skull, surrounding soft tissue.
.metastasis : LN(common),
bone, lung.
.the primary Tx :
irradiation
458.3 Carcinoma Of The Stomach
.extremely rare in children
.usual Sx : noticeable mass
.most common malignant
lesion : lymphoma or soft tissue sarcoma(leiomyosarcoma)
458.4 Pancreatic Tumors
.rare
.usual site of origin : head
of the pancreas
.initial clinical findings :
upper abdominal mass, weight loss, pain, icterus, obstructive
jaundice(obstruction of the CBD)
.Tx : resection when
possible
CTx agent-5FU, the nitrosoureas, doxorubicin, alkylating agent)
=Pancreatoblastoma
.a benign exocrine tumor located
in the head of the pancreas
.encapsulated and not
communicated with the pancreatic ducts-can be removed without
interfering with pancreatic function
.Sx : abdominal mass
.Px : favorable after
resection
=β-Cell endocrine tumor
.in the form of diffuse
islet cell malformation or dysplasia
.Dx : hypoglycemia
high serum level of insulin even at low glucose levels.
confirm-autonomous behavior of islet cell
.Tx : pancreatectomy
458.5 Colonic Polyps
.about 85% of all polypoid lesions
in colon and rectum-the juvenile or retention polyp
.most common presenting Sx and Sg : bright red rectal
bleeding.(painless)
.become symptomatic when
children are 3-5 yr of age
.most can be removed through
a sigmoidoscope. a new polyp and
polyps develops
( 25%) .not a
premalignant lesion
.adenomatous
polyps-associated with the development of adenocarcinoma of the large
bowel
458.6 Adenocarcinoma Of The Colon And Rectum
.represent fewer than 1% of
malignant tumors in children
.affected pt. present
-bloody stools, melena, abdominal pain, anorexia, weight loss
intestinal obstruction
.Dx : barium enema, direct
endoscopic examination
CT-detect hepatic metastasis, retroperitoneal lymphadenopathy,
ovarian
metastasis
.predisposing condition :
-familial
multiple polyposis
-ulcerative
colitis
-regional
enteritis
-Peutz-Jeghers
syndrom
Chapter 459. Carcinomas
459.1 Clear Cell Adenocarcinoma Of The Vagina And Cervix
.associated with
intrauterine exposure to diethylstilbestrol
.anomalies of the cervix may
also occur in affected pt.
459.2 Carcinoma Of The Thyroid (In Chapter 524)
.incidence is increased-head
and neck irradiation
.spontaneous thyroid cancer
: F>M, papillary in nature, grow slowly
.medullary carcinoma-associated with
Marfan-like habitus, mucosal neuroma, MEN
459.3 Carcinoma Of The Adrenal Gland
.occur at any age during childhood-more
common during the first few years
.associated with-hemangiomas of
the skin,
hemihypertrophy
urinary tract anomalies
astrocytoma
girls predominate
.affected children present sings
of adrenal hyperfuntion(Cushing syndrome, virilization,
feminization)
.Px is dependent on tumor size,
extend of tumor, resectability
Chapter 460. Cancer Of The Skin
460.1 Malignant Melanoma
.during the first two decades
.rapidly growing, easily
traumatized, dark pigmented ulcerative lesion
.giant hairy cell nevus syndrome
or dysplastic nevus syndrome
predispose to the
development of melanoma
.Tx : wide local resection
metastatic disease-vincristine, cyclophosphamide, dactinomycin
460.2 Xeroderma Pigmentosum
.an autosomal recessive
.a defective mechanism for DNA
repair
-exposure to sunlight
: UV radiation produces breaks in DNA
-mutant malignant
growth.
.Tx : surgical resection
Chapter 461. Benign Tumor
461.1 Benign Tumors And Tumor-Like Processes Of Bone
㉿Table 461-1
Osteoid Osteoma
.in adolescents, esp in boys.
(10-25yr)
.usually involves the femur or
tibia.
.clinical feature : pain (more
severe at night and relieved by aspirin)
-localized
tenderness, but signs of inflammation are unusual
.roentgenogram : a sharply
demarcated radiolucent nidus of osteoid tissue surrounded
by sclerotic bone
.Tx : surgical (nidus must be
completely removed to prevent recurrence)
Fibrous Dysplasia
.most common developmental osseous
anomaly
.manifest in late childhood
.association with a pathologic
Fx-common cause of nonunion
.Albright syndrome : polyostotic
fibrous dysplasia + skin hyperpigmentation
+
endocrine dysfunction
Benign Fibrous Cortical Defects
.occur in 30∼40%
of children
.most commonly from 4-8yr of age
.located in the distal femur
.asymptomatic and heal
spontaneously
.chronic bone pain and pathologic
Fx may be evident with large lesion
.중요한 것은 malignant lesion 으로 오인하지 않는 것이다.
.plain radiograph : ecentrically
located, ovoid, have a loculated portion with a
sclerotic medullary border
Osteochondroma
: .MC benign tumor of bone
.2nd decade of life
.often involves the distal
metaphysis of the femur and proximal metaphysis of
the tibia
.epiphyseal plate의
closure가 일어날 때까지 커짐
.만약 epiphyseal closure 후에 다시 재발하면
malignant lesion을 의심하고 excisional Bx를
시행함
.x-ray : pedunculated or sessile
Enchondroma
.MC in metadarpals, metatarsals,
phalanges
.lesion in the hand or feet :
benign
.lesion in the large long bones,
in any diaphysis, or in membraneous bone : malignant
potential을 가지며,
조직학적으로도 malignant lesion과 구별하기 어려움
.Ollier disease : presence of
multiple enchondroma
.Tx : curettage for well-contained
lesion, autologous bone grafting for extensive
lesions in the metarcarpals or phalanges
Aneurysmal Bone Cyst
.radiographically
-lytic expansile
lesion
-lacks a sclerotic
ring
.Tx : curettage, bone grafting,
cryosurgery
Simple Unicameral Bone Cyst
.proximal humerus and proximal
femur
.cavity is unilocular or
multilocular and contains fluid or blood
.origin : unknown
.attributed to traumatic hematoma
.Sx : absent or scant
.upper extremity cysts-not need Tx
lower extremity pose a
greater risk of Fx-Tx with curettage or excision
Fibromatoses
.less then 1% of all pediatric
solid tumor
.MC neoblastic myoblastic-fibroblastic
growth I children
.characterized by the presence of
multiple painless cutaneous papules located in the
head, back and extremities
.only definitive Tx : surgical
excision
461.2 Hemangioma
;
*▲common
tumor in infants
;
common site
- *the skin : 60% head and neck
;
solitary
;
predominate in girls
;
proliferative growth phase for 6-10mo
;
involutional phase
- 50% by age 5yr
- *90% by age 10yr
;
Treatment
- prednisone
- *INF alpha-2a(Roferan-A)
/
regression in most infants with life-threatening hemangiomas
- surgical resection
- laser photocoagulation
Kasabach-Merritt Syndrome
;
Cavernous hemangioma, microangiopathic hemolytic anemia, thrombocytopenia,
consumptive coagulopathy
;
Treatment
- supportive therapy directed
toward improving the coagulopathy using PLT, cryoprecipitate, FFP
- steroid
Hemangioendothelioma
.initial Sx : jaundice, vomiting,
diarrhea, abdominal swelling
.radiograph : enlarged liver and
calcification in the tumor
.Tx : 1)initial-prednisone and or
radiation
2)surgical resection
3)hepatic a, catheter embolization
461.3 Lymphatic Malformation (=Lymphangiomas)
;
2nd common benign vascular tumor in children
;
localized or generalized
;
common site
- *the cervicofacial lesion, axilla, and thorax
;
appear early in life
- evident by the age of 3yr
;
rarely regress spontaneously and obstruct aerodigestive tract
;
Treatment
- staged surgical resection
461.4 Thymoma
.rare in children
.equal frequency in boys and girls
.associated conditions
-myasthenia gravis
-red cell aplasia
-hypogammaglobulinemia
.with tumor growth-progressive
compression of surrounding tissue
-cough, dyspnea,
dysphagia, superior vena cava compression
.slow growing, rarely metastasize,
radiosensitive
.TOC-surgical excision