Part 22. Neoplastic Diseases and Tumors
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
- Rb tumor-suppressor gene
- p53 tumor-suppressor gene
# *childhood cancer는 environmental factors보다 host factors가 더 중요하다.
.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
.exposure of sunlight-skin cancer
.genetic predisposition(eg, xeroderma pigmentosa,other congenital defect in DNAS repair)
있는 경우 ultraviolet에 neoplasm의 risk 더 높다.
.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
.high fat intake, obesity-breast
1)RNA viruses; lymphatic leukemia & lymphoma
-type C RNA virus in animal
Kaposi sarcoma AIDS
2)DNA viruses; EBV IM(미국), Burkitts' lymphoma(아프리카)
3)papova viruses; warts, papilloma
type 6 & 11-laryngeal papilloma
carcinoma of the uterine Cx.
(sub type 16, 18)
Chapter 446. Molecular Pathogenesis
; endogenous human DNA sequence arising from protooncogene
; develope to tumorigenesis
; activating ras oncogene point mutation
# Burkitts lymphoma
; chr. translocation t(8:14)(q24q32) in protooncogens(C-myc) on chromosome 8
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
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
-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.
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
.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.
<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
# ★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
- adequate hydration & allopurinol before chemotherapy
# bone marrow suppression
; 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.
; radiation-related problems
- *not obvious until patients is fully grown
/ 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,
.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
-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
<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
; first curable disseminted cancer with chemotherapy & irradiation
; ♥Asso. with diseases
- immunodeficiency ; congenital hypogammaglobulinemia, ataxia-telangiectasia
- consititutional chromosomal defect ; trisomy 21
; subclassed according to morphologic, immunologic, genetic feature of leukemic blast.
; definite diagnosis-BMA
; ★FAB system(morphologic subtypes)
1) L1 - predominantly small with little cytoplasm
- larger & pleomorphic with increased cytoplasm
- irregular nuclear shape, prominent nucleoli
- *finely stippled and homogenous nuclear chromatin
- prominent nucleoli
- *deep blue cytoplasm with prominent vacuolization
; chromosomal abnormalities
- 80-90% in childhood ALL
; *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
- usually extending less than 6cm below the costal margin
; *less common hepatomegaly
; *significant bone pain and arthralgia
; 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
-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
-a chest radiograph is necessary to determine whether there is a mediastinal mass
-CSF should be examined for leukemic cells
# aplastic anemia, myelofibrosis, infectious mononucleosis
# ♥Pediatric Tumors That Can Infiltrate Marrow
3) Ewing sarcoma
4) rarely retinoblastoma
# ★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
-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
-With more intensive multidrug regimen
-B-cell cases with L3 morphology and surface immunoglobulin expression once had a
; ★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
- *include irradiation of the gonads
; *▲important prognostic factors
# clinical features
; initial WBC counts
- 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
; *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).
; 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
- localized mass of leukemic cells
- *retro-orbital, epidural location
- maybe precede leukemic cell infiltration of bone marrow
; initially with only anemia, leukopenia, or thrombocytopenia
-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
-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
-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.
-with aggressive therapy, 40-50% of patients who achieve remission(3-40%overall cure
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
-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
-Southern blot analysis or polymerase chain reaction technique reveal the bcr-abl
-Sxs of hypermetabolism, including wt. loss, anorexia, and night sweats.
-Sxs of leukostasis, such as visual disturbance or priapism, occur rarely.
-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.
-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
-Myeloid leukemia appears marked leukocytosis, petechiae, ecchymoses, and
extramedullary involvement massive hepatosplenomegaly, cutaneous nodule, and CNS
-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
# peak age
; *the middle to late 20s
; age of 50yrs
# *whites male
# *EB virus may be involved in the pathogenesis
# 4 histologic subtypes
1) lymphocytic predominance
; mature lymphocytes or a mixture of lymphocytes and benign histiocytes
- occasionally Reed-Sternberg cells
; *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
; *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
; 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
- nephrotic syndrome
; *impaired cellular immunity
- *varicella-zoster infection
- fungal infection
/ cryptococcosis, histoplasmosis, candidiasis
; transiently depressed humonral immunity
; suspected in the patient with persistent unexplained lymphadenopathy
; in a significant percentage of patients
-> a history of relatively recent antecedent serologically proven infectious
-> 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
- 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
; localized disease (stage I or IIa)
- radiation alone to standard fields with doses of 3500-4406 rad
- radiation + combination chemotherapy
; advanced disease
/ nitrogen mustard, vincristine(oncovin), procarbazine, prednisone
/ doxorubicin(adriamycin), bleomycin(blenoxane), binblastine(vleban), dacarbazine
- MOPP/AVDG alternating with low-dose (2000-2500cGy) radiotherapy
/ more useful
/ cure rate 70-90%
: 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
- 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
; 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
# secondary malignancy
; *5-10yr after treatment
; 1.2-13% at 10yr
; ★acute myeloid leukemia
450.2 Non-Hodgkin Lymphoma
; malignant clonal proliferations of primarily T or B lymphocytes
# ♥High Risk Diseases
; Wiskott-Aldrich syndrome
; combined immune deficiencies
; X-linked lymphoproliferative(XLP) syndrome
- marked sensitivity to EBV-induced disease
- fatal infectious mononucleosis case 57%
# 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
; ★▲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
/ 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
; 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
·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
; mass screening programs
- urinary catecholamine metabolites(VMA)
- at 6 mo in japan
; originate in neural crest cells of sympathetic nervous system
- anywhere from post. fossa to coccyx
- *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
- 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
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
; *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
; 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
- detecting intraspinl extension, vessel encasement or displacement, bone marrow involvement
# 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
# 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
; 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
; infants with disseminated disease or children with localized unresectable disease
- cyclophosphamide, doxorubicin
; older children with locally advanced & disseminated neuroblastoma
- *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
; *most neuroblastomas are radiosensitive
; 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
; 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
# 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.
; *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%
; 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.
. 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
; renal cysts
; mesoblastic nephroma
; other renal malignancies ; renal cell carcinoma
; Neuroblastoma (가장 중요)
# pulmonary metastases ;
.evident on roentgenogram in 10∼15% of patients at time
.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
-임상적으로 von Willebrand disease와 유사한 양상 보임.
# surgical removal of the kidney
; usual immediate treatment
; pulmonary metastases가 존재하더라도 시행
# *Wilms tumor is sensitive both chemotherapy and to radiotherapy
; *술후 모든 환자에게 시행
; 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.
# ★▲significant prognostic variables
; Histologic subtype and stage
# 재발시 poor prognosis
452.2 Other Renal Neoplasms
. immature renal elements (nephrogenic rests)
-33% of unilateral Wilms tumor에서 발생
. precursor lesions
-unifocal and deep within renal parenchyma (intralobar rest)
-multifocal (perilobar rest)
* Mesoblastic Nephroma
. grossly and microscopically resembling
-low-grade leiomyosarcoma with trapped nephrons.
. EM상 fibroblasts 혹은 myofibroblasts 보임.
. renin production
Renal Cell Carcinoma
. 10대에 발생
. abdominal mass and hematuria
. 어른의 renal cell ca,와 비슷한 현미경 소견과 임상 경과를 가짐.
Chapter 453. Soft Tissue Sarcomas
. 50%이상이 rhabdomyosarcoma
; *▲common soft tissue sarcoma
. male (많이 발생)
; head and neck (40%)
; genitourinary tract (20%)
; extremities (20%)
; trunk (10%)
# risk patients
; maternal breast cancer in the Li-Fraumeni syndrome.
# "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.
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%.
; *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
; *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
. in head and neck;
-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.
. the most essential element of the diagnostic workup;
-the exam of tumor tissue.
. 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
-primary disease in parameningeal sites(nasopharynx, paranasal sinuses etc)
-with intracranial extension.
. 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
. histologic types
-malignant fibrous histiocytoma(12%)
-trunk or lower extremities
Chapter 454. Neoplasms Of Bone
; 2nd decade of life
; male (우세)
; 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
; multiple hereditary exostoses
; osteogenesis imperfecta
; local irradiation for Ewing sarcoma
. 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
. rare subtype
a well differentiated, extramedullary tumor,
low metastatic potential
surgical resection alone is often adequate therapy
more aggressively clinically.
bloody, cystic lesion.
radiographically, no new bone formation
--> confused with aneurysmal bone cyst.
. multifocal sclerosing osteosarcoma;
- 동시에 여러 장소에서 tumor가 발병하는 형태를 말하며,
주로 osteoblastic pattern을 나타낸다.
; *localized pain and swelling
- *▲common presenting symptom
- local swelling, tenderness, warmth
- limited range of motion
. CBC, Chemistry; 대개 Nl
. metastases occur most often
-lungs and other bones
. 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;
-a marker to follow the effect of therapy.
. conformation; by histologic exam.
; *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
. best with low-grade tumors, such as parosteal osteosarcoma.
. high-grade osteosarcoma and no evidence of metastasis.
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.
-전형적으로 extensive soft tissue component가짐.
-lung과 bone이 가장 전이가 잘 되는 부위
# special histochemical staining for DDx from rhabdomyosarcoma, neuroblastoma, lymphoma
; *specific staining for cell-surface glycoprotein p30/32MIC2(HBA 71)
# specific chromosomal translocation
--> results in a *chimeric EWS and FLi1 gene product
; pain, swelling, tenderness in involved sites
; the two conditions most often mistaken clinically for Ewing sarcoma
- eosinophilic granuloma
; 때때로 항생제를 쓰면 Ewing sarcoma의 증상이 좋아지는 경우도 있으므로 bacterial culture 에서 음성으로 나타나는 osteomyelitis를 대하면 반드시 Ewing sarcoma를 고려해야 한다.
.clinical history and radiologic features
.확진; surgical biopsy
.BM; 전이가 의심될 때.
.MRI; primary lesion의 extent를 평가하는 데 가장 좋다.
특히 , 치료에 대한 반응을 평가하는 데 유용하다.
# 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.
454.3 Rare Bone Tumors
.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.
.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
; 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
usually develops in the posterior portion of the retina
consists of small, round, closely packed malignant cells with scanty cytoplasm
-arises in the internal nuclear layers of the retina
-> growing into the vitreous cavity
-easily seen with the ophthalmoscope
-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
; 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%
--> ★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
; define optic nerve invasion
# ★DDx Of Leukokoria
; retinal detachment
; persistent hyperplastic primary vitreous
; nematode endophthalmitis
; bacterial panendophthlmitis
; coloboma of the choroid
; the retinopathy of prematurity
# Radionuclide bone scan
# bonemarrow exam
# CSF study
# carcinoembryonic antigen
; rarely found at diagnosis
; recur시 다시 상승
-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.
; overall survival rate: 90%이상
Chapter 456. Gonadal And Germ Cell Neoplasms
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
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
; 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
; 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
; 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
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
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
-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
-benign ovarian cyst: 50% of ovarian tumors
torsion-mimic an acute abdomen
-granulosa-theca cell tumor: benign
ovarian stromal origin
-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
; *▲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
- 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
- *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
complete surgical excision is the only effective Tx
respond to CTx are in 30-40%
457.3 Benign tumors
-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
.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)
.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
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,
urinary tract anomalies
.affected children present sings of adrenal hyperfuntion(Cushing syndrome, virilization,
.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
.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)
.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
: .MC benign tumor of bone
.2nd decade of life
.often involves the distal metaphysis of the femur and proximal metaphysis of
.epiphyseal plate의 closure가 일어날 때까지 커짐
.만약 epiphyseal closure 후에 다시 재발하면 malignant lesion을 의심하고 excisional Bx를
.x-ray : pedunculated or sessile
.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
-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
.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
; *▲common tumor in infants
; common site
- *the skin : 60% head and neck
; predominate in girls
; proliferative growth phase for 6-10mo
; involutional phase
- 50% by age 5yr
- *90% by age 10yr
- *INF alpha-2a(Roferan-A)
/ regression in most infants with life-threatening hemangiomas
- surgical resection
- laser photocoagulation
; Cavernous hemangioma, microangiopathic hemolytic anemia, thrombocytopenia, consumptive coagulopathy
- supportive therapy directed toward improving the coagulopathy using PLT, cryoprecipitate, FFP
.initial Sx : jaundice, vomiting, diarrhea, abdominal swelling
.radiograph : enlarged liver and calcification in the tumor
.Tx : 1)initial-prednisone and or radiation
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
- staged surgical resection
.rare in children
.equal frequency in boys and girls
-red cell aplasia
.with tumor growth-progressive compression of surrounding tissue
-cough, dyspnea, dysphagia, superior vena cava compression
.slow growing, rarely metastasize, radiosensitive