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Part 22. Neoplastic Diseases and Tumors

¹Î¼öÁø ¼±»ý´Ô

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 cancer´Â environmental factorsº¸´Ù host factors°¡ ´õ Áß¿äÇÏ´Ù.

Environmental Factors

¡ÚTable 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

   .leukemia´Â radiation exposureÈÄ 5³âÀÌ peak incidence timeÀÌ´Ù.

   .breast cancer; 10¼¼ ÀÌÀü¿¡ ³ëÃâµÈ Áß³âÀÇ ¿©¼º¿¡¼­ ºóµµ Áõ°¡

   .thyroid tumor

   .brain tumor

Ultraviolet Radiation

   .exposure of sunlight-skin cancer

   .genetic predisposition(eg, xeroderma pigmentosa,other congenital defect in DNAS repair)

    ÀÖ´Â °æ¿ì ultraviolet¿¡  neoplasmÀÇ risk ´õ ³ô´Ù.

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(¹Ì±¹), Burkitts' lymphoma(¾ÆÇÁ¸®Ä«)

                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

¡ÚTable 446-1

¡ÚTable 446-2

Tumor Suppressor Genes

.cancer¹ß»ýÀ» ¾ïÁ¦ÇÏ´Â tumor suppressor gene(antioncogene)ÀÇ down regulationÀº

 malignant growth¸¦ ÀڱؽÃŲ´Ù.

.retinoblastoma; submicroscopic deletion in chr 13

.Rb gene 1)nuclear phosphoprotein with DNA biredig activity(cell cycle regulation

           ¿¡ Áß¿äÇÏ´Ù.

          2)Á¤»óÀο¡ Á¸ÀçÇϸç, cell growth¸¦ °üÀåÇÏ´Â µ¥ retinoblastomaȯ¾Æ¿¡¼­´Â ¾ø´Ù.

Li-fraumeri synd.; °¡Á·ÀûÀ¸·Î ´Ù¾çÇÑ childhood solid tumor°¡ ¹ß»ý.(bone , breast, lung

                   cancer)ÇÏ´Â ÀÓ»óÁõÈıºÀ¸·Î, p-53 tumor suppressor geneÀÇ germline

                   mutationÀÌ ³ªÅ¸³­´Ù.

                  -p53 tumor suppressor geneÀÇ product´Â apoptosis(programmed natural

                   cell death)¸¦ °üÀåÇÏ´Â µ¥, À̰ÍÀÇ °á¿©·Î ÀÎÇØ excessive tumor cell                        growth °¡ »ý±ä´Ù.

Other Mechanisms And Implications

.underlying genetic disorder¿Í malignancy¿Í ¿¬°üµÇ¾î ÀÖ´Â °æ¿ì°¡ ¸¹Àº µ¥, À̰ÍÀº oncogenesis ÀÇ ´Ù¸¥ mechanismÀ» ¾Ï½ÃÇÑ´Ù.

.ex1)xeroderma pigmentosa, ataxia-telangiectasia,Bloom synd. Fanconi anemia´Â malignancyÀÇ  risk°¡ ³ô´Ù.

.ex2)immmunodeficiency stateÀÎ Wiskott-Aldrich synd, congenital X-linked immunodeficiency°æ¿ì lymphoid malignancyÀÇ È®·üÀÌ ³ô´Ù.

.malignancy ȯ¾ÆÀÇ evaluation½Ã , familial association°ú congenital synd.À» È®ÀÎÇØ¾ß ÇÑ´Ù.

Chapter 447. Principles Of Diagnosis

.most childhood cancers are curable

.Px relates most strongly to tumor type, extent at diagnosis, effectiveness of tx.

.´ëºÎºÐÀÇ physicianÀÌ È¯ÀÚ¸¦ óÀ½ ´ëÇÒ ¶§, cancer¸¦ ¶°¿Ã¸®Áö ¾Ê±â¿¡, ³õÄ¡´Â ¼ö°¡ ÀÖ´Â

 µ¥, atypical course¸¦ ±â¾ïÇØ¾ß ÇÑ´Ù.

¡ÚTable 447-1

osteosarcoma, Ewing's sarcoma´Â 10´ë¿¡ Àß »ý±â°í, ÀÌ ³ªÀ̰¡ physical activity°¡ ¿Õ¼ºÇϹÇ

 ·Î, bone pain½Ã±â¿Í trauma½Ã±â°¡ Áߺ¹µÇ´Â ¼ö°¡ ¸¹´Ù.

   -radiologic examÀÌ µµ¿òÀ» ÁÙ ¼ö ÀÖ´Ù.

.nasopharynx or middle ear tumor´Â inf.°ú À¯»çÇÏ´Ù.

  Áö¼ÓµÇ´Â ÀÌÅë, ÀÌ·ç, retropharyngeal swelling½Ã´Â malignancy¸¦ ÀǽÉÇØ¾ß ÇÑ´Ù.

.cervical lymph node enlargement½Ã´Â inf.°ú lymphoma¸¦ ±¸ºÐÇØ¾ß ÇÑ´Ù.

 (Sx. Áö¼Ó½Ã LN.bx. ½ÃÇàÇÑ´Ù.)

.leukemiaÀÇ Ãʱâ Áõ¼¼°¡ low grade fever, bone pain, joint pain¿¡ ±¹ÇÑµÉ ¼ö ÀÖÀ¸¸ç, PB¿¡¼­

 blast°¡ ¾È º¸ÀÏ ¼öµµ ÀÖ´Ù. anemia, neutropenia, mild thrombocytopenia ÀÖÀ» ½Ã BMA¸¦

 ÇØ¾ß ÇÑ´Ù.

.bx¿¡ ¾Õ¼­ metastasisÀ¯¹« º¸±â À§ÇÑ stage work upÀ» Àß ÇØ¾ß ÇÑ´Ù.

->surgeonÀÌ operation½Ã,  resection¹üÀ§¸¦ °áÁ¤ÇÏ°Ô µÈ´Ù.

.Dx.ÀÇ Áß½ÉÀº histologic typeÀÌ´Ù.

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

¡ÚTable 448-1

<phase I study>; low dose¿¡¼­ startÇØ¼­ max. tolerate dose±îÁö ÃøÁ¤

<phase II study>; specific tumor typeÀÇ tx. efficacy¸¦ ÃøÁ¤

<phase III study>; protocolÀÇ ±âÁ¸ÀÇ ¾à°ú °°ÀÌ schedule¿¡ ÀԷ½ÃÄÑ È¿°úÃøÁ¤ÇÑ´Ù.

Acute Complications & Supportive Care

# Early complications

    ; metabolic disorders

  ; bone marrow suppressions

  ; immunosuppressions

# ¡ÚTumor Lysis Syndrome

    ; substantial breakdown of tumor cells

           --> tubular precipitates of uric acids crystals

           --> impaired renal functions

    ; *symptomatic hyperphosphatemia, hypocalcemia, hyperkalemia

    ; *¡ãoften in hematologic malignancy

    ; large solid tumorµµ °¡´ÉÇÏ´Ù.

           - e.g.) Burkitt's lymphoma, germ cell tumor, neuroblastoma

    ; Treatment

           - adequate hydration & allopurinol before chemotherapy

# bone marrow suppression

    ; Granulocytopenia(500/mm3ÀÌÇÏ)

    ; life threatening inf.ÀÌ »ý±æ ¼ö ÀÖ´Ù.

=>febrile granulocytopenic pt.´Â broad spectrum antibiotics¸¦ »ç¿ëÇØ¾ß Çϸç, 1ÁÖ ÀÌ»ó

   Áö¼Ó½Ã´Â antifungal agentµµ °í·ÁÇØ¾ß ÇÑ´Ù,.

.ƯÈ÷, candida ȤÀº aspergillus species°¡ ÈçÇÏ´Ù.

.opportunistic inf.; pneumocystitis carinii

   ->±×·¡¼­, bactrimÀ» ¿¹¹æÀûÀ¸·Î »ç¿ë

. Ç×¾ÏÄ¡·á ȯ¾Æ¿¡¼­, varicella¿¡ ³ëÃâµÇ¸é varicella zoster immunoglobulinÀ» ¸Â°í, ÀÓ»óÁõ¼¼ »ý±â¸é ÀÔ¿øÇؼ­, iv·Î acyclovir¸¦ Åõ¿©ÇÑ´Ù.

3)Ç×¾Ï Ä¡·áÈÄ pt.ÀÇ ´ëºÎºÐÀÇ Æò¼Ò B.WdÀÇ 10%¸¦ ¼Ò½ÇÇÑ´Ù.( tx associated nausea, vomiting)

 -intensive CTx, total body irradiation, abd. head, neckÀÇ irradiation txȯ¾Æ´Â malnutritionÀÌ  À§ÇèÇϸç TPNÀÌ ÇÊ¿äÇÏ´Ù.

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

; ¡Úchemotherapy can cause severe organ damage

  - high-dose MTX : leukoencephalopathy

    - anthracyclin : myocardial damage

  - bleomycin : pul. fibrosis

    - asparaginase : pancreatitis

    - cisplatin : hearing loss

    - irreversible change

; baseline testÈÄ, adequate monitoringÀÌ ÇÊ¿ä

; *¡ãserious 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; BM¿¡ Ä¡¸íÀûÀÎ ¿ë·®ÀÇ radiation tx ȤÀº chemotherapy½ÃÇàÇÒ ¶§,

 ¸ÕÀú ȯ¾ÆÀÇ BMÀ» µû·Î º¸°üÇÑ ÈÄ, txÈÄ ´Ù½Ã autologous marrow¸¦ reinfusion

  ->ALL, AML, neuroblastoma, Hodgkin's dz, Non Hodgkin's dz, Ewing's sarcoma,

    brain tumor

.¹®Á¦Á¡; À̽ÄÇÑ BMÀÇ residual malignant cellÀÌ relapseÇÒ ¼ö ÀÖ´Ù´Â Á¡.

.allogenic BMT-ȯÀÚÀÇ HLA¿Í "match"µÇ´Â donor·ÎºÎÅÍ °ñ¼ö·ê À̽ĹÞÀ½.

 -the best donor is major MHC°¡ °°Àº sibling(È®·ü ; 20-30%)

 -morbidity; GVHD, marrow rejection

 -matched sibling donor¶ó¼­, ¾î´À Á¤µµÀÇ alloreactivity´Â ÀÖ´Ù.( minor HLA typingÀº

  Ʋ¸®¹Ç·Î )

 -serious post transplantation problems;

.graft versus host disease

  ;¾î¸° ȯ¾ÆÀϼö·Ï ´ú ¹ß»ýÇϰí, ÃÖ±Ù¿¡´Â cyclosporinÀÇ Åõ¿©·Î ±× ¹ß»ýÀÌ °¨¼ÒµÇ°í ÀÖÀ¸³ª,

   GVHDÀÇ ¹ß»ýÀÌ °¨¼ÒÇÒ¼ö·Ï cancer relapse°¡ Áõ°¡

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

; ¡ã 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/¸¸¸í (¹éÀÎ)

  - 24/¸¸¸í (ÈæÀÎ)

        --> due to lower incidence of ALL in black

449.1 ALL

; first curable disseminted cancer with chemotherapy & irradiation

; ¢¾Asso. 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

; ¡ÚFAB 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.

# ¡ÚChildren With T-Cell ALL

    ; older and more often male

    ; 66% anterior mediastinal mass

¡ÚTable 449-1

Diagnosis

-on initial exam, most have anemia, about 25% have Hb levels below 6g/gÀÌÇÏ

-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

# ¢¾Pediatric Tumors That Can Infiltrate Marrow

    1) neuroblastoma

  2) *rhabdomyosarcoma

  3) Ewing sarcoma

  4) rarely retinoblastoma

Treatment 

# ¡ÚAverage 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

¡ÚTable 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

    ; ¡Úbone marrow

           - *¡ãcommon site of relapse

    ; experience bone marrow relapse during treatment, intensive chemotherapy followed by

 bone marrow transplantation

    ; ¡ÚCNS and the testes

           - *¡ãimportant 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

# ¡ÚTreatment

    ; *¡ãimportant prognostic factors

# clinical features

    ; initial WBC counts

    ; age

           - older than 10yr, younger than 12mo : poor

# ¡ÚChromosomal 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 pe¸¸ 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

; ¡Úchloroma

    - localized mass of leukemic cells

    - *retro-orbital, epidural location

           / *¡ãcommon

    - maybe precede leukemic cell infiltration of bone marrow

; initially with only anemia, leukopenia, or thrombocytopenia

    - ¡ÚMDS

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

    ; ¡Úchromosomal 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

           ; *¡ãbest prognosis

    2) nodular sclerosing type

       ; *¡ãcommon 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

           - ¡ãcommon 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 ¥³

  ; BM involvement

           - neutropenia, thrombocytopenia and anemia

    ; ¡Úimmune 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(+)

   -> µû¶ó¼­ infectious mononucleosis¸¦ ¾ÎÀº ÈÄ enlarged LN°¡ ÁÙ¾îµéÁö ¾ÊÀº °æ¿ì

       Bx¸¦ ½ÃÇàÇÏ¿©¾ß ÇÑ´Ù.

; 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

# ¡ÚStaging 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

           - *ÇöÀç´Â findingsÀÌ Ä¡·á ¹æÇâÀ» Á¿ìÇÒ °æ¿ì¿¡¸¸ ½ÃÇà

    ; ¡ÚBM biopsies

¢¾Table 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%

                   / ¢¾why?

                           : 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 ¥° and ¥± will be crued

 - in stages ¥² ; 75% cured

 - in stage ¥³ : 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

   ; µû¶ó¼­ ¼ºÀå¹®Á¦ ¶§¹®¿¡ children¿¡°Ô¼­´Â standard dose radiationÀ» ÁÖÁö ¾Ê´Â´Ù.

 -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

    ; ¡Úacute myeloid leukemia

           - *¡ãfrequently

450.2 Non-Hodgkin Lymphoma

; malignant clonal proliferations of primarily T or B lymphocytes

# ¢¾High 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

  ¨ç small noncleaved cell (Burkitt and non-Burkitt subtypes)

           ; B cell tumor

       ; express surface immunoglobulin

           ; ¡Úcontain one of three chromosomal translocations

                   - *t(8;14), t(2;8), t(8;22)

           ; ¡Úinvolved c-myc oncogene, immunoglobulin gene (mu heavy chain, kappa light chain, lambda light chain)

  ¨è Lymphoblastic lymphoma

           ; T-cell origin

           ; *contain a translocation involving a T-cell receptor gene

    ¨é Large cell NHL

           ; T-cell, B-cell, non-B, non-T cell phenotypes

           ; t(2;5)(p23;q35) asso. with CD30

Clinical Manifestations

    ; ¡Ú¡ãcommon primary site

           - *abdomen(31.4%), mediastinum(26%), head/neck region including Waldeyer ring and/or cervical lymph nodes (29%), non cervical LN(6.5%)

    ; ¡Ústriking 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 Áõ°¡, cranial nerve palsies

Diagnosis

¡ÚTable 450-2

Treatment

    ; common TLS

    ; ¡ØCNS prophylaxis

    ; multiagent chemotherapy

           - cyclophosphamide-based COMP regimen

                   / SNCC type

           - intensive multiagent LSA2L2 regimen

                   / Lymphoblastic type

           - ¡ÚCHOP regimen (cyclophosphamide, doxorubicin, vincristine, predisone)

                   / *¡ãeffective protocols for large cell type

Prognosis

 ¡¤2-yr event-free survival (EFS) : 90% for children with limited-stage disease

                                   70% for those with stage ¥² and ¥³

 ¡¤improvement in the treatment of advanced-stage SNCC NHL ; 90% 2-yr EFS

                                   (70% for those with central nervous system disease)

CHAP. 451. Neuroblastoma

; *¡ã extracranial solid tumor of childhood (8-10% of all children cancer)

; *¡ãfrequently 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%(ÁÖ·Î 1¼¼ÀÌÇÏ, 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)

; ¢¾Cytogenetic Abnormality

    ; 80%

  1) partial deletion of the short arm of chromosome 1, chromosome 17

    2) genomic amplification of the ¡ÚN-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

    ; ¡Úacute 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

           - *¡ãuseful 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 procedureÀ» ÇϱâÀü¿¡ ¹Ýµå½Ã BM aspiration & biopsyÀ» ½ÃÇàÇÏ¿© ÀüÀÌ¿©ºÎ¸¦ È®ÀÎÇØ¾ß ÇÑ´Ù.

# ¢¾Definite Diagnosis

    ; histologic studies of tumor tissue

    ; documentation of bone marrow involvement plus increased urine or serum catecholamine level

# ¡ÚDNA 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

¡ÚBone 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

           - ¡Úliver biopsy should be in infant

; ¡Úsecond-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

    - *¡ã 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%

; ¡ÚBiologic And Genetic Markers

    - DNA content(ploidy)

           /hyperdiploid(DNA index more than 1)

                   : 80% survival expectancy compared with 20% for diploid tumors

    - ¢ÞN-myc amplication

           / *poor outcome in all age/stage tumors

¡Ø96 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%) : ¡ãcommon

  ; hemihypertrophy(2.9%)

  ; sporadic aniridia(1.1%).

# ¡Údeletion 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

    ; ¡Ú2 subtype

           - Rhabdoid tumor

                   / composed of cells with fibrillar eosinophilic inclusions

                   / *¡ãoften 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

    - *¡ãfrequent sign

; smooth and firm and rarely crosses the midline

. mean diameter ; ll cm

. 50% - abdominal pain, vomiting, or both

. ½Å°æ¾Æ ¼¼Æ÷Á¾¿¡ ºñÇØ ¿¬·ÉÀÌ ³ô°í less ill ÇÏ°Ô º¸ÀÓ

. Hypertension (60%)

   -owing to pressure of the tumor on the renal a.

Diagnosis

   . microscopic ȤÀº gross hematuria (10¡­25%)

   . ultrasonography ; the mass is intrarenal. (½Å°æ¾Æ ¼¼Æ÷Á¾°úÀÇ °¨º°ÀÌ Áß¿ä)

   . 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 (°¡Àå Áß¿ä)

# pulmonary metastases ;

   .evident on roentgenogram in 10¡­15% of patients at time

     of diagnosis.

   .more common in neuroblastoma.

   .CT scan of chest ; plain radiograph·Î ¹ß°ßÇϱ⠾î·Á¿î

                      the dome of the diaphragm

                      ¾Æ·¡ÂÊÀÇ metastatic lung lesionsÀ»

                      ¹ß°ßÇϴµ¥ µµ¿òÀÌ µÈ´Ù.

hepatic metastasis ÀǽɽÃ

  -CT of abdomen

evaluation of bone and BM.°í·Á.

  -persistent bone pain

  -unfavorable histologic subtype

paraneoplastic syndrome

  -1.produce erythropoietin->polycythemia

   2.secondary hypercalcemia

      -ÀÓ»óÀûÀ¸·Î von Willebrand disease¿Í À¯»çÇÑ ¾ç»ó º¸ÀÓ.

Treatment

# surgical removal of the kidney

    ; usual immediate treatment

    ; pulmonary metastases°¡ Á¸ÀçÇÏ´õ¶óµµ ½ÃÇà

# *Wilms tumor is sensitive both chemotherapy and to radiotherapy

# radiotherapy

    ; *¼úÈÄ ¸ðµç ȯÀÚ¿¡°Ô ½ÃÇà

# chemotherapy

    ; NWTS groups¿¡¼­ combination therapy°¡ single agent therapyº¸´Ù È¿°úÀûÀ¸·Î ÀÎÁ¤

    ; *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

# ¡Ú¡ãsignificant prognostic variables

    ; Histologic subtype and stage

# Àç¹ß½Ã poor prognosis

452.2 Other Renal Neoplasms

Nephroblastomatosis

. immature renal elements (nephrogenic rests)

        -33% of unilateral Wilms tumor¿¡¼­ ¹ß»ý

        -´ë°³ 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.

. EM»ó fibroblasts ȤÀº myofibroblasts º¸ÀÓ.

. ³²¾Æ

. renin production

Renal Cell Carcinoma

. 10´ë¿¡ ¹ß»ý

. abdominal mass and hematuria

        -initial finding

. ¾î¸¥ÀÇ renal cell ca,¿Í ºñ½ÁÇÑ Çö¹Ì°æ ¼Ò°ß°ú ÀÓ»ó °æ°ú¸¦ °¡Áü.

Chapter 453. Soft Tissue Sarcomas

. 50%ÀÌ»óÀÌ rhabdomyosarcoma

453.1 Rhabdomyosarcoma

Epidemiology

; *¡ãcommon soft tissue sarcoma

. male (¸¹ÀÌ ¹ß»ý)

# 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.

    ; ¡Ø96 DDx

           - *Ewing sarcoma, neuroblastoma, neuroectodermal tumor, non-hodgkin lymphoma

# histologic subtypes ( 4 °¡Áö )

  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, Ư¡; t(2;13) chromosomal translocation.

  4.pleomorphic; adult form, 1% of cases.

  -undifferentiated tumor; about 20%.

Clinical Manifestation

; *painful or not painful mass

    - *¡ãcommon 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; óÀ½ Çѵ¿¾ÈÀº hematoma·Î ¿ÀÀÎÇϱ⠽±´Ù.

. 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.

. tumor°¡ ¾î´À À§Ä¡¿¡ ÀÖµçÁö »ó°ü¾øÀÌ early disseminationÀÌ ¹ß»ýÇϸç

    pulmonary  metastasis¶§ ¹ß»ýÇÏ´Â the presenting symptomÀº 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 chemotherapy½ÃÇà

   -primary disease in parameningeal sites(nasopharynx, paranasal sinuses etc)

   -with intracranial extension.

Prognosis

. resectable tumor; prolonged tumor free survival in 80-90%

. unresectable tumor¶óµµ orbit¿Í °°Àº favorable site¿¡ ¹ß»ýÇÏ´Â °æ¿ì high likelihood of cure¸¦ °¡Áø´Ù.

. 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; 12¼¼

. M:F=2.3:1

. histologic types

    -synovial sarcoma(42%)

    -fibrosarcoma(13%)

    -malignant fibrous histiocytoma(12%)

    -neurogenic tumors(10%)

 È£¹ßºÎÀ§

    -trunk or lower extremities

Chapter 454. Neoplasms Of Bone

; 2nd decade of life

; male (¿ì¼¼)

¢ÞTable 454-1

454.1 Osteosarcoma

# È£¹ßºÎÀ§

    ; 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

# ¡ÚOthers 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 osteosarcomaÀÇ ºÐ·ù

   ; 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;

      - µ¿½Ã¿¡ ¿©·¯ Àå¼Ò¿¡¼­ tumor°¡ ¹ßº´ÇÏ´Â ÇüŸ¦ ¸»Çϸç,

         ÁÖ·Î osteoblastic patternÀ» ³ªÅ¸³½´Ù.

Clinical Manifestations

; *localized pain and swelling

    - *¡ãcommon presenting symptom

; P/Ex

      - local swelling, tenderness, warmth

      - limited range of motion

. CBC, Chemistry; ´ë°³ 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.

. stage¸¦ °áÁ¤Çϱâ À§ÇÑ ÃÖ¼ÒÇÑÀÇ °Ë»ç;

     -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

    ; *¼ö¼úÀÚü¸¸À¸·Î´Â 5³â »ýÁ¸À²ÀÌ 20%¹Ì¸¸

# ¡Ø97 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

; *¡ãoften in 2nd decade of life

; ¡Ú¡ãoften sites

    - *flat bones(pelvis, chest walls, vertebrae)

    - diaphyseal region of long bones

; soft tissues tumors

   -most often in the trunk.

   -50%ÀÌ»óÀÌ chestÁÖÀ§¿¡¼­ ¹ß»ýÇÔ.

.Ewing sarcoma

  -ÀüÇüÀûÀ¸·Î extensive soft tissue component°¡Áü.

  -lung°ú boneÀÌ °¡Àå ÀüÀ̰¡ Àß µÇ´Â ºÎÀ§

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

; ¶§¶§·Î Ç×»ýÁ¦¸¦ ¾²¸é Ewing sarcomaÀÇ Áõ»óÀÌ ÁÁ¾ÆÁö´Â °æ¿ìµµ ÀÖÀ¸¹Ç·Î bacterial culture ¿¡¼­ À½¼ºÀ¸·Î ³ªÅ¸³ª´Â osteomyelitis¸¦ ´ëÇÏ¸é ¹Ýµå½Ã Ewing sarcoma¸¦ °í·ÁÇØ¾ß ÇÑ´Ù.

Diagnosis

.clinical history and radiologic features

.È®Áø;  surgical biopsy

.CT scan

.Bone scan

.BM; ÀüÀ̰¡ ÀÇ½ÉµÉ ¶§.

.MRI; primary lesionÀÇ extent¸¦ Æò°¡ÇÏ´Â µ¥ °¡Àå ÁÁ´Ù.

      ƯÈ÷ , Ä¡·á¿¡ ´ëÇÑ ¹ÝÀÀÀ» Æò°¡ÇÏ´Â µ¥ À¯¿ëÇÏ´Ù.

Treatment

# response to both radiotherapy and chemotherapy.

    ; *amputation is rarely indicated

# Multiagent chemotherapy

  ; 4 drug CTx

           - cyclophosphamide, doxorubicin, vincristine, dactinomycin

    - Ãß°¡ ¾àÁ¦;  ifosfamide and etoposide

. local RTx

    -È¿°úÀûÀ̱ä ÇÏÁö¸¸ high-dose radiotherapy½ÃÇàÀÌ ºÎÀÛ¿ë

                   1)failure of bone growth

                   2)soft tissue fibrosis

                   3)secondary malignancy(ƯÈ÷, osteosarcoma)

.long-term F/UÀÌ ÇÊ¿ä

    -Áø´Ü 10³â ȤÀº À̻󿡼­µµ Àç¹ßÀÌ ÀÖÀ» ¼ö Àֱ⠶§¹®.

Prognosis

454.3 Rare Bone Tumors

* Chondrosarcoma

.rare in children, usually seen during the second decade.

.most common in the pelvis.

.lung and boneÀ¸·Î metastasis°¡ °¡´ÉÇÏÁö¸¸ ´ë°³´Â local extension.

.histologic exam; osteosarcomaµµ chondrosarcomatous component¸¦ ¸¹ÀÌ °¡Áö°í ÀÖ±â

                              ¶§¹®¿¡ ÁÖÀǸ¦ ¿äÇÑ´Ù.

.Tx;

  -surgical removal

  -relatively radioresistant.

 

* Fibrosarcoma

.rare

.soft tissue¿¡¼­ ¹ß»ý

.ÁÖÄ¡·á ¹æ¹ý; surgical resection

Chapter 455. Retinoblastoma

# ¡ÚAverage 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

# ¡ÚGenetic 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 tumor·ÎºÎÅÍ ¶³¾îÁ® ³ª¿Â tumor fragment°¡ vitreous ³»¿¡¼­ ¶°µ¹´Ù°¡

          ´Ù¸¥ retina·Î seeding µÇ´Â °æ¿ì large tumor¸¦ Çü¼ºÇϰí poor prognosis¸¦ ³ªÅ¸³½´Ù.

choroid·Î extension µÇ¾î ÀÖ´Â °æ¿ì hematogenous metastasis ÀÇ °æÇâÀ» º¸ÀδÙ.

retinoblastoma´Â ´ë°³ metastasis °¡ µå¹°±â ¶§¹®¿¡ Áø´Ü ´ç½Ã ÁÖ°ü ½ÉÀº useful vision             À» º¸Á¸ÇÏ´Â °ÍÀÌ´Ù

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

    --> ¡Úa 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

# ¡ÚDDx 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

    ; recur½Ã ´Ù½Ã »ó½Â

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

-½ÉÇÏ°Ô Ä§¹üµÈ ÂÊÀÌ º¸´Ù ´õ dramatic response¸¦ º¸ÀÏ ¼ö ÀÖ±â

   ¶§¹®¿¡ radiation therapy´Â both eye¿¡ ½ÃÇàÇÑ´Ù.

-ÇÑÂÊ ´«ÀÌ useful visionÀÌ ³²¾Æ ÀÖÁö ¾ÊÀ» Á¤µµ·Î ½ÉÇÏ°Ô Ä§¹üµÇ°Å³ª

   complicationÀ¸·Î painful glaucoma°¡ ¹ß»ýÇÏ¸é  ±× ÂÊ ´«À» enuculationÇÑ´Ù.

             -enuculationÈÄ gross or microscopic residual disease °¡ ³²¾Æ ÀÖÀ¸¸é

               radiation therapy¿Í ´õºÒ¾î chemotherapy(cytoxan+doxorubicin)°¡ °í·ÁµÈ´Ù.

Prognosis

; overall survival rate: 90%ÀÌ»ó

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 tumorÀÇ ºóµµ ¼ö°¡

    ¸¹À¸¹Ç·Î  female predominance                            

14¼¼ ÀÌÈÄ testicular tumor°¡ ¸¹À¸¹Ç·Î 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 °æÇâÀº primary site ¿Í age ¿¡ µû¶ó ´Ù¸§

   ovarian germ cell tumor : 10 ¼¼ ÀÌÇÏ¿¡¼­ ´ë°³ benign

                              adolescence¿¡¼­´Â 30%¿¡¼­ malignant

   sacrococcygeal tumor :malignancy ºóµµ°¡ 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 ¥â-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

    ; ¡Úno 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

; *¡ãcommon primary malignant liver neoplasm

; mostly younger than 3yr

; male > female

; ¡Úassociated 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

    - ¼Ò¼ö¿¡¼­ ³ªÅ¸³­´Ù.

; *jaundice - rare

; *isosexual precocious puberty due to ¥â-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

; *¡ãoften 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

  =¥â-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

¢ÞTable 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

   .Áß¿äÇÑ °ÍÀº malignant lesion À¸·Î ¿ÀÀÎÇÏÁö ¾Ê´Â °ÍÀÌ´Ù.

   .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 plateÀÇ closure°¡ ÀϾ ¶§±îÁö Ä¿Áü

   .¸¸¾à epiphyseal closure ÈÄ¿¡ ´Ù½Ã Àç¹ßÇϸé malignant lesionÀ» ÀǽÉÇϰí excisional Bx¸¦

    ½ÃÇàÇÔ

   .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

    potentialÀ» °¡Áö¸ç, Á¶Á÷ÇÐÀûÀ¸·Îµµ malignant lesion°ú ±¸º°Çϱ⠾î·Á¿ò

   .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

; *¡ãcommon 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