Dr. Ahmadwirawan, SpB, SpBASub Divisi Bedah Anak

Bagian Bedah FKUnhas

SISTEM ONKOLOGIFK UMI

Tumor Perinatal

Cadangan tumor 2010

• 1 Introduction• .2 Overview • .2.1 Clinical Presentation• .2.2 Oncogenesis and Genetic Risk Factors • .2.3 Diagnostic Investigations • .2.4 Therapeutic Interventions• .2.4.1 Surgical Management • .2.5 Radiotherapy • .2.6 Chemotherapy

• .3 Teratomas• .3.1 Sacrococcygeal Teratoma (SCT)• .3.1.2 Operative Treatment • .3.1.3 Open Fetal Surgery • .3.1.4 Postnatal Intervention• .3.1.5 Adjuvant Chemotherapy• .3.1.6 Long-Term Outcomes • .3.2 Head and Neck Teratomas • .3.2.1 Intracranial Teratomas • .3.2.2 Cervicofacial Teratomas• .3.2.3 Retroperitoneal Teratomas

NEUROBLASTOMA• .4.1 Clinical Presentation • .4.2 Diagnostic Evaluation• .4.3 Antenatal• .4.4 Postnatal • .4.5 Stage 4S Disease• .4.6 Treatment and Prognosis • .6.1 Stages 1 and 2• .4.6.2 Cystic Neuroblastoma• .4.6.3 Stages 3 and 4 • .4.6.4 Stage 4S

• 5 Soft Tissue Sarcomas • .5.1 Congenital Fibrosarcoma • .5.2 Rhabdomyosarcoma • .5.3 Non-Rhabdomyosarcoma Soft Tissue

Sarcomas

RENAL TUMOR• 6.1 Congenital Mesoblastic Nephroma • 6.2 Wilms’ Tumor

7 Liver Tumors • 7.1 Infantile Hepatic Hemangiomas • 7.2 Mesenchymal Hamartomas • 7.3 Hepatoblastoma

8 Retinoblastoma

Introduction/overview• Most solid tumors observed in early infancy are benign.• Malignant tumors diagnosed during the neonatal period are

rare. incidence of 1:27,000 live births in the USA . Management of affected infants is extremely challenging. Because factors such as drug absorption, metabolism, distribution,

• and elimination are affected by age and physiologic maturity, complications associated with the immature physiology of the neonate are common. Age-dependent maturation of the renal, hepatic, hematopoietic, and neurodevelopmental systems make the neonate particularly vulnerable to the deleterious effects of aggressive multimodal therapy involving extirpative surgery, chemotherapy, and radiotherapy .

• Over the past three decades, the long-term effects of administering anticancer therapies to neonates have become increasingly evident . An additional complicating factor is that many neonatal malignancies differ significantly from similar tumors in older children with respect to their biological behavior .

• Certain benign tumors (e.g., sacrococcygeal teratoma) may have malignant potential and undergo malignant change if untreated.

• Other tumors that are histologically malignant (e.g., fibrosarcoma) may exhibit benign behavior.

• Some benign tumors may be life threatening because of their size, anatomic location, and impact on infant physiology. Additionally, congenital neuroblastoma may have an unpredictable course, with many tumors involuting spontaneously and others progressing to a fatal outcome.

• Due to the rarity of malignant neoplasms in neonates, existing treatment protocols are based on studies that predominantly comprise older children.

• These protocols may not consider the unique aspects of treating perinatal tumors. In an effort to shed light on this topic, I will address the distinguishing clinical features, management, and prognosis of the most common perinatal neoplasms, including teratomas,neuroblastoma, sarcomas, renal and hepatic tumors, and retinoblastoma.

CLINICAL PRESENTATION• Nearly 50% of tumors occurring in neonates are observed at

birth; another 20–29% become evident within the first week of life

• teratomas and neuroblastoma account for approximately two thirds of reported neoplasms. The most common finding on physical examination is a palpable mass.

• Nonspecific symptoms such as irritability, lethargy, failure to thrive, and feeding difficulties may indicate the presence of an occult neoplasm.

Petechial hemorrhages and other hematologic abnormalities may indicate extensive bone marrow replacement by tumor cells such as neuroblastoma or leukemia .

The association between congenital abnormalities and tumors is well documented

15%

• Many such associations are related to chromosomal defects, particularly trisomies 13, 18, and 21. An increased incidence of (a).leukemia and retroperitoneal teratoma has been reported in neonates with Down syndrome , and (b).teratomas are associated with regional and distal congenital anomalies (cloaca, limb hypoplasia, and spina bifida)

Oncogenesis and Genetic Risk Factors

• Many neonatal malignancies are inherited or occur spontaneously as the result of a de novo mutational event.

• The etiology of these tumors is likely multifactorial,( genetic and environmental)

• . Both genetically determined syndromes and constitutional chromosomal defects may result in an increased risk of malignancy.

• Single gene malignancy-related syndromes and the familial associations of tumors .

• These anomalies have been identified in retinoblastoma (13q) and nephroblastoma (11p) . In Denys-Drash syndrome, there is an association genetic mutations located at 11p13 and WT1. These patients commonly have Wilms’ tumor.

• The specific site of the point mutation identified in most cases is located on the WT1 gene exon 9. Other examples of constitutional chromosomal anomalies associated with neoplasms include an increased risk of leukemia in patients with Down syndrome and a high frequency of poor-prognosis neonatal leukemia involving the 11q23 locus of the MLL gene. This specific genetic defect is rare in older children . Genes that confer a higher risk of neoplasia by enhancing susceptibility to oncogenic factors are likely to exist and may play a role in certain inherited syndromes. For example, there is an increased risk of hepatoblastoma and rhabdomyosarcoma in patients with Li-Fraumeni syndrome (p53 mutation)

Diagnostic investigation• The selection of imaging studies is dependent upon

suspected pathology, affected anatomic site, and differential diagnosis. Dramatic improvements in prenatal ultrasonography (US) and magnetic resonance imaging (MRI) have had a significant impact on prenatal diagnosis, management, and fetal outcome .

• Prenatal US has been particularly useful in identifying large sacrococcygeal or cervical teratomas that may complicate vaginal delivery or be responsible for intrauterine fetal demise or postnatal complications. US can also detect adrenal or thoracic masses in the fetus, providing useful information regarding both the nature of the mass and, in most cases, its origin.

Fetal MRI can better characterize and delineate specific anatomic details and the extent of tumor involvement.

• These complementary techniques help to facilitate the development of a comprehensive plan of action that determines the mode, timing, and location of delivery as well as the initial postnatal management strategy.

• Fetal surgery and the ex utero intrapartum treatment (EXIT) procedure have proven useful in treating nonimmune hydrops and congestive heart failure caused by neoplasms. The EXIT procedure has also been successfully used to salvage infants with high-grade airway obstruction caused by tumors .

• Contrast-enhanced computed tomography (CT) provides excellent postnatal images of most neoplasms, though it has limitations in evaluating intraspinal involvement.

• MRI, however, is particularly useful for evaluating tumors that involve the central nervous system or spinal canal. It is also extremely useful in the preoperative delineation of the vascular anatomy of the tumor and adjacent organs.

Cytogenetic• Cytogenetics is playing an increasingly important role

in the diagnosis, risk stratification, and monitoring of patients with neonatal tumors.

• Most cancer cells are thought to have a high incidence of chromosomal changes and genetic mutations that frequently are identifiable and, in some cases, are prognostically important. For example, N-myc amplification is a specific molecular marker that characterizes a subset of aggressive neuroblastomas that usually has a poor prognosis.

Therapeutic Interventions• Surgical extirpation remains the definitive treatment

modality in most neonates with solid tumors. • The timing of the surgical procedure and the surgical

strategies employed must take into account the physiologic and metabolic needs of the neonate. Avoidance of hypoglycemia and hypothermia, especially if significant fluid or blood replacement is required or prolonged exposure occurs are important considerations.

• The impact of surgery on the subsequent growth and development of the neonate can be profound, especially when major tumor extirpations are extensive or resection of unaffected tissues integral for normal structure and function has occurred.

• In some patients, appropriate surgical management may result in impairment of gastrointestinal or bladder function, ambulation, or future sexual function, thereby creating life-long physical and emotional burdens for patients.

• Interrupting or traversing normal growth centers in order to resect tumors can have a profound effect on structural symmetry and function. For example, intrathecal tumor removal extending over several vertebral segments often results in some degree of postlaminectomy scoliosis later in childhood. Preserving function and structure without compromising survival is thus the paramount principle guiding contemporary surgical and multimodal treatment strategies.

• For many patients in whom a tumor is initially unresectable (e.g., those with stage 3 neuroblastoma) or involves important structures that should be preserved, the administration of several courses of preoperativechemotherapy has been extremely beneficial.

• Th is approach has allowed delayed complete primary resection with preservation of vital structures, thus improving surgical outcomes and quality of life.

radiotherapy Many malignant tumors in childhood are radiosensitive,• Radiotherapy plays an important role in the management of

advanced-stage tumors. In light of the scarcity of neonatal data, however, treatment parameters such as dosing schedules have been extrapolated largely from data in older children. Because the neonate experiences rapid growth of organs and structures, radiotherapy has a profound impact on subsequent development. The sensitivity and detrimental effects of radiation therapy on the central nervous system, skeletal growth, and visceral organs appear to be inversely related to the child’s age and directly related to the radiation dose .

• In a seminal study of children younger than age 2 years, found that growth disturbances and musculoskeletal abnormalities were the most common late effects of radiation therapy.

Approximately 85% of patients had some degree of bone or soft tissue abnormality; this problem was most severe in children who had received thoracic or spinal irradiation. Other authors have documented a wide spectrum of significant late radiation effects, including scoliosis and severe bony deformities (70%) and delayed physical development . Children receiving radiation to the cerebrospinal axis for leukemia or brain tumors reportedly experience major delays in cognitive development, and infants treated with cranial irradiation have a high incidence of learning disabilities and mental retardation . Th e severity of these disabilities is strongly correlated with radiation dose. As in older children, other significant late effects of radiation therapy in neonates include breast agenesis, aortic arch dysgenesis, second malignancies (particularly leukemias and breast and thyroid cancer), and chronic renal and hepatic insufficiency .

Chemotherapy• The lack of substantial pharmacologic data on newborns

significantly complicates the administration of chemotherapeutic agents. Knowledge of drug interactions, metabolism and clearance, and toxicity are all areas of notable deficiency. They remain the focus of intense ongoing discussion and contemporary investigation.

• In an overview of a recent (2003) workshop concerning cancer pharmacology in infants and young children, a significantly greater incidence of neurotoxicity for vincristine, hepatic toxicity for actinomycin D, and ototoxicity for cisplatin was observed in infants and young children

• For virtually all of these older agents and the newer camptothecin agents, the limited available data indicate that weight-based dosing in young children normalizes the drug clearance profiles and may improve the toxicity profiles, bringing them in line with that of older children .

TERATOMA• Teratomas are embryonal neoplasms that contain tissues from at least two

of the three germ layers ( ectoderm, endoderm, and mesoderm). These neoplasms arise in both gonadal and extragonadal sites, with location

• thought to correspond to the embryonic resting sites of primordial totipotential germ cells. Tumor location correlates with the age of the patient. Teratomas occurring in infancy and early childhood are generally

• extragonadal, whereas those presenting in older children more commonly occur in the ovary or testis . More than 50% of teratomas are evident at birth and are most commonly seen in the sacrococcygeal area.

• Although more than one third of teratomas of the testis are recognized in the first year of life, these lesions are rarely diagnosed in the neonatal period. The sacrococcyx is also the most common extragonadal location irrespective of age (45–65%) . Cervicofacial and central nervous system tumors and tumors of the retroperitoneum are seen less frequently. Teratomas presenting in the mediastinum, heart, and liver are rarely seen. Excluding testicular teratomas, 75–80% of teratomas occur in females. Approximately 20% of tumors contain malignant components, the most common being endodermal sinus tumor.

• During the course of the second National Wilms’ Tumor Study, the prescribed doses of actinomycin D, vincristine, and doxorubicin were reduced by 50% due to observed excessive myelodepression in infants younger than 1 year of age.

• Interestingly, reduction of dose did not compromise therapeutic eff ectiveness. A similar dose reduction approach was followed in the Intergroup Rhabdomyosarcoma Study protocols.

• Excessive drug-related toxicity has not been observed in infants with leukemia. Moreover, reduced dosage protocols have had a detrimental effect on clinical response and outcome.

• Teratomas are embryonal neoplasms that contain tissues from at least two of the three germ layers ( ectoderm, endoderm, and mesoderm). These neoplasms arise in both gonadal and extragonadal sites, with location

• thought to correspond to the embryonic resting sites of primordial totipotential germ cells. Tumor location correlates with the age of the patient. Teratomas occurring in infancy and early childhood are generally

• extragonadal, whereas those presenting in older children more commonly occur in the ovary or testis . More than 50% of teratomas are evident at birth and are most commonly seen in the sacrococcygeal area.

• Although more than one third of teratomas of the testis are recognized in the first year of life, these lesions are rarely diagnosed in the neonatal period. The sacrococcyx is also the most common extragonadal location irrespective of age (45–65%) . Cervicofacial and central nervous system tumors and tumors of the retroperitoneum are seen less frequently. Teratomas presenting in the mediastinum, heart, and liver are rarely seen. Excluding testicular teratomas, 75–80% of teratomas occur in females. Approximately 20% of tumors contain malignant components, the most common being endodermal sinus tumor.

• A wide range of congenital anomalies is seen in association with teratomas, and the type of anomaly frequently depends on the tumor site and size. Single or combined malformations of the genitourinary tract, rectum, anus,vertebrae , and caudal spinal cord are sometimes found in patients with extensive sacrococcygeal teratomas . Disfiguring cleft palate defects are found in newborns with massive cranial and nasopharyngeal teratomas .

• Teratomas can present as solid, cystic, or mixed solid and cystic lesions. Most teratomas that are present at birth consist of ectodermal and mesodermal

• components. Epidermal and dermal structures such as hair, sebaceous glands, sweat glands, and teeth are frequently present. Virtually all teratomas have mesodermal components, including fat, cartilage, bone, and muscle. Endodermal components commonly include intestinal epithelium and cystic structures lined by squamous, cuboidal, or flattened epithelium . Pancreatic,

• adrenal, and thyroid tissue, as well as mature and immature neuroepithelial and glial tissue is also frequently seen

• Tumors are histologically classifi ed as either mature or immature, with most pediatric teratomas classified as mature. These tumors exhibit an absence of coexisting malignant cells and little or no tendency to malignant

• degeneration. They nevertheless may be fatal if the airway is compromised or if vital structures such as the brain or heart are involved. Moreover, depending

• on location and size, even benign tumors may be inoperable and incompatible with extrauterine life.

• Although useful tumor grading systems have been developed , these systems are of limited use in regard to the fetus or newborn in that embryonic or

• immature elements may be appropriate for the stage of development .

• Regardless of tumor grade in these patients, immature teratomas are associated with a favorable prognosis, and only in rare cases does immature

• neuroglial tissue metastasize to adjacent lymph nodes, lungs, and other distant organs from an immature primary site .

• The most important predictor of recurrence in pediatric immature teratomas appears to be the presence of microscopic foci of yolk sac tumor [58]. Because of their small size, these tumors may be missed by the pathologic sampling process. Such oversights may account for metachronous metastases after resection of the immature teratoma metastasis.

• In general, the prognosis of neonates depends upon the resectability of the tumor and the presence of metastases or metastatic potential.

TERATOMA• Definisi • Adalah tumor pada bayi dan anak yang dibentuk dari 3

macam jaringan Germinativum. Teratoma dapat ditemukan pada berbagai umur dan bisa bersifat Benigna atau Maligna.

• Umumnya terdapat pada daerah Sakrokokigius, ovarium, testis dan retroperitoneum walaupun dilaporkan juga dapat dijumpai di otak, mulut, leher, rongga perut, Mediastinum dan jantung.

Patofisiologi• Karena berasal dari sel Germinativum, maka

sangat sering di gonad dan daerah sakrokokigius.• Bentuk benigna menyebabkan penekanan organ

sekitar dan puntiran.• Sedangkan yang malignan dapat menginvaginasi

dan metastasis.• Jaringan endokrin yang berfungsi kadang-kadang

ditemukan dalam teratoma dan dapat memberi gejala. seperti ditemukannya sekresi insulin dan Gonadotropin oleh jaringan tumor.

Teratoma Ovarium• Merupakan teratoma yang paling sering.

Teratoma ovarium merupakan 70 % dari seluruh kasus tumor ovarium.

Teratoma SakrokoksigusGambaran Klinis• Merupakan teratoma yang hampir selalu dapat dijumpai begitu anak

lahir. Ukuran teratoma ini sangat bervariasi dari tak tampak sampai massa besar yang menyebabkan gangguan persalinan / distosia. ¾ kasus teratoma ini ditentukan pada anak perempuan.

Artman membagi teratoma Sakrokoksigus menjadi 4 tipe menurutletaknya :• Tipe I :Bila sebagian besar ditemukan diluar rongga pelvis.• Tipe II :Bila bagian yang terletak diluar dan didalam rongga

pelvis hampir sama• Tipe III :Bila sebagian besar ditemukan didalam rongga pelvis• Tipe IV :Bila teratoma terletak didalam rongga pelvis.

DiagnosisMassa tumor biasanya jelas tampak pada pemeriksaan fisik, tapi bila kecil, tumor baru ditemukan setelah umur beberapa bulan atau tahun yaitu setelah tumor tumbuh membesar.Pada colok dubur teraba massa di posterior rektum sakrum biasanya normal.

pemeriksaan radiologi khusus.– Diferensial Diagnosis

• Myelomeningokel ; letaknya lebih ke cranial, biasanya berhubungan dengan kelemahan otot tungkai atau perineum. Dengan penekanan massa tampak benjolan Fontanela/ubun-ubun besar. Pada pemeriksaan radiologik sakrum tampak Disraphism.

Penanganan Pada dasarnya dilakukan eksisi tumor

lengkap disertai tulang ekornya (Coccyx). Bila tumor sangat besar dan meluas sampai intra pelvis diperlukan insisi laparotomi.

Prognosis• Teratoma Sakrokoksigus, berhubungan erat

dengan umur saat dilakukan operasi. 90 % teratoma sakroksigus bersifat benigna, tetapi bila tumor diangkat setelah umur 2 bulan maka kemungkinan yang terjadi ganas adalah 90 %.

• tumornya dgn jaringan benigna, tak diperlukan terapi lain. Jarang terjadi rekuren kl ada perlu reeksisi – hasil baik.

• Jika tumor Malignan (Embrional Karsinoma, Yolk Sac Carcinoma Germinoma), diperlukan pemberian khemoterapi adjuvantiva Bila terjadi rekurensi maka prognosisnya jelek .

Teratoma Lain

• Retroperitoneal Teratoma : Tumor dapat tumbuh dalam jaringan ginjal sehingga sulit dapat dibedakan dengan Wilm’s tumor. Tumor ini sering menyebabkan obstruksi usus karena penekanan.

• Pada pemeriksaan radiologi tampak kalsifikasi dan kadang-kadang tampak gambaran gigi.

Sacrococcygeal Teratoma (SCT)

• 9.3.1.1 Clinical Presentation and Diagnosis• SCT is the predominant teratoma as well as the most common

neoplasm of the fetus and newborn. The tumor has an estimated incidence of 1:20 000 to 1:40 000 live births and a female predominance ranging from 2:1 to 4:1 .

• Ten percent to 20% of patients with SCT have coexisting congenital anomalies such as tracheoesophageal fistula, imperforate anus, anorectal stenosis, spina bifida, genitourinary malformations,meningomyelocele, and anencephaly . Also, many patients have significant structural abnormalities of juxtaposed organs resulting from displacement by a large teratoma.

• A classification system developed by Altman, et• al.divides SCTs into four distinct anatomic types that differ in the degree of

intra- and extrapelvic extension (Fig. 9.3).• Type I (46.7%) is predominantly external, with minimal presacral extension.

Type II (34.7%) arises externally and has a signifi cant intrapelvic component. Type III (8.8%) is primarily pelvic and abdominal but is apparent externally. Type IV (9.8%) is presacral and has no external manifestation.

• Th e incidence of malignant components not only correlated with anatomic type (8% in type I vs. 38% in type IV) but also with age at diagnosis and gender; however, the size of the tumor was unrelated. The rate of malignancy of tumors in older infants (>6 months) and children is significantly higher than that of the visible exophytic tumors seen in neonates. Malignant change appears to be more frequent in males, particularly those with solid

• versus complex or cystic tumors . The most common malignant elements identified within sacrococcygeal lesions are yolk sac tumor and embryonal

• carcinoma (Fig. 9.4) .

• In countries where antenatal US screening is carried out, most large SCTs are diagnosed before birth.

• Uterine size larger than expected for a gestational date ( polyhydramnios or tumor enlargement) is the most common obstetrical indication for initiating maternal-fetal US examination. Sonography may reveal an external mass arising from the sacral area of the fetus (Fig. 9.5). This mass is composed of solid and cystic areas, with foci of calcification sometimes apparent.

• Most prenatally diagnosed SCTs are extremely vascular and can be seen on color-flow Doppler studies.

• Lumbosacral myelomeningocele is the most likely condition to be confused with SCT. Lumbosacral myelomeningocele and cystic SCT may show similar fi ndings on US. Since both are associated with elevated maternal levels of alpha fetoprotein (AFP), these levels are not helpful in distinguishing between the two entities.

• Bayi dan anak berbeda secara fisiologi dengan orang dewasa demikian juga jenis jaringan tumor, dan efek terapi jangka panjang terhadap perkembangan anak dalam pertumbuhannya maka penanganan tumor ganas pada bayi dan anak perlu dibahas tersendiri.

• Hasil terapi tumor pada bayi dan anak telah mengalami kemajuan yang pesat, terutama karena kemajuan pembedahan, khemoterapi dan radioterapi. Hal tersebut ditunjang dengan adanya penelitian dan kerjasama antara ahli terkait.

• Protokol penanganan tumor pada bayi dan anak tidak hanya telah meningkatkan hasil terapi, tetapi membuatnya lebih aman bagi anak. Ini sangat berbeda dengan tumor pada dewasa.

Prinsip Pembedahan

• yang pertama harus dilakukan oleh ahli bedah adalah eksplorasi seluruh

rongga abdomen atau rongga dada secara teliti untuk menilai perluasan dari

penyebaran tumor sehingga bisa dilakukan staging dan mengetahui apa perlu

diberikan adjuvant khemoterapi selain menentukan apakah tumor dapat

diangkat atau tidak.

• Bila tumor tak dapat diangkat, artinya tumor ini telah melibatkan struktur vital

atau kritis, atau menurut penilaian ahli bedah, sulit dan berbahaya, maka

hanya dilakukan biopsi saja kemudian diberikan khemoterapi atau

radioterapi.untuk menyusutkan/mengecilkan massa tumor. Reseksi tumor

biasanya memungkinkan pada “Second Look” operasi. Jika tumor tak dapat

diangkat total, dengan berkurangnya massa tumor karena partial reseksi, dapat

menambah keefektifan obat khemoterapi.

Tindakan heroic• “Prinsip tumor harus dapat diangkat”. Seluruhnya, mengorbankan

organ sekitar atau membahayakan penderita tidak dibenarkan, • Jika mengangkat tumor , maka jangan dilakukan pengangkatan

organ seperti uterus atau kandung kencing dahulu tetapi lakukan biopsi atau partial reseksi dan diikuti pemberian khemoterapi.

• Beberapa tumor adanya metastase jauh bukan berarti incurable.• Neuroblastoma pada bayi yang bermastase ke hepar, sumsung

tulang ,kulit biasanya survive setelah tumor primernya diangkat.• Metastase paru dari Wilms’ Tumor, Osteosarkoma dan beberapa

tumor lain jika bersifat isolated dapat diangkat atau di eradikasi dengan khemoterapi atau radioterapi.

Prinsip Khemoterapi

• obat Khemoterapi sangat efektif pada saat pembelahan sel. Karena pembelahan sel tumor tak terjadi pada waktu yang sama, maka pemberian secara berulang perlu dilakukan.

• Makin kecil massa tumor, makin efektif obat khemoterapinya. Karena itu hasil terbaik didapatkan jika pemberian khemoterapi dilakukan setelah operasi.

• Pulse terapi yaitu pemberian khemoterapi yang menggunakan dosis tinggi dan diberikan dalam rentang waktu lama.

Prinsip Radioterapi

• Pancaran radiasi ionisasi selain merusak sel yang bermitosis dan imatur juga merusak sel normal. Masalah itu dapat diatasi dengan menggunakan High Voltage Energy dan Refinement Dosage dengan menggunakan metode atau teknik lebih tepat sasaran.

• Side efek jangka panjang akan menyebabkan gangguan pertumbuhan, gangguan fungsi ginjal, hati, paru dan gonad. Karena radioterapi ini juga berefek onkogenesis, maka dapat menyebabkan timbulnya Second Malignancy. Apalagi bila disertai pemberian khemoterapi.

WILMS’ TUMOR (Nephroblastoma)

Definisi • Adalah tumor kongenital yang berasal dari jaringan embrional

ginjal / Nephroblast ; Angka kejadian 8 : 100.000 anak/ tahun. Tumor ini merupakan tumor abdomen tersering pada anak dan sangat mudah disembuhkan. Tersering adalah umur 3 tahun, 1/3 penderita terdiagnosis dibawah umur 2 tahun. Tak ada perbedaan antara ras dan jenis kelamin.

Patofisiologi

• Secara histologis tumor Wilms’ terdiri dari campuran jaringan Mesensim dan Epitel dengan berbagai stase maturasi.

• Tampak sel blastoma ginjal, Glomerulus dan tubulus. • Gambaran anaplastik terjadi pada 10 % kasus dan berprognosa jelek.• Pertumbuhan Neoplastik menyebabkan distorsi jaringan ginjal

normal, jarang menyebabkan obstruksi, perdarahan atau nyeri. Tumor biasanya tak terdeteksi sampai ukuran besar (Silent For Along Time).

Gejala Klinik

• Tampak sebagai massa intra abdomen yang tak bergejala. Tumor mudah diraba oleh orang tua dan dokter pada pemeriksaan fisis.

• Keluhan dan nyeri perut jarang dijumpai, hilang nafsu makan,dan kehilangan berat badan sering dijumpai. Hematuri 20 % kasus.

• Pemeriksaan fisis: Terasa tumor yang keras, dan terfiksasi pada daerah Retroperatoneum. Tumor juga tak bergerak mengikuti pernafasan. Hipertensi bisa juga terjadi.

• Kelainan yang menyertai 15 % dengan Hipospadia, Duplikasi saluran kencing, Hemihipertrofi dan Aniridia.

• Metastase paru 5 - 7 % dijumpai preoperasi dan 7 % dengan Metastase Intra Abdomen.

Diagnosa Pemeriksaan saat ini adalah CT Scan,

pemeriksaan ini dapat membedakan dgn tumor2 lain seperti ( Neuroblastoma ), dapat mengetahui penyebaran intra abdomen,Kelenjar Limfe; , vena cava dan fungsi ginjal kontra lateral sekaligus.

• Dengan IVP tak dapat mencapai kebutuhan informasi sebanyak CT Scan.

• Ateriografi dan venografi tak diindikasikan kecuali hasil CT tak jelas apakah tumor ginjal atau hepar.

Permasalahan Differessial Diagnosa• Hidronefrosis• Neuroblastoma• Ginjal Multikistik • Tumor Ginjal atau tumor Retro Peritoneal lain

• Tumor Wilms’ Bilateral• Dilakukan reseksi lokal / Nodul dan pemberian

Khemoterapi•

Penanganan • Stage I :Tumor lokal, dapat di eksisi lengkap• Stage II :Tumor Invasi Lokal atau Spill, dapat

dieksisi lengkap.• Stage III :Tak dapat di eksisi lengka, massive

spillage of Tumor atau kelenjar Limfe Regional positif.

• Stage IV :Penyebaran / Metastase jauh : Paru atau

Hepar

Pembedahan• Pengangkatan jaringan tumor adalah penting. Penemuan

Macro Operasi menentukan stage tumor. Jika tumor tak dapat di reseksi, maka hanya dilakukan biopsi dan staging saja. Kemudian diberikan Khemoterapi untuk mengecilkan tumor serta dilakukan pembedahan kembali setelah 6 – 8 minggu.

• Khemoterapi • Diberikan untuk semua penderita. Tumor Wilms’ sangat

responsif terhadap actinomisin dan vincristin. Doxorubisin ditambahkan bila :– Ada Metastase– Unfavorable Histologik

Radioterapi

• Diberikan Bila :• Masih terdapat gross residual tumor

setelah eksisi tumor.• Histologik Unfavorable• Metastase Paru

Persiapan Pembedahan

• Thorax Foto : Untuk melihat Gross metastase

• Urine untuk VMA (Vanillyl Madelic Acid) pada neuroblastoma

• Darah untuk transfusi selama operasi

Prognosa

• Tergantung pada :• Stage / stadium• Gambaran Histologik• Ukuran Tumor• Umur : Makin muda makin baik

Hasil Akhir

• Survival Rate :• Stage I : 95 %• Stage II :85 %• Stage III :75 – 80 %• Unfavorable :25 – 50 %

• BREAK• ISTIRAHAT 10 MENIT

NEUROBLASTOMA• Definisi • Neuroblastoma tumor berasal dari jaringan

Neural Crest sepanjang Ganglion simpatik atau medula Suprarenalis .

• tersering pada abdomen 75 %, Mediastinum Posterior 20 %, leher dan organ lain. 5 % berkembang pada Medula Supra Renal.

• Angka Kejadian : 1 : 10. 000.

PatofisiologiNeuroblastoma sangat unik karena :– Dapat mengalami Maturasi– Berubah menjadi bentuk benigna– Menjadi ganglioneuroma– Bahkan menghilang

• Karena itu diperkirakan bahwa suatu Neuroblastoma kecil ditemukan pada bayi dengan angka kejadian 100 kali dengan angka kejadian penderita dengan tumor pada kehidupan lanjut.

• Katekolamin dan produk pemecahan metabolismenya ditemukan pada 90 % kasus Neuroblastoma yaitu berupa Adrenalin, Neoradrenalin, Dopa, Metanephrine, Homovanillic Acid, Vanillyl Mandelic Acid dan Vanillyl Glicolic Acid. Marker ini berguna untuk mendeteksi adanya rekurensi setelah pengangkatan tumor.

• Metastase tejadi dini dan berprognosa buruk. Tempat yang sering adalah : sumsum tulang, hepar,KGB, kortek tulang dan paru. Kadang-kadang juga bermetastase sebagai Nodul Subkutan.

Menjadi ganglioneuromaBahkan menghilang

• .

LOKASI PENYAKITDitemukan disemua tempat sel simpatikMedula adrenal (40 -60 %)Retroperitonial lainnya (20%)Mediastinum (10 %)Pelvis (2-6 %)Leher (2%)

Gejala Klinik• Neuroblastoma adalah tumor pada anak dan 50 % sebelum 2 tahun, 90 %

sebelum 8 tahun.• Adanya massa pada abdomen 75 %.• Kehilangan berat badan, nyeri perut, distensi, demam, anemia dan

kegagalan tumbuh kembang oleh karena gejala hipertensi 25 % yang disebabkan oleh adanya Katekolamin.

• Tumor pada mediastinum sering tak bergejala kecuali bila melibatkan Ganglion Stelata yang menyebabkan Horner’s Sindrom. Jarang terjadi distres nafas atau disfagia karena penekanan pada bronkhus atau Esofagus.

• Ptosis dan Periorbital Ecchymoses adalah gejala pertama dari Metastase orbital.

• Para Plegi akibat tumor menekan Spinal Cord.• Timbulnya Flushing (Kulit kemerahan), berkeringat dan iritability akibat

adanya katerolamin.• Ataxia Serebelar, Opsomioklonus dan Nistagmus sering ada oleh sebab

yang tidak diketahui.• Diare terus-menerus oleh adanya VIP (Vasoartive Intestinal peptide) yang

diproduksi tumor.

GEJALA KLINIS Tergantung letak tumor dan penyebarannya Tampak massa abdomen Anoreksia Malaise Nyeri abdomen Diare Tulang : nyeri tulang Vertebra : paralisis Leher: respiratory distressOrbita : ptosis, sweling periorbita, ekimosisHati : regresi spontan

Diagnosis CT Scan dan MRI• Dapat dijumpai adanya Kalsifikasi halus 80 %. Terlibatnya pembuluh darah

besar, perluasan ke hati, ginjal dan organ dapat ditemukan dengan CT Scan; juga metastase paru.

• Yang berbeda dengan Wilms Tumor oleh karenanya Wilms tumor berasala dari ginjal

• tumor neuroblastoma ini besar dan menginvasi jaringan sekitar sangat sulit dibedakan perioperatif.

• Neuroblastoma mediastinal berlokasi diposterior dan hampir selalu mennyebabkan erosi foramen nervus spinalis dan erosi pada segmen posterior tulang IGA.

• Metastase sumsum tulang ditemukan dengan pemeriksaan aspirasi sumsung tulang.

• Pemeriksaan isotop scan dan skeletal survey dilakukan untuk mengetahui metastase ke tulang.

• Myelografi dilakukan pada penderita tumor mediastinal dengan gangguan neurologik karena kompressi sumsum tulang belakang akibat ”Dumbbel” Tumor.

Penanganan• Pengankatan tumor primer adalah terapi utama.• Khemoterapi dan Radioterapi dan prognosis tergantung ; staging .• Stage I :Tumor pada satu organ, dapat direksesi lengkap.• Stage II :Tumor meluas keuar organ tapi belum menyilang garis

tengah.• Stage III :Tumor melewati garis tengah, tak dapat direseksi atau

meninggal sisa.• Stage IV :Metastase jauh ke organ dan tulang.• Stage IV S:Tumor stage IV pada pasien umur dibawah 1 tahun dengan

metastase terbatas ke hepar, kulit dan sumsum tulang.• Khemoterapi ; tak memuaskan, pengecilan tumor yang didapatkan

dengan khemoterapi atau radioterapi tak memperbaiki hasil Cure Rate.• Total Body Irradiasi dan Transpantasi sumsum tulang belakang tak

menunjukkan hasil yang baik.• Sifat Imuunologis, Limfosit dapat menghambat pertumbuhan tumor

pada kultur jaringan.

prognosa Hasil terapi neuroblastoma tergantung dari umur, stage, letak tumor dan

derajat maturitas tumor.

• umur muda prognosis lebih baik• Bayi : 75 %• 1 – 2 tahun : 50 %• Lebih 3 tahun : 20 %

• Stage dan survival rate• Stage I : 90 -100 %• Stage II : 80 %• Stage III : 35 – 50 %• Stage IV : 10 – 20 %• Stage IV S : 80 % Tumor abdomen : 1/3 Survive• Tumor Mediastinel dan leher : 80 – 100 % Survive. Bayi dengan opsomyoclonus atau Vip diare : Pronosis baik dengan survival

lebih 80 %.

TUMOR TESTIS PADA ANAK

INCIDEN : 1-2% dari seluruh tumor anak Benign >pada anak dari pada dewasa Peak incidens umur 2 tahun. Pada pubertas <dari pada umur 2tahun 65% Germ Ceel Tumor

PEMBAGIAN :A. Ca INSITU (C.I.S)B. GERM CELL TUMOR : (YORK SAC TUMOR (PL. SERING), TERTOMA, TERATO Ca,

SEMINOMA).C. NON GERM CEEL TUMOR : 1). TU. CEEL LEYDIG, 2). TU. CEEL SIRTOLI, 3).

GONADOBLASTOMA.

GEJALA KLINIKMass yang tidak nyeri :

• Tak tegang• Tak trans luscen• Urinalisis tak abnormal

DD : HERNIAHDROKEL

** Bila tumor timbul pada UDT mudah torsi Acute abdominal pain. **

PEMERIKSAANBila ada Tumor Testis maka dilakukan :1. USG Sensitifitas tinggi sehingga dapat menemukan

Tumor testis yang ada dalam hidrokel. Color dan power Doppler US :> baik

2. MRI Bila Tumor kecil dengan gejala fungsional yang tak dapat di USG : T. Sel Leydig.

3. CT Harus dilakukan bila kita mendiagnosa Ca untuk melihat pembesaran ln. RETROPERITONEAL , - CT. dapat menggantikan fungsi R.P.L.N.D. untuk stangging tumor, - untuk melihat metastase

4. Ro”. Thorax : Melihat metastase5. Serum Marker : 1). Untuk DX, 2). Follow up R/.

** antara lain : A.F.P. suatu glucoprotein yang dihasilkan : - Fetal york sac, - Liver, - G.I.tract **

I. INTERAKSI ENDOKRIN

I. Peran Androgen Dehidrotestoteren

HIPOFISE ANTERIOR

GONADOTROPIN

LH F.S.H

SEL LEYDIG

INTERTITIEL

PLACENTA

HCG

EPIDERMAL

GROWTH FACTOR

TESTEL

Maternal

Estrogen

N. Genito

Femoralis

SEL SIRTOLI

Spermatogenesis

Mg IX

Efek L.H

Testoteron Dehiorotestosteron

Descensus

Testis (DT)

CGRP

Pertumbuhan gubernaculum

Dilatasi can Inguinalis Membentuk jalan

bagi testis

Kontraksi

Creamster

DESCENDIN

(Androgen indipendent growth faktor

Pertumbuhan

Reduksi

Mencegah

Obstruksi anatomi

Mg VI-VII

MIF

CARCINOMA INSITU (CIS)• CIS :

• Suatu lesi premalinan• 50% Ca testis• CIS yang berkembang pada UDT dan intersec Ca

– Bila Os. UDT Prepubertas Orchiopexy + biopsi, bila hasil CIS – maka post pubertas Biopsi ulang

– Pada orang dewasa dengan Orchiopexy 1.7 – 3% CIS

CIS

PREPUBERTAS

BIOPSI ULANG Setelah Pubertas

(Post Pubertas

D E W A S A

-Pemeriksaan tiap tahun- USG tiap tahun

Dibeberapa negara : - Low Dose radiasi, - Biopsi Contra Lateral

GERM CELL TUMOR1. York sac tumor (Y.S.T)

– Bentuk pl. sering pada prepubertal testis tumor.

– Pl. sering pada 2 tahun pertama kehidupan

– Macroscopic : 1. Adanya SCHILLER DUVA BODIES2. Mengand AFP

METASTASIS– Ke Retroperitoneal : Jarang– Pada anak 95% terbatas pad testis– Metastase jauh pl. sering : paru-paru– S.Y.S.R : 99%

STANDAR TERAPI : Radical Inguinal Orchioctomi

– R.P.L.N.D. pada anak masih contraversi– Pada R.I.O. : Pertama-tama seperti

cord di klem/ligosise proximal manglin untuk mengurangi metastase waktu. Manipulasi testes sp. Cord + pada diangkat mell. Can. Ing.

STRATEGI Y.S.T

Tak

meningkat

FOLLOW UP AFP

R. I . O

Mening –

kat

Tidak -RPLNDRPLND

GERM CELL TUMOR

1. York sac tumor (Y.S.T)– Bentuk pl. sering pada prepubertal

testis tumor.– Pl. sering pada 2 tahun pertama

kehidupan– Macroscopic :

1. Adanya SCHILLER DUVA BODIES2. Mengand AFP

METASTASIS– Ke Retroperitoneal : Jarang– Pada anak 95% terbatas pad testis– Metastase jauh pl. sering : paru-paru– S.Y.S.R : 99%

STANDAR TERAPI : Radical Inguinal Orchioctomi

– R.P.L.N.D. pada anak masih contraversi– Pada R.I.O. : Pertama-tama seperti

cord di klem/ligosise proximal manglin untuk mengurangi metastase waktu. Manipulasi testes sp. Cord + pada diangkat mell. Can. Ing.

STRATEGI Y.S.T

Tak

meningkat

FOLLOW UP AFP

R. I . O

Mening –

kat

Tidak -RPLNDRPLND

Stage ITU. Terbatas pada testesTindakan : - RIO

- CT Lihat RPLN- Periksa Periksa tumor marker AFP

Th. I : Follow up tiap bulan T. marker, CT ABD, RoTHTh. II : Follow up T. Marker adalah 2 bulan

RoTH adalah 2 bulanCT ABD adalah 6 bulan

Th. III : Follow up adalah 6 bulan – 1tahun

Stage IITu. Metastase micro pada RPLN- Bila tujuan utama terdiagnose mell biopsi transcrotal maka selain RIO juga dilakukan

Hemiscrotektomi oleh karena drainase limfe scrotum Ln Inguinal Khemoterapi :VAC (Vincristine, Actinomisin D, Cyclofofa) dengan tanpa – Adriamicin, Etoposide, - Blcomisin , vinblastinSY.S.R 100% pada primary germ cell tetap pada testis.

Stage III

• Tampak penyebaran RPLN iniaging dan yang ditandai dengan adanya peningkatan tumor marker setelah orchhiectomi sebagai tanda adanya penyebaran tersembunyi

• Tindakan RPLND sebagai pengobatan tak umum dilakukan pada anak. Sebab perbaikan sudah dapat dilakukan dengan KHEMOTERAPI

Stage IV- Sudah ada penyebaran diluar retroperitonem dan viscera lain

TERATOMA- Mengandung 3 macam jaringan embrional- Pada prepubertal gambaran jinak Tindakan :

Pada anak > tua Cenderung metastase , Dialkukan R.I.O

III. TERATOCARCINOMA- Mixed germ cell tumor- 20% dari seluruh germ cell tumor- Mengadung campuran YST, Embrional Ca, Chasio Ca,

Seminoma1. Chosio Ca, Pragnoses jelek2. Tratoca terbatas pada testis 80%

RPLND biasanya juga dilakukan mskipun pada stage I, stage II dan seterusnya Khemoterapi

IV. SEMINOMA- Jarang pada anak- Dilakukan R.I.O. dan Retro peritoneal L.N. Radiasi

NON GERM CELL TUMORGONADAL STROMAL TUMOR

1) Leydig cell tumor2) Sirtoli cell tumor3) Gonado blastoma

1. TUMOR SEL LEYDIG( LEYDIG SEL TUMOR )

• Paling Sering• Umur terbanyak 5-9 tahun• Memproduksi : – Testoteren , Androgen lainGelaja : Pubertas Pecox• Tumor testis yang tak nyeri• GynecomastiaDD adanya pubertas Precox1. Lesi Pituitary 2. Adrenal Hiperplasia :

1. Glucocorticoid2. Mineralocorticoid3. Androgen

Untuk membedakan dilakukan pemeriksaan Pituitary Adrenal axis dengan 1. Pengukuran 17 Kortikosteroid2. Dexanuthazon suppresion test

Diagnosa : Patognomonis “ Reinke’s cristal” ditemukan 40% penderitaTerapi : Standar Op R.I.O, dapat juga dilakukan Enucleasi testis sebelah.Prognosa : Cendereng jinak.

2. SIRTOLI CELL TUMOR– Jarang– Prognosa : Cenderung jinakGejala : – Pembesaran testis yang tak nyeri – Gynecomastia : walaupun jarang

3. GONADOBLASTOMA– Berhubung dengan intersex– Chromosom 46xy

• Fenotipe : Female• Dengan Intra abd testis

Gejala :– Anak agak Virilizasi– 1/3 penderita mengalami tesi bilateral– Gambaran klinik : Jinak/benigna– Tapi komponen tumor ini dapat bergenerasi Maligna.Terapi : Gonadectomi

T. U. bila pasien phenotipe wanita

TORSI TESTIS• Emergensi US sering pada saat UG. Anak• Dsb juga Acute Scrotum• Bila terlambat ditangani kehilangan testis

DIAGNOSA DIFERENSIALI. Mayol DD

I. Torsi appendiculas : I.Testis AppendixII.Epididymis AppendixIII.Paradidymis AppIV.Vas Aberrans

II. Epididymitis/orchitisIII. InfeksiIV. Trauma

II. Minor DD :• Idiopatic scrotal edema• Hernia/hidrokel• Henoch scholein purpura• Tumor Testis

INSIDENS – Baru lahir – 70 thn– Paling sering :» Akhir masa anak (± 14 tahun)» Awal adolescence (± 14 tahun)

Gejala Klinik1. Nyeri : 80%

– Sifat Nyeri : • Grandual atau tiba-tiba• Menjalar ke atas – inguinal atau kwadran bawah perut.

– Berhubungan dengan gejala G.I seperti mual, muntah2. Pemeriksaan Fisis

– Pemeriksaan yang gentle dan teliti dapat membedakan antara tenderness oleh karena epididymitratan testicular tendenss (Torsi testis) atau appendicular tenderness (Torsi appendix).

– Posisi abnormal testis dalam kantong scrotomi yaitu tranversal– Letak/posisi anterior dari epididymis– Elevasi testis oleh karena pemendekan Spermatic cord– Hilangnya rejler cremaster

KASUS PALING SERING• Nyeri perut bawah pada penderita dengan scrotum kosong

dengan/tanpa mass pada inguinal kemungkinan torsi dari testis yang undescensus

• Bila kita DX suatu hernia inguinalis incarcerata lihat juga scrotomnya bila testis (-) mungkin suatu torsi UDT.

TERIMA KASIH