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3. Giant Cell Tumor

GIANT  CELL TUMOR

Oleh Dr H Subagyo SpB - SpOT

 

BAB I

PENDAHULUAN

Neoplasma adalah pertumbuhan sel baru, abnormal, progresif, dimana sel-sel tersebut tidak pernah menjadi dewasa. Istilah tumor sering digunakan sebagai pengganti istilah neoplasma, walaupun sebenarnya kurang tepat, karena tumor hanya berarti benjolan. Insidens neoplasma tulang bila dibandingkan dengan neoplasma jaringan lain adalah jarang. 1

Neoplasma dapat bersifat jinak atau ganas. Dikatakan ganas bila neoplasmanya mempunyai kemampuan untuk mengadakan anak sebar (metastase) ke tempat organ lain dan disebut juga dengan istilah kanker. Neoplasma jinak tidak mengadakan metastase ke tempat atau organ lain. Neoplasma tulang primer merupakan neoplasma yang berasal dari sel yang membentuk jaringan tulang sendiri, sedangkan neoplasma tulang sekunder merupakan anak sebar (metastase) ganas organ bukan tulang ke tulang. 1

Berdasarkan penilaian klinis, radiologis, dan histologis yang cermat dari masing-masing neoplasma tulang, maka dapat ditentukan staging neoplasma tersebut. Dengan menetapkan staging neoplasma tulang, maka dapat ditetapkan terapi yang tepat, memperkirakan prognosis, kemungkinan ada tidaknya rekurensi lokal atau metastasis di kemudian hari. 1

Diagnosis neoplasma tulang didasarkan pada :

  1. Evaluasi klinis yang dimulai dengan anamnesis dan pemeriksaan fisik. Adalah penting mengetahui umur penderita dan lokasi neoplasma, karena dari kedua keterangan ini dapat dipikirkan kemungkinan jenis neoplasmanya
  2. Pemeriksaan Radiologi berupa : Pemeriksaan x-ray biasa, bone scan, tomograti, angiograti, (CT-scan, sampai ke pemeriksaan yang mutakhir seperti Magnetic Resonance Imaging (M R I)
  3. Biopsi. Agar terapi dapat tepat berhasil, maka harus ditentukan diagnosis histologis yang akurat, dimana diperlukan biopsi. Biopsi dapat berupa Biopsi Insisional atau Eksisional

Pada biopsi insisional, dilakukan pengambilan sebagian jaringan neoplasma, sedangkan biopsi eksisional, seluruh neoplasma dieksisi, biasanya dilakukan pada neoplasma yang berukuran kecil. 1

Sebaiknya, tindakan biopsi dilakukan oleh dokter juga yang akan mengerjakan tindakan definitif terhadap neoplasma yang bersangkutan, terutama pada neoplasma yang dicurigai bersifat ganas. 1

Jaringan tulang rangka dewasa dibentuk oleh empat komponen, yaitu tulang, tulang rawan, jaringan ikat, dan sumsum tulang, dimana dari keempat komponen ini dapat timbul neoplasma. Dengan demikian, neoplasma tulang dapat diklasifikasikan atau digolongkan secara histologis menurut macam sel asal neoplasma, jadi didapat neoplasma golongan osteogenik/fibrogenik, dan miogenik, serta neoplasma golongan lain. 1

Berikut adalah klasifikasi dari lesi pada tulang yang menyerupai neoplasma. 15

  1. Osteogenic
  • Osteoma (ivory exostosis)
  • Single osteochondroma (osteocaltilage inous exostosis)
  • Multiple osteochondromata (multiple hereditary exostoses)
  • Osteoid osteoma
  • Benign osteoblastoma (giant osteoid osteoma)

 

  1. Chondrogenic
  • Enchondroma
  • Multiple enchondromata (ollier’s dyschondroplasia)
  • Subperiosteal cortical defect (metaphyseal fibrous defect)
  • Nonosteogenic fibroma (nonossifiying fibroma)
  • Monostotic fibrous dysplasia
  • Polyostotic fibrous dysplasia
  • Osteofibrous dysplasia (campanacci syndrome)
  • “brown tumor” (hyperparathyroidism)
  • Angioma of bone (hemangioma and lymphangioma)
  • Aneurismal bone cyst (ABC)
  • Simple bone cyst (unicameral bone cyst) (UBC)
  1. Fibrogenic
  1. Angiogenic
  1. Uncertain origin

Berikut adalah klasifikasi dari neoplasma primer pada tulang (true primary neoplasma of the bone).

  1. Osteogenic
  • Osteosarcoma (osteogenic sarcoma)
  • Surface osteosarcoma (paraosteal sarcoma; periosteal sarcoma)
  • Benign chondroblastoma
  • Chondromyxoid fibroma
  • chondrosarcoma
  • Fibrosarcoma of bone
  • Malignant fibrous histiocytoma of bone
  1. Chondrogenic
  1. Fibrogenic
  1. Angiogenic
  • Angiosarcoma of bone
  • Myeloma of bone (multiple myeloma)
  • Ewing’s sarcoma (Ewing’s tumor)
  • Hodgkin’s lymphoma of bone
  • Non hodgkin’s lymphoma (reticulum cell sarcoma)
  • Skeletal reticuloses (langerhans’ cell hostiocytoses)
  • leukemia
  • Giant cell tumor of the bone (osteoclastoma)
  1. Myelogenic
  1. Uncertain origin

 The Bones

Tubuh manusia dibentuk oleh lebih dari 200 tulang yang beraneka ragam bentuk dan ukuran (Gambar 1). Tulang memiliki osteosit yang berikatan dengan bahan keras yang menyerupai kalsium. Hal ini membuat tulang menjadi kuat, keras, dan kaku (rigid). Beberapa tulang memiliki kemampuan untuk menyokong beban hingga 12.000 pound per square inch. Bahkan, dibutuhkan beban sebesar 1.200 – 1.800 pound untuk dapat memecah sebuah femur (tulang paha). Bagian luar dari tulang terdiri dari jaringan penyambung fibrosa yang disebut "matriks", dimana di dalamnya terdapat deposit kalsium. 2

Tulang memiliki gaung (lubang-lubang) yang terisi dengan bahan "seperti bunga karang" (spongy), disebut "sumsum" (marrow). Sumsum dari beberapa tulang hanya terdiri dari jaringan lemak. Sedangkan sumsum dari tulang lainnya merupakan gabungan dari sel-sel lemak dan sel-sel pembentuk darah (hematopoietic cells). Sel-sel hematopoietic ini memproduksi sel darah merah, sel darah putih, dan keping darah (blood platelet). Terdapat juga sel-sel lain di dalam sumsum tulang, seperti sel plasma, fibroblas, dan sel retikuloendotelial. 2

Pada tiap-tiap ujung tulang terdapat zona "cartilago", suatu bahan yang keras, kuat, dan fleksibel, yang menyerupai tulang. Cartilago terbentuk dari matriks jaringan fibrosa dengan substansi yang "menyerupai gel". Tidak seperti tulang, cartilago tidak menyimpan banyak kalsium. Cartilago berfungsi sehagai "bantalan" tulang, dan bersama dengan ligamen dan beberapa jaringan lainnya membentuk persendian antar­tulang. Karena cartilago lebih elastis bila dibandingkan dengan tulang, maka hal ini memungkinkan tulang untuk bergerak bebas pada persendiannya. 3

Tulang memiliki berbagai fungsi penting. Kerangka tulang memberi kekuatan pada tubuh dan persendian, berfungsi sebagai "tuas" atau "pengungkit" sehingga tubuh dapat bergerak. Tulang juga berfungsi sebagai pelindung berbagai organ tubuh, seperti tulang iga yang melindungi jantung dan paru-paru. Selain itu, tulang juga memiliki fungsi sebagai media penyimpan berbagai mineral yang diperlukan tubuh, khususnya kalsium. 3

 

Gambar 1. The Bones 3

 

Skeletal Growth and Phisiology

Sistem skeletal pada awalnya dibentuk oleh cartilago, kecuali pada tulang craniofacial dan clavicula. Kedua tulang ini tidak memiliki persamaan dengan kartilaginosa dan dibentuk langsung oleh jaringan membranosa. Proses pembentukan tulang tanpa diperantarai oleh pembentukan cartilago disebut intramembranous bone formation (Gambar 2). Sebagian besar tulang pada orang dewasa dibentuk dengan cara ini. 4

Enchondral ossification adalah pembentukan tulang yang diawali dengan pembentukan model cartilago yang nantinya model ini akan menjadi tulang. Di dalam uterus, sistem skeletal dibentuk sebagai cartilago; namun, mendekati kelahiran beberapa struktur prebone ini sudah berada pada jalur pembentukan tulang sesungguhnya. Pembentukan tulang ini pertama kali dimulai dari pertengahan diafisis, dikenal sebagai pusat ossifikasi primer. Kemudian, pada pusat ossifikasi sekunder, tulang akan mulai dibentuk pada bagian akhir struktur prebone. Pusat ossifikasi sekunder memiliki cartilago di sekeliling permukaan sendi dan epiphyseal cartilage (gambar 4) pada permukaan pusat ossifikasi primer. Tulang tumbuh panjang melalui epiphyseal growth plate, yang memproduksi cartilago yang akan membentuk ossifikasi enchondral (gambar 3) 4

 

 

Gambar 2. Intramebranous Ossification

 

Gambar 3. Ossifikasi Endokondral

Epiphyseal growth plate dibentuk oleh proliferasi sel-sel cartilago yang nantinya akan mati. Setelah sel-sel cartilago tersebut mati, osteoblas akan melapisi matriks cartilago yang telah mengalami calcificasi yang sebelumnya diproduksi oleh chondrocyte, yang nantinya akan membentuk tulang.

 

 

Gambar 4. Bone Growth at an Epiphyseal Cartilage

 

Epiphyseal growth plate (gambar 5) terbagi dalam beberapa zona. Pembagian zona ini bervariasi pada berbagai literatur, tergantung dari pengarangnya; meski demikian, general consensus menspesifikasikan epiphyseal growth plate dalam lima zona. 16

1. Zona resting (reserve zone)

Merupakan zona yang menyatukan epiphyseal plate dengan epiphysis. Zona ini mengandung immature condrosit dan kaya akan pembuluh darah yang berfungsi untuk memperbarui fungsi sel-sel tulang pada selurut plate.

2. zona proliferatif (the proliverative zone)

Merupakan zona yang paling aktif pertumbuhannya.

3. zona maturasi (the maturation zone)

Merupakan zona dimana terjadi pematangan dan penambahan ukuran sel-sel cartilage sampai menyatu dengan metafisis. Kondrosit pada daerah ini mengandung akumulasi glikogen pada sitoplasmanya dan memproduksi enzim fosfatase yang berfungsi dalam proses calcificasi.

4. zona degradasi (the degeneration zone)

5. zona calcificasi (the zone of calcification)

Merupakan zona yang paling lemah pada epiphyseal plate, karena pada zona ini sel-sel kondrosit telah mati akibat proses calcificasi.

Zona maturasi, degenerasi, dan calcificasi seringkali Iebih dikenal sebagai zona hipertrofi (the hypertrophic zone). Awalnya, pembentukan tulang terdiri dari spikula (spicules of bone) dengan inti kartilaginosa yang telah mengalami calcificasi dan disebut sebagai primary spongiosa. Cartilago yang mengalami calcificasi ini nantinya akan menghilang seutuhnya seraya tulang melanjutkan proses remodeling. Area tulang dimana terdapat primary spongiosa disebut sebagai metaphysis. Tulang ini kemudian akan berubah bentuk diafisis yang lebih sempit (gambar 6) . Pembentukan awal tulang pada proses ini lebih dikenal sebagai the woven bone. Tulang ini tidak terorganisasi baik dari segi gambaran  microscopis (gross)  maupun microscopis. 4

 

 

Gambar 5. Hubungan antara fungsi dan struktur pada lempeng pertumbuhan

 

Gambar 6. Bone structure

 

Gambar 7. The histology of compact bone

Sejalan tulang ini mengalami remodel dan maturasi, akan terbentuk lamellar bone. Tulang lamellar (lamellar bone) ini dapat sebagai tulang kortikal dengan supply darah dan sistem Havers atau tulang trabekular (trabecular bone) yang tidak memiliki sistem Havers. 4

Tulang dibentuk oleh osteoblas, yang nantinya menjadi osteosit jika terjebak di antara matriks tulang.

Osteoklas adalah sel-sel multinukleus yang memiliki kemampuan untuk resorpsi tulang. Osteoklas dan osteosit dikenali secara microscopis karena matriks yang diproduksinya.

Chondrocyte adalah sel yang bertanggung jawab terhadap pembentukan cartilago dan berada di antara matriks cartilago. 4

 

Gambar 8. The periosteum and endosteum

Tulang mengalami perubahan bentuk (remodel) secara terus-menerus, terutama di bawah pengaruh beban mekanis (mechanical load). Dalam 30 tahun pertama kehidupan, secara keseluruhan massa skeletal seseorang mengalami peningkatan terus­-menerus; namun, setelah melewati usia 30 tahun, keseluruhan massa skeletal akan menurun, dimana wanita akan mengalami penurunan cepat sesaat setelah menopause. Semakin banyak massa tulang yang terbentuk sampai usia 30 tahun, semakin kecil kemungkinan seorang pria mapun wanita mengalami osteoporosis. 4

Joint Anatomy and Physiology

Diarthrodial joint merupakan tempat terjadinya suatu pemisahan yang sempurna antara jaringan-jaringan penyambung. Diarthrodial joint terdiri dari cairan synovial yang melumasi dua lapisan cartilago sendi sehingga mencegahnya untuk saling bergesek satu dengan yang lain. Cartilago sendi unik dalam koefisien gesek di antara dua permukaan sendinya dengan jumlah cairan synovial yang normal, diperkirakan 10 kali lebih kecil bila dibandingkan dengan koefisien gesek di antara dua blok es. Hal ini memungkinkan adanya pergerakan bebas. 4

Jumlah cartilago sendi yang dicapai hingga pertumubuhan sempurna (usia pertengahan remaja) merupakan jumlah total yang akan dimiliki seseorang hingga akhir massa hidupnya. Sekali cartilago sendi ini mengalami kerusakan, maka tidak akan dapat diganti. Perbaikan cartilago (fibrocartilago) dapat terlihat serupa dan bahkan memiliki kemiripan komponen (tidak identik) dengan cartilago sendi, tetapi tidak memiliki mekanisme untuk mempertahankan beban berat pada permukaan sendi. Terlebih, fibrocartilago akan bertahan hingga beberapa tahun selama masih terdapat tekanan yang melintasi sendi normal. Penelitian masih terus dilanjutkan untuk mengetahui cartilago dalam hubungannya untuk mengganti bagian sendi yang rusak sebelum sendi tersebut mengalami kerusakan menyeluruh. 4

Cartilago sendi tersusun dari cartilago hyaline dimana 60 - 80 % di antaranya merupakan air. Sisa komposisinya terdiri dari makromolekul — kolagen, proteoglycan, dan protein nonkolagen -- dimana secara keseluruhan komposisinya berupa asam amino dan gula. Kolagen tipe II membentuk sekitar 95 % kolagen pada cartilago sendi. Terdapat tiga proteoglycan utama pada cartilago sendi dimana semuanya terdiri dari rantai polisakarida dengan inti protein. Dua proteoglycan yang lebih besar dapat sebagai uggrecan, bersama air, mengisi rongga interfibrillar dan cartilago merupakan komponen mekanisnya. Satu bagian terutama terdiri dari chondroitin sulfate dan lainnya berupa keratin sulfite. Bagian yang lebih kecil terutama terdiri dari sulfate. 4

Cartilago sendi terbagi menjadi empat zona atau lapisan, yaitu :

  1. superficial (gliding).
  2. middle (transitional).
  3. deep (radial).
  4. calcified.

Masing-masing zona memiliki pengaturan, komponen kolagen dan proteoglikan, serta fungsi sendiri. Gangguan yang terjadi pada berbagai lapisan tersebut dapat menyebabkan cartilago sendi tidak dapat menjalankan fungsinya (malfunction). Terdapat banyak protein minor pada cartilago sendi yang penting untuk fungsi normal cartilago. 4

Kemampuan cartilago yang sangat terbatas untuk dapat memperbaiki diri sangat berbeda dengan tulang. Tulang memiliki kemampuan untuk memperbaiki tidak hanya setelah tulang mengalami kerusakan ataupun luka namun juga pada saat tidak adanya jaringan parut (scar). Cartilago tidak dapat memiliki kemampuan untuk menyembuhkan diri. Luka yang terjadi pada cartilago sendi akan diikuti dengan respons dari chondrocyte, namun respons ini sangat terbatas dan tidak akan diikuti dengan penyembuhan terhadap luka-luka yang terjadi. 4

Jika luka, termasuk laserasi, yang terjadi superficial dan tidak mengenai tulang subchondral, maka tidak akan terdapat penyembuhan secara klinis. Jika luka hingga mengenai tulang subchondral maka akan terjadi perdarahan, dan akan menimbulkan adanya respons penyembuhan; meskipun demikian, cartilago yang mengalami penyembuhan tidak identik bila dibandingkan dengan cartilago sendi asli dan tidak memiliki fungsi yang sama karena cartilago restorative ini mengalami penyembuhan dengan cepat dan tidak dapat menahan tekanan yang normal ditimbulkan oleh sendi. 4

 

What is Cancer ?

Berbagai organ dan jaringan tubuh dibentuk oleh blok-blok kecil pembangun yang disebut dengan "sel". Sel-sel ini di berbagai bagian tubuh yang berbeda memberikan perbedaan dalam rupa maupun fungsinya. Namun, kebanyakan dari sel-sel tersebut memiliki kesamaan dalam hal memperbanyak diri. Sel secara terus-menerus akan berubah menjadi lebih tua dan akhirnya mati, selanjutnya akan terbentuk sel-sel baru yang akan menggantikannya. Normalnya, pembelahan dan pertumbuhan sel terkontrol dengan tertib dan rapi. Namun, bila untuk berbagai alasan proses ini menjadi tidak terkontrol, maka sel-sel tersebut akan terus-menerus membelah, membentuk sel­sel abnormal yang nantinya akan membentuk suatu "gumpalan" yang disebut "tumor". Tumor ini dapat jinak ataupun ganas. "Kanker" merupakan sebutan yang digunakan untuk tumor yang berbahaya / ganas (malignant). 5,6

Seringkali, sel-sel kanker menyebar ke berbagai bagian tubuh dimana mereka akan berkembang menggantikan jaringan yang normal. Proses ini disebut sebagai "metastasis". Tanpa memperhatikan ke organ atau jaringan tubuh mana kanker menyehar, kanker ini selalu diberi nama sesuai dengan darimana sel kanker tersebut pertama kali muncul. 6

Pada tumor jinak, sel-sel tidak menyebar ke berbagai bagian dari tubuh dan juga tidak bersifat sebagai "kanker". Meskipun demikian, jika sel-sel ini terus-menerus berkembang di tempat semula maka akan menimbulkan masalah berupa penekanan ke organ-organ di sekitarnya. 5

Sel-sel kanker terbentuk karena terdapat kerusakan pada DNA (gambar 9). DNA terdapat pada setiap sel dan secara langsung mempengaruhi kerja dari sel tersebut. Pada umumnya, ketika DNA rusak maka tubuh akan mampu untuk mcmperbaikinya. Pada sel-sel kanker, kerusakan DNA tidak dapat diperbaiki. Seseorang dapat mewarisi DNA yang rusak tersebut, yang nantinya akan bermanifestasi sebagai inherited cancer. Seringkali, DNA seseorang menjadi rusak karena terpapar oleh sesuatu hal di lingkungan, seperti merokok. 6

Penting untuk diketahui, bahwa kanker bukan merupakan satu penyakit dengan satu tipe pengobatan. Terdapat lebih dari 200 tipe kanker yang masing-masing memiliki nama dan pengobatan tersendiri. 5

 

 

Gambar 9. Normal cells and cells forming a tumor

 

Tumors of The Musculoskeletal System

Insidens

Tumor primer musculosceletal jarang terjadi. Insidens dari neoplasma berkaitan dengan usia, misalnya osteosarcoma terjadi kebanyakan pada anak dan remaja, dan osteoclastoma terjadi kebanyakan pada masa dewasa. Tipe histogenetik dari tumor tergantung darimana jaringan tumor tersebut berasal. Lagipula, beberapa lesi spesifik cenderung pada tulang-tulang khusus atau area tulang, biasanya pada area dimana terjadi pertumbuhan maksimal atau remodelling. 2

Giant cell tumor (osteoclastoma) terjadi di dekat growth plate, dimana di sini terjadi resorpsi utama sebagai bagian dari remodeling; osteosarcoma muncul pada metaphysis, dimana terjadi pertumbuhan maksimal tulang baru. Tumor cartilago meliputi metaphysis dekat daerah growth plate, sedangkan round cell tumor pada bagian metafisis / diafisis sumsum tulang (gambar 12). Proses neoplastik ini menggambarkan kekacauan terhadap pertumbuhan normal dan fungsi remodeling tulang, yang menjadi tidak terkontrol. 2

Etiology

Kebanyakan neoplasma tulang dan jaringan lunak tidak diketahui penyebabnya. Kebanyakan tumor tipe histogenetik memiliki derajat agresivitas bervariasi dan timbul dalam bentuk jinak (benign) ataupun ganas (malignant). (Tabel 2) mengilustrasikan berbagai insidens dan histogenesis dari neoplasma musculosceletal. Perilaku biologis tumor dapat bervariasi, direfleksikan oleh grade patologis tumor. Walaupun system grading bervariasi untuk berbagai macam tumor yang berbeda-beda, pada umumnya sistem simpel yang diadopsi oleh Musculosceletal Tumor Society meretleksikan perbedaan perilaku tumor secara keseluruhan dalam bentuk jinak (benign), keganasan derajat rendah (low-grade malignant), dan keganasan derajat tinggi (high-grade malignant). 2

Karakteristik

Foto rontgen dapat memberi keterangan penting:  7

  • Tumor jinak berbatas tegas dan korteks selalu utuh
  • Batas tumor ganas biasanya kurang jelas atau samar
  • Umumnya terlihat pembentukan tulang baru
  • Lokalisasi pada tulang vertebra:
    • Jinak: Osteoma osteoid, osteoblastoma, atau hemangioma
    • Ganas: Metastasis atau myeloma
    • Lokalisasi pada tulang pipih seperti pelvis atau scapula
      • Metastasis, myeloma, atau chondrosarcoma
      • Lokalisasi pada tulang panjang
        • Epiphysis: Chondrosarcoma atau giant cell tumor
        • Metafisis: Osteosarcoma
        • Diafisis: Metastasis atau Ewing’s tumor
        • Kista tulang aneurisma

 

Diagnosis Banding tumor primer berdasarkan foto rontgen adalah: 7

  • Metastasis Karsinoma
  • Osteomielitis
  • Kista Tulang Soliter
  • Kalus bekas tulang patah Kista tulang aneurisma
  • Tumor coklat pada hiperparatiroid
  • Displasia fibrosa
  • Miositis osifikans

Sel neoplasma tidak selalu merusak tulang, tetapi keberadaanya menyebabkan resorpsi tulang atau osteoklastik lokal. Sebaliknya, sel neoplasma tertentu dapat bersifat osteoblastik lokal dan membentuk tulang normal yang disebut kelainan tulang reaktif. Sel neoplasma kelompok osteogenik adalah sel yang dapat menghasilkan osteoid dan tulang, sedangkan sel kelompok osteolitik adalah sel yang meresorpsi tulang yang tampak pada gambaran radiologik sebagai osteolisis atau osteosklerosis. 7

Neoplasma musculosceletal dicirikan sebagai pertumbuhan sentrifugal yang berasal dari satu fokus, pseudoencapsulation (pembentukan zona reactive tissue disekeliling lesi yang berkembang, dimana lesi keganasan dapat diinvasi secara lokal oleh tumor), dan memiliki kecenderungan untuk berada pada batas anatomi pada awal perkembangan tumor. Tumor-tumor ini memiliki kecenderungan untuk menyebar sepanjang bidang fascial dan cenderung mengandung sisa kompartemen anatomis, suatu karakteristik yang sangat penting untuk derajat dan pengobatan pembedahan pada lesi ini. Yang termasuk dalam kompartemen anatomis adalah tulang, kompartemen otot, persendian, jaringan subkutan dan kulit, dan pada beberapa kasus major neurovascular sheath. 7

Tulang yang lemah karena kerusakan lokal akibat resorpsi osteoclastic mudah mengalami patah tulang patologis. 7

Metastasis

Metastasis dari neoplasma ganas musculosceletal dihubungkan dengan prognosis yang buruk. Metastasis seringkali ke paru-paru, walaupun beberapa tumor cenderung melibatkan pembuluh limfe regional, dan juga kemungkinan metastasis ke tulang. Metastasis ke otak dan visceral tidal( lazim, umumnya muncul hanya pada penyebaran penyakit tahap akhir (terminal end-stage disseminated disease). 2

Staging

Sistem staging yang banyak digunakan untuk neoplasma musculoskeletal, ditunjukkan pada tabel telah diaplikasikan baik pada lesi jaringan lunak maupun tulang. Lesi jinak (benign lesion) dibedakan dalam derajat laten, aktif, atau agresif. Lesi ganas (malignant lesion) dibedakan berdasarkan high grade (derajat II) atau low grade (derajat I), dan intracompartmental (A) atau extracompartmental (B). Tanpa memperhatikan penyebaran setempat, tumor yang mengalami metastasis semuanya merupakan derajat III dan memiliki prognosis yang buruk. Sistem staging ini dapat menunjukkan taksiran yang baik dalam memprediksi kelangsungan hidup seseorang. 2

Stage

Characteristic

Metastases

Benign

1

2

3

 

Latent

Active

Aggresive

 

No

No

No

Malignant

IA

IB

IIA

IIB

III

 

Low grade: intracompartmental

Low grade: extracompartmental

High grade: intracompartmental

High grade: extracompartmental

Low or high grade: intra or extracompartmental

 

No

No

No

No

Yes

 

Tabel 1. Surgical staging system for musculoskeletal tumor

 Manifestasi klinis

Penderita dengan tumor primer tulang umumnya datang karena pembengkakan, nyeri, atau patch tulang patologik. Sering pada diagnosis pertama disangka distorsi atau cedera olah raga karena sering didapat riwayat trauma lokal pada neoplasma musculosceletal. 7

Secara tipikal, pasien biasanya menunjukkan adanya riwayat nyeri yang seringkali memburuk pada malam hari dan biasanya tidak berhubungan dengan aktivitas. Mula-mula nyeri hanya sedang saja dan hilang timbul, tetapi akhirnya menjadi progresif, difus, dan terus-menerus. Nyeri umumnya karena periost dan endosteum yang sensitif. 7

Dapat juga timbul massa atau pembengkakan. Pembengkakan lokal biasanya dapat diketahui apabila kelainan telah menembus batas tulang. Pembengkakan dari kelainan jinak biasanya menetap dan tidak nyeri, kecuali pada osteoma osteoid. Gejala konstitusional (berat badan turun, demam, keringat malam, malaise) biasanya tidak ditemukan, kecuali pada kasus-kasus yang sudah mengalami penyebaran. Lesi yang berdekatan dengan persendian dapat menyebabkan efusi, kontraktur, dan nyeri pada pergerakan. Tumor jaringan lunak seringkali tidak terdapat nyeri, kecuali jika struktur neurovascular ikut terlibat. Penekanan terhadap vena atau pembuluh limfe pada limb dapat menyebabkan edema pada bagian distal, dan massa yang lebih besar akan menunjukkan adanya gambaran distensi vena. 2

Massa ganas jaringan lunak dapat menjadi keras dan terpancang pada jaringan subkutan, otot, atau tulang, dan biasanya tidak lunak. Rasa hangat di daerah setempat dapat dirasakan dengan jelas karena lesi ganas ini menyebabkan local angiogenesis. Pasien mungkin juga datang dengan fraktur patologis sebagai manifestasi lesi intraosseus jinak atau gangs, dengan destruksi pada tulang dan diikuti oleh gangguan mekanisme. Nyeri ketika mengangkat beban berat merupakan gejala klinis yang seringkali mengindikasikan adanya impending fracture. Nyeri hebat dan tiba-tiba biasanya disebabkan oleh fraktur patologis. 2

Evaluasi sebaiknya meliputi riwayat dan pemeriksaan fisik pada regio yang terlibat, dengan perhatian khusus pada struktur sendi, otot, neurologis, dan vascular. Pemeriksaan pembuluh limfe regional dan pembuluh limfe jauh merupakan hal penting, sebagaimana pemeriksaan paru-paru dan abdomen untuk menilai adanya kemungkinan penyakit yang bermetastasis. 7

 

Gambaran radiologi

Pemeriksaan foto polos merupakan satu-satunya pemeriksaan yang berguna untuk menentukan diagnosis banding dari lesi pada tulang. Hal yang digunakan sebagai pertimbangan meliputi:  2

Histology

Benign

% Cases

Malignant

% Cases

Hemopoietic

(28%)

 

 

Myeloma

Lymphoma

24.7

3.1

Chondrogenic

(27%)

Osteochondroma

Enchondroma

Chondroblastoma

Chondromyxoid fibroma

12.0

4.3

0.7

0.6

Primary chondrosarcoma

8.7

Osteogenic (25%)

Osteoid osteoma

Osteoblastoma

2.5

0.7

Osteosarcoma

Chondroblastic osteosarcoma

Fibroblastic osteosarcoma

Parosteal osteosarcoma

9.9

6.0

 

4.6

0.9

Unknown origin (12%)

Giant cell tumor

4.8

Ewing’s sarcoma

Giant cell tumor

Adamantinoma

6.3

0.5

0.2

Fibrogenic (4%)

Fibroma

1.5

Fibrosarcoma

2.5

Notochordal (3.5%)

 

 

Chordoma

3.5

Vascular (0.8%)

Hemangioma

Hemangiopericytoma

0.6

0.1

Hemangioendothelioma

0.1

 

Neurogenic (<0.1%)

Neurilemmoma

<0.1

 

 

 

Tabel 2. Incidence of bone tumor

Dengan menggunakan kriteria ini, diagnosis banding yang akurat dapat dirumuskan pada kehanyakan kasus. Keadaan infeksi (osteomyelitis) dapat memberikan gambaran radiografik yang sangat bervariasi. Kondisi metabolik, inflamasi, displasia, trauma, kongenital dan degeneratif juga hares selalu dipertirnhangkan. lesi jaringan Iunak dapat dievaluasi Iehih baik dengan MRI dihandingkan pencitraan radiograti lainnya. 7

Diagnosis

Anamnesis. gambaran klinik, dan pemeriksaan radiologik adalah komponen penting untuk mendiagnosis suatu neoplasma. Selain itu, biopsi dan penemuan laboratorium biokimia juga penting. Bone scan dapat dipergunakan untuk menentukan lokasi neoplasma primer atau sekunder. 7

Tomografi dapat membuat visualisasi tiga dimensi neoplasma musculosceletal, umpamanya neoplasma di pelvis atau tulang belakang yang sulit ditentukan dengan pemeriksaan radiologik lain. 7

Pemeriksaan laboratorium rutin meliputi hitung darah lengkap dan hitung jenis; erythrocyte sedimentation rate (ESR); serum fosfatase alkali, jumlah kalsium dan fosfat, fungsi ginjal dan hati, dan urinalisis. Jika multiple myeloma merupakan diagnosis banding, maka harus dilakukan pemeriksaan jumlah serum protein dan imunoelektroforesis. Pada kebanyakan tumor primer, kedua pemeriksaan utama ini dalam batas normal. Peninggian konsentrasi protein total serum memungkinkan adanya suatu mieloma multipel, yang ditunjukkan pula dengan pemeriksaan protein Bence Jones pada urine. 7

Fosfatase alkali mencerminkan aktivitas osteoblas, biasanya dapat meningkat pada keadaan osteosarcoma, dan hitung darah serta pemeriksaan ESR dapat membantu menyingkirkan adanya kemungkinan diagnosis ini. Langkah pemeriksaan lanjutan tergantung dari lokasi lesi, kemungkinan diagnosis, usia pasien, dan kemungkinan keganasan. 2

Bone scan hampir selalu digunakan untuk menilai aktivitas dan luas lesi primer dan juga untuk menyingkirkan adanya lesi di tempat lain. ,Soft-tissue tumor bone scan digunakan untuk menilai lesi yang berada di dekat tulang atau bila dicurigai terjadi suatu keganasan. Untuk berbagai lesi yang memiliki potensi keganasan, dianjurkan untuk dilakukan pemeriksaan pencitraan tiga dimensi (CT scan atau MRI) sebelum dilakukan biopsi untuk menilai luas lesi dan prosedur biopsi yang akan dipilih, meminimalisasi kontaminasi ke berbagai lokasi, selanjutnya dapat dipikirkan tindakan pembedahan. Pemeriksaan radiografi thorax (atau lebih baik dengan CT scan) dan CT scan abdomen digunakan untuk menyingkirkan kemungkinan adanya metasatasis dari penyakit lain. 7

Biopsi

Dalam kaitan dengan pengobatan, biopsi merupakan tindakan untuk mencegah diagnosis yang terlewat dan yang berlebihan. Sampel biopsi hendaknya cukup besar dan representatif. Biopsi secara pembedahan lebih bermakna daripada biosi aspirasi. Pada keganasan yang dicurigai telah menyebar dalam sumsum tulang seperti pada mieloma multipel, biopsi aspirasi sumsum tulang sternum atau crisla illiaca biasanya cukup adekuat. 7

Tergantung dari pengalaman ahli bedah dan ahli patologi anatomi, needle atau trochar biopsy merupakan pilihan utama untuk tumor jaringan lunak dan tumor tulang. Prinsip umum prosedur biopsi adalah sebagai berikut : 7

  1. Sayatan biopsi dilakukan secara longitudinal sejajar sumbu ekstremitas
  2. Harus ditentukan metode biopsi yang akan digunakan, needle biopsy atau trochar biopsy, sehingga pada waktu pengangkatan tumor secara en bloc
  3. Harus sudah dilakukan pemeriksaan radiologi untuk keakuratan teknik
  4. Sebaiknya dilakukan pemeriksaan frozen-section untuk memastikan jaringan yang didapat sudah cukup
  5. Sebaiknya dilakukan pemeriksaan kultur dan mikrobiologi yang sesuai
  6. Window biopsi tulang korteks harus sekecil mungkin dan berbentuk oval untuk meminimalisasi resiko fraktur patologis
  7. Biopsi diambil dari pinggir tumor untuk membantu menghindari bagian tengah atau daerah yang nekrosis
  8. Pajanan terhadap berbagai macam struktur neurovaskular harus dihindari
  9. Hemostasis dilakukan secara teliti untuk menghindari terjadinya hematoma yang dapat bertempat di semua kompartemen; untuk Iesi tulang yang curiga keganasan, daerah dimana dilakukan biopsi harus diisi dengan semen methacrylate untuk mencegah terjadinya hematoma
  10. Penggunaan torniquet intraoperative berguna untuk ketelitian dalam pembedahan
  11. Penggunaan sistem drain di pinggir dan daerah sekitar sayatan biopsi akan memudahkan pengangkatan tumor secara en bloc
  12. Kompartemen yang tidak terlibat harus dihindari
  13. Secara umum, kapanpun akan dilakukan biopsi maka ahli bedah yang akan melakukan tindakan pembedahan definitif yang harus melakukannya; hal ini biasanya juga melibatkan pusat rujukan perawatan tersier

Keputusan akhir mengenai diagnosis dan pengobatan secara ideal dilakukan bersama oleh tim yang terdiri dari ahli bedah, ahli ortopedi, ahli radiologik, ahli radioterapi, ahli onkologi, dan ahli patologi. 7

 

 

    

                       Needle biopsy                                                             Open biopsy

Gambar 10. Biopsy

Pengobatan

Tujuan utama pengobatan tumor musculoskeletal jinak dan ganas yang belum bermetastasis adalah eradikasi dari penyakit; penyembuhan fungsi tungkai merupakan hal kedua yang penting untuk dipertimbangkan. Hasil jangka panjang meningkat secara dramatis dalam dua dekade lampau, dan pendekatan terapi bagi lesi ganas telah mengalami perubahan, dengan menyingkirkan prosedur amputasi dan lebih ke arah limb salvage. Terapi bervariasi tergantung dari lesi, tetapi biasanya merupakan kombinasi dari beberapa hal, yaitu pembedahan, kemoterapi, dan radioterapi. 2

Lesi jinak biasanya dapat diobati dengan pembedahan. Defek tulang ditutup dengan bone graft.

Neoplasma musculosceletal primer yang ganas secara umum ditanggulangi dengan pembedahan yang biasanya disertai dengan radioterapi dan kemoterapi sebagai terapi tambahan (adjuvant therapy). Beberapa neoplasma menunjukkan radiosensitivitas yang bervariasi. Sebagai contoh, Ewing's sarcoma dan sarkoma sel retikulum relatif radiosensitif, sedangkan chondrosarcoma radioresisten.     Agen kemoterapi yang umum digunakan adalah doxoruhicin, melhotrexate, cyclophopsphamide, ifbbsfamide, vincrislin, dan aclinomycin D. Terapi radiasi diberikan pre-operatif, post-operatif, atau melalui kateter yang ditanam pada waktu operasi yang diikuti oleh pembebanan dengan short-range isotop post-operatif (brachytherapy). Dosis yang efektif digunakan untuk mengontrol microscopic disease umumnya berkisar antara 50 — 60 Gy. 7

Pada tindak bedah kuratif harus dikeluarkan semua jaringan ganas. Sedapat mungkin tidak dilakukan amputasi sehingga reseksi harus dilakukan dengan mempertahankan saraf besar. Kemajuan teknologi juga menyumbangkan kontribusi untuk perubahan pendekatan terapi, yaitu dengan kemampuan komputerisasi untuk membuat implantasi prosthetic, yang dapat menggantikan semua bagian tulang atau sendi; teknik pemanjangan ekstremitas; dan teknik mikrovaskular untuk memindahkan jaringan bebas tulang dan jaringan lunak. Pembuluh nadi yang vital untuk ekstremitas dapat diganti dengan prostesis arteri sedangkan tulang diganti dengan prostesis atau cangkok tulang yang bervaskularisasi. Untuk anak terdapat prostesis yang panjangnya dapat disesuaikan dengan pertumbuhan ekstremitas selama beberapa tahun. 7

Prosedur pembedahan

Prosedur pembedahan yang digunakan untuk pengobatan tumor adalah : 2

  1. Intralesional : meninggalkan sisa microscopis maupun maksroskopis, seperti curettage pada lesi jinak
  2. Marginal : membuang keseluruhan zona reaktif dari tumor; kemungkinan meninggalkan sisa microscopis pada tumor ganas
  3. Wide : membuang beberapa jaringan normal melebihi zona reaktif dalam berbagai arah
  4. Radical : membuang semua kompartemen (tulang, otot, sendi) termasuk tumor ataupun zona reaktifnya

Untuk lesi jinak derajat I atau II, intralesional atau marginal excision sudah cukup memadai, namun pada lesi agresif derajat III dibutuhkan marginal hingga wide resection untuk dapat mengobati. Tumor ganas low-grade (derajat I) dapat diobati dengan radical surgical excision, atau wide excision ditambah dengan terapi adjuvant, dengan perbandingan angka kekambuhan antara 5 — 10 %. Pada pengobatan tumor dengan margin yang sama, basil antara amputasi dan reseksi adalah sebanding. Hal ini merupakan dasar penggunaan pembedahan limb salvage pada beberapa tahun terakhir.

Kuretase tidak dilakukan pada tumor ganas, tetapi berguna sekali untuk tumor jinak atau giant cell tumor. Fraktur patologis ditanggulangi dengan reduksi terbuka dan fiksasi interna. 7

Prognosis

Tumor ganas musculoskeletal merupakan penyakit yang serius dan mengancam jiwa, walaupun prognosisnya sudah mengalami peningkatan pada lebih dari dua dekade terakhir. [untuk lesi derajat 11, 5 -year survival rule antara 40 – 80 %, sedangkan pada Iesi derajat 1 5 -year survival rate antara 70 – 90 %. Pada beberapa tipe tumor kemampuan untuk mengontrol lokasi Iesi setempat diperkirakan sekitar 90 % atau lebih. Kekambuhan setempat pada lesi jinak hervariasi, tergantung dari derajat dan tipe tumor. 7

Mengingat permasalahan utama pengobatan keganasan skeletal meninggalkan metastasis di kemudian hari, diperlukan penelitian lebih lanjut di bidang ini. Penelitian terakhir telah menemukan adanya multiple drug resistence gene expression pada pasien yang diterapi dengan kemoterapi dimana tumor menjadi resisten terhadap obat tersebut. Gen ini memicu produksi ATPase (P-glycoprotein) yang memompa berbagai macam obat secara luas keluar dari sel-sel tumor, menjaga sublethal intracellular level. Terdapat juga berbagai mekanisme resistensi obat dan radiasi. Penelitian farmakologis yang dapat meningkatkan efektivitas kemoterapi saat ini sedang dalam penelitian dan memperlihatkan suatu janji akan meningkatkan outcome pengobatan sarcoma. Metode eksperimental lain yang dipergunakan untuk pengobatan metastatic sarcoma sedang dalam penelitian, termasuk penggunaan dari imunoterapi, dimana sistem kekebalan tubuh pasien dibuat peka oleh antigen tumor, dan transplantasi sumsum tulang, dengan didahului oleh high-intensity chemotherapy dan diikuti oleh reintroduksi autologue marrow. 2

Bone Tumor

Kebanyakan tumor tulang adalah jinak (benign). Beberapa bersifat "kanker" atau ganas (malignant). Adakalanya, infeksi, fraktur, dan berbagai kondisi non-tumor dapat menyerupai tumor. Tumor jinak biasanya tidak mengancam jiwa. Sedangkan, tumor ganas (malignant) dapat menyebarkan sel-sel kankernya ke berbagai bagian tubuh (metastasis). Hal ini dapat terjadi melalui darah ataupun sistem limfatik. Kanker yang berasal dari tulang (primary bone cancer) berbeda dengan kanker yang berasal dari tempat lain dalam tubuh dan menyebar ke tulang (secondary bone cancer). 8

Benign Bone Tumor

Tumor tulang jinak (benign bone tumor) tidak menyebar ke berbagai jaringan dan organ tubuh lain serta tidak mengancam jiwa. Biasanya tumor ini sembuh dengan pembedahan. Yang termasuk dalam benign bone tumor adalah osteoid osteoma, osteoblastoma, osteochondroma, enchondroma, dan chondromixoid, fibroma 8

Malignant Bone Tumor

1. Osteosarcoma (Osteogenic Sarcoma)

Merupakan kanker tulang yang berasal dari tulang itu sendiri, dan merupakan tulang yang paling sering terjadi. Osteosarcoma muncul pada dua atau tiga orang baru per juta orang tiap tahunnya. Meskipun kebanyakan kasus timbul pada usia 10 – 30 tahun, namun sekitar 10 % kasus ditemukan pada usia 60 – 70an. Laki-laki lebih sering terkena kanker ini bila dibandingkan dengan perempuan. Kebanyakan tumor ini muncul di daerah sekitar lutut. Lokasi tersering lainnya yaitu daerah lengan, pelvis, dan bahu. 3

2. Chondrosarcoma

Kanker ini berasal dari sel-sel cartilago dan merupakan primary bone cancer kedua yang banyak dijumpai. Kanker ini tidak umum dijumpai pada orang yang berusia lebih muda dari 20 tahun. Setelah berusia 20 tahun, resiko untuk timbulnya chondrosarcoma meningkat hingga mencapai usia sekitar 75 tahun. Kemungkinan untuk terkena kanker ini sebanding antara laki-laki dan perempuan. Kebanyakan ka.sus dijumpai di daerah sekitar panggul dan pelvis, tulang kaki atau tulang lengan, dan bahu. Adakalanya, chondrosarcoma timbul pada trachea, larynx, dan dinding dada. Tempat lain yang mungkin dapat terkena adalah daerah scapula, tulang iga, atau tulang tengkorak (skull). Chondrosarcoma diklasifikasikan berdasarkan grade, yaitu dengan mengukur seberapa cepat pertumbuhannya. Hal ini dibedakan oleh ahli patologi. Kebanyakan chondrosarcoma merupakan low grade (grade 1), yang berarti belum menyebar, atau intermediate grade (grade II). High grade (grade III) seringkali sudah menyebar, namun hal ini lebih jarang dijumpai. 8

3. Ewing Tumor (Ewing 's Sarcoma)

Kanker ini diberi nama demikian setelah Dr. James Ewing pertama kali menemukannya pada tahun 1921. Ewing tumor biasanya berasal dari tulang, dan kurang dari 10 % timbul pada jaringan dan organ lainnya. l,okasi yang sering dijumpai adalah daerah proksimal dan distal kaka, pelvis, daerah proksimal lengan dan tulang iga. 8

Ewing tumor merupakan primary bone cancer ketiga terbanyak yang sering ditemukan. Kanker ini seringkali timbul pada usia 5 - 20 tahun (anak-anak dan remaja) dan tidak umum dijumpai pada orang di atas 30 tahun. Ewing tumor banyak dijumpai pada orang kulit putih dan jarang dijumpai pada African American ataupun Asian American. 3

4. Malignant fibrous histocytoma (MFH)

Kanker ini Iebih sering dijumpai pada jaringan lunak (tipe jaringan penyambung selain tulang, seperti ligamen, tendon, lemak, dan otot). Namun, dapat juga timbul dari tulang, walaupun jarang. Ketika kanker ini timbul dari tulang, biasanya mengenai kaki (seringkali daerah lutut) atau lengan. Kanker ini umumnya timbul pada orang tua dan middle-aged adult, dan jarang timbul pada usia anak-anak. MFH memiliki kecenderungan untuk tumbuh cepat. Kanker ini sering menyebar ke bagian tubuh lain, paling sering ke pembuluh limfe dan paru-paru. 2

5.Fibrosarcoma

Merupakan tipe kanker yang lebih sering berasal dari jaringan lunak dibandingkan tulang. Fibrosarcoma umumnya muncul pada orang tua dan usia pertengahan. Tulang yang sexing terkena meliputi kaki, lengan, dan tulang rahang. 8

6.Giant Cell Tumor of Bone

Tipe ini memiliki bentuk jinak dan ganas. Tipe jinak (non-cancerous) Iebih sering dijumpai. Tumor ini hiasanya mengenai kaki (umumnya, di daerah sekitar lutut) atau tulang lengan, pada usia muda dan pertengahan. Kurang dari 10 % giant cell bone tumor hersifat "kanker" dan menyebar ke bagian tuhuh lain. Setelah dilakukan pembedahan giant cell bone tumor seringkali berulang di daerah setempat dimana kanker tersebut pertama kali muncul. Ketika giant cell bone tumor berulang, maka akan lebih menyebar lagi ke berbagai bagian tubuh, terlebih bila ia berulang beberapa kali. 8

7.Chordoma

Tumor primer tulang ini biasanya muncul di dasar tulang tengkorang dan tulang belakang. Tumor ini umumnya timbul pada orang yang berusia lebih dari 30 tahun, dan dua kali lebih sering dijumpai pada laki-laki dibandingkan perempuan. Chordoma memiliki kecenderungan untuk tumbuh lambat dan biasanya tidak menyebar ke berbagai organ tubuh. Namun, chordoma sering berulang di daerah yang sama bila pada pembedahan tumor ini tidak diangkat secara komplit. Ketika tumor ini menyebar, maka pembuluh limfe, paru-paru, dan Kati merupakan organ yang sering disinggahi. 3

 

BONE GIANT CELL TUMOR

Pendahuluan

Giant cell tumor (GCT) pada tulang merupakan jenis tumor yang relatif jarang terjadi. Karakteristiknya adalah ditemukannya multinucleated giant cells. Jenis tumor ini biasanya digolongkan dalam jenis tumor jinak yang agresif. GCT jarang terjadi pada anak-anak dan dewasa diatas usia 65 tahun. Nama “Giant cell tumor” sendiri diberikan berdasarkan bentuknya yang terlihat diatas mikroskop, yang terlihat seperti sel raksasa dengan jumlah yang banyak yang terbentuk dari proses menyatunya beberapa sel individual menjadi sebuah sel kompleks yang besar. 9

Banyak dari tumor tulang dan kondisi lain (termasuk tulang normal) mengandung giant cell, namun pada GCT ditemukan penampakan secara konstan sel raksasa dalam jumlah yang sangat banyak. Seringkali tumor tulang terjadi pada flared portion dekat dengan ujung dari tulang panjang (metaphysis), namun GCT terjadi hampir secara selektif terdapat pada akhir dari tulang panjang dekat persendian (epiphysis). Pada kasus yang sangat jarang, tumor ini dapat menyebar ke paru-paru. 9

Definisi

Nama “Giant cell tumor” sendiri diberikan berdasarkan bentuknya yang terlihat diatas mikroskop, yang terlihat seperti sel raksasa dengan jumlah yang banyak yang terbentuk dari proses menyatunya beberapa sel individual menjadi sebuah sel kompleks yang besar. 9

Tipe ini memiliki bentuk jinak dan ganas. Tipe jinak (non-cancerous) Iebih sering dijumpai. Tumor ini biasanya mengenai kaki (umumnya, di daerah sekitar lutut) atau tulang lengan, pada usia muda dan pertengahan. Kurang dari 10 % giant cell bone tumor bersifat "kanker" dan menyebar ke bagian tubuh lain. Setelah dilakukan pembedahan giant cell bone tumor seringkali berulang di daerah setempat dimana kanker tersebut pertama kali muncul. Ketika giant cell bone tumor berulang, maka akan lebih menyebar lagi ke berbagai bagian tubuh, terlebih bila ia berulang beberapa kali. 10

Epidemiologi

Incidence GCT diperkirakan terjadi pada 1 dari 1 juta orang per tahunnya. Biasanya tumor tersebut terletak pada knee joint bagian bawah dari tulang paha (femur) atau bagian atas dari tulang betis (tibia). Lokasi lainnya biasanya terdapat pada pergelangan tangan, tulang panggul, tulang bahu dan tulang belakang (antara tulang pelvis dan spine). Tulang yang bersangkutan umumnya menjadi lunak dan area disekitarnya membengkak (hematom). GCT juga merupakan salah satu tumor yang paling sering terjadi pada distal phalang. Tentang letak awal timbulnya tumor, dari epiphysis ataupun metafisis hanya merupakan sebuah kontroversi, namun tumor biasanya hanya terjadi saat epiphysial plate telah menutup. 10

Cooper pertama kali melaporkan adanya giant cell tumors pada abad ke 18. Pada 1940, Jaffe dan Lichtenstein  mengklasifikasikan giant cell tumor dari tumor tulang lainnya. Giant cell tumor biasanya  terjadi secara de novo namun dapat juga terjadi sebagai komplikasi yang jarang pada penyakit Paget pada tulang. 9

Frekuensi bone giant cell tumor adalah 4-5% dari tumor primer tulang dan 18.2% dari tumor tulang jinak. Incidence ini meningkat pada pasien dengan penyakit Paget, dimana giant cell tumor merupakan komplikasi neoplasma yang jarang. Giant cell tumor merupakan komplikasi yang jarang bila dibandingkan dengan Paget sarcoma dimana incidencenya kurang dari 5%.  9,10

Giant cell tumor biasanya merupakan tumor jinak, tetapi dapat menjadi malignant pada 5-10% pasien. Keganasan tersebut biasanya merupakan akibat dari transformasi pasca terapi radiasi. 10

Semua ras dapat menderita penyakit ini, dengan incidence tertinggi yaitu pada ras mongoloid, dimana incidencenya adalah sekitar 20% dengan tumor tulang primer. Persentase ini lebih tinggi sebanyak 4-5% dibandingkan dengan ras kaukasian. Wanita lebih sering terkena dibandingkan pria, kurang lebih 50-57% kasus terjadi pada pasien wanita. 10

Giant cell tumor lebih sering terjadi pada pasien dewasa muda yang berusia 20-40 tahun, dengan incidence tertinggi pada usia 20-30 tahun. Pada anak-anak penyakit ini lebih jarang terjadi, dengan persentase sebanyak 5.7%. Tumor yang berlokasi pada vertebrae biasanya terjadi pada pasien yang berusia lebih muda, yaitu 29% kasus terjadi pada usia 0-20 tahun. Multicentric giant cell tumors juga terjadi pada kelompok muda dimana incidence tertinggi pada usia 10-20 tahun. Incidence tumor ini biasanya terjadi kurang dari 1% pasien.  11

Seringkali giant cell tumors terjadi pada tulang-tulang panjang. Kira-kira 60% kasus, dan hampir semuanya berlokasi di articular end of the bone (gambar 11). Daerah metafisis juga dapat merupakan daerah terbentuknya tumor, namun biasanya terjadi pada tulang-tulang pasien dengan usia muda. Daerah tersebut mencakup tibia proksimal, distal femur, distal radius (gambar 13), dan humerus proksimal, disamping itu juga pernah ditemukan di daerah tulang pubis, calcaneus, and kaki (gambar 12). 10,11

 

Gambar 11. Tumor at the articular end of the bone

  

Gambar 12. Variasi letak tumor

 

Gambar 13. Letak tumor di distal radius

Patologi

Gambaran mikroskopik dari bone giant cell tumor memiliki karakteristik tertentu, walaupun tidak terlalu khas tetapi tidak sulit untuk menegakkan diagnosis penyakit ini berdasarkan pemeriksaan patologi anatomi.  Biasanya tumor tampak sebagai massa yang lunak, berwarna kecoklatan. Area perdarahannya, tampak seperti  berwarna merah gelap, dan area kolagennya tampak berwarna abu-abu. 10

Pada potongan spesimen biasanya dapat terlihat jaringan yang nekrosis dan ruangan-ruangan yang terisi darah. Reseksi utuh dari spesimen tumor tersebut jarang dilakukan karena biasanya pasien diterapi dengan kuretase. Secara umum, hasil kuretase berupa jaringan lunak, dan berwarna coklat gelap. Sel pembentuk giant cell tumor yaitu mononuclear stromal cell yang memiliki karakteristik seperti osteoclastlike giant cells yang terdistribusi secara homogen (gambar 14). Asal dari mononuclear stromal cell tersebut belum diketahui secara pasti, diduga merupakan derivat dari  berasal dari primitive mesenchymal stem cells atau cells of a histiocytic macrophage origin. 12

 

Gambar 14. Osteoclastlike giant cells in a background of mononuclear cells

Osteoclastlike giant cells memiliki gambaran morfologi yang serupa, dimana diperkirakan terbentuk akibat menyatunya  mononuclear stromal cells. Mononuclear cells biasanya berinti bulat atau lonjong, namun dapat juga berbentuk kumparan. Mereka memiliki  eosinofial sitoplasma yang bervariasi. Pada mononuclear atau multinucleated giant cells tidak ada matriks interseluler yang diproduksi. Aktivitas mitosis sangat bervariasi namun tidak berhubungan dengan prognosis dari penyakit tersebut atau dapat berarti tinggi rendahnya gradasi dari besarnya tumor tidak berhubungan dengan angka prognosis. Walaupun giant cell tumor of the bone tidak sulit untuk didiagnosa, variasi dari gambaran histologinya relatif jarang. 10,11

Secara histologi tumor ini dapat dibagi menjadi tiga grade menurut Jaffe (1940) atau dibagi menjadi empat grade berdasarkan Netherlands Committee on Bone Tumours. Berdasarkan system grading yang terbaru, didapatkan keterangan sebagai berikut :

  • Grade 1 dan 2 merupakan tumor jinak,
  • Grade 3 merupakan batas antara tumor jinak yang mengarah ke keganasan dan
  • Grade 4 merupakan  tumor ganas (tabel 3).

Tumor Grade 4 secara histologis memiliki gambaran yang mirip dengan malignant fibrous hystiocytoma pada tulang. Pembagian grading diatas, menentukan teknik operasi yang akan dilakukan. Namun  beberapa literature, sebanyak 20 persen giant cell tumor akan mengalami rekurensi walaupun telah diterapi dengan teknik operasi yang terbaru. 13

Bersamaan dengan resiko terbentuknya metastasis ke paru, menurut pandangan beberapa penulis, penggunaan grading masih memiliki arti klinis. Pada sistem grading, gambaran mitosis, pleiomorphism dari spindled mononuclear cells, giant cells secara individual dapat diperhitungkan yang berhubungan dengan aktivitas mitosis yang merupakan hal terpenting, dimana hal tersebut berhubungan dengan angka rekurensi serta metastase pada paru. Jika pada satu lapangan pandang microscopis, terdapat  lebih dari 1 mitosis maka secara signifikan, pasien tersebut memiliki resiko terjadinya residif dan metastasis pulmonal (23 persen) dimana tumor Grade 2 memiliki angka prevalensi terbesar (grade 1: 4%, grade 2: 88%, grade 3: 5%, grade 4: 3%). 10,12,13

Grade

Ground pattern cells

Giant cells

I

No atypia

Rare mitotic figure

Numerous

Big sized

II

Little polymorphia

Regular mitotic figures, but less than 1 mitosis / hpf (250µm)

Less numerous

III

Atypia

More than 1 mitosis / hpf (250µm)

Less numerous

Smaller sized

IV

Sarcomatous dediffirentiation

Small amount

Small sized

Tabel 3. Grading tabel of tumor

Walaupun giant cell tumor tidak membentuk matriks interselular, fokus dari formasi tulang yang reaktif dapat terlihat, terutama pada tumor dengan komplikasi fraktur. Area infark dapat terlihat pada gambaran giant cell tumors. Intravascular tumor emboli juga dapat ditemukan pada daerah perifer dari tumor tersebut, namun temuan ini tidak bisa dikorelasikan dengan potensi tumor tersebut untuk bermetastasis. Jarang sekali, giant cell tumor of the bone dapat bermetastasis, jika terjadi biasanya penyebaran yang terjadi ke daerah paru (gambar 15). 2

 

Gambar 15. metastasis ke daerah paru

Satu hal yang perlu diperhatikan bahwa multinucleated osteoclastlike giant cells bukan merupakan suatu patognomonik dari giant cell tumor pada tulang, karena osteoclastlike giant cells dapat ditemukan pada keadaan normal, reactive, benign, dan malignant neoplastic. Brown tumor pada hyperparathyroid bone disease merupakan gambaran penting nonneoplastic dari giant cell tumors. Keduanya secara histologi dapat terlihat identik, namun keduanya memiliki gambaran klinis dan radiologis yang berbeda. Hyperparathyroid bone disease umumnya merupakan penyakit metabolik dengan didapatkannya kenaikan angka serum kalsium dalam darah, sedangkan giant cell tumor merupakan penyakit pada tulang dengan tempat yang terlokalisasi. 10,14

Tumor primer lainnya yang juga memiliki gambaran osteoclastlike giant cells termasuk chondroblastoma, chondromyxoid fibroma, and giant cell osteosarcoma. 9

Giant cell tumors juga dapat terjadi di vertebrae (gambar 16),  juga sering terlihat di daerah sakrum. Tumor sakrum dapat begitu ekstensif hingga terlihat memenuhi seluruh sakrum. Namun jarang sekali meluas sampai mengenai sacroiliac joint atau ilium  dan diskus L5-S1 untuk melibatkan bagian posterior dari tulang L5. Lokasi terjadinya giant cell tumors pada spinal dapat bervariasi dan sering melibatkan vertebral body, dan arkus vertebral. Pada costae juga jarang terjadi giant cell tumors (gambar 17). 13

 

Gambar 16. Giant cell tumors di vertebrae

 

Gambar 17. Giant cell tumors di costae

Faktor Resiko

Giant cell tumors pada tulang terjadi secara spontan. Terbentuknya tumor tidak dipengaruhi oleh trauma, faktor lingkungan maupun diet makanan tertentu. Dari faktor genetik, tumor ini juga tidak diturunkan. Pada beberapa kasus yang jarang , mungkin berhubungan dengan hiperparatiroid. 9

Gejala klinis

Gejala utama yang dirasakan oleh pasien adalah rasa sakit disekitar area terbentuknya tumor. Rasa sakit juga dapat tercetuskan oleh pergerakan sendi sekitarnya, dan akan meningkat saat aktifitas dan berkurang saat beristirahat. Pada awal perjalanan penyakit, rasa sakit yang dirasa awalnya ringan namun secara progresif akan meningkat. Seiring perjalanan penyakit, area tulang yang terdapat tumor akan melemah dan dapat terjadi fraktur yang menyebabkan rasa sakit yang amat sangat dengan onset yang cepat. Terkadang pasien menyadari adanya massa pada bagian tubuhnya yang konsistensinya melunak dan tidak disertai rasa nyeri. 9,10

Giant cell tumors sering terjadi pada pasien usia 20-40 tahun. Pasien sering mengeluhkan rasa sakit dan bengkak pada daerah sekitar tumor. Fraktur patologi terjadi pada  10% kasus (gambar 18). Vertebral giant cell tumors dapat meluas ke dalam canalis spinalis sehingga dapat menekan spinal cord, dan dapat menyebabkan gejala neurologis. Giant cell tumors jarang berbentuk multicentric (gambar 19). Kondisi ini harus diperhatikan pada pasien dengan giant cell tumors yang berlokasi di tangan, hal ini disebabkan incidence dari tumor tersebut meningkat pada tulang yang berukuran kecil seperti tangan dan sakrum. 9

 

Gambar 18. Fraktur patologis

 

Gambar 19. Gambaran tumor yang multisentrik

Terapi

Jika tidak diberi pengobatan, maka tumor tersebut akan terus berkembang dan merusak struktur jaringan tulang. Tindakan operatif telah terbukti merupakan tindakan yang paling efektif untuk pengobatan GCT. Terapi radiasi merupakan pengobatan optional non-bedah yang terbukti cukup efektif. Walaupun pada 15% dari pasien yang menjalani terapi radiasi, akan berkembang menjadi keganasan. Sehingga, terapi radiasi hanya dipakai pada kasus-kasus sulit dimana tindakan operatif tidak bisa dilakukan. Pada beberapa center pengobatan, dilaporkan bahwa pengobatan dengan embolisasi untuk GCT cukup baik, dimana pembuluh darah yang mensuplai perdarahan ke tumor disumbat dengan bantuan catheter yang diarahkan ke pembuluh darah sekitar tumor lewat arteri utama. Dengan memblokir suplai darah ke tumor tersebut, diharapkan tumor akan mengecil bahkan menghilang yang disebabkan tumor tersebut kehilangan nutrisi. Studi control trial dengan pemberian interferon sedang diteliti, obat ini bekerja dengan mengintervensi kemampuan tumor untuk membentuk pembuluh darah baru, karena suplai darah berkurang, maka menyebabkan tumor mengecil bahkan menghilang. Seperti terapi radiasi, embolisasi dan pemberian interferon secara umum dilakukan untuk kasus-kasus tumor yang sulit dilakukan terapi pembedahan atau pada situasi dimana tumornya tetap kembali muncul. 10

Metastase paru merupakan penyebab kematian tersering, dilaporkan pada 16-25% kasus. Deteksi dini dan manajemen yang tepat sangat diperlukan dalam penatalaksanaan penyakit ini. Metastase paru dapat diobati dengan reseksi luas, kemoterapi, terapi radiasi dan interferon alpha. Bila memungkinkan pembedahan berupa reseksi secara luas merupakan pilihan terapi.  9,10,12

Bila pembedahan eksisi secara komplit tidak dapat dilakukan pada metastase paru, maka dianjurkan pemberian terapi adjuvant seperti kemoterapi dan terapi radiasi.  Sebagai tambahan, dimana tidak dapat dilakukan reseksi pada metastase yang terjadi maka dianjurkanlah kemoterapi dan terapi radiasi pada saat yang bersamaan.  11

Transformasi GCT menjadi malignant secara spontan jarang terjadi. Transformasi menjadi malignant dapat didefinisikan sebagai sarkoma yang dihubungkan dengan GCT tipe benigna atau sarkoma yang terjadi dari lokasi awal GCT. Transformasi tersebut dapat berupa osteosarcoma, fibrosarcoma, atau malignant histiocytoma. Kasus transformasi maligna tersebut pernah dilaporkan pada usia 4-40 tahun. 10

Banyak penulis yang melaporkan keterkaitan antara terapi radiasi dengan transformasi maligna dari GCT. Bagaimanapun, informasi ini kebanyakan berasal dari era radiasi orthovoltage. Penelitian terbaru mengatakan bahwa efek dari radiasi megavoltage sangat berhubungan dengan terjadinya transformasi maligna.  GCT yang telah bertransformasi menjadi malignant akan diterapi sama seperti sarkoma.  10,14

Terapi radiasi dan embolisasi biasanya dilakukan apabila terapi pembedahan tidak memungkinkan untuk dilakukan, misalnya apabila lokasi tumor tidak dapat dijangkau, atau bila kemungkinan terjadi  relaps yang membutuhkan pembedahan ulang. Radiasi megavoltage yang direkomendasikan berkisar antara  35-70 Gy. Angka rekurensinya mencapai 10-15% dengan jarangnya terjadi transformasi maligna. Bagaimanapun follow-up jangka panjang masih sangat diperlukan. 9,14

Pembedahan

Pada masa lampau, GCT diterapi dengan amputasi atau reseksi luas dan rekonstruksi.. 13

Mengangkat tumor dengan tindakan kuretase secara umum dilakukan, hal tersebut menyisakan lubang pada tulang, dimana lubang tersebut dapat ditutup dengan bone graft. Bone graft dapat diambil dari bagian tubuh lain dari pasien (autograft) atau dari kadaver (allograft). Jika tindakan kuretase tidak dilakukan dengan baik dan hanya mengandalkan bone graft saja, maka 45% kemungkinan tumor akan rekuren. Penggunaan bone cement diduga menghasilkan angka rekurensi yang lebih rendah. Tindakan kuretase dengan bor kecepatan tinggi atau dengan penggunaan agen tertentu seperti nitrogen cair, hidrogen peroksida, atau fenol lalu diikuti dengan bone graft menggunakan bone cement dapat mengurangi angka rekurensi sekitar 10-29 persen. Pengangkatan tumor yang lebih kompleks dan rekonstruksi tulang terkadang dibutuhkan pada kasus dimana tumor telah menghancurkan secara luas area tulang atau sering terjadi rekurensi. 12,13

Pada beberapa kasus yang jarang terjadi, dimana tumor telah menyebar ke paru-paru, pengangkatan tumor pada paru dapat menyembuhkan 75 persen penyakit pasien. 14

Terdapat beberapa pilihan terapi pada literature terbaru, antara lain mencakup:

(1)  curettage

(2)  curettage dan bone grafting

(3)  curettage dan insersi polymethylmethacrylate (PMMA)

(4)  cryotherapy setelah dilakukannya curettage

(5)  curettage and a chemical adjuvant (phenol, zinc chloride alcohol,             

       and H2O2) prior to the insertion of PMMA or a bone graft

(6)  primary resection

(7)  radiation therapy

(8)  embolization of the feeding vessels

Resection

Meskipun prosedur intralesional merupakan terapi pilihan pada kebanyakan GCT, reseksi en bloc secara luas juga memiliki angka rekurensi yang rendah dan direkomendasikan untuk lesi pada lokasi tertentu. Pada proximal fibula, reseksi luas tanpa  rekonstruksi biasanya sering digunakan. GCT pada distal radius juga sering dilakukan reseksi dan direkonstruksi dengan autograft atau allograft (gambar 20). Bagaimanapun, pada tulang panjang yang dilakukan reseksi maka harus dilakukan pembuatan prosthetic atau allograft reconstruction.  Pada lesi grade III, ini merupakan pilihan pembedahan yang terbaik, tetapi reseksi dan rekonstruksi merupakan pembedahan yang cukup besar dengan morbiditas fungsional. 

Intralesional procedures. 10

 

Gambar 20. Intraoperative photograph of giant cell tumor in the distal femur

 

Intralesional curettage dan bone grafting merupakan pilihan yang sering digunakan karena memberikan hasil yang baik secara fungsional pada sebagian besar kasus.  Bagaimanapun, simple curettage dengan atau tanpa bone graft memiliki angka rekurensi sebesar 27-55%. Angka rekurensi yang tinggi yang dilakukan oleh beberapa ahli bedah untuk mengganti bone graft pada lesi dengan PMMA packing (gambar 21). Panas yang dihasilkan oleh PMMA mengakibatkan nekrosis secara thermal yang memudahkan dilakukannya curettage pada sel tumor. 8

 

Gambar 21. typical chocolate brown and spongy appearance

Teknik PMMA, bila dibandingkan dengan bone grafting, maka akan memberikan banyak keuntungan, seperti kurangnya morbiditas pada lokasi yang digunakan sebagai donor untuk bone-grafting, persediaan yang tidak terbatas, terjaganya stabilitas struktural, selain itu juga  lebih murah dan mudah digunakan. Sebagai tambahan,  barium yang terkandung di dalam methylmethacrylate merupakan subtansi yang bersifat radiopaque yang secara samar terlihat kontras dengan jaringan tulang di sekitarnya. Rekurensi local akan lebih mudah terdeteksi dibandingkan dengan teknik bone graft.  (gambar 22). 8,10,11

         

Gambar 22. reveals blood-filled cystic areas and inner yellow and orange discoloration

Kerugian menggunakan cement yaitu sulitnya mengangkat kembali bila diperlukan revisi dan kemungkinan pemakaian subchondral cement merupakan faktor predisposisi untuk terjadinya penyakit degeneratif lebih awal seperti  osteoarthritis. Selanjutnya, teori tersebut harus dibuktikan lebih lanjut. Pada penelitian terbaru oleh Frassica et al dengan menggunakan model seekor anjing menunjukkan bahwa  subchondral PMMA tidak mengakibatkan penyakit degenerasi pada sendi. Bagaimanapun, pada penelitian berikutnya, Frassica et al menunjukkan bahwa subchondral bone grafts  lebih unggul dibandingkan restorasi dengan menggunakan cement pada jaringan subchondral. 10

Beberapa penulis menambahkan teknik high-speed burring setelah dilakukannya simple intralesional curetagge pada cavitas tersebut. Dengan dilakukkannya hal tersebut maka jaringan tumor dapat diambil secara keseluruhan. (gambar 23). Sehingga hal ini dapat menurunkan angka rekurensi sebesar 12-25%. The high-speed burr tidak hanya memberikan komponen thermal untuk mengeradikasi tumor tersebut tetapi juga dapat mengambil jaringan tumor secara keseluruhan, tanpa ada yang tersisa. High-speed burring dari cavitas tersebut dilanjutkan dengan pemberian substansi adjuvant seperti zat kimia atau fisika pada lesi dengan penggunaan PMMA atau bone graft. 10,13

 

Gambar 23. Gross specimen of a giant cell tumor that fills the entire distal radius

Adjuvant therapies

Terapi adjuvant, seperti phenol, H2O2, atau nitrogen cair, dan argon beam coagulation, memiliki keuntungan dan kerugian tersendiri. Bagaimanapun, terapi tersebut adalah metode untuk mengeradikasi penyakit mikroskopik. Banyak penulis menganjurkan phenol sebagai zat yang efektif untuk mengurangi angka rekurensi dari GCT. Setelah dilakukan curettage dan perforasi pada tulang, tambahkan phenol pada cavitas tersebut. Hasilnya, kematian jaringan seluller pada kedalaman sekitar 1-2 mm. Maka penggunaan phenol 5% dianjurkan  sebagai terapi adjuvant. 7,15

Angka rekurensi dengan penggunaan curettage,  phenol dan packing with PMMA atau bone grafts sebesar 5-17%. Phenol bersifat toksik secara sistemik.  Penghindaran paparan terhadap jaringan sekitar cavitas yang telah dikuretase cukup sulit. Ini akan mengakibatkan luka bakar secara kimia yang serius, dan zat tersebut juga diabsorpsi melalui kulit dan mukosa. Zat tersebut memiliki efek yang membahayakan pada system persarafan, liver, jantung dan ginjal. Zat tersebut juga dapat merusak sel DNA, protein koagulasi, dan nekrosis jaringan seluller. 8,12,14,16

Banyak penulis yang menganjurkan teknik cryosurgery sebagai adjuvant Nitrogen cair merupakan reagen kimia yang digunakan dalam cryosurgery. Pada teknik direct-pour, setelah dilakukan curettage dan perforations tulang secara keseluruhan, nitrogen cair dituangkan atau ditambahkan melalui  stainless steel funnel ke dalam cavitas. (gambar 24). Nitrogen cair tersebut akan berada di dalam cavitas sampai terevaporasi.  Kemudian jaringan sekitarnya akan diirigasi dengan larutan sodium chloride hangat untuk mengurangi terjadinya kerusakan pada jaringan sekitar akibat thermal.  Proses tersebut dapat diulang sebanyak 2-3 kali, untuk mendapatkan hasil kematian seluller pada kedalaman sekitar 1-2 mm. Defek pada cavitas kemudian akan direkonstruksi dengan menggunakan PMMA atau bone grafts. 17,18

Angka rekurensi dengan teknik cryosurgery dilaporkan sebanyak 2-12%. Kerugian dari teknik ini mencakup diperlukannya paparan yang luas, perlindungan terhadap jaringan lunak, nekrosis kulit, osteonekrosis dan fraktur. have been reported to be 2-12%. Fraktur merupakan komplikasi yang paling sering terjadi pada teknik operasi ini.  Malawer et al menambahkan bahwa fiksasi internal dengan Steinmann pins dan rekonstruksi pada defek cavitas dengan  PMMA secara signifikan dapat mengurangi incidence terjadinya fraktur dan dianjurkan pada semua pasien yang menjalani cryosurgery yang bertujuan sebagai stabilisator internal. 1,2,7

 

Gambar 24. Multinucleated giant cells are dispersed throughout on a background of mononuclear cells.

Beberapa penulis, memiliki teknik alternatif lain selain penggunaan cryosurgery dan terapi phenol, yaitu dengan menggunakan terapi argon-beam coagulation.  Bahaya yang ditimbulkan lebih rendah dibanding phenol dan nitrogen cair.  Koagulasi thermal yang digunakan melalui gas argon yang terkonsentrasi digunakan untuk melapisi cavitas tumor.  (gambar 25). Penetrasinya cukup dalam yaitu mencapai 2-3 mm. Angka rekurensinya bila dibandingkan dengan penggunaan PMMA dilaporkan sebanyak 7%. Tidak ada komplikasi akut yang pernah dilaporkan. Follow-up jangka panjang harus dilakukan untuk menjamin efek dari argon beam coagulation pada sendi dan atau  jaringan subchondral dan incidence dari fraktur patologis.  8,10,13,19

 

Gambar 25. Mitotic activity and rare cellular atypia

Diferensial diagnosis:

  1. Telangiectatic or fibrogenic variants of osteosarcoma
  2. Malignant fibrous histiocytoma (bone)
  3. Metastasis
  4. Plasmacytoma

Pemeriksaan Penunjang

Radiografi

Padapemeriksaan radiografi, giant cell tumors lebih mudah dibedakan dari tumor tulang lainnya. Giant cell tumors biasanya bersifat lytic, subarticular dan eccentric; terkadang terdapat sedikit tepi yang sklerotik. Bagaimanapun, variasi yang tidak biasanya dapat menyulitkan penegakkan diagnosis berdasarkan pemeriksaan radiografi.  10

Penemuan dari pemeriksaan radiografi yang terpenting dari giant cell tumor mencakup lokasi tumor, daerah lisis dan respon tubuh host. Umumnya, giant cell tumors bersifat expansile, osteolytic, radiolucent lesions tanpa tepi sclerotic dan biasanya tanpa reaksi periosteal. Septum dapat terlihat pada lesi dari 33-57 %  patients (gambar 26); hal tersebut mewakili gambaran pertumbuhan tulang yang tidak seragam. Tumor tersebut biasanya sudah berukuran besar pada saat terdeteksi, dengan diameter lesi berkisar 5-7 cm. 10

 

Gambar 26. Septate lytic lesion in the subarticular location of the proximal femur

Kebanyakan giant cell tumors (85%) terjadi pada tulang panjang, kurang lebih 50% berlokasi di tulang di sekitar lutut. Menentukan lokasi sangat penting dalam penegakkan diagnosis giant cell tumor.  Kebanyakan tumor bersifat eksentrik dan biasanya berlokasi di subarticular (gambar 27). 10,20

 

Gambar 27. expanded lytic lesion in the subarticular position of the distal ulna

Bagaimanapun tumor yang berasal dari metafisis dan melibatkan epiphysis tergantung dari usia penderita, karena hal ini berkaitan dengan kematangan tulang. Lesi awal biasanya terdapat pada daerah metafisis. Gambaran giant cell tumor pada daerah spine agak sulit dibedakan dengan gambaran tumor lain karena gambaran yang tidak biasa pada tumor jenis lain dapat menyerupai gambaran giant cell tumor, namun pada sakrum dapat dibedakan dengan baik.  10,21

Telangiectatic atau fibrogenic varian dari osteosarcoma dapat memiliki gambaran ossifications atau calcifications yang tidak terlihat. Varian tersebut dapat terlihat eccentric, dan tumor tersebut dapat meluas ke permukaan subarticular sehingga tampak seperti giant cell tumor.  10

Malignant fibrous histiocytomas dapat terjadi pada grup umur yang sama dengan giant cell tumor, sehingga dapat menjadi penyulit untuk mengidentifikasi gambar. 10

Chondroblastomas dapat menjadi salah satu diagnosa yang salah karena letaknya yang menyerupai bone giant cell tumor, yaitu pada are subarticular. Namun jika diperhatikan dengan baik, dapat terlihat gambaran pusat tumor pada epiphysis dibandingkan dengan di metafisis. Dan terlihatnya chondroid calcifications dapat membantu mendiagnosa chondroblastoma.

Aneurysmal bone cysts dapat terlihat menyerupai bone giant cell tumor, karena letaknya yang dapat meluas ke korteks subarticular. Kista tersebut dapat terjadi pada pasien dengan usia yang lebih muda. Kira- kira sekitar 29 persen dari aneurysmal bone cysts dilaporkan terlihat bersamaan dengan lesi tumor tulang solid lain,  dan sekitar 39 persen dapat ditemukan bersamaan dengan giant cell tumors. 11

 

CT SCAN

Pada gambaran CT scan didapatkan gambaran yang mirip dengan x-ray (gambar 28). Namun marginal sclerosis, cortical destruction, and soft-tissue masses (gambar 29) dapat terlihat lebih jelas dengan menggunakan CT scan jika dibandingkan dengan X-ray. Fluid levels beberapa kali dapat terlihat, namun gambaran tersebut tidak spesifik. Gambaran CT scans lebih terlihat baik pada tulang dengan bentuk yang kompleks, seperti  tulang vertebrae atau tulang pelvis. 10,11,22

 

Gambar 28. Coronal CT scan of a giant cell tumor of the distal ulna seperti gambar 27

 

Gambar 29. giant cell tumor arising from the temporal bone

 

MRI

MRI cukup sensitif untuk mendeteksi perubahan dari jaringan lunak, intra-articular dan sumsum tulang. MRI merupakan metode terbaik untuk menentukan sejauh mana terjadi invasi ke daerah subchondral dan ekstensi tumor pada persendian di sekitarnya. Diagnosis dengan menggunakan MRI sangat akurat, terutama bila MRI diintrepretasikan dengan bantuan pemeriksaan penunjang lain yang dapat membantu menegakkan diagnosis. 10

Pada gambaran T1-weighted, karakteristik giant cell tumors dapat terlihat heterogeneous or homogeneous pada intensitas sinyal  yang rendah maupun sedang, namun pada area tertentu dengan intensitas sinyal yang tinggi dapat terlihat gambaran area yang mengalami perdarahan. 10,13

Pada gambaran T2-weighted, tumor tampak heterogeneous yang solid melalui intensitas sinyal yang rendah sampai sedang (gambar 30). Hemosiderin dapat terdeteksi pada lebih dari 63% of giant cell tumors, dan hal tersebut mungkin disebabkan oleh sel darah merah yang mengalami ekstravasasi dan juga proses fagositosis oleh tumor tersebut. Area kistik terlihat pada gambaran T2-weighted dengan intensitas sinyal yang tinggi. Gambaran Fluid level dapat terlihat (gambar 31). 10

 

Gambar 30. T2-weighted coronal MRIs of the wrist show a giant cell tumor located in a subarticular position in the distal radius. The lesion is heterogeneous and hyperintense

Gambaran MRI giant cell tumor pada lower spine dapat menjadi tumpang tindih dengan gambaran tumor lain seperti osteoblastoma, aneurysmal bone cyst, and metastasis, karena pada spine, tumor tersebut dapat ditemukan pada lokasi yang sama dengan letak ditemukannya giant cell tumors. 10

 

Gambar 31. T2-weighted axial MRI of the knee shows multiple fluid-fluid levels in a giant cell tumor of the distal femur

Kelemahan MRI antara lain disamping biayanya yang relatif mahal, dan juga ketersediaan alat yang sangat terbatas. Beberapa pasien mengalami claustrophobia saat proses pemeriksaan sehingga membutuhkan sedasi. MRI juga merupakan kontraindikasi untuk pasien dengan cardiac pacemakers, orbital foreign bodies, dan noncompatible aneurysmal clips.  10,23

Angiografi

Angiografi biasanya tidak diperlukan dalam mengevaluasi giant cell tumor karena neovaskularisasi sekitar 80 persen terlihat pada gambaran giant cell tumor yang secara bersamaan terlihat dengan kapiler intens dan inhomogen yang dapat terlihat juga pada tumor tulang ganas, jinak maupun yang bukan neoplasma,  sehingga dapat terlihat tumpang tindih, dan dapat menyulitkan klinisi untuk membuat diferensial diagnosis. 19

Walaupun angiografi dapat digunakan untuk melihat penyebaran jaringan  tumor ke intraosseous and extraosseous, yang sangat berguna dalam perencanaan operasi yang akan dilakukan, namun penggunaan  MRI tetap menjadi tolak ukur utama dalam perencaan operasi. 8,14

preoperatif embolisasi dapat dilakukan untuk mengurangi perdarahan dan untuk mempermudah dalam melakukan reseksi pada tumor yang kaya akan pembuluh darah. Dengan membuang secara total komponen extraosseous dapat mencegah rekurensi lokal. Pembedahan biasanya dilakukan sesaat setelah embolisasi dan kolateralisasi pembuluh darah dibentuk. 14,19

Embolisasi pembuluh darah arteri pada tumor juga dilakukan pada pasien-pasien yang menderita tumor yang tidak dapat dioperasi atau kondisi pasien yang tidak memungkinkan untuk dilakukan tindakan operatif, sehingga embolisasi dilakukan dengan tujuan untuk mengurangi rasa nyeri secara paliatif. 19

 

DAFTAR  PUSTAKA

  1. Bagian Bedah Staf Pengajar Fakultas Kedokteran Universitas Indonesia. Kumpulan Kuliah Ilmu Bedah. Jakarta: Penerbit Binarupa Aksara; 1995. page 589-90.
  2. What is Bone Cancer. January 24, 2006. Available From: Hiperlink http://www.cancer.org/docroot/CRI/content/CRI_2_4_IX_What_Is_bone_cancer_2.asp?sitearea
  3. The Bones. February 1, 2004. Cancer Back Up. Available From: Hiperlink http://www.cancerbackup.org.uk/Cancertype/Bone/General/Thebones
  4. Osteosarkoma, Childhood. Available From: Hiperlink http://www.plwc.org/portal/site/PLWC/menuitem.6067beb227103
  5. What is Bone Cancer. November 1, 2002. Available From: Hiperlink http://www.cancerbackup.org.uk/Aboutcancer/Whatiscancera
  6. What is Bone Cancer. June 2, 2006. Available From: Hiperlink http://www.cancer.org/docroot/CRI/content/CRI_2_4_IX_What_Is_bone_cancer_2.asp?sitearea
  7. Sjamsuhidayat R & de jong W. Buku Ajar Ilmu Bedah. Edisi Revisi. Jakarta: EGC; 1997.p.1264-9
  8. Bone Tumor October 2004. Amercian Academy of Ortopaedic Surgeons. Available From: Hiperlink http://orthoinfo.aaos.org/fact/thr_report,cfm?thread_ID=278&topcategory=about%20Ortophaedic
  9. Lewis V.O, Giant Cell Tumor. Available From: Hiperllink http://www.emedicine.comorthopedtopic496.htm
  10. Lesley A.G, Giant Cell Tumor. Available From: Hiperllink http://www.emedicine.comradiotopic307.htm
  11. Klein G.L, Bone Giant Cell Tumors . Available From: Hiperlinkhttp://www.emedicine.com/ped/topic1683.htmForsyth R.G, Bone Giant Cell Tumors Atlas Genet Cytogenet Oncol Haematol. June 2003. Available From: Hiperlink http://AtlasGeneticsOncology.org/Tumors/BoneGiantCellTumID5150.html
  12. Bone Tumor October 2006. Amercian Academy of Ortopaedic Surgeons. Available From: Hiperlinkhttp://orthoinfo.aaos.org/fact/thr_report,cfm?thread_ID=278&topcategory=about%20Ortophaedic
  13. Bone Tumor.org. February 7, 2007. Cancer Back Up. Available From: Hiperlink http://www.cancerbackup.org.uk/Cancertype/Bone/General/Thebones
  14. Salter R.B. Neoplasm of Musculoskeletal Tissue. Dalam: Textbook of Disorders amd injury of the Musculoskeletal System, third edition, 1998, hal 397-9
  15. Salter R.B. Normal Structure and Function of Musculoskeletal Tissue. Dalam: Textbook of Disorders amd injury of the Musculoskeletal System, third edition, 1998, hal 10-11
  16. Complications. In: Bone Cancer. Available From: Hiperlink http://www.mayoclinic.com/health/bonecancer/DS00520/DSECTION=6
  17. Eds Pizzo et al. Principles and Practice of Paediatric Oncology. 4th edition. Lippincott Williams and Wilkins; 2002
  18. Prando A, deSantos LA, Wallace S, Murray JA: Angiography in giant-cell bone tumors. Radiology 1979
  19. Biscaglia R, Bacchini P, Bertoni F: Giant cell tumor of the bones of the hand and foot. Cancer 2000 May 1; 88(9): 2022-32
  20. Benjamin RS: Interferon a2b as anti-angiogenesis therapy of giant cell tumors of bone: implications for the study of newer angiogenesis-inhibitors. Proc Am Soc Clin Oncol 1999; 18: 548a.
  21. Brien EW, Mirra JM, Kessler S, et al: Benign giant cell tumor of bone with osteosarcomatous transformation ("dedifferentiated" primary malignant GCT): report of two cases. Skeletal Radiol 1997 Apr; 26(4): 246-55
  22. Saraf SK, Goel SC. Complication of resection and reconstruction in Giant cell tumor of distal end of radius-An analysis. Indian J Orthop 2005;39:206-11

 

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Lucille | 23 Februari 2017 - 06:05:08 WIB