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HODGKIN PEDIATRI
Pembimbing:
dr. Fendy Matulatan, Sp.B(K)BA
PENDAHULUAN
• Non Hodgkin’s Limphoma (NHL) neoplasma ganas jaringan limfoid
berasal dari turunan progenitor/sel matur dari sel Limfosit B dan T.
• NHL Anak vs Dewasa berbeda presentasi, terapi dan outcome
• Massa expanding, riwayat simptomatik singkat evaluasi diagnostik
adalah suatu urgensi, jika bukan suatu emergensi.
• Komplikasi pendesakan anatomis struktur berdekatan dan gangguan
metabolik akibat lisis tumor.
• Peranan ahli bedah onkologi pediatrik stadium I & II reseksi tumor
primer mempersingkat durasi kemoterapi meningkatkan disease
free survival (DFS) dan overall survival (OS)
Lewing KB, Gamis AS. Lymphomas in Holcomb GW, Murphy JP. 2010. Ashcraft’s pediatric surgery. 5th ed. Philadelphia. Saunders Elseviers.
Termuhlen AM, Gross TG. Overview of non-Hodgkin lymphoma in children and adolescents. 2016. www.uptodate.com
DEFINISI
• Non Hodgkin’s Lymphoma (NHL): kelompok heterogen keganasan
jaringan limfoid, dibedakan dari Limfoma Hodgkin berdasarkan lokasi
asal, variasi tipe sel, perilakunya yang lebih ganas, dan tidak
ditemukannya sel Reed-Sternberg (RS).
• Limfoma mewakili sekitar 12% dari semua kanker anak di AS.
• Limfoma Pediatri 60% NHL (8% Keganasan pada anak-anak).
• Kanker pediatrik paling umum pada anak < 15 tahun (7-11 tahun), bayi
(≤1 persen).
• Laki-laki : perempuan (3:1), kulit putih > Afrika Amerika.
Sandlund JT, Downing JR, Crist WM. Non-Hodgkin’s lymphoma in childhood. N Engl J Med 1996;334:1238–1248.
Kaatsch P. Epidemiology of childhood cancer. Cancer Treat Rev 2010; 36:277.
Crump C, Sundquist K, Sieh W, et al. Perinatal and family risk factors for non-Hodgkin lymphoma in early life: a Swedish national cohort study. J
Natl Cancer Inst 2012; 104:923.
Cairo MS, Perkins H. Non-Hodgkin’s Lymphoma in Children. In Bast RC Jr, Kufe DW, Pollock RE, et al., editors. Holland-Frei Cancer Medicine.
5th edition. Hamilton (ON): BC Decker; 2000.Chapter 138D
Prasad R, Arthur LG. Mattei P. Cervical Lymphadenopathy in Fundamentals of Pediatric Surgery. 2011. New York. Springer. p213-22
History
Dorothy Reed
Mendenhall
(1874-1964)
Marvin J. Stone, MD. "Thomas Hodgkin: medical immortal and uncompromising idealist." Proc (Bayl Univ Med Cent). 2005 Oct; 18(4): 368–75
NHL pediatri vs dewasa
Sandlund JT, Downing JR, Crist WM. Non-Hodgkin’s lymphoma in childhood. N Engl J Med 1996;334:1238–1248
ETIOLOGI
FAKTOR RISIKO:
• Translokasi kromosom
• Infeksi (EBV, HBV, HCV, HIV, HTLV-I, H.
pylori)
• Faktor lingkungan (chemical,
chemotx, radiotx)
• Immunodefesiensi
• Inflammasi kronik
Termuhlen AM, Gross TG. Overview of non-Hodgkin lymphoma in children and adolescents. 2016. www.uptodate.com
Sandlund JT, Downing JR, Crist WM. Non-Hodgkin’s lymphoma in childhood. N Engl J Med 1996;334:1238–1248
Vinjamaram S, Besa EC, Non Hodgkins Lymphoma. 2016. www.medscape.com
DIAGNOSIS
Freedman AS, Friedberg JW, Aster JC. Clinical presentation and diagnosis of non-Hodgkin lymphoma. www.uptodate.com Last update 30 September 2017.
LAB
Termuhlen AM, Gross TG. Overview of non-Hodgkin lymphoma in children and adolescents. 2016. www.uptodate.com
PENCITRAAN:
• Foto polos
• USG
• CT Scan
• PET Scan
• MRI
Krishnan A, Shirkhoda A, Tehranzadeh J et al. Primary Bone Lymphoma: Radiographic–MR Imaging Correlation.. RSNA
Radiographics. November 2003 Volume 23, Issue 6
Hassani KIM, El bouhaddouti H, Ousadden A et al. Non-Hodgkin’s lymphoma revealed by an ilio-colic intussusception in a Moroccan patient: a case
report. Pan African Medical Journal, 2010 4:11
BIOPSI:
• Klinis limfadenopati lokal maupun general atau massa, tanpa kelainan pada
darah tepi dan sumsum tulang belakang FNAB urgent (skrining awal,
diagnosis pasti tidak bisa).
• Populasi monomorphic large lymphoid (blastic) leukemia atau limfoma.
• Limfadenopati spesifik: supraklavikula (75-90%), servikal dan aksila (60-70%),
inguinal (30-40%).
• Indikasi: limfadenopati suspicious, persisten, progresif.
HISTOPATOLOGI:
• Biopsi core, incisional, excisional: pemeriksaan + klasifikasi histologi,
immunologi, serta biologi molekular jaringan
• Populasi monomorfik sel limfoid ukuran sedang dgn kromatin terbuka &
berukuran kecil namun memiliki nukleus yang tegas (distinct).
• Bentukan uniform populasi blue staining cell diselingi makrofag (starry sky
appearance)
Venkateswaran K. Iyer. Pediatric Lymphoma Diagnosis: Role of FNAC, Biopsy, Immunohistochemistry and Molecular Diagnostics.
Indian J Pediatr (September 2013) 80(9):756–763
Karakteristik Histologis dan Klinis NHL Pediatri. A. Gambaran histologis small-noncleaved-cell (Burkitt’s) lymphoma B.
Lymphoblastic lymphoma C. Anaplastik large-cell lymphoma. D. Encasement lumen usus oleh limfoma Burkitt E. Kompresi jalan
nafas oleh limfoma limfoblastik F. Destruksi os tibia oleh large-cell lymphoma.
Sandlund JT, Downing JR, Crist WM. Non-Hodgkin’s lymphoma in childhood. N Engl J Med 1996;334:1238–1248
IMUNOHISTOKIMIA
• B-cell marker (CD20 dan CD79a), T-cell marker (CD3 dan CD5)
• Limfoma Burkitt: (1) panel IHC: CD45 (LCA), CD20, CD3, CD 10, Ki-67, BCL2, BCL6, TdT atau (2) analisis marker
permukaan sel melalui flow cytometry: kappa/lambda, CD45, CD20, CD3, CD5, CD19, CD10, TdT.
• DLBCL: (1) panel IHC: CD20, CD3, CD5, CD10, CD45, BCL2, BCL6, Ki-67, IRF/MUM1, MYC, additional (Cyclin
D1, CD30, CD 138, EBER-ISH, ALK, HHV8) atau (2) analisis marker permukaan sel melalui flow cytometry:
kappa/lamda, CD45, CD3, CD5, CD19, CD10, CD20.
• Limfoma limfoblastik: (1) panel IHC CD45 (LCA), CD19, CD20, CD79a, CD3, CD2, CD5, CD7, TdT, CD1a, CD10,
cyclin D1 atau (2) analisis marker permukaan sel melalui flow cytometry: kappa/lambda, CD45, CD3, CD5, CD4, CD7,
CD8, CD19, CD20, CD10, TdT, CD13, CD33, CD1a, cytoplasmic CD3, CD22, myeloperoxidase.
• Anaplastik panel IHC: CD30, CD15, PAX5, ALK, ABV-EBER, cytotoxic granule protein (granzyme B, perforin, TIA1),
CD25, MUM1.
Morsi A, El Ghani A, El Shafiey M et al. Clinico-Pathological Features and Outcome of Management ofPediatric Gastrointestinal Lymphoma. Journal of the
Egyptian Nat. Cancer Inst. Vol. 17, No. 4, December: 251-259, 2005
DIAGNOSTIK MOLEKULER:
Sandlund JT, Downing JR, Crist WM. Non-Hodgkin’s lymphoma in childhood. N Engl J Med 1996;334:1238–1248
Morphologic, Immunologic, Molecular, and Cytogenetic Findings in Pediatric NHL
Sandlund JT, Downing JR, Crist WM. Non-Hodgkin’s lymphoma in childhood. N Engl J Med 1996;334:1238–1248
STAGING
St. Jude’s
French American
British (FAB)
DIFFERENTIAL DIAGNOSIS
Agrawal R, Wang J: Pediatric follicular lymphoma: a rare clinicopathologic entity. Arch Pathol Lab Med 133 (1): 142-6, 2009
TERAPI
Kemoterapi:
Pengobatan dasar
yang memungkinkan
dicapainya disease
free survival jangka
panjang
Sandlund JT, Downing JR, Crist WM. Non-Hodgkin’s lymphoma in childhood. N Engl J Med 1996;334:1238–1248
Outcome Kemoterapi Berbasis Stadium pada NHL
Pediatri
Sandlund JT, Downing JR, Crist WM. Non-Hodgkin’s lymphoma in childhood. N Engl
J Med 1996;334:1238–1248
Pembedahan:
• Reseksi mayor atau komplit pada NHL pediatri umumnya tidak diperlukan,
kecuali:
• Stadium 1 atau grup A (localized disease).
• Bila tidak kemoterapi intensif tidak tersedia reseksi total limfoma Burkitt
abdomen bersifat kuratif.
• Indikasi laparotomi emergensi pada komplikasi massa tumor misalnya
intussusepsi atau perforasi intestinal.
Radioterapi:
• Radiasi saja atau kombinasi dengan kemoterapi: tidak lebih superior
dibandingkan kemoterapi intensif.
• Indikasi terbatas: paraplegi sekunder karena kompresi medulla spinalis,
sindroma vena cava superior.
• Efek samping: gangguan pertumbuhan tulang dan jaringan lunak, keganasan
sekunder
Delarue A1, Bergeron (payudara danF,tiroid),
C, Mechinaud-Lacroix danM,penurunan
Coze C, Raphael Patte C. Pediatric fungsi paru
non-Hodgkin's lymphoma: primary surgical management
of patients presenting with abdominal symptoms. Recommendations of the Lymphoma Committee of the French Society to Combat Pediatric
Cancers (SFCE). J Chir (Paris). 2008 Sep-Oct;145(5):454-8
Braithwaite KA, Cairo MS. Non Hodgkin Lymphoma in Children and Adolescent in Pediatric Hematology oncology Secrets. 2002. New York.
Hanley and Belfus. P123-28
KOMPLIKASI
Meyers PA, Potter VP, Wollner N, Exelby P. Bowel Perforation During Initial Treatment forChildhood Non-Hodgkin 's Lymphoma. Cancer
56:259-261, 1985.
Wossmann W, Schrappe M, Meyer, Zimmermann M, Reiter A. Incidence of tumor lysis syndrome in children with advanced stage Burkitt’s
lymphoma/leukemia before and after introduction of prophylactic use of urate oxidase. Ann Hematol (2003) 82:160–165
Ortega JA, Mahour H, Isaacs H, Higgins GR. Airway Obstruction and Superior Vena Cava Syndrome Secondary to Non Hodgkins Lymphoma.
Pediatric Research (1978) 12, 470–470
PROGNOSIS
• Kemoterapi multimodal prognosis NHL pediatric meningkat
dramatis.
• Tingkat kesembuhan (cure rate) >70% untuk semua pediatrik NHL.
• Pasien dengan limited stage disease prognosis sangat baik
(excellent) dengan cure rate 85-90%.
FOLLOW UP
• CT atau MRI assessment ukuran massa
• PET aktivitas metabolik massa residual.
• Tujuan terapi tercapainya complete response (CR) pada kriteria
International Pediatric NHL:
Braithwaite KA, Cairo MS. Non Hodgkin Lymphoma in Children and Adolescent in Pediatric Hematology oncology Secrets.
2002. New York. Hanley and Belfus. P123-28
Sandlund JT, Downing JR, Crist WM. Non-Hodgkin’s lymphoma in childhood. N Engl J Med 1996;334:1238–1248.
KESIMPULAN
• Gejala klinis NHL pediatri tergantung pada jenis dan area yang terlibat.
• Potensial komplikasi emergensi dapat muncul saat diagnosis dan
evaluasi awal.
• Kemoterapi kombinasi: modalitas primer.
• Prognosis umumnya baik, cure rate >70%, limited stage disease
prognosis excellent cure rate 85-90%.
• Survivors anak resiko meningkat sequele jangka panjang follow up.
• Intususepsi pada limfoma Burkitt berusia lebih tua dari kasus
intususepsi anak pada umumnya reseksi komplit