Tutorial A14BLOK ONCOGEN

pemicuA, laki-laki,15thn, datang ke poliklinik rawat jalan

RSUP HAM dengan keluhan pembengkakan di daerah leher kiri tanpa rasa sakit disertai demam berulang sejak 4 bulan. Berat badan makin menurun, disertai keringat pada malam hari. A, sering mengeluh mudah capek ddan nafsu makan kurang. Pada pemeriksaan fisik anak sadar, tampak pucat, ukuran 13 x 9 x 8cm dan regio axilla kiri dengan ukuran 11 x 9x 6cm dengan konsistensi keras, permukaan rata, batas tidak tegas,immobil, tidak merah, tidak nyeri dan tidak panas.

Apa yang terjadi pada A?

More info hasil pemeriksaan darah rutin ditemukan kadar

Hb 8.2 g/dL, leukosit 4500/mm33 , trombosit 115.000/mm33 , , hitung jenis E5/B0/NB11/NS23/L43/M6, apusan darah tepi ditemukan sel atipik. Hasil pemeriksaan foto thoraks dijumpai pelebaran mediastinum. Hasil pemeriksaan biopsi jaringan histopatologi ditemukan sel Reed-Sternberg.

Bagaimana pendapat anda sekarang mengenai kasus A?

BENJOLAN

SAKITTIDAK SAKIT

INFEKSI PERADANGA

N

INFEKSI PERADANGA

NANAMNESISPEM. FISIKPEM LABBIOPSY

STAGING SEGERA RUJUKPENANGANAN

KERANGKA KONSEP

ANATOMI LEHER

KGB DAN SALURAN

Lymph node at the neck region• Anterior cervical lymph nodes: are located directly above and beneath the

muscles which enable you to flex and rotate your head.• Posterior cervical lymph nodes: are present at the back of your neck.• Tonsillar lymph nodes: can be found right below your jaw bone.• Submandibular lymph nodes: underlines both sides of your lower jaw.• Submental lymph nodes: located immediately below your chin.• Supraclavicular lymph nodes: are present in the hollow of the collar bone.

or

Submaxillary. Superficial Cervical.

Submental. Anterior Cervical.

Deep Cervical.

The submaxillary glands (lymphoglandulæ submaxillares) : 3-6 lymph nodes, are placed beneath the body of the mandible in the submaxillary triangle, and rest on the superficial surface of the submaxillary salivary gland.

One gland, the middle gland of Stahr, which lies on the external maxillary artery as it turns over the mandible, is the most constant of the series; small lymph glands are sometimes found on the deep surface of the submaxillary salivary glands. The afferents of the submaxillary glands drain the medial palpebral commissure, the cheek, the side of the nose, the upper lip, the lateral part of the lower lip, the gums, and the anterior part of the margin of the tongue; efferent vessels from the facial and submental glands also enter the submaxillary glands. Their efferent vessels pass to the superior deep cervical glands.

The submental or suprahyoid glands are situated between the anterior bellies of the Digastrici. Their afferents drain the central portions of the lower lip and floor of the mouth and the apex of the tongue; their efferents pass partly to the submaxillary glands and partly to a gland of the deep cervical group situated on the internal jugular vein at the level of the cricoid cartilage.

The superficial cervical glands (lymphoglandulæ cervicales superficiales) lie in close relationship with the external jugular vein as it emerges from the parotid gland, and, therefore, superficial to the Sternocleidomastoideus. Their afferents drain the lower parts of the auricula and parotid region, while their efferents pass around the anterior margin of the Sternocleidomastoideus to join the superior deep cervical glands.

The anterior cervical glands form an irregular and inconstant group on the front of the larynx and trachea. They may be divided into

(a)a superficial set, placed on the anterior jugular vein; (b) a deeper set, which is further subdivided into prelaryngeal, on

the middle cricothyroid ligament, and pretracheal, on the front of the trachea. This deeper set drains the lower part of the larynx, the thyroid gland, and the upper part of the trachea; its efferents pass to the lowest of the superior deep cervical glands.

The deep cervical glands (lymphoglandulæ cervicales profundæ)

1.are numerous and of large size: they form a chain along the carotid sheath, lying by the side of the pharynx, esophagus, and trachea, and extending from the base of the skull to the root of the neck.

2. They are usually described in two groups: superior deep cervical Inferior deep cervical

(1) the superior deep cervical glands lying under the Sternocleidomastoideus in close relation with the accessory nerve and the internal jugular vein, some of the glands lying in front of and others behind the vessel; The superior deep cervical glands drain the occipital portion of the scalp, the auricula, the back of the neck, a considerable part of the tongue, the larynx, thyroid gland, trachea, nasal part of the pharynx, nasal cavities, palate, and esophagus. They receive also the efferent vessels from all the other glands of the head and neck, except those from the inferior deep cervical glands

The efferents of the superior deep cervical glands pass partly to the inferior deep cervical glands and partly to a trunk which unites with the efferent vessel of the inferior deep cervical glands and forms the jugular trunk. On the right side, this trunk ends in the junction of the internal jugular and subclavian veins; on the left side it joins the thoracic duct.

(2) the inferior deep cervical glands extending beyond the posterior margin of the Sternocleidomastoideus into the supraclavicular triangle, where they are closely related to the brachial plexus and subclavian vein.A few minute paratracheal glands are situated alongside the recurrent nerves on the lateral aspects of the trachea and esophagus. The inferior deep cervical glands drain the back of the scalp and neck, the superficial pectoral region, part of the arm, occasionally, part of the superior surface of the liver, In addition, they receive vessels from the superior deep cervical glands.

Molecular Basic of Cancer

Viral carcinogenesis

•Oncogenic RNA virus •Oncogenic DNA virus

Oncogenic RNA virus

• The only retrovirus that cause cancer: Human T-cell Leukemia ( HTLV-1).

• Causes a T-cell leukemia , endemic in Japan and the Caribbean

• Tropism for CD4+ T cells; T-cell = major target

Genome of HTLV-1: have retroviral genes + a unique region: pX

Encodes several genes: TAX (necessary and sufficient for cellular transformation

Interact with transcription factors, eg. NF-ĸB

TX transactivate the expression of genes that encode cytokines, cytokine receptors, costimulating molecules

•Autocrine signaling loops and increase activation of pro-mitogenic signaling cascades•Directly bind to and activate cyclins drive progression through cell cycle•Repress fx of tumor suppressor gene (CDKN2A and p53)•Turns on cytokines gene and their receptors (IL-2, IL2-R, IL-15, IL15R); setting up autocrine systems and drives T-cell proliferation* IL-15 more improtant.•Parallel paracrine pathway activated by increase production of granulocyte-macrophage colony-stimulating factors stimulate neighbouring macrophage produce other T-cell mitogens

Oncogenic DNA viruses:

• 4 DNA virus:• HPV• EBV• Kaposi sarcoma herpesvirus (KSHV)/ HHV8• HBV

EBV• Pathogenesis of Burkitt lymphomas, B-cell

lymphomas w/ immunodeficiency synd, Hodgkin lymphoma, nasopharyngeal carcinoma

• All=B-cell tumors. Except , nasopharyngeal carcinoma

EBV- uses complement receptor (CD21)

Attach and infect B cells

Polyclonal B-cell proliferation and generation of B-lymphoblastoid cell lines

EBV- encoded genes / genome

LMP-1

Promotes B-cell proliferation by activating signaling pathways, eg. NF-

ĸB and JAK/STAT, which mimic B-cell activationi via the B-cell surface molecule

CD40

Prevent apoptosis by activating BCL-2

Virus “borrows” normal B cell activation pathway promote

own replication by expanding the pool of cell susceptible to infection

EBNA-2

Transactivates several host

genes ie. Cyclin D and src family

genes

Have viral cytokines, vIL-10

(pirated from host genome)

Prevent macrophage and monocytes from activating T-cells and is required for EBV-

dependent transformation of B-cells

• Immunologically normal human EBV driven polyclonal proliferation = readily controlled. So asymptomatic or develop self-limited episode of infectious mononucleosis.

• Key step = evasion of the immune system• Lymphoma cells emerge only whn

additional mutation eg. t (8;14) translocation activate the MYC oncogene. Activation substitute for LMP-1 signaling tumor cells down-regulate LMP-1 and evade the immune system.

Fungsi p53• protein 53 (p53) sebagai supressor tumor diduga

paling banyak berperan. • Fungsi p53 wild type sebagai negative control cell

cycle danguardian of genom mengalami degradasi karena membentuk kompleks p53-E6 atau mutasi p53.

• Kompleks p53-E6 dan p53 mutan adalah stabil, sedangkan p53 wild type adalah labil dan hanya bertahan 20-30 menit. Apabila terjadi degradasi fungsi p53 maka proses karsinogenesis berjalan tanpa kontrol oleh p53.

• Juga dipanggil sebagai “guardian of genome”

• P53 menjalankan 3fungsi:–Temporary cycle arrest–Permenant cycle arrest–apoptosis

P53 FUNCTION p53 protein has been shown to function as a transcriptional regulatory protein.In its wild-type state, the p53 protein is capable of binding to specific DNA sequences with its central core domain. The aminoterminal sequences of p53 function as a transcriptional activation domain, and the carboxy terminal sequences appear to be required for p53 to form dimers and tetramers with itself. p53 activates transcription of a number of genes with roles in the control of the cell cycle, including WAF1/CIP1/p21 (which encodes a regulator of Cdk activity), GADD45 (a growth-arrest DNA damage-inducible gene), MDM2 (as noted above, encoding a protein that is a known negative regulator of p53), and 14-3-3s (a regulator of G2/M progression), as well as various genes that likely function in apoptosis, including BAX, NOXA, and PUMA, and a number of genes encoding proteins involved in the generation of reactive oxygen species.

Other studies suggest that p53 may also function to repress the transcription of certain genes.98 While the specific mechanisms of p53 repression are not well understood and its importance to neoplasia is unclear, several candidate targets of p53 repression have been suggested, including the gene for the microtubule-associated protein MAP4,106 the multidrug-resistance-associated protein 1 (MRP1),107 and the gene for FKBP25, an FK506/rapamycin-binding protein.

Hodgkin Lymphoma

Definition of Lymphoma

• Lymphoma is a cancer in the lymphatic of the immune system and presents as a solid tumor of lymphoid cells. These malignant cells often originate in lymph nodes, presenting as an enlargement of the node (a tumor). Morphologically they are small round blue cell tumors and are subdivided into two major categories: non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL)

Hodgkin's lymphoma is a malignant tumour of the lymphatic system that is characterised histologically by the presence of multinucleated giant cells (Reed-Sternberg cells) and associated abnormal and smaller mononuclear cells originating from B lymphocytes in the germinal centres of lymphoid tissue.

Definition of Hodgkin Lymphoma

Etiology

• infectious agents, particularly EBV.• Patients who had developed mononucleosis

have an increased risk of developing Hodgkin's disease.

• Use of drugs which affect the function of the immuno system (immune suppressant).

• Other risk factors include HIV and cigarette smoking.

Nodular sclerosing• more commonly seen in young adults• usually involves the lymph glands of the neckand chestMixed cellularity• more commonly seen in older people (over50 years)Lymphocyte-richLymphocyte depleted• disease tends to be more widespread atdiagnosisNodular lymphocyte predominant• tends to be slow growing• responds well to radiotherapy andchemotherapy

WHO CLASSIFICATION

STAGING

Gejala klinis

Gejala PenyebabKemungkinan timbulnya

gejala

Gangguan pernafasan Pembengkakan wajah

Pembesaran kelenjar getah bening di dada

20-30%

Hilang nafsu makan Sembelit berat Nyeri perut atau perut kembung

Pembesaran kelenjar getah bening di perut

30-40%

Pembengkakan tungkaiPenyumbatan pembuluh getah bening di selangkangan atau perut

10%

Penurunan berat badan Diare Malabsorbsi

Penyebaran limfoma ke usus halus

10%

Pengumpulan cairan di sekitar paru-paru (efusi pleura)

Penyumbatan pembuluh getah bening di dalam dada

20-30%

Daerah kehitaman dan menebal di kulit yang terasa gatal

Penyebaran limfoma ke kulit 10-20%

Penurunan berat badan Demam Keringat di malam hari

Penyebaran limfoma ke seluruh tubuh 50-60%

Anemia (berkurangnya jumlah sel darah merah)

Perdarahan ke dalam saluran pencernaan Penghancuran sel darah merah oleh limpa yang membesar & terlalu aktif Penghancuran sel darah merah oleh antibodi abnormal (anemia hemolitik) Penghancuran sumsum tulang karena penyebaran limfoma Ketidakmampuan sumsum tulang untuk menghasilkan sejumlah sel darah merah karena obat atau terapi penyinaran

30%, pada akhirnya bisa mencapai 100%

Mudah terinfeksi oleh bakteriPenyebaran ke sumsum tulang dan kelenjar getah bening, menyebabkan berkurangnya pembentukan antibodi

20-30%

Patofisiologi

If the patient has Hodgkin’s Lymphoma, therefore :

Immunoglobulin gene mutation of B cells

Production of B cells with ‘crippled’ immunoglobulin gene leading to formation of Reed-Sternberg (RS) cells

Reed-Sternberg cells

have high levels of transcription factor, ( NF-kB)

excessive proliferation of B cells

membentuk massa ( tumor )

tumor menyerang jaringan limfoid ( pembengkakan KGB ) dan jaringan sekitarnya hingga merampas

oksigen dan nutrisi yang diperlukan untuk bertahan hidup dan berfungsi secara normal

penekanan sel darah merah,trombosit dan sel darah

putih (sstl)

limfoma yang hadir dalam sstl Anemia

somatic mutation

Failure to inhibit ( NF-kB)

butuh energi lebih banyak

katabolisme tubuh meningkat

produksi panas tubuh meningkat

vasodilatasi pemb darah perifer untuk membuang panas

keringat malam

TNF – alpha,IL 1 beta,INF,IL 6

melepaskan sitokin inflamasi

sintesis protein turun

Sindroma Kaheksia Kanker

( lemah,capek,nafsu makan dan berat badan berkurang )

supresi pusat makan (sitokin pro-

inflamasi- cachectin)

IL 5

aktivasi eusinofil

sel inflamatori melepaskan faktor-faktor inflamatori

eg.Pirogen

memicu pelepasan prostaglandin

aktifkan hypothalamus (thermostat)

Set point meningkat

demam

IL 13

autocrine stimulation towards

RS cells

Diagnosis Banding Limfoma Hodgkin

• Diagnosis banding serupa dengan yang dijelaskan untuk limfoma non Hodgkin pada pasien dengan limfadenopati di leher, infeksi misalnya faringitis bakteri atau virus, mononucleosis infeksiosa dan toksoplasmosis harus disingkirkan.

• Keganasan lain,misalnya limfoma non Hodgkin, kanker nasofaring dan kanker tiroid dapat menimbulkanadenopati leher local.

• Adenopati ketiak harus dibedakan dengan limfoma non Hodgkindan kanker payudara.

• Adenopati mediastinum harus dibedakan dengan infeksi, sarkoid dan tumor lain.

• Pada pasien tua, diagnosis banding mencakup tumor paru dan mediastinum, terutamakarsinoma sel kecil dan non sel kecil. Medistinitis reaktif dan adenopati hilus akibat histoplasmosis dapat mirip dengan limfoma, karena penyakit tersebut timbul pada pasien asimtomatik.

• Penyakit abdomen primer dengan hepatomegali, splenomegali dan adenopati massif jarang ditemukan, dan penyakit neoplastik lain, terutama limfoma nonHodgkin harus disingkirkan dalam keadaan ini

Masalah lain untuk Be Dianggap• Setiap penyakit menyajikan dengan limfadenopati dan

gejala konstitusional• Infeksi HIV• Reaksi hipersensitivitas• Lain solid tumor• Kadang-kadang, penyakit Hodgkin ('s Limfoma

Hodgkin) dapat hadir dengan sindrom hemophagocytic (lymphohistiocytosis hemophagocytic). sindrom Hemophagocytic dikaitkan dengan ekspresi antigen EBV oleh-Sternberg sel Reed dan secara klinis ditandai dengan pansitopenia, demam; hepatosplenomegali dengan uji kelainan fungsi hati; serum tingkat feritin dan trigliserida, dan fagositosis sel keturunan hematopoietic oleh makrofag jinak.

Diagnosis Banding Limfoma HodgkinSitomegalovirusSipilisInfectious mononucleosisSistemik Lupus EritematosusKanker paru-paru, Oat Cell (Cell Kecil)ToxoplasmosisLimfoma, Non-HodgkinTuberkulosisRheumatoid ArthritisSarkoidosisSerum Sickness

Dasar-dasar penegakan diagnosis

Pem. FisikAspek dari segi PK,PA

Pem penunjang

1. ANAMNESIS• ADA TIDAKNYA DEMAM > 38˚C YANG

PERSISTEN, KERINGAT MALAM ATAU DALAM 6 BULAN BERAT BADAN TURUN LEBIH DARI 10% TANPA ETIOLOGI LAIN YANG DAPAT MENJELASKAN

• ADA TIDAKNYA RIWAYAT INFEKSI BERULANG

• ADA TIDAKNYA NYERI DADA, BATUK, SESAK NAFAS – DAPAT DITEMUI PADA PEMBESARAN KELENJAR LIMFE DI BAGIAN MEDIASTINUM ATAU TERJADI LUNG INVOLVEMENT

• RIWAYAT KELUARGA TERPAPAR PADA TOKSIN, PEKERJAAN IBU BAPA , PENYAKIT IMMUNE DEFICIENCIES DAN FAMILIAL CANCER

2. PEMERIKSAAN FISIK• PEMBESARAN KELENJAR LIMFE

(LIMFADENOPATI) – SAIZ DAN LOKASI• PERHATIKAN AREA LIMFATIK DAN CINCIN

WALDEYER FARING• MANIFESTASI PADA KULIT• UKURAN HATI DAN LIMPA• ADA TIDAKNYA NYERI TEKAN TULANG

3. PEMERIKSAAN LABORATORIUM• DARAH LENGKAP• URINALISIS RUTIN• FUNGSI HATI DAN GINJAL• LAJU ENDAP DARAH• ELEKTROLIT DARAH• BIOKIMIA RUTIN (GULA DARAH, LDH SERUM,

FOSFATASE ALKALI, ASAM URAT DLL)• FUNGSI IMUNITAS (BILA FASILITAS TERSEDIA)

Imaging Studies• Chest radiography is performed with anteroposterior and lateral

projections to assess the bulk of the mediastinal mass. Mediastinal mass with a thoracic ratio of 33% or greater is of prognostic importance.

• CT or MRI of neck, chest, abdomen, and/or pelvis may be indicated to assess sites of disease (nodal and extranodal) as well as to assess liver and spleen involvement.

• Ultrasonography can be used to assess the abdominal and pelvic structures in centers with limited resources in which CT scanning or MRI is not available.

• On positron emission tomography (PET), uptake of the radioactive glucose analog 2-[18F]fluoro-2-deoxy-D-glucose (FDG) is correlated with proliferative activity in tumors undergoing anaerobic glycolysis. PET scans are used with increasing frequency to identify the extent of disease at diagnosis and for follow up. After two cycles of therapy with doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine (ABVD), a positive PET scan finding may be predictive of poor outcome.

• Gallium scanning is rarely used and has been replaced by PET scanning.• Bone scan is necessary only when bony metastases are suspected

because of an elevated alkaline phosphatase level. However, the same information may be obtained with PET scanning.

Procedures• Staging laparotomy is no longer advocated in pediatric

Hodgkin lymphoma.• Lymph node biopsy findings may be helpful.

– Histopathologic studies consist of hematoxylin and eosin staining and special immunohistochemical staining for surface markers such as CD15, CD20, CD30, and CD45.

– Consider other immunohistochemical staining to ensure that they are negative and to rule out non-Hodgkin lymphoma, such as CD3 and anaplastic lymphoma kinase (ALK).

• Fine-needle aspiration is not recommended because of lack of stromal tissue and the difficulty of classifying the Hodgkin lymphoma into one of the classic subtypes versus the nodular lymphocyte–predominant (NLP) subtype.

• Bilateral bone marrow biopsy is necessary in all patients with suspected involvement of the bone marrow and in those with stage IIB, III, or IV disease.

Histologic Findings• Classification • The most recent and currently accepted classification is the Revised European-

American Lymphoma (REAL) classification as modified and adopted by the WHO reflects the distinction of NLP Hodgkin lymphoma from classic Hodgkin lymphoma.3 The system is as follows:2

• Classic nodular sclerosing: This class is notable for fibrous bands that result in a nodular pattern and lacunar-type Hodgkin-Reed-Sternberg (HRS) cells wherein the cytoplasm in formalin-fixed specimens retracts, forming a lacuna around the nucleus. This is the most common type in all age groups (77% of adolescents and 72% of adults), although it affects only 44% of younger children.

• Classic mixed cellularity: This class may have interstitial fibrosis, but fibrous bands are not observed. HRS cells are classic in appearance or mononuclear. Lymphocytes may predominate in the cellular background. This subtype is more common in young children (33%) than in adolescents (11%) or adults (17%).

• Classic lymphocyte rich: This class has classic or lacunar-type HRS cells with rare or absent eosinophils on a cellular background. This type is extremely rare.

Classic lymphocyte depleted: This class has large numbers of HRS cells with sarcomatous variants and a hypocellular background because of fibrosis and necrosis. This type is also extremely rare.

NLP: This form may be nodular, but fibrosis is unusual. The HRS cell variants are known as lymphocytic and histiocytic (L&H) or popcorn cells. The nuclei are multilobed and vesicular with small nucleoli. The characteristic halo of the classic H-RS cell is absent. The background consists of histiocytes and lymphocytes with a B-cell predominance in contrast to the cellular background in classic Hodgkin disease, which has a T-cell predominance.

ImmunophenotypingThe classic subtypes of Hodgkin lymphoma are positive for CD15

and CD30 and may be positive for CD20, whereas NLP Hodgkin lymphoma is negative for CD15 and CD30 but positive for CD20 and CD45.

Lumbar Puncture Lumbar puncture—also known as a spinal tap—

is a procedure in which a thin needle is inserted through the lumbar (lower) backbone, below the level of the spinal cord. Cerebrospinal fluid (CSF) is withdrawn through the needle, and is then analyzed for the presence of lymphoma cells. This test is performed to see whether lymphoma has spread to the central nervous system.

Penanganan

KemoterapiRadioterapi

BedahTerapi penunjang/suportif

Treatment :• The doctor will present each type of treatment, discuss the

pros and cons, and make recommendations based on published treatment guidelines and his or her own experience.

Treatment for lymphoma depends on the type and stage. Factors such as age, overall health, and whether one has already been treated for lymphoma before are included in the treatment decision-making process.

The decision of which treatment to pursue is made with the doctor (with input from other members of the care team) and family members, but the decision is ultimately the patient's.

Chemotherapy

• Chemotherapy is a treatment of cancer with drugs (or medication). A chemotherapy drug acts by killing tumor cells. When chemotherapy is delivered, either in the form of an injection or an oral medication, the drug travels through the blood to reach the tumor. There it can act on tumor cells in many ways, ultimately causing their death.

Common chemotherapy schedules include ABVD, R-CHOP and CHOP.

ABVD is an abbreviated name of a chemotherapy combination commonly used to treat Hodgkin's Disease. The drugs used are Adriamycin, Bleomycin, Vinblastine, and Dacarbazine (DTIC). These medicines are administered as injections and are usually repeated every 2 weeks.

It is a relatively new combination which adds the drug Rituximab - a monoclonal antibody, to the standard combination called CHOP. CHOP consists of four chemotherapy drugs. Rituximab is administered as an infusion over a few hours on the first day of treatment, while the drugs of the CHOP regimen may be started the next day. The entire course is usually repeated every three weeks for 6-8 cycles.

CHOP consists of four drugs - Cyclophosphamide (also called Cytoxan/Neosar), Doxorubicin (or Adriamycin), Vincristine (Oncovin) and Prednisolone.

The first three drugs of the CHOP chemotherapy regimen are usually given as injections or infusions in veins on a single day, while prednisolone is taken as pills for five days.Each cycle is repeated every 3 weeks for 6-8 cycles.

RadiotherapyRadiotherapy– High energy rays that are directed

at the tumor. Radiotherapy can be delivered over small areas (involved field radiation) or large areas (extended field radiation).

Antibody therapy(also called biological therapy) – Using drugs like Rituximab that target special molecules on the surface of cancer cells.

Bone marrow or stem cell transplant– Using high doses of chemotherapy or radiation to kill all cancer cells while saving the bone marrow with transplantation of marrow or stem cells.

Prevention

• Cancer is largely a preventable illness.• Two-thirds of cancer deaths in the U.S. can be linked

to tobacco use, poor diet, obesity, and lack of exercise.

• The overwhelming majority of cases of Hodgkin’s disease cannot be prevented since we do not know the cause.

• Scientists around the world have been working on vaccine strategies against Epstein-Barr virus associated diseases. This work has been hampered by an inability to identify the characteristics of the virus when it remains dormant in the body.

Diet modification

• Real culprit is an excess of calories.• Studies show that excessive caloric intake from both fats and

carbohydrates have the same result of excess body fat.• Ideal way to prevent excess body fat is to limit caloric intake and/or

balance caloric intake with ample exercise.• Studies show that high consumption of red meat and dairy products

can increase the risk of certain cancers. One strategy for positive dietary change is to replace red meat with chicken, fish, nuts, and legumes.

• High fruit and vegetable consumption has been associated with a reduced risk for developing at least 10 different cancers. This may be a result of potentially protective factors, such as carotenoids, folic acid, vitamin C, flavonoids, phytoestrogens, and isothiocyanates.

• Strong evidence that moderate to high alcohol consumption also increases the risk of certain cancers. One reason for this relationship may be that alcohol interferes with the availability of folic acid. Alcohol in combination with tobacco creates an even greater risk.

Exercise: Higher levels of physical activity may reduce the incidence of some cancers.

Screening for Hodgkin’s Lymphoma• The term screening refers to the regular use of certain

examinations or tests in persons who do not have any symptoms of a cancer but are at high risk for that cancer.

• When individuals are at high risk for a type of cancer, this means that they have certain characteristics or exposures, called risk factors that make them more likely to develop that type of cancer than those who do not have these risk factors.

• An awareness of these risk factors is important . Persons who are at high risk for developing a cancer can often undergo regular screening measures that are recommended for that cancer type.

• Hodgkin’s disease is usually diagnosed because patients have signs and symptoms, including a painless swelling in the lymph nodes in the neck, under the arm, or in the groin; unexplained fevers; night sweats; unexplained weight loss; and/or itchy skin.

• In order for screening to be effective, patients at risk for Hodgkin’s disease need to be identifiable. This is not currently possible, with the exception of identifying patients who have one of a few genetic diseases and screening them accordingly.

Surgery-For diagnosis and treatment-Removal of lymph node and lymphatic tissue

Stem cell transplantation• In blood stream and bone marrow• diseased bone marrow is replaced by highly specialized cells,

called hematopoietic stem cells • Allogenic-stem cells are obtained from a donor whose tissue

matches the patient’s on a genetic level, called HLA-typing. • Autologous-patient’s own stem cells are used as the

replacement. The stem cells are obtained from the patient when he or she is in remission from previous treatment. The stem cells are then frozen until the high-dose treatment for the transplant is completed.

• goal of transplantation is to destroy cancer cells in the marrow, blood, and other parts of the body and have replacement blood stem cells create healthy bone marrow

Supportive therapy

• Fever-antiinflamation-indomethacin/ naproksen

• Nutrition• Pain- VAS 1-3 –acetaminophen VAS 4-6 – acetaminophen + opiod

ringan VAS 7-10- +morfin• Ca, Mg, Vit D

KesimpulanR menderita Hodgkin Limfoma dan harus dirujuk segera.