62883229 JURNAL THT Nasopharyngeal Carcinoma 2 INGGRIS

7/28/2019 62883229 JURNAL THT Nasopharyngeal Carcinoma 2 INGGRIS

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Nasopharyngeal carcinomaBernadette Brennan

Correspondence: Bernadette [email protected] AffiliationsRoyal Manchester Children's Hospital, Hospital Road, M27 4HA Manchester, UK

Orphanet Journal of Rare Diseases 2006, 1:23 doi:10.1186/1750-1172-1-23

The electronic version of this article is the complete one and can be found online at:

http://www.OJRD.com/content/1/1/23

Received: 12 May 2006

Accepted: 26 June 2006

Published:26 June 2006

2006 Brennan; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons AttributionLicense (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use,distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Nasopharyngeal carcinoma (NPC) is a tumor arising from the epithelial cells that cover the

surface and line the nasopharynx. The annual incidence of NPC in the UK is 0.3 per million at

age 014 years, and 1 to 2 per million at age 1519 years. Incidence is higher in the Chinese and

Tunisian populations. Although rare, NPC accounts for about one third of childhoodnasopharyngeal neoplasms. Three subtypes of NPC are recognized in the World Health

Organization (WHO) classification: 1) squamous cell carcinoma, typically found in the olderadult population; 2) non-keratinizing carcinoma; 3) undifferentiated carcinoma. The tumor can

extend within or out of the nasopharynx to the other lateral wall and/or posterosuperiorly to the

base of the skull or the palate, nasal cavity or oropharynx. It then typically metastases to cervical

lymph nodes. Cervical lymphadenopathy is the initial presentation in many patients, and thediagnosis of NPC is often made by lymph node biopsy. Symptoms related to the primary tumor

include trismus, pain, otitis media, nasal regurgitation due to paresis of the soft palate, hearing

loss and cranial nerve palsies. Larger growths may produce nasal obstruction or bleeding and a

"nasal twang". Etiological factors include Epstein-Barr virus (EBV), genetic susceptibility and

consumption of food with possible carcinogens volatile nitrosamines. The recommendedtreatment schedule consists of three courses of neoadjuvant chemotherapy, irradiation, and

adjuvant interferon (IFN)-beta therapy.

Definition

Nasopharyngeal carcinoma (NPC) is a tumor arising from the epithelial cells that cover the

surface and line the nasopharynx. NPC was first described as a separate entity by Regaud and
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Schmincke in 1921 [1,2]. Approximately one third of nasopharyngeal carcinomas of the

undifferentiated type are diagnosed in adolescents or young adults. Although rare, NPC accounts

for one third of childhood nasopharyngeal neoplasms (data from USA) [3].

Epidemiology

The annual incidence of NPC in the UK is 0.25 per million (age standardized, age 014 years),

0.1 per million at age 09 years and 0.8 per million at age 1014 years. It seems reasonable to

assume, on the basis of England and Wales cancer registry data, that at least 80% of

nasopharyngeal cancers at age 1519 years are carcinomas. This suggests an incidence of 1 to 2per million for NPC at age 1519 years.

In comparison with other countries, the incidence in the UK is low. In particular, in Tunisia theincidence is relatively high [4]. In southern parts of China, Southeast Asia, the Mediterranean

basin and Alaska the incidence of NPC is moderately elevated; an incidence of 2 per million of

NPC in China has been reported [5]. In other countries, for example in India, the incidence is

comparable to that in the UK at 0.9 per million. Furthermore, the younger age peak in the seconddecade found in India [6], is also found in the UK[7].

Etiology

NPC is the commonest epithelial cancer in adults. The detection of nuclear antigen associated

with Epstein-Barr virus (EBNA) and viral DNA in NPC type 2 and 3, has revealed that EBV caninfect epithelial cells and is associated with their transformation [8]. The etiology of NPC

(particularly the endemic form) seems to follow a multi-step process, in which EBV, ethnic

background, and environmental carcinogens all seem to play an important role.

Lo et al. showed that EBV DNA was detectable in the plasma samples of 96% of patients withnon-keratinizing NPC, compared with only 7% in controls [9]. More importantly, EBV DNAlevels appear to correlate with treatment response [9-11] and they may predict disease recurrence

[11], suggesting that they may be an independent indicator of prognosis [12].

In adults, other likely etiological factors include genetic susceptibility, consumption of food (in

particular salted fish) containing carcinogenic volatile nitrosamines, and as in children, EBV

[13,15-19].

Clinical presentation

NPC usually originates in the lateral wall of the nasopharynx, which includes the fossa ofRosenmuller. It can then extend within or out of the nasopharynx to the other lateral wall and/or

posterosuperiorly to the base of the skull or the palate, nasal cavity or oropharynx. It then

typically metastases to cervical lymph nodes. Distant metastases may occur in bone, lung,mediastinum and, more rarely, the liver.

Cervical lymphadenopathy is the initial presentation in many patients, and the diagnosis of NPCis often made by lymph node biopsy. Symptoms related to the primary tumor include trismus,
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pain, otitis media, nasal regurgitation due to paresis of the soft palate, hearing loss and cranial

nerve palsies. Larger growths may produce nasal obstruction or bleeding and a "nasal twang".

Metastatic spread may result in bone pain or organ dysfunction. Rarely, a paraneoplasticsyndrome of osteoarthropathy may occur with widespread disease.

HistopathologyThree subtypes of NPC are recognized in the World Health Organisation (WHO) classification

[20]:

type 1: squamous cell carcinoma, typically found in the older adult population

type 2: non-keratinizing carcinoma

type 3: undifferentiated carcinoma

Most cases in childhood and adolescence are type 3, with a few type 2 cases [21]. Type 2 and 3are associated with elevated Epstein-Barr virus titers, but type 1 is not [22]. The Colognemodification of the WHO scheme by Krueger and Wustrow [23] includes the degree of lymphoid

infiltration. Types 2 and 3 may be accompanied by an inflammatory infiltrate of lymphocytes,

plasma cells, and eosinophils, which are abundant, giving rise to the term lymphoepithelioma.Two histological patterns may occur: Regaud type, with a well-defined collection of epithelial

cells surrounded by lymphocytes and connective tissue, and Schmincke type, in which the tumor

cells are distributed diffusely and intermingle with the inflammatory cells. Both patterns may be

present in the same tumor.

Diagnostic methods

Diagnostic methods include:

1. Clinical evaluation of the size and location of cervical lymph nodes.

2. Indirect nasopharyngoscopy to assess the primary tumor.

3. Neurological examination of cranial nerves.

4. Computed tomography (CT)/magnetic resonance imaging (MRI) scan of the head and neck to

below clavicles to assess base of skull erosion.

5. Chest radiotherapy (anteroposterior and lateral) to see if NPC has spread to the lungs.

6. Bone scintigraphy by Tc 99 diphosphonate to show whether cancer has spread to the bones.

7. Full blood count.

8. Urea, electrolyte, creatinine, liver function, Ca, PO4, alkaline phosphate.
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9. EBV viral capsid antigen and EBV DNA.

10. Biopsy of either the lymph nodes or primary tumor for histological examination.

Staging

The tumor, node, metastasis (TNM) classification of the American Joint Committee on Cancer

[24]sixth edition (Table1) is usually used to determine the tumor staging (Table2). This latest

TNM classification takes into account Ho's [25] modifications for NPC, which utilizes theprognostic importance of affected nodes extending into the lower cervical and supraclavicular

areas.

Table 1.The tumor, node, metastasis (TNM) classification of the American Joint Committee onCancer [24]

Table 2.Stage grouping

Treatment

Surgery

Due to the anatomical position of NPC and its tendency to present with cervical lymph node

metastases, it is not amenable to surgery for local control. Biopsy of the involved lymph node is

the usual surgical procedure. The nasopharyngeal primary tumor is rarely biopsied.

Chemotherapy

Several factors are taken into account in deciding the chemotherapy regimen.

Firstly, efficacy: the figures for event-free survival are similar for most small chemotherapy

series but therapy usually involves fairly high-dose radiotherapy to the nasopharynx 60 to 65

Gy. However, the most promising results with a recent update, are those obtained using the

Mertens protocol NPC-91-GPOH (Society of Pediatric Oncology and Hematology). Thisprotocol should therefore be considered as the best current treatment. Uniquely, the NPC-91-

GPOH protocol includes immunotherapy with interferon-beta after chemotherapy and

radiotherapy, which may explain its superior results compared to regimens without interferontreatment [27].

Secondly, late effects: in terms of chemotherapy, the Manchester regimen doxorubicin,methotrexate and cyclophosphamide would produce infertility in boys (total dose ofcyclophosphamide 12 gm/m

2) and possible anthracycline toxicity (total dose of doxorubicin 360

mg/m2) [36]. The NPC-91-GPOH protocol might produce some infertility in older boys but the

total dose of cisplatinum is only 300 mg/m2. Furthermore, the incidence of renal toxicity should

be relatively low but auditory toxicity would be higher because of the additional effect of

irradiation on the auditory apparatus. The degree of pituitary dysfunction obviously depends on

the radiotherapy field and, potentially, on the dose of radiotherapy but some degree of
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hypopituitarism is expected. Furthermore, irradiation to the neck would result in hypothyroidism

for the majority of patients and irradiation to the oropharynx would result in xerostomia and

resultant poor dentition. The later may be relieved by amifostine, as demonstrated in adultstudies.

Radiotherapy

Although treatment with radiotherapy controls the primary tumor[28-30], it does not prevent the

appearance of distant metastases [28,31].

Radiotherapy is given with megavoltage equipment after initial chemotherapy. A maximum doseof 45 Gy is given to the clinical target volume, which is a 1 cm margin around the MRI-detected

primary site, and inferiorly down to the clavicles to include the lymph nodes. Treatment is given

in two phases:

Phase I parallel pair (mostly lateral unless the tumor extends anteriorly between the eyes).

Eyes, brain and brain stem are shielded as much as possible. A mid-plane dose of 30 Gy in 15fractions is given.

Phase II a lateral parallel pair or three-fields technique is used for the primary site, delivering

15 Gy in seven fractions to the clinical target volume of the tumor with a 1 cm margin. Brainstem and eyes should be shielded. Any overlap with the neck field should be shielded. A

matching anterior neck node field is used to deliver a prescribed maximum subcutaneous dose of

15 Gy in seven fractions. The spinal cord should be shielded in this field. This prescription forradiotherapy is used in Manchester, but it is recognized that higher doses may be used in some

centers, possibly to a total of 60 Gy to the tumor volume. In an current GPOH study, patients in

complete remission (CR) after three courses of chemotherapy, will have their radiotherapy

dosage reduced to 54 Gy instead of 59 Gy.

Recommendation

In the current GPOH protocol NPC-2003-GPOH, low-risk patients with Stage I and II tumors

receive radiotherapy only, followed by 105 g/Kg of adjuvant interferon beta (IFNbeta),intravenously (i.v.), three times a week for 6 months. High-risk patients receive cisplatinum (100

mg/m2

over 6 hours on day 1 with standard hydration), mannitol and electrolyte replacement, and

folinic acid (25 mg/m2

every 6 hours for a total of six doses) as well as 5-fluorouracil (1000

mg/m2per day from day 2 for 5 days) as a continuous infusion. They receive three courses of

chemotherapy every 21 days or on full blood count recovery, followed by irradiation and

IFNbeta as for low-risk patients. Methotrexate has been dropped because of severe mucositis.

Patients not in CR after three courses of chemotherapy will receive concomitant cisplatinum (20

mg/m2/day for 3 days with radiotherapy for two courses).

Prognostic factors

Presentation with lymphadenomegalia implies that the disease has spread beyond the primary

site. However, in childhood the presence of metastatic disease in cervical lymph nodes at
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diagnosis does not adversely affect prognosis [30-33]. Factors associated with a poor prognosis

are skull base involvement [33-35], extent of the primary tumor [31,32] and cranial nerve

involvement [33,34].

Unresolved questions

1. What is the optimum radiotherapy dose?

2. Would exclusion of interferon from the treatment produce similar results?

3. The relationship between late effects and dose of radiotherapy should be investigated, as well

as the exact nature and incidence of late effects.

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2. Schmincke A: ber lymphoepitheliale Geschwlste.Beitr Pathol Anat1921, 68:161-170.

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http://www.ojrd.com/pubmed/15999363http://www.ojrd.com/pubmed/15999363http://www.ojrd.com/pubmed/15999363http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=15999363http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=15999363http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=15999363http://www.ojrd.com/pubmed/15641027http://www.ojrd.com/pubmed/15641027http://www.ojrd.com/pubmed/15641027http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=15641027http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=15641027http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=15641027http://www.ojrd.com/pubmed/638955http://www.ojrd.com/pubmed/638955http://www.ojrd.com/pubmed/638955http://dx.doi.org/10.1002/1097-0142%28197803%2941:3%3C1128::AID-CNCR2820410348%3E3.0.CO;2-Shttp://dx.doi.org/10.1002/1097-0142%28197803%2941:3%3C1128::AID-CNCR2820410348%3E3.0.CO;2-Shttp://dx.doi.org/10.1002/1097-0142%28197803%2941:3%3C1128::AID-CNCR2820410348%3E3.0.CO;2-Shttp://www.ojrd.com/pubmed/12119964http://www.ojrd.com/pubmed/12119964http://www.ojrd.com/pubmed/12119964http://dx.doi.org/10.1016/S0022-3476%2874%2980560-3http://dx.doi.org/10.1016/S0022-3476%2874%2980560-3http://dx.doi.org/10.1016/S0022-3476%2874%2980560-3http://www.ojrd.com/pubmed/7459824http://www.ojrd.com/pubmed/7459824http://www.ojrd.com/pubmed/7459824http://dx.doi.org/10.1002/1097-0142%2819810115%2947:2%3C360::AID-CNCR2820470225%3E3.0.CO;2-3http://dx.doi.org/10.1002/1097-0142%2819810115%2947:2%3C360::AID-CNCR2820470225%3E3.0.CO;2-3http://dx.doi.org/10.1002/1097-0142%2819810115%2947:2%3C360::AID-CNCR2820470225%3E3.0.CO;2-3http://www.ojrd.com/pubmed/7390929http://www.ojrd.com/pubmed/7390929http://www.ojrd.com/pubmed/7390929http://www.ojrd.com/pubmed/7087893http://www.ojrd.com/pubmed/7087893http://www.ojrd.com/pubmed/7087893http://www.ojrd.com/pubmed/4337403http://www.ojrd.com/pubmed/4337403http://www.ojrd.com/pubmed/4337403http://www.ojrd.com/pubmed/6016269http://www.ojrd.com/pubmed/6016269http://www.ojrd.com/pubmed/6016269http://www.ojrd.com/pubmed/7053813http://www.ojrd.com/pubmed/7053813http://www.ojrd.com/pubmed/7053813http://dx.doi.org/10.1002/1097-0142%2819820101%2949:1%3C163::AID-CNCR2820490132%3E3.0.CO;2-8http://dx.doi.org/10.1002/1097-0142%2819820101%2949:1%3C163::AID-CNCR2820490132%3E3.0.CO;2-8http://dx.doi.org/10.1002/1097-0142%2819820101%2949:1%3C163::AID-CNCR2820490132%3E3.0.CO;2-8http://www.ojrd.com/pubmed/3153224http://www.ojrd.com/pubmed/3153224http://www.ojrd.com/pubmed/3153224http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B36http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B35http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B34http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B33http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B32http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B31http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B30http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B29http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B28http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B27http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B26http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B36http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B35http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B34http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B33http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B32http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B31http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B30http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B29http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B28http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B27http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B26http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B36http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B35http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B34http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B33http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B32http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B31http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B30http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B29http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B28http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B27http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B26http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B36http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B35http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B34http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B33http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B32http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B31http://www.ojrd.com/sfx_links?ui=1750-1172-1-23&bibl=B30http://www.ojrd.com/sfx_links?ui=1750-1172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TERJEMAHAN JURNAL THT 2 INGGRIS

Karsinoma nasofaring

Bernadette Brennan

Korespondensi: Bernadette Brennan bernadette.brennan @ cmmc.nhs.uk

Penulis AfiliasiManchester kerajaan Anak Rumah Sakit, Rumah Sakit Road, M27 4HA Manchester, Inggris

Orphanet Jurnal Penyakit, Langka 2006 01:23 DOI: 10.1186/1750-1172-1-23

AbstrakKarsinoma nasofaring (NPC) adalah tumor yang timbul dari sel-sel epitel yang menutupi

permukaan dan garis nasofaring. Kejadian tahunan NPC di Inggris adalah 0,3 per juta pada usia

0-14 tahun, dan 1 sampai 2 per juta pada usia 15-19 tahun. Insidensi lebih tinggi pada populasi

Cina dan Tunisia. Meskipun jarang, NPC menyumbang sekitar sepertiga dari masa kanak-kanakneoplasma nasofaring. Tiga subtipe NPC diakui di Organisasi Kesehatan Dunia (WHO)

klasifikasi: 1) karsinoma sel skuamosa, biasanya ditemukan pada populasi orang dewasa yang

lebih tua; 2) non-keratinizing karsinoma; 3) karsinoma dibeda-bedakan. Tumor dapat

memperpanjang dalam atau keluar dari nasofaring ke dinding lateral lain dan / atauposterosuperiorly ke dasar tengkorak atau langit-langit mulut, rongga hidung atau orofaring. Ini

kemudian biasanya metastasis ke kelenjar getah bening leher. Limfadenopati serviks merupakan

presentasi awal pada banyak pasien, dan diagnosis NPC sering dibuat oleh biopsi kelenjar getahbening. Gejala terkait dengan tumor primer meliputi trismus, nyeri, otitis media, regurgitasi

hidung karena paresis dari langit-langit lunak, kehilangan pendengaran dan kelumpuhan saraf

kranial. Pertumbuhan yang lebih besar dapat menghasilkan obstruksi hidung atau perdarahan dan

"aksen hidung". Faktor etiologi termasuk virus Epstein-Barr (EBV), kerentanan genetik dankonsumsi makanan dengan kemungkinan karsinogen - nitrosamine volatile. Jadwal pengobatan

yang dianjurkan terdiri dari tiga program dari neoadjuvant kemoterapi, radiasi, dan adjuvan

interferon (IFN)-beta terapi.

DefinisiKarsinoma nasofaring (NPC) adalah tumor yang timbul dari sel-sel epitel yang menutupipermukaan dan garis nasofaring. NPC pertama kali dijelaskan sebagai entitas yang terpisah olehRegaud dan Schmincke pada tahun 1921 [1,2]. Sekitar sepertiga dari karsinoma nasofaring tipe

dibedakan didiagnosis pada remaja atau dewasa muda. Meskipun jarang, NPC account untuk

satu sepertiga dari neoplasma anak nasofaring (data dari AS) [3].

EpidemiologiKejadian tahunan NPC di Inggris adalah 0,25 per juta (umur standar, usia 0-14 tahun), 0,1 per

juta pada usia 0-9 tahun dan 0,8 per juta pada usia 10-14 tahun. Tampaknya masuk akal untukberasumsi, berdasarkan Inggris dan kanker Wales data registri, bahwa setidaknya 80% dari

kanker nasofaring pada usia 15-19 tahun adalah karsinoma. Hal ini menunjukkan kejadian 1

sampai 2 per juta untuk NPC pada usia 15-19 tahun.Dibandingkan dengan negara lain, kejadian di Inggris rendah. Secara khusus, di Tunisia insiden

ini relatif tinggi [4]. Di bagian selatan China, Asia Tenggara, cekungan Mediterania dan Alaska

kejadian NPC adalah cukup tinggi, sebuah kejadian 2 per juta NPC di Cina telah dilaporkan [5].


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Di negara-negara lain, misalnya di India, insiden sebanding dengan yang di Inggris pada 0,9 per

juta. Selanjutnya, puncak usia muda pada dekade kedua ditemukan di India [6], juga ditemukan

di Inggris [7].

Etiologi

NPC merupakan kanker epitel yang paling umum pada orang dewasa. Deteksi antigen nuklirdikaitkan dengan virus Epstein-Barr (EBNA) dan DNA virus tipe 2 dan 3 NPC, telahmengungkapkan bahwa EBV dapat menginfeksi sel epitel dan berhubungan dengan transformasi

mereka [8]. Etiologi NPC (terutama bentuk endemik) tampaknya mengikuti proses multi-

langkah, di mana EBV, latar belakang etnis, dan lingkungan karsinogen semua tampaknyamemainkan peran penting.

Lo dkk. menunjukkan bahwa DNA EBV terdeteksi pada sampel plasma 96% dari pasien dengan

non-keratinizing NPC, dibandingkan dengan hanya 7% dalam kontrol [9]. Lebih penting lagi,

EBV tingkat DNA tampaknya berkorelasi dengan respon pengobatan [9-11] dan mereka dapatmemprediksi kekambuhan penyakit [11], menunjukkan bahwa mereka dapat menjadi indikator

independen prognosis [12].

Pada orang dewasa, faktor lainnya kemungkinan etiologi termasuk kerentanan genetik, konsumsimakanan (dalam ikan asin khususnya) yang mengandung nitrosamin mudah menguap

karsinogenik, dan seperti anak-anak, EBV [13,15-19].

Presentasi Klinis

NPC biasanya berasal di dinding lateral nasofaring, yang meliputi fosa dari Rosenmuller. Hal inikemudian dapat memperpanjang dalam atau keluar dari nasofaring ke dinding lateral lain dan /

atau posterosuperiorly ke dasar tengkorak atau langit-langit mulut, rongga hidung atau orofaring.

Ini kemudian biasanya metastasis ke kelenjar getah bening leher. Metastasis jauh dapat terjadi ditulang, mediastinum paru-paru, dan, lebih jarang, hati.

Limfadenopati serviks merupakan presentasi awal pada banyak pasien, dan diagnosis NPC sering

dibuat oleh biopsi kelenjar getah bening. Gejala terkait dengan tumor primer meliputi trismus,

nyeri, otitis media, regurgitasi hidung karena paresis dari langit-langit lunak, kehilanganpendengaran dan kelumpuhan saraf kranial. Pertumbuhan yang lebih besar dapat menghasilkan

obstruksi hidung atau perdarahan dan "aksen hidung". Penyebaran metastasis dapat

menyebabkan sakit tulang atau disfungsi organ. Jarang, suatu sindrom paraneoplastic dariosteoarthropathy dapat terjadi dengan penyakit luas.

HistopatologiTiga subtipe NPC diakui di Organisasi Kesehatan Dunia (WHO) klasifikasi [20]:

Tipe 1: karsinoma sel skuamosa, biasanya ditemukan pada populasi orang dewasa yang lebih

tua

tipe 2: non-keratinizing karsinoma tipe 3: karsinoma dibedakan

Sebagian besar kasus di masa kecil dan masa remaja adalah tipe 3, dengan beberapa jenis 2 kasus

[21]. Tipe 2 dan 3 terkait dengan peningkatan titer Epstein-Barr virus, tapi tipe 1 tidak [22].

Modifikasi Cologne dari skema WHO oleh Krueger dan Wustrow [23] termasuk tingkat infiltrasilimfoid. Jenis 2 dan 3 bisa disertai dengan peradangan menyusup limfosit, sel plasma, dan

eosinofil, yang berlimpah, sehingga menimbulkan lymphoepithelioma panjang. Dua pola

histologis dapat terjadi: jenis Regaud, dengan koleksi yang didefinisikan dengan baik sel epiteldikelilingi oleh limfosit dan jaringan ikat, dan jenis Schmincke, di mana sel-sel tumor


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didistribusikan difus dan berbaur dengan sel-sel inflamasi. Kedua pola dapat hadir dalam tumor

yang sama.

Diagnostik metodeMetode diagnostik mencakup:

1. Klinis evaluasi dari ukuran dan lokasi kelenjar getah bening leher.2. Nasopharyngoscopy tidak langsung untuk menilai tumor primer.3. Neurologis pemeriksaan saraf kranial.

4. Computed tomography (CT) / magnetic resonance imaging (MRI) scan kepala dan leher ke

bawah klavikula untuk menilai dasar erosi tengkorak.5. Dada radioterapi (anteroposterior dan lateral) untuk melihat apakah NPC telah menyebar ke

paru-paru.

6. Skintigrafi tulang oleh Tc 99 diphosphonate untuk menunjukkan apakah kanker telah

menyebar ke tulang.7. Kendali hitung darah.

8. Urea, elektrolit, kreatinin, fungsi hati, Ca, PO4, fosfat alkali.

9. EBV antigen kapsid virus EBV dan DNA.10. Biopsi baik kelenjar getah bening atau tumor primer untuk pemeriksaan histologis.

PementasanTumor, node, metastasis (TNM) klasifikasi dari American Komite Bersama Kanker [24] - edisikeenam (Tabel 1) biasanya digunakan untuk menentukan staging tumor (Tabel 2). Klasifikasi

TNM terbaru memperhitungkan Ho [25] modifikasi untuk NPC, yang memanfaatkan pentingnya

prognostik node terkena memperluas ke daerah leher rahim dan supraklavikula rendah.Tabel 1. Tumor, node, metastasis (TNM) klasifikasi dari American Komite Bersama Kanker [24]

Tabel 2. Tahap pengelompokkan

PengobatanOperasiKarena posisi anatomi NPC dan kecenderungan untuk hadir dengan metastasis kelenjar getah

bening leher rahim, tidak setuju untuk operasi untuk kontrol lokal. Biopsi kelenjar getah beningyang terlibat adalah prosedur pembedahan biasa. Tumor primer nasofaring jarang dibiopsi.

KemoterapiBeberapa faktor yang diperhitungkan dalam menentukan rejimen kemoterapi.Pertama, keberhasilan: angka-angka untuk kelangsungan hidup acara bebas sama untuk seri

kemoterapi yang paling kecil tapi terapi biasanya melibatkan cukup tinggi dosis radioterapi

nasofaring - 60 sampai 65 Gy. Namun, hasil yang paling menjanjikan dengan update terbaru,

adalah mereka diperoleh dengan menggunakan protokol Mertens NPC-91-GPOH (MasyarakatPediatric Onkologi dan Hematologi). Protokol ini seharusnya dianggap sebagai pengobatan

terbaik saat ini. Uniknya, NPC-91-GPOH protokol termasuk imunoterapi dengan interferon-beta

setelah kemoterapi dan radioterapi, yang dapat menjelaskan hasil yang lebih unggul

dibandingkan dengan rejimen tanpa pengobatan interferon [27].Kedua, efek akhir: dalam hal kemoterapi, rejimen Manchester - doxorubicin, methotrexate dan

cyclophosphamide - akan menghasilkan kemandulan pada laki-laki (total dosis siklofosfamid 12

gm/m2) dan toksisitas anthracycline mungkin (total dosis doxorubicin 360 mg/m2) [ 36]. NPC-91-GPOH protokol mungkin menghasilkan beberapa infertilitas pada laki-laki yang lebih tua


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1. Berapa dosis optimal radioterapi?

2. Apakah pengecualian dari pengobatan interferon menghasilkan hasil yang sama?

3. Hubungan antara efek akhir dan dosis radioterapi harus diselidiki, serta sifat yang tepat dankejadian efek akhir.

62883229 JURNAL THT Nasopharyngeal Carcinoma 2 INGGRIS

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