Lingkar Kepala dan Ukuran Fontanel Bayi

KARSINOMA NASOFARING

Merupakan salah satu jenis kanker terbanyak di Indonesia. Terdiri atas 3 jenis berdasarkan penggolongan WHO.

WHO criteria
Type 1	Differentiated squamous cell carcinoma
Type 2	Nonkeratinizing carcinoma
Type 3	Undifferentiated carcinoma

ETIOLOGI

a.        Herediter(1), gen HLA-A2,B-17,Bw26(2)

Orang yang keluarganya pernah mengidap penyakit ini uga lebih rentan.

b.       Virus (EBV)(1), HPV-18 (3)

c.        Lingkungan(4)

-          Zat karsinogen

-          Radiasi

Faktor ini terutama faktor eksogen dapat menyebabkan terbentuknya sel tumor lewat mutasi gen nya seperti Gen yang biasa terganggu adalah  (onkogen: bcl2, ras, myt. Tsg: p53, rb,, SPLUNC1, UBAP1, BRD7, Nor1, NGX6, and LTF (5) kehilangan kromosom heterozigot (6), pengulangan kromosom 3p21 (2)(7).

FAKTOR RESIKO

a.        Alkohol dan rokok(8)

b.       Pria  lebih banyak  2-3 kali daripada yang perempuan (4)

c.        Ras kaukasian jarang, sedangkan pada ras mongolian lebih banyak,. Diketahui nbhwa indonesia merupakan daerah endemic tetapi dengan mortalitas yg lebih rendah dari china, taiwan dan malaysia. (9) angka mortalitas tahun 2004 yaitu sebesar 127/100.000 jiwa (10)

d.       Perempuan yg pernah melakukan koitus di usia 16-18 tahun menunjukkan adanya ebv di secret genitalnya(11)(12)(12).

e.       Masyarakat yang sering memakan ikan asin (mengandung nitrosamin) sebagai karsinogen

f.         Tukang masak (lebih sering terpapar asap (13)

g.        Tempat kerja, orang yang sering terpapar formaldehida lebih rentan (10)(14)

GEJALA DAN MANIFESTASI KLINIS

Manifestasi klinis CNP biasanya dihubungkan dengan letak anatomiknya terhadap hidung, tuba eustachii dan  dasar tengkorak dan adanya jaringan submukosa luas pembuluhh limfe.

-          Epistasis (pendarahan dari hidung)

-          Hidung tersumbat

-          Pilek yg sudah lebih dari 1 bulan. Terutama pada orang usia diatas 40tahun.

-          Lendir berdarah di tenggorokan belakang

-          Suara berdengung di telinga (tinusitis)

-          Kehilangan pendengaran

-          Tidak berfungsinya saraf otak (n V, VI, X)

-          Sakit kepala (biasanya dimulai dengan unilateral baru bilateral)(13)

-          Gangguan neurologik kelumpuhan gangguan fungsi penglihatan(terganggunya kiasama optikum)

-          Pembengkakan leher (biasanya karena pembengkakan kelenjar limfe

PATOFISIOLOGI

Virus EBV yang masuk akan menyebabkan  terjadi nya sel-sel abnormal lewat mutasi gen nya.

Langkah awal infeksi litik EBV ditandai dengan aktivitas protein ZEBRA yang disandi oleh gen BZLF1 yang terdapat pada sel epitel dan limfosit B. Beberapa produk yang berbeda-beda dari gen yang mempuyai korelasi dengan tahapan siklus replikasi litik dapat diidentifikasi dan dikategorikan menjadi: Early Membrane Antigen (EMA), Early Intra- Celulair Atigen (EA), Viral capcid Antigen (VCA),Late Membrane Antigen (LMA). Pada infeksi latent terjadi ekspresi dari beberapa protein antara lain: Epstein Barr Nucleus Antigen 2 & 5 (EBNA 2 & 5) yang dapat diteksi 2-5 jam setelah infeksi, Latent Membrane Protein 1 & 2 (LMP 1&2) yang dapat diteksi 5-7 jam setelah infeksi.

Infeksi laten yang bersifat diam dan tidak memproduksi partikel-partikel virus yang baru, dikaitkan salah satunya dengan KNF. Bentuk laten infeksi EBV pada KNF termasuk tipe II dengan karakteristik terekspresinya protein LMP disamping protein EBER dan EBNA1.

Virus EBV akan menyerang sel epitel nasofaring, menghasilkan LMP (laten membran protein) yg mencegah sel diapoptosis.  Gen LMP ditemukan hampir disebagian besar penderita CNP

PEMERIKSAAN FISIK DAN PENUNJANG

Pemeriksaan fisik

-          Inspeksi

-          Palpasi

Pemeriksaan Penunjang

-          Endoskopy,  rinoskopi (tetapi akan susah dilihat, soalnya sudah membengkak)

-          MRI

-          CT scan

-          Biopsi aspirasi (pemeriksaan serologic)

-          Biopsi nasofaring (periksaan histologi)

-          Tes antigen EBV

STADIUM

Table. TNM classification

Primary tumor (T)
TX	Primary tumor cannot be assessed
T0	No evidence of primary tumor
Tis	Carcinoma in situ
T1	Tumor confined to the nasopharynx, or tumor extends to oropharynx and/or nasal cavity without parapharyngeal extension (eg, without posterolateral infiltration of tumor)
T2	Tumor with parapharyngeal extension (posterolateral infiltration of tumor)
T3	Tumor involves bony structures of skull base and/or paranasal sinuses
T4	Tumor with intracranial extension and/or involvement of cranial nerves, hypopharynx, or orbit, or with extension to the infratemporal fossa/masticator space
Regional lymph nodes (N)
NX	Regional nodes cannot be assessed
N0	No regional lymph node metastasis
N1	Unilateral metastasis in cervical lymph nodes =6cm in greatest dimension, above the supraclavicular fossa, and/or unilateral or bilateral retropharyngeal lymph nodes =6 cm in greatest dimension (midline nodes are considered ipsilateral nodes)
N2	Bilateral metastasis in cervical lymph nodes =6cm in greatest dimension, above the supraclavicular fossa (midline nodes are considered ipsilateral nodes)
N3	Metastasis in a lymph node >6cm and/or to the supraclavicular fossa (midline nodes are considered ipsilateral nodes)
N3a	>6cm in dimension
N3b	Extension to the supraclavicular fossa
Distant metastasis (M)
M0	No distant metastasis
M1	Distant metastasis

Table. Histologic grade

Histologic grade (G)
GX	Grade cannot be assessed
G1	Well differentiated
G2	Moderately differentiated
G3	Poorly differentiated
G4	Undifferentiated

Table. Anatomic stage/prognostic groups

Stage	T	N	M
0	Tis	N0	M0
I	T1	N0	M0
II	T1	N1	M0
	T2	N0	M0
	T2	N1	M0
III	T1	N2	M0
	T2	N2	M0
	T3	N0	M0
	T3	N1	M0
	T3	N2	M0
IVA	T4	N0	M0
	T4	N1	M0
	T4	N2	M0
IVB	T Any	N3	M0
IVC	T Any	N Any	M1

TERAPI

Stages 0 and I

The usual treatment for these early stage cancers is radiation therapy aimed at the nasopharyngeal tumor.

Although the cancer has not yet spread to lymph nodes in these stages, the nearby lymph nodes in the neck are usually treated with radiation therapy as well. This is considered preventive (prophylactic) radiation. Some patients may have cancer cells in these lymph nodes that can’t be detected. Although there are too few cancer cells in the lymph nodes to cause them to be enlarged, these cells could continue to grow and spread if not destroyed by radiation therapy.

Stages II, III, IVA and IVB

These cancers have spread outside of the nasopharynx and often to lymph nodes in the neck or above the collarbone. Patients with these stages of NPC usually receive chemoradiation (chemotherapy given along with radiation therapy to the nasopharynx and neck lymph nodes). The chemotherapy (chemo) drug most often used is cisplatin, but sometimes another drug is used as well. This is usually followed by more chemo, most often with cisplatin plus 5-FU. Most studies have found that chemoradiation helps patients live longer than just radiation therapy alone. But adding chemo leads to more side effects, which can affect quality of life. It’s important to understand what the side effects are likely to be before starting this treatment.

If cancer is still in the lymph nodes after this treatment, surgery (neck dissection) may be done to remove the lymph nodes.

Stage IVC

These cancers have spread to distant parts of the body and can be hard to treat. The usual treatment is chemo, often with cisplatin and one other drug. If there is no sign of the cancer after chemotherapy, radiation therapy to the nasopharynx and the lymph nodes in the neck or chemoradiation is given to try to kill any remaining cancer cells. Another option in some cases is to give chemoradiation as the first treatment.

If there are still signs of cancer after the initial chemotherapy, another chemotherapy regimen using different drugs may be tried. Chemotherapy plus the targeted drug cetuximab (Erbitux) may be another option.

Because these cancers can be hard to treat effectively, taking part in a clinical trial of newer treatments may be a good option.

Recurrent nasopharyngeal cancer

Cancer is called recurrent when it come backs after treatment. Recurrence can be local (in or near the same place it started) or distant (spread to organs such as the lungs or bone). If your cancer returns after treatment, the choices available to you depend on the location and extent of the cancer, which treatments were used the first time around, and your overall health. It is important to understand the goal of any further treatment – whether it is to try to cure the cancer, to slow its growth, or to help relieve symptoms – as well as the likelihood of benefits and risks.

Some tumors that recur in the nasopharynx can be removed by surgery using an approach through the nose (called endoscopic skull base surgery). This is a specialized surgery that should only be done by a surgeon with a great deal of experience in this procedure, so it’s not available at all medical centers.

Recurrent NPC in regional (neck area) lymph nodes can sometimes be treated by additional radiation therapy. But if doctors believe that more radiation would cause serious side effects or if the initial response to radiation was incomplete, surgery (neck dissection) may be used instead.

Cancer that recurs in distant sites is usually treated with chemotherapy. If chemotherapy has been given already, different chemo drugs may be tried. The targeted drug cetuximab may be given along with chemo, generally on a clinical trial.

New drug treatments being tested in clinical trials and new surgical procedures may help some patients with recurrent NPC, as well as improve knowledge that can help others with NPC in the future.

If the cancer can’t be cured, further treatments may be aimed at slowing its growth or relieving symptoms caused by the distant spread of the cancer. For example, if the cancer has spread to the spine, radiation therapy may be given to the area to relieve pain and reduce the chances of further complications. Even if a cure is not possible, it is important to remember that there are many options to relieve symptoms of advanced cancer. (http://www.cancer.org/cancer/nasopharyngealcancer/detailedguide/nasopharyngeal-cancer-treating-by-stage)

Bisa juga lewat imunoterapi

DAFPUS

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4.             WHO Classifications of Tumoure.

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6.             He X, Deng M, Yang S, Xiao Z, Luo Q, He Z, et al. The tumor supressor function of STGC3 and its reduced expression in nasopharyngeal carcinoma. Cell Mol Biol Lett. 2008 Sep;13(3):339–52.

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10.           V10. Cancer, all sites; personal history of malignant neoplasm [Internet]. Capitola, United States: Timely Data Resources, Inc.; 2013 First Quarter p. 0. Available from: http://search.proquest.com/docview/1267795637/140FECEDF41601E4F6F/6?accountid=48149

11.           Crawford DH, Swerdlow AJ, Higgins C, McAulay K, Harrison N, Williams H, et al. Sexual history and Epstein-Barr virus infection. J Infect Dis. 2002 Sep 15;186(6):731–6.

12.           Thomas R, Macsween KF, McAulay K, Clutterbuck D, Anderson R, Reid S, et al. Evidence of shared Epstein-Barr viral isolates between sexual partners, and low level EBV in genital secretions. J Med Virol. 2006 Sep;78(9):1204–9.

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14.           Duhayon S, Hoet P, Van Maele-Fabry G, Lison D. Carcinogenic potential of formaldehyde in occupational settings: a critical assessment and possible impact on occupational exposure levels. Int Arch Occup Environ Health. 2008 May;81(6):695–710.

http://www.cancer.org/acs/groups/cid/documents/webcontent/003124-pdf.pdf