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NASOPHARYNGEAL CARCINOMA (NPC)

Identitas Pasien

Nama: Ibu TH Umur: 48 tahun Pekerjaan: Pendidikan: Tanggal Periksa: Poli THT RSUDSH Purworejo, 5 Desember 2013

Anamnesis

Keluhan Utama: Pasien kontrol ke Poli RSUDSH tanggal 5 desember 2013 karena post biopsy 2 minggu sebelum periksa. Saat ini terdapat benjolan pada leher sebelah kanan ukuran 4x3x3 cm pada leher, keras, tidak mobile.

Riwayat Penyakit Sekarang Pasien dilakukan biopsy 2 minggu sebelum periksa Saat ini hanya terdapat keluhan benjolan pada leher. Sesak (-), dysphagia (-). Sebelum biopsi OS merasakan sering pilek, cairan jernih, terkadang berdarah, terutama pada hidung kanan. Bersin (-), nasolalia (+), rhinalgia (), foetor (+), hyposmia (+) Os juga terkadang merasakan berdenging pada telinga. Otorrhea (-/-), deafness (-/-), otalgia (-/-), itching (-/-)

Tidak ada keluhan penurunan berat badan, pengelihatan ganda, nyeri kepala, sulit menelan, kelumpuhan bahu, sulit bicara, serak, sesak, batuk darah. RPD: Riwayat penyakit serupa (-), riwayat pengobatan (+: obat warung), RPK: Riwayat keganasan keluarga (-), keluhan serupa (-) Riwayat Alergi: (-)

Pemeriksaan Fisik

Keadaan Umum: Compos Mentis Vital Sign: Tensi: 100/70 RR: 20x/m Nadi: 74x/m Suhu: 36.7 C Kepala: Conjunctiva anemis (-/-), Ikterik (-/-) Leher: Terdapat benjolan 4x3x3 cm pada Lnn Coli Dextra, keras, tidak mobile, batas tidak tegas Paru: Tidak dilakukan Jantung: Tidak dilakukan Anggota gerak: Tidak dilakukan

No Pemeriksaa Telinga Kanan n Telinga 1 Tragus Nyeri Tekan (-), Edema (-)

Telinga Kiri Nyeri Tekan (-), Edema (-)

Daun Telinga
Liang Telinga

Bentuk dan ukuran dbn, hematoma (-), nyeri tarik (-)

Bentuk dan ukuran dbn, hematoma (-), nyeri tarik (-)

Serumen (-), Serumen (-), Hiperemis (-), Hiperemis (-), furunkel furunkel (-), Edema (-), otorrhea (-) (-), Edema (-), otorrhea (-)

Membran Timpani

Retraksi (-), Bulging (- Retraksi (-), Bulging (-), hiperemis ), hiperemis (-), (-), edema (-), perforasi (-), cone edema (-), perforasi (- of light (+) ), cone of light (+)

Pemeriksaan hidung
Pemeriksaan hidung Hidung Luar Hidung Kanan Bentuk normal, hiperemis (-). Nyeri tekan (-), deformitas (-) Normal, ulkus (-) Hidung Kiri Bentuk normal, hiperemis (-). Nyeri tekan (-), deformitas (-) Normal, ulkus (-)

Rhinoskopi anterior Vestibulum nasi Cavum nasi Meatus nasi media Bentuk normal, mukosa Bentuk normal, mukosa pucat (-), hiperemis (-) pucat (-), hiperemis (-) Mukosa hiperemis, sekret (+), bening, massa (-) Edema (-), mukosa hiperemis (-) Deviasi (-), perdarahan (-), ulkus (-) Mukosa hiperemis, sekret (+), bening, massa (-) Edema (-), mukosa hiperemis (-) Deviasi (-), perdarahan (-), ulkus (-)

Konka nasi inferior Septum nasi

Pemeriksaan Tenggorokan Bibir Mulut Mukosa bibir basah, pucat Mukosa mulut basah berwarna merah muda

Lidah
Gigi Uvula Palatum Mole Faring Tonsila Palatina

Permukaan lidah pink, saat dijulurkan simetris


Karies (+), tambalan (-) Simetris Simetris, massa (-), bercak putih (-) Hiperemis (-) Hipertrofi (-)

Nasopharynx
Dinding

Belakang Choanae Muara Tuba eustachii Adenoid Tumor

Tidak diperiksa

Laryngopharynx
Dinding Belakang Parapharynx

Tidak diperiksa

Larynx
Epiglotis Aritenoid Plica Vocalis Gerakan Plica vocalis Tumor Subglotis Trachea

Tidak diperiksa

Pemeriksaan Penunjang

Pemeriksaan Pathology Anatomy


Makroskopik:
Kiri:

Jaringan pecah belah sebanyak 0.5 cc berwarna coklat kehitaman, semua cetak (A) Kanan: Jaringan pecah belah sebanyak 0.5 cc berwarna coklat kehitaman, semua cetak (B)
Mikroskopik
A dan

B kedua sediaan menunjukkan jaringan nasofaring dengan diantara haringan limfoid ditemukan sarang kecil karsinoma sel skuamosa tanpa keratinisasi Non Keratinizing Carcinoma (WHO tipe II)

Kesimpulan
Nasofaring:

Diagnosis

Non Keratinizing Carcinoma of Nasopharynx

Plan

Rujuk RSUP dr Sardjito

Anatomy

Anatomy

Anatomy

Foramen rotundum Foramen ovale Foramen spinosum Foramen lacerum

CT anatomy

A nasopharyngeal carcinoma (NPC) is the most common primary malignancy of the nasopharynx. It is of squamous cell origin and some types of which are strongly associated with Epstein Barr virus (EBV).

Epidemiology

Nasopharyngeal carcinomas account for approximately 70% of all primary malignancies of the nasopharynx. Although it is rare in western populations, it is one of the most common malignancies encountered in Asia, especially China.

Incidence

Department of Radiotherapy, PGIMER, Chandigarh

Incidence: Sex

Etiology
Normal Epithelium
Deletion of Chromosomes 3p and 9p

Low Grade Dysplasia


Inactivation of Chromosome p14, 15 and 16

High Grade Dysplasia


Gain Chromosome 12
EBV infection

Deletion 11 and 13

Invasive Carcinoma
P53 Mutation

Metastatic Carcinoma

Risk

Environmental
Viruses

well documented viral fingerprints in tumor cells and also anti-EBV serologies with WHO type II and III NPC HPV - possible factor in WHO type I lesions
EBV-

Nitrosamines

- salted fish Others - polycyclic hydrocarbons, chronic nasal infection, poor hygiene, poor ventilation

Clinical Manifestation

Clinical presentation, and often only when the tumor has grown significantly in size and has invaded adjacent structures. Actual presentation is often delayed until more sinister signs are evident including nodal masses in the neck (most common), cranial nerve palsies, tinnitus, headache or even diplopia and proptosis.

Cervical adenopathy 60% Epistaxis & Nasorespiratory symptoms Audiological symptoms 30% Neurological symptoms 20%

Cervical adenopathy

NPC has a tendency for early lymphatic spread. Retropharyngeal node of Rouviere is the first echelon node. Commonest first palpable node is the J.D. node and the apical node under sternomastoid muscle.

Epistaxis & Nasal symptoms

Commonly seen in advanced NPCs. Complete nasal obstruction is a late presentation. Ozaena occurs as a result of tumour necrosis.

Tinnitus & Aural symptoms

Serous otitis media is common Acute otitis media Aural block Tinnitus

Nerve palsies

All cranial nerves can be affected Frequently involved are iv, v, vi, ix, & x. Nerves ix & x are invariably involved together. Nerves of the ocular muscles are the next commonly affected.

Pain & Headache

This is an ominous symptom Severe pain is hallmark of terminal disease. Signifies tumour erosion into skull base. If accompanied by trismus,the disease is very advanced and has extended into pterygopalatine fossa.

Metastasis

Tumors arising from fossa of Rosenmuller frequently extend to paranasopharyngeal space, then along trigeminal nerve Often metastasizes to regional nodes; common presentation is unilateral cervical lymphadenopathy; 25% have bilateral nodal metastases May have distant metastases to bones After radiation therapy, risk of 0.4% of subsequent carcinoma in nasal cavity of nasopharynx; differentiate from recurrence based on > 5 year delay, different histology, EBV negative

Local Spread
Sphenoid sinus Cavernous Sinus

Base of Skull, Clivus

Nasal cavity & PNS Orbital invasion

Lateral Parapharyngeal space Middle ear cavity Oropharynx (tonsillar pillars) C1 vertebrae

Nodal Spread

Cranial Nerve involvement


50 45 40 35 30 25 20 15 10 5 0 I II III IV V VI VII VIII IX Leung et al X XI XII Lederman et al

Diagnosis

Diagnosis is usually achieved with endoscopic guided biopsy. A minority of patients have submucosal disease, with normal appearing overlying mucosa. MRI is then essential in guiding biopsy. blind biopsies, particularly in fossa of Rosenmuller, can also be done(70% sensitive)

Nasopharyngeal biopsy
Methods: 1. Transnasal a. Blind b. Post. Mirror rhinoscopy c. Endoscopy rigid and flexible 2. Transoral a. Yankauer speculum b. Rigid endoscopy

Laboratory: IgG against early EBV antigen is suggestive, but has 30% false positives; IgA against viral capsid antigen has 9-18% false positives

Immunology

EB virus antigens a. Viral capsid antigen (VCA) b. Early antigen (EA) c. Nuclear antigen

Serological markers

IgA and IgG to viral capsid antigen IgA and IgG to early antigen Antibody to nuclear antigen Antibody dependent cellular cytotoxic antibodies.

Radiographic features

Imaging is crucial in delineating the extent of local tumor extension, as well as detecting nodal metastases which are present in the vast majority of patients at the time of diagnosis (75-90%). Unfortunately imaging in isolation is not only unable to distinguish between the various types of nasopharyngeal carcinoma, but also unable to distinguish NPCs from other primary malignancies of the nasopharynx.

CT Findings
Mildly

enhancing off-midline nasopharyngeal

mass Metastatic nodes often large, necrosis Retropharyngeal nodes often subtle on imaging as appears isodense to muscle

Bone CT: May show destruction of clival cortex or pterygoid plates

MR Findings T1WI

Asymmetric mass, hypo- to isointense to muscle Sensitive for infiltration of parapharyngeal fat Marrow involvement results in low T1 signal Moderate hyperintensity of NPC compared to muscle Obstructed middle ear secretions markedly hyperintense Best illustrates infiltration of deep face, intracranial, and cavernous sinus disease

T2WI

T1WI C+ FS

Coronal images aid in this evaluation

Mild homogeneous tumor enhancement

(Left) Axial T7WI MR shows isointense right lateral pharyngeal recess NPCa (arrow). Note low signal in pterygoid plates (open arrow) & right clivus (curved arrow) due to bony tumor invasion. (Right) Axial T2WI MR reveals low signal intensity mass in lateral pharyngeal recess, invading prevertebral muscles (arrow), right pterygoid plates & parapharyngeal space

(Left) Axial T7 C+ MR shows a large, invasive right NPCa. Tumor has invaded prevertebral muscles (arrow), nasopharyngeal carotid space (open arrow) and parapharyngeal space (curved arrow). (Right) Coronal T7 C+ MR in same patient reveals NPCa has destroyed large area of skull base bone (arrows) surrounding the foramen ovale. Opposite normal foramen ovale

(Left) Axial T2WI MR demonstrates a small, minimally invasive NPCa (arrow). Despite its small size, nodal metastatic tumor is already visible in the contralateral lateral retropharyngeal node (open arrow).

(Right) Coronal T7 C+ MR in a patient with NPCa reveals bulky bilateral cervical adenopathy (arrows). Notice that a smaller, right lateral retropharyngeal node can also be seen

Nuclear Medicine Findings PET/CT


Markedly

FDG-avid tumor, nodes, and metastases If small primary, can miss with thick slices due to brain FDG uptake
Need

thin collimation, review in coronal plane

MR

still necessary for skull base & intracranial disease

Imaging Recommendations Best imaging tool


MR

is recommended by AJCC for staging

Most

sensitive for skull base and intracranial tumor spread More sensitive than clinical exam/US/CT for detection of retropharyngeal nodes CECT is alternative choice
PET/CT

often obtained if N2/3 disease at staging or recurrent tumor

Staging

Several staging systems are in use:


Complex

anatomy and spread patterns Lack of international consensus:


Separate

Chinese, Hong Kong and American staging

systems

Systems available:
Fletcher

(1967) Hos staging (1978) IUAC (1988) Huaqing staging (1994) AJCC (revised in 2010)

AJCC Nasopharynx Staging (2010)


Tumor Stage (T) T1: Confined to nasopharynx or extension to oropharynx or nasal cavity T2: Extension to parapharyngeal fat T3: Clivus or paranasal sinus invasion Nodal Stage (N) N1: 1 unilateral metastasis 6 cm &/or unilateral/bilateral retropharyngeal nodes 6 cm N2: Bilateral nodal metastases 6 cm N3a: Nodal metastases > 6 cm

T4: Intracranial spread, cranial N3b: Nodal metastasis to nerve, orbit, hypopharynx, masticator supraclavicular fossa space Distant Metastasis (M) M0: No distant metastasis, M1: Distant metastasis NOTE: This nodal staging is unique to NPC

AJCC

Some authors consider carcinomas to be of two types:


Keratinizing Non keratinizing


Keratinizing Squamous Non Keratinizing Squamous Lymphoepithelioma Undifferentiated carcinomas

Others consider carcinomas to be of 4 types:


Pathology

Nasopharyngeal carcinomas are divided into three types (WHO)


type

I - keratinizing squamous cell carcinoma type II - non-keratinizing squamous cell carcinoma (aka lymphoepithelioma) type III - undifferentiated carcinoma

All three types express cytokeratin, and types II and III have incorporation of the EBV into their genome, and circulating IgA antibodies to EBV in peripheral blood.

Keratinizing squamous cell carcinoma of nasopharynx Also called WHO type 1 Minority of nasopharyngeal carcinomas Often EBV negative, older age group 5 year survival is close to 0% Treatment: dont respond to radiotherapy, but tend to remain localized Micro: squamous differentiation with intercellular bridges or keratinization in most of tumor; rarely adenoid or acantholytic forms that mimic adenocarcinoma

Nonkeratinizing nasopharyngeal carcinomadifferentiated Also called WHO type 2 Rare in childhood 5 year survival 35-50% Treatment: variably radiosensitive, may metastasize to regional lymph nodes Micro: cells lack squamous differentiation but have variable levels of maturation; cells are stratified with well defined cell margins that interdigitate in a pavement stone pattern; no mucin or glandular differentiation; variable chronic inflammatory cells Positive stains: CK5/CK6, CK8, CK13, CK14, CK19 Negative stains: CK4, CK7

Nonkeratinizing nasopharyngeal carcinoma-undifferentiated Also called WHO type 3 Very rare in US, common in Taiwan and China (EBV endemic areas) Often called lymphoepithelioma, although lymphocytes are not neoplastic and some cases lack lymphocytes Bimodal age distribution (teens, 50+); in Taiwan, median age is 58 years (range 36-75 years); 2/3 male 5 year survival after radiation therapy alone is based on stage--confined to nasopharynx (stage I): 50-60%; cervical node involvement (stage II): 2030%; invasion of surrounding structures (stage III): 5-30% Survival does not vary based on Regaud or Schminke patterns below Tends to metastasize to regional lymph nodes Treatment: supervoltage radiotherapy and cis-platinum based chemotherapy (70-90% 5 year survival overall) Micro: syncytial arrangement of relatively uniform cells with indistinct cell margins; cells have vesicular nuclei and prominent nucleoli; may have spindle cells and scattered effete (worn out) cells with shrunken, hyperchromatic nuclei that are more variable than sinonasal undifferentiated carcinoma; usually (but not always) non-neoplastic lymphocytic infiltrate (often T cells) with plasma cells, eosinophils and

Nasopharyngeal nonkeratinizing carcinoma, differentiated type. This carcinoma is characterized by the presence of interconnecting cords of neoplastic cells. B, at higher magnification the cellular infiltrate of the nasopharyngeal nonkeratinizing carcinoma, differentiated type shows the absence of keratinization

Most cases in childhood and adolescence are type 3, with a few type 2 cases. Type 2 and 3 are associated with elevated Epstein-Barr virus titers, but type 1 is not 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.

Endemic NPC

Known to occur in China, Hong Kong, South Eastern Asia, Greenland Associated with EBV virus infection Present a decade younger. Associated with undifferentiated carcinoma ( WHO II and III) Associated with more advanced disease at presentation Nodal stage also more advanced and more frequently involved. Both chemo and radio sensitive

Histologically more vascularized (Better Rx response) Greater % of cell in the growth fraction.

Better loco regional control and survival than sporadic variants. Several markers for predicting biological behavior

D/D

Adenoidal Benign Lymphoid Hyperplasia


Children

and teens typically have large adenoids Reactive hypertrophy seen in HIV patients Symmetric enlargement without infiltration of adjacent tissues

Nasopharyngeal Non-Hodgkin Lymphoma


symmetric mass, deep infiltration to prevertebral muscles In clivus, tends to expand rather than infiltrate
Midline

Nasopharyngeal Minor Salivary Gland Malignancy


Uncommon primary tumor May be small primary with extensive infiltration Associated nodal metastases uncommon

Pituitary Macroadenoma
Large sella mass extending through sphenoid to nasopharynx Expansion of sella is key imaging finding

Pharyngeal Mucosal Space Sarcoma


Rare; more common differential in children Submucosal, aggressive mass

Treatment

Treatment for stage I NPC Patients with stage I disease should be treated with RT alone. IMRT alone is effective at treating over 90% of patients with stage I NPC

Treatment for stage II NPC the outcomes in patients with stage II disease have been reported to be less favorable The Society of Clinical Oncology terminology, the European Head and Neck Society European Society for Medical Oncology European Society for Radiotherapy and Oncology Clinical Practice Guidelines also considered CCRT for stage II NPC as level I evidence with a grade B recommendation

Treatment for stages IIIIVb NPC Role of exclusive concurrent chemoradiotherapy The current standard of care for locoregionally advanced (AJCC stages IIIIVb) NPC is cisplatin-based CCRT 31% improvement in 3-year OS compared to RT alone using concurrent RT and high-dose cisplatin followed by adjuvant cisplatin and fluorouracil they were accompanied by severe toxicity,

the dose of cisplatin during the concurrent phase of CCRT had a significant impact on locoregional control, while additional adjuvant chemotherapy with a fluorouracil-containing combination contributed to improved distant control No other regimens have been reported to be as effective as cisplatin and fluorouracil for treating NPC in an adjuvant setting

The NCCN guidelines currently include induction + CCRT as an option (category 3). Adjuvant chemotherapy is poorly tolerated, and compliance is limited because patients suffer substantial toxicities from CCRT Compared with adjuvant chemotherapy, induction chemotherapy appears to be better tolerated, even with more aggressive regimens.

Treatment for stage IVc NPC Patients who present with distant metastasis (stage IVc disease) might account for approximately 10% of all NPC cases in the endemic area of NPC in a study of 125 patients with stage IVc NPC, Yeh et al found improved 1-year OS in patients receiving RT alone versus chemotherapy alone or versus no treatment (48% vs 36% vs 25%, respectively), despite using conventional RT

In light of the poor prognosis in stage IVc NPC, treatment has conventionally been palliative in nature. It is reasonable to assume that a combination of chemotherapy and RT might have potential survival benefits for selected patients with stage IVc NPC

Treatment for reccurent NPC

about 10% of patients still develop recurrent disease either in the neck or at the primary site The options include brachytherapy, external RT, stereotactic radiosurgery, nasopharyngectomy, and microwave coagulation therapy, either alone or in different combinations Salvage nasopharyngectomy carried out for 246 selected patients showed a 5-year local control of disease of 74% and the 5-year disease-free survival was 56%

Endoscopic nasopharyngectomy is a choice for recurrent NPC with central roof or floor lesions with minimal lateral extension. Hua et al reported the long-term treatment outcome of 151 recurrent NPC patients treated with salvage IMRT. The 5-year local control rate and OS for restage I, II, III, and IV were 80.0%, 85.0%, 80.0%, 78.7% and 71.4%, 62.9%, 35.5%, 30.2%

When the recurrent disease is only in the neck lymph nodes, salvage surgery is the optimal treatment method. Radical neck dissection is currently an accepted surgical management for recurrent nodal disease in patients with NPC, with well-proven efficacy and safety

Novel systemic therapy

Epidermal growth-factor receptor (EGFR) and vascular endothelial growth-factor receptor (VEGFR) targeted therapies have been clinically studied in NPC patients. Cetuximab is a chimeric anti-EGFR immunoglobulin G1 monoclonal antibody, the first EGFR inhibitor that is clinically tested to treat NPC A phase II study by Ma et al recently evaluated the feasibility of adding cetuximab to current cisplatin and IMRT in locoregionally advanced NPC

Several phase I and II studies that have generated EBV-Specific Cytotoxic T Cells for posttransplant lymphoproliferative disorders have shown potential efficacies against NPC Autologous EBV-transformed B-lymphoblastoid cell line (LCL) reactivated T cells were generated in vitro and used to treat advanced cases of NPC. Smith et al recently reported the effectiveness of a phase I study involvingadenoviral-based EBV vaccine (referred to as AdE1-LMPpoly)-stimulated T-cell immunotherapy for EBV-associated recurrent and metastatic NPC.

Irradiation with protons instead of the currently used photons generally results in a significantly lower physical dose in the coirradiated healthy tissues, due to its superior beam properties

Dose response

Significant dose response relationship exists. Several series demonstrate that an increaseddose leads to better survival
Doses

of 90 Gy delivered by boost increase the local control and the distant metastasis free rate significantly over doses > 70 Gy Price however paid in increased morbidity

Local recurrence rate reduced with the use of larger fields (Field size more than 250 cm2 associated with a doubling of local control as compared to field size of 100 cm2)

Dose-response
100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 50 - 60 Gy 60 - 67.5 Gy > 67.5 Gy T1 T2 T3 T4

Doses used

Radical radiotherapy:

60 66 Gy in 2 Gy per fraction over 6 6 weeks Higher dose can be given with more conformal techniques: ICBT IMRT 3 DCRT In our patients with poor nutrition, advanced disease and absence of individualized care split course radiotherapy is an alternative 35 Gy in 15 # 25 30 Gy in 10 15 # after 2-3 weeks 30 Gy / 10# 20 Gy / 5# 800 -1000 cGy single fraction

Palliative radiotherapy:

Treatment
Surgical management

Mainly diagnostic - Biopsy


consider

clinic bx if cooperative patient must obtain large biopsy clinically normal NP - OR for panendo and bx

Surgical treatment
primary

lesion regional failure with local control ETD

Treatment
Surgical management

Primary lesion
consider

for residual or recurrent disease approaches


infratemporal

fossa transparotid temporal bone approach transmaxillary transmandibular transpalatal

Prognostic factors

Most important stage. Parapharyngeal extension is associated with a poorer prognosis. A Chinese series found that 4th cranial nerve involvement poor prognosis. Nodal disease status:

Bilateral cervical lymphadenopathy Supraclavicular lymphadenopathy Lymph node fixity

Lymphoepithelioma histology: better prognosis Undifferentiated histology: better prognosis Molecular markers:

Ki -67 over expression P 53 E cadherin expression

EBV and NPC prognosis

JCO 2006 Dec.1

Key facts

Terminology
Nasopharyngeal

carcinoma (NPC) Mucosal tumor of lateral pharyngeal recess (fossa of Rosenmller), strongly associated with EBV infection

Imaging
MR

best demonstrates parapharyngeal fat, skull base infiltration, & intracranial tumor Nodal disease in 90% at presentation: Retropharyngeal, levels II & V most common Metastatic nodes often large necrosis

Clinical Issues
Peak

incidence: 40-60 years Pediatric NPC rare; most often undifferentiated NK Bloody nasal discharge or epistaxis 50-70% present with mass from metastatic nodes Nitrosamines - salted fish Serous otitis from eustachian tube obstruction Nonkeratinizing NPC has 5-year survival ~ 75% Keratinizing NPC has 5-year survival 20-40% BSCC generally poor prognosis

Top Differential Diagnoses


Adenoidal benign lymphoid hyperplasia Nasopharyngeal non-Hodgkin lymphoma Nasopharyngeal minor salivary gland malignancy Pituitary macroadenoma

Pathology
(previously type I) Nonkeratinizing NPC (NK NPC)

25% keratinizing NPC

Strongly associated with EBV 15% differentiated (previously type II) 60% undifferentiated (previously type III)

Rarely basaloid squamous cell carcinoma