Nasal cavity
Nasopharyngeal carcinoma
Nonkeratinizing nasopharyngeal carcinoma - undifferentiated

Author: Abul Ala Syed Rifat Mannan, M.D. (see Reviewers page)
Editor: Songyang Yuan, M.D., Ph.D.

Revised: 5 May 2017, last major update March 2014

Copyright: (c) 2004-2017, PathologyOutlines.com, Inc.

PubMed Search: Nonkeratinizing nasopharyngeal carcinoma
Cite this page: Nonkeratinizing nasopharyngeal carcinoma - undifferentiated. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/nasalnonkeratinizingundiff.html. Accessed May 27th, 2017.
Definition / general
  • Type of squamous cell carcinoma originating from the nasopharyngeal mucosa
  • One of the two subtypes of 'nonkeratinizing' nasopharyngeal carcinoma (NPC), according to the WHO classification
  • WHO Classification of NPC:
    • Keratinizing
    • Nonkeratinizing
      • Differentiated
      • Undifferentiated
Terminology
  • Also known as lymphoepithelioma, Rigaud and Schmincke types of lymphoepithelioma
  • Lymphoepithelioma is a misnomer, as the tumor is purely of epithelial origin, and the lymphocytes present are not neoplastic; some cases even lack lymphocytes
  • Prior WHO terminologies, such as type I (squamous cell carcinoma), type II (nonkeratinizing carcinoma) or type III (undifferentiated carcinoma) are no longer used
Epidemiology
  • Most common subtype of NPC, > 60% of all cases
  • Also most frequent type of pediatric NPC
  • Uncommon in U.S.; only 0.25% of all cancers, but high incidence in Chinese, Southeast Asians, North Africans (e.g. Algeria and Morocco), and natives of Arctic region (e.g. in Canada and Alaska)
  • Hong Kong has highest incidence of NPC: 1 in 40 men develop NPC before age 75 years
  • Affects men more than women
  • Peak incidence in 4th-6th decades
  • Less than 20% occur in pediatric age group
    • Pediatric NPC most common in northern and central Africa, accounting for 10-20% of all NPC cases, but accounts for only 2% of NPC cases in China
Sites
  • Lateral wall of nasopharynx (Fossa of Rosenmuller) is most common, followed by superior posterior wall
Etiology
  • Strongly associated with Epstein-Barr virus (EBV), which indicates a probable oncogenic role (Semin Cancer Biol 2002;12:431)
  • EBV also found in preinvasive lesions
  • Other risk factors include:
    • High levels of nitrosamines in preserved food
    • Cigarette smoking
    • Occupational exposure to chemical fumes, smoke, formaldehyde
Clinical features
  • Commonly presents with painless upper cervical lymphadenopathy, typically localized to posterior cervical triangle
  • Other presenting symptoms include nasal obstruction, nasal discharge, epistaxis, serous otitis media, otalgia, hearing loss
  • Headache and symptoms of cranial nerve involvement in advanced disease
Radiology description
Prognostic factors
  • Average 5 year survival is 65% for nonkeratinizing NPC (differentiated and undifferentiated subtypes)
  • Tumor stage is the most important prognostic factor
  • Five year disease specific survival is 98% for stage I, 95% for stage IIA-B, 86% for stage III, and 73% for stage IVA-B
  • NPC frequently metastasizes to regional lymph nodes, which reduces survival by 10-20%
  • Younger age and female gender are associated with better prognosis
  • High plasma/serum EBV DNA titers are associated with advanced stage and active disease; remission is usually associated with very low titers
Case reports
Treatment
  • Radiation therapy is the mainstay of treatment for all histologic types of NPC
  • Surgery is reserved for patients who fail to respond to radiation therapy
Gross description
  • Gross appearance is variable: smooth mucosal bulge, raised nodule with or without surface ulceration, infiltrative mass lesion or occult lesion identified only on microscopy
Microscopic (histologic) description
  • Either syncytial arrangement of cohesive cells with indistinct cell margins (Regaud pattern) or diffuse cellular infiltrate of non-cohesive cells (Schminke pattern) resembling non-Hodgkin lymphoma (growth patterns have no clinical significance)
  • Tumor cells have moderate eosinophilic to amphophilic cytoplasm, round nuclei, prominent eosinophilic nucleoli, vesicular chromatin
  • No significant keratinization
  • Apoptosis and brisk mitotic activity are invariably present
  • Usually (but not always) prominent non-neoplastic lymphoplasmacytic infiltrate accompanying the tumor
  • No necrosis
Microscopic (histologic) images

Images hosted on PathOut server:

Contributed by Songyang Yuan, M.D

Syncytial growth with oval or round vesicular nuclei and prominent nucleoli

CK5/6+

EBER+

p63+



Contributed by Andrey Bychkov, M.D., Ph.D
Missing Image

EBER ISH

Missing Image

LMP1



Case of Week #100

Core biopsy

CK5/6+

EBER+




Images hosted on other servers:

Various images


Sheets of tumor cells

Syncytial architecture with lymphocytes

Various images

EBV+ by ISH

Keratin CK5/6 (upper) and 34βE12 (K903, lower)

Cytology images

Images hosted on PathOut server:

Pap stain

Cell block

Contributed by Marino E. Leon, MD

Positive stains
Negative stains
Molecular / cytogenetics description
  • Detection of EBV by PCR or ISH found in 75-100% of cases
Differential diagnosis
  • Diffuse large B cell lymphoma: CD45+, CD20+, CK-, EBV-
  • Mucosal malignant melanoma: HMB45+, MelanA+, negative for CK and EBV
  • Oropharyngeal nonkeratinizing carcinoma: tonsillar and base of tongue carcinomas share similar histology, but are p16+, EBV- (useful markers to determine primary in nodal metastases)
  • Rhabdomyosarcoma: myogenic markers+ (desmin, myoglobin, myogenin), negative for CK, EBV
  • Sinonasal undifferentiated carcinoma: arises in nasal cavity and paranasal sinuses only, hyperchromatic tumor cells with coarse chromatin, individual cell necrosis and necrosis of cell nests, EBER negative (Am J Surg Pathol 2002;26:371)