Nasal cavity, paranasal sinuses, nasopharynx
Nasopharyngeal carcinoma
Nonkeratinizing - differentiated

Topic Completed: 1 February 2014

Revised: 19 February 2019

Copyright: 2004-2018,, Inc.

PubMed Search: Nonkeratinizing nasopharyngeal carcinoma differentiated

Rifat Mannan, M.D.
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Cite this page: Mannan A.A.S.R. Nonkeratinizing nasopharyngeal carcinoma - differentiated. website. Accessed January 18th, 2020.
Definition / general
  • Squamous cell carcinoma of the nasopharyngeal mucosa, showing light microscopic or ultrastructural evidence of squamous differentiation
  • One of two subtypes of nonkeratinizing nasopharyngeal carcinoma (NPC), according to WHO classification
  • Also known as lymphoepithelioma, transitional carcinoma
  • ~12% of all NPCs, the least common subtype
  • Uncommon in United States, ~0.25% of all cancers
  • High incidence in Chinese, Southeast Asians, North Africans (e.g. in Algeria and Morocco), native people of Arctic region (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 is in fourth and sixth decades of life
  • Most common site of origin is lateral wall of the nasopharynx (fossa of Rosenmüller), followed by the superior posterior wall
  • Most important factor related to the development of NPC is Epstein-Barr virus (EBV); the strong association indicates a probable oncogenic role (Semin Cancer Biol 2002;12:431)
Clinical features
  • Painless upper cervical lymphadenopathy is the most common presentation
  • Other presenting symptoms include nasal obstruction, nasal discharge, epistaxis, serous otitis media, otalgia, hearing loss
  • Headache and symptoms of cranial nerve involvement are present in advanced disease
Radiology description
  • MRI is the preferred imaging modality for assessing the extent of disease and intracranial extension
Prognostic factors
  • 5 year survival is ~65% for nonkeratinizing NPC (differentiated and undifferentiated subtypes)
  • Tumor stage is the most important prognostic factor; 5 year disease specific survival is 98% for stage I, 95% for stage IIA - B, 86% for stage III and 73% for stage IVA - B
  • 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 EBV titers
  • Radiation therapy is the mainstay of treatment of NPC of all histologic types
  • Surgery is reserved for patients who fail to respond to radiation therapy
Gross description
  • Varies from smooth mucosal bulge, raised nodule with or without surface ulceration, infiltrative mass lesion or an occult lesion identified only on microscopy
Microscopic (histologic) description
  • Usually interconnecting cords or trabeculae, with little or no keratinization; growth pattern is similar to urothelial carcinoma
  • Tumor cells show well defined cell borders, with variable intercellular bridges
  • Background stroma demonstrates variable lymphoplasmacytic infiltrate
  • Usually no desmoplastic response to invading tumor
  • Subclassification of nonkeratinizing NPC into differentiated and undifferentiated subtypes is optional, as it is not clinically or prognostically significant; if there is overlapping histology within the same tumor, classify according to the dominant component
Microscopic (histologic) images

Images hosted on other servers:

Nonkeratinizing NPC, differentiated

Positive stains
Negative stains
Electron microscopy description
  • Convincing evidence of squamous differentiation - at least some tumor cells show small bundles of tonofilaments and well formed desomsomes
Differential diagnosis
Additional references
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