Nasal cavity, paranasal sinuses, nasopharynx
Nasopharyngeal carcinoma

Topic Completed: 1 February 2014

Minor changes: 11 July 2020

Copyright: 2004-2020,, Inc.

PubMed Search: Nonkeratinizing nasopharyngeal carcinoma differentiated

Rifat Mannan, M.D.
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Cite this page: Mannan A.A.S.R. Nonkeratinizing-differentiated. website. Accessed August 10th, 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

Contributed by Dr. Songyang Yuan

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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