8 November 2007 – Case of the Week #100


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We thank Dr. Lisa A. Cerilli, University of New Mexico Health Sciences, Albuquerque, New Mexico (USA), for contributing this case.  To contribute a Case of the Week, please email info@PathologyOutlines.com with the clinical history, your diagnosis and microscopic images in JPG, GIF or TIFF format (send as attachments in any size, we will shrink if necessary).  Please include any other images (gross, immunostains, etc.) that may be helpful or interesting.  We will write the discussion (unless you want to), list you as the contributor, and send you a check for $35 (US dollars) for your time after we send out the case.  Please only send cases with a definitive diagnosis, and preferably cases that are out of the ordinary.


Case of the Week #100


Clinical History


A 50 year old man had bilateral enlarging neck masses for 10 months.  A core needle biopsy and cytology specimens were obtained.


Micro images:  pap staincell blockcore biopsy

Immunostains:  CK 5/6


What is your diagnosis?




























Nasopharyngeal carcinoma - favor undifferentiated subtype (metastatic)




EBER stains were strongly immunoreactive (EBER #1EBER #2).


Nasopharyngeal carcinoma is rare in the US (incidence of 0.4 per 100K in whites), but it is endemic in South China (21.4 per 100K in Hong Kong, see table) and parts of Africa.  It is strongly associated with Epstein Barr virus infection.  Other risk factors include consumption of salt-preserved fish containing carcinogenic nitrosamines, family history, specific HLA class I genotypes, tobacco smoking, chronic respiratory tract conditions and low consumption of fresh fruits and vegetables (Cancer Epidemiol Biomarkers Prev 2006;15:1765).  The patient in this case was a native of New Mexico - other risk factors are unknown.


Nasopharyngeal carcinoma is classified into three histologic subtypes - keratinizing squamous cell carcinoma (WHO type 1), nonkeratinizing-differentiated (WHO type 2) and nonkeratinizing-undifferentiated (WHO type 3).


The undifferentiated subtype is composed of a syncytial arrangement of relatively uniform cells with indistinct cell margins.  The cells have vesicular nuclei and prominent nucleoli.  The tumor cells may be spindled.  There is usually an inflammatory infiltrate of lymphocytes (often T cells), plasma cells, eosinophils and macrophages.  There is usually no necrosis.  The Schmincke pattern exists when the infiltrate is extensive, causing isolation of tumor cells, and resembling lymphoma.  The Regaud pattern exists when tumor cells form well defined nests separated by inflammatory cells.  Tumor cells are immunoreactive for keratins , including CK 5/6, and EBER1 by in situ hybridization.  Nonkeratinizing squamous cell carcinoma is more differentiated.  Tumor cells have distinct cell borders, a pavement stone pattern, more abundant eosinophilic cytoplasm and hyperchromatic nuclei (Mod Path 2002;15:229)


The differential diagnosis includes sinonasal undifferentiated carcinoma (SNUC) and melanoma.   SNUC arises only in the nasal cavity and paranasal sinuses.  Tumor cells are hyperchromatic with coarse chromatin, and individual cell necrosis and central necrosis of cell nests are common.  Tumor cells are EBER-1 negative (AJSP 2002;26:371).  Melanoma usually has different clinical characteristics and immunostaining properties, although the histology may be similar.


Treatment of undifferentiated nasopharyngeal carcinoma consists of immunotherapy with interferon, chemotherapy and radiation therapy.  The 5 year survival is 50-60%.


Additional references: Orphanet J Rare Dis 2006;1:23, PathologyOutlines.com-Nasal cavity, paranasal sinuses, nasopharynx chapter




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