A 56-year-old man comes to the office due to several months of progressive neck swelling. He has also had intermittent epistaxis and headaches. The patient has no chronic medical conditions and takes no medications. He does not use tobacco, alcohol, or illicit drugs, and he emigrated to the United States from rural China 12 years ago. Physical examination shows several enlarged, firm, and nontender cervical lymph nodes. Nasopharyngeal evaluation reveals a mass arising from the pharyngeal recess. Histopathological examination of the mass shows undifferentiated malignant cells of epithelial origin. Further analysis of these cells is most likely to reveal the presence of nucleic acid sequences from which of the following viruses?

Question

A 56-year-old man comes to the office due to several months of progressive neck swelling.  He has also had intermittent epistaxis and headaches.  The patient has no chronic medical conditions and takes no medications.  He does not use tobacco, alcohol, or illicit drugs, and he emigrated to the United States from rural China 12 years ago.  Physical examination shows several enlarged, firm, and nontender cervical lymph nodes.  Nasopharyngeal evaluation reveals a mass arising from the pharyngeal recess.  Histopathological examination of the mass shows undifferentiated malignant cells of epithelial origin.  Further analysis of these cells is most likely to reveal the presence of nucleic acid sequences from which of the following viruses?

Quizplus · Accepted Answer

Nasopharyngeal carcinoma is an epithelial tumor that usually originates in the pharyngeal recess. Local tumor growth often leads to epistaxis and headaches, and metastatic spread to cervical lymph nodes frequently causes firm, fixed neck swelling. NPC is relatively uncommon in the United States but is endemic to southern China, where genetic and dietary factors (eg, consumption of salted fish) predispose to premalignant nasopharyngeal epithelial lesions. Subsequent malignant transformation is then induced by Epstein-Barr virus (EBV). EBV is a ubiquitous human herpes virus that causes infectious mononucleosis in a minority of patients (primary infection is usually asymptomatic). Initial infection is followed by life-long latent infection in memory B cells. While latent, the EBV genome exists as an episome in the nucleus of infected cells and expresses a restricted subset of EBV genes (latency genes) which do the following: Promote periodic viral reactivation from memory B-cells, leading to recurrent (asymptomatic) mucosal infections. Promote survival of infected memory B cells by encoding for proteins (eg, EBNA-1, LMP1) that prevent apoptosis. In a minority of patients, these proteins are oncogenic and lead to malignant transformation of infected B cells (eg, Burkitt lymphoma, Hodgkin lymphoma) or premalignant epithelial cells (eg, nasopharyngeal carcinoma, salivary cancer). Individuals who do not have premalignant epithelial lesions are at very low risk of EBV-associated epithelial cancers like NPC. (Choice A) Adenovirus causes acute upper respiratory infection with pharyngitis, coryza, otitis media, bronchitis, and/or pneumonia. It is not associated with nasopharyngeal carcinoma. (Choice B) Coronavirus is one of the most common causes of upper respiratory tract infection (eg, common cold) but has no association with nasopharyngeal or other cancers. (Choices C and E) Cytomegalovirus (CMV) and human herpes virus 8 (HHV-8) are also herpes viruses; as such, they cause acute infection followed by latent disease. Although CMV can reactivate in immunocompromised individuals (eg, HIV, post-transplantation) and cause severe end-organ disease (eg, retinitis, gastroenteritis), it is not an oncogenic virus. HHV-8 reactivation also primarily occurs in immunocompromised individuals and is associated with Kaposi sarcoma. (Choice F) The BK and JC viruses are members of Polyomaviridae and cause life-long latent infections in the kidney. BK reactivation can cause nephropathy in renal transplant recipients, and JC virus causes progressive multifocal leukoencephalopathy (primarily in patients with advanced HIV). Educational objective: Nasopharyngeal cancer is endemic in southern China due to genetic and dietary factors that promote nasopharyngeal epithelial pre-malignant lesions. In almost all cases, malignant transformation occurs due to infection of premalignant cells with Epstein-Barr virus and the subsequent expression of oncogenic viral proteins. __________ References: Epstein-Barr virus and nasopharyngeal carcinoma. (http://www.ncbi.nlm.nih.gov/pubmed/25418193)

A 56-Year-Old Man Comes to the Office Due to Several