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Herpes simplex virus infection presenting as a piriform sinus mass.


Evidence is accumulating that herpes simplex virus Herpes simplex virus
A virus that can cause fever and blistering on the skin, mucous membranes, or genitalia.

Mentioned in: Conjunctivitis

herpes simplex virus
 (HSV) infection is implicated in oncogenesis oncogenesis /on·co·gen·e·sis/ (-jen´e-sis) tumorigenesis; the production or causation of tumors.oncogenet´ic

The formation and development of tumors.
. HSV antigens have been observed in some oral cancers. We present the case of a 62-year-old man who presented with dysphagia, odynophagia, and dysphonia dysphonia /dys·pho·nia/ (-fo´ne-ah) a voice impairment or speech disorder.dysphon´ic

Difficulty in speaking, usually evidenced by hoarseness.
 and who was found on computed tomography (CT) to have a mass in his piriform sinus. We suspected a malignancy, but histopathology of biopsy specimens revealed that the mass exhibited the classic signs of the HSV cytopathic effect, including the presence of intranuclear in·tra·nu·cle·ar  
Situated or occurring within the nucleus of an atom or cell.
 inclusion bodies, ballooning degeneration of epithelial cells, and a ground-glass appearance of some nuclei. The patient responded well to antiviral therapy, and posttherapy CT revealed that the mass had resolved completely. To the best of our knowledge, this is the first report in the literature of a case of HSV infection presenting as a piriform sinus mass.


Herpes simplex virus (HSV) is one among a spectrum of viruses known to affect the upper aerodigestive tract, although it is usually confined to the lips and oral cavity. (1) It is transmitted via saliva, and it can produce a constellation of symptoms in its host that range from vague malaise to life-threatening illness. There is increasing evidence that the virus contributes in various steps along the carcinogenic cascade. (2) In fact, HSV antibodies are elevated in some patients with oral cancer. (3,4) In this article, we describe a case of HSV infection that manifested as a mass in the piriform sinus. To the best of our knowledge, this is the first such case to be reported to be spoken of; to be mentioned, whether favorably or unfavorably.

See also: Report
 in the literature.

Case report

A 62-year-old man presented to the emergency room with a 7-day history of dysphagia and odynophagia and a 3-day history of dysphonia. Several days prior to presentation, he had been placed on antibiotics, but his symptoms persisted. His medical history was significant for gastroesophageal reflux and chronic obstructive pulmonary disease chronic obstructive pulmonary disease
n. Abbr. COPD
A chronic lung disease, such as asthma or emphysema, in which breathing becomes slowed or forced.
. Previous surgeries included a cholecystectomy, appendectomy, and bilateral total knee arthroplasties. His social history was significant for both tobacco (40 pack-years) and alcohol (several beers per day). Laboratory studies were grossly normal. A lateral x-ray of the soft tissues of the neck was read as demonstrating a rounded area of density in the subglottic region. The patient was admitted, and the otolaryngology service was consulted.

Physical examination revealed that the patient appeared to be generally healthy and in no acute distress. He was afebrile afebrile /afe·brile/ (a-feb´ril) without fever.



without fever.

afebrile adjective Feverless
, and his vital signs were stable. His oral mucosa was devoid of any abnormalities. His nares demonstrated mild rhinitis with clear rhinorrhea. There was no sinus tenderness to palpation palpation /pal·pa·tion/ (pal-pa´shun) the act of feeling with the hand; the application of the fingers with light pressure to the surface of the body for the purpose of determining the condition of the parts beneath in physical diagnosis. . Examination of the neck did not reveal any adenopathy or thyromegaly, and his tracheal structures were in the midline. Findings on the otologic examination were unremarkable. Flexible nasopharyngoscopy demonstrated a fullness in the left piriform sinus with no exophytic changes. His vocal folds were mobile, and his airway was adequate.

Computed tomography (CT) detected a 2-cm mass in the left piriform sinus with some impingement on the hypopharynx (figure 1). Magnetic resonance angiography Magnetic resonance angiography
A noninvasive diagnostic technique that uses radio waves to map the internal anatomy of the blood vessels.

Mentioned in: Cerebral Aneurysm

magnetic resonance angiography 
 was obtained to investigate the possibility of a vascular parapharyngeal contribution, and it demonstrated oropharyngeal oropharyngeal /oro·pha·ryn·ge·al/ (-fah-rin´je-al)
1. pertaining to the mouth and pharynx.

2. pertaining to the oropharynx.
 asymmetry with fullness and heterogeneity of the left tonsillar tonsillar /ton·sil·lar/ (ton´si-lar) of or pertaining to a tonsil.

ton·sil·lar or ton·sil·lar·y
Of or relating to a tonsil, especially the palatine tonsil.
 pillar, vallecula vallecula /val·lec·u·la/ (vah-lek´u-lah) pl. valle´culae   [L.] a depression or furrow.vallec´ular

vallecula cerebel´li
, and piriform sinus. The patient was taken for direct laryngoscopy. On examination with a Jackson laryngoscope, there were no mucosal abnormalities, but a generalized fullness of the left piriform sinus and vallecula was observed, as well as some fullness of the lingual tonsils and faucial pillars. Several biopsies were taken.


Based on the patient's risk factors, we suspected a squamous cell cancer Squamous cell cancer
A form of skin cancer that usually originates in sun-damaged areas or pre-existing lesions; at first local and superficial, it may later spread to other areas of the body.

Mentioned in: Cryotherapy
, but biopsies of the apparent tumor were unexpectedly negative for malignancy. Instead, histopathology of specimens taken from the left piriform sinus, left aryepiglottic fold, left vallecula, and left tonsillar pillar demonstrated a viral cytopathic effect and necrosis consistent with HSV infection. Signs of the classic HSV cytopathic effect included the presence of intracellular proteinaceous fluid, ballooning degeneration of epithelial cells, and acantholysis (figure 2, A) as well as intranuclear inclusion bodies and a ground-glass appearance of some nuclei (figure 2, B). (5) Also identified were several zones of coagulative necrosis. None of the specimens exhibited dysplasia, granuloma granuloma /gran·u·lo·ma/ (gran?u-lo´mah) pl. granulomas, granulo´mata   an imprecise term for (1) any small nodular delimited aggregation of mononuclear inflammatory cells, or (2) such a collection of modified macrophages , or malignancy.


The patient was started on intravenous acyclovir and tested for human immunodeficiency virus human immunodeficiency virus

Human immunodeficiency virus (HIV)
A transmissible retrovirus that causes AIDS in humans.
 (HIV). He responded well to the antiviral medication, and his symptoms resolved completely. We do not know whether the piriform sinus mass actually represented just a localized inflammatory reaction instigated by the viral infection, but follow-up CT revealed that it too had resolved completely after antiviral therapy. Results of the patient's HIV serum antibody test were negative, and he was discharged home on valacyclovir.


The features of this case bring to mind the increasing evidence of a link between viral infection and malignancy of the head and neck. (6,7) Of note, our patient had risk factors for developing a malignancy, which may further implicate HSV in the development of squamous cell carcinoma squamous cell carcinoma
A carcinoma that arises from squamous epithelium and is the most common form of skin cancer. Also called cancroid, epidermoid carcinoma.
. First, our patient's demographic characteristics placed him at a higher risk of developing a malignancy. Second, he compounded his risk by regularly using both tobacco and alcohol. In fact, studies have demonstrated that herpes virus acts synergistically with tobacco to produce oral cancer in animals. (8,9) It is possible that cigarette smoking predisposes patients to mucosal HSV infection by suppressing the host defenses, such as natural killer cell natural killer cell
Abbr. NK cell A killer cell that is activated by double-stranded RNA and fights off viral infections and tumors.
 activity, that are required to control HSV. (2,10)

The HSV genome itself has been found to have distinct transforming regions. (11) Park et al demonstrated that immunization against HSV prevented the co-carcinogenic activity of the virus with the oral carcinogen dimethylbenzanthracene. (12) Additional evidence of a viral link to carcinogenesis was provided by the discovery that serum antibodies to HSV are elevated in patients with head and neck cancer. (3,4)

Although viruses are unlikely to be the prime agents involved in the etiology of oral cancer, mechanisms do exist that allow viral DNA or its gene products to act at different stages along the carcinogenic cascade. (2) This theory is consistent with the multifactorial process of cancer development. We must be mindful of these associations when treating our head and neck cancer patients.


(1.) Pou AM, Vrabec JT, Jordan J, et al. Prevalence of herpes simplex virus in malignant laryngeal lesions. Laryngoscope 2000;110: 194-7.

(2.) Cox MF, Scully C, Maitland N. Viruses in the aetiology of oral carcinoma? Examination of the evidence. Br J Oral Maxillofac Surg 1991;29:381-7.

(3.) Hollinshead AC, Lee O, Chretien PB, et al. Antibodies to herpesvirus herpesvirus, any of the family (Herpesviridae) of common DNA-containing viruses, many of which are associated with human disease. See cytomegalovirus; Epstein-Barr virus; herpes simplex; herpes zoster.  nonvirion antigens in squamous carcinomas. Science 1973;182: 713-15.

(4.) Kumari TV, Shanmugam J, Prabha B, Vasudevan DM. Prevalence of antibodies against herpes simplex and adenovirus in oral and cervical cancer patients--A preliminary report. Indian J Med Res 1982;75:590-2.

(5.) Myerowitz RL, Guggenheimer J, Barnes L. Infectious diseases of the head and neck. In: Barnes L, ed. Surgical Pathology of the Head and Neck. 2nd ed. New York: Marcel Dekker; 2001:1795-1813.

(6.) Scully C. Viruses and cancer: Herpesviruses Herpesviruses
A family of viruses responsible for cold sores, chicken pox, and genital herpes.

Mentioned in: Skin Resurfacing
 and tumors in the head and neck. A review. Oral Surg Oral Med Oral Pathol 1983;56: 285-92.

(7.) Scully C. Viruses in the aetiology of cancer. Br Dent J 1988;164: 362-4.

(8.) Hirsch JM, Johansson SL, Vahlne A. Effect of snuff and herpes simplex virus-1 on rat oral mucosa: Possible associations with the development of squamous cell carcinoma. J Oral Pathol 1984; 13: 52-62.

(9.) Park NH, Sapp JP, Herbosa EG. Oral cancer induced in hamsters with herpes simplex infection and simulated snuff dipping. Oral Surg Oral Med Oral Pathol 1986;62:164-8.

(10.) Lopez C, Kirkpatrick D, Fitzgerald P. The role of NK (HSV-1) effector cells in the resistance to herpes virus infections in man. In: Herberman RB, ed. NK Cells and Other Natural Effector Cells. New York: Academic Press; 1985:1445-52.

(11.) Hayashi Y, Iwasaka T, Smith CC, et al. Multistep transformation by defined fragments of herpes simplex virus type 2 DNA: Oncogenic oncogenic /on·co·gen·ic/ (-jen´ik) giving rise to tumors or causing tumor formation; said especially of tumor-inducing viruses.

on·co·gen·ic or on·cog·e·nous
 region and its gene product. Proc Natl Acad Sci U S A 1985;82: 8493-7.

(12.) Park K, Cherrick HM, Min BM, Park NH. Active HSV-1 immunization prevents the cocarcinogenic activity of HSV-1 in the oral cavity of hamsters. Oral Surg Oral Med Oral Pathol 1990;70:186-91.

Laurie A. Brigandi, DO; Paul V. Lanfranchi, DO; Edward D. Scheiner, DO, FOCOO; Scott L. Busch, DO, FACS FACS Fellow of the American College of Surgeons.

Fellow of the American College of Surgeons


fluorescence-activated cell sorter.

From the Department of Otolaryngology--Head and Neck Surgery, School of Osteopathic Medicine, University of Medicine and Dentistry of New Jersey The University of Medicine and Dentistry of New Jersey is the state-run health sciences institution of New Jersey and comprises eight distinct academic units: the New Jersey Medical School, the New Jersey Dental School, the Graduate School of Biomedical Sciences, the School of , and the Kennedy Memorial Hospitals/University Medical Center, Stratford, N.J.

Reprint requests: Laurie A. Brigandi, DO, The New England Center for Ear, Nose, and Throat Surgery, 280 Main St., Nashua, NH 03060. Phone: (603) 577-3150; fax: (603) 577-3151; e-mail:
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Author:Busch, Scott L.
Publication:Ear, Nose and Throat Journal
Geographic Code:1USA
Date:Jul 1, 2006
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