eMedicine Specialties > Otolaryngology and Facial Plastic Surgery > Head & Neck Surgery

Neck Cancer, Unknown Primary Site

Philip E Zapanta, MD, Assistant Professor of Surgery, Associate Director of Otolaryngology Residency Program, Division of Otolaryngology-Head and Neck Surgery, George Washington University Medical Center; Consulting Staff, Division of Otolaryngology-Head and Neck Surgery, Medical Faculty Associates
Guy J Petruzzelli, MD, PhD, MBA, FACS, The Charles Arthur Weaver Professor of Cancer Research, Professor and Senior Attending Physician, Director of Head, Neck, and Skull Base Surgery, Department of Otolaryngology, Rush University Medical Center; Ahmed Mohyeldin, PhD, George Washington University School of Medicine and Health Sciences, Washington, DC; Jeremy B White, MD, Resident Physician, Division of Otolaryngology-Head and Neck Surgery, George Washington University School of Medicine and Health Sciences, Washington, DC

Updated: Mar 12, 2009

Introduction

History of the Procedure

Presentation with metastatic cervical lymphadenopathy is not uncommon for patients with squamous cell carcinoma of the head and neck. In most cases, a thorough head and neck examination and various imaging modalities determines the primary site (origin) of the cancer. When clinicians are unable to determine the origin of the metastatic cervical lymphadenopathy, the cancer is said to originate from an unknown primary site.

CT/positron emission tomography (PET) fusion; areas of uptake on the PET scan are mapped to the CT scan, and this image depicts the primary lesion in the left floor of mouth with metastatic disease to level II.

Problem

When the primary site of the carcinoma is known, clinicians are able to administer focused therapy to the primary site and cervical lymphadenopathy. Without this knowledge, clinicians are obligated to treat the entire pharyngeal axis and larynx to cover the possible origins of the metastatic carcinoma. The occult primary treatment regimen results in a significant increase in morbidity, predominantly due to radiation and chemotherapy.

Frequency

Cancers with no known primary lesion site represent a heterogeneous group of malignancies that have been estimated to account for 0.5–10% of all tumors. Patients with cervical lymph node metastases represent a significant fraction of these cases. Recent data suggests that unknown primary carcinoma presenting as cervical lymph node metastasis accounts for approximately 2-9% of all head and neck malignancies. Approximately 90% of these neoplasms are squamous cell carcinoma (SCC), with the remainder being adenocarcinoma, melanoma, and other rare histologic variants.¹

Etiology

The etiology of metastatic squamous cell carcinoma depends on the potential site of the unknown primary cancer.^2,3

• Upper aerodigestive tract
  • Alcohol
  • Tobacco products
  • Betel nut
  • Plummer-Vinson syndrome
  • Potential risk factors -Human papillomavirus, poor oral hygiene, gastroesophageal reflux disease, and malnutrition
• Nasopharynx
  • Environmental factors - Nitrosamines, polycyclic hydrocarbons, wood dust, and nickel exposure
  • Epstein-Barr virus
• Sinonasal - Nickel, wood dust, and thorotrast exposure
• Cutaneous
  • Ultraviolet light exposure
  • Genetic disorder xeroderma pigmentosum (autosomal recessive)

Pathophysiology

The origin of the occult primary squamous cell carcinoma of the head and neck is most likely the exposure of mucosa or skin to carcinogens that initially results in genetic mutations and eventually leads to invasive carcinoma (see the Etiology section).

In 1983, Syrjanen et al first proposed the participation of human papillomavirus (HPV) in oral and oropharyngeal carcinogenesis. A more recent meta-analysis was done to compare HPV in biopsies of oral squamous cell carcinoma with all head and neck squamous cell carcinoma biopsies, underscoring the relevance of viral oncogenes in the pathogenesis of this disease.⁴

The pathophysiology of the unknown primary carcinoma is the same as that of known carcinoma of the head and neck. However, the occult primary carcinoma either metastasizes early to the cervical lymphatics or develops in an anatomical site that is not detectable with endoscopy or imaging techniques until it is of considerable size (T3, T4).

Presentation

The typical presentation of an unknown primary cancer of the head and neck is a complaint of a painless neck mass. According to the patient, the neck mass has usually been present for weeks to months.

History

A thorough history is obtained. The history should focus on questions regarding the presence or absence of the symptoms (see Table), and this can help direct the clinician in the search for the unknown primary cancer.

Possible Source of Unknown Primary Cancer Based on Symptoms

A social history should include occupational hazards (eg, exposure to ultraviolet light, industrial chemicals, or metals). Information concerning alcohol consumption and tobacco product usage should be obtained. The patient's country of origin is important for increasing a clinician's awareness of a possible occult nasopharyngeal carcinoma. The incidence of nasopharyngeal carcinoma is significantly increased in persons from China (particularly the Kwantung province and Hong Kong). An increased incidence also exists in patients from North Africa.

Physical

The physical examination should focus on the head and neck, beginning with inspection and palpation of the skin. Inspect the scalp and the external ears in detail, noting any abnormal skin lesions. Next, inspect and palpate the neck. Thoroughly palpate all zones of the neck in an effort to find additional lymphadenopathy or masses. The size of the neck mass, fixation of the overlying skin or underlying structures, the location of the mass in relation to relevant structures (eg, mandible, great vessels), and the presence or absence of bilateral lymphadenopathy can then be determined. Thoroughly inspect the nasal vestibule and the oral cavity/oropharynx. Because submucosal lesions are not typically evident with visual inspection, manual palpation of the oral cavity and the oropharynx is essential to a complete head and neck examination. Pay special attention to the base of the tongue during palpation because it is often a site of a submucosal occult primary cancer.

Because of the advances of fiberoptic technology and the easy access to fiberoptic nasopharyngoscopes, no physical examination of the head and neck is complete without their use. After topical anesthesia of the nasopharyngeal mucosa, the flexible nasopharyngoscope allows quick and easy access to the nasal cavities, the nasopharynx, the oropharynx, the hypopharynx, and the glottis. Make note of any mucosal lesions or suspicious areas. In the hands of an experienced practitioner, mirror examination of the nasopharynx, the base of the tongue, and the hypopharynx can be useful and revealing. When accessible, a biopsy should be performed on any suspicious lesions in the office.

A complete physical examination of the head and neck must include an examination of the cranial nerves. Any deficits should be noted and can be used to determine the extent of the neck disease and, possibly, the site of an occult primary cancer.^5,6

Indications

After documentation of metastatic squamous cell carcinoma lymphadenopathy and confirmation of the absence of any obvious primary tumor of the head and neck, the physician is obligated to perform a panendoscopy of the upper aerodigestive tract. Biopsy samples should be obtained from high-yield anatomical sites (nasopharynx, tonsils, pyriform sinus, hypopharynx, postcricoid area, the base of the tongue) and any other suspicious areas. The best opportunity to find the primary tumor is at the initial examination of the head and neck in the office. Surgical treatment of cervical lymphadenopathy in certain clinical situations may be performed at the same time as the panendoscopy.⁷

Relevant Anatomy

Knowledge of the levels of the lymph nodes in the neck with most common metastatic disease presentation helps the otolaryngologist tailor the search for the unknown primary.^8,9

• Occipital nodes are responsible for drainage of the posterior scalp, which is posterior to an imaginary anatomical line drawn across the scalp that connects tragal cartilage to tragal cartilage.
• Postauricular nodes are responsible for the lymphatic drainage of the posterior scalp, the mastoid, and the posterior auricle.
• Parotid nodes are divided into extraglandular and intraglandular nodes. The extraglandular nodes are responsible for drainage of the anterior scalp (anterior to the aforementioned imaginary anatomical line). The intraglandular nodes are found in the parenchyma of the parotid gland and are responsible for the same anatomical regions as the extraglandular nodes and the parotid gland.
• Retropharyngeal nodes are responsible for lymphatic drainage of the posterior region of the nasal cavity, the sphenoid and ethmoid sinuses, the hard and soft palate, the nasopharynx, and the posterior pharyngeal wall.
  • Level IA: The centrally located submental lymph nodes drain the mentum, the middle two thirds of the lower lip, the anterior gingiva, and the anterior tongue. The boundaries of this triangle are the anterior bellies of the digastric muscle and the hyoid bone.
  • Level IB: The submandibular nodes drain the ipsilateral lower and upper lip, the cheek, the nose, the medial canthus, and the oral cavity up to the anterior tonsillar pillar. The boundaries are the body of the mandible and the anterior and posterior bellies of the digastric muscle.
  • Levels IIA and IIB: These upper jugular nodes are located along the superior third of the sternocleidomastoid (SCM). Anteriorly, it is bounded by the stylohyoid muscle, and the posterior boundary is the posterior portion of the SCM. Inferiorly, its limit is a horizontal plane through the inferior body of the hyoid bone. The dividing line between the 2 sublevels of level II is the spinal accessory nerve (CN XI). Anything posterior to CN XI is level IIB, and the area anterior to CN XI is level IIA. Level II typically drains the oral cavity, nasal cavity, nasopharynx, oropharynx, hypopharynx, larynx, and parotid gland. Statistically, level IIB is more at risk of receiving metastatic disease from the oropharynx, while level IIA typically harbors metastatic disease from the oral cavity and larynx.
  • Level III: The middle jugular nodes are found along the middle third of the SCM. Its superior boundary is the horizontal plane through the inferior portion of the body of the hyoid, and its inferior limit is the horizontal plane through the inferior portion of the cricoid. It extends anteriorly to the sternohyoid and posteriorly to the posterior border of the SCM. This area typically drains disease from the oral cavity, oropharynx, nasopharynx, hypopharynx, and larynx.
  • Level IV: The lower jugular nodes are located along the inferior third of the SCM. The defined area extends superiorly from the horizontal plane through the inferior border of the cricoid to the clavicle inferiorly. Like levels II and III, the anterior border is the sternohyoid, and the posterior margin is the posterior border of the SCM. These lymph nodes likely have disease from the hypopharynx, thyroid, cervical esophagus, and larynx.
  • Levels VA and VB: The posterior triangle nodes are found in a large region bounded superiorly by the junction of the SCM and trapezius, inferiorly by the clavicle, anteriorly by the posterior border of the SCM, and posteriorly by the anterior border of the trapezius. A horizontal line through the inferior border of the cricoid divides the area into VA and VB. Level VA is superior and contains the spinal accessory nodes. Level VB is inferior and contains the nodes along the transverse cervical blood vessels and the supraclavicular nodes. Level V typically contains disease that drains from the nasopharynx, oropharynx, and the skin of the posterior scalp and neck. Disease in level VB with aerodigestive tract malignant features is a poor prognostic sign, and disease from the abdomen should be considered.
  • Level VI: The anterior or central compartment includes the pretracheal nodes, paratracheal nodes, perithyroidal nodes, and the precricoid (Delphian) node. This area extends superiorly to the hyoid bone, inferiorly to the suprasternal notch, and laterally to the bilateral common carotid arteries. Disease from the thyroid gland, glottic and subglottic larynx, apex of the pyriform sinus, and the cervical esophagus drains here.

Armed with the knowledge of various lymphatic drainage patterns and the nodal levels, the clinician can focus on the laterality of the neck mass. Knowing if a lesion is unilateral or bilateral can help guide the examining clinician. If the neck mass is unilateral, the primary lesion should be sought in ipsilateral mucosal or cutaneous sites (eg, tonsil, scalp). If the neck mass is bilateral, the occult primary lesion is likely from a midline structure (eg, base of tongue, supraglottis, nasopharynx). The other explanation of bilateral cervical lymphadenopathy is a laterally based lesion that extends past the midline.

The site of the metastatic lymphadenopathy can also be useful information for the clinician. For example, when the lymphadenopathy is located in the supraclavicular space, the lower deep lateral cervical chain, or the lower posterior triangle, the primary lesion is often not from the upper aerodigestive tract. The clinician should broaden the search for the primary lesion based on the pathology (eg, adenocarcinoma is suggestive of lung neoplasm).¹⁰

Contraindications

Contraindications to panendoscopy center on the initial workup that points to possible primary sites other than the upper aerodigestive tract (eg, supraclavicular lymphadenopathy with a lesion on the chest radiograph). In this scenario, the patient is better served by a further primary pulmonary neoplasm workup. If the clinical scenario is consistent with an occult primary malignancy of the head and neck, the clinician must complete the workup by performing a panendoscopy with biopsies.

Workup

Laboratory Studies

• Per anesthesia guidelines, routine labs (ECG, chemistries, CBC count, chest radiography) should be obtained in preparation for a panendoscopy and possible neck dissection in the operating room. Chemistries (eg, liver function tests [LFTs]) may also help to diagnose distant metastatic disease and to aid in the complete workup of staging the disease (TNM system).
• In addition to general lab studies, serology positive for Epstein-Barr virus has been shown to correlate with the presence of nasopharyngeal carcinoma.^11,12 However, the physical examination of the nasopharynx via endoscopy and directed biopsies of suspicious areas offers a higher yield.
• More recently, a study was published that attempted to determine the site of the primary tumors by identifying HPV-related carcinomas via fine needle aspiration, both morphologically and by using in situ hybridization (ISH), in metastatic cervical lymph nodes. Nonkeratinizing morphology or HPV-positivity were highly predictive of oropharyngeal origin of the tumor.¹³

Imaging Studies

• Chest radiography (posteroanterior and lateral views)
  • This study allows the physician to screen for lung metastases from the occult primary malignancy or a concurrent primary lung neoplasm. Also, chest radiography helps in the complete staging of the disease process. If a suspicious lesion is found on chest radiograph, further investigation with a CT scan of the chest is warranted. Although no guidelines exist for screening for distant metastatic disease in advanced head and neck squamous cell carcinoma, recent studies had suggested that chest CTs were adequate screening tools for distant disease. Brouwer et al (2005) documented that the sensitivity and specificity was only 73% and 80%, respectively.¹⁴ His group suggests that FDG-PET scans may be a better alternative.
  • If the results are consistent with metastases, the lesion obviates the need for surgical intervention and makes the patient a possible candidate for radiation/chemotherapy.
  • If the findings on the CT scan are consistent with a primary lung neoplasm, this represents either a synchronous primary malignancy or a source of the cervical metastases.
  • If a primary lung neoplasm is discovered, the patient's care should be shared with the appropriate oncologist.
• CT scan of the head and neck with intravenous contrast
  • In terms of availability, cost effectiveness, quickness, and patient compliance, CT scanning is the imaging modality of choice for both the evaluation of cervical lymphadenopathy and the identification of occult primary lesions. Newer technology and methods of acquisition, such as the helical CT scanner, allows better image quality and resolution, better reconstructive capabilities, quicker scans, and decreased artifact. The quicker scans allow dynamic maneuvers to be used. The puffed cheek and modified Valsalva techniques can help open opposed mucosal surfaces in the oral cavity, oropharynx, and hypopharynx. This may allow the easier detection of unknown mucosal primaries.¹⁵ Nonetheless, critical evaluation of the CT scan helps in the location of directed biopsies during panendoscopy in the workup of the unknown primary tumor.³
  • With respect to the evaluation of cervical lymphadenopathy, a CT scan of the neck is helpful in assessing the involvement of vital structures. It also provides the clinician with useful data regarding surgical resectability.
  • In addition to its usefulness in evaluating the clinically obvious neck mass, a CT scan can be used to evaluate clinically negative cervical lymph node zones (see Image 1). Radiographic criteria of potential pathological lymph nodes include rounding of the lymph node, a size greater than 1.5 cm in the jugulodigastric region or greater than 1 cm in other regions, and a hypodense center of the lymph node that signifies necrosis.

CT scan of neck with contrast. The arrows indicate metastatic lymphadenopathy. Image courtesy of Head and Neck Cancer-Multidisciplinary Approach, Davidson, BJ.

• MRI or magnetic resonance angiography of the head and neck
  • In the primary author's opinion, MRI is superior to CT scanning in anatomical detail and is helpful in iodine-allergic patients who need a contrast study. Unfortunately, MRI is slower than a CT acquisition and some patients may not be able to tolerate the physical constraints of the scanner.
  • MRI may be useful in the evaluation of the superior extent of metastatic cervical lymphadenopathy (ie, intracranial extension).
  • MRI may have a role in the preoperative workup of a patient with cancer of the head and neck once the primary site is known. The literature is limited in the use of current MRI technology (inversion recovery MRI, dynamic contrast enhanced MRI, MR spectroscopy, ultrasmall superparamagnetic iron oxide particles [USPIO], diffusion-weighted imaging) for the detection of the unknown primary; however, inversion recovery MRI has the best potential to identify the unknown primary. MRI is ideal for a patient with cancer on the base of the tongue or of the sinonasal tract.¹⁵
  • Although angiography is the criterion standard for evaluating the integrity of the great vessels, magnetic resonance angiography (MRA) is a less-invasive procedure and can provide useful information. This information can be used in the determination of resectability.¹⁶
• Positron emission tomography imaging with 2-fluoro-2-deoxyglucose
  • Positron emission tomography (PET) is not typically used in the workup of occult primary tumors of the head and neck. With a radio-labeled glucose molecule, this imaging modality works on the assumption that areas of high metabolism pick up the tracer. Cancer cells have a high standard uptake value (SUV); in addition, areas of inflammation and infection also show signs of high metabolism.
  • Historically, this imaging modality is most often used after the workup for an unknown primary cancer is complete but has not yet revealed the primary site. At the primary author's institution, the PET scan is often used in the initial workup of an unknown primary tumor to help guide biopsies during panendoscopy. One study claimed a sensitivity and specificity rate of 100% and 94%, respectively, for PET, compared with conventional methods rates of 92% and 76%, respectively.¹⁷ This is in contrast to a more recent study in which the PET sensitivity and specificity was 66% and 92.9%, respectively. The positive predictive and negative predictive values were 88.8% and 76.5%, respectively.¹⁸ Depending on the situation, the authors often fuse the PET scan with a CT scan to further delineate the lesions (see Image 2). Theoretically, a fused PET/CT can visualize lesions larger than 5 mm.

CT/positron emission tomography (PET) fusion; areas of uptake on the PET scan are mapped to the CT scan, and this image depicts the primary lesion in the left floor of mouth with metastatic disease to level II.

• Because of the limited access to PET imaging and the controversy regarding the mixed evidence of PET imaging in the detection of unknown primary cancers, it is not part of a standard workup.^19,20 The use of fusing PET scans with CT scans for the workup of the unknown primary tumor is even further debated.²¹ However, more recent evidence suggests that the combination of PET and panendoscopy detected 45.2% of unknown primary tumors of the head and neck.¹⁸

Diagnostic Procedures

Fine-needle aspiration is the main diagnostic procedure in the workup of occult primary tumors of the head and neck. It is used to obtain a histological diagnosis of the presenting neck mass. The histology allows the clinician to narrow the differential diagnosis and to focus diagnostic and therapeutic treatment.

Histologic Findings

Histologic appearance of metastatic squamous cell carcinoma. Image courtesy of Atlas of Head and Neck Pathology, Wenig, BM.

Treatment

Medical Therapy

This section targets the treatment of patients without an identifiable primary lesion of the head and neck after a thorough examination of the head and neck, a panendoscopy, and possible neck dissection. Jesse et al demonstrated the added advantage of radiation therapy to locoregional control following the surgical removal of cervical metastases. Patients with metastatic cervical lymphadenopathy (N1-N3) had a locoregional failure rate of 13-32% when treated with surgery alone. Compare this with the locoregional failure rate of 0-18% associated with primary surgery (neck dissection) followed by adjuvant external beam radiotherapy. The research following this study further demonstrated the improvement in locoregional control of patients with occult primary squamous cell carcinoma.²²

Although the value of radiation therapy has been confirmed, the field to be covered by the radiation therapy is controversial. Grau et al demonstrated the improvement of locoregional control of cancer with bilateral neck irradiation versus ipsilateral irradiation. Patients treated with ipsilateral irradiation had a relative risk of recurrence in the head and neck of 1.9 compared with patients treated with bilateral irradiation. With further research, bilateral cervical irradiation with surgical therapy improves locoregional control of cancer and is accepted as the standard of care for patients with advanced cervical disease (>N2).^23,24

The entire pharyngeal axis is generally accepted as the mucosal sites to be included in the radiation field in patients with occult primary lesions. Theoretically, this should prevent the occurrence of the primary lesion. In order to decrease the morbidity of radiation induced xerostomia, some practitioners would not include the nasopharynx within the radiation field if the results of the endoscopy and the findings on imaging studies are negative.⁵

Chemotherapy is generally reserved for patients with clinical or pathologic indicators of aggressive disease or primary nasopharyngeal carcinoma. Patients with extensive lymphadenopathy (>N2C), pathologic evidence of extracapsular spread of the carcinoma outside of individual lymph nodes, unresectable local disease, or distant metastatic spread of the carcinoma often undergo chemotherapy for curative intent or palliative treatment.

Aggressive medical management consisting of both chemotherapy and radiation is reserved for advanced disease in patients who are deemed poor candidates for surgery, inoperable, or palliation. A recent study discusses that concurrent chemoradiotherapy of N2 and N3 nodal disease from an unknown primary was able to give patients a 5-year survival rate and control rate of 75% and 87%, respectively.²⁵ Also, patients with nasopharyngeal carcinoma are treated with combined chemoradiation therapy without surgery.

Surgical Therapy

Panendoscopy is the primary surgical therapy used to discover an occult primary lesion. The procedure begins with nasal endoscopy using a 0° rigid endoscope to examine the nasopharynx. Generous biopsy samples of the nasopharynx are obtained for both frozen sectioning and permanent sectioning. Frozen sectioning of the nasopharynx is the first portion of the endoscopy. If the results are positive for carcinoma, the procedure is halted because definitive treatment of nasopharyngeal carcinoma is radiation and chemotherapy. By performing this aspect of the procedure first and by obtaining results that are positive, the patient is spared both the additional morbidity of alternate biopsies of the site and the probable surgical treatment of the cervical lymphadenopathy.

If the results from the frozen sections of the nasopharynx are negative, the oral cavity, oropharynx, hypopharynx, and larynx are inspected and palpated. These areas can be evaluated with a laryngoscope. Next, a rigid cervical esophagoscope is used to examine the esophagus. If any suspicious lesions are present, biopsy samples are obtained and sent for permanent sectioning.

After thoroughly palpating the base of the tongue, the examiner obtains biopsy samples. The tonsillar fossa is then inspected. Considerable controversy surrounds the proper sampling technique of a tonsil. Some clinicians obtain biopsy samples of any suspicious sites found on the tonsil. Others perform elective tonsillectomy to eliminate sampling errors. The unilateral tonsillectomy adds little morbidity and allows thorough sampling of this site. Others argue that bilateral tonsillectomy also adds little morbidity and decreases confusion of asymmetric tonsils in follow-up examination. Koch et al reported a 10% spread of metastatic cancer from the contralateral tonsil; therefore, they recommend a bilateral tonsillectomy. The only clinical situation that apparently justifies a bilateral tonsillectomy is the presence of bilateral metastatic cervical lymphadenopathy.^26,27

Depending on the results of the panendoscopy, either the newly found primary lesion (other than the nasopharynx) is addressed surgically along with the cervical lymphadenopathy or the lymphadenopathy is addressed separately with the appropriate neck dissection.

Preoperative Details

As stated above, the panendoscopy requires use of frozen sectioning. The clinician should ensure the availability of a pathologist skilled in the use of frozen sections.

Postoperative Details

Postoperative details are unchanged when compared to patients with squamous cell carcinoma from a known primary lesion.

Follow-up

The usual postoperative care following a neck dissection is administered. The workup required for patients with cancer from an unknown primary site does not necessitate any upgrade in the level or complexity of the care.

Long-term follow-up care of this patient population consists of thorough examinations of the head and neck and does not differ when compared to the other patient groups with squamous cell carcinoma of the head and neck.

Complications

The number and the type of complications generated by the surgical workup of patients with an unknown primary lesion are not significantly different from those associated with the surgical treatment of patients with a known primary lesion and metastatic cervical lymphadenopathy. Complications of panendoscopy include the following:

• Chipped teeth (most common)
• Hemorrhage from site of biopsy (ie, same incidence of tonsillar fossa hemorrhage with panendoscopy as with primary tonsillectomy)
• Pharyngeal and/or esophageal puncture/rupture from endoscopy (rare)

Outcome and Prognosis

Patients with metastatic squamous cell carcinoma of the head and neck from occult primary lesions have clinical features and prognosis similar to those patients with carcinoma from known primary sites. With multimodality treatment, locoregional control of the cancer has improved in this patient population, but little improvement has occurred in overall disease-free survival. The 3- and 5-year disease-free survival rates are 40-60% and 10-25%, respectively. Prognostic factors include nodal stage at presentation, extracapsular spread, and tumor differentiation.^23,24,28

Future and Controversies

The treatment of cervical lymphadenopathy from metastatic squamous cell carcinoma with an occult primary lesion is in flux. Large institutional studies are currently evaluating the efficacy of chemoradiation therapy as the sole treatment modality. This treatment regimen will be compared against the traditional combined modality treatment of neck dissection followed by radiation and/or chemotherapy.

In addition to comparing different treatment modalities, advances in science allow the use of oncogenes and microarray complementary deoxyribonucleic acid (cDNA) technology to determine which patients will respond to specific treatments.

Multimedia

Media file 1: CT scan of neck with contrast. The arrows indicate metastatic lymphadenopathy. Image courtesy of Head and Neck Cancer-Multidisciplinary Approach, Davidson, BJ.

Media file 2: CT/positron emission tomography (PET) fusion; areas of uptake on the PET scan are mapped to the CT scan, and this image depicts the primary lesion in the left floor of mouth with metastatic disease to level II.

Media file 3: Histologic appearance of metastatic squamous cell carcinoma. Image courtesy of Atlas of Head and Neck Pathology, Wenig, BM.

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Keywords

neck cancer, head and neck cancer, head neck cancer, cancer, cancer diagnosis, fine-needle aspiration, head and neck cancer unknown primary, metastatic cervical lymphadenopathy, occult primary squamous cell carcinoma of the head and neck, unknown primary carcinoma, metastatic squamous cell carcinoma, unknown primary cancer

Contributor Information and Disclosures

Author

Philip E Zapanta, MD, Assistant Professor of Surgery, Associate Director of Otolaryngology Residency Program, Division of Otolaryngology-Head and Neck Surgery, George Washington University Medical Center; Consulting Staff, Division of Otolaryngology-Head and Neck Surgery, Medical Faculty Associates
Philip E Zapanta, MD is a member of the following medical societies: American Academy of Otolaryngic Allergy, American Academy of Otolaryngology-Head and Neck Surgery, American College of Surgeons, Christian Medical & Dental Society, and Medical Society of the District of Columbia
Disclosure: Nothing to disclose.

Coauthor(s)

Guy J Petruzzelli, MD, PhD, MBA, FACS, The Charles Arthur Weaver Professor of Cancer Research, Professor and Senior Attending Physician, Director of Head, Neck, and Skull Base Surgery, Department of Otolaryngology, Rush University Medical Center
Guy J Petruzzelli, MD, PhD, MBA, FACS is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American Association for the Advancement of Science, American Association of Clinical Anatomists, American College of Surgeons, American Medical Association, American Society for Head and Neck Surgery, American Society of Clinical Oncology, Chicago Medical Society, North American Skull Base Society, Society of Surgical Oncology, Society of University Otolaryngologists-Head and Neck Surgeons, and Southwest Oncology Group
Disclosure: Nothing to disclose.

Ahmed Mohyeldin, PhD, George Washington University School of Medicine and Health Sciences, Washington, DC
Disclosure: Nothing to disclose.

Jeremy B White, MD, Resident Physician, Division of Otolaryngology-Head and Neck Surgery, George Washington University School of Medicine and Health Sciences, Washington, DC
Jeremy B White, MD is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, and American Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Benoit J Gosselin, MD, FRCSC, Associate Professor of Surgery, Dartmouth Medical School; Director, Comprehensive Head and Neck Oncology Program, Norris Cotton Cancer Center; Staff Otolaryngologist, Division of Otolaryngology-Head and Neck Surgery, Dartmouth-Hitchcock Medical Center
Benoit J Gosselin, MD, FRCSC is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, American Head and Neck Society, American Medical Association, American Rhinologic Society, Canadian Medical Association, Canadian Society of Otolaryngology-Head & Neck Surgery, College of Physicians and Surgeons of Ontario, New Hampshire Medical Society, North American Skull Base Society, and Ontario Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Nader Sadeghi, MD, FRCS(C), Associate Professor of Surgery, Director of Head and Neck Surgery, Division of Otolaryngology, George Washington University
Nader Sadeghi, MD, FRCS(C) is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American Head and Neck Society, Federation of Medical Specialists in Quebec, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

CME Editor

Christopher L Slack, MD, Otolaryngology-Facial Plastic Surgery, Private Practice, Associated Coastal ENT; Medical Director, Treasure Coast Sleep Disorders
Christopher L Slack, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Arlen D Meyers, MD, MBA, Professor, Department of Otolaryngology-Head and Neck Surgery, University of Colorado School of Medicine
Arlen D Meyers, MD, MBA is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, and American Head and Neck Society
Disclosure: Covidien Corp Consulting fee Consulting; US Tobacco Corporation unstricted gift unknown

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