Head and Neck Cancer of Unknown Primary

Boris Hristov and Giuseppe Sanguineti

 Background

H&N cancers of an unknown primary represent what % of H&N cancers?

~3%–5% of all H&N cancers are of an unknown primary.

What is the most commonly presumed general site of origin for H&N cancers of an unknown primary?

The oropharynx (OPX) is the presumed site of origin for most cases (less common are the nasopharynx [NPX], hypopharynx [HPX], and larynx).

What subsites constitute the OPX?

Soft palate, tonsils, tonsillar pillars, base of tongue (BOT), and pharyngeal walls

What are the 2 most common originating sites/primary locations if the cancer is presumed to be of oropharyngeal origin?

Tonsils and BOT. Up to 80% of presumed oropharyngeal tumors are thought to originate from these 2 sites.

Approximately what % of pts with tonsillar primaries harbor Dz in both tonsils?

~5%–10% of pts with tonsillar primaries harbor Dz in both tonsils.

A primary can be identified in what % of H&N cancers of unknown primary?

A primary site of origin can ultimately be identified in ~40% of pts.

 Workup/Staging

What is the most common presentation for H&N cancers of an unknown primary?

Painless upper neck LAD (IB–III) is the most common presentation.

What is the T staging if no primary H&N site is found after workup?

T0 (not TX) is the assigned T stage if no primary is found.

On what are the overall stage groupings based if the primary is not known?

LN involvement determines the stage groupings:

1. 
   

   Stage III: N1

   
   
2. 
   

   Stage IVA: N2

   
   
3. 
   

   Stage IVB: N3

   
   
4. 
   

   Stage IVC: M1

What % of pts with an unknown primary present with bilat LAD (N2c)?

~10% of pts present with bilat neck Dz.

What does the workup include for pts with an unknown H&N primary?

Unknown H&N primary workup: H&P, CT/MRI, FNA of involved node, panendoscopy + directed Bx, and bilat tonsillectomy (+/− PET, bronchoscopy, esophagoscopy)

If FNA is negative in H&N pts with an unknown primary, what other kind of nodal Bx can be attempted?

If FNA is negative, a core Bx can be attempted next. Avoid incisional/excisional Bx, as this would result in “neck violation.”

What does cystic appear-ance of the involved LNs suggest in pts with H&N cancers?

Cystic appearance on imaging suggests HPV positivity/etiology.

What is the significance of nodal location in terms of likely primary sites?

If upper neck nodes are involved, they are more likely to be due to a H&N primary (e.g., if level I LNs, oral cavity [OC]; if upper level V, NPX primary). If lower neck or supraclavicular nodes are involved, they are more likely to be due to a chest or abdominal primary.

What is the significance of histology in terms of likely primary sites?

1. 
   

   Squamous cell: more likely to be a H&N primary

   
   
2. 
   

   Adenocarcinoma: more likely to be a chest or abdominal primary

What sites are traditionally biopsied for level II nodal involvement?

The BOT, NPX, pyriform sinus, and tonsils are typically biopsied with level II LN involvement.

When is a PET scan indicated for pts with an unknown H&N primary?

Per NCCN guidelines, PET is indicated only if other workup is unrevealing. It can be useful in excluding a larynx/HPX primary.

Why is it problematic to obtain the PET scan after endoscopy and Bx in pts with an unknown H&N primary?

Post-Bx inflammation may lead to false+ results. This is why some advocate that if used, PET scans should be done initially.

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