Head And Neck Cancer, Squamous

Head And Neck Cancer, Squamous

Todd M. Blodgett, MD

Alex Ryan, MD

Marios Papachristou, MD

Axial CT (left) and fused PET/CT (right) show a right parapharyngeal space mass image and a mucosal lesion only identified on the fused PET/CT image.

Follow-up axial CT (left) and fused PET/CT (right) after surgery demonstrate no residual or recurrent tumor.


Abbreviations and Synonyms

  • Squamous cell carcinoma of the head and neck (SCCHN)

  • Squamous cell carcinoma (SCCA) nodes

  • Unknown mucosal primary

  • Therapeutic assessment/restaging


  • Primary, regional, and distant malignancy from tumors of squamous cell origin in the head and neck

  • Primary unknown: Metastatic squamous cell carcinoma of the neck without an identifiable mucosal primary lesion

    • Undetectable mucosal lesions by clinical exam or

    • Negative anatomical imaging

  • Head and neck cancers include those arising from the lip, oral cavity, nasal cavity, paranasal sinuses, pharynx, and larynx

    • 90-95% are squamous cell carcinomas arising from mucosal linings of upper aerodigestive tract


General Features

  • Best diagnostic clue

    • Intensely FDG-avid nodes in the neck on PET or PET/CT

    • Enlarged or necrotic lymph nodes in the neck ± enhancement on CT

    • Primary unknown

      • PET shows asymmetrical focal fluorodeoxyglucose (FDG) uptake, with or without an identifiable abnormality on CT

      • Sensitivity for PET and PET/CT is 26-43% in cases where primary has eluded diagnosis

      • Fused PET/CT images often helpful for determining whether potential FDG abnormalities are mucosal lesions

      • Helpful for directing clinicians to areas for directed biopsies

    • Intense FDG activity in or around treated primary tumor with corresponding CT evidence of residual tumor

  • Location

    • Primary squamous cell lesions may involve any mucosal surface

      • Commonly involve the base of tongue, tonsils, or adenoids

      • Mucosal surfaces of the oropharynx, nasopharynx, and hypopharynx

    • Lymph node metastases involve neck nodes in expected drainage pattern based on primary tumor

    • SCCHN has high propensity to harbor malignancy in small lymph nodes

    • Most common metastatic sites: Lung, liver, skeletal system

  • Size

    • Early primary SCCHN may be undetectable (unknown primary SCCHN)

    • Lymph node metastases may range in size from normal (< 1 cm) to several centimeters

  • Morphology

    • Mass effect, abnormal enhancement, or necrosis may exist in larger tumors

    • Fatty lymph node hilum usually denotes benign lesion on CT (may be positive on PET if occult malignancy present)

    • Indistinct borders usually denote extranodal spread

Imaging Recommendations

  • Best imaging tool

    • PET/CT key for several clinical scenarios

      • Delineate extent of regional lymph node involvement

      • Detect distant metastases

      • Further evaluate potentially abnormal findings on another exam, such as mediastinal adenopathy detected by chest CT

      • Identify unknown primary tumor

      • Detect occasional synchronous primary

      • Monitor treatment response to select appropriate patients for salvage surgery

      • Conduct long-term surveillance for recurrence and metastases

      • Check any patient who presents with clinical evidence of recurrent disease

    • TNM staging

      • MR better than CT for specific questions such as presence of perineural spread or invasion of bone marrow

    • N stage

      • CT generally superior to MR for detection of regional lymph node metastases

    • M stage

      • Only patients at substantial risk of nodal or hematogenous metastases, T3 or T4, should undergo routine PET/CT for staging

    • Combined PET/CT may offer additional localization information and improve interpreting physician’s confidence level

      • Overall sensitivity and specificity of FDG PET and PET/CT > 90%; PET/CT sensitivity 96% and specificity 98%

      • PET/CT more helpful for radiation therapy planning; can lead to changes in gross tumor volume

      • Extended field FDG PET staging may detect disease outside of the head and neck in up to 21% of patients with head and neck cancer

      • Sensitivity for PET and PET/CT 26-43% in which primary has eluded diagnosis

      • Sensitivity for PET/CT better for accurate localization of lesion and directed biopsy recommendations

    • MR typically initial imaging study of choice for staging

      • Compared to noncontrast PET/CT, more accurate delineation of tumor extent, perineural involvement, and intracranial extent

      • Nearly comparable in accuracy in detecting regional LN metastases

    • Contrast-enhanced CT used only in laryngeal cancer; PET/CECT may be better for this indication than MR or CECT alone

    • Restaging: Combined PET/CT is more sensitive and specific than CT alone

  • Protocol advice

    • High resolution PET/CT from top of head to carina using standard head and neck protocol (especially for unknown primary)

    • Scan with arms down on PET/CT to avoid beam hardening artifact

      • Whole-body scan performed with arms above head and shorter acquisition time

      • Use neck immobilization device

    • Scan in mask for radiation planning PET/CT

      • Display images with PET intensity kept low-moderate (avoid “blooming”)

    • Pre-treatment with benzodiazepines in patients with excessive muscular FDG uptake on FDG PET

    • Warm patients before and after injection of FDG to reduce brown fat FDG uptake

    • Restaging

      • Scan with arms down, CECT, and neck immobilization device

      • Consider dual-time point imaging to help differentiate between inflammatory and neoplastic FDG activity

CT Findings

  • CECT: Early enhancement, rim enhancement, central necrosis, indistinct borders

  • Post-therapy neck difficult to interpret

    • Accuracy of CT ranges from 50-70%

    • Loss of fat planes and extensive post-surgical changes reduce the specificity of CT

    • Distortion of normal anatomy can be due to bony-cartilaginous necrosis, edema, and desmoplastic changes

    • CT may show enhancement, necrosis, or mass effect with residual/recurrent tumor

    • Best method of detection using CECT is serial examination

  • CT and MR may be negative for unknown primary if

    • Tumor is subtle or difficult to separate from adjacent normal structures (as with lingual tonsillar tissue)

    • Primary is superficial or very small

    • Scan is limited by motion or streak artifact

  • Abnormal size criteria for CT: ≥ 1 cm for most nodes; ≥ 1.5 cm for level I-II nodes; ≥ 8 mm for retropharyngeal nodes

    • FDG PET can detect smaller positive nodes (limited by spatial resolution)

  • Central necrosis specific for malignancy, but it is a late marker of metastatic adenopathy

    • Usually seen only in nodes ≥ 20 mm, which is beyond the typical cutoff of 10 mm for suspicion of malignancy

  • Contrast enhancement generally improves detection of malignancy

  • Round morphology more suspicious than reniform

Nuclear Medicine Findings

  • PET/CT is more accurate than PET and CT separately; PET is more accurate than CT alone

    • FDG PET sensitivity and specificity for residual disease 90% and 83%, respectively

    • PET/CT sensitivity, specificity, and accuracy 98%, 92%, and 94%, respectively

    • PET/CT decreases number of equivocal lesions by ˜ 50% and provides improved biopsy localization information

    • 74% better localization with PET/CT compared to PET in regions previously treated; 58% for untreated regions

  • Initial diagnosis

    • Squamous cell carcinoma almost always FDG avid

    • Look for primary lesion along the mucosal surfaces

    • Unknown primary: FDG PET typically shows focal asymmetrical FDG uptake in the mucosal primary

      • 5-10% of cases involve primary that cannot be found by physical exam, panendoscopy, or conventional radiographic imaging

      • PET/CT has been shown to find primary in 40% of patients whose primary was not identified in office or with surgical panendoscopy

      • False negatives with PET/CT means that this modality is a supplement to, but not a substitute for, endoscopy and biopsy with unknown primary

    • FDG PET shows no advantage over traditional techniques for identification and characterization of primary head/neck tumors for stage I/II lesions

      • Rarely adds information regarding initial T staging of primary

      • Exception is unknown primary

  • Staging

    • Screening for distant metastases advised for patients who have

      • Four or more lymph node metastases

      • Bilateral positive nodes

      • Nodes greater than 6 cm

      • Zone 4 nodes

      • Recurrent SCCHN

      • Second primary tumor

    • In one study, 24% of patients newly diagnosed with SCCA of the oral cavity had distant metastases picked up by PET/CT

      • However, PET/CT cannot preclude neck dissection in patients with advanced primaries but clinically node-negative necks

    • PET/CT may alter TNM score in 30-35% of patients by identifying nodal disease not apparent on CT, MR, or clinical exam

    • PET/CT has advantage in identifying distant disease because it can detect occult metastatic disease (e.g., subtle bone metastases)

      • Present in as many as 10% of patients with advanced local-regional disease

    • PET may alter treatment in many patients, decreasing toxic wide-field radiotherapy

    • Unclear whether PET/CT useful in identification of nodal metastases in patients with SCCHN and N0 necks on exam

    • Stage III/IV patients have high risk of distant metastases, creating a greater role for FDG PET

      • PET has a distinct advantage over CT/bronchoscopy, especially in the lung

    • Target volumes for IMRT and stereotactic radiosurgery may be modified in as many as 20% of cases with PET/CT vs. CT alone

      • PET/CT used primarily to include normal-sized lymph nodes with increased metabolic activity as part of high dose target volume

      • Helpful for contouring primary tumors whose borders are difficult to distinguish by anatomic imaging alone, as with some tongue-based tumors

    • PET/CT limited in staging local lymph node involvement if patient’s disease is clinically stage N0 after physical examination and anatomic imaging

      • Due to limited spatial resolution

      • Selective neck dissection or sentinal lymph node biopsy is more definitive

      • However, even in stage N0 disease PET/CT may be useful

      • Serves as a baseline to differentiate incidental physiologic FDG-avid foci from malignant foci on subsequent post-treatment exams

      • Otherwise a significant interpretive challenge if comparison images are not available

  • Restaging

    • Following surgery, no detectable tumor should be present

      • Variable amounts of post-surgical change expected

    • Post-surgery: Usually wait 4-6 weeks after to reevaluate with PET and PET/CT to avoid false positive studies due to inflammation

      • Reevaluation following surgery may be particularly helpful in cases where surgical margins are positive

    • Post-radiation

      • Positive PET one month after XRT has a positive predictive value of ˜ 100%

      • Negative PET one month after XRT has a lower negative predictive value (14%) early; fewer false negatives with longer follow-up period

  • Response to therapy

    • Following chemoradiation, metabolic response may precede reductions in tumor volume

    • Post-chemotherapy (approximately 1 month after completion): Sensitivity and specificity of FDG PET 90% and 83%

      • Little data evaluating early response to chemotherapy

      • Inflammatory changes seen with radiotherapy are not seen, and PET can be performed at earlier time point, such as 4-8 weeks

    • Post-chemoradiation

      • PET/CT has high negative predictive value and allows confident exclusion of residual cancer, thereby deferring planned neck dissection

    • Pitfalls and limitations

      • Several structures in the neck with variable physiologic FDG activity

      • Common muscles with asymmetrical FDG activity: Pterygoids, sternocleidomastoid, strap muscles, and mylohyoid

      • Glands: Salivary glands (submandibular and parotid); can have intense FDG activity following some chemo regimens

      • Lymphoid tissue: Lingual tonsils, palatine tonsils, and adenoids (Waldeyer ring)

      • Brown fat: Can be symmetrical or asymmetrical, can be focal anywhere in the neck

      • FDG PET may not detect small areas of residual/recurrent disease, leading to early false negative exams after therapy

      • PET frequently fails to identify hypermetabolism in areas of marrow space infiltration and perineural extension

      • Cartilage necrosis may be FDG avid indefinitely

      • Cricoarytenoids typically FDG avid and often asymmetric


Metastatic Disease from Thyroid or Melanoma

  • May look identical to squamous cell carcinoma

Abscess or Suppurative Nodes

  • Usually has central necrosis; identical in appearance to necrotic lymph node

  • FDG PET not helpful for differentiation; biopsy required

  • Often indistinguishable from tumor; correlate clinically


  • Difficult to differentiate from SCCHN based on imaging; associated mucosal lesion favors SCCHN

  • NHL: May mimic tonsillar inflammatory disease

Residual/Recurrent Malignancy

  • Often indistinguishable from abscess/inflammation

  • Short-term serial evaluation very helpful

  • CT may show asymmetrical mass effect

Radiation-Induced Inflammation

  • FDG uptake from inflammation usually present for 4-8 weeks following therapy

  • Osteoradionecrosis can cause false positive early (before frank necrosis causes negative PET)

  • Dual-time point PET imaging at 1 hour and 3 hour post FDG injection may be helpful in differentiating tumor vs. inflammation

    • FDG uptake from 1-3 hours: Tumor may increase; inflammation may plateau or decrease

Physiologic Activity

  • Benign tonsil FDG uptake typically will be symmetrical but can be intense

  • Muscle activity may be focal and asymmetrical

    • Correlate PET with CT; pre-treatment with benzodiazepines may reduce muscle uptake

  • Measure Hounsfield units (HU); -50 to -150 compatible with brown fat

    • Warm patient before FDG injection to reduce brown fat uptake of FDG

Reactive Nodes

  • Tend to be normal to minimally enlarged, symmetrical, low level FDG uptake

  • May be associated with diffuse tonsillar uptake if recent upper respiratory or viral infection

  • Careful history for recent upper respiratory infection is advisable


General Features

  • General path comments

    • Nodal level classification scheme

    • American Joint Committee on Cancer (AJCC) and American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS)

      • Level IA: Submental nodes between anterior digastrics

      • Level IB: Submandibular, lateral to IA anterior to the posterior margin of submandibular gland (SMG)

      • Level IIA: Upper internal jugular nodes; anterior, lateral, or posterior and touching the jugular vein

      • Level IIB: Posterior, not touching jugular

      • Level III: Mid-internal jugular nodes, extend from inferior hyoid to cricoid arch

      • Level IV: Low internal jugular nodes, extend from cricoid arch to the level of the clavicle

      • Level V: Spinal accessory group, nodes in the posterior triangle; level VA: Above cricoid; level VB: Below inferior cricoid border

      • Level VI: Upper visceral nodes; between the carotid arteries from bottom of the hyoid to the top of the manubrium

      • Level VII: Superior mediastinal nodes; between the carotid arteries from below the top of the manubrium above the innominate vein

      • Supraclavicular nodes: At or caudal to the level of the clavicle and lateral to the carotid artery

      • Retropharyngeal nodes: Within 2 cm of the skull base medial to the carotid arteries

      • Parotid: Nodes within the parotid gland

    • Initial workup with physical exam, office endoscopy, and MR/CT

      • If definitive for nodal disease, PET/CT is appropriate for accurate evaluation of nodal metastases

      • Suggestive PET/CT findings should prompt fine needle aspiration (FNA)

      • If FNA is negative, definitive treatment is pursued and PET/CT is optional, to serve as baseline prior to therapy

    • If a focus of unknown primary is suspected on metabolic imaging

      • Panendoscopy and frozen section biopsy

      • Panendoscopy includes oropharynx, hypopharynx, nasopharynx, larynx, and upper esophagus

    • If negative, further biopsy specimens may be obtained from most common sites for primary tumors

      • Base of tongue

      • Nasopharynx

      • Contralateral tonsillar fossa

      • Pyriform sinus

      • Ipsilateral tonsillar fossa

    • Reassessment

      • Biopsy areas that appear suspicious on PET or PET/CT

      • Alternatively, short-term interval follow-up PET or PET/CT

  • Etiology: Smoking, chewing tobacco, alcohol abuse

  • Epidemiology

    • SCCHN newly diagnosed in 40,000 patients annually in United States

    • Mortality is 23%

    • Average 5 year survival 56%

  • Associated abnormalities: Risk factors also predispose to esophageal and lung cancer

Staging, Grading, or Classification Criteria

  • T stage: Assessment requires knowledge of size of primary lesions, depth of invasion, and involvement of surrounding structures

  • N stage: AJCC characteristics include number of nodes involved, size of nodes, location (laterality and level), and morphology

  • Staging of SCCHN requires

    • Complete history and physical

    • Histologic confirmation

    • Characterization of primary

    • Recognition of local/regional nodal disease

    • Identification of distant metastatic disease



  • Most common signs/symptoms

    • May present with pain associated with primary mass or neck mass

    • Symptoms of residual/recurrent tumor overlap with post-treatment complications; pain is most common

  • Other signs/symptoms: Mass on clinical exam


  • Age: Generally > 40-45 years

  • Gender: M > F

Natural History & Prognosis

  • Nodal metastasis is most accurate prognostic factor for SCCHN

    • Unilateral nodal involvement indicates 50% reduction in expected lifespan; bilateral nodal involvement indicates 75% reduction

    • 10 year survival drops from 85% to 10-40% in patients with positive nodes

    • Carotid artery involvement or encasement portends dismal prognosis with 100% mortality

    • Majority of patients do not have metastatic disease within cervical nodes at presentation

      • 20% risk of occult metastasis in patients with clinically node-negative necks

  • 10-15% of patients with SCCHN will present with distant metastases

  • Unknown primary

    • PET and PET/CT can help direct biopsy

    • 2-9% of SCCHN patients present with cervical lymph node metastases without clear evidence of primary site

Sep 22, 2016 | Posted by in MAGNETIC RESONANCE IMAGING | Comments Off on Head And Neck Cancer, Squamous

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