Locally Advanced Thyroid Cancer
Author: Rodrigo Arrangoiz MS, MD, FACS, FSSO
My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida.
I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016.
Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida.
Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.
Anatomy of the Nasopharynx
- Overview:
- The nasopharynx is the uppermost part of the pharynx:
- A cuboidal muscular-mucosal space behind the nasal cavity and above the soft palate, anterior to the atlas (C1) and axis (C2)
- It functions purely as a respiratory conduit:
- Communicating anteriorly with the nasal cavity via the choanae and laterally with the middle ear via the Eustachian (pharyngotympanic) tubes
- The nasopharynx is the uppermost part of the pharynx:
- Boundaries (walls)
- Anterior:
- Paired choanae (posterior nasal openings)
- Bony margin bounded:
- Anteroinferiorly by the horizontal plate of the palatine bone
- Superiorly by the sphenoid body and vaginal process of the medial pterygoid plate
- Laterally by the medial pterygoid plates
- Roof and posterior wall:
- Continuous, sloping surface formed by the sphenoid body and basilar (clival) occipital bone superiorly, continuing over the anterior arches of C1 and C2:
- Mucosa adherent to the pharyngobasilar fascia
- Continuous, sloping surface formed by the sphenoid body and basilar (clival) occipital bone superiorly, continuing over the anterior arches of C1 and C2:
- Lateral walls:
- Organized around the Eustachian tube orifice
- Floor / inferior boundary:
- Open inferiorly, communicating with the oropharynx via the pharyngeal isthmus:
- Upper surface of the soft palate forms the effective floor, and the isthmus closes during swallowing to prevent nasal reflux:
- The nasopharyngeal cavity opens into the cavity of the oropharynx through the pharyngeal isthmus, which lies between the posterior border of the soft palate and the posterior pharyngeal wall:
- This region is marked on the posterior pharyngeal wall by a fold of mucosa formed by the palatopharyngeal sphincter between the palatopharyngeus muscle and the superior pharyngeal constrictor muscle:
- During swallowing, elevation of the soft palate and constriction of the palatopharyngeal sphincter seals off the pharyngeal isthmus, separating the nasopharynx from the oropharynx:
- This prevents the retrograde flow of materials into the nasopharynx and nasal cavity
- During swallowing, elevation of the soft palate and constriction of the palatopharyngeal sphincter seals off the pharyngeal isthmus, separating the nasopharynx from the oropharynx:
- This region is marked on the posterior pharyngeal wall by a fold of mucosa formed by the palatopharyngeal sphincter between the palatopharyngeus muscle and the superior pharyngeal constrictor muscle:
- The nasopharyngeal cavity opens into the cavity of the oropharynx through the pharyngeal isthmus, which lies between the posterior border of the soft palate and the posterior pharyngeal wall:
- Upper surface of the soft palate forms the effective floor, and the isthmus closes during swallowing to prevent nasal reflux:
- Open inferiorly, communicating with the oropharynx via the pharyngeal isthmus:
- Anterior:
- Lateral wall structures:
- Torus tubarius:
- Prominent posterior lip of the tubal orifice:
- Elevated by tubal cartilage
- Prominent posterior lip of the tubal orifice:
- Salpingopalatine fold:
- Anterior lip of the orifice
- Torus levatorius:
- Inferior elevation overlying the levator veli palatini
- Salpingopharyngeal fold:
- Mucosal fold below the torus tubarius overlying salpingopharyngeus
- Fossa of Rosenmüller (pharyngeal recess):
- Deep lateral mucosal depression behind the torus tubarius:
- Its apex points toward the internal carotid artery:
- With the foramen lacerum above:
- Most common site of origin of nasopharyngeal carcinoma and a key surgical landmark
- With the foramen lacerum above:
- Its apex points toward the internal carotid artery:
- Deep lateral mucosal depression behind the torus tubarius:
- Torus tubarius:
- Musculature:
- Tensor veli palatini:
- Opens the Eustachian during swallowing.
- Levator veli palatini:
- Elevates the soft palate:
- Forms the torus levatorius
- Elevates the soft palate:
- Salpingopharyngeus:
- Runs in the salpingopharyngeal fold:
- Mucosal fold below the torus tubarius
- Runs in the salpingopharyngeal fold:
- Superior constrictor:
- Forms the muscular posterolateral wall
- Pharyngobasilar fascia:
- Suspends the pharynx from the skull base.
- Tensor veli palatini:
- Lymphoid tissue
- Prominent components of Waldeyer’s ring:
- Nasopharynx-associated lymphoid tissue
- The nasopharyngeal tonsil (adenoids):
- Lies on the roof / posterior wall:
- Is prominent in children and atrophies with age:
- Hypertrophy can obstruct nasal breathing or the Eustachian tube orifice
- Is prominent in children and atrophies with age:
- Lies on the roof / posterior wall:
- Tubal tonsils sit near the tubal orifices
- Prominent components of Waldeyer’s ring:
- Epithelium
- Largely respiratory (ciliated pseudostratified columnar) epithelium:
- With areas of stratified squamous epithelium at contact / friction sites
- Largely respiratory (ciliated pseudostratified columnar) epithelium:
- Neurovascular and clinical relations
- Sensory innervation:
- Trigeminal (V2, pharyngeal branch) and glossopharyngeal nerves
- Deep lateral-wall structures:
- Parapharyngeal internal carotid artery (lateral to the fossa of Rosenmüller)
- Foramen lacerum and clivus posteriorly
- Foramen ovale (V3) and pterygopalatine fossa contents (vidian nerve, sphenopalatine ganglion
- V2 laterally / anteriorly:
- These explain pathways of local spread and perineural invasion in nasopharyngeal carcinoma
- Sensory innervation:
- References
- Endoscopic endonasal transpterygoid nasopharyngectomy: Anatomical considerations and technical note. Liu J, Zhao J, Wang Y, et al. Head & Neck. 2024;46(2):306-320. doi:10.1002/hed.27581.
- Anatomy and assessment of the pediatric airway. Adewale L. Paediatric Anaesthesia. 2009;19 Suppl 1:1-8. doi:10.1111/j.1460-9592.2009.03012.x.
RTOG-0129 was a Phase 3 Randomized Trial – Accelerated-Fractionation Radiotherapy vs. Standard-Fractionation
- RTOG-0129:
- Was a phase 3 randomized trial (enrolled 2002 to 2005) conducted by the Radiation Therapy Oncology Group:
- That tested whether accelerated-fractionation radiotherapy improves outcomes over standard-fractionation radiotherapy:
- When each is given concurrently with cisplatin in locally advanced (stage III to IV) head and neck squamous-cell carcinoma
- That tested whether accelerated-fractionation radiotherapy improves outcomes over standard-fractionation radiotherapy:
- Its primary comparison was negative :
- The two radiotherapy schedules produced equivalent survival:
- But its retrospective HPV analysis became a landmark:
- Establishing tumor HPV status as a strong independent prognostic factor in oropharyngeal cancer
- Was a phase 3 randomized trial (enrolled 2002 to 2005) conducted by the Radiation Therapy Oncology Group:
- Design:
- Population:
- Patients with locally advanced (stage III to IV) squamous-cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx:
- 743 randomized:
- 738 analyzed
- 743 randomized:
- Patients with locally advanced (stage III to IV) squamous-cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx:
- Standard-fractionation arm:
- 70 Gy in 2 Gy fractions once daily, 5 days / week over 7 weeks (35 fractions), with cisplatin 100 mg/m² on days 1, 22, and 43 (3 cycles)
- Accelerated-fractionation arm (concomitant boost):
- 72 Gy over 6 weeks — 1.8 Gy / fraction to the large field, plus a second daily 1.5 Gy boost fraction during the last 12 treatment days — with cisplatin 100 mg/m² on days 1 and 22 (2 cycles)
- Technique:
- IMRT was not permitted:
- Treatment used 2D / 3D conformal radiotherapy
- IMRT was not permitted:
- Median follow-up was 4.8 years in the original report, with long-term follow-up of 7.9 years in later analyses
- Population:
- Primary result (fractionation):
- There was no significant difference between arms
- The 3-year overall survival was 70.3% with accelerated fractionation versus 64.3% with standard fractionation (P=0.18; HR for death 0.90, 95% CI 0.72–1.13), and rates of high-grade acute and late toxicity were similar
- This supported the conclusion that accelerated fractionation offers no efficacy advantage over conventional fractionation when combined with concurrent cisplatin
- Landmark HPV finding:
- Among patients with oropharyngeal cancer, 63.8% (206/323) had HPV-positive tumors
- These patients were younger, more often white, had fewer pack-years, and smaller primaries:
- 3-year overall survival:
- 82.4% (HPV-positive) vs 57.1% (HPV-negative); P<0.001
- After adjustment for age, race, tumor / nodal stage, tobacco, and treatment:
- HPV-positive status conferred a 58% reduction in risk of death (HR 0.42, 95% CI 0.27–0.66)
- The 8-year overall survival rate was 70.9% vs 30.2% (HR 0.30, 95% CI 0.21–0.42)
- 3-year overall survival:
- References:
- Ang KK, Harris J, Wheeler R, et al. Human Papillomavirus and Survival of Patients with Oropharyngeal Cancer. N Engl J Med. 2010.
- Ang KK, Harris J, Wheeler R, et al. Human Papillomavirus and Survival of Patients with Oropharyngeal Cancer. N Engl J Med. 2010.
- Lacas B, Bourhis J, Overgaard J, et al. Role of Radiotherapy Fractionation in Head and Neck Cancers (MARCH): An Updated Meta-Analysis. Lancet Oncol. 2017.
- De Felice F, Bonomo P, Sanguineti G, Orlandi E. Moderately accelerated intensity-modulated radiation therapy using simultaneous integrated boost: Practical reasons or evidence-based choice? A critical appraisal of literature. Head Neck. 2020.
- Driessen CM, Janssens GO, van der Graaf WT, et al. Toxicity and efficacy of accelerated radiotherapy with concurrent weekly cisplatin for locally advanced head and neck carcinoma. Head Neck. 2016.
- National Comprehensive Cancer Network. Head and Neck Cancers. 2026.
Chow LQM. Head and Neck Cancer. N Engl J Med. 2020. - Budach V, Tinhofer I. Novel Prognostic Clinical Factors and Biomarkers for Outcome Prediction in Head and Neck Cancer: A Systematic Review. Lancet Oncol. 2019.
Signs and Symptoms of Nasopharyngeal Carcinoma
- Overview:
- Nasopharyngeal carcinoma (NPC):
- Typically presents with a painless upper-neck mass plus nasal, aural, and cranial nerve symptoms:
- Reflecting the tumor’s origin in the fossa of Rosenmüller with lateral (parapharyngeal) and superior (skull base) spread
- Typically presents with a painless upper-neck mass plus nasal, aural, and cranial nerve symptoms:
- Early symptoms are non-specific:
- So most patients present at advanced stage (III to IV)
- Nasopharyngeal carcinoma (NPC):
- Presenting features by mechanism:
- Neck mass (regional nodal spread):
- Most common presentation (~75%):
- Painless enlarged upper cervical node:
- Often the first / only sign
- Painless enlarged upper cervical node:
- Retropharyngeal and level II nodes:
- Are first echelons
- May occur without a visible primary
- Most common presentation (~75%):
- Nasal symptoms (primary tumor):
- Epistaxis or blood-tinged discharge
- Unilateral nasal obstruction
- Rhinorrhea (nasal dysfunction ~73%)
- “Nasal twang” or voice change with large tumors
- Aural / eustachian tube dysfunction:
- Unilateral serous otitis media
- Conductive hearing loss
- Tinnitus
- Aural fullness (~62%):
- The feeling of pressure, clogging, or fullness inside the ear:
- Often described as having water or air trapped inside
- The feeling of pressure, clogging, or fullness inside the ear:
- Skull-base / cranial nerve involvement:
- Headache (~35%)
- Facial pain / numbness (CN V)
- Diplopia (~11%, CN VI)
- Cranial nerve palsy in ~20% of the cases at diagnosis
- Most affected nerves:
- CN V and VI, plus III and XII
- Advanced disease may cause cavernous sinus syndrome and multiple cranial neuropathies
- Less common findings:
- Trismus (~3%, pterygoid muscle invasion)
- Nasal regurgitation (soft-palate paresis)
- Symptoms of distant metastasis:
- Bone, lung, liver
- Anorexia / weight loss uncommon:
- If present, raise suspicion for distant spread
- Neck mass (regional nodal spread):
- Evaluation:
- Complete head and neck exam with nasopharyngeal fiberoptic endoscopy; neck palpation
- EBV testing:
- Endemic undifferentiated / nonkeratinizing subtypes strongly EBV-associated
- Biopsy of nasopharyngeal lesion
- MRI skull base to clavicle
- References:
- Wei WI, Sham JS. Nasopharyngeal Carcinoma. Lancet. 2005.
- Chua MLK, Wee JTS, Hui EP, Chan ATC. Nasopharyngeal Carcinoma. Lancet. 2016.
- Ayan I, Kaytan E, Ayan N. Childhood Nasopharyngeal Carcinoma: From Biology to Treatment. Lancet Oncol. 2003.
- Expert Panel on Neurological Imaging, Gule-Monroe MK, Calle S, et al. ACR Appropriateness Criteria® Staging and Post-Therapy Assessment of Head and Neck Cancer. J Am Coll Radiol. 2023.
- Kumari B, Goyal MK, Lal V. Pearls & Oy-Sters: Bilateral Cavernous Sinus Syndrome as Presenting Manifestation of Nasopharyngeal Carcinoma. Neurology. 2014.
- Brennan B. Nasopharyngeal Carcinoma. Orphanet J Rare Dis. 2006.
- Her C. Nasopharyngeal Cancer and the Southeast Asian Patient. Am Fam Physician. 2001.
- Albilali A, Alotaibi NH, Alfadley A, Alqarni KM, Alhajlah A. Extensive Locally Invasive Nasopharyngeal Carcinoma Involving 10 Cranial Nerves Palsies: An Interesting Case Report. Front Oncol. 2024.
- Kumari B, Goyal MK, Lal V. Pearls & Oy-Sters: Bilateral Cavernous Sinus Syndrome as Presenting Manifestation of Nasopharyngeal Carcinoma. Neurology. 2014.
- Kumari B, Goyal MK, Lal V. Pearls & Oy-Sters: Bilateral Cavernous Sinus Syndrome as Presenting Manifestation of Nasopharyngeal Carcinoma. Neurology. 2014.
- Zhou P, Zhu Y, Xu B, et al. Cavernous Sinus Syndrome in a Patient With Occult Nasopharyngeal Carcinoma: A Diagnostic Challenge. Oral Oncol. 2025.
- National Comprehensive Cancer Network. Head and Neck Cancers. 2026.
- Chad Zender. Nasopharynx. Essential Cases in Head and Neck Oncology. 2022.
Diagnostic Workup of Nasopharyngeal SCC
- History, Physical Exam, and Endoscopy
- Complete H&P including full head and neck exam, with mirror examination as clinically indicated:
- Nasopharyngeal fiberoptic examination
- Documentation of tobacco (pack-years) and alcohol use with cessation counseling:
- Distress screening
- Complete H&P including full head and neck exam, with mirror examination as clinically indicated:
- Tissue Diagnosis
- Biopsy of primary site or FNA of the neck:
- Image-guided (US or CT) needle biopsy of cystic neck nodes may improve yield over palpation-guided FNA
- Core biopsy preferred when systemic therapy is planned for unresectable / metastatic disease:
- Allows biomarker testing
- Biopsy of primary site or FNA of the neck:
- Imaging of Primary and Neck
- MRI with and without contrast from skull base to clavicle, ± CT skull base/neck with contrast
- MRI preferred for:
- Skull base invasion, cranial nerve involvement, perineural spread, intracranial / orbital extension, marrow invasion
- CT complementary for cortical bone erosion / destruction
- MRI preferred for:
- MRI with and without contrast from skull base to clavicle, ± CT skull base/neck with contrast
- Imaging for Distant Metastases
- FDG-PET / CT and / or chest CT with contrast:
- Bone scan if PET / CT not done
- FDG-PET/CT preferred for locoregionally advanced disease (T3 to T4 or ≥ N1)
- Dedicated contrast-enhanced brain MRI:
- Reserved for histologies where brain metastasis is a concern
- FDG-PET / CT and / or chest CT with contrast:
- Virology and Biomarkers
- EBV / DNA testing:
- For nonkeratinizing or undifferentiated histology:
- Test tumor tissue and blood
- For nonkeratinizing or undifferentiated histology:
- Tissue:
- ISH for EBV-encoded RNA (EBER) or IHC for latent membrane protein (LMP)
- Blood:
- Plasma / serum EBV DNA load by PCR (BamHI-W, EBNA, or LMP targets):
- Reflects prognosis and treatment response
- Plasma / serum EBV DNA load by PCR (BamHI-W, EBNA, or LMP targets):
- Consider HPV testing (may inform etiology)
- EBV / DNA testing:
- Additional Evaluations as Clinically Indicated
- Dental / prosthodontic evaluation
- Nutrition, speech, and swallowing evaluation/therapy
- Audiogram
- Consideration of ophthalmologic and endocrine evaluation
- Fertility / reproductive counseling
- Screening for hepatitis B
- Multidisciplinary consultation
- Staging
- Clinical staging follows AJCC / UICC TNM (9th ed.):
- Distinct from other head and neck subsites:
- Nodal criteria use a 6-cm size cutoff and the caudal border of the cricoid cartilage as a landmark
- T0 defined by EBV-positive cervical nodes without identifiable primary
- Workup culminates in classification into M0 vs M1 pathway
- Distinct from other head and neck subsites:
- Clinical staging follows AJCC / UICC TNM (9th ed.):
- Key Practical Points
- Endoscopy plus biopsy is the diagnostic gold standard:
- Most tumors arise in the fossa of Rosenmüller:
- Targeted / blind biopsies appropriate:
- When no tumor is visible but suspicion is high
- Targeted / blind biopsies appropriate:
- Most tumors arise in the fossa of Rosenmüller:
- MRI is the preferred modality for local staging:
- Reported 100% sensitivity, 84% specificity in one series
- FDG-PET / CT is the most sensitive test for nodal and distant metastasis
- Plasma EBV DNA is more sensitive / specific than serum IgA / VCA titers:
- Correlates with stage, and normalizes with successful treatment:
- Useful for baseline risk stratification and post-treatment monitoring
- Correlates with stage, and normalizes with successful treatment:
- WHO histology:
- Keratinizing SCC
- Nonkeratinizing carcinoma:
- Differentiated
- Undifferentiated:
- Lymphoepithelioma-like carcinoma is a variant of the undifferentiated type
- Basaloid SCC
- In non-endemic regions:
- A larger fraction of NPC is EBV-negative:
- More often keratinizing / HPV-associated):
- Lowering EBV DNA diagnostic yield
- More often keratinizing / HPV-associated):
- A larger fraction of NPC is EBV-negative:
- Endoscopy plus biopsy is the diagnostic gold standard:
- References
- Head and Neck Cancers. National Comprehensive Cancer Network. Updated 2026-05-12.
- ACR Appropriateness criteria® for nasopharyngeal carcinoma. Saba NF, Salama JK, Beitler JJ, et al. Head & Neck. 2016;38(7):979-86. doi:10.1002/hed.24423.
- Nasopharyngeal Carcinoma. Chua MLK, Wee JTS, Hui EP, Chan ATC. Lancet (London, England). 2016;387(10022):1012-1024. doi:10.1016/S0140-6736(15)00055-0.
- The Role of Cross-Sectional Imaging in Suspected Nasopharyngeal Carcinoma. Shayah A, Wickstone L, Kershaw E, Agada F. Annals of the Royal College of Surgeons of England. 2019;101(5):325-327. doi:10.1308/rcsann.2019.0025.
- Nasopharyngeal Carcinoma. Chen YP, Chan ATC, Le QT, et al. Lancet (London, England). 2019;394(10192):64-80. doi:10.1016/S0140-6736(19)30956-0.
- Comparison of Plasma Epstein-Barr Virus (EBV) DNA Levels and Serum EBV Immunoglobulin a/Virus Capsid Antigen Antibody Titers in Patients With Nasopharyngeal Carcinoma. Shao JY, Li YH, Gao HY, et al. Cancer. 2004;100(6):1162-70. doi:10.1002/cncr.20099.
- Epstein-Barr Virus DNA in Nasopharyngeal Carcinoma: A Brief Review. Xue F, He X. Methods in Molecular Biology (Clifton, N.J.). 2020;2204:99-107. doi:10.1007/978-1-0716-0904-0_9.
- Circulating Tumor DNA in Head and Neck Cancer. Kansara S, Contrera K, Roof S, et al. JAMA Otolaryngology– Head & Neck Surgery. 2026;:2851926. doi:10.1001/jamaoto.2026.2045.
The Paraglottic Space (PGS)
- The paraglottic space (PGS):
- Is a bilateral, deep fascial compartment of the larynx:
- Filled with fat and loose connective tissue
- Definition:
- The paraglottic space (PGS) is a fat- and muscle-containing connective tissue compartment of the larynx:
- Whose greatest clinical importance is:
- As a preferential pathway for the spread of laryngeal cancers:
- Particularly transglottic tumors
- As a preferential pathway for the spread of laryngeal cancers:
- As a prognostic and surgical planning determinant
- Whose greatest clinical importance is:
- It surrounds the laryngeal ventricle:
- Lies deep to the true and false cords:
- Between the mucosa and inner surface of the thyroid cartilage:
- It communicates directly with the preepiglottic space:
- Allowing tumor to move rapidly between compartments
- It communicates directly with the preepiglottic space:
- Between the mucosa and inner surface of the thyroid cartilage:
- Lies deep to the true and false cords:
- It spans the supraglottic, glottic, and subglottic regions:
- Playing a critical role in clinical oncology:
- Because it acts as a primary, hidden pathway for the “transglottic” spread of laryngeal cancers
- Playing a critical role in clinical oncology:
- The paraglottic space (PGS) is a fat- and muscle-containing connective tissue compartment of the larynx:
- Is a bilateral, deep fascial compartment of the larynx:
- Anatomical Boundaries
- It was first described by:
- Tucker and Smith in 1962
- The paraglottic space is a tetrahedral-shaped compartment bounded by several cartilaginous and fibroelastic structures:
- Anterolaterally:
- The inner surface of the thyroid cartilage
- Superomedially:
- The quadrangular membrane:
- Which separates it from the false vocal folds
- The space is continuous with (or, in some specimens, separated by a collagenous septum from) the preepiglottic space
- The quadrangular membrane:
- Inferomedially:
- The conus elasticus:
- Which separates it from the subglottis
- The conus elasticus:
- Posteriorly / Posterolaterally / Dorsally:
- The mucosal lining of the piriform sinus
- Anteriorly:
- It communicates directly with the pre-epiglottic space
- Anterolaterally:
- It was first described by:
- Content of the Space:
- The paraglottic space houses several vital neurovascular and muscular structures embedded within its protective layer of loose areolar and adipose tissue:
- Adipose tissue:
- Abundant fat:
- That makes the space highly visible on CT and MRI scans
- Abundant fat:
- Intrinsic laryngeal muscles:
- Including the thyroarytenoid, lateral cricoarytenoid, and posterior cricoarytenoid muscles
- Blood vessels and nerves:
- Glands, blood vessels, and branches of the superior and inferior laryngeal nerves
- Adipose tissue:
- The paraglottic space houses several vital neurovascular and muscular structures embedded within its protective layer of loose areolar and adipose tissue:
- Clinical Significance:
- The primary clinical importance of the paraglottic space:
- Lies in laryngeal oncology and tumor staging:
- Transglottic Spread:
- Because the PGS crosses the level of the laryngeal ventricle without physical barriers:
- A squamous cell carcinoma originating in the true vocal cords can easily migrate vertically through this space into the false vocal cords (or vice versa):
- This is known as transglottic spread
- A squamous cell carcinoma originating in the true vocal cords can easily migrate vertically through this space into the false vocal cords (or vice versa):
- Because the PGS crosses the level of the laryngeal ventricle without physical barriers:
- Cancer Staging:
- Invasion of the inferior paraglottic space can limit vocal fold mobility
- In the TNM staging system, tumor invasion into the paraglottic space:
- Automatically elevates a glottic or supraglottic laryngeal cancer to a T3 stage:
- Altering the treatment trajectory from localized therapy to systemic options or extensive surgery
- Automatically elevates a glottic or supraglottic laryngeal cancer to a T3 stage:
- Surgical Planning:
- Knowledge of the paraglottic space borders is vital for performing voice-sparing, partial laryngectomies
- If a tumor completely infiltrates this space:
- A total laryngectomy may be required to ensure clean margins
- Transglottic Spread:
- Lies in laryngeal oncology and tumor staging:
- The primary clinical importance of the paraglottic space:
- References:
- Joo YH, Park JO, Cho KJ, Kim MS. Relationship between paraglottic space invasion and cervical lymph node metastasis in patients undergoing supracricoid partial laryngectomy. Head Neck. 2012.
- Tamaki A, Miles BA, Lango M, Kowalski L, Zender CA. AHNS Series: Do you know your guidelines? Review of current knowledge on laryngeal cancer. Head Neck. 2018.
- Reidenbach MM. The Paraglottic Space and Transglottic Cancer: Anatomical Considerations. Clin Anat. 1996.
- Reidenbach MM. Borders and Topographic Relationships of the Paraglottic Space. Eur Arch Otorhinolaryngol. 1997.
- Joo YH, Park JO, Cho KJ, Kim MS. Relationship between paraglottic space invasion and cervical lymph node metastasis in patients undergoing supracricoid partial laryngectomy. Head Neck. 2012.
- Ferrari M, Schreiber A, Mattavelli D, et al. Surgical anatomy of the parapharyngeal space: Multiperspective, quantification-based study. Head Neck. 2019.
- Wang XR, Wang H, Gao Y, et al. Study on the Ultrasonic Characteristics of the Paraglottic Space at the Glottic Level in Normal Adults. Head Neck. 2026.
- Virós Porcuna D, Pollán Guisasola CM, Viña Soria C, et al. Transoral robotic parapharyngeal space dissection. Head Neck. 2024.
- Mohamed A, Paleri V, George A. A cadaveric study quantifying the anatomical landmarks of the facial artery and its parapharyngeal branches for safe transoral surgery. Head Neck. 2019.
- Hearn MW, Vogel CT, Laughlin RM, et al. Review of Spaces. Atlas of Operative Oral and Maxillofacial Surgery. 2022.
- Dammann F, Wartenberg J. Diseases of the Head and Neck. Radiology-Nuclear Medicine Diagnostic Imaging. 2023.
Histological Subtypes of Nasopharyngeal Carcinoma (NP)
- WHO Classification:
- Keratinizing Squamous Cell Carcinoma (formerly WHO Type I):
- Shows squamous differentiation with intercellular bridges and / or keratinization over most of its extent
- More common in non-endemic areas:
- Accounts for > 75% of NPC in the non-Asian US population (Caucasian)
- Typically found in older adults:
- Associated with smoking / alcohol
- Carries the worst prognosis among the subtypes
- Not typically associated with EBV:
- HPV has emerged as a potential factor in this subtype
- Non-Keratinizing Carcinoma (formerly WHO Types II and III):
- The dominant subtype worldwide:
- Constituting > 95% of cases in endemic regions:
- Southern China
- Southeast Asia
- Constituting > 95% of cases in endemic regions:
- Strongly associated with:
- EBV infection
- More radiosensitive than the keratinizing subtype
- Subdivided into:
- Differentiated (formerly WHO Type II):
- Cells show a maturation sequence without evident squamous differentiation on light microscopy
- Fusiform or oval nuclei with scant cytoplasm
- Display a stratified appearance and distinct cell margins
- Undifferentiated (formerly WHO Type III):
- Oval or round vesicular nuclei with prominent nucleoli, scant eosinophilic cytoplasma
- Indistinct cell margins with a syncytial rather than pavemented appearance
- Often called lymphoepithelioma (Schminke tumor) due to prominent admixed non-malignant lymphoid infiltrate
- Most common subtype in endemic areas (~ 95% in southern China) and in children (~ 90%)
- Basaloid Squamous Cell Carcinoma (added in 2005 WHO classification):
- A rare subtype:
- Also associated with EBV infection
- Comprises a minimal subset of patients
- A rare subtype:
- Differentiated (formerly WHO Type II):
- The dominant subtype worldwide:
- Keratinizing Squamous Cell Carcinoma (formerly WHO Type I):
- Evolution of the Classification:
- The original 1978 WHO system:
- Used a numerical scheme:
- Types I, II, III
- Used a numerical scheme:
- In 1991:
- Types II and III were combined into a single “non-keratinizing carcinoma” category:
- The numerical designations were dropped
- Types II and III were combined into a single “non-keratinizing carcinoma” category:
- The basaloid squamous cell carcinoma category:
- Was added in the 2005 WHO classification
- The original 1978 WHO system:
- Geographic Distribution of Subtypes:
- North America:
- ~25% type I, 12% type II, 63% type III
- Southern China:
- 2% type I, 3% type II, 95% type III
- In the US:
- Non-keratinizing subtypes:
- Predominate in East / Southeast Asian populations
- The discrepancy is explained by the racial /ethnic composition of the study populations:
- In the US, disproportionately develop non-keratinizing (type III) NPC:
- Which skews the overall North American numbers toward type III
- When restricted to White / non-Asian patients, keratinizing SCC predominates
- In the US, disproportionately develop non-keratinizing (type III) NPC:
- Non-keratinizing subtypes:
- North America:
- References:
- Chen YP, Chan ATC, Le QT, et al. Nasopharyngeal Carcinoma. Lancet. 2019.
- KO, Mazul AL, Skillington SA, et al. The prognostic significance of race in nasopharyngeal carcinoma by histological subtype. Head Neck. 2021.
- Alsavaf MB, Marquardt M, Abouammo MD, et al. Patient Characteristics and Treatment Outcomes of Nasopharyngeal Carcinoma in Nonendemic Regions. JAMA Netw Open. 2025.
- Wei WI, Sham JS. Nasopharyngeal Carcinoma. Lancet. 2005.
- Ayan I, Kaytan E, Ayan N.
hybridization showing strong nuclear labeling of tumor for Epstein-Barr
virus in nasopharyngeal carcinoma.
chromatin, and prominent nucleoli. (Hematoxylin-eosin stain; ×400.) B, Abundant lymphoid infiltrate that obscures nests of tumor cells (arrow).
(Hematoxylin-eosin stain; ×100.)
HPV Positive Oropharyngeal Squamous Cell Carcinoma (OPSCC) – Radiation Therapy (RT) + Cetuximab vs RT + Cisplatin (Why Substitution Fails)
- HPV Positive Oropharyngeal Squamous Cell Carcinoma (HPV⁺ OPSCC):
- Radiation therapy (RT) + cetuximab vs RT + cisplatin (why substitution fails)
- Clinical rule:
- In cisplatin-eligible HPV⁺ oropharynx cancer:
- Do not replace cisplatin with cetuximab:
- To “de-intensify”
- Do not replace cisplatin with cetuximab:
- Two large phase III trials showed:
- Worse survival and control with cetuximab
- RTOG-1016 (Lancet 2019; non-inferiority trial):
- Design:
- RT + cetuximab vs RT + cisplatin 100 mg / m² × 2 in HPV⁺ OPSCC
- Primary endpoint OS:
- Non-Inferiority (NI) margin HR 1.45
- Results (median f/u ~ 4.5 y):
- 5-yr OS:
- 77.9% cetuximab vs 84.6% cisplatin:
- HR 1.45 → non-inferior criterion failed:
- Inferior with cetuximab
- HR 1.45 → non-inferior criterion failed:
- 77.9% cetuximab vs 84.6% cisplatin:
- PFS:
- HR 1.72:
- Worse with cetuximab
- HR 1.72:
- Locoregional failure:
- HR 2.05:
- Higher with cetuximab
- HR 2.05:
- Acute / late grade ≥ 3 toxicity:
- Overall similar rates (different profiles):
- So efficacy — not toxicity — drives the choice PubMed+1
- Overall similar rates (different profiles):
- 5-yr OS:
- Design:
- De-ESCALaTE HPV (Lancet 2019; “low-risk” HPV⁺):
- Design:
- RT + cetuximab vs RT + cisplatin
- Primary end point:
- Severe toxicity
- Efficacy (≈ 2 y):
- OS:
- 97.5% cisplatin vs 89.4% cetuximab:
- HR ~ 5.0:
- Significantly worse with cetuximab
- HR ~ 5.0:
- 97.5% cisplatin vs 89.4% cetuximab:
- Recurrence:
- 6.0% cisplatin vs 16.1% cetuximab:
- HR ~ 3.4
- 6.0% cisplatin vs 16.1% cetuximab:
- Severe toxicity:
- Similar overall rates
- More sever adverse effects (SAEs) with cisplatin:
- But not enough to offset the clear efficacy loss with cetuximab The Lancet+2Taylor & Francis Online+2
- OS:
- Design:
- Reinforcing data:
- ARTSCAN III (mixed HNSCC, HPV- subset reported):
- Concurrent cisplatin outperformed cetuximab with RT:
- Mature results reiterate inferior outcomes with cetuximabPMC+1
- Concurrent cisplatin outperformed cetuximab with RT:
- Guidelines:
- NCCN and contemporary reviews state that RT + cisplatin remains standard for eligible HPV⁺ OPSCC:
- Cetuximab – RT is reserved for:
- True cisplatin ineligibility:
- CrCl < 50 mL / min, grade ≥ 2 SNHL / neuropathy) JNCCN
- True cisplatin ineligibility:
- Cetuximab – RT is reserved for:
- NCCN and contemporary reviews state that RT + cisplatin remains standard for eligible HPV⁺ OPSCC:
- ARTSCAN III (mixed HNSCC, HPV- subset reported):
- In cisplatin-eligible HPV⁺ oropharynx cancer:
- How to use this at tumor board:
- Eligible for cisplatin?
- RT + cisplatin:
- q3-weekly 100 mg / m² × 2 to 3, or weekly in appropriate settings:
- To achieve ≥ 200 mg/m² cumulative if feasible (De-escalation ≠ drug substitution) PubMed
- q3-weekly 100 mg / m² × 2 to 3, or weekly in appropriate settings:
- Cisplatin-ineligible?
- RT + cetuximab (or institutionally accepted alternatives) with explicit counseling that efficacy:
- Is inferior to cisplatin in HPV⁺ disease:
- Use only because platinum cannot be given JNCCN
- Is inferior to cisplatin in HPV⁺ disease:
- RT + cetuximab (or institutionally accepted alternatives) with explicit counseling that efficacy:
- RT + cisplatin:
- Eligible for cisplatin?
Squamous Cell Carcinoma of the Parotid Gland
- Primary squamous cell carcinoma of the parotid gland (pSCCP):
- Is a rare, aggressive salivary gland malignancy diagnosed only by exclusion:
- After metastatic / secondary spread from a cutaneous or mucosal head and neck SCC, high-grade mucoepidermoid carcinoma, salivary duct carcinoma with squamous differentiation, and direct extension have all been ruled out
- It is a contested entity:
- Contemporary genomic data show that nearly all “parotid SCCs” carry a UV-induced mutational signature indicating cutaneous origin:
- So the great majority of cases coded as primary are in fact metastatic (mSCCP)
- Contemporary genomic data show that nearly all “parotid SCCs” carry a UV-induced mutational signature indicating cutaneous origin:
- Is a rare, aggressive salivary gland malignancy diagnosed only by exclusion:
- Definition and the diagnosis-of-exclusion problem
- True pSCCP is thought to arise from squamous metaplasia of excretory duct epithelium:
- By convention requires no evidence of any other primary squamous source
- True pSCCP is thought to arise from squamous metaplasia of excretory duct epithelium:
- pSCCP and mSCCP are histologically nearly identical:
- Every criterion proposed to favor a primary (e.g., ductal dysplasia) can also occur when metastatic tumor grows along preexisting ducts
- SCC differentiation can also be seen in genetically defined salivary carcinomas :
- NUT carcinoma, high-grade mucoepidermoid carcinoma, basal-type salivary duct carcinoma:
- Further narrowing the space for a “true” primary
- NUT carcinoma, high-grade mucoepidermoid carcinoma, basal-type salivary duct carcinoma:
- Epidemiology
- SCC accounts for roughly 0.3% to 1.5% of salivary gland tumors in classic series:
- Though registry data (which cannot distinguish primary from metastatic) label a much higher share:
- Up to ~ 23% of parotid cancers in one German national study, and ~ 2% of parotid neoplasms at a single institution after strict histologic review
- Registry-based incidence has risen (~ 0.87 to 2.0 per million in SEER over 42 years):
- Paralleling rising cutaneous SCC incidence and an aging population:
- Most likely reflecting misclassified metastatic disease
- Paralleling rising cutaneous SCC incidence and an aging population:
- The German registry found:
- SCC-type parotid cancer was strongly associated with a prior head and neck SCC (adjusted OR 5.48), median interval 365 days:
- Supporting frequent secondary origin
- SCC-type parotid cancer was strongly associated with a prior head and neck SCC (adjusted OR 5.48), median interval 365 days:
- Though registry data (which cannot distinguish primary from metastatic) label a much higher share:
- Typical patient:
- Elderly (7th decade)
- Male predominance:
- Roughly 2:1
- Presentation is often advanced, with a parotid mass, facial nerve dysfunction, and / or cervical nodes:
- The majority present at stage IV
- SCC accounts for roughly 0.3% to 1.5% of salivary gland tumors in classic series:
- Pathohistology and immunohistochemistry:
- Keratinizing to nonkeratinizing infiltrative squamous nests with intercellular bridges / keratinization:
- Keratinization is seen in ~1 in 6 metastatic SCC cases and is rare in the main mimics
- Squamous markers p40, p63, CK5/6 are positive:
- Mucicarmine should be negative:
- Positive mucin points to mucoepidermoid carcinoma
- Mucicarmine should be negative:
- Androgen receptor (AR) and / or HER2 positivity:
- Should raise salivary duct carcinoma with squamous differentiation rather than pSCCP:
- AR / CK7 expression does not exclude SDC
- Should raise salivary duct carcinoma with squamous differentiation rather than pSCCP:
- FNA differential includes:
- Warthin tumor (well-differentiated cases)
- High-grade mucoepidermoid carcinoma
- Salivary duct carcinoma
- UV-signature mutational analysis:
- Is now the most useful ancillary tool to establish cutaneous (metastatic) origin
- Keratinizing to nonkeratinizing infiltrative squamous nests with intercellular bridges / keratinization:
- Work-up:
- The NCCN Head and Neck Cancers guidelines outline evaluation of any parotid mass:
- Complete H&P with full head and neck exam (including mirror / fiberoptic exam), FNA biopsy, and, as clinically indicated, contrast CT / MRI from skull base to clavicle, chest CT, dental / nutrition / speech evaluation, and multidisciplinary consultation
- Because SCC histology mandates excluding a metastatic source:
- Workup should additionally include a thorough cutaneous exam of the face / scalp / ear (cutaneous SCC is the most common tumor to metastasize to the parotid), and an occult-primary / mucosal SCC evaluation when no skin primary is found:
- EUA, direct laryngoscopy, tonsillectomy, chest / abdomen / pelvis CT or FDG-PET/CT, with p16 / HPV and EBV testing
- Workup should additionally include a thorough cutaneous exam of the face / scalp / ear (cutaneous SCC is the most common tumor to metastasize to the parotid), and an occult-primary / mucosal SCC evaluation when no skin primary is found:
- FNA:
- Reliably distinguishes benign from malignant (sensitivity ~ 80%, specificity ~ 97%) and is highly accurate for high-grade cancers
- The NCCN Head and Neck Cancers guidelines outline evaluation of any parotid mass:
- Staging:
- Historically staged with the AJCC 8th edition (2017) TNM for major salivary glands
- T category is size / extraparenchymal-extension based:
- T1 ≤ 2 cm
- T2 > 2 to 4 cm
- T3 > 4 cm and / or extraparenchymal extension
- T4a skin / mandible / ear canal / facial nerve
- T4b skull base / pterygoid plates / carotid encasement)
- An important caveat:
- The newly published AJCC / UICC 9th edition (TNM9) creates a unified salivary-gland-specific system but explicitly excludes squamous cell carcinoma (along with neuroendocrine and basosquamous carcinoma) from salivary gland staging:
- Practically, parotid SCC is therefore staged using the head and neck cutaneous / mucosal SCC or cervical-node / unknown-primary frameworks rather than the salivary-gland schema
- The newly published AJCC / UICC 9th edition (TNM9) creates a unified salivary-gland-specific system but explicitly excludes squamous cell carcinoma (along with neuroendocrine and basosquamous carcinoma) from salivary gland staging:
- Management:
- No prospective trials exist; management is extrapolated from salivary gland and cutaneous / metastatic SCC guidelines and retrospective series
- The consistent message across data sets is that surgery is essential:
- Outcomes without resection are poor
- The core approach for resectable disease is:
- Total (at least superficial) parotidectomy + neck dissection + adjuvant radiotherapy
- Per NCCN for major salivary gland cancers:
- Primary treatment:
- Complete surgical resection, with neck dissection for high-grade and / or T3 to 4 tumors (or clinically N+ disease):
- The facial nerve is preserved when feasible
- Complete surgical resection, with neck dissection for high-grade and / or T3 to 4 tumors (or clinically N+ disease):
- Adjuvant therapy:
- Adjuvant RT is preferred for adverse features:
- High grade, close / positive margins, perineural / neural invasion, nodal metastases, lymphovascular invasion, or high-grade T3 to T4a tumors (SCC qualifies as high grade)
- Adjuvant RT is preferred for adverse features:
- –Unresectable / gross residual disease:
- Definitive RT, or concurrent systemic therapy / RT (category 2B)
- Primary treatment:
- ASCO guidelines:
- Recommend that for advanced (T3 to T4) or high-grade parotid cancers, at least a superficial parotidectomy with removal of additional at-risk parotid tissue be performed (given planned adjuvant RT):
- Balancing oncologic clearance against facial nerve risk:
- There are no data that more aggressive parotidectomy improves survival or locoregional control when adjuvant RT is used
- Balancing oncologic clearance against facial nerve risk:
- Recommend that for advanced (T3 to T4) or high-grade parotid cancers, at least a superficial parotidectomy with removal of additional at-risk parotid tissue be performed (given planned adjuvant RT):
- Prognosis:
- Uniformly aggressive regardless of primary-vs-metastatic classification
- Reported median survival is roughly 13 to 24 months, and 5-year overall survival does not exceed ~ 50%
- Larger tumor size, extraparenchymal extension, nodal metastases, distant metastases, and advanced age independently predict worse survival
- Recurrent disease carries a particularly poor prognosis (median ~14.5 months)
- Secondary (metastatic) parotid SCC has worse survival than true primary salivary cancers and higher rates of facial nerve sacrifice
- References:
- Primary Squamous Cell Carcinoma of the Parotid Gland: Study and Review of the Literature. Horáková Z, Stárek I, Kalfert D, et al. In Vivo (Athens, Greece). 2024 Jan-Feb;38(1):358-364. doi:10.21873/invivo.13446.
- Metastatic Cutaneous Squamous Cell Carcinoma Accounts for Nearly All Squamous Cell Carcinomas of the Parotid Gland. Bradley PJ, Stenman G, Thompson LDR, et al. Virchows Archiv : An International Journal of Pathology. 2024;485(1):3-11. doi:10.1007/s00428-024-03798-5.
- Squamous Carcinoma in a Major Salivary Gland: A Review of the Diagnostic Considerations. Taxy JB. Archives of Pathology & Laboratory Medicine. 2001;125(6):740-5. doi:10.5858/2001-125-0740-SCIAMS.
- Histogenesis of Salivary Gland Neoplasms. Regezi JA, Batsakis JG. Otolaryngologic Clinics of North America. 1977;10(2):297-307.
- Salivary duct carcinoma with squamous differentiation: histomorphological and immunophenotypical analysis of six cases. Dababneh MN, Griffith CC, Magliocca KR, Stojanov IJ. Histopathology. 2024;85(4):590-597. doi:10.1111/his.15217.
- Squamous cell carcinoma of the parotid gland. Ying YL, Johnson JT, Myers EN. Head & Neck. 2006;28(7):626-32. doi:10.1002/hed.20360.
- Squamous Cell Carcinoma of the Parotid Gland: A Population-Based Registry Study of Primary Versus Metastatic Disease. Oesterling F, Möller L, Kajüter H, et al. Cancer Epidemiology. 2026;102:103085. doi:10.1016/j.canep.2026.103085.
- Primary Squamous Cell Carcinoma of the Parotid Gland: The Importance of Correct Histological Diagnosis. Flynn MB, Maguire S, Martinez S, Tesmer T. Annals of Surgical Oncology. 1999;6(8):768-70. doi:10.1007/s10434-999-0768-y.
- Incidence and survival trends of parotid malignancies over 42 years. Gupta A, Koochakzadeh S, Neskey DM, Nguyen SA, Lentsch EJ. Head & Neck. 2020;42(9):2308-2315. doi:10.1002/hed.26172.
- Prognostic factors for squamous cell cancer of the parotid gland: An analysis of 2104 patients. Chen MM, Roman SA, Sosa JA, Judson BL. Head & Neck. 2015;37(1):1-7. doi:10.1002/hed.23566.
- The key radiologic and cytomorphologic features of oncocytic and oncocytoid lesions of the salivary gland. Lubin D, Song S, Zafar HM, Baloch Z. Diagnostic Cytopathology. 2019;47(6):617-636. doi:10.1002/dc.24175.
- Head and Neck Cancers. National Comprehensive Cancer Network. Updated 2026-05-12.
- Cutaneous squamous cell carcinoma of the head and neck metastasizing to the parotid gland—A review of current recommendations. O’Hara J, Ferlito A, Takes RP, et al. Head & Neck. 2011;33(12):1789-95. doi:10.1002/hed.21583.
- Occult Primary (Cancer of Unknown Primary [CUP]). National Comprehensive Cancer Network. Updated 2026-05-04.
- Management of Salivary Gland Malignancy: ASCO Guideline. Geiger JL, Ismaila N, Beadle B, et al. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2021;39(17):1909-1941. doi:10.1200/JCO.21.00449.
- Key Updates on the Version 9 AJCC/UICC Staging System for Salivary Gland Carcinoma. Huang SH, Seethala RR, Patel SG, et al. Annals of Surgical Oncology. 2026;33(6):4958-4963. doi:10.1245/s10434-026-19350-5.
- Proposed Version Nine of the AJCC and UICC TNM Classification for Salivary Gland Carcinoma. Huang SH, Cotler J, Palis B, et al. JAMA Otolaryngology– Head & Neck Surgery. 2026;152(4):366-375. doi:10.1001/jamaoto.2025.5396.
- Primary Squamous Cell Carcinoma of the Parotid Gland: Clinicopathological Characteristics, Treatment, and Prognosis. Xiao M, Liu J, You Y, Yang X, Wang Y. International Journal of Oral and Maxillofacial Surgery. 2021;50(2):151-157. doi:10.1016/j.ijom.2020.06.010.
- Primary and Secondary Tumors of the Parotid Gland: Clinical Features and Prognosis. Pecorari G, Pizzo C, Briguglio M, Cravero E, Riva G. Cancers. 2023;15(4):1293. doi:10.3390/cancers15041293.
T Staging of Oral Pharyngeal Squamous Cell Carcinoma (OPSCC) Human Papilloma Virus (HPV) Negative
- NCCN Guidelines, Head and Neck Cancers (v2.2026) still base clinical staging definitions on AJCC 8th edition (ST-4 for p16-negative, ST-7 for p16-positive):
- Version 9 is not yet incorporated
- Version 9 changes apply only to:
- HPV-positive (p16+) oropharyngeal carcinoma
- The p16-negative oropharynx / hypopharynx system:
- Is unchanged in the current NCCN tables
- T – Tumor:
- TX – Primary tumor cannot be assessed
- Tis – Carcinoma in situ
- T1 – Tumor 2 cm or smaller in greatest dimension
- T2 – Tumor larger than 2 cm but not larger than 4 cm in greatest dimension
- T3 – Tumor larger than 4 cm in greatest dimensión or extensión to lingual surface of epiglottis
- T4 – Moderately advanced or very advanced local disease
- T4a – Moderately advanced local disease
- Tumor invades the larynx, extrinsic muscle of tongue, medial pterygoid, hard palate, or mandible
- T4b – Very advanced local disease
- Tumor invades lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, or skull base or encases carotid artery
- T4a – Moderately advanced local disease
Rodrigo Arrangoiz MS, MD, FACS, FSSO 