• Structural incomplete response (SIR) in differentiated thyroid cancer (DTC):
  • Is defined as persistent or newly identified locoregional or distant metastases on imaging:
    • Usually in conjunction with elevated thyroglobulin (Tg) and / or anti-thyroglobulin antibody (TgAb) levels
  • It is one of four response-to-therapy categories in the ATA dynamic risk stratification system:
    • Alongside excellent, indeterminate, and biochemical incomplete responses
• Criteria by Treatment Context:
  • The definition of SIR is consistent regardless of surgical extent:
    • Structural evidence of disease confirmed by suspicious imaging or biopsy-proven local or distant metastatic disease
  • The TSH goal for patients with SIR:
    • Is maintained below the normal reference range
• Prevalence and Outcomes:
  • SIR occurs in approximately 2.8% to 10% of DTC patients after initial therapy
  • In a cohort of 501 patients treated with total thyroidectomy and RAI:
    • 2.8% had SIR at initial assessment:
      • By last follow-up, 10.2% had structurally incomplete responses
    • Key outcome data include:
      • Patients with an initial SIR:
        • Had an 83.9% rate of continued structural disease over long-term follow-up (mean 10.3 years)
      • All patients categorized as SIR after total thyroidectomy without RAI:
        • Experienced continued presence of disease
      • SIR requires multidisciplinary management tailored to disease status (regional vs. distant metastases, iodine-avid vs. non-iodine-avid disease)
• Management:
  • Management of SIR depends on:
    • Disease location, RAI avidity, resectability, and rate of progression
  • Locoregional disease:
    • Surgery is preferred for resectable locoregional recurrence:
      • With formal compartmental dissection for previously undissected basins
    • RAI therapy:
      • If radioiodine imaging is positive
    • Active surveillance:
      • Is appropriate for non-progressive disease that is stable and distant from critical structures:
        • Small-volume lymph node recurrences often show little progression over years
    • Local therapies (ethanol ablation, RFA, cryoablation):
      • May be considered for limited-burden nodal disease
    • RAI-refractory or progressive disease:
      • Somatic molecular testing for actionable mutations (BRAF, RET, NTRK, ALK fusions; dMMR/MSI/TMB) is recommended for advanced, progressive, or threatening disease
    • Systemic therapy for progressive and/or symptomatic disease:
      • Lenvatinib (preferred; PFS 18.3 vs. 3.6 months, ORR 65%)
      • Sorafenib (PFS 10.8 vs. 5.8 months)
      • Cabozantinib after prior VEGFR TKI (PFS 11.0 vs. 1.9 months)
      • Targeted therapies:
        • Dabrafenib / trametinib (BRAF V600E)
        • Selpercatinib / pralsetinib (RET fusion)
        • Larotrectinib / entrectinib (NTRK fusion)
        • Pembrolizumab (MSI-H/dMMR or TMB-H)
  • Disease monitoring is often appropriate for asymptomatic patients with indolent, non-progressive disease and no brain metastases:
    • TKI therapy may not be appropriate for stable or slowly progressive disease
  • TSH suppression should be maintained with TSH
• References:
  • 2025 American Thyroid Association Management Guidelines for Adult Patients With Differentiated Thyroid Cancer. Ringel MD, Sosa JA, Baloch Z, et al. Thyroid : Official Journal of the American Thyroid Association. 2025;35(8):841-985. doi:10.1177/10507256251363120.
  • SNMMI Procedure Standard/Eanm Practice Guideline for Nuclear Medicine Evaluation and Therapy of Differentiated Thyroid Cancer: Abbreviated Version. Avram AM, Giovanella L, Greenspan B, et al. Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2022;63(6):15N-35N.
  • Thyroid Carcinoma. National Comprehensive Cancer Network. Updated 2025-03-27.
    Thyroid Cancer. Chen DW, Lang BHH, McLeod DSA, Newbold K, Haymart MR. Lancet (London, England). 2023;401(10387):1531-1544. doi:10.1016/S0140-6736(23)00020-X.

• Type A:
  • Adherent to the posterior thyroid parenchyma:
    • Posterior to the upper pole of the thyroid:
      • But not intrathyroidal
  • Type A glands are in the accepted, expected location of a normal parathyroid gland
• Type B:
  • Behind the thyroid parenchyma
  • Type B glands are exophytic to the thyroid parenchyma and lie in the tracheoesophageal groove:
    • This category includes adenomas in:
      • Retroesophageal, retropharyngeal, high lateral pharyngeal, and carotid sheath locations
  • A ‘‘B+’’ subcategory can be used to document the location of adenomas above the level of the hyoid bone:
    • The ‘‘+’’ is meant to reflect cranial elevation
• Type C:
  • Caudal to the thyroid parenchyma:
    • In the tracheoesophageal groove
  • A type C gland is more inferior than a type B gland on lateral images:
    • Located inferior to the inferior pole of the thyroid:
      • Closer to the clavicle
• Type D:
  • Directly over the recurrent laryngeal nerve:
    • At the level of the inferior thyroid vessels
  • The dissection may be difficult:
    • Because a type D gland is dangerously close to the recurrent laryngeal nerve
• Type E:
  • Located in the external aspect of the inferior pole of the thyroid
  • A type E gland is in a location that is:
    • More superficial in an anterior–posterior plane than the recurrent laryngeal nerve:
      • It is the easiest to resect
• Type F:
  • ‘‘Fallen’’ into the thyrothymic ligament:
    • Below the inferior pole of the thyroid in a pretracheal plane
  • A type F gland is frequently referred to as an ectopic gland:
    • Its resection usually involves:
      • Transcervical delivery of the thyrothymic ligament or superior portion of the thymus
• Type G:
  • A gauge, true intrathyroidal gland location

• This nomenclature system has been designed that takes into account the pathologic position of the parathyroid glands (Figure):
  • Superior and inferior glands:
    • Are defined by the location of the gland’s pedicle and its relationship to the RLN:
      • Superior parathyroid glands:
        • Anatomically have a vascular pedicle superior and lateral to the RLN (type A through D glands)
      • Inferior parathyroid glands:
        • Anatomically have a vascular pedicle inferior and medial to the RLN (type D through F glands)
    • Type G glands:
      • Represent intrathyroidal parathyroid lesions
  • This information not only helps radiologists communicate potential parathyroid lesions of interest to surgeons:
    • But also helps surgeons direct their dissection in relation to the RLN

• A novel nomenclature to classify parathyroid adenomas:
  • World Journal of Surgery. 2009;33(3):412–416
• Background and Rationale:
  • Traditional descriptions of parathyroid adenomas (e.g., “left inferior,” “ectopic”):
    • Are inconsistent and often imprecise:
      • Particularly in reoperative surgery or when imaging is discordant
  • Problem:
    • Variable embryologic descent → unpredictable locations
    • Poor communication between surgeons, radiologists, and endocrinologists
    • Difficulty standardizing outcomes and reporting
  • Goal of Perrier et al:
    • Develop a standardized, anatomically reproducible nomenclature based on predictable embryologic migration patterns
• Embryologic Basis (Core Concept)

• During the fifth to sixth week of intrauterine development:
  • The embryonic pharynx is marked:
    • Externally by:
      • Four branchial clefts of ectoderm origin
    • Internally by:
      • Five branchial pouches of endoderm origin
  • The branchial apparatus is made up by:
    • The branchial clefts and branchial pouches:
      • Together with the branchial arches of mesoderm origin:
        • Found in between them
  • This apparatus undergoes normal involution:
    • Leaving behind some derivatives which include the:
      • Thyroid gland, parathyroid glands, thymus, ultimobranchial body, Eustachian tube, middle ear, and external auditory canal
• The parathyroid glands:
  • Develop as epithelial thickenings of the dorsal endoderm of the:
    • Third and fourth branchial pouches
  • The superior parathyroid glands:
    • Are derived from the fourth branchial pouch:
      • Which also gives rise to the ultimobranchial bodies:
        • The ventral aspect of these pouches is believed to fuse with the rudimentary fifth branchial pouches:
          • To from the ultimobranchial bodies
    • The superior parathyroid glands follow the migration of the ultimobranchial bodies:
      • Which descend a relative limited path toward the lateral thyroid region:
        • Ultimately giving rise to the parafollicular cells of the thyroid
      • The superior parathyroid glands separate from the ultimobranchial bodies:
        • As the median and lateral thyroid anlages fuse and incorporate the ultimobranchial bodies:
          • This separation event determines the final anatomic position of the superior parathyroid glands relative to the thyroid (Type A gland)
  • The inferior parathyroid glands:
    • Are derived from the third branchial pouch (dorsal aspect):
      • Along with the thymus (derived from the ventral aspect of the third branchial pouch)
• The parathyroid glands:
  • Remain intimately connected with their respective branchial pouch derivatives
• The normal anatomic location of the superior parathyroid glands:
  • Is more constant than the inferior parathyroid glands:
    • With 80% of the superior glands being found near the posterior aspect of the thyroid gland:
      • At the junction of the upper and middle portion of the thyroid lobes:
        • At the level of the cricoid cartilage:
          • Each gland with its own capsule of connective tissue:
            • Type A gland
  • Roughly one percent  (1%) of the superior parathyroid glands:
    • May be found in the paraesophageal or retroesophageal space, retrolaryngeal space, high lateral pharyngeal, and carotid shealth locations:
      • Type B glands:
        • Behind the thyroid parenchyma:
          • Type B glands are exophytic to the thyroid parenchyma:
            • Lie in the tracheoesophageal groove
      • Type C glands:
        • Caudal to the thyroid parenchyma:
          • In the tracheoesophageal groove
        • A type C gland is more inferior than a type B gland on lateral images and located inferior to the inferior pole of the thyroid (closer to the clavicle)
  • Enlarged superior parathyroid glands:
    • May descend in the tracheoesophageal groove and come to lie below the inferior parathyroid glands (Type C gland)
  • Truly ectopic superior parathyroid glands:
    • Are extremely rare:
      • But may be localized to the middle or posterior mediastinum or in the aortopulmonary window 
• During intrauterine development:
  • The thymus and the inferior parathyroid glands:
    • Migrate caudally in the neck
  • The most common location for the inferior parathyroid glands:
    • Is within 1 cm from a point centered where the inferior thyroid artery and the recurrent laryngeal nerve (RLN) cross
  • In roughly 50% of the cases:
    • The inferior parathyroid gland is located at the level of the inferior thyroid lobe:
      • Anterior of the posterolateral surface:
        • Type E:
          • Located in the external aspect of the inferior pole of the thyroid
          • A type E gland is in a location that is more superficial in an anterior-posterior plane than the recurrent laryngeal nerve
          • It is the easiest to resect
            
  • Approximately 15% to 50% of the inferior glands:
    • Are found in the thyrothymic ligament or the thymus
  • The inferior parathyroid gland is typically situated within a pocket of thymic derived fatty tissue:
    • But may be closely adherent to the thyroid capsule
  • The position of the inferior parathyroid glands:
    • However, tends to be more variable due to their longer migratory route:
      • Undescended inferior glands may be found near the:
        • Skull base, angle of the mandible, or above the superior parathyroid glands:
          • Along with an undescended thymus
  • The frequency of intrathyroidal glands:
    • Is approximately 2% 
• Superior parathyroid glands (4th branchial pouch):
  • Short migration
  • More constant location
  • Posterior to RLN, near cricothyroid joint
• Inferior glands (3rd branchial pouch):
  • Long migration with thymus
  • Highly variable
  • Can be anywhere from angle of mandible → mediastinum
• The classification is built on this predictable vs variable descent pattern

The Perrier Classification System

The authors propose categorizing adenomas based on their relationship to key anatomic landmarks, especially:

• Thyroid gland
• Recurrent laryngeal nerve (RLN)
• Thymus
• Carotid sheath

📍 Four Main Categories

Type A — Orthotopic (Normal Position)

• Located in expected anatomical position
• Adjacent to thyroid gland
• Most common

👉 Clinical relevance:

• Ideal for minimally invasive parathyroidectomy (MIP)
• High concordance with sestamibi + ultrasound

Type B — Ectopic but Cervical

Includes:

• Retroesophageal
• Carotid sheath
• Intrathyroidal
• High cervical (undescended)

👉 Key point: Still in the neck but outside usual location

👉 Surgical implication:

• May require focused but modified approach
• Intrathyroidal → partial thyroid resection

Type C — Thymic / Thyrothymic

• Along thymic descent pathway
• Thyrothymic ligament
• Within cervical thymus or upper mediastinum

👉 Most common ectopic site for inferior glands

👉 Surgical implication:

• Cervical thymectomy often required
• Important in failed initial exploration

Type D — Mediastinal

• Below thoracic inlet
• Aortopulmonary window, pericardium, deep thymus

👉 Rare but critical

👉 Surgical implication:

• May require:
  • VATS
  • Sternotomy
  • Interventional radiology localization

📊 Key Findings from Perrier et al.

• Majority of adenomas are Type A (orthotopic)
• Ectopic locations (Types B to D) account for:
  • ~15% to 20% of cases
• Inferior glands → disproportionately represented in ectopic group

👉 The classification correlates strongly with:

• Embryology
• Preoperative imaging success
• Surgical difficulty

🎯 Clinical Impact

1. Improves Communication

• Standard language across:
  • Surgeons
  • Radiologists
  • Endocrinologists

2. Enhances Preoperative Planning

• Predicts:
  • Likelihood of MIP vs BNE
  • Need for extended exploration

3. Reduces Failed Explorations

• Particularly valuable in:
  • Reoperative cases
  • Discordant imaging

4. Facilitates Research Standardization

• Enables:
  • Comparable outcome reporting
  • Better stratification in studies

🧠 Surgical Algorithm Integration

⚠️ Limitations of the Study

• Retrospective classification
• Single-institution experience (MD Anderson)
• No direct comparison with alternative systems
• Does not incorporate modern imaging (e.g., 4D-CT, PET)

📚 Key References

1. Perrier ND et al. World J Surg. 2009;33:412–416
2. Akerström G et al. Anatomy and embryology of parathyroid glands. World J Surg. 1984
3. Wang C. Parathyroid gland location study (645 cases). Ann Surg. 1976
4. Kunstman JW et al. Parathyroid localization techniques. J Surg Oncol. 2013
5. Cheung K et al. 4D-CT in parathyroid localization. Radiology. 2012

💡 Take-Home Messages (Chairman-Level)

• This classification is simple, reproducible, and embryology-driven
• Helps predict surgical complexity before incision
• Particularly powerful in:
  • Reoperative parathyroid surgery
  • Ectopic gland localization
• Should be integrated into:
  • Operative reports
  • Radiology reporting
  • Multidisciplinary discussions

• Mechanism of Action (CDK4/6 inhibition in HR+ disease):
  • Core biology (why surgeons should care):
    • Ribociclib is a selective CDK4/6 inhibitor:
      • Blocks Cyclin D + CDK4/6 → RB phosphorylation → G1→S transition
      • At baseline, a breast cancer cell moves from G1 → S phase (DNA replication) only if a key checkpoint is passed
      • The core engine – Cyclin D + CDK4/6 = active complex:
        • This complex’s job is to turn OFF the brake (RB protein)
      • The critical step:
        • RB (retinoblastoma protein) normally acts as a brake
        • When phosphorylated → RB becomes inactive
        • This releases E2F transcription factors
        • E2F turns on genes needed for DNA synthesis (S phase)
      • 👉 So – Active CDK4/6 = cell allowed to divide
      • CDK4/6 Inhibitors:
        • Results in cell-cycle arrest in luminal (ER+) tumor cells
    • Key downstream effects:
      • Prevents proliferation of ER-driven clones
      • Enhances endocrine therapy sensitivity (synergistic with AI)
      • May reduce micrometastatic outgrowth → recurrence prevention
  • Clinical interpretation:
    • Not cytotoxic → cytostatic disease control
    • Most impactful in:
      • Luminal A/B biology
      • Late recurrence–prone disease:
        • Rationale for long-duration adjuvant use (3 years)
• NATALEE Trial Design (context for surgeons):
  • Phase III randomized control trial:
    • ~ 5100 patients 
    • Population:
      • HR+ / HER2− early breast cancer
      • Stage II to III:
        • Including selected N0 high-risk
    • Treatment:
      • Ribociclib (400 mg, 3 yrs) + AI ≥ 5 yrs
        vs AI alone
    • Broad inclusion → more “real-world” than monarchE
• 5-Year Update (ESMO 2025 / latest analyses):
  • Efficacy (key numbers):
  • iDFS HR ~0.72 → ~ 28% relative risk reduction 
  • 5-year iDFS:
    • 85.5% (ribociclib) vs 81.0% (ET alone):
      • Absolute benefit ~ 4.5% 
    • Benefit persists after stopping drug (3-year exposure):
      • Indicates true disease-modifying effect 
  • Other endpoints:
    • ↓ Distant recurrence (DDFS HR ~0.71) 
    • ↓ DRFS / RFS consistently improved 
    • OS trend positive but immature 
  • Important nuance:
    • Absolute benefit increases over time (3 → 5 yrs):
      • Supports late recurrence suppression
• Indications (current clinical positioning):
  • Regulatory / guideline-aligned use:
  • Adjuvant therapy with AI for:
    • HR+ / HER2− early breast cancer
    • Stage II to III at high risk of recurrence 
    • “High-risk” (NATALEE definition):
      • Includes:
        • Stage IIB to III or
        • Stage IIA with N+ or
        • N0 + high-risk biology (e.g., Ki-67 ≥ 20%, grade 3, genomic risk) 
• Unique positioning vs abemaciclib:
  • Broader population:
    • Includes:
      • Node-negative high-risk
      • Lower tumor burden
      • Lower starting dose → better tolerability strategy
• Practical Implications for Breast Surgeons:
  • Expands “systemic adjuvant” discussion at MDT
  • You now need to identify patients who may benefit before finalizing adjuvant plan:
    • Candidates to flag early:
    • Stage II (even N0) with:
      • High grade
      • High Ki-67
      • Genomic high risk
    • Any Stage III HR+ disease
• Impacts surgical-pathologic reporting priorities:
  • Surgeons should ensure:
    • Accurate nodal staging
    • Grade
    • Ki-67
    • Genomic assay (if used) integrated early
      • These directly influence eligibility for CDK4/6 therapy
• Reinforces importance of recurrence biology:
  • Luminal cancers:
    • Long natural history
    • Late relapse risk
    • Ribociclib addresses micrometastatic dormancy
      → shifts mindset from:
      “Local control + endocrine therapy”
      → to
      “Extended systemic control strategy”
• Treatment duration considerations:
  • Ribociclib:
    • 3 years
  • Endocrine therapy:
    • ≥ 5 years
• Implication:
  • Long-term adherence planning begins at surgical consultation
• Safety Profile (surgeon-relevant highlights):
  • Common:
    • Neutropenia (non-febrile)
    • LFT elevation
    • QT prolongation
  • No new long-term safety signals at 5 years 
  • Clinical takeaway:
    • Manageable → supports use in early-stage curative setting
• Key Takeaways for Surgical Practice:
  • Ribociclib is now a standard adjuvant option in HR+/HER2− EBC:
    • Especially stage II to III and biologically high-risk disease
  • 5-year data confirms durability:
    • Benefit persists beyond treatment window:
      • Increasing absolute benefit over time
  • Expands eligible population:
    • Includes node-negative high-risk patients
  • Multidisciplinary coordination is critical:
    • Surgeons play a role in:
      • Early identification
      • Pathologic risk stratification
      • Timely referral to medical oncology
• Bottom line (surgeon-focused):
  • Ribociclib from NATALEE represents a shift toward proactive systemic prevention of recurrence in luminal breast cancer, with durable 5-year benefit and broader eligibility than prior CDK4/6 strategies—making early risk identification at the surgical stage increasingly important

The Phase III LEAP-10 trial represents a major collaborative effort between Merck & Co. and Eisai, addressing a persistent unmet need in recurrent /metastatic head and neck squamous cell carcinoma (R/M HNSCC).

In patients with PD-L1 CPS ≥1 disease, the combination of lenvatinib + pembrolizumab demonstrated:

• Improved objective response rate (ORR)
• Prolonged progression-free survival (PFS)

However, these gains did not translate into an overall survival (OS) benefit compared with pembrolizumab monotherapy, which remains the backbone of first-line treatment.

Clinical Context: Why OS Remains Elusive

Despite encouraging activity, the absence of OS improvement reinforces the durability of the current standard established by KEYNOTE-048 trial, where:

• Pembrolizumab ± chemotherapy continues as standard of care
• Survival benefit is tightly linked to PD-L1 expression and patient selection

The LEAP-10 findings highlight a recurring challenge in HNSCC:

Early efficacy signals (ORR, PFS) do not reliably predict survival benefit, particularly in an immunotherapy-sensitive disease where post-progression treatments and tumor biology heavily influence OS.

Biologic Interpretation

The addition of lenvatinib, a multi-kinase inhibitor targeting VEGFR, FGFR, and others, likely:

• Enhances tumor microenvironment modulation
• Improves initial tumor shrinkage and disease control

However, potential limitations include:

• Lack of deep, durable immune reprogramming
• Emergence of resistance mechanisms
• Possible toxicity-related treatment discontinuation

These factors may blunt long-term survival impact despite improved early endpoints.

Where the Field Is Heading: EGFR and Beyond

Attention is now shifting toward next-generation EGFR-targeted strategies, with the hypothesis that:

• More precise targeting of EGFR-driven signaling
• Coupled with immune engagement mechanisms

may yield more durable survival benefits.

Key players advancing this space include:

• Dana-Farber Cancer Institute
• Genmab
• Bicara Therapeutics
• Johnson & Johnson
• Merus N.V.
• Harvard Medical School

Emerging modalities include:

• Bispecific antibodies (EGFR × immune targets)
• Antibody-drug conjugates (ADCs)
• Combination immunotherapy strategies

These approaches aim to:

• Overcome primary and acquired resistance
• Deliver more sustained immune activation
• Ultimately shift the OS curve, not just early endpoints

Key Takeaway for Clinical Practice

While lenvatinib + pembrolizumab shows meaningful biologic and clinical activity, it does not currently challenge pembrolizumab-based regimens as standard of care in PD-L1–positive R/M HNSCC.

The central question remains:

What therapeutic strategy will meaningfully and reproducibly improve overall survival in first-line HNSCC?

The next wave of EGFR-targeted and immune-engaging therapies may be the most promising path forward.

Maxillary Artery

• The maxillary artery supplies deep structures of the face.

• It branches from the external carotid artery just deep to the neck of the mandible.

• Structure:

  • The maxillary artery, the larger of the two terminal branches of the external carotid artery:

    • Arises behind the neck of the mandible, and is at first imbedded in the substance of the parotid gland.

  • It passes forward between the ramus of the mandible and the sphenomandibular ligament, and then runs, either superficial or deep to the lateral pterygoid muscle, to the pterygopalatine fossa.

  • It supplies the deep structures of the face.

• May be divided into:

  • Mandibular portion (first part / bony part)

  • Pterygoid portion (second part / muscular part)

  • Pterygopalatine portions (third part).

• Mandibular portion (first part / bony part):

  • The first or mandibular portion (or bony portion) passes horizontally forward, between the neck of the mandible and the sphenomandibular ligament:

    • Where it lies parallel to and a little below the auriculotemporal nerve.

    • It crosses the inferior alveolar nerve, and runs along the lower border of the lateral pterygoid muscle.

    • Branches include:

      • Deep auricular artery

      • Anterior tympanic artery

      • Middle meningeal artery

      • Inferior alveolar artery:

        • Which gives off its mylohyoid branch just prior to entering the mandibular foramen

      • Accessory meningeal artery

• Pterygoid portion (second part / muscular part):

  • The second or pterygoid portion (or muscular portion) runs obliquely forward and upward under cover of the ramus of the mandible and insertion of the temporalis muscle:

    • On the superficial (very infrequently on the deep) surface of the lateral pterygoid muscle.

    • It then passes between the two heads of origin of this muscle and enters the fossa.

  • Branches include:

    • Masseteric artery

    • Pterygoid branches

    • Deep temporal arteries:

      • Anterior and posterior

    • Buccal (buccinator) artery

• Pterygopalatine portions (third part):

  • The third or pterygopalatine portion lies in the pterygopalatine fossa in relation with the pterygopalatine ganglion.

  • This is considered the terminal branch of the maxillary artery.

  • Branches include:

    • Sphenopalatine artery:

      • Nasopalatine artery is the terminal branch of the maxillary artery

    • Descending palatine artery:

      • Greater palatine artery

      • Lesser palatine artery

    • Infraorbital artery

    • Posterior superior alveolar artery

    • Artery of pterygoid canal

    • Pharyngeal artery

    • Middle superior alveolar artery (could be a branch of the infraorbital artery)

    • Anterior superior alveolar arteries (could be a branch of the infraorbital artery)

Rodrigo Arrangoiz MS, MD, FACS a head and neck surgeon at the Braman Comprehensive Cancer Center at Mount Sinai Medical Center in Miami, Florida.

He is first author on some publications on oral cavity cancer:

• Oral Tongue Cancer: Literature Review and Current Management 

  • https://www.oatext.com/pdf/CRR-2-153.pdf

• Understand Cancer: Research and Treatment Oral Cavity Cancer: Literature Review and Current Management. 

  • https://www.researchgate.net/publication/303366031_Understand_Cancer_Research_and_Treatment_Oral_Cavity_Cancer_Literature_Review_and_Current_Management

Training:

• General surgery:

• Michigan State University:

• 2004 al 2010

• Surgical Oncology / Head and Neck Surgery / Endocrine Surgery:

• Fox Chase Cancer Center (Filadelfia):

• 2010 al 2012

• Masters in Science (Clinical research for health professionals):

• Drexel University (Filadelfia):

• 2010 al 2012

• Surgical Oncology / Head and Neck Surgery / Endocrine Surgery:

• IFHNOS / Memorial Sloan Kettering Cancer Center:

• 2014 al 2016

• The main trunk of the maxillary artery:
  • Is divided into three parts:
    • Which are named according to related structures along the artery’s course
  • These three parts are:
    • The mandibular division (1st part / bony part):
      • Named as such because it winds around deep to the neck of the mandible
    • The pterygoid division (2nd part / muscular part):
      • It has this name because it travels between the two heads of the lateral pterygoid muscle
    • The pterygopalatine division (3rd part):
      • This part derived its name from the pterygopalatine fossa, into which it enters
  • Conventionally, these three parts are described as the:
    • Part before-, part on-, and part beyond the lateral pterygoid muscle
    • This is also useful since out of the 15 branches of the maxillary artery:
      • The five branches from the second part (part on the lateral pterygoid muscle):
        • Are regarded as branches to soft tissues:
          • That do not course through foramina in bones
      • However, the remaining 10 branches:
        • From the first and third parts:
          • Go through foramina in bones
• Course:
  • The maxillary artery:
    • Continues as one of the terminal divisions of the external carotid artery:
      • At the level of the neck of the mandible:
        • Passing forward between the neck of the mandible and the sphenomandibular ligament
      • It continues its path by running deeply to the lower head and passes forward between the two heads of the lateral pterygoid muscle:
        • To break into its terminal branches at the pterygopalatine fossa

• Maxillary artery branches:
  • Branches of the first (mandibular) division:
    • The deep auricular artery:
      • Is the first branch of the mandibular part:
        • This branch runs upwards to enter the ear and courses superficially to the tympanic membrane, passing between the cartilage and bone
      • It supplies the external acoustic meatus of the ear and the deep surface of the tympanic membrane
      • The anterior tympanic artery:
        • Is the second branch that courses near the tympanic membrane
        • It passes deep to the membrane:
          • Through the petrotympanic fissure to the middle ear:
            • To join the circular anastomosis around the tympanic membrane
      • The middle meningeal artery:
        • Passes straight upwards through the foramen spinosum:
          • To join the two roots of the auriculotemporal nerve
        • It supplies bones of the skull (calvaria) and the dura mater
      • The inferior alveolar artery:
        • Runs inferiorly and anteriorly towards the inferior alveolar nerve:
          • To meet the nerve at the inferior alveolar (a.k.a. mandibular) foramen
        • The artery runs further anteriorly in the mandible:
          • Supplying the pulps of the mandibular teeth (with its dental branches) and the body of the mandible
        • Its other branch, the mental branch:
          • Emerges from the mental foramen and supplies the lower lip and skin of the chin 
      • The accessory meningeal artery:
        • Is the main source of blood supply to the trigeminal ganglion
        • It passes upwards through the foramen ovale to supply the dura mater of the floor of the middle fossa and of the trigeminal cave (Meckel’s cave)
  • Branches from the 2nd (pterygoid / muscular) segment:
    • All branches from the pterygoid part supply only soft tissues
    • The masseteric artery:
      • Accompanies the lingual nerve
      • It is small, and passes laterally through the mandibular notch to the deep surface of the masseter muscle
    • The pterygoid arteries:
      • Are small branches that vary in number
      • They supply the lateral pterygoid muscle and medial pterygoid muscle
    • The deep temporal arteries:
      • Course between the temporalis muscle and the pericranium
      • The main function of this branch is to:
        • Provide arterial supply to the temporalis muscle
    • The buccal (buccinator) artery:
      • Runs obliquely forward, between the medial pterygoid muscle and the insertion of the temporalis muscle, to the outer surface of the buccinator muscle
      • It mainly supplies the:
        • Buccinator muscle
      • Along its course, it forms anastomoses with branches of the facial and infraorbital arteries
  • Branches from the 3rd (pterygopalatine) segment:
    • The sphenopalatine artery:
      • Mainly supplies the nasal cavity:
        • Which is why it is also referred to as the nasopalatine artery
      • It passes through the sphenopalatine foramen and enters the nasal cavity
      • Here it gives off its posterior lateral nasal branches
      • Crossing the inferior surface of the sphenoid:
        • The sphenopalatine artery ends on the nasal septum giving off the posterior septal branches
    • The descending palatine artery:
      • Descends through the greater palatine canal:
        • With the greater and lesser palatine branches:
          • Of the pterygopalatine ganglion
        • It terminates by dividing into the greater and lesser palatine arteries:
          • That provide blood supply for the hard palate and soft palate, respectively
    • The infraorbital artery:
      • Passes forwards through the inferior orbital fissure:
        • Along the floor of the orbit and infraorbital canal:
          • To emerge with the infraorbital nerve on the face.
    • The posterior superior alveolar artery:
      • Supplies the maxillary teeth
      • It gives branches that accompany the corresponding nerves through foramina in the posterior wall of the maxilla
    • The middle superior alveolar artery:
      • Is most often a branch of the infraorbital artery
      • It arises within the infraorbital canal:
        • Where it descends to supply the maxillary sinus and plexus at the level of the canine tooth
    • The pharyngeal artery:
      • Supplies structures such as the pharynx and roof of the nose
    • The anterior superior alveolar artery:
      • Is branch of the infraorbital artery. 
    • The artery of the pterygoid canal:
      • Runs into the pterygoid canal:
        • It passes backwards along the pterygoid canal with the corresponding nerve
      • It supplies the upper part of the pharynx, and sends a small division into the tympanic cavity to anastomose with the tympanic arteries
        
        
        
        

The proximity or direct extension of a primary tumor of the oral cavity to the mandible requires appropriate radiological studies to establish the presence and extent of bone involvement:

• Although the absence of radiographic findings does not rule out bone invasion:

  • Bone destruction as seen on the radiograph confirms tumor invasion

• Radionuclide bone scans:
  • Often are positive before the radiographic appearance of bone destruction:
    • But they seldom provide accurate information regarding the extent of bone invasion
  • Bone scans also may be positive in non-neoplastic conditions:
    • Such as inflammatory lesions
• Plain radiographs of the mandible in the antero-posterior and oblique views:
  • Are not satisfactory as a routine screening test to establish or rule out bone destruction
• A panoramic view of the mandible (an orthopantomogram):
  • Is helpful to assess the general architecture of the mandible in relation to the dento-alveolar structures and invasion by the tumor (Figure)

• However, for technical reasons:

  • The midline of the mandible near the symphysis is not adequately evaluated by a panoramic view

  • In addition, early invasion of the lingual cortex of the mandible is not seen on a panoramic view

  • Occlusal films of the body of the mandible and intraoral dental films:

    • Often are most accurate in demonstrating early invasion by a tumor

      
      
• CT scans of the mandible:
  • Generally are not optimal for routine screening:
    • But may be considered in certain circumstances:
      • Such as primary tumors of the mandible and lesions where soft tissue extension from tumors involving the ascending ramus of the mandible is suspected (Figure)

Three-dimensional reconstructions of CT images provide an excellent overview of the mandible or maxilla from any desired angle

• A computerized tomogram of the oral cavity and neck:
  • Is the standard initial radiographic study for assessment of locoregional extent of the tumor
  • It allows comprehensive evaluation of neck nodes and also the relationship of the primary tumor to adjoining bone:
    • Especially in situations such as primary tumors of the mandible and lesions where soft-tissue extension from tumors involving the ascending ramus of the mandible is suspected

• Three-dimensional reconstructions of the mandible of a patient with an ossifying fibroma of the body of the mandible on the left-hand side causing expansion and involving the lingual cortex are shown in the Figures

  
  

• A three-dimensional CT scan and a one-to-one reproduction of the CT scan:

  • Are of great value to the surgeon for mandible reconstruction with a microvascular free flap

• The basis and need for elective nodal treatment in head and neck cancer:
  • Have been based largely on surgical series evaluating pathologic nodal involvement found on elective neck dissection in patients with clinically negative necks
• In a consecutive series of 1,081 head and neck cancer patients undergoing radical neck dissection:
  • The incidence of pathologic node involvement:
    • Was 33% among those undergoing elective neck surgery
  • The pathologic findings identified the nodal stations at risk by tumor site:
    • To establish the rationale for selective neck dissection (SND) as the elective surgical procedure
• Several reports have summarized the risk for metastases and nodal stations at risk
• Some general observations from such data can be made:
  • Regarding larynx cancers:
    • Candela reported the Memorial Sloan Kettering Cancer Center (MSKCC) experience in determining the patterns of cervical nodal metastases in 247 larynx cancer patients undergoing radical neck dissections:
      • Seventy-eight underwent elective radical neck dissection whereas 118 underwent immediate radical dissection for clinically node-positive disease
      • The majority of patients (n = 189) were supraglottic larynx and 58 were glottic
      • Pathologic nodal involvement:
        • Was found in 37% undergoing elective neck dissection
      • It is noted that cervical nodes spread in a similar fashion whether the patients are clinically node negative or positive:
        • With predominant involvement of:
          • Level II and III jugular nodes
      • In clinically node-negative patients:
        • The incidence of involvement of level I and V:
          • Is less than 5% with less than 10% involvement of level IV
      • In node-positive patients:
        • The incidence of level IV node increases from 15% to 31% with greater involvement of levels II and III
      • In clinically node-positive patients:
        • Very rarely did patients present with isolated level I nodal metastases without involvement of the jugular nodes
• Shah and Candela reported that among oropharynx or hypopharynx cancers:
  • Treated with elective radical neck dissection:
    • Occult metastases are found in 26%
  • Level I and V were involved in only 1.4%:
    • Always in association with nodal disease at level II to IV
  • No skip metastases were reported
  • Among oropharynx patients:
    • Levels II to IV were predominantly involved
  • Among hypopharynx lesions:
    • The primary levels involved were levels II and III
  • In patients clinically node positive undergoing therapeutic neck dissection:
    • The incidence of level I and V involvement increased to about 10% to 15%:
      • However, levels II to IV were predominantly involved
    • Level V involvement:
      • Only occurred in association with nodal involvement at levels II to IV
    • Whereas the incidence isolated level I involvement without levels II to IV involvement (“skip metastasis”):
      • Occurred in 0.4%:
        • Thus, based on these studies, elective treatment of the neck in oropharynx or hypopharynx can be directed at levels II to IV
• Among oral cavity patients:
  • The incidence of nodal disease was 34% on elective evaluation
  • The majority of metastatic nodes involved:
    • Levels I to III:
      • With only 1.5% incidence of skip metastasis to level IV
  • Level V involvement:
    • Is found in only 0.5% with occult disease simultaneously involving other levels
  • Among those undergoing therapeutic neck dissections:
    • The incidence of level IV involvement increased to 20%
    • Level V was 4% always restricted to lower gum or floor of mouth primary sites
• The need for elective treatment not only relates to the estimated probability of nodal involvement and usually is implemented when the risk is 20% or greater but also relates to the morbidity of such treatment as well as the adequacy of coverage

• Big Picture:
  • AJCC 8th Edition (2017):
    • Introduced Depth of Invasion (DOI) as a major determinant of T stage in oral cavity squamous cell carcinoma (OCSCC)
  • AJCC 9th Edition (2024 / 2025 update):
    • Retains DOI as a core component of T staging, with refinements and clarifications, not a paradigm shift

• Key Concepts Introduced:
  • DOI ≠ tumor thickness
  • DOI measured from basement membrane of adjacent normal mucosa
  • DOI strongly correlates with:
    • Nodal metastasis
    • Survival
• AJCC 9th Edition (What Changed?):
  • DOI Thresholds: UNCHANGED
    • The 5 mm and 10 mm cutoffs remain identical
    • DOI continues to upstage tumors independent of surface dimensions
    • This is critical:
      • No numeric change in DOI staging thresholds
  • Clarification of Measurement Technique:
    • The 9th edition places stronger emphasis on standardization and reproducibility:
      • Clearer distinction between:
        • Exophytic tumors (avoid overestimation)
        • Ulcerated lesions (reconstruct mucosal surface)
      • Addresses interobserver variability among pathologists
      • Reinforces:
        • Measurement from reconstructed basement membrane line
  • Integration With Other Risk Factors:
    • While DOI remains central, AJCC 9 emphasizes its interpretation within a broader biologic context:
      • DOI alone is not sufficient for prognosis
      • Must be integrated with:
        • Perineural invasion (PNI)
        • Lymphovascular invasion (LVI)
        • Worst pattern of invasion (WPOI) (not formally in AJCC but increasingly relevant)
        • Nodal disease / ENE
• This reflects modern understanding:
  • Tumor biology > single metric
• Clinical vs Pathologic DOI:
  • Reinforces distinction:
    • cDOI (imaging / clinical) vs pDOI (pathologic gold standard)
  • Encourages better use of:
    • MRI / ultrasound for preoperative planning
• What Did NOT Change
  • DOI is still:
    • A T-category modifier, not a standalone staging variable
    • Only used in oral cavity cancers (not oropharynx, etc)
    • No change to:
      • T1 / T2 / T3 definitions based on DOI
      • Surgical decision-making thresholds (though clinical use continues evolving)
• Practical Clinical Impact (2025 Reality):
  • Surgical Oncology Perspective:
    • DOI continues to guide:
      • Elective neck dissection:
        • DOI ≥ 3 mm to 4 mm → strong consideration
      • Margin planning
      • Adjuvant therapy discussions
  • Research / Modern Trends:
    • DOI is increasingly being:
      • Combined with molecular markers
      • Supplemented by AI-based histologic risk models
      • Some argue DOI may eventually be:
        • Refined or replaced by composite risk scores