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.

T Staging of Oral Pharyngeal Squamous Cell Carcinoma (OPSCC) Human Papilloma Virus (HPV) Negative

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • 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 muscle, 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
#Arrangoiz #HeadandNeckSurgeon #CancerSurgeon #SurgicalOncology #OropharyngealCancer #Teacher #Surgeon #MountSinaiMedicalCenter #MSMC #BramanComprehensiveCancerCenter #BCCC #Miami #Mexico

Lymphatic Metastasis in Oropharyngeal Squamous Cell Carcinoma (OPSCC)

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Lymph node metastases:
    • At presentation are common in OPSCC:
      • With over half of patients:
        • Having clinical or radiological evidence of cervical metastasis
      • Around a third of patients diagnosed as cN0:
        • Having pathologic evidence of lymph node metastasis
    • The lymphatic drainage from the oropharynx:
      • Is mainly to:
        • Levels II, III and IV
      • It also drains into:
        • The retropharyngeal (RP) nodes:
          • Which need to be considered in the assessment of disease in this area
          • The risk of metastasis to RP lymph nodes depends on subsite:
            • A meta-analysis of papers suggests risk of RP lymphadenopathy being:
              • 19% for soft palate
              • 12% for tonsil
              • 6% for base of tongue and
              • 21% to 57% for posterior pharyngeal wall tumors:
                • Including hypopharynx
        • The prognostic impact of positive RP lymph node metastasis is disputed:
          • Some authors showing an adverse impact:
            • And others not
    • A particular feature of OPSCC:
      • Is the propensity to metastasis to the contralateral neck:
        • This occurring in up to 30% of patients overall in one series:
          • The subsites in which this is mostly likely to occur are the:
            • Soft palate
            • Base of tongue
            • Posterior pharyngeal wall:
              • However:
                • Even tonsil cancers have an approximate rate:
                  • Of contralateral nodal spread of 10%
#Arrangoiz #HeadandNeckSurgeon #HeadandNeckCancer #CancerSurgeon #SurgicalOncologist #Doctor #Surgeon #MountSinaiMedicalCenter #MSMC #BramanComprehensiveCancerCenter #BCCC #Miami #Mexico

Epidemiology of Thyroid Nodules

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Palpable thyroid nodules increase in frequency throughout life:
    • Reaching a prevalence of about 5% in the U.S. population for individuals ≥50 years having palpable thyroid nodules
  • Nodules are even more prevalent when the thyroid gland is examined at autopsy or surgery, or when using ultrasonography:
    • 50% of the thyroids studied have nodules:
      • Which are almost always benign
  • New nodules develop at a rate of about 0.1% per year:
    • Beginning in early life
  • They develop at a much higher rate (approximately 2% per year):
    • After exposure to head and neck irradiation
  • Thyroid nodules are approximately four times more common in individuals assigned female at birth (AFAB) than in individuals assigned male at birth (AMAB)
  • By contrast, thyroid carcinoma is uncommon:
    • For the U.S. population:
      • The lifetime risk of being diagnosed with thyroid carcinoma is:
        • 1.2%
      • It is estimated that approximately 43,720 new cases of thyroid carcinoma will be diagnosed in the United States in 2023
      • As with thyroid nodules:
        • Thyroid carcinoma occurs two to three times more often in individuals AFAB than in individuals AMAB
      • Thyroid carcinoma is currently the seventh most common malignancy diagnosed in individuals AFAB
      • The disease is also diagnosed more often in white North Americans than in African Americans
    • The main histologic types of thyroid carcinoma are:
      • Differentiated (including papillary, follicular, and oncocytic)
      • Medullary
      • Anaplastic:
        • Which is an aggressive undifferentiated tumor
    • Of 63,324 patients diagnosed with thyroid carcinoma from 2011 to 2015:
      • 89.8% had papillary carcinoma
      • 4.5% had follicular carcinoma
      • 1.8% had oncocytic carcinoma
      • 1.6% had medullary carcinoma
      • 0.8% had anaplastic carcinoma
  • A population-based study of data collected by the International Agency for Research on Cancer from 1998 to 2012:
  • Showed that the global incidence of papillary thyroid carcinoma (PTC) increased during this time
  • Mortality rates for thyroid carcinoma are, in general, very low
  • Differentiated thyroid carcinomas usually have an excellent prognosis:
    • With 10-year survival rates exceeding 90% to 95%
  • In contrast, anaplastic thyroid carcinoma (ATC) is almost uniformly lethal
  • However, since differentiated thyroid carcinomas represent more than 95% of all cases:
    • Most thyroid carcinoma deaths are from:
      • Papillary, follicular, and oncocytic carcinomas
  • In 2023, it is estimated that approximately 2120 cancer deaths will occur among persons with thyroid carcinoma in the United States
  • Though thyroid carcinoma occurs more often in individuals AFAB:
    • Mortality rates are lower for younger individuals AFAB
  • Although the estimated incidence of thyroid carcinoma previously increased by an average of ~5% annually between 2004 and 2013:
    • The incidence rate has more recently stabilized:
      • Likely due to more conservative indications for thyroid biopsy and the reclassification of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)
    • Because overall mortality has not dramatically increased since 1975 (1150 vs. 2060 deaths):
      • The previous increase in incidence may reflect, at least in part, earlier detection of subclinical disease (ie, small papillary carcinomas):
        • However, data show the incidence has increased by varying degrees across all tumor sizes and age groups
          • The stable age- and gender-adjusted mortality rate for thyroid carcinoma contrasts distinctly with the declining rates for other solid tumors in adults
  • A cohort study of 2000 to 2016 data from U.S. cancer registries:
    • Showed an increase in incidence of aggressive PTC
  • In addition, an analysis of 1992 to 2018 SEER data showed that there is no evidence of an improvement in disease-specific survival (DSS) in patients with distantly metastatic differentiated thyroid cancer
#Arrangoiz #ThyroidSurgeon #CancerSurgeon #ThyroidAwarenessMonth #HeadandNeckSurgeon #SurgicalOncologist #ThyoridCancer #MountSianiMedicalCenter #MSMC #Miami #Mexico

Locally Advanced Thyroid Cancer with Gross Extrathyroidal Extension (gETE)

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Gross extrathyroidal extension (ETE):
    • Is defined as direct tumor extension beyond the thyroid capsule into perithyroidal structures:
      • Identified clinically, on imaging, or on gross pathology:
        • This is the defining feature of locally advanced thyroid cancer
    • It must be distinguished from microscopic (minimal) ETE (mETE):
      • Which is detected only histologically and, because of poor interobserver reproducibility (kappa ≈ 0.14) and negligible independent prognostic weight:
        • Was removed from AJCC 8th edition T-staging in 2017
      • Only gross ETE (gETE) now drives T-category and stage
  • Management is stratified by which structure is involved:
    • Strap muscles vs. recurrent laryngeal nerve (RLN), trachea, larynx, esophagus vs. prevertebral fascia / great vessels:
      • With the central principle that complete gross resection with acceptable morbidity, followed by risk-adapted RAI and / or EBRT:
        • Offers the best locoregional control
  • Definitions and classification of ETE
    Microscopic (minimal / minor) ETE (mETE):
    • Tumor extension into immediate perithyroidal soft tissue or skeletal muscle:
      • Seen only on histology:
        • Not appreciated clinically or grossly
    • Associated with a 3% to 9% recurrence risk:
      • With no consistent independent effect on disease-specific (DSS) or overall survival (OS)
  • Gross (extensive) ETE:
    • Macroscopic invasion evident at surgery, on preoperative imaging, or on gross specimen exam:
      • Into strap muscles (T3b) or into subcutaneous soft tissue, larynx, trachea, esophagus, RLN (T4a), or prevertebral fascia / carotid / mediastinal vessels (T4b)
    • Recurrence risk of 23% to 40%
    • Disease-specific mortality of 23% to 52%
    • The following Kaplan-Meier curves illustrate the sharp prognostic divergence:
      • Recurrence-free survival for mETE overlaps with no ETE (both near 100%), whereas gETE falls to roughly 35%
Adverse Outcome Based on the Degree of Extrathyroidal Extension
  • Epidemiology:
    • ETE is present in roughly:
      • 10% to 15% of thyroid cancers at presentation:
        • Up to ~ 23.5% of papillary carcinomas in some pathologic series:
          • Most commonly involving the strap muscles
    • Frank aerodigestive-tract invasion is less common:
      • Tracheal invasion occurs in an estimated:
        • 1% to 8% of thyroid carcinomas
      • RLN is involved in:
        • 33% to 61% of the subset of tumors classified as “invasive”
      • Overall, roughly 10% to 15% of DTC patients have locoregionally advanced disease:
        • Carrying substantially higher recurrence and mortality risk
  • Prognosis:
    • Gross ETE (gETE):
      • Is an independent predictor of reduced disease-specific survival (DSS), higher local recurrence, and greater risk of nodal and distant metastasis
    • In a SEER cohort of > 107,000 patients:
      • Cancer-specific mortality rates per 1,000 person-years rose stepwise:
        • 1.4 (thyroid-confined)
        • 5.1 (mETE)
        • 29.7 (gETE)
    • Among invaded structures, tracheal invasion carries particular weight:
      • In one T4 DTC series it was the only factor significantly associated with recurrence, and airway obstruction from local spread accounts for a substantial share of DTC deaths:
        • Coexisting macroscopic extranodal extension further worsens outcomes:
          • With unresectable macroscopic ENE dropping 5-year DSS to ~ 82%
  • Staging (AJCC 8th edition):
    • The T-category is anchored to the depth of gross ETE, and staging is heavily age-dependent (cutoff 55 years):
      • Below is the NCCN reproduction of the AJCC 8th edition TNM definitions for differentiated (and anaplastic) carcinoma

In patients < 55 years, any T with M0 is Stage I regardless of ETE. For anaplastic carcinoma, all disease is Stage IV (IVA /IVB / IVC), with the same T definitions. Note gETE also mandates total thyroidectomy and excludes a patient from active surveillance.
  • Management by structure involved:
    • Surgery is the mainstay:
      • The goal is complete gross tumor removal (R0 / R1) balanced against functional morbidity:
        • Followed by risk-adapted adjuvant therapy
    • A multidisciplinary team at a high-volume center:
      • Is recommended for bulky or viscerally invasive disease
    • The overall airway / aerodigestive management framework hinges on:
    • Whether invasion is:
      • Extraluminal:
        • Amenable to shave excision versus
      • Intraluminal:
        • Requiring formal resection
Algorithm for the management of locally advanced thyroid cancer.
  • Strap muscles (T3b):
    • En bloc resection of the involved strap muscle with the thyroid:
      • This is well tolerated and does not compromise function
  • Recurrent laryngeal nerve (T4a):
    • Management is dictated by preoperative vocal cord function and the extent of invasion:
      • Functioning nerve with tumor adherent /encasing but mobile cords:
        • Attempt preservation:
          • Shave / partial-layer resection to remove all gross disease while keeping neural continuity, followed by adjuvant therapy
          • Preserving a functioning nerve, even at the cost of microscopic residual,, does not worsen survival
      • Nonfunctioning nerve (preoperative paralysis) and / or complete encasement:
        • Resection of the involved segment is appropriate:
          • Ideally with immediate reconstruction (direct / end-to-end anastomosis, ansa cervicalis–to–RLN anastomosis, or nerve grafting) to restore phonatory and swallowing function
          • Keep in mind contralateral nerve, want to avoid tracheostomy
        • Intraoperative nerve monitoring (NIM) and staged contralateral surgery help avoid bilateral paralysis:
          • If signal is lost on the first side during planned total thyroidectomy, defer the contralateral lobe
    • The following decision algorithm summarizes the RLN approach based on cord mobility and neural continuity:
  • Trachea (T4a):
    • Extent of resection follows depth of invasion:
      • Shin classification
    • Superficial invasion not penetrating perichondrium / cartilage:
      • Tangential shave excision achieves local control up to ~ 95%:
        • Though positive-margin and recurrence rates are higher:
          • So adjuvant therapy is typically added
    • Intraluminal invasion or significant cartilage involvement:
      • Circumferential sleeve resection with end-to-end anastomosis:
        • Feasible for defects < ~ 5 cm / up to ~ half circumference)
      • Window resection with flap reconstruction is preferred for durable local control
      • Systematic review of 656 patients undergoing (crico)tracheal resection reported ~ 2% perioperative mortality, ~ 27% complications (mainly RLN palsy), 4% permanent tracheostomy, and 5-year DSS of 75.8% to 90%
  • Larynx / esophagus (T4a):
    • Partial-thickness (“shave”) resection of the esophageal muscular wall or partial laryngeal / tracheal windowing is preferred when the lumen / mucosa is not breached
    • Transmural esophageal or full laryngeal involvement may require segmental esophageal resection with flap reconstruction, partial / total laryngectomy, or laryngopharyngectomy — reserved for highly selected cases
  • Prevertebral fascia / carotid / mediastinal vessels (T4b):
    • Often unresectable or borderline resectable:
      • Options include cervical exenteration at expert centers in selected patients, or non-surgical management with EBRT ± systemic therapy when curative resection is not feasible or acceptable
  • Adjuvant therapy (RAI and EBRT):
    • After surgery, the NCCN algorithm:
      • Branches on presence of gross residual disease, resectability, and RAI avidity
    • For locoregionally invasive disease or rapid progression:
      • EBRT or systemic therapy is considered
  • RAI:
    • Indicated for iodine-avid residual / high-risk disease and is preferred when uptake is present:
      • Many invasive tumors, however, are relatively iodine-refractory
  • EBRT:
    • The 2025 ATA guidelines state that adjuvant EBRT may be considered in select DTC patients with high-risk features for locoregional progression:
      • Aggressive histology
      • gETE
      • Positive margins
      • Visceral / soft-tissue invasion:
        • Especially when future progression would not be salvageable surgically:
          • Weighing improved locoregional relapse-free survival against toxicity and absence of a demonstrated overall survival benefit
    • EBRT ± concurrent chemotherapy:
      • Is also an option for gross residual or locally advanced unresectable disease
      • Retrospective and propensity-matched data show:
        • Improved locoregional control:
          • e.g., 10-year local failure-free survival 88% for EBRT+RAI vs. 72% RAI alone in pT4a PTC
          • LRR reduced from 51% to 8% after tracheal shave without consistent OS gain
    • Typical adjuvant EBRT doses for non-anaplastic thyroid cancer are:
      • 60 to 66 Gy to microscopic disease / thyroid bed
      • 50 to 56 Gy to elective nodal regions
      • 66 to 70 Gy for gross / unresectable disease:
        • Delivered by IMRT
    • For BRAF V600E–mutated anaplastic carcinoma:
      • Neoadjuvant dabrafenib / trametinib and multimodal EBRT / chemoradiation apply on separate ATC-specific algorithms
  • References:
    • Ringel MD, Sosa JA, Baloch Z, et al. 2025 American Thyroid Association Management Guidelines for Adult Patients With Differentiated Thyroid Cancer. Thyroid. 2025.
    • Sessa L, De Crea C, Voloudakis N, et al. Single Institution Experience in the Management of Locally Advanced (pT4) Differentiated Thyroid Carcinomas. Ann Surg Oncol. 2024.
    • Scognamiglio T. Aggressive follicular cell derived thyroid carcinoma: what do you need from the pathologist. Virchows Arch. 2026.
    • Xu B, Ghossein RA. Crucial parameters in thyroid carcinoma reporting – challenges, controversies and clinical implications. Histopathology. 2018.
    • Xu B, Ghossein RA. Crucial parameters in thyroid carcinoma reporting – challenges, controversies and clinical implications. Histopathology. 2018.
    • Shindo ML, Caruana SM, Kandil E, et al. Management of invasive well-differentiated thyroid cancer: An American Head and Neck Society consensus statement. Head Neck. 2014.
    • Li M, Tang Q, Yang X, et al. Application of modified spiral tracheoplasty in thyroid carcinoma with trachea invasion: a retrospective analysis of 15 cases. World J Surg Oncol. 2024.
    • Laskar SG, Mohanty S, Sinha S, et al. Adjuvant External Beam Radiotherapy in Differentiated Thyroid Cancers: An Audit of Clinical Practice, Adapting to New Evidence. Head Neck. 2025.
    • Yuan SS, Zhang XR, Yu XQ, et al. Prediction model for extrathyroidal extension in thyroid papillary carcinoma based on ultrasound radiomics. Sci Rep. 2025.
    • Liu Z, Huang Y, Chen S, et al. Minimal Extrathyroidal Extension Affects the Prognosis of Differentiated Thyroid Cancer: Is There a Need for Change in the AJCC Classification System? PLoS One. 2019. 12.
    • Liu Y, Zhang X, Liu J, et al. Prognostic significance of the extent of extranodal extension in patients with pN1b papillary thyroid carcinoma: a retrospective cohort study. Eur Arch Otorhinolaryngol. 2026.
    • National Comprehensive Cancer Network. Thyroid Carcinoma. NCCN Clinical Practice Guidelines in Oncology. 2026.
    • Perrier ND, Brierley JD, Tuttle RM. Differentiated and Anaplastic Thyroid Carcinoma: Major Changes in the American Joint Committee on Cancer Eighth Edition Cancer Staging Manual. CA Cancer J Clin. 2018.
    • Patel R. Thyroid. In: Essential Cases in Head and Neck Oncology. 2022.
    • Fundakowski CE, Hales NW, Agrawal N, et al. Surgical management of the recurrent laryngeal nerve in thyroidectomy: American Head and Neck Society Consensus Statement. Head Neck. 2018.
    • Perros P, Boelaert K, Colley S, et al. Guidelines for the management of thyroid cancer. Clin Endocrinol (Oxf). 2014.
    • Masuoka H, Miyauchi A. Intraoperative Management of the Recurrent Laryngeal Nerve Transected or Invaded by Thyroid Cancer. Front Endocrinol (Lausanne). 2022.
    • Rai S, Agarwal M, Bansal K, et al. Intraoperative management of recurrent laryngeal nerve invasion in thyroid carcinoma: Oncologic and functional outcomes with a surgical decision algorithm. Eur Arch Otorhinolaryngol. 2026.
    • Wang S, Li S, Yang X, et al. Surgical treatment for patients with papillary thyroid carcinoma invading the cervical trachea. Eur Arch Otorhinolaryngol. 2026.
    • Piazza C, Lancini D, Tomasoni M, et al. Tracheal and Cricotracheal Resection With End-to-End Anastomosis for Locally Advanced Thyroid Cancer: A Systematic Review of the Literature on 656 Patients. Front Endocrinol (Lausanne). 2021.
    • Mercader-Cidoncha E, Zaraín-Obrador L, Lasso JM, Simón-Adiego C. Surgical Resources in Advanced Thyroid Cancer Treatment With Aerodigestive Tract Invasion. Surg Oncol. 2023.
    • Scharpf J, Tuttle M, Wong R, et al. Comprehensive management of recurrent thyroid cancer: An American Head and Neck Society consensus statement. Head Neck. 2016.
    • Piazza C, Lancini D, Paderno A. Cervical Exenteration and Its Variants for Locally Advanced Thyroid Cancer: When, Why, and How? Curr Opin Otolaryngol Head Neck Surg. 2023.
    • Kiess AP, Agrawal N, Brierley JD, et al. External-beam radiotherapy for differentiated thyroid cancer locoregional control: A statement of the American Head and Neck Society. Head Neck. 2016.
    • Kawamoto T, Shikama N, Fukumori T, Hoshi M, Yamada T. Propensity score matching analysis of adjuvant external-beam radiotherapy for the treatment of papillary thyroid carcinoma with other organ invasions. Endocrine. 2023.
    • Laskar SG, Mohanty S, Sinha S, et al. Adjuvant External Beam Radiotherapy in Differentiated Thyroid Cancers: An Audit of Clinical Practice, Adapting to New Evidence. Head Neck. 2025.
Screenshot
Screenshot
Screenshot

Thyroid Cancer Preoperative Imaging

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Before removal of thyroid cancer:
    • It is critical to perform a thorough evaluation:
      • To determine the extent of disease
  • Preoperative imaging should include:
    • A comprehensive ultrasound (US) of the neck to examine the contralateral lobe of the thyroid, the central neck compartments, and the lateral neck lymph nodes (LN):
      • Such imaging may change the surgical approach in up to 40% of cases
  • The anterior neck is divided into seven contiguous compartments in which thyroid cancer metastatic LN spread occurs
  • The central neck compartment (level VI) contains the thyroid and poses the greatest challenge to clinicians when deciding the optimal surgery:
    • It is bordered laterally by the carotid arteries, inferiorly by the clavicles, and superiorly by the hyoid bone
    • Level VI is the compartment that is most frequently involved with LN metastases:
      • But sonographic identification of diseased nodes is hampered by poor preoperative sensitivity:
        • The intact thyroid gland obscures visualization of the majority of nodal metastases
  • The lateral neck is further subdivided into four compartments lateral to the carotid:
    • Level IV is bordered laterally by the sternocleidomastoid (SCM), inferiorly by the clavicle, and superiorly by the cricoid cartilage
    • Level III, located immediately cephalad to level IV, extends superiorly to the carotid bifurcation
    • Level II is located below the mandible and extends to the hyoid bone
    • Level V nodes are located in the posterior triangle, lateral to the lateral edge of the SCM.
  • The presence of malignancy in sonographically suspicious nodes:
    • Can be confirmed with FNA for cytologic analysis and measurement of thyroglobulin (Tg) in the needle washout
  • If advanced, bulky nodal disease is identified on US, or the patient has clinical signs or symptoms of advanced disease (hoarseness, hemoptysis, a nonmobile thyroid mass):
    • CT or magnetic resonance imaging (MRI) of the neck may be considered to search for additional metastases in areas that cannot be visualized sonographically, including within the mediastinum, at the skull base, and posterior to the trachea
#Arrangoiz #ThyroidSurgeon #CancerSurgeon #MountSinaiMedicalCenter #MSMC #Doctor #Surgeon #HeadandNeckSurgeon #SurgicalOncologist #Miami #Mexico

Oropharyngeal Tumor Histological Types

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Oropharyngeal tumor histological types:
    • Squamous cell carcinoma (SCC):
      • Is the most common malignancy of the oropharynx:
        • Making up 90% of the tumors in this region
    • Non-Hodgkin’s lymphomas:
      • Accounts for 8% of tumors in these region
    • Minor salivary gland tumors:
      • Account for 2% of tumors in these region
  • With regard to squamous cell carcinoma:
    • The most frequent locations of affected sites is:
      • Tonsil / lateral wall:
        • 60% of the cases
      • Tongue base:
        • 25% of the cases
      • Soft palate:
        • 10% of the cases
      • Posterior pharyngeal wall:
        • 5% of the cases
#Arrangoiz #Doctor #HeadandNeckSurgeon #HeadandNeckCancer #CancerSurgeon #SurgicalOncologist #Teacher #Surgeon #MountSinaiMedicalCenter #MSMC #BramanComprehensiveCancerCenter #BCCC

Pathology of Oropharyngeal Squamous Cell Carcinoma (OPSCC)

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Two Distinct Disease Entities:
    • OPSCC is now classified as two biologically and prognostically distinct diseases:
      • Based on high-risk HPV status: 
        • HPV-associated (p16-positive) and HPV-independent (p16-negative) carcinoma:
          • A division formalized in the WHO classification and the AJCC 8th edition staging system
    • HPV-associated tumors:
      • Carry a markedly better prognosis:
        • With 8-year overall survival of 70.9% versus 30.2% for HPV-negative disease in RTOG 0129:
          • HR 0.30; 95% CI 0.21–0.42
  • Histopathology:
    • HPV-Associated (
    • ) OPSCC:
      • These tumors arise from the specialized reticulated epithelium lining the tonsillar crypts rather than the surface mucosa
      • Characteristic features include:
        • Nonkeratinizing growth:
          • Lobules and sheets of immature basaloid cells with high nuclear-to-cytoplasmic ratios and hyperchromatic nuclei; absent or minimal keratinization
        • Basaloid cytology:
          • Resembling deep crypt epithelium, with lobular / endophytic growth and smooth pushing borders
        • Permeating tumor-infiltrating lymphocytes:
          • Within and around tumor nests
        • Absence of surface dysplasia:
          • Dysplasia is confined to crypts
        • Cystic nodal metastases:
          • Which can mimic branchial cleft cysts
      • In a 4-year prospective study of 435 OPSCCs:
        • Strictly defined nonkeratinizing morphology had a 99.1% positive predictive value for p16 positivity and 100% PPV for HR-HPV mRNA positivity
        • A “nonkeratinizing with maturation” (hybrid) intermediate pattern is p16-positive in ~92% of cases
    • HPV-Independent (Keratinizing) OPSCC:
      • These resemble conventional keratinizing SCC of the upper aerodigestive tract:
        • With keratin pearl formation
        • Individual cell keratinization
        • Intercellular bridges
        • Progressive squamous maturation
        • Origin from dysplastic surface epithelium
      • Molecularly they are characterized by high rates of:
        • TP53 mutation
        • CCND1 (cyclin D1) copy-number gains
        • 9p21 / CDKN2A loss
  • A Note on Grading:
    • Although HPV-associated tumors appear “poorly differentiated” by conventional criteria:
      • They paradoxically carry the best prognosis:
        • Westra has argued they may be best viewed as well-differentiated given their resemblance to native crypt epithelium
    • Both the 2018 CAP guideline and its 2025 update recommend against providing traditional grade / differentiation status for HPV-associated OPSCC:
      • Instead recommend reporting the WHO histologic subtype
    • Conventional grading (G1 to G4) still applies to HPV-independent OPSCC
    • Certain morphologic features retain prognostic value even within p16-positive disease:
      • Tumor cell anaplasia (nuclei ≥ 5 lymphocyte diameters) and multinucleation:
        • Independently predicted worse disease-specific survival (HR 9.9 and 11.9, respectively), and “non-classic” HPV-positive morphology was associated with poorer 5-year survival (58.4% vs 83.9%)
      • Keratinization:
        • Independently predicts worse survival
The 2025 CAP update enumerates the recognized morphologic subtypes.
  • Histologic Variants:
    • Basaloid SCC:
      • Is a mixed entity resolvable by HPV status:
        • HPV-positive:
          • Younger patients
          • p16+ / p53−
          • Prognosis – favorable
        • HPV-negative:
          • Older patients
          • Tobacco / alcohol-related
          • p53 overexpression
          • Biology – aggressive
    • Lymphoepithelial-like carcinoma:
      • Requires mandatory dual HPV and EBV testing:
        • As it closely mimics metastatic nasopharyngeal carcinoma
  • HPV / p16 Testing:
    • Who to Test:
      • All patients with newly diagnosed OPSCC should undergo HR-HPV testing, regardless of histologic subtype:
        • A strong CAP recommendation, endorsed by ASCO and listed as required in NCCN workup
      • Testing may be performed on the:
        • Primary tumor, a nodal metastasis, or FNA of a cervical node
      • Routine testing is not recommended for:
        • Nonsquamous oropharyngeal or non-oropharyngeal head and neck carcinomas (except sinonasal)
      • p16 IHC — the First-Line Test:
        • p16 immunohistochemistry is the recommended primary test:
          • Positivity requires:
            •  ≥ 70% nuclear AND cytoplasmic expression with at least moderate-to-strong intensity:
              • Typically in a confluent / block-like pattern
        • The E6H4 clone is most widely used and validated
        • With these criteria:
          • Sensitivity for transcriptionally active HR-HPV approaches 100% with specificity of ~ 85% to 95% in the oropharynx
        • Cases with 50% to 70% staining are equivocal and warrant HPV-specific testing
        • p16 and HPV may be used interchangeably only within the oropharynx
      • HPV-Specific (Direct) Testing:
        • The 2025 CAP update expanded indications for confirmatory HPV-specific testing beyond p16 IHC:
  • HPV-specific testing should be performed in:
    • Low-prevalence geographic regions
    • Equivocal p16 staining
    • Discrepancy between p16 and morphology (e.g., p16+ but keratinizing)
    • Large multisite tumors
    • Non-tonsillar / non-base-of-tongue subsites
    • Clinical trials
    • SCC of unknown primary
  • Discordant Results:
    • p16+ / HPV− discordance occurs in ~ 4% to 20% of cases:
      • In the multinational HNCIG-EPIC-OPC analysis (n=7,654):
        • Discordant patients had intermediate prognosis:
          • Significantly worse than double-positive and better than double-negative: 

Initial Thyroid Surgery for Thyroid Cancer

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Surgery is the initial treatment for most thyroid cancers and is often curative for those with low-risk disease
  • Historically, the majority of cancers measuring greater than 1 cm were recommended for total thyroidectomy:
    • To facilitate surveillance, allow for radioiodine therapy, and reduce the likelihood of recurrence
  • Newer data, however, has cast doubt on the necessity of removal of the entire gland:
    • The recent trend to the use of less radioiodine therapy has obviated the need to perform total thyroidectomy in many patients with low-risk thyroid cancer
    • Further strengthening the argument for less extensive surgery is the recognition that the risk of complications with total thyroidectomy is double that seen in lobectomy, regardless of the surgeon’s experience level
    • Most importantly, multiple retrospective studies have revealed that outcomes are equivalent in patients with low-risk disease treated with lobectomy compared with total thyroidectomy when controlled for tumor size and extent of disease
  • Those tumors measuring 4 cm or with preoperative evidence of nodal involvement or ETE, regardless of size:
    • Should proceed with total thyroidectomy
#Arrangoiz #ThyroidSurgeon #HeadandNeckSurgeon #CancerSurgeon #SurgicalOncologist #MountSiniaMedicalCenter #MSMC #Miami #Mexico

Indications for Radioactive Iodine Therapy in Thyroid Cancer

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • There are three main indications for postoperative iodine-131 (131I) use:
    • To treat any known (or unknown) residual disease
    • To reduce the risk of recurrence
    • To destroy remaining noncancerous thyroid cells:
      • This last indication:
        • Called remnant ablation, improves the sensitivity of serum Tg and may also be used as a staging tool to identify previously undiagnosed tumors
  • The use of RAI therapy is a contentious issue with conflicting findings regarding recurrence and survival benefit:
    • Largely stemming from the lack of prospective, randomized, and controlled trials
  • The patients for whom RAI may be beneficial can be clarified based on the initial risk stratification of the individual tumor (Table) and the postoperative disease status
RAI, radioactive iodine, ATA, American Thyroid Association, TNM, The Tumor, Node, and Metastases scoring system, ETE, extrathyroidal extension, ENE, extranodal extension.
Modified from Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26(1):1–133.
  • Studies have consistently shown that patients with American Thyroid Association (ATA) low-risk tumors measuring 1 cm lacking nodal and distant metastases:
    • Do not benefit from RAI therapy, and its use is not recommended
  • Additionally, low-risk tumors measuring 1 to 4 cm lacking local or distant metastases with complete tumor resection and no tumor invasion into the locoregional tissues or structures:
    • Do not derive mortality benefit from adjuvant RAI therapy:
      • As such, RAI therapy should not be routinely used in this group unless there is an aggressive histology or evidence of vascular invasion
  • In contrast, RAI does appear to be beneficial in terms of mortality and disease-free survival for those patients with a high-risk tumor:
    • Its use is routinely recommended in the postoperative management of these patients
  • For the remaining patients, including those with intermediate risk for recurrence:
    • There is conflicting data regarding the benefits of therapy:
      • Use of RAI in this cohort of patients should be considered on a case-by-case basis
#Arrangoiz #Surgeon #Doctor #CancerSurgeon #ThyroidSurgeon #ParathyroidSurgeon #HeadandNeckSurgeon #SurgicalOncologist #MountSinaiMedicalCenter #MSMC #Miami #Mexico #ThyroidCancer

American Thyroid Association Response to Therapy Classification in Thyroid Cancer

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Excellent Response to Therapy:
    • Patients with no biochemical (unstimulated serum thyroglobulin (Tg) < 0.2 or stimulated Tg < 1.0 ng/mL) or radiographic evidence of disease are classified as having an excellent response to therapy
    • Patients with an initial low to intermediate risk of recurrence who meet these criteria:
      • Are recommended to have serum Tg monitored every 12 to 24 months
    • Patients with initially high-risk disease:
      • Should continue to have a serum Tg measurement at least every 6 to 12 months
  • Biochemical Incomplete Response to Therapy:
    • Patients who have undergone total thyroidectomy and remnant ablation and have an unstimulated serum Tg > 1 ng/mL or a stimulated Tg > 10 ng/mL or a rising thyroglobulin antibody (TgAb) titer with negative imaging:
      • Are classified as having a biochemical incomplete response to therapy
    • Such patients should undergo imaging with sonography of the neck:
      • If the disease is unable to be located:
        • Cross-sectional imaging of the neck and chest should be performed
    • Serum Tg should be followed at least every 6 to 12 months.
  • Structural Incomplete Response to Therapy:
    • Those patients with structurally or functionally (on diagnostic whole-body scan [DxWBS] or 18(FDG-PET) evident disease are classified as:
      • Having a structural incomplete response to therapy
    • Unfortunately, the majority of patients in this category will have persistent disease in spite of additional treatments
    • Disease-specific death rates are high in this group:
      • 11% with locoregional metastases
      • 50% with distant metastases
  • Indeterminate Response to Therapy:
    • Patients with biochemical or structural findings that cannot be confidently classified as either excellent response or persistent disease:
      • Are deemed as having an indeterminate response to therapy
    • Such patients may be carefully followed with biochemical testing and serial imaging to better delineate which category is ultimately appropriate
    • It is estimated that up to 20% of these patients will eventually develop conclusive evidence of disease requiring additional therapy
#Arrangoiz #Doctor #Surgeon #ThyroidSurgeon #ParathyroidSurgeon #HeadandNeckSurgeon #CancerSurgeon #MountSinaiMedicalCenter #MSMC #Miami #Mexico #ThyroidCancer