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Age plays an important role in how thyroid cancer behaves, how it is staged, and how it is treated.

👶 Thyroid cancer in younger patients

More common in women Often presents with lymph node involvement Tumors may look aggressive on imaging 👉 Despite this, prognosis is excellent

✔️ Patients under 55 years are staged differently

✔️ Even with lymph nodes, survival rates exceed 98–99%

✔️ Treatment focuses on curing disease while preserving quality of life

👴 Thyroid cancer in older patients

Less common, but tumors may be biologically more aggressive Higher likelihood of: Extrathyroidal extension Distant metastases Higher-stage disease Outcomes are still often very good, but treatment may need to be more comprehensive

⚖️ Why age matters

Age helps determine:

AJCC stage Expected prognosis Intensity of treatment and follow-up

🧠 Important clarification:

Age alone does not determine outcome.

➡️ Tumor biology, pathology, and response to treatment matter most.

🦋 What this means for patients

Thyroid cancer is not the same disease in every patient.

The goal is personalized, risk-adapted care—not one-size-fits-all treatment.

👨‍⚕️ Dr. Rodrigo Arrangoiz, MD

Surgical Oncologist – Thyroid, Head & Neck, Breast

Mount Sinai Medical Center

📌 Take-home message:

Young patients do extremely well.

Older patients still have excellent outcomes with expert, individualized care.

📚 References

AJCC Cancer Staging Manual, 8th Edition Haugen BR et al. ATA Guidelines for Differentiated Thyroid Cancer. Thyroid Tuttle RM et al. Risk-adapted management of thyroid cancer. Lancet Diabetes Endocrinol

• Updated 2018 American Society for Radiation Oncology (ASTRO) guidelines:
  • State that patients 50 and younger, and 51 to 70 years of age with high-grade tumors or positive margins:
    • Should receive a tumor bed boost
  • A boost may be omitted for women:
    • Older than 70 with hormone receptor positive and low- or intermediate-grade disease with widely negative margins (> 2 mm)
  • If the patient does not meet either of those criteria, individualized decision making is recommended
  • For ductal carcinoma in situ (DCIS):
    • Tumor bed boost may be used for women:
      • 50 years of age and younger
      • Close (less than 2 mm) or positive margins
      • High-grade disease
    • It may be omitted for patients:
      • Older than 50 with screening detected
      • Total size less than 2.5 cm
      • Low to intermediate nuclear grade
      • Widely negative margins:
        • Greater than 3 mm
    • Long-term 20-year follow-up of a phase 3 trial of boost vs. no boost:
      • Reported a benefit in all groups with the largest absolute risk reduction in younger patients
• References
  • Smith BD, Bellon JR, Blitzblau R, et al. Radiation therapy for the whole breast: executive summary of an American Society for Radiation Oncology (ASTRO) evidence-based guideline. Pract Radiat Oncol. 2018;8(3):145-152.
  • Bartelink H, Maingon P, Poortmans P, et al. Whole-breast irradiation with or without a boost for patients treated with breast-conserving surgery for early breast cancer: 20-year follow-up of a randomised phase 3 trial. Lanc Oncol. 2015;16(1):47-56.

• The regional state of lymph nodes:
  • Is one of the most important parameters determining prognosis in patients with head and neck squamous cell carcinoma (HNSCC)
• The presence of only one positive lymph node:
  • Can decrease survival by up to 50% in most HNSCC
• The risk of lymph node metastasis can be predicted in relation to:
  • Differentiation of tumor:
    • The more poorly differentiated the tumor:
      • The greater the risk
  • To the size and depth of the invasion (DOI)
  • The availability of capillary lymphatics
• The risk of lymphatic spread:
  • Increases with tumor recurrence
• Embryologically:
  • The lymphatic system is formed:
    • From its germination from the venous system:
      • Explaining the close anatomical relationship between these two systems
  • Blood capillaries have tight endothelial junctions:
    • That normally do not reabsorb larger molecules and cells
  • However, lymphatic capillaries have relatively open endothelial junctions:
    • That allow molecules and larger cells to be more easily reabsorbed:
      • Explaining the reason for easier lymphatic than vascular propensity
• The lymphatic system of the head and neck:
  • Is the region of the body composed by more lymphatic capillaries, lymphatic trunks and lymph nodes:
    • Epithelium, bone and cartilage:
      • Are devoid of lymphatic capillaries:
        • While a small minority is found in the periosteum and perichondrium
• Lymph node arrangement is archetypal and each group receives drainage (directly or indirectly) from specific areas:
  • In a deep cervical group (a terminal group for the head and region of the neck) before finally flowing into the lymphatic duct (right) / thoracic duct (left) in the jugular-subclavian junction
• Due to the absence of lymphatic vessels in the epithelium:
  • The tumor must penetrate the lamina propria before lymphatic invasion
• In the superficial layer:
  • The diameter of lymphatic capillaries is usually narrower than it is in the deeper layer
• The richness of the capillary network in each subsite can increase the relative incidence of lymph node metastases:
  • The nasopharynx, pyriform sinus (hypopharynx), supraglottic larynx and oropharynx:
    • Have the most profitable network of capillary lymphatic vessels:
      • Which is the clinical reflection of the potential presence of neoplastic lymph nodes
  • Paranasal sinuses, middle ear and vocal folds:
    • Have few or no capillary lymphatics:
      • Which is consistent with the low rate of lymph node metastases when the tumor is confined to these sites
• The involvement of lymph nodes usually follows an ordered progression and, rarely, skip nodal metastasis is revealed (exception lateral ventral tongue)
• Well lateralized lesions:
  • Determine ipsilateral lymph node metastases
• Lesions near the midline or lateral margin of tongue or nasopharyngeal lesions:
  • Can also spread contra-laterally or bilaterally:
    • But generally, tend to spread from the side of the lesion
• Patients with ipsilateral tumor nodal disease are at risk of contralateral disease:
  • Especially if the lymph node exceeds a certain size or if multiple lymph nodes are involved
• Obstruction of lymphatic pathways:
  • Caused by surgery or radiation therapy:
    • Can divert lymphatic flow on the opposite side of the neck:
      • Through anastomotic channels
• Finally, it should be remembered that metastases in cervical-cephalic regions:
  • Occur in approximately 10% of patients as neoplastic metastases from unknown primary sites
  • The histopathology of these metastases is generally referable to squamous cell carcinomas in various degrees of differentiation:
    • But metastases of adenocarcinomas, melanomas, or anaplastic tumors can also be found
  • The lymph node level is indicative of possible neoplastic origin
• Distant metastasis (DM):
  • In the absence of nodal metastasis is very rare in HNSCC
  • Untreated occult disease in the lymphatic venous system:
    • Can produce DM while the lymph node is growing
  • Patients with advanced disease have a high incidence of DM:
    • Particularly in the presence of jugular vein invasion or extensive soft tissue disease in the neck:
      • The rate of DM increases by:
        • Up to 25% to 30% for N3 disease compared to 18% to 20% for N2 disease

• 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

Thyroid Cancer Staging (Simplified for Patients)

Staging describes how far a cancer has spread. In thyroid cancer, staging helps guide treatment intensity and follow-up, but it’s important to know that most patients do very well regardless of stage.

🧠 What factors are used to stage thyroid cancer?

The AJCC staging system considers:

Tumor size and whether it extends beyond the thyroid Lymph node involvement in the neck Distant spread (lungs or bones—uncommon) Age (patients under 55 are staged differently and typically have an excellent prognosis)

📊 What do the stages mean?

Stage I–II: ✔️ Most common ✔️ Often confined to the thyroid or nearby lymph nodes ✔️ Excellent long-term survival Stage III–IV: ✔️ Less common ✔️ More extensive local disease or distant spread ✔️ Still often highly treatable with modern, multidisciplinary care

⚖️ A key clarification for patients

Stage is not the same as risk of recurrence.

We also use ATA risk stratification to estimate the chance of the cancer returning and to tailor:

Extent of surgery Use of radioactive iodine Intensity of follow-up

🦋 Why this matters

Staging helps us:

Avoid overtreatment in low-risk patients Focus resources on patients who truly need more intensive therapy Provide accurate reassurance and individualized care

👨‍⚕️ Dr. Rodrigo Arrangoiz, MD

Surgical Oncologist – Thyroid, Head & Neck, Breast

Mount Sinai Medical Center

📌 Take-home message:

In thyroid cancer, stage helps guide care—but prognosis is excellent for the vast majority of patients.

📚 References

AJCC Cancer Staging Manual, 8th Edition Haugen BR et al. ATA Guidelines for Differentiated Thyroid Cancer. Thyroid Tuttle RM et al. Risk-adapted management of thyroid cancer. Lancet Diabetes Endocrinol

Most thyroid nodules are benign, and most people with thyroid nodules will never develop thyroid cancer.

Still, certain factors are associated with a higher risk and deserve closer evaluation.

☢️ Strongly Associated Risk Factors

Radiation exposure to the head and neck, especially during childhood or adolescence Prior therapeutic radiation for benign or malignant conditions Family history of thyroid cancer (especially first-degree relatives)

🧬 Genetic & Medical Factors

Certain inherited syndromes (rare, but important) Medullary thyroid cancer associated with RET mutations Autoimmune thyroid disease (e.g., Hashimoto’s thyroiditis) increases nodule prevalence; cancer risk remains low but evaluation is important

👥 Demographic Factors

Female sex (thyroid cancer is more common in women) Age (extremes of age can influence behavior and management)

🧠 Important clarification for patients

Having risk factors does NOT mean you have cancer.

➡️ Most patients with thyroid cancer have no identifiable risk factors.

➡️ Risk factors help guide how carefully we evaluate, not whether we panic.

🔍 What matters most?

High-quality ultrasound Appropriate biopsy when indicated Expert interpretation and risk-adapted management

👨‍⚕️ Dr. Rodrigo Arrangoiz, MD

Surgical Oncologist – Thyroid, Head & Neck, Breast

Mount Sinai Medical Center

📌 Take-home message:

Risk factors inform evaluation — ultrasound and pathology drive decisions.

📚 References

Haugen BR et al. ATA Guidelines for Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid Schneider AB et al. Radiation exposure and thyroid cancer. J Clin Endocrinol Metab SEER Cancer Statistics Review

Byers RM, Weber RS, Andrews T, McGill D, Kare R, Wolf P. Frequency and therapeutic implications of “skip metastases” in the neck from squamous carcinoma of the oral tongue. Head Neck. 1997 Jan;19(1):14-9. doi: 10.1002/(sici)1097-0347(199701)19:1<14::aid-hed3>3.0.co;2-y. PMID: 9030939.

• Background: 
  • Supraomohyoid neck dissection (Levels I, II, III):
  • Is an adequate operation for the elective treatment of the neck for patients with oral cavity cancer
• Squamous cell carcinoma of the oral tongue:
  • Metastasize to clinically negative nodes:
    • In 20% to 30% of patients:
      • These nodes usually are located in:
        • Levels I to III
• Methods:
  • The medical records of 277 previously untreated patients with squamous cell carcinoma of the oral tongue were reviewed between the years 1970 and 1990
  • All patients had a glossectomy and neck dissection as part of their initial treatment
  • Patients were evaluated as to the findings in their neck
  • The following group of patients were included:
    • Patients who had level III nodes positive, without disease in levels I and II
    • Patients with disease in level IV
    • Patients with disease in level IIB or IIIB
    • Patients who were electively dissected and whose neck did not demonstrate any pathologically involved nodes:
      • But level IV was not included in the dissection and the patient subsequently developed pathologically positive nodes in level IV
• Results: 
  • Of all patients:
    • 15.8% had either level IV metastasis as the only manifestation of disease in the neck or the level III node was the only node present without disease in level I to II
• Conclusion: 
  • The usual supraomohyoid neck dissection is inadequate for a complete pathologic evaluation of all the nodes at risk for patients with squamous carcinoma of the oral tongue
  • This may create a dilemma in determining whether postoperative radiotherapy is necessary
  • Consequently, all patients with squamous cell carcinoma of the oral tongue should have levels I to IV nodes (Extended Supraomohyoid Neck Dissection) removed if an elective neck dissection is part of their initial therapy

Extended Endocrine Therapy in Very Young (≤40) Node-Positive HR+ Early Breast Cancer

Very young, node-positive, hormone receptor–positive (HR+) early breast cancer patients represent a uniquely high-risk subgroup, largely driven by persistent ovarian function and aggressive tumor biology. Emerging long-term data suggest that patients who remain premenopausal after completing 5 years of ovarian function suppression (LHRHa)–based endocrine therapy may derive clinically meaningful benefit from extended endocrine treatment.

In this population, extended endocrine therapy was associated with:

Improved invasive breast cancer–free survival (IBCFS) • 5-year IBCFS: 85% vs 78% • Hazard ratio (HR): 0.63, indicating a 37% relative risk reduction Improved distant recurrence–free survival (DRFS) • 5-year DRFS: 91% vs 83% • HR: 0.49, corresponding to a 51% relative reduction in distant relapse

Importantly, these efficacy gains were achieved without a major increase in long-term toxicity. Rates of fractures and cardiovascular events remained low (~1%), reinforcing the favorable therapeutic index of prolonged endocrine therapy in carefully selected young patients.

Clinical Implications

Chronologic age ≤40 years, node-positive disease, and persistent premenopausal status after 5 years identify a subgroup with sustained estrogen-driven recurrence risk. Extended endocrine therapy should be actively discussed in this setting, with shared decision-making that incorporates: Residual recurrence risk Tolerance of prior endocrine therapy Bone health and cardiovascular risk monitoring These data further support a risk-adapted, biologically driven approach to endocrine duration rather than a fixed 5-year strategy in very young patients.

Key References

Pagani O, et al. Long-term outcomes of adjuvant endocrine therapy in premenopausal women with hormone receptor–positive breast cancer. New England Journal of Medicine. 2014;371:107–118. Francis PA, et al. Tailoring adjuvant endocrine therapy for premenopausal breast cancer. New England Journal of Medicine. 2018;379:122–137. Regan MM, et al. Extended follow-up of the SOFT and TEXT trials: recurrence patterns and long-term toxicity. Journal of Clinical Oncology. 2022;40:3697–3708. Burstein HJ, et al. Endocrine therapy for hormone receptor–positive breast cancer: ASCO guideline update. Journal of Clinical Oncology. 2023.

Thyroid cancer is one of the most treatable cancers—and outcomes are excellent for the vast majority of patients.

📈 Survival in perspective

Overall 5-year survival >98% for most differentiated thyroid cancers Papillary thyroid cancer (the most common type) has >95% long-term survival Many patients live normal, full lives after treatment

🧠 What drives these excellent outcomes?

Several factors work in patients’ favor:

Slow tumor growth for most thyroid cancers Early detection with high-resolution ultrasound Accurate risk stratification (ATA / TI-RADS) Highly effective surgery when indicated Selective use of radioactive iodine and tailored follow-up

⚖️ Modern management matters

Today, thyroid cancer care focuses on:

✔️ Avoiding overtreatment for low-risk disease

✔️ Escalating treatment only when biology and risk justify it

✔️ Preserving quality of life without compromising cure

🦋 What this means for patients

A thyroid cancer diagnosis is serious—but not all thyroid cancers are the same.

The key is individualized, evidence-based care by an experienced team.

👨‍⚕️ Dr. Rodrigo Arrangoiz, MD

Surgical Oncologist – Thyroid, Head & Neck, Breast

Mount Sinai Medical Center

📌 Take-home message:

With proper evaluation and treatment, most patients with thyroid cancer do extremely well.

📚 References

SEER Cancer Statistics Review Haugen BR et al. ATA Guidelines for Differentiated Thyroid Cancer. Thyroid Tuttle RM et al. Risk-Adapted Management of Thyroid Cancer. Lancet Diabetes Endocrinol

• Surgical excision of an area of atypical duct hyperplasia (ADH) found on core needle biopsy:
  • Is recommended to rule out underlying occult breast cancer:
    • Which can be found in 15% to 30% of patients
• Studies consistently show higher rates of upgrade to DCIS (2/3 of the cases) compared to invasive carcinoma (1/3 of the cases)
• A multivariable model assessing predictors for risk of upgrade at the time of excision of ADH found that:
  • Lesions that were less than 50% removed by core biopsy, compared to those with greater than 90% removed:
    • Had a significantly higher risk of upgrade (OR 3.8)
  • Similarly, ADH with individual cell necrosis (OR 4.3) and with multiple foci of atypia on core biopsy (OR 2-3 foci 2.1; OR >3 foci 3.6 compared to 1 foci) were more likely to have a subsequent upgrade
• ADH is associated with an increased risk of future development of breast cancer when identified on a core needle biopsy or at time of surgery:
  • With a relative risk of approximately 4
• Increasing number of foci of atypia:
  • Has also been reported to be associated with increasing future breast cancer risk
• A study by Degnim and colleagues combined outcomes for women with a history of atypical hyperplasia from the Mayo Clinic and the Nashville Cohort:
  • In the combined analysis, among women with ADH, the relative risk of breast cancer was 2.65 with 1 foci, 5.19 with 2 foci, and 8.94 with >3 foci, p<.001
• As the vast majority of subsequent cancers in this population are estrogen positive:
  • Patients with ADH may benefit from chemoprevention as demonstrated in the NSABP P-1 study:
    • Which demonstrated a 49% reduction in the development of invasive breast cancer in high-risk patients with the use of tamoxifen compared to placebo (p<0.00001), with the greatest benefit seen in women with atypical hyperplasia or lobular carcinoma in situ:
      • However, tamoxifen did not effect overall survival
• References
  • Mooney K, Bassett LW, Apple SK. Upgrade rates of high-risk breast lesions diagnosed on core needle biopsy: a single-institution and literature review. Modern Pathol. 2016;29(12):1471-1484.
  • Pena A, Shah SS, Fazzio RT, Hoskin TL, Brahmbhatt RD1, Hieken TJ, at al. Multivariate model to identify women at low risk of cancer upgrade after a core needle biopsy diagnosis of atypical ductal hyperplasia. Breast Cancer Res Treat.2017;164(2):295-304.
  • Hartmann LC, Degnim AC, Santen RJ, Dupont WD, Ghosh K. Atypical hyperplasia of the breast – risk assessment and management options. NEJM. 2015;372(1):78-89.
  • Degnim AC, Dupont WD, Radisky DC, et al. Extent of atypical hyperplasia stratifies breast cancer risk in 2 independent cohorts of women. Cancer. 2016;122(19):2971-2978.