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• The 15.8% skip metastasis rate reported by Byers et al. (1997):
  • Is widely considered an overestimate due to several important methodological issues that have been carefully dissected in subsequent literature:
    • Most notably by Warshavsky et al. in their 2019 JAMA Otolaryngology meta-analysis [1][2]
• What Byers Reported:
  • Byers et al. reviewed 277 previously untreated patients with oral tongue SCC (1970 to 1990):
    • Who underwent glossectomy and neck dissection
  • They reported that 15.8% of all patients had either:
    • Level IV metastasis as the only manifestation of neck disease
    • Level III as the only positive node without disease in levels I to II
    • Subsequent level IV recurrence after initial dissection that did not include level IV
  • Based on this, they recommended routine dissection of levels I to IV for all oral tongue SCC [2]
• Why the 15.8% Figure Is Misleading:
  • Warshavsky et al. performed a careful reanalysis of the Byers data and identified several critical flaws that inflated the rate [1]:
    • Conflation of skip metastasis definitions:
      • Byers combined true level IV skip metastasis with level III skip metastasis (level III positive without levels I to II involvement):
        • These are fundamentally different clinical scenarios — level III disease is already captured by a standard supraomohyoid neck dissection (levels I to III)
        • By lumping both together, the rate was artificially elevated
    • Inclusion of neck recurrences as “skip metastases”:
      • Nine patients (9.9%) who developed level IV recurrences after an initial dissection that did not include level IV were counted toward the 15.8% figure:
        • As Warshavsky et al. noted, counting neck recurrence as a missed pathological lymph node is problematic because the neck has lost its normal anatomical lymphatic drainage and, in many cases, has been irradiated
        • This makes it impossible to determine whether these were true skip metastases or recurrences from altered lymphatic flow [1]
    • True level IV skip metastasis rate was only 5.5%:
      • When the data are restricted to patients with cN0 disease who had level IV metastasis found in the initial neck dissection specimen (i.e., true pathologic skip metastasis):
        • The rate drops to 5.5% — roughly one-third of the reported figure [1]
      • Even the most generous calculation yields only 4.8%:
        • When accounting for all cases mentioned in the study (both initial pathologic findings and subsequent recurrences), the combined incidence of skip metastasis or subsequent recurrence in level IV was only 4.8% (13 of 270), not 15.8% [1]
  • Mixed cN0 and cN+ populations:
    • The study included patients across all clinical N stages, and the data were not clearly stratified by preoperative nodal status, making it difficult to isolate the true elective (cN0) skip metastasis rate
  • Era of the study (1970 to 1990):
    • Preoperative imaging was far less sophisticated, meaning some patients classified as cN0 may have had undetected nodal disease, further confounding the results
• What Modern Data Shows:
  • The Warshavsky et al. meta-analysis of 13 studies (1,359 cN0 patients):
    • Found the true skip metastasis rate to level IV is only 0.50% (95% CI, 0.09%–1.11%):
      • With an overall level IV involvement rate of 2.53% [1]
    • Even for oral tongue specifically — the highest-risk subsite:
      • The level IV involvement rate was 3.60% [1]
  • A large Tata Memorial audit of 761 early-stage cN0 patients:
    • Found skip metastasis to level IV in only 0.3% [3]
• In summary, the Byers 15.8% figure resulted from a broad definition of “skip” that included level III skips (already addressed by SOHND), conflation of initial pathologic findings with subsequent recurrences, and lack of stratification by preoperative nodal status:
  • Modern evidence overwhelmingly supports that true skip metastasis to level IV in cN0 oral tongue SCC is a rare event (~0.5%), and supraomohyoid neck dissection (levels I to III) remains adequate for the elective setting
• References:
  • 1. Assessment of the Rate of Skip Metastasis to Neck Level IV in Patients With Clinically Node-Negative Neck Oral Cavity Squamous Cell Carcinoma: A Systematic Review and Meta-analysis. Warshavsky A, Rosen R, Nard-Carmel N, et al. JAMA Otolaryngology– Head & Neck Surgery. 2019;145(6):542-548. doi:10.1001/jamaoto.2019.0784.
  • 2. Frequency and Therapeutic Implications of “Skip Metastases” in the Neck From Squamous Carcinoma of the Oral Tongue. Byers RM, Weber RS, Andrews T, et al. Head & Neck. 1997;19(1):14-9. doi:10.1002/(sici)1097-0347(199701)19:13.0.co;2-y.
  • 3. Incidence and Impact of Skip Metastasis in the Neck in Early Oral Cancer: Reality or a Myth?. Gurmeet Singh A, Sathe P, Roy S, et al. Oral Oncology. 2022;135:106201. doi:10.1016/j.oraloncology.2022.106201.

• Epidemiology:
  • The tall cell subtype of papillary thyroid carcinoma (PTC-TC):
    • Accounts for approximately 3% to 5% of all PTCs
      • Its incidence has been rising:
        • Partly due to evolving diagnostic criteria
  • The WHO 5th edition (2022) defines PTC-TC as:
    • PTC with ≥ 30% tall cells:
      • Height-to-width ratio ≥ 3:1
  • Patients tend to be older:
    • Mean ~ 50 years vs. 42 for classic PTC
  • PTC-TC have higher rates of:
    • Extrathyroidal extension (~ 60%)
    • Vascular invasion (~ 15%)
    • Lymph node metastasis
    • Advanced stage at presentation
  • Recurrence rates range from:
    • 27% to 42% compared to 16% to 31% for classic PTC
  • 5-year disease-specific survival of:
    • Approximately 82% vs. 98% for all PTC
  • An important recent distinction is:
    • Between PTC-TC (without high-grade features) and high-grade differentiated thyroid carcinoma with tall cell phenotype (HGDTC-TC):
      • Defined by ≥ 5 mitoses / 2 mm² and / or tumor necrosis
        • When HGDTC-TC is excluded PTC-TC has a more indolent course (10-year disease-specific survival ~99%)
• Genetics and Molecular Features:
  • BRAF V600E mutation:
    • Present in ~ 80% to 90% of cases:
      • Drives MAPK pathway activation and suppresses sodium-iodide symporter expression:
        • Contributing to RAI refractoriness
  • TERT promoter mutations:
    • Independent predictor of recurrence:
      • More frequent in PTC-TC
  • BRAF V600E + TERT co-mutation:
    • Identifies a subset with particularly poor outcomes
• Surgical Management:
  • Type of Thyroidectomy:
    • Standard indications for total thyroidectomy apply:
      • Distant metastases
      • Extrathyroidal extension
      • Lateral or gross central neck node metastases
      • Tumor > 4 cm
      • Bilateral disease
    • For tumors 1 cm to 4 cm without these features:
      • Either total thyroidectomy or lobectomy may be considered
  • Key evidence:
    • A 2026 SEER analysis of 1,463 PTC-TC patients showed total thyroidectomy had superior cancer-specific survival vs. lobectomy:
      • 5-year CSS 97.8% vs. 90.7%, p = 0.019, independent of RAI
    • A Memorial Sloan Kettering study of T1 / T2 N0 PTC-TC:
      • Found no difference in outcomes with lobectomy alone, with 100% disease-specific survival in both groups
  • Summary:
    • For small (T1 / T2), node-negative PTC-TC without high-grade features:
      • Lobectomy may be adequate
    • Larger or higher-stage tumors:
      • Should undergo total thyroidectomy
• Central Compartment Neck Dissection:
  • Therapeutic central neck dissection:
    • Recommended for clinically involved nodes (cN1a)
  • Prophylactic central neck dissection:
    • Not routinely indicated per NCCN
  • Thorough preoperative ultrasound of central and lateral compartments is essential:
    • With FNA of suspicious lateral nodes
• Radioactive Iodine (RAI):
  • NCCN classifies tall cell histology as a “high-risk subtype”:
    • For which RAI is selectively recommended based on the combination of clinical factors
  • PTC-TC is classified in the ATA intermediate risk category
  • Key considerations:
    • BRAF V600E-driven PTC-TC downregulates the sodium-iodide symporter:
      • Making these tumors frequently RAI-refractory
    • For tumors > 2 cm:
      • RAI after total thyroidectomy improved overall survival:
        • 83.4% vs. 70.0%
    • For tumors ≤ 2 cm:
      • No survival benefit from RAI was demonstrated
    • A SEER-based propensity-matched study:
      • Found no significant CSS benefit from RAI in PTC-TC overall:
        • HR 0.54, 95% CI 0.25–1.17
    • Repeated RAI should be limited to patients demonstrating continued therapeutic response
• Follow-Up:
  • After total thyroidectomy with RAI, recommended surveillance includes:
    • Physical examination, TSH, thyroglobulin (Tg), and anti-thyroglobulin antibodies (TgAb)
    • Neck ultrasound at 6 to 12 months, then every 1 to 3 years for 5 to 8 years, then discontinue
  • Rising Tg or new TgAb:
    • Should prompt additional imaging:
      • Neck CT / MRI, chest / abdomen CT, FDG-PET, or RAI imaging
  • TSH suppression with levothyroxine:
    • Per risk stratification
  • For patients with no evidence of disease (NED) at low risk after 10 to 15 years:
    • No further thyroid cancer monitoring is indicated
• RAI-Refractory Disease:
  • For RAI-refractory progressive disease:
    • Molecular analysis for actionable alterations should be pursued:
      • BRAF V600E → dabrafenib / trametinib or vemurafenib / cobimetinib
      • RET fusions → selpercatinib or pralsetinib
      • NTRK fusions → larotrectinib or entrectinib
      • ALK fusions → targeted therapy
• References:
  • Shi X, Liu R, Basolo F, et al. Differential Clinicopathological Risk and Prognosis of Major Papillary Thyroid Cancer Variants. J Clin Endocrinol Metab. 2016.
  • Wu SS, Joshi N, Sharrett J, et al. Risk Factors Associated With Recurrence and Death in Patients With Tall Cell Papillary Thyroid Cancer. JAMA Otolaryngol Head Neck Surg. 2023.
  • Holoubek SA, MacKinney EC, Khokar AM, et al. Radioactive Iodine Does Not Improve Overall Survival for Patients With Aggressive Variants of Papillary Thyroid Carcinoma Less Than 2 Cm. Surgery. 2022.
  • Jin X, Koga S, Zhou X, Khan NZ, Baloch ZW. Clinicopathologic Characteristics of Papillary Thyroid Carcinoma, Tall Cell Subtype and Subtype With Tall Cell Features, an Institutional Experience. Hum Pathol. 2025.
  • Parvathareddy SK, Siraj AK, Qadri Z, et al. Tall Cell Variant Histology Predicts Poorer Disease-Free Survival in Papillary Thyroid Carcinoma: A Propensity-Matched Cohort Study. World J Surg. 2025.
  • Ghossein R, Katabi N, Dogan S, et al. Papillary Thyroid Carcinoma Tall Cell Subtype (PTC-TC)
    
    
    

• For patients diagnosed with asymptomatic primary hyperparathyroidism (PHPT – 5% of the cases):
  • Additional evaluation is necessary to make subsequent management decisions
• In order to make management recommendations for patients with asymptomatic PHPT, I usually send the following studies:
  • Urinary calcium excretion
  • Serum 25-hydroxyvitamin D
  • Serum creatinine and estimated glomerular filtration rate (eGFR):
    • To assess for renal compromise
  • Bone density to determine if it is low
  • I some situations I will also get the following imaging studies:
    • Ultrasound of the kidneys to assess for occult kidney stones
    • Spine to assess for asymptomatic vertebral compression fracture
• The Fourth International Workshop guidelines recommended further assessment to help in the decision regarding surgery for PHPT:
  • This includes renal imaging (plain radiographs or ultrasound) to determine if the patient has a clinically silent kidney stone and vertebral imaging (spine radiograph or vertebral fracture assessment [VFA] of dual-energy x-ray absorptiometry [DXA] image) for subclinical vertebral fracture
  • Urinary stone risk profile is also recommended:
    • But only if urinary calcium excretion is extremely elevated (> 400 mg/day) and a patient is unsure about parathyroid surgery
      • However, these tests are more expensive, may not be readily available to all clinicians, and there are few data to support their role in managing patients with PHPT
• Urinary calcium excretion:
  • In asymptomatic patients:
    • The urinary calcium excretion is helpful to assess the risk of renal complications (when urine calcium is high) and thus determine subsequent management
  • The Fourth International Workshop on Asymptomatic Primary Hyperparathyroidism guidelines recommended surgical intervention as opposed to observation in asymptomatic patients who have:
    • A 24-hour urinary calcium excretion greater than 400 mg/day (> 10 mmol/day)
      • It should be noted that urinary calcium levels are considered to be elevated at a significantly lower level of excretion (250 mg/24 hours in women and 300 mg/24 hours in men):
        • There are no specific data assessing the cut-point of 400 mg calcium excretion daily
          • This particular recommendation reflected expert opinion regarding a level above which there is consensus that patients should be sent for surgery even in the absence of other criteria
• Serum vitamin D:
  • I measure serum 25(OH)D in all patients with suspected or diagnosed PHPT
  • Measurement of 25(OH)D is important:
    • To identify patients with PHPT and vitamin D deficiency (which is a significant proportion of patients)
  • Due to the significant prevalence of vitamin D insufficiency in individuals with PHPT:
    • The Fourth International Workshop on Asymptomatic Primary Hyperparathyroidism recommended measuring 25(OH)D in all patients with the disease and repleting those with low levels (defined as ≤ 20 ng/mL [50 nmol/L]) prior to making any management decisions:
      • Specially if calcium levels are within the normal range
      • In some cases, the decision regarding surgery will be clear despite the low vitamin D level:
        • In such patients, it is still advisable to replete vitamin D if this can be done safely:
          • In order to mitigate postoperative hypocalcemia
• Serum creatinine:
  • The serum creatinine concentration provides information about renal function:
    • Which can be diminished by hypercalcemia
  • Rather than using serum creatinine alone, the eGFR can be estimated in patients with a stable serum creatinine concentration:
    • An eGFR of 60 mL/min is the threshold of chronic kidney disease for deciding:
      • Which asymptomatic individuals with PHPT may benefit from early surgical treatment
• Renal imaging:
  • In several studies, clinically silent kidney stones were reported in 7%to 21% of patients with PHPT:
    • Patients with undiagnosed (subclinical) nephrocalcinosis or calcium kidney stones:
      • Are regarded as having symptomatic disease:
        • Regardless of the absence of symptoms
      • Thus, these patients meet criteria for surgical intervention
  • For the few patients who do not have other overt indications for surgery:
    • Obtaining renal imaging (ultrasound, computed tomography [CT], or abdominal radiograph):
      • To look for nephrocalcinosis or asymptomatic nephrolithiasis at the time of the original evaluation for PHPT
        • Ultrasound is typically the imaging modality used
• Bone mineral density:
  • Patients with PHPT may have decreased bone mineral density (BMD):
    • In particular at more cortical sites (forearm and hip) as compared with more trabecular (cancellous) sites (spine)
  • Although measurement of BMD is not required for the diagnosis of PHPT:
    • It is an essential part of the management of the disease:
      • BMD must be measured at the:
        • Spine, hip, and distal one-third forearm sites
  • The degree of bone loss:
    • Is reflective of the severity of hyperparathyroidism and is useful for making recommendations for parathyroid surgery or observation with monitoring in asymptomatic patients (minority of the cases)
• Assessment for vertebral fracture:
  • Patients with subclinical, idiopathic vertebral compression fractures are regarded as having osteoporosis:
    • Independent of BMD findings
  • Vertebral compression fractures are underdiagnosed in all populations:
    • Many studies have demonstrated an increased risk of asymptomatic vertebral fractures in patients with PHPT
  • In order to diagnose asymptomatic vertebral compression fractures:
    • The Fourth International Workshop guidelines recommended imaging to assess for vertebral fracture in asymptomatic patients who do not have osteoporosis on BMD testing (patients with clinical osteoporotic fractures or with BMD in the osteoporosis range already meet criteria for surgery):
      • If a vertebral fracture is present by VFA or radiograph:
        • Parathyroidectomy is recommended
      • Vertebral assessment can be performed with plain radiographs or with VFA by DXA:
        • The latter can be done at the time of BMD testing, at greater patient convenience, less cost, and lower radiation exposure than conventional radiography of the spine
• Other tests:
  • Biochemical renal stone prediction:
    • For asymptomatic patients with hypercalciuria (> 400 mg/day [10 mmol/day]):
      • The Fourth International Workshop Guidelines on the Management of Asymptomatic Primary Hyperparathyroidism recommended:
        • Assessment of the urine composition to identify patients at highest risk for nephrolithiasis [32]:
          • There are no specific data to suggest that urine stone risk profiling can predict risk of nephrolithiasis in patients with PHPT
          • Some experts believe that urinary calcium excretion > 400 mg/day alone raises sufficient enough concern about long-term renal complications to warrant a recommendation for parathyroidectomy
    • If an asymptomatic patient with a urinary calcium >400 mg/day is unsure about proceeding to surgery, a stone risk profile might provide useful information for making a decision about surgery. (See “The first kidney stone and asymptomatic nephrolithiasis in adults”.)

For asymptomatic patients at high risk for nephrolithiasis (24-hour urinary calcium >400 mg and high-risk urinary biochemical profile), the Fourth International Workshop guidelines recommended parathyroidectomy [32]. (See “Primary hyperparathyroidism: Management”, section on ‘Candidates for surgery’.)

Serum phosphorus — The serum phosphorus concentration may be decreased but typically is in the lower range of normal. Some patients have mild hyperchloremic acidosis. (See “Primary hyperparathyroidism: Clinical manifestations”.)

Markers of bone turnover — Biochemical markers of bone turnover (collagen crosslinks, osteocalcin, bone-specific alkaline phosphatase) are often at the upper end of normal or mildly elevated in asymptomatic PHPT (see “Bone physiology and biochemical markers of bone turnover”). In those with more severe disease, they are typically high. They are only occasionally helpful in the management of hyperparathyroidism and should not be routinely measured [8].

Localization studies — The diagnosis of PHPT is established by appropriate biochemical testing. Localization studies with ultrasonography, technetium-99m sestamibi, CT, or magnetic resonance imaging (MRI) scanning should not be used to establish the diagnosis of PHPT or to determine management. Localization studies should be performed only after a decision for surgery has been made. Their utility is questionable when bilateral neck exploration is planned. However, they are commonly used now, along with intraoperative parathyroid hormone (PTH) monitoring, to facilitate unilateral exploration and minimally invasive surgery in those with probable single gland disease. (See “Preoperative localization for parathyroid surgery in patients with primary hyperparathyroidism”.)

• The 10 signs of malignancy include:
  • Shadowing
  • Hypoechoic echotexture
  • Spiculation
  • Angular margins
  • Thick echogenic halo
  • Microlobulation
  • Taller than wide dimensions
  • Duct extension
  • Branching pattern
  • Calcifications
• Well-defined smooth border and posterior acoustic enhancement:
  • Are found in both malignant and nonmalignant lesions
• Layering / teacup mammographic microcalcifications:
  • Are usually associated with benign disease
• Sonographic mass with a benign mammographic imaging:
  • Is managed based on ultrasound features

• References
  • Evaluation and imaging features of malignant breast masses. In: Cardenosa G. Clinical Breast Imaging: The Essentials. Philadelphia, PA: Wolters Kluwer; 2015:234-282.
  • Stavros AT. Breast Ultrasound. Philadelphia, PA: Lippincott Williams & Wilkins; 2004.

• While all patients with symptomatic primary hyperparathyroidism (PHPT) should consider surgery (95% of patients are usually symptomatic when appropriate history is taken):
  • It is also indicated in some asymptomatic patients (5% of the cases of PHPT):
    • Indications:
      • Age less than 50
      • Kidney disease:
        • GFR less than 60
      • Osteoporosis
      • Serum calcium greater than 1 mg/dl above normal
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5393490/

#Arrangoiz #ParathyroidSurgeon #ParathyroidExpert #Hyperparathyroidism #PrimaryHyperparathyroidism #CancerSurgeon #EndocrineSurgery #Teacher #Surgeon #HeadandNeckSurgeon #SurgicalOncologist #ParathyroidAdenoma #Hypercalcemia #ElevatedCalciumLevels #Miami #MountSinaiMedicalCenter #MSMC #Mexico #Hialeah

👉The overproduction of parathyroid hormone (PTH), termed hyperparathyroidism (HPT), can be categorized as primary, secondary, or tertiary.

👉Primary hyperparathyroidism (PHPT) arises from an unregulated overproduction of PTH from an abnormal parathyroid gland.

👉Increased PTH levels may also occur as a compensatory response to hypocalcemic states resulting from chronic renal failure or gastrointestinal (GI) malabsorption of calcium. This secondary HPT can be reversed by correction of the underlying problem (e.g., kidney transplantation for chronic renal failure).

👉However, chronically stimulated parathyroid glands may occasionally become autonomous, resulting in persistence or recurrence of the hypercalcemia after successful renal transplantation, resulting in tertiary HPT. This review paper will focus on PHTP

#Arrangoiz #ParathyroidSurgeon #ParathyroidExpert #Hyperparathyroidism #EndocrineSurgery #Hypercalcemia #MountSinaiMedicalCenter #MSMC #Miami #Mexico

Follow-Up After Curative Treatment for Stage I–III Breast Cancer

The 2026 ASCO guideline emphasizes risk-adapted survivorship care while reaffirming that routine imaging and laboratory testing to detect distant recurrence do not improve survival in asymptomatic patients.

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1. History and Physical Examination

Clinical follow-up should be individualized according to recurrence risk, treatment received, patient preferences, and survivorship needs.

Recommended schedule:

• Years 1–3: Every 3–6 months
• Years 4–5: Every 6–12 months
• After 5 years: Annually

Each visit should include:

• Interval history
• Breast/chest wall examination
• Regional lymph node examination
• Evaluation for signs or symptoms of recurrence
• Assessment of treatment-related toxicities (lymphedema, neuropathy, menopausal symptoms, cardiotoxicity, bone health)
• Review of endocrine therapy adherence when applicable
• Counseling regarding healthy lifestyle, exercise, weight management, alcohol moderation, and smoking cessation

Virtual follow-up visits may be appropriate for selected patients.

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2. Breast Imaging

After Breast-Conserving Surgery

• First mammogram 6–12 months after completion of radiation therapy (or approximately 1 year after the preoperative mammogram if radiation is omitted).
• Annual mammography thereafter.

After Unilateral Mastectomy

• Annual mammography of the contralateral breast.

After Bilateral Mastectomy

• Routine mammography is not recommended.

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3. Breast MRI

Routine MRI surveillance is not recommended.

MRI should be reserved for patients who meet established high-risk screening criteria, including:

• BRCA1 or BRCA2 mutation
• TP53 or PALB2 mutation
• Lifetime breast cancer risk ≥20–25%
• Selected patients with very dense breasts and high genetic risk

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4. Imaging for Distant Recurrence

Routine imaging is not recommended in asymptomatic patients.

Do not routinely obtain:

• CT scans
• PET/CT
• Bone scan
• Liver ultrasound
• Chest radiograph
• Brain MRI

These studies should only be performed when symptoms, physical examination, or laboratory findings suggest recurrence.

---

5. Laboratory Testing

Routine laboratory surveillance is not recommended.

Do not routinely obtain:

• Complete blood count (CBC)
• Comprehensive metabolic panel (CMP)
• Liver function tests
• Alkaline phosphatase

unless clinically indicated.

---

6. Tumor Markers

Routine measurement of serum tumor markers is not recommended.

Do not routinely obtain:

• CA 15-3
• CA 27.29
• CEA

in asymptomatic patients.

---

7. Circulating Tumor DNA (ctDNA)

Routine surveillance with circulating tumor DNA (ctDNA) is not recommended outside of clinical trials, as current evidence has not demonstrated an improvement in survival or quality of life when molecular recurrence is detected before clinical recurrence.

---

8. Survivorship Care

Survivorship visits should include:

• Management of endocrine therapy adherence
• Assessment of long-term toxicities
• Lymphedema screening
• Bone health assessment
• Cardiovascular risk reduction
• Exercise counseling
• Weight management
• Smoking cessation
• Alcohol moderation
• Psychosocial support
• Sexual health counseling
• Coordination with the primary care physician

---

Key Recommendations

• History and physical examination: Every 3–6 months for years 1–3, every 6–12 months for years 4–5, then annually.
• Annual mammography remains the only recommended routine surveillance imaging.
• Routine CT, PET/CT, bone scan, MRI, ultrasound, or chest X-ray are not recommended in asymptomatic patients.
• Routine CBC, chemistry panels, liver function tests, and tumor markers (CA 15-3, CA 27.29, CEA) are not recommended.
• Routine ctDNA surveillance is not recommended outside clinical trials.
• Follow-up should be individualized according to recurrence risk and survivorship needs, with increasing emphasis on healthy lifestyle interventions and management of treatment-related toxicities.

Reference:
Runowicz CD, et al. ASCO Guideline Update: Breast Cancer Follow-Up and Management After Primary Treatment. Journal of Clinical Oncology. 2026.

• Differential Diagnosis of Hypercalcemia:Primary hyperparathyroidism:Solitary adenoma:85% to 90% of the cases
  • • Multigland Disease:Multigland hyperplasia:3% of the cases
      • Doble adenoma:6% to 9% of the cases
      • Triple adenoma:0.3% of the cases
  • Secondary hyperparathyroidism
  • Tertiary hyperparathyroidism
  • Familial hypocalciuric hypercalcemia
  • Medications:
    • Lithium
    • Hydrochlorothiazide
  • Malignancy:
    • Parathyroid carcinoma
    • Multiple myeloma
    • Tumors producing PTH-related peptide:Ovarian cancer
      • Lung cancer
    • Acute or chronic leukemia
  • Granulomatous diseases:
    • Sarcoidosis, histioplasmosis, tuberculosis
  • Thyrotoxicosis
  • Paget disease
  • Increased intake:
    • Milk-alkali syndrome
    • Vitamin A toxicity
    • Vitamin D toxicity

• Primary hyperparathyroidism (PHPT):Is caused by an inappropriate, autonomous  secretion of parathyroid hormone (PTH) by the parathyroid gland(s):Which leads to an elevated serum calcium concentration or wide variations of the serum calcium concentration
  • Single gland disease:Caused by a single, enlarged, overactive gland, is found in 85% to 90% of cases
  • Multiple gland disease occurs in 10% to 15% of the cases:Multiple gland disease may consist of:Double adenomas (6% to 9% of the cases)
    • • Four-gland hyperplasia (3% of the cases)
      • Three enlarged and one normal appearing gland (0.3% of the cases).Because asymmetric hyperplasia is common, it is difficult to distinguish between multiple adenomas and hyperplasia and the term multiple gland disease is preferred
  • PHPT in the United States usually presents quite early:Often when hypercalcemia is noted during routine laboratory testing
  • Signs may include:Nephrolithiasis, decreased bone density, and fragility fractures, and subjective symptoms may include fatigue, cognitive changes, depression, constipation and other gastrointestinal complaints, musculoskeletal pain, nocturia, and rarely pruritus:Many patients may appear asymptomatic:A detailed history often uncovers symptoms:95% of the cases have symptoms when appropriate history is taken:The recently revised guidelines for asymptomatic PHPT include a more extensive evaluation of the skeletal and renal systems
  • A family history of endocrine disorders should be investigated:As hyperparathyroidism alone can be familial or can present as a component of multiple endocrine neoplasia (MEN) types 1 and 2A

Medullary Thyroid Cancer (MTC) accounts for 1% to 2% of thyroid cancers in the United States.

• MTC is different from other types of thyroid cancers (which are derived from thyroid follicular cells – the cells that make thyroid hormone), because it originates from the parafollicular C cells (also called “C cells”) of the thyroid gland. These cells do not make thyroid hormone and instead make a different hormone called calcitonin.

MTC can, and frequently does, spread to lymph nodes and can also spread to other organs.

MTC is likely to run in families (inherited forms) in up to 25% of diagnoses, and inherited forms can be associated with other endocrine tumors, in syndromes called Multiple Endocrine Neoplasia (MEN) 2A and MEN 2B.

• In addition to MTC, patients with MEN2A may have tumors of the adrenal glands called pheochromocytomas or in the parathyroid glands (parathyroid adenomas). Patients with MEN2B, have MTC, pheochromocytomas and neuromas (typically a benign growth or tumor of nerve tissue) in the lining of the mouth and/ or gastrointestinal track.
• Patients with an inherited form of MTC usually have a mutation in a gene called the RET proto-oncogene. This mutation is present in all of the cells in their body (a germline mutation) and these mutations cause the development of MTC. This is important because in family members of a person with an inherited form of MTC, a blood test for a mutation in the RET protooncogene can lead to an early diagnosis of MTC and, to curative surgery to remove it. However, in the majority of patients (~ 75%) a germline mutation is not found – indicating that MTC is not an inherited or inheritable condition. In these cases, MTC is called sporadic.

Whether MTC is sporadic or familial can be determined by a blood test for the RET protooncogene. Anyone diagnosed with MTC should have this test run to determine whether the MTC is familial (meaning other family members may also have MTC that has not yet been diagnosed) or sporadic.

What are the Symptoms of Medullary Thyroid Cancer?

Medullary thyroid cancer usually presents as a lump or nodule in the thyroid. It may be noted by the patient or discovered during routine neck examination by the doctor. Sometimes, the nodule is discovered incidentally by imaging studies done for other unrelated reasons (CT of the neck, PET scan, or carotid ultrasound). The nodule may cause no symptoms, but in some cases the tumor may have spread to lymph nodes in the neck, which may be enlarged on physical examination.

Patients with advanced MTC may complain of pain in the neck, jaw, or ear. If a nodule is large enough to compress the windpipe or the esophagus, it may cause difficulty with breathing or swallowing. Hoarseness can be present if the cancer invades the nerve that controls the vocal cords.

MTC is usually more aggressive than the other more common types of thyroid cancer, and it is usually easier to treat and control if it is found before it spreads to lymph nodes in the neck or other parts of the body.

Thyroid function tests such as TSH are usually normal, even when MTC is present.

If you have a family history of MTC and have tested positive for the RET mutation, then you should see an endocrinologist to help determine how best to follow you or treat you.

How is Medullary Thyroid Cancer Diagnosed?

A diagnosis of thyroid cancer is usually made by a fine needle aspiration (FNA) biopsy of a thyroid nodule, or after the nodule is surgically removed. Patients in whom the results of an FNA biopsy (or histopathology) are suggestive or indicative of MTC should be further evaluated with measurement of the proteins calcitonin and carcinoembryonic antigen (CEA) in the blood, which are typically elevated in patients with MTC. These tests are useful to confirm the diagnosis of MTC which can help ensure the surgeon plans the correct surgery, and also serve as tumor markers during long-term follow-up to detect any remaining disease or recurrence of the cancer.

What is a RET Mutation?

The RET proto-oncogene is located on chromosome 10. A genetic mutation in the RET oncogene is seen in all cells in the body in patients with the hereditary forms of MTC. Mutations in RET can also be seen only in the tumor cells in patients with sporadic MTC. Since the discovery of the RET oncogene, more than 100 different mutations have been identified in the gene in patients with MTC.

Genetic counseling and testing for RET gene mutations should be offered to patients diagnosed with MTC and first-degree relatives (parents, siblings and children of someone diagnosed with MTC) of all patients with proven germline mutations (hereditary MTC). If close relatives, especially children, are found to have the RET mutation on a blood test, the thyroid gland can be removed before MTC has a chance to develop or at least in its very early stages.

How is Medullary Thyroid Cancer Treated?

The primary treatment for MTC is surgery, and the currently accepted approach is to remove the entire thyroid gland (total thyroidectomy) (See thyroid surgery brochure). Often patients with MTC will have thyroid cancer present in the lymph nodes of the neck or upper chest. These lymph nodes are usually removed at the time of thyroid surgery or sometimes, at a later surgery if found subsequently. After surgery, patients need to take thyroid hormone replacement medication for life.

Unlike papillary and follicular thyroid cancer, medullary thyroid cancer does not take up iodine, and consequently radioactive iodine treatment is not a treatment option for patients with MTC.

Patients with MTC with very high levels of calcitonin should have imaging prior to surgery to determine whether the tumor has spread to sites outside the thyroid and/or outside the neck. If there is evidence of cancer outside the neck, surgery may be more palliative, aimed at reducing local complications caused by the tumor, rather than completely eliminating all tumor. Other treatment options (external beam radiation, or chemotherapy) may need to be used together with surgery after careful discussion with the patient.

New chemotherapeutic agents that have shown promise treating other advanced cancers are increasingly available for treatment of thyroid cancers. Two such agents, Vandetanib and Cabozantinib have been FDA approved for use by patients with MTC. These drugs do not cure advanced cancers that have spread widely throughout the body, but they can often slow down or partially reverse the growth of the cancer. These treatments are usually given by an oncologist (cancer specialist) and require care at specialized medical centers.

What is the Follow-Up of Patients with Medullary Thyroid Carcinoma?

Periodic follow-up examinations are essential for all patients with MTC because the thyroid cancer can return, sometimes many years after successful initial treatment. These follow-up visits include a careful history and physical examination, with particular attention to the neck area. Neck ultrasound is also a very important tool to visualize the neck and look for nodules, lumps or enlarged lymph nodes that might indicate that the cancer has recurred.

Blood tests are also important in the follow-up of MTC patients. All patients who have had their thyroid glands removed require thyroid hormone replacement with levothyroxine. Thyroid stimulating hormone (TSH) should be checked periodically, and the dose of levothyroxine adjusted to keep TSH in the normal range. There is no need to keep TSH suppressed in patients with MTC.

Measurement of calcitonin and CEA are a necessary routine part of the follow-up of patients with MTC. Following thyroidectomy, it is hoped that calcitonin levels will be essentially undetectable for life. A detectable or rising calcitonin level should raise suspicion for possible cancer recurrence. Detectable calcitonin levels may require additional tests.

 

Rodrigo Arrangoiz MS, MD, FACS

• He is an expert in the management medullary thyroid carcinoma.

• Articles published on MTC:

  • https://www.gavinpublishers.com/articles/Review-Article/Journal-of-Clinical-Endocrinology-and-Diabetes/Medullary-Thyroid-Carcinoma-Literature-Review-and-Current-Management

  • http://www.remedypublications.com/american-journal-of-otolaryngology-and-head-and-neck-surgery/articles/pdfs_folder/ajohns-v1-id1026.pdf

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

#Arrangoiz

#Teacher

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#CancerSurgeon

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#HeadandNeckSurgeon

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#EndocrineSurgery

#CirujanodeCabezayCuello

• It is a surgical sub-specialty that deals mainly with benign and malignant tumors of the head and neck region, including:
  • The scalp, facial region, eyes, ears, nose, nasal fossae, paranasal sinuses, oral cavity, pharynx (nasopharynx, oropharynx, hypopharynx), larynx (supraglotic larynx, glottis larynx, subglotic larynx), thyroid gland, parathyroid gland, salivary glands (parotid glands, submandibular glands, sublingual glands, minor salivary glands), soft tissues of the neck, skin of the head and neck region.
• The head and neck surgeon’s work area:
  • Does not cover tumors or diseases of the brain and other areas of the central nervous system or those of the cervical spine:
    • This is the neurosurgeon field
• Among the diagnostic procedures performed by the head and neck surgeon, are the following:
  • Nasopharyngolaryngoscopy:
    • Performed to examine, evaluate and, possibly perform a biopsy, of oral cavity, pharyngeal and laryngeal lesions
• The surgeries most commonly performed by the head and neck surgeon are:
  • Total or near total thyroidectomies
  • Hemithryoidectomies (lobectomies)
  • Comprehensive neck dissections
  • Selective neck dissections
  • Maxillectomies:
    • Total maxillectomy
    • Subtotal maxillectomy
    • Infrastructure maxillectomy
    • Suprastructure maxillectomy
    • Medial maxillectomy
  • Mandibulectomy:
    • Segmental
    • Marginal
  • Tracheostomy
  • Salivary gland surgeries:
    • Parotid gland operations:
      • Limited superficial parotidectomy with identification and preservation of the facial nerve
      • Superficial parotidectomy with identification and preservation of the facial nerve
      • Near total parotidectomy with identification and preservation of the facial nerve
      • Total parotidectomy
    • Submandibular gland resection
    • Sublingual gland resection
  • Resection of tumors of the oral cavity:
    • Glossectomy
    • Resection of the floor of the mouth tumors
  • Resection of tumors of the pharynx
  • Resection of tumors of the larynx
  • Split-thickness skin grafts
  • Full-thickness skin grafts
  • Sentinel lymph node mapping and sentinel lymph node biopsy
  • Resection of malignant skin tumors (BCC, SCC, melanoma) of the head and neck region
• The training of the head and neck surgeon includes mastering the following subjects:
  • Surgical Anatomy
  • History and Basic Principles of Head and Neck Surgery
  • Epidemiology, Etiology, and Pathology of Head and Neck Diseases
  • Diagnostic Radiology of the Head and Neck Region
  • Tumors of the Scalp, Skin and Melanoma
  • Eyelids and Orbit
  • Nasal Cavity and Paranasal Sinuses
  • Skull Base and Temporal Bone
  • Lips and Oral Cavity
  • Pharynx and Esophagus
  • Larynx and Trachea
  • Cervical Lymph Nodes
  • Thyroid and Parathyroid Glands
  • Salivary Glands
  • Neurogenic Tumors and Paragangliomas
  • Soft Tissue Tumors
  • Bone Tumors and Odontogenic Lesions
  • Reconstructive Surgery
  • Oncologic Dentistry and Maxillofacial Prosthetics
  • Principles of Radiation Oncology
  • Principles of Chemotherapy
  • Molecular Oncology, Genomics and Immunology
  • Nutrition
  • Biostatistic

My name is Rodrigo Arrangoiz I am a board-certified surgical oncologist who sub-specializes in breast cancer and head and neck cancer. I earned his medical degree at the Anahuac University Medical School in Mexico City, Mexico and graduated Suma Cum Laude. I completed his internship and residency in general surgery at Michigan State University, where he was named chief resident during his fifth year of residency. I also completed a complex surgical oncology, head and neck fellowship at the Fox Chase Cancer Center in Philadelphia and at the same time he undertook a master’s in science (Clinical Research for Health Care Professionals) at Drexel University in Philadelphia. I participated in a two-year global online fellowship in head and neck surgery and oncology through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center.

I have participated in multiple courses and academic congresses as a lecturer and guest professor and has also participated in several publications on topics related to his specialty that include oral cavity cancer, hyperparathyroidism, thyroid cancer, breast cancer, endocrine tumors, squamous cell carcinoma of the head and neck, and more. I am board certified by the American Board of Surgery, the Mexican Board of General Surgery and the Mexican Board of Oncology.

I am a member of various medical associations such as the American College of Surgeons, American Thyroid Association, American Head and Neck Society, American Medical Association, American Society of Clinical Oncology, Association of Academic Surgeons, Society of Surgical Oncology, among others.

https://www.msmc.com/doctor/rodrigo-arrangoiz/

#Arrangoiz #HeadandNeckSurgeon #CancerSurgeon #SurgicalOncologist #MountSinaiMedicalCenter #MSMC #Mexico #Miami #ThyroidSurgeon #ParathyroidSurgeon