Medullary Thyroid Carcinoma Part 2

• Diagnosis:The diagnosis of medullary thyroid cancer (MTC):Is usually made after fine-needle aspiration (FNA) biopsy in a patient who has a solitary thyroid nodule (or a dominant nodule within a multinodular goiter):The sensitivity of FNA is 50% to 80%:Although higher sensitivity can be obtained by the addition of immunohistochemical staining for calcitoninIf the clinical suspicion for MTC is high:Patient with diarrhea, flushing, and a thyroid nodule):Calcitonin can be measured in the washout of the FNA biopsy needle:Although this may not be readily available in many commercial laboratoriesIn some cases:The diagnosis of MTC is made after thyroid lobectomy for a suspicious or indeterminate FNA biopsy:Surgical specimens from patients with MTC show:Spindle-shaped and frequently pleomorphic cells without follicle development:Because these cells originate from the calcitonin-producing parafollicular C cells of the thyroid
  • The use of serum calcitonin screening to complement ultrasound and FNA in the routine diagnosis of thyroid nodules is controversial in the United States:Measurement of serum calcitonin has not been a part of the routine evaluation of patients with thyroid nodules in the United States:The high frequency of falsely elevated serum calcitonin values, the inability to confirm the high calcitonin by pentagastrin stimulation in the United States, and the accuracy of FNA biopsy:Would argue against a change in this recommendation
    • • • Further, occasional patients with locoregional metastases or locally invasive MTC will have normal unstimulated serum calcitonin concentrations
        • In some countries (eg, European countries) where pentagastrin is available, however, serum basal and stimulated calcitonin levels are routinely used in the evaluation of thyroid nodules to facilitate the preoperative diagnosis of MTC

• Differential Diagnosis:The differential diagnosis in a patient presenting with a neck mass:Is extensive and varies with the age of the patient at presentationThe majority of these masses represent benign thyroid nodules and cysts
  • • Neck masses that are not of thyroidal origin may be from:Congenital:Vascular anomaly)Inflammatory:Lymph node enlargement)Other neoplastic:Primary or metastatic disease disorders
  • In addition to medullary thyroid cancer (MTC):Elevated calcitonin results may also be seen in patients with:Hypercalcemia
    • • Hypergastrinemia
      • Neuroendocrine tumors
      • Renal insufficiency
      • Papillary and follicular thyroid carcinomas
      • Goiter
      • Chronic autoimmune thyroiditis
    • Prolonged treatment with:Omeprazole (greater than two to four months)Beta blockersGlucocorticoids:Has been associated with hypercalcitoninemia
    • In addition, the presence of heterophilic antibodies to calcitonin:Can falsely elevate serum calcitonin levels 
  • Elevated carcinoembryonic antigen (CEA) levels can also occur in patients with:Heterophilic antibodiesGastrointestinal tract inflammatory diseaseBenign lung disease
    • Nonthyroid malignancies
    • Cigarette smoking
• Evaluation:For patients diagnosed with medullary thyroid cancer (MTC) on the basis of cytologic evaluation of a thyroid nodule:Evaluation should include:Measurement of serum calcitonin, carcinoembryonic antigen (CEA), ultrasonography of the neck (if not already performed), genetic testing for germline RET mutations, and biochemical evaluation for coexisting tumors, especially pheochromocytoma. Serum calcitonin and CEA:The serum calcitonin and carcinoembryonic antigen (CEA) concentrations should be measured in patients diagnosed with MTC on the basis of cytologic evaluation of a thyroid nodule:
  • • • • These tests can establish that the tumor is capable of hypersecreting the hormones and, if so, the values can be compared with postoperative values
      • Postoperatively:Results may provide a prognostic factor or indicate biochemical cure
    • In a study of 226 patients with MTC:Preoperative serum calcitonin concentrations:Where significantly correlated with tumor size in both the sporadic and familial casesIn addition, among 45 patients who had a preoperative serum calcitonin concentration of 50 pg/mL or less:44 had normal concentrations after surgery:In contrast, only 50 of 120 patients with preoperative serum calcitonin concentrations higher than 50 pg/mL had normal concentrations after surgery
    • In a second study of 224 patients with MTC:62% of patients without nodal metastases had normal calcitonin postoperatively:10% of node positive patients had normal postoperative calcitonin levels
    • Assessment of calcitonin and CEA doubling times postoperatively:Provides sensitive markers for progression and aggressiveness of metastatic MTC:Postoperative calcitonin doubling time was a prognostic factor for survival in a study of 65 patients followed for 3 to 30 years: Ten-year survival was: 8%, 37%, and 100% for doubling times:Under six months, between six months and 24 months, and greater than 24 months, respectively
  • Radiologic evaluation:MTC can spread by:Local invasion or metastasis:Within the neck or distantlyWhen MTC is diagnosed by fine-needle aspiration (FNA) biopsy:Ultrasonography of the neck is indicated to look for cervical lymph node involvementFor patients with local lymph node metastases on ultrasound or with preoperative serum basal calcitonin > 500 pg/mL (indicating high risk of local or distant metastatic disease):Additional imaging is required to assess for metastatic disease:In this setting, based con literature review I suggest cross-sectional imaging including:Chest computed tomography (CT)
    • • • • Neck CT with IV contast
          • Three-phase contrast-enhanced liver CT or contrast-enhanced liver magnetic resonance imaging (MRI)
          • Axial MRI, and bone scintigraphy:In patients suspected of having skeletal metastases:MRI may be superior to other imaging modalities
      • I do not recommend 18-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) imaging or somatostatin receptor imaging:For routine initial screening for metastatic disease:The sensitivity of FDG-PET scanning for detecting metastatic disease is variable:But improves with higher calcitonin levels:Sensitivity 78% versus 20% for basal calcitonin value greater than or less than 1000 pg/mL, respectively)
        • • The use of radionuclide imaging with 111-In-octreotide or 99m-Tc-DMSA:Is not currently recommended for routine initial screening for metastatic disease:However, three patients have been described who had regional and distant metastases of MTC detected by somatostatin receptor scintigraphy but not by CT scan
            • • How to select patients with a negative CT scan to undergo somatostatin receptor scintigraphy is not clear:Scanning may be more useful in localizing residual or recurrent disease after primary therapy
• Genetic screening in sporadic MTC:Germline RET testing:In all patients with newly diagnosed C cell hyperplasia or apparently sporadic MTC:Initial germline testing in patients with C cell hyperplasia or apparently sporadic MTC should include:Sequencing of exons 10, 11, and 13 through 16 of the RET gene
  • • • • Sequencing of the remaining exons in the RET gene should be considered in patients with:Clinical features or family history highly suggestive of hereditary medullary syndromes:Who demonstrate no mutations in exons 10, 11, or 13 through 16
        • While it is possible for clinicians to directly order genetic testing from reference laboratories:It is strongly encourage to have a consultation with genetic counselors who are familiar with both the ethical issues and legal informed consent requirements (which can vary significantly in different regions) that are involved in germline testing
  • When the index patient is positive for a germline mutation:Family members should be offered genetic counseling and genetic screening
  • An important question is what proportion of patients with apparently sporadic MTC have unsuspected germline mutations in the RET proto-oncogene (the underlying defect in MEN2) and, therefore, have heritable disease:Studies of unselected patients with MTC have found, on average:That approximately 6% to 7%  (range 1.5% to 24%) have germline RET mutationsIn one report:35 of 482 patients (7.3%) with apparently sporadic MTC had mutations, and in 18 of these 35:Gene carriers were identified in relatives
  • 75% of the familial medullary cases:Had no prior family history:A much higher percentage (approximately 60%) of patients with sporadic MTC have somatic (acquired) mutations in the RET gene within the tumor cells:These mutations are present only in the tumor cells and are not detected by standard genetic testing, ie, using leukocyte DNA
    • • • The presence of somatic RET mutations correlate with:Lymph node metastasesPersistent diseaseLower survivalHowever, in one study:Only mutations in exons 15 and 16 of the RET gene:Were associated with the worse prognosis:While those in other exons had a more indolent course
      • Since it is unclear how knowledge of a specific somatic (acquired) RET mutation should impact clinical management:I do not routinely test tumor samples
  • Testing for coexisting tumors:Most patients require biochemical evaluation for coexisting tumors (particularly pheochromocytoma and hyperparathyroidism) prior to thyroidectomy:Even when genetic screening is performed preoperatively:The results are rarely known prior to surgery.For patients with unknown RET mutational status and for patients who have a germline RET mutation:Serum calcium:To rule out hyperparathyroidism requiring concomitant surgical interventionPlasma fractionated metanephrines:As the initial screen for pheochromocytoma):Normal plasma fractionated metanephrines values:Exclude a symptomatic catecholamine-secreting neoplasm
    • • • • Mildly elevated values of normetanephrine could be falsely positive:In which case additional evaluations including 24-hour urinary fractionated metanephrines, catecholamines, and adrenal imaging may be required to effectively rule in or rule out pheochromocytoma prior to surgery:Adrenal imaging should not be performed unless there is biochemical evidence suggesting a possible pheochromocytoma. (See 
  • In a patient with negative RET proto-oncogene testing and no family history of MEN2 syndrome:Biochemical testing for coexisting tumors is typically not required

 

• What is Head and Neck Surgery?:
  • 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 formation 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

 

• Rodrigo Arrangoiz MS, MD, FACS a head and neck surgeon / endocrine surgeon / surgical oncologist and is a member of Sociedad Quirúrgica S.C at the America British Cowdray Medical Center in Mexico City:

 

• Rodrigo Arrangoiz MS, MD, FACS:
  • Is a member of the American Head and Neck Society

• • He is a member of the American Thyroid Association:

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

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