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Malignant disorders of thyroid gland

Thyroid malignancies are classified into four main types: differentiated thyroid cancer (including papillary and follicular histology), undifferentiated thyroid cancer, medullary thyroid cancer, and anaplastic thyroid cancer. Each type has distinct prognosis and treatment options. Thyroid cancer has an incidence of 2-3 new cases per 100,000 people annually, and it is two to four times more common in females than in males. Genetic factors also play a significant role in the development of these cancers.

Papillary thyroid carcinoma

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, accounting for 65-70% of cases. It generally has the best prognosis among all thyroid cancers. Most cases occur in the third and fourth decades of life, with a higher prevalence in females, who are two to three times more likely to be affected. PTC can also occur in children, sometimes presenting with cervical and distant metastases, yet still often having a favourable prognosis.

PTC originates from the follicular cells of the thyroid. The tumour consists of a fibrovascular stalk with cancerous follicular cells forming a papilla. The cells typically have abundant pale cytoplasm and distinctive nuclei that are folded or grooved with intranuclear cytoplasm. Prominent nucleoli give a characteristic “Orphan Annie eye” appearance, which aids in diagnosis through fine needle aspiration cytology (FNAC). PTC may undergo cystic changes and present with laminated calcium bodies called psammoma bodies.

Risk Factors for Developing Papillary Thyroid Carcinoma

  1. Ionizing Radiation: Exposure to ionizing radiation, particularly in low doses to the head and neck several years prior, increases the risk. This includes fallout from nuclear events like the Chernobyl accident and the bombings of Hiroshima and Nagasaki, which cause gene mutations.
  2. Familial History: Approximately 5-10% of PTC patients have a family history of thyroid cancer. Syndromes such as Cowden (characterized by multiple hamartomas, breast tumors, skin tags, and thyroid cancer) and Gardner’s (familial colonic polyposis with thyroid cancer) also increase the risk. PTC is more common in areas with adequate iodine intake, unlike follicular carcinoma, which is more common in low-iodine areas.

Clinical Presentation

  1. An asymptomatic mass in the thyroid.
  2. Metastatic nodes in the neck, with about one-third of patients having palpable neck nodes.
  3. Symptoms of local invasion affecting the strap muscles, trachea, esophagus, or laryngeal nerves.
  4. Pulmonary or bone metastases, which can present with or without a thyroid mass.

Diagnosis

Diagnosis involves a combination of history, clinical examination, and FNAC. Ultrasound of the thyroid and neck is essential to identify additional lesions and neck node involvement. Thyroid function tests are usually normal, though hyperthyroidism may be present. Chest X-rays can detect pulmonary metastases, and CT/MRI scans may be necessary to determine the extent of the disease.

Treatment

  1. Microcarcinoma: Tumors less than 1.5 cm, clinically non-palpable, without capsular invasion or cervical nodes, often discovered incidentally, are treated with lobectomy and isthmusectomy.
  2. Intrathyroidal Tumors: Tumors over 1.5 cm without contralateral nodules or palpable neck nodes require lobectomy and isthmusectomy.
  3. Gross Disease in Both Lobes: Requires total or near-total thyroidectomy if no cervical nodes are present.
  4. High-risk patients: Also require total thyroidectomy.
  5. Tracheal Invasion: Needs tracheal segmental excision and repair along with tumour excision.
  6. Cervical Lymph Node Dissection: Performed if nodes are palpable; elective neck dissection is not recommended.

Follow-Up

Post-total thyroidectomy, the residual disease may be present in areas like the ligament of Berry, pyramidal lobe, or superior poles of the thyroid. This requires postoperative radioiodine ablation to manage any remaining cancerous tissue.  

 

Follicular Carcinoma

Follicular carcinoma originates from the follicular cells of the thyroid and accounts for about 10-15% of thyroid malignancies. It usually presents around the age of 50 and is more common in females, with a female-to-male ratio of 3:1. Clinically, it appears either as a solitary thyroid nodule or as a rapid increase in the size of a pre-existing nodule. Unlike papillary cancer, follicular carcinoma is less likely to involve lymph nodes and more likely to spread hematogenously. Fine needle aspiration cytology (FNAC) may indicate a follicular neoplasm, but a definitive diagnosis of carcinoma requires evidence of capsular or vascular invasion obtained after surgical removal of the specimen.

Treatment

  1. If FNAC suggests a follicular neoplasm (but not cancer), a lobectomy with isthmusectomy, including the pyramidal lobe, should be performed. If the lobectomy specimen is diagnosed as carcinoma, a completion thyroidectomy is necessary, followed by a radioiodine scan and possible ablation of metastatic disease.
  2. If FNAC confirms follicular carcinoma, a total thyroidectomy is required.
  3. For nodules larger than 4 cm in elderly patients diagnosed as follicular neoplasm, a total thyroidectomy is recommended due to the higher risk of carcinoma.
  4. Neck dissection is performed only if palpable nodes are present; prophylactic neck dissection is not indicated.

The prognosis for follicular carcinoma is poor if the patient is over 50 years old, the tumour is larger than 4 cm, or distant metastases are present.  

 

Hurthle Cell Carcinoma

Also known as oncocytic carcinoma, Hurthle cell carcinoma consists of large oncocytes rich in mitochondria, which stain pink. It can be multifocal and bilateral, spreading to regional nodes or causing distant metastases. Its behaviour is more aggressive than follicular carcinoma, and these tumours do not absorb radioactive iodine as effectively.

Treatment

  1. Hurthle cell adenoma (benign) requires lobectomy and isthmusectomy.
  2. If histopathology shows capsular or vascular invasion, a completion thyroidectomy is performed.
  3. If FNAC diagnoses Hurthle cell carcinoma, a total thyroidectomy with clearance of paratracheal nodes is required. Neck dissection is performed if lateral nodes are palpable.
  4. Follow-up includes technetium scans since Hurthle cells do not take up radioiodine.

The prognosis for Hurthle cell carcinoma is worse than that for follicular or papillary carcinoma.  

Anaplastic Carcinoma

Anaplastic carcinoma is uncommon and represents less than 5% of all thyroid cancers. It predominantly affects patients aged 60-80 years. It is more common in women than men, with a ratio of 3:2. This type of carcinoma is highly aggressive, rapidly involving surrounding structures and causing symptoms such as hoarseness, stridor, dyspnea, dysphagia, and thoracic inlet obstruction. Cervical lymph node involvement is present in 80% of patients at diagnosis, and distant metastases, often in the long bones and brain, are found in 50% of cases.

Treatment

Treatment options for anaplastic carcinoma are limited, with a median survival of only 3-5 months. Surgery, radiation, and chemotherapy have minimal effectiveness. Quality of life and palliation, including tracheostomy and nutritional support, is often the primary treatment approach.  

 

Medullary Carcinoma

Medullary carcinoma arises from the parafollicular C cells of the thyroid, which are neuroectodermal in origin. This carcinoma constitutes about 5% of thyroid malignancies and is associated with multiple endocrine neoplasia (MEN) types IIA and IIB. It typically presents in the middle and upper thirds of the thyroid lobes. They comprise about 5% of thyroid malignancies.

Medullary carcinoma typically presents with a neck mass and cervical node enlargement, usually in individuals aged 50-60 years. Both sexes are equally affected. Due to its aggressive nature and local invasion, it can cause pain, dyspnoea, dysphagia, and hoarseness. About half of the cases show distant metastases in the mediastinum, lung, and bone at the time of diagnosis.

Types and diagnosis

Medullary carcinoma can be sporadic or familial. The familial type may be associated with Multiple Endocrine Neoplasia (MEN) type IIA and IIB or occur without any endocrinopathy. Parafollicular cells secrete calcitonin and carcinoembryonic antigen, which are used for diagnosis and postoperative follow-up. Sporadic carcinoma usually presents as a unifocal lesion without associated endocrine pathologies. The familial type often presents at a younger age, is multicentric and bilateral. There is a variant called mixed medullary cancer, which has similar behavior and treatment to medullary carcinoma.

 

Diagnosis and Screening

Diagnosis is confirmed through Fine Needle Aspiration Cytology (FNAC) and elevated calcitonin levels. Patients should be tested for RET proto-oncogene mutations in peripheral lymphocyte DNA. Additional tests include measuring serum calcium levels for parathyroid function and 24-hour urine tests for catecholamines/metanephrines to screen for pheochromocytoma. Relevant imaging studies are also performed. Screening of all first-degree relatives and children for RET-proto-oncogene mutations is essential, especially in cases associated with MEN type IIA and IIB.

Treatment

Total thyroidectomy is the treatment of choice due to the aggressive and multicentric nature of the lesion. This surgery includes the removal of level VI lymph nodes, even if they are not involved. If level VI nodes are affected, a comprehensive neck dissection (levels II-V) is also performed. For primary lesions larger than 2 cm, an ipsilateral elective neck dissection and removal of level VII nodes are recommended. If pheochromocytoma is present, it should be removed before thyroidectomy to avoid hypertensive crisis during surgery. Postoperative follow-up involves measuring calcitonin levels to detect residual, recurrent, or metastatic disease. Radioactive iodine and chemotherapy are not effective, and the role of external beam radiation remains controversial.

Surgical Timing for Familial Cases

Children with medullary cancer and those with MEN type IIA should undergo thyroidectomy by the age of 6 years. Those with MEN type IIB should have the surgery within the first year of life.

Lymphoma

Thyroid lymphomas are mostly B-cell non-Hodgkin type, typically affecting patients aged 60-80 years and more common in females (3:1 ratio). Pre-existing Hashimoto’s disease increases the risk. It typically presents similarly to anaplastic thyroid cancer. Patients often have a rapidly growing, painless thyroid mass. This mass can invade surrounding structures, causing hoarseness, stridor, dyspnoea, dysphagia, and thoracic inlet obstruction. Additionally, cervical lymph nodes are usually enlarged. Lymph node enlargement can also occur in other body regions depending on the disease stage. Patients often exhibit hypothyroidism.

Diagnosis and Treatment. Diagnosis requires immunohistochemistry to differentiate from anaplastic carcinoma and Hashimoto’s disease.

Treatment Based on Disease Stage. It varies by disease stage and may include surgery, radiation, and chemotherapy.  

  • Stage I and II: When the disease is localized to the thyroid (stage I) or the thyroid and neck nodes (stage II), treatment options include surgery and radiotherapy. Surgery might be limited to an open biopsy, tracheostomy, or removal of the early localized disease. Radiotherapy can also be employed for these stages.

  • Stage III and IV: For more advanced stages, such as stage III (disease on both sides of the diaphragm) or stage IV (disseminated disease), a combination of radiotherapy and chemotherapy is used.

 

Metastases to the Thyroid

Metastatic disease to the thyroid can occur from primary cancers of the breast, kidney, lung, head and neck, and melanoma. FNAC aids diagnosis, though it can be challenging to distinguish from anaplastic carcinoma.

TNM Clinical Classification for Thyroid Cancer (latest 8th edition)
T – Primary Tumour*
TX Primary tumour cannot be assessed
T0 No evidence of primary tumour
T1 Tumour 2 cm or less in greatest dimension, limited to the thyroid
T1a Tumour 1 cm or less in greatest dimension, limited to the thyroid
T1b Tumour more than 1 cm but not more than 2 cm in greatest dimension, limited to the thyroid
T2 Tumour more than 2 cm but not more than 4 cm in greatest dimension, limited to the thyroid
T3 Tumour more than 4 cm in greatest dimension, limited to the thyroid with gross extrathyroidal extension invading only strap muscles (sternohyoid, sternothyroid, or omohyoid muscles)
T3a  Tumour more than 4 cm in greatest dimension, limited to the thyroid
T3b  Tumour of any size with gross extrathyroidal extension invading strap muscles (sternohyoid, sternothyroid, or omohyoid muscles)
T4a Tumour extends beyond the thyroid capsule and invades any of the following: subcutaneous soft tissues, larynx, trachea, oesophagus, recurrent laryngeal nerve
T4b Tumour invades prevertebral fascia, mediastinal vessels, or encases carotid artery
Note: *Including papillary, follicular, poorly differentiated, Hürthle cell and anaplastic carcinomas.
N – Regional Lymph Nodes
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis
N1a  Metastatis in Level VI (pretracheal, paratracheal, and prelaryngeal/Delphian lymph nodes) or upper/superior mediastinum
N1b  Metastasis in other unilateral, bilateral or contralateral cervical (Levels I, II, III, IV or V) or retropharyngeal nodes
M – Distant Metastasis
M0 No distant metastasis
M1 Distant metastasis

 

TABLE: FNAC findings classification and action required (Bethesda System)

Diagnostic category

Cytological diagnosis

Management

I

Non-diagnostic

Repeat US-guided FNA

II

Benign

Clinical follow-up

III

Atypia/follicular lesion of undetermined significance

Repeat FNA

IV

Suspicious

Surgical hemithyroidectomy

V

Suspicious

Near-total thyroidectomy / surgical hemithyroidectomy

VI

Malignant

Near-total hemithyroidectomy

———- End of the chapter ———–

Learning resources.

  • Scott-Brown. Textbook of Otorhinolaryngology Head and Neck Surgery.
  • Harrison’s principles of internal medicine.
  • David J. Terris. William S. Duke. Textbook of Thyroid and Parathyroid Diseases Medical and Surgical Management.
  • Stell and Maran’s. Textbook of Head and Neck Surgery and Oncology.
  • Hans Behrbohm. Textbook of Ear, Nose, and Throat Diseases With Head and Neck Surgery.
  • P L Dhingra. Textbook of Diseases of Ear, Nose and Throat.
     
            Author:

Dr. Rahul Bagla ENT Textbook

Dr. Rahul Bagla
MBBS (MAMC, Delhi) MS ENT (UCMS, Delhi)
Fellow Rhinoplasty & Facial Plastic Surgery.
Designation: Faculty, Associate Professor
Government Institute of Medical Sciences,
Greater Noida, India
Mail: msrahulbagla@gmail.com

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