Thyroid Neoplasm - MU

Thyroid Neoplasm Classification

• Benign thyroid neoplasms include follicular adenomas.
• Malignant thyroid neoplasms are classified using the Dunhill classification.

Primary Malignant Tumors

• Follicular epithelium gives rise to papillary thyroid carcinoma (60% distribution), follicular thyroid carcinoma (17%), papillofollicular carcinoma (behaves like papillary carcinoma), and Hürthle cell carcinoma (behaves like follicular carcinoma).
• Parafollicular cells give rise to Medullary carcinoma (6% distribution).
• Lymphoid cells give rise to Malignant Lymphoma (4% distribution).
• Well-differentiated tumors are more common (80%)
• Undifferentiated tumors are less common (20%)
• Anaplastic thyroid carcinoma has a distribution of 13%.

Secondary Thyroid Neoplasms

• Rare and often metastatic from the colon, kidney, melanoma, or breast, or from direct invasion.

Follicular Adenoma Characteristics

• Clinically presents as solitary nodules.
• Histological examination is necessary to differentiate between an adenoma and follicular carcinoma.
• Invasion of the capsule is absent in adenomas but present in follicular carcinomas.
• Invasion of pericapsular blood vessels is absent in adenomas but present in follicular carcinomas.

Types of Follicular Adenoma

• Colloid: This is the most common type, Colloid, lacks potential for microinvasion.
• Fetal: Microfollicular, and has potential for microinvasion.
• Embryonal: Atypical, has potential for microinvasion.
• Hürthle cell: Has potential for microinvasion.
• Hyalinizing trabecular adenoma occurs.

Follicular Adenoma Treatment and Follow-Up

• Treatment involves surgical excision, preferably a hemithyroidectomy (lobectomy of the side of the adenoma with isthmectomy).
• Prolonged follow-up is unnecessary if the remaining thyroid tissue is normal.

Malignant Tumors: Incidence and Etiology

• Higher incidence in females (3:1 ratio).

Etiology of Thyroid Malignancy

• Radiation (external or radioiodine) is a predisposing factor for papillary carcinoma.
• Pre-existing multinodular goiter predisposes to Follicular carcinoma.
• Familial history is a predisposing factor for medullary carcinoma.
• Hashimoto's thyroiditis predisposes to NHL or papillary carcinoma.
• Elevated TSH predisposes to papillary carcinoma.
• Genetics is a predisposing factor for Cowden syndrome.

Cowden Syndrome Details

• Inheritance: Autosomal dominant.
• Etiology: Germ cell mutation of the PTEN tumor suppressor gene.
• Clinical Presentation: Includes differentiated thyroid carcinoma and oncogenes such as C myc + C erb + C fos + Ras, breast cancer, and multiple hamartomas.
• NHL = Non-Hodgkin's Lymphoma.

Types of Malignant Tumors: Differentiated Thyroid Carcinoma (DTC)

• Arises from follicullar cells
• Origin: Derived from follicular cells.
• Types: Papillary, follicular, papillofollicular, and Hürthle cell carcinomas.
• Incidence: Accounts for 90% of thyroid malignancies.
• Clinical Presentation: Thyrotoxicosis occurs in 2% of DTCs.
• Spread: Papillary carcinoma spreads through nodes, while follicular carcinoma spreads through blood.

Pathology of Thyroid Neoplasm

• Histological indications of malignancy include penetration and invasion of the capsule.
• The presence of papillae, follicles, or both, arranged irregularly.
• Active and irregular mitosis and the presence of rich vascularity.

Psammoma Bodies

• Small areas of perivascular calcification in necrotic hyalinized cells, which are "Pathognomonic of malignancy".
• Appear as multiple small specks of granular calcification, indicating malignancy.
• Benign calcification appears as irregular blotchy areas and is larger in size.

Papillary Carcinoma

• Incidence: 70-80% (most common)
• Age: 20-40 years (young age)
• Sex: Common in females
• Etiology: Radiation either external or radioactive iodine therapy.

Follicular Carcinoma

• Incidence: 10-15%
• Age: 30-50 (middle age)
• Sex: Common in females (2:1)
• Etiology: Either de novo or in pre-existing multinodular goiter

Anaplastic Carcinoma

• Incidence: 1%
• Age: 50 & Above (Old age)
• Sex: Common in females

Papillary Carcinoma Classifications (Woolner Classification)

• Occult (30%)
  • One primary tumor is less than 1 cm.
  • Presentation is via +ve cervical lymph nodes.
• Intrathyroidal (50%)
  • Presented as a Solitary Thyroid Nodule (STN)
• Extrathyroidal (15%)
  • Presented as extracapsular spread of the tumor or multiple foci in the thyroid gland.

Follicular Carcinoma Classifications (Woolner Classification)

• Minimally Invasive (50%)
  • Well encapsulated
  • Presented as STN
• Highly Invasive (50%)
  • Presented as multiple foci within the thyroid gland.

Gross Appearance of Thyroid Tumors

• Papillary: Soft to firm or cystic, solitary or multinodular, and contains brownish-black fluid.
• Follicular: not defined.
• Anaplastic: Presents as a bulky, irregular mass that invades through the gland capsule, encircles cervical structures, and extends into the mediastinum.

Microscopic Features of Thyroid Tumors

• Papillary: Cystic spaces, papillary projections with psammoma bodies (50% cases), malignant cells with Orphan Annie eye nuclei, nuclear grooves, and nuclear pseudo-inclusions; commonly multicentric.
• Follicular: Follicular cells with variable differentiation and solid sheets may be present; diagnosis depends on capsular and vascular invasion or metastasis.
• Anaplastic: Appears in 3 forms - Spindle cell type (predominant cells are spindle-shaped, may be confused with undifferentiated sarcoma), Small cell type (sheets of small, round, fairly uniform cells with little cytoplasm, may be mistaken for lymphocytic lymphoma), Giant cell type (contains a great proportion of large, pleomorphic & multinucleated giant cells).

Spread of Thyroid Tumors

• Papillary: Spreads mainly via lymphatics but usually has no blood spread. Extrathyroidal spread has cause blood-borne secondaries.
• Follicular: Spreads primarily through blood. Metastasis to bones, lungs and liver. Lymph node spread occurs in Hürthle cell variants.
• Anaplastic: Multiorgan involvement through lymphatics, blood, and direct invasion.

Prognosis of Thyroid Tumors

• Papillary: Excellent, slowly progressive, less aggressive, and one of the curable malignancies.
• Follicular: Good, aggressive tumor, encapsulated in 97% cases & invasive in 70% cases..
• Anaplastic: Very poor (worst); most patients die within the first 2 years as it’s an aggressive carcinoma.

Medullary Carcinoma Types

• Incidence: Uncommon (5%) type of thyroid malignancy.
• Sporadic:
  • Occurs in the 5th/6th decade.
  • More common in females.
  • Usually solitary (70%) and unifocal,
  • Posterior part of the thyroid resulting in compression.
• MCT with MEN II Syndrome:
  • More aggressive, affects younger individuals including infants & children
  • Marfanoid features
  • Bilateral, multifocal/multicentric with MEN type IIb
  • Ppheochromocytoma with hypertension; most aggressive.
• Familial Non-MEN MCT (20%):
  • Least malignant.
  • Occurs in 4th and 5th decades
  • Commonly multicentric, autosomal dominant on chromosome 10 (Germline mutation of RET-Proto oncogene).

Medullary Carcinoma Characters

• Grey-white in color
• Well demarcated
• Non-encapsulated
• Varying considerably in size

Microscopic Features:

• Derived from the parafollicular c-cells comes from the neural crest.
• Has characteristic amyloid stroma (immunohistochemistry reveals calcitonin in amyloid).
• Calcintonin : Calcitonin blood levels are high, a useful tumor marker
• Secretes 5-HT, Prostaglandin, ACTH and VIP

Medullary Carcinoma Spread Location

• Mainly to lymph nodes (60%).

Medullary Carcinoma Hormonal Activity

• Not TSH dependent and doesn't take up radioactive iodine.

Clinical Picture of Thyroid Neoplasms

• Can have a recent rather than rapid enlargement of the gland or nodule, and can also present with painful swelling.
• Onset can insidious with pain or tenderness
• Site can be local to the mass or referred to the ear.
• Can occur as a primary thyroid nodule

Compression Manifestation

• Dyspnea caused by compression on the trachea resulting in compression or cord paralysis.
• Dysphagia, uncommon, results from RLN paralysis or results from trachea-esophageal LN enlargement.
• Fixity of the nodule to the trachea due to a loss in rocking movement.
• Occult presentation, and sometimes 2ry LN in the neck may be the 1st sign with bone and lung metastasis.
• Patient may only present once the above is present.

Clinical Presentation of Thyroid Carcinoma

• Classified based on the following groups: Carcinoma on preexisting multinodular goiter and symptomless STN in the healthy gland of a young male child.

Carcinoma on Preexisting Multinodular Goiter Characteristics

• Occurs in females (middle-aged and elderly).
  • Recent increase in goiter size.
  • Hoarseness of voice.
  • Persistent dry cough.
  • Dyspnea, with local or referred pain described as a late feature.
• They typically report a bony swelling or pathological fracture
• Nodules are hard
  • Excessive induration and Fixity may cause increased suspicions, enlarged cervical lymph nodes

Symptomless STN in the Healthy Gland of a Young Male Child

• A symptomless STN in a child or adolescent should be labelled as carcinoma unless proved otherwise.
• Histologically, it is papillary carcinoma.

Lump in the Neck with an Occult Primary Tumors on the Thyroid

• The patient is commonly a young or middle-aged male.
• Reports a unilateral lump in the neck without a history of sore throat, tuberculosis, or buccal ulcer.
• Thyroid is not enlarged, and the LNs on one side of the neck are enlarged, matted, firm, and not tender.
• Biopsy of the LN's show papillary carcinoma
• Patients usually live many years after operation

Rapidly Increasing Swelling of the Thyroid

• Presents with hoarseness of voice, and dyspnea.
• Occurs in an elderly male or female, who reports rapidly increasing swelling of the neck of the neck, Hoarseness of voice, and difficulty in breathing, no thyroid swelling noticed before.
• Thyroid gland shows thyroid swelling with a diffuse margin and firm consistency.
• The cervical LNs may be enlarged, firm and hard, irregular, and not tender and are fixed to the infrahyoid muscles & trachea.
• Histopathology shows anaplastic carcinoma

Complications of Malignant Tumors of Thyroid Gland

• Include spread, pressure, fungation, ulceration, hemorrhage & infection
• First, multifocal lesions spread to affect the whole gland, then to trachea, esophagus, and neighboring tissues.

Lymphatic Spread

• Invasion of lymphatics accompanies the vessels and may give enlargement (invasion) in the Pretracheal, Internal jugular (deep cervical), along the RLN, Supraclavicular in posterior triangle, Upper mediastinal LNs.
• when lymphatics are blocked, retrograde lymphatic spread may involve: Base of the skull, Cervical spine or clavicle, Hilar glands & medial part of lung parenchyma.

Blood Spread

• is more common in follicular than in papillary cancers
• Affected organs include the Lung & Bone
• In occult carcinoma, secondary deposits appear before the primary, where Removal of the primary may lead to regression of the metastasis.

Pressure Manifestations of Thyroid Tumors

• Result from local infiltration.
• Trachea: Dyspnea
• Esophagus: Dysphagia
• RLN: Hoarseness of voice

Thyroid Cancer Investigation

• Include, lab, imaging, and pathological elements

Lab Investigations for Thyroid Disease

• TSH - Free T3 - Free T4.
• Raised in carcinoma
• Markers include serum thyroglobulin, and Medullary carcinoma (S-calcitonin).

Imaging Investigations for Thyroid Cancer

• Ultrasound (Neck US)
  • Gives good anatomical images of the thyroid and surrounding structures.
  • To identify nodules, number, size, vascularity, and echogenicity.
  • To do USG-guided FNAC and to identify neck lymph nodes.
  • To detect recurrent cases and to find out the solid or cystic nature.
  • 50% present as multiple nodules with a prominent one
• Benign masses are hyperechoic and cysting with well defined margins, peripheral eggshell calcification, with sonolucent rim halos, and no vasculatiry
• Malignant masses are hypoechoic, with poorly defined margins, mirco-calcification and high levels of vascularity.

Plain X-ray and Isotope Scans

• Stippling calcification (Psammoma bodies).
• Pulmonary metastases.
• Isotope scan:
  • Usually done for nodule appearing solid in US
  • Malignant lesions usually appears cold areas in scan
  • Benign lesions also appear cold areas as Cysts, Hemorrhage, Degenerative module and Thyroiditis.

Pathological Investigations Thyroid Cancer

• FNAC (Fine Needle Aspiration and Cytology)
  • Investigation of choice for concluding pathological diagnosis in thyroid diseases. Useful for Papillary/Anaplastic /Medullary carcinoma, Lymphomas and Colloid nodules and Thyroiditis
  • Suspicious nodules are aspirated.
  • 95% sensitivity.
  • 85% specificity.
  • Graded from 1-5 and can be repeated if cyst recurs
• FNNAC (fine needle non-aspiration cytology) is more reliable
• Tru-cut biopsy- a deeper biopsy with an increased risk for Hemorrhage - pain - injury for trachea & nerves
• Open biopsy- surgical removal of a sample for biopsy -hemithyroidectomy is indicated

Assessment of Metastases

• visualization of vocal cords → 3% asymptomatic cord paralysis.
• Includes bone survey, abdominal US, BA swallow infiltration of esophagus and Venography in SVC obstruction TNM Clinical Classification
• T=Tumor N = Node M=Metastasis
• The classification applies only to carcinoma. & there should be histological confirmation by histological type
• Age is included in staging which is an important factor.

Staging for Differentiated Thyroid Carcinomas

• T0: No evidence of primary tumor.
• T1: Tumor 2-4 cm
• T1a: < 1 cm.
• T1b: 1-2 cm.
• T2: Tumor 2-4 cm
• T3: Tumor > 4 limited to the thyroid or in soft external tissue.
• T4A: Invasion to subcutaneous tissue.

Nodal Staging for Differentiated Thyroid Carcinomas

• NX: Regional lymph nodes cannot be assessed.
• N0: No regional lymph.
• N1a: Level VI spread (pre/paratracheal, prelaryngeal).

Distant Metastases Staging

• Mx: Metastasis can't be assessed.
• M0: No distant spread.
• M1: Distant metastasis present.

Risk Factors

Differentiated thyroid carcinoma Risk group definitions:

• Low risk group:
• Age: Men of 40 years & younger + women of 50 years & younger "Without distant metastases"
• All older patients with intra-thyroid papillary carcinoma or follicular carcinoma with minor capsular involvement in association with tumors < 5 cm in diameter & no distant metastases.
• High risk group
• All patients with distant metastases.
• All older patients with extra-thyroid papillary carcinoma or Follicular carcinoma with major capsular Involvement and tumors ≥ 5 cm in diameter regardless of extent of disease.

European Consensus report defined three risk categories for DTC:

• Very low risk
  • Unifocal T1 (<1 cm) NO MO
  • No extension beyond the thyroid capsule
  • Favorable histology variant
• Low risk
  • T1 (>1 cm). or T2 NΟ ΜΟ
  • Multifocal T1 NO MO
• High risk
  • Any T3 & T4 or any T, N1 or M1

Prognostic systems:

• AMES scoring : Age , Metastasis extracapsular spread, and Size
• AGES scoring: Age grade extracapsular spread and Size
• MACIS scoring: Metastasis Age Completeness spread and Size

Risk (Good vs Poor)

• Age
  • Good prognosis, Male: ≤ 40 years, and Female: ≤ 50 years
  • Poor prognosis, Male: > 40 years, and Female: > 50 years
• Metastasis
  • Good prognosis = absent
  • Poor prognosis = present
• Extrathyroidal Spread
  • Good prognosis = absent
  • Poor prognosis = present
• Tumor Size
  • Good prognosis < 5 cm -Poor prognosis ≥ 5cm

Treatment (Depends on Pathological Type)

• PAPILLARY and FOLLICULAR CARCINOMA (DIFFERENTIATED)
  • Total thyroidectomy for the entire gland
  • Hemithyroidectomy done if tumor is less 1 cm, no nodal involvement, unifocal, with intra thyroidal disease
  • Modified block neck if positive nodal involvement
• 3-5 weeks following surgery a whole body scan using iodine is conducted TSH should be < .01

Thyroid Tumor Removal

Thyroid tumore can be removed using the following methods

• Aim: To suppress the production of TSH “As the tumor is hormone dependent”

• Aim: Reduse reoccurance. Ablate residual thyroid tissue to remove metastases and LN

• Medical therapy Mainly for advanced DTC . Using Srorafenib and more

• Total thyroidectomy if thyroid has to be removed.

• External radiation can happen after the fact

• Surgery (excision) is isolated for bone injuries like clavial and sternum

  • The tumor is derived from cells , the Exclusion of other components of MEN type II should be considered

Treatment for Medullary Carcinoma

• Requires total thyroidectomy with removal of the central block to prevent future growth

Malignant Lymphoma

• Is controlled with chemotherapy but in some cases a total thyroidectomy might be needed

Andplatic Carcinoma

• No surgery is performed
• Patients under go irradiation and chemotherapy