Diseases of the Thyroid Gland

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Pathology of the Thyroid Gland

• Edward B. Stelow, M.D.
• May 10, 2007

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Reading Assignment

• Rubin and Farber, 4th ed., pp. 1134-49
• You are responsible for all the information in
  the handout
• Questions to es7yj_at_virginia.edu

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You and Your Thyroid

• Anatomy and Physiology
• Congenital Disease
• Hyperplasia / Goiter
• Hypo and Hyperthyroidism
• Graves, Thyroiditis
• Neoplasia

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Anatomy

• Normal - Two lobes, connected by the isthmus,
  below the thyroid cartilage anterior to the
  trachea
• 20 g

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Anatomy / Development

• The thyroid gland forms via the thyroglossal duct
  which develops at the foramen cecum (base of the
  tongue) and grows caudally
• 4th and 5th branchial pouches also contribute
  with possibly neural-crest derived C-cells
• Duct should involute

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Histology

• Follicles lined by single layer of cuboidal to
  columnar epithelium surrounding proteinaceous
  material (colloid). C-cells cannot normally be
  seen

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Physiology

• Triiodothyronine (T3) and tetraiodothyronine (T4)
  secreted by thyrocytes under influence of thyroid
  stimulating hormone (TSH), which is in turn under
  the influence of thyrotropin releasing hormone
  (TRH)
• Feedback loop
• Normal loop requires iodine

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Physiology

• T3 is most active form
• Active form is unbound by thyroxine binding
  globulin
• Stimulates basal metabolic rate (catabolism and
  anabolism)

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Congenital Anomalies

• Lingual Thyroid
• Thyroglossal Duct Cyst
• Ectopic Thyroid Tissue
• Lateral Aberrant Thyroid
• Congenital Hypothyroidism

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Thyroglossal Duct Cyst
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Congenital Hypothyroidism

• Dysgenesis, dyshormonogenetic goiter, enzyme
  deficiencies
• Associated with developmental abnormalities and
  mental retardation

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Hyperplasia / Goiter

• Non-neoplastic, non-inflammatory enlargement of
  the thyroid gland
• Diffuse and/or nodular simple or multiple
• Most commonly results from compensatory
  hypertrophy due to iodine deficiency (Patients
  often still euthyroid, for the most part)
• Present due to mass
• Female to male 8 to 1

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Hyperplasia / Goiter

• Gland is enlarged diffusely or with nodules
• Follicles of variable size lined by cuboidal to
  columnar cells
• Stromal hemorrhage and fibrosis are often present

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Hypothyroidism

• Defective synthesis of thyroid hormone.
• Inadequate function of thyroid parenchyma
• Inadequate secretion of TSH

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Hypothyroidism

• Myxedema (proteoglycan accumulation). (boggy,
  hoarse, dry and cool skin, ecchymoses). Bloated
  appearance
• Depression, lethargy, sensory defects, dulled
  tendon reflexes
• Cardiomegaly
• Constipation
• Anovulation Erectile Dysfunction

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Hyperthyroidism

• Presence of abnormal thyroid stimulator.
• Intrinsic thyroid disease.
• Excess TSH production.

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Hyperthyroidism

• Exophthalmos
• Tachycardia, sweating, weight loss despite
  appetite, tremor, oligomenorrhea
• Fine Hair
• Goiter
• Diarrhea
• Causes include Graves disease, toxic goiter, and
  toxic neoplasm (adenoma)

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Graves Disease

• Most frequent cause of hyperthyroidism
• IgG antibodies to TSH receptor function as
  agonists
• Thyroid becomes hyperplastic
• Antibodies actually heterogeneous
• Genetic factors (familial), Sex (more common in
  women), Psychology?, Smoking

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Graves Disease

• Pathology, Gross- symmetrically enlarged (35-50
  g), firm and red
• Pathology, Micro- Hyperplastic with tall,
  columnar epithelium with scalloped colloid.
  Epithelial tufting or papillary formation

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Thyroiditis

• Inflammation of the thyroid gland
• Autoimmune, infectious and other etiologies

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Autoimmune Thyroiditis

• Hashimoto Thryoiditis
• Active T-helper cells (CD4) stimulate cytotoxic
  T-cells (CD8) and B-Cells (Ab against thyrocyte
  antigens thyroid microsomal peroxidase (95),
  thyroglobulin (60) and TSH receptor)

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Autoimmune Thyroiditis

• Lymphocytes accumulate and destroy thyroid and
  block TSH receptor
• Results in goitrous change and can result in
  hypothyroidism (most common cause of goiter in
  children)
• Associated with genetics (familial) and
  environment (iodine intake)
• 10x more common in women

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Autoimmune Thyroiditis

• Pathology Gross- Diffusely enlarged and somewhat
  nodular thyroid (60-200 g)
• Pathology Micro- Lymphoplasmacytic inflammatory
  infiltrate with atrophic follicles and oncocytic
  (Hurthle/Askanazy cell) metaplasia. Fibrosis can
  be present.

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Acute and Subacute Thyroiditis

• Acute- Rare, hematogenous spread of bacteria
  (Staph or Strep), treated with antibiotics.
• Subacute (De Quervains)- possible viral
  etiology, variable, self-limited course, fever,
  thyroid dysfunction, mass. 5x more common in
  women.
• Subacute histology- Macrophages, lymphocytes and
  giant cells surround damaged follicles.

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Neoplasia

• Papillary Carcinoma
• Anaplastic Carcinoma
• Follicular Adenoma
• Follicular Carcinoma
• Medullary Carcinoma
• Lymphoma

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Papillary Carcinoma

• Most common thyroid malignancy (70-90)
• Women Men 31
• Risk factors include Iodine excess, radiation,
  genetics (RET translocation), thryoiditis,
  hyperplasia

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Papillary Carcinoma

• Pathology, Gross- Unifocal or multifocal, lt5mm
  (occult) to large, pale, firm and gritty
• Pathology, Micro- Branching papillae with
  fibrovascular cores and/or follicle formation.
  Cuboidal to columnar cells with definitive
  nuclear features (enlargement, overlap, central
  clearing, pseudoinclusions, grooves). Fibrosis
  and psammoma bodies can be present.

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Papillary Carcinoma

• Patients present with thyroid or lymph node
  nodule
• Will frequently metastasis to the lymph nodes
  (50)
• Excellent prognosis even with metastases
  (patients rarely die of disease)

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Follicular Adenoma

• Benign neoplasm with follicular architecture
• Presents as solitary mass
• Most common neoplasm of the thyroid
• Women Men 71
• 4th to 5th decade

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Follicular Adenoma

• Pathology, Gross- Single, well-defined,
  surrounded by a capsule, fleshy, lt5 cm
• Pathology, Micro- Uniform follicles (most
  commonly micro-follicles) surrounded by a fibrous
  capsule (other patterns can exist)
• Pathology, Micro- !!Should not have vascular
  invasion or extra-capsular extension (Follicular
  Carcinoma)!!

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Follicular Carcinoma

• Uncommon, lt15 of thyroid malignancy
• Follicular patterned carcinoma without papillary
  formations or nuclear features of papillary
  carcinoma
• Minimally invasive (3 develop mets) or widely
  invasive (50 develop mets)
• Minimally Invasive- focal angio-invasion or
  capsular penetration
• Tumor spreads hematogenously (bone and lung),
  unlike papillary carcinoma

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Anaplastic Carcinoma

• 10 of thyroid cancer
• ANAPLASTIC Sheets of bizarre cells.
• Develop in pre-existing papillary carcinoma in
  older individuals
• Large, invade adjacent vital structures.
• Universally fatal (6 mo)

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Medullary Carcinoma

• 5 of thyroid carcinoma
• Arises from C-cells
• 80 sporadic, 20 familial (MEN 2A and B, RET
  mutation)
• Familial (AD) presents at a younger age and is
  associated with C-cell hyperplasia
• Secrete calcitonin (can be measured as a serum
  level).
• 50 5 year survival
• Can have both lymph node and hematogenous spread

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Medullary Carcinoma

• Pathology, Gross- Superior thyroid, can be
  multicentric (familial), circumscribed, grey
  white
• Pathology, Micro- Variable histologic appearance
  often with amyloid. Tumor cells often have
  nested appearance.

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Lymphoma

• 2 of thyroid cancers
• Arise in background chronic thyroiditis
• Prognosis like that of other lymphoma unless
  tumor is low-grade and restricted to the thyroid
  (prognosis is then excellent)

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Questions