DSA04 - Pathology of the Thyroid

Pyramidal; Persistant remnant of the thyroglossal duct

The () lobe of thyroid is a normal anatomical variant seen in 15-50% of the population. What does it represent?

External Carotid

The Superior part of the thyroid is supplied by the Superior Thyroid Artery - what is this a branch of?

Thyrocervical trunk (branch of subclavian artery)

The Inferior part of the thyroid is supplied by the Inferior Thyroid Artery - what is this a branch of?

Supplies all intrinsic muscles of larynx - except cricothryoid (SLN)

What is the function of the Recurrent Laryngeal Nerve (runs near INFERIOR THYROID ARTERY)?

Forms as an outgrowth from the floor of the primitive pharynx - primordium originates at the FORAMEN CECUM

How does the Thyroid begin to grow in Embryology?

endoderm

Thyroid follicular cells are derived from (endoderm/mesoderm/ectoderm)

Follicle Epithelial Cells

What cells in the Thyroid...

> Acts a a single layer of cuboidal cells surrounding the follicles

> Synthesize Thyroglobulin (Convert T3 to T4) --> Thyroglobin stored in LUMEN of follicles as colloid (pink, proteinaceous material)

Parafollicular Cells

What cells in the Thyroid...

> Sit at the corner of 4 follicles

> Synthesize Calcitonin

4th pharyngeal pouch

Parafollicular cells arise from what?

7th week

When should the Thyroid reach its final position during gestation?

Ectopic Thyroid Tissue

Define Condition:

Thyroid tissue located OUTSIDE of normal position in anterior neck

-Hx/Path: MC Secondary to failure of embryological descent

-Sx/PE:

> MC at Base of Tongue (LINGUAL)

-Prog: Removal --> Hypothyroidism (if it's the only thyroid tissue present)

10th week

When should the Thyroglossal duct be obliterated during gestation?

Thyroglossal Duct Cyst

Define Condition:

When portion of thyroglossal duct fails to involute

-Sx/PE:

> Anterior Midline Neck Mass moving w/ swallowing or tongue protrusion

-Dx: (Histo)

> Thyroid follicles in cyst/duct wall

> Lining can either by Nonkeratinizing Squamous Cells (if near foramen cecum) OR Ciliated Epithelium (if in lower neck)

-Basal Metabolic Rates

-Beta-Adrenergic Effects

-Blood Sugar Increase

-Breakdown Lipids

-Bone Growth

-Brain Maturation

-Bowel Movements

-Baby Surfactant

What are the functions of the Thyroid Hormone? (8 Bs)

Hyperthyroidism

Define Condition:

Increased levels of Thyroid Hormones (T3/T4)

-Hx:

> Graves disease

> Hyperfunctioning ("Toxic") Multinodular Goiter

> Hyperfunctional ("Toxic") adenoma of Thyroid

-Path: Metabolism speeds up and increase ANS activity

-Sx/PE:

> Hyperactivity

> Heat Intolerance

> Sweating

> Wt Loss

> Diarrhea

> Tachycardia

> Anxiety

> Tremor

-Prog: THYROID STORM

> Thyrotoxic crisis

> Abrupt onset of severe pathology

> MEDICAL EMERGENCY (can die of cardiac arrhythmia)

Graves Disease

Define Condition:

MCC of Hyperthyroidism

-Path: Autoimmune response against multiple thyroid antigens (most important = TSH receptor) --> TSH-receptor Antibody (TRAb), aka Thyroid-stimulating Immunoglobulin (TSI)

> IgG Autoantibody that mimics TSH --> Binds TSH receptor --> Follicular cells release TH --> More T3/T4, but Less TSH

-Sx/PE:

> Diffuse thyroid enlargement

> Bulging Eyes (infiltrative ophthalmopathy w/ exophthalmos)

>> CD4 T cells secreting cytokines and orbital fibroblasts have TSH receptors -> TSH receptors stimulated by TRAb -> fibroblast proliferation and secretion of hydrophilic glycosaminoglycans -> draws in water -> swelling

> Pretibial Myxedema (aka Infiltrative Dermopathy)

>> Deposition of glycosaminoglycans (HA) in dermis and subcutis

>> Early lesions are bilateral, firm, non-pitting, asymmetrical plaques or nodules

>> Can coalesce to form scaly, thickened and hardened skin areas

>> Overlying skin may be discolored

-Dx:

> Gross = Diffusely enlarged thyroid

> Micro =

>> Tall, crowded epithelial cells --> papillae

>> Pale, scalloped colloid

>> Lymphocytes (mostly T cells), plasma cells

Hypothyroidism

Define Condition:

Deficient Thyroid Hormone (T3/T4) production

-Path: Metabolism slows down

-Sx/PE:

> Lethargy

> Fatigue

> Cold Intolerance

> Wt Gain

> Constipation

> Bradycardia

Congenital Hypothyroidism

Define Condition:

Thyroid Hormone deficiency AT BIRTH; Most Common TREATABLE CAUSE of Intellectual Disability

-Hx:

> Thyroid dysgenesis (abnormal gland developmet)

> Dyshormonogenesis (abnormal TH synthesis), ex = mutations in thyroid peroxidase

> Iodine Deficiency in mother during pregnancy

-Tx: Supplemental TH therapy

-Sx/PE/Prog: (if no Tx) = 6 Ps

> Pot bellied

> Puffy-faced (coarse facial features)

> Protruding umbilicus (umbilical hernia)

> Protuberant tongue (macroglossia)

> Poor brain development (poor myelin sheath development)

> Poor bone growth (short stature)

Hashimoto (Chronic Lymphocytic) Thyroidits - aka Autoimme Thyroiditis

Define Condition:

MCC of Hypothyroidism in Iodine Sufficient Regions

-Hx: A/w... (Autoimmune Diseases)

> SLE

> T1DM

-Path: Autoimmune response against Thyroid antigens (d/t breakdown of immune self-tolerance to thyroid autoantigens)

> CD8+ T cells attack thyroid epithelial cells

> Activation of CD4+ T cells --> inflammatory cytokines (INF-gamma) release --> Macrophage recruitment/activation --> Follicle damage

> Antithyroid Abs (Anti-TPO/Tg) = Cell mediated Cytotoxicity/Complement dependent damage

-Sx/PE:

> NONTENDER thyroid enlargement (preceded by transient hyperthyroid state - aka Hashitoxicosis - d/t follicular reupture and TH release)

-Dx:

> Labs =

>> (+) Anti-TPO (antimicrosomal Ab)

>> (+) Anti-Tg

> Gross = Diffusely and symmetrically enlarged thyroid

> Micro

>> Diffuse infiltration of thyroid parenchyma w/ lymphocytes and plasma cells

>> Lymphoid follicles w/ germinal centers

>> Atrophic thyroid follicles

>> Hurthle cell (abundant pink, granular cytoplasm) metaplasia d/t ongoing injury

-Prog: Risk of Non-Hodgkin B cell Lymphoma

Subacute Granulomatous (de Quervain) Thyroiditis

Define Condition:

Self-limiting Granulomatous inflammation of the thyroid

-Hx: Transient Hyperthroidism --> Euthyroid State --> Hypothyroidism --> Euthyroid State

-Path: URI shortly before (d/t viral infection or inflammation in response to infection)

-Sx/PE:

> PAINFUL/TENDER Thyroid

-Dx:

> Gross = Firm, enlarged (unilateral or bilateral) thyroid)

> Micro =

>> Mixed inflammatory infiltrate (Partial destruction of follicles with a mononuclear lymphocytic infiltrate)

>> Follicle disruption --> granulomatous inflammation (macrophages and mulitnucleated giant cells)

Riedel Thyroiditis

Define Condition:

Invasive fibrous thyroiditis

-Path: IgG4 related disease

> IgG4-producing plasma cells and lymphocytes

> Fibrosis and complete/partial obstruction of medium sized veins

> Hypothyroidism ONLY in 1/3 pts

-Sx/PE:

> Hard, fixed, NONTENDER, thyroid

-Dx:

> Gross =

>> "ROCK HARD" fixed thyroid mass adherent to surrounding tissues --> mimics malignancy

>> Cut surface = Tan/gray, WOODY, avascular

> Micro =

>> Dense, thick fibrosis --> replacing normal thyroid tissue

>> Marked lymphoplasmacytic infiltrate

-Tx:

-Prog: Fibrosis extending to local structures (trachea, esophagus) --> MIMICS ANAPLASTiC CARCINOMA

Thyroid Neoplasms

Define Condition:

-Sx/PE: Solitary Thyroid Nodule

-Prog: MOST ARE BENIGN

-Dx:

> Check TSH to determine if functional or non-functional

> Fine Needle Aspiration

> Functional

>> Low TSH

>> Radioactive iodine uptake (RAIU) confirm it to be "hot"

> Non-Functional

>> Normal or High TSH

>> RAIU show low uptake/cold (10% cold = MALIGNANT)

Follicular Adenoma

Define Condition:

MC Benign Thyroid Neoplasm (proliferation of thyroid follicles)

-Sx/PE: Solitary NONPAINFUL nodule (most non-functional, but functional = toxic adenoma)

-Dx:

> Gross = Solitary nodule w/ well-defined intact capsule

> Micro = Thyroid tissue completely surrounded by fibrous capsule - can't differentiate this from carcinoma b/c entire capulse can't been see in frozen section

Papillary Thyroid Carcinoma

Define Condition:

MC Thyroid Carcinoma

-Hx: RADIATION EXPOSURE

> Children who had radiation for cancer Tx

> Chernobyl nuclear disaster

-Path: Activation of MAP kinase signaling pathway

> MC = BRAF mutation

> RET/PTC fusion

-Sx/PE: NONPAINFUL Neck Mass

-Dx:

> Gross = Solid, white cut surface; Solitary OR Multifocal

> Micro (Dx based on NUCLEAR FEATURES - via FNA)=

>> Branching papillae w/ fibrovascular core

>> Optically clear (empty, ground glass) nuclei = OPRHAN ANNIE Nuclei

>> Nuclear pseudoinclusions

>> Intranuclear grooves

>> Psammoma bodies (concentric calcifications)

-Prog: Spreads to cervical LNs, but prognosis is good (>95% 10 yr survival)

Follicular Thyroid Carcinoma

Define Condition:

-Hx:

> Peak = 40-60 y/o

> MC in areas of dietary iodine deficiency

-Path: A/w RAS mutation and PAX8-PPARG translocation

-Sx/PE: Solitary Cold Thyroid Nodule

-Dx:

> Micro (Dx on FNA) = Similar to Adenoma; Capsular invasion and/or vascular invasion

-Prog: Spreads hematogenously --> LUNGS, BONES, LIVER, but GOOD PROGNOSIS

Medullary Thyroid Carcinoma (MTC)

Define Condition:

Malignant proliferation of parafollicular "C" cells

-Hx:

> 70% are SPORADIC (nonhereditary)

>> Ages 40-60

>> Solitary

> 30% are FAMILIAL (hereditary)

>> Younger (mean = 35 y/o)

>> Bilateral and Multicentric

>> Seen w/ Multiple Endocrine Neoplasia (MEN) Syndrome 2A and 2B but not associated

>> ALL a/w RET mutations

-Path: More CALCITONIN --> ↓ serum Ca2+ by inhibiting osteoclasts (↓bone resorption) and ↓ kidney Ca2+ reabsorption, but not important in normal Ca2+ homeostasis

> Altered Calcitonin Deposits ==> AMYLOID DEPOSITS

-Dx:

> Gross: Solid, Gray-Tan yellow

> Micro:

>> Polygonal to spindle-shaped tumor cells arranged in nests, cords, or glands

>> Round nuclei with finely stippled to coarsely clumped chromatin (“Salt and pepper” chromatin)

>> Amyloid deposits in stroma (homogeneous pink extracellular material -> stains red on Congo red stain and shows apple green birefringence under polarized light)

>> Tumor cells AND Amyloid = (+) CALCITONIN IHC Stain

Anaplastic Thyroid Carcinoma

Define Condition:

Undifferentiated malignant tumor of thyroid follicular epithelium

-Hx:

> A/w TP53 mutation

> Mean Age = 65 y/o

> Arises from well-differentiated PTC or FTC (or de novo)

-Path/Sx/PE: VERY AGGRESSIVE (rapidly invades/compresses local tissue)

> Trachea = Dyspnea

> Esophagus = Dysphagia

> RLN = Hoarseness

-Dx:

> Micro = Anaplastic Cells (large, pleomorphic tumors cells)

-Prog: POOR PROGNOSIS (mortality rate ~ 100% w/n less than 1 yr) d/t aggressive local growth and compromising vital structures in neck