Slide 1
Thyroid Lesions Surgical Pathology
OBJECTIVE:
Identify the different thyroid lesions
To Know the following :
Pathogenesis
Clinical Presentation
Gross & Microscopic
Prognosis/ Behavior
Staging
Treatment
Heterotropic Thyroid Tissue
Found anywhere along the course of the thyroiglossal duct (
Midline )
Frequently Base of the tongue
Difficulty in swallowing
Respiratory obstruction
70% with (+) gross lingual thyroid Develop hypothyroidism after
its removal
Heterotropic Thyroid Tissue
Thyroiditis
Acute Thyroiditis
Granulomatous Thyroiditis
Autoimmune Thyroiditis
Riedels Thyroiditis
Acute Thyroiditis
Infectious Nature Bacterial > Viral
Neutrophilic infitrates + Thyroid Necrosis
Diagnosis : FNAB
Treatment
Medical with Drainage of Abscess
Fistulectomy
Granulomatous Thyroiditis de Quervains
The immune response is not self-perpetuating, so the process is
limited.
Viral antigen or thyroid antigen is released
Antigen w/in macrophages stimulates the formation of cytotoxic T
lymphocytes, which then damage thyroid follicular cells.
Granulomatous Thyroiditis de Quervains
DESCRIPTION
Middle age Women (3 to 5:1) M< W
30-40s
Unknown Etiology
Believed to be a postviral inflammatory process
CLINICAL MANIFESTATION
Acute Symptoms
Sorethroat, Painful swallowing, Fever, Malaise
Marked Tenderness on the thyroid
Thyroid inflammation and hyperthyroidism are transient, usually
diminishing in 2 to 6 weeks, even if the patient is not
treated.
Transient Hperthyroidism is Due to:
Due to disruption of thyroid follicles and release of excessive
thyroid hormone
Nearly all patients have high serum T4 and T3 and low serum TSH
levels.
Radioactive iodine uptake is low because of suppression of
TSH
Unlike hyperthyroid state
( Graves ) RAI uptake is INCREASED
Later followed by
Transient, usually asymptomatic hypothyroidism lasting from 2 to
8 weeks,
Recovery is virtually always complete
Repaired by Fibrosis
Advanced Stage Firm Thyroid gland
Granulomatous Thyroiditis de Quervains
Morphology:
Assymetric gland enlargement : Usually 2x normal
On cut section, the involved areas are firm and yellow-white and
stand out from the more rubbery, normal brown thyroid substance
Micro: Marked inflam + Giant cell Granulomas about damaged
follicles
Granulomatous Thyroiditis de Quervains
TypeMicroscopicAll show extensive lymphocytic infiltration of
the glands with germinal centersLymphocytic ThyroiditisIntervening
follicles are relatively NormalHashimotos ThyroiditisFollicles are
lined by oncocytic cellsGraves DiseaseHyperplastic intervening
follicles
Hashimotos Thyroiditis Struma Lymphocymatosa
DESCRIPTION:
Most common cause of hypothyroidism in areas of the world where
iodine levels are sufficient.
Women Over 40y/o
W>M 10:1 to 20:1
Patients with Hashimoto disease are at increased risk for the
development of B-cell lymphomas.
Diffuse thyroid Enlargement
Firm / Painless
Tracheal & Esophageal Compression
Not Adherent to surrounding structure
Initial Mild Hyperthroidism
High FT3, FT4, Low TSH , Low RAIU
Later Hypothyroidism
Low FT3, FT4,
Compensatory increase in TSH
DESCRIPTION:
Pathogenesis:
Both cellular and humoral factors contribute to thyroid
injury
This disease is believed to be caused primarily by a defect in T
cells.
(1 ) They interact with B cells and stimulate the secretion of a
variety of antithyroid antibodies, which may activate
antibody-dependent cytotoxicity mechanisms
Anti- Thyroglobulin & Thyroid peroxidase
Anti-TSH receptor
Anti- Iodine Transporter
(2) Helper T cells may induce the formation of CD8+ cells, which
can be cytotoxic to thyroid cells.
(3) Cytokine mediated cell death: CD4 T cell IFN macrophage
recruit
Activated T cells have two roles in the disease
Gross:
Diffusely enlarged or Localized enlargement.
The capsule is intact, and the gland is well demarcated from
adjacent structures.
The cut surface is pale, gray-tan, firm, and somewhat
nodular
Microscopic:Small Atropic folliclesLined by Hurthle
cellExtensive lymphos + germinal center
MANAGEMENT:
Treatment :
1. No therapy
2. Subtotal Thyroidectomy 2o large lesions or pressure
or confused as Ca.
Complications:
Evolve Gradually
Malignant Lymphoma
Leukemia
Hurthle cell Ca
Riedels ThyroiditisFibrous Thyroiditis or Invasive
Thyroidits
Riedels ThyroiditisFibrous Thyroiditis or Invasive
Thyroidits
Etremely rare
Female Adults & Elderly
Not Preceeded by :
Acute Inflammatory condition
Tenderness on thyroid
Regional L.N. not involved
Clinical :
Ill-Defined Mass
Profound Dyspnea
Extremely Firm Lesion Compress Trachea Slit like state
Microscopic :
Extensive fibrous tissue
Skeletal muscles are infiltrated
Patchy mononuclear inflammation
Important Dxtic feature
Vasculitis (medium veins) encased by fibrosis
Therapy :
Steroid effective
Most Require Surgery
Incidence of Post-Op Hypothyroidism is VeryLow
HYPERPLASTIC THYROID DISORDER
Major Types of Hyperplastic Thyroid Disorder
TypeMechanismPathologyFunctional StatusDyshormogenetic
GoiterGenetically Determined error in Thyroid hormoneNodularLess
Freq- Diffuse hyperplasiaHypothyroidGraves DiseaseAutoimmuneDiffuse
HyperplasiaHyperthyroidEndemic GoiterIodine DeficiencyNodular
HyperplasiaUsually- EuthyroidSometimes- Hypo thyroidSporadic
GoiterUnknownNodular HyperplasiaUsually- EuthyroidSometimes-
Hypothyroid Hyperthyroid
Graves Disease
Young Adult Females
20-0 y/o
Genetic factors impt etiology
HLA-B8 and DR3
Triad of Clinical Findings
Hyperthyroidism
Muscle Weakness , Weight Loss
Increase SNS
Infiltrative Ophthalmopathy
Exopthalmus
Localized, infiltrative dermopathy
Pretibial Edema minority of cases
Shin area scaly thickening and induration
Laboratory
Elevated free T3 T4
Increased RAI uptake in the presence of TSH < 0.1mU/L
Due to stimulation of follicles by TSI
Depressed TSH levels
MORPHOLOGY
Gross
Symmetric enlargement
Reddish , Succulent
Microscopic
Markedly Hyperplastic Follicles
Prominent Papillary formation
Some glands grow outside into the skeletalmuscle
1-9% incidence of malignant transformation
PATHOGENESIS
TSH is NOT involved in pathogenesis
IgG against TSH receptor
TSI IMMUNOGLOBULIN
TBII THYROTROPIN-BINDING INHIBITOR IMMUNOGLOBULIN
Increased Incidence after Irradiation to neck lesions
Also caused by Amiodarone associated Thyrotoxicosis ( 37% iodine
)
TREATMENT
Antithyroid Drugs
Radioactive Iodine (ablation)
Subtotal Thyroidectomy
Thyroid remnant regenerates if 5g on each side is left
Preoperative Therapy
Iodine
Block Thyroglobulin secretion
Cause involution of the epithelial cells
Accumulation of colloid
Nodular Hyperplasia
THYROID
Nodular Hyperplasia
Most Common Thyroid disease
Some Cases Associated w/ Hashimotos
Types of Simple Goiter ( Diffuse NonToxic Goiter)
Endemic Goiter
Sporadic Goiter
Endemic Goiter
Due to low Iodine
Lead to Decreased synthesis of Thyroid Hormones
Compensatory Increase TSH secretion Goiter
Initially Hyperactive thyroid
Later Follicular atrophy Goitrous Hypothyroidism
Sporadic (Nodular) Goiter
Less frequent than endemic
Female Preponderance
Puberty or Young adult
Pathogenesis- Unknown
Features
Mild Dietary Deficiency of iodine
Slight Hormonal Impairment
Increase Renal Clearance of iodide
Simple Goiter
Gross
Diffusely enlarged thyroid gland
Rarely exceeds 100-150 grams
Clinical Manifestation
Euthyroid majority
Mass effect
T3,T4 normal
TSH usually elevated or upper range
Virtually All Longstanding Simple Goiters convert to
MULTINODULAR GOITER
Gross- Multinodular Goiter
Thyroid enlarged & Distorted shape- Asymmetrical
May weigh > 2000grams
Capsule Stretch out
Multiple nodules on cutting w/ partial or complete capsule
Hges/ calcification/ cystic degeneration
Microscopic
Nodular hyperplasia w/ papillary formation
Granulomatous rxn to ruptured follicles
Variable follicular size
No compression of adjacent parenchyma
Nodules are polyclonal by cytogenetic studies
Treatment
Mild Asymptomatic Require No Tx
Suppressive Medical Therapy with Exogenous Thyroid Hormones
Moderately Effective
Bilateral Subtotal Thyroidectomy
Disfugurement / Pressure symptoms
Clues to nature of given nodule
Solitary nodules tend to be Neoplastic than are multiple
nodules
Nodules in young patients are likely Neoplastic than in older
patients
Nodules in males are more likely neoplastic than females
History of radiation to Head/Neck is associated with Increased
incidence of Thyroid Malignancy
Hot Nodules in scan are more likely Benign
DESCRIPTION
Benign encapsulated
Most Common Thyroid Neoplasm
Usually Euthyroid w/ Cold CT scan
Many (+) Elevated Thyroglobulin
Few are toxic adenomas
Autonomous functioning tumor
More Common in iodine deficient regions
DESCRIPTION
GROSS:
Almost Always Solitary
Thin Capsule
Signs of compression
Degenerative changes
MANAGEMENT
DDx
Dominant Nodular Hyperplasia
Minimally Invasive Follicular Ca
Treatement
Lobectomy
Toxic Adenoma (warm nodules) Medical Tx Less than
Satisfactory
Levothyroxine
Thyroid Carcinomas
Papillary Ca 75% to 85%
Follicular Ca 10% to 20%
Medullary Ca 5%
Anaplastic Ca 90% of thyroid malignancy in children
5-10% has History of Irradiation to Head/Neck
Increase incidence in Hashimotos but vary widely
67% Localized thyroid lesion
13% Thyroid & L.N lesion
20% L.N lesion
DESCRIPTION:
MORPHOLOGY-Gross
Variable size
Solid , whitish, firm, clearly invasive
Papillary / Cystic changes
Papillae
About half (+) PSammoma Bodies
Ground glass Nuclei
* Impt Clue to Dx
Scant mitosis
MORPHOLOGY- Microscopic
Immunohistochemical Stain
High Molecular Weight Keratin
Reactivity to Thyroglobulin
S-100
Vimentin
Estrogen receptor
Variants:
Papillary Microcarcinoma
Measuring < 1cm.
Common incidental finding
1/3 assoc w/ cervical mets
Distant mets Exceptionally Rare
Excellent Prognosis
Variants :
Encapsulated Variant
Totally surrounded by capsule
Incidence of distant mets/ tumor death is Nearly Zero
Still assoc. with nodal mets
Diffuse Sclerosing Variant
Bilateral dense sclerosis + severe lympho infiltrates &
Psammoma
Clincally mistaken for Hashimotos
Nodal Mets nearly all (+)
Lung mets common
Disease free survival rate is LOWER than conventional
papillary
Tall/ Columnar Variant
Tend to affect Older Patients more often than conventional
More Aggressive
Variant:
Follicular Variant
Composed almost entirely of follicles
Ground glass nuclei
Scalloped edges
Behavior similar to conventional papillary Ca
High Nodal Mets
Mets usually exhinit papillary type
Variants :
Spread & Metastasis :
show extension to tissues of the neck
Lymphatic mets > Blood
Cervical mets
Very Common
Usually young patient
May be the !st sign
Lungs
most common Blood Mets
CT scan
Prognosis :
Prognosis
General Excellent Prognosis
Prognosis decreases with:
AgeMale
Tall VariantSize
MulticentricityDistant Mets
Reactivity EMA , LeuMI
Aneuploidy
Factors that NOT generally correlate w/ Prognosis
Proportion of papillae to follicles
Psammoma bdies
Cervical node Mets
Fibrosis
Prognosis :
Thyroid
Follicular Carcinoma
DESCRIPTION :
Malignant tumor exhibiting follicular cell differentiation
Women Usually >50y/o
Diagnosis : (+) Capsular or Vascular Invasion
Psammoma Bodies are Absent
Almosy Always Solitary, Never Occult lesion
Metastasis Usually Blood Borne
Lungs & Bones
Confirmed by (+) Thyroglobulin stain
Prognosis:
Minimally Invasive
Clearly Invasive architecture & Cytologic
differentiation
DESCRIPTION :
IMMUNOCHEMISTRY
Immunohistochemical
Reactivity for Thyroglobulin & Low M.W. Kerain
Oncogene ras point mutation is higher in follicular than
papillary
PROGNOSIS
Minimally Invasive
Grossly encapsulated
Solid, Fleshy
Full thickness capsular invasion and expand like mushroom
Vascular Invasion
Venous invasion w/in capsule
Must contain one or more clusters of tumor attched to the
wall
Mets 1cm but not more than 4cmT3Tumor > 4cm in greatest
dimension limited to the thyroidT4Tumor of any size extending
beyond the thyroid capsule
STAGING OF THYROID TUMORS
LYMPH NODE Regional nodes are the Cervical and Upper Mediastinal
LN
NXRegional LN cannot be assessesN0No regional LN
metastasisN1Regional LN metastasisN1aMetastasis in Ipsilateral
Cervical LNN1bMetastasis in Bilateral , Midline, or Contralateral
Cervical or Mediastinal LN
STAGING OF THYROID TUMORS
DISTANT METASTASIS
MXPresence of Distant Metastasis cannot be AssesedM0No distant
metastasisM1Distant metastasis
