Transcript thyroid 2014

THYROID PATHOLOGY
Thyroid gland
Normal anatomy
Congenital abnormalities
Thyroiditis
Hyperplasia
Tumors
THYROID-ANATOMY
Butterfly-two lateral lobes-isthmus
15-20 g
A thin fibrous capsule
Red-brown
Follicle
Round oval-single layer of epithelial cells
(Flattened-cuboidal-columnar)-on basement
membrane
C-cells-NE cells-calcitonin
Lumen of the follicle-kolloid
Homeostasis in the hypothalamus-pituitary-thyroid axis and mechanism of action of thyroid hormones. Secretion of thyroid hormones (T3
and T4) is controlled by trophic factors secreted by both the hypothalamus and the anterior pituitary. Decreased levels of T3 and T4
stimulate the release of thyrotropin-releasing hormone (TRH) from the hypothalamus and thyroid-stimulating hormone (TSH) from the
anterior pituitary, causing T3 and T4 levels to rise. Elevated T3 and T4 levels, in turn, suppress the secretion of both TRH and TSH. This
relationship is termed a negative-feedback loop. TSH binds to the TSH receptor on the thyroid follicular epithelium, which causes
activation of G proteins, and cyclic AMP (cAMP)-mediated synthesis and release of thyroid hormones (T3 and T4). In the periphery, T3
and T4 interact with the thyroid hormone receptor (TR) to form a hormone-receptor complex that translocates to the nucleus and binds to
so-called thyroid response elements (TREs) on target genes initiating transcription.
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Congenital abnormalities
Thyroglossal duct anomalies
Localized-persistence of the throglossal duct
Thyroglossal duct cyst
Midline of the neck
Mic:cyst: Pseudostratified-squamous epitelium
Heterotopic thyroid tissue
Tongue,sublingual,lingual,prelaringeal,substernal
Thyroiditis
Acute thyroiditis
Granulomatous (de Ouervain’s)
Thyroditis
Other granulomatous inflammations
Autoimmune (lymphocytic and
Hashimoto’s) thyroiditis
Riedel’s Thyroiditis
Acute thyroiditis
Infectious nature-pharyngitis,tonsillitis
St. Haemolyticus, Staph aureus,
Pneumoccus
Mic:neutrophilic infiltration,tissue necrosis
Granulomatous(de Ouervain’s)
Thyroditis
Ages:30- 50 ,F/M:3:1 to 5:1
Clinical Course
The presentation of subacute thyroiditis
may be sudden or gradual.
It is characterized by pain in the neck,
which may radiate to the upper neck, jaw,
throat, or ears, particularly when
swallowing
Nearly all patients have high serum T4
and T3 levels and low serum TSH levels.
Pathogenesis
Subacute thyroiditis- viral infection or a postviral
inflammatory process- a history of an upper
respiratory infection
A viral infection that provides an antigen, either
viral or a thyroid antigen that is released
secondary to virus-induced host tissue damage.
This antigen stimulates cytotoxic T lymphocytes,
which then damage thyroid follicular cells.
Morphology
The gland may be unilaterally or bilaterally
enlarged and firm, with an intact capsule.
On cut section, the involved areas are firm and
yellow-white and stand out from the more
rubbery, normal brown thyroid substance.
Histologically.
Early in the active inflammatory phase, scattered
follicles- replaced by neutrophils forming
microabscesses.
Later, aggregations of lymphocytes, histiocytes,
and plasma cells about collapsed and damaged
thyroid follicles.
Multinucleate giant cells enclose naked pools
or fragments of colloid , hence the designation
granulomatous thyroiditis.
Subacute thyroiditis. The thyroid parenchyma
contains a chronic inflammatory infiltrate with a
multinucleate giant cell (above left) and a colloid
follicle (bottom right).
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Other granulomatous
inflammations
Palpation thyroiditis
Tuberculosis
Sarcoidosis
Mycoses
Postoperattive necrotizing granulomas
Autoimmune (lymphocytic and Hashimoto’s)
thyroiditis
Some authors use terms lymphocytic and
Hashimoto thyroiditis synonymously
Another autoimmune -Graves’ disease
Mechanism: Humoral and cellular nature
Circulating autoab-TG-follicular cell Ag-TSH
receptor
Follicle epithelial cell- ag
Morphological common finding autoimmune
thyroiditis: extensive lymphocytic infiltration with
gland associated-germinal center formation.
Lymphocytic thyroiditis
Children
Juvenil form lymphocytic thyroiditis
Silent-painless thyroiditis with hyperthyroidism
Grossly: Diffusely enlarged-nodular, white,
nodular cut surface.
Mic: lymphocytic nodules with germinal
centers,follicles
Hashimoto’s thyroiditis
Hashimoto thyroiditis (or chronic
lymphocytic thyroiditis) is the most
common cause of hypothyroidism in areas
of the world in 45 and 65 years of age
A female predominance of 10:1 to 20:1
Epidemiologic studies have demonstrated
a significant genetic component to
Hashimoto thyroiditis
Specifically the HLA-DR3 and HLA-DR5
alleles, are linked to Hashimoto thyroiditis
Pathogenesis
Hashimoto thyroiditis is an autoimmune
disease.
The overriding feature of Hashimoto
thyroiditis is progressive depletion of
thyroid epithelial cells (thyrocytes)gradually replaced by mononuclear cell
infiltration and fibrosis.
Multiple immunologic mechanisms may
contribute to the death of thyrocytes
CD8+ cytotoxic T cell-mediated cell death
Cytokine-mediated cell death
Binding of antithyroid antibodies (anti-TSH
receptor antibodies, antithyroglobulin, and
antithyroid peroxidase antibodies) followed
by antibody-dependent cell-mediated
cytotoxicity
Pathogenesis of Hashimoto thyroiditis. Three proposed models for mechanism of
thyrocyte destruction in Hashimoto disease. Sensitization of autoreactive CD4+ T
cells to thyroid antigens appears to be the initiating event for all three mechanisms of
thyroid cell death.
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Morphology
The thyroid is often diffusely enlarged
The capsule is intact, and the gland is well
demarcated from adjacent structures. The cut
surface is pale, yellow-tan, firm, and somewhat
nodular.
Mic:extensive infiltration of the parenchyma by a
mononuclear inflammatory infiltrate
containing small lymphocytes, plasma cells, and
well-developed germinal centers
The thyroid follicles are atrophic - lined in many
areas by epithelial cells distinguished by the
presence of abundant eosinophilic, granular
cytoplasm, termed Hurthle cells- metaplastic
cells.
Hashimoto thyroiditis. The thyroid parenchyma contains a dense lymphocytic infiltrate
with germinal centers. Residual thyroid follicles lined by deeply eosinophilic Hurthle
cells are also seen.
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Clinical Course
Hypothyroidism develops gradually.
It may be preceded by transient thyrotoxicosis
caused by disruption of thyroid follicles, with
secondary release of thyroid hormones
("hashitoxicosis").
Patients with Hashimoto thyroiditis are at
increased risk for developing other concomitant
autoimmune diseases, both endocrine (type 1
diabetes, autoimmune adrenalitis), and
nonendocrine (systemic lupus erythematosus,
myasthenia gravis, and Sjögren syndrome
*Increased risk for the development of
B-cell non-Hodgkin lymphomas.
SUBACUTE LYMPHOCYTIC (PAINLESS)
THYROIDITIS
Subacute lymphocytic thyroiditis, which is also
referred to as painless thyroiditis or silent
thyroiditis, is an uncommon cause of
hyperthyroidism.
Middle-aged adults and is more common in
women, especially during the postpartum period
(postpartum thyroiditis), than in men
The pathogenesis of this disorder is unknown.
An autoimmune basis has been suggested
because some patients have elevated levels of
antibodies to thyroglobulin and thyroid
peroxidase or a family history of thyroid
autoimmune disease
Morphology
Mild symmetric enlargement, the thyroid
appears normal on gross inspection.
The most specific histologic features
consist of lymphocytic infiltration with
hyperplastic germinal centers within the
thyroid parenchyma and patch disruption
and collapse of thyroid follicles.
Clinical Course
The principal clinical manifestation of
painless thyroiditis is hyperthyroidism.
Symptoms usually develop over 1 to 2
weeks and last from 2 to 8 weeks
Laboratory findings during periods of
thyrotoxicosis include elevated levels of T4
and T3 and depressed levels of TSH.
Riedel thyroiditis
A rare disorder of unknown etiology
characterized by extensive fibrosis involving the
thyroid and contiguous neck structures.
The presence of a hard and fixed thyroid mass
clinically simulates a thyroid carcinoma.
Grossly: asymmetric-stony hard
Mic:Fibrous tissue involves gland
Inflammatory fibrosclerosis-idiopathic disorders
Palpation thyroiditis, caused by vigorous
clinical palpation of the thyroid gland,
results in multifocal follicular disruption
associated with chronic inflammatory cells
and occasional giant cell formation.
Unlike De Quervain thyroiditis,
abnormalities of thyroid function are not
present
Hyperplasia
Dyshormonogenetic goiter
Graves’ Disease(Diffuse toxic goiter)
Diffuse nontoxic goiter
Multinodular-goiter-Nodular
hyperplasia
Name
Mechanism
Dyshormono
genetic
goiter
Graves’
disease
Nodular –
difuse
hyperplasia
-Endemic
goiter
Sporadic
goiter
Genetically
Pathology
Nodular or
less diffuse
hyperplasia
Autoimmune Diffuse
hyperplasia
Iodine
Nodular
deficiency
hyperplasia
Unknown
Nodular
hyperplasia
Functional
status
Hypotyhroid
Hyperthyroid
Usually
eutyroid;
sometimes
hypothyroid
Usually euthyroid:
sometimes hyper
or hypo
Dyshormonogenetic goiter
Enzyme defects in hormone synthesis
Genetic mutations
Grossly:enlarged-multinodular
Mic:Hyperplastic follicles are lined by
marked nuclear pleomorphism, fibrosis.
Graves’ Disease
(Diffuse toxic goiter)
Graves disease is the most common cause of
endogenous hyperthyroidism. It is characterized
by a triad of clinical findings:
Hyperthyroidism owing to hyperfunctional,
diffuse enlargement of the thyroid
Infiltrative ophthalmopathy with resultant
exophthalmos
Localized, infiltrative dermopathy, sometimes
called pretibial myxedema, which is present in a
minority of patients
Ages of 20 and 40, F/M:7/1
HLA-B8 and -DR3
Pathogenesis
Graves disease is an autoimmune disorder in which a
variety of antibodies may be present in the serum,
including antibodies to the TSH receptor, thyroid
peroxisomes, and thyroglobulin.
Thyroid-stimulating immunoglobulin (TSI): Almost 50
years ago, serum from patients with Graves disease was
found to contain a long-acting thyroid stimulator (LATS)
Thyroid growth-stimulating immunoglobulins (TGI):
TSH-binding inhibitor immunoglobulins (TBII): These antiTSH receptor antibodies prevent TSH from binding
normally to its receptor on thyroid epithelial cells resulting
in the stimulation of thyroid epithelial cell activity.
Morphology
Symmetrically enlarged because of diffuse hypertrophy
and hyperplasia of thyroid follicular epithelial cells.
Cut surface: meaty appearance resembling normal
muscle.
Histologically, too many cells. The follicular epithelial
cells in untreated cases are tall and more crowded than
usual.
The formation of small papillae,
Lymphoid infiltrates, consisting predominantly of T cells,
with fewer B cells and mature plasma cells, are present
throughout the interstitium; germinal centers are
common
Diffusely hyperplastic thyroid in a case of Graves disease. The follicles are
lined by tall, columnar epithelium. The crowded, enlarged epithelial cells
project into the lumens of the follicles. These cells actively resorb the colloid
in the centers of the follicles, resulting in the scalloped appearance of the
edges of the colloid.
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Clinical Course
The clinical findings in Graves disease
include changes referable to thyrotoxicosis
as well as those associated uniquely with
Graves disease: diffuse hyperplasia of the
thyroid, ophthalmopathy, and dermopathy.
Laboratory findings:
Elevated free T4 and T3 levels
Depressed TSH levels.
Radioactive iodine uptake is increased,
and radioiodine scans show a diffuse
uptake of iodine.
Diffuse non-toxic Goiter
This disorder occurs in both an endemic and a
sporadic distribution.
Endemic goiter -occurs in geographic areas where
the soil, water, and food supply contain only low
levels of iodine.
The lack of iodine leads to decreased synthesis
of thyroid hormone and a compensatory
increase in TSH, leading to follicular cell
hypertrophy and hyperplasia and goitrous
enlargement-diffuse or nodular colloid goiter.
Sporadic goiter
Occurs less frequently than does endemic goiter.
There is a striking female preponderance and a
peak incidence at puberty or in young adult life.
Mild dietary deficiency of iodine
Slight impairment of hormone synthesis
Increased iodide clearance by kidneys
Morphology
Two phases can be identified in the
evolution of diffuse non-toxic goiter:
the hyperplastic phase and the phase of
colloid involution. Diffusely and
symmetrically enlarged, although the
increase is usually modest, and the gland
rarely exceeds 100 to 150 gm.
The follicles are lined by crowded columnar
cells, which may pile up and form
projections similar to those seen in Graves
disease. The accumulation is not uniform
throughout the gland, and some follicles are
hugely distended, whereas others remain
small.
If dietary iodine subsequently increases or
if the demand for thyroid hormone
decreases, the stimulated follicular
epithelium involutes to form an enlarged,
colloid-rich gland (colloid goiter). In these
cases, the cut surface of the thyroid is
usually brown, somewhat glassy, and
translucent.
Histologically, the follicular epithelium is
flattened and cuboidal, and colloid is
abundant during periods of involution.
Clinical Course
The vast majority of patients with simple
goiters are clinically euthyroid.
The clinical manifestations are primarily
related to mass effects from the enlarged
thyroid gland
Serum T3 and T4 levels are normal, the
serum TSH is usually elevated or at the
upper range of normal
MULTINODULAR GOITER –
Nodular hyperplasia
Recurrent episodes of hyperplasia and
involution combine to produce a more irregular
enlargement of the thyroid, termed multinodular
goiter.-Nodular hyperplasia
They may be nontoxic or may induce
thyrotoxicosis (toxic multinodular goiter).
Multinodular goiters produce the most extreme
thyroid enlargements - mistaken for neoplastic
involvement
Multinodal goiters may arise because of
variations among follicular cells in responses to
external stimuli, such as trophic hormones.
If some cells in a follicle have a growth
advantage, perhaps because of intrinsic genetic
abnormalities similar to those that give rise to
adenomas, those cells will develop into clones of
proliferating cells.
This may result in the formation of a nodule
whose continued growth could even be
autonomous, without the external stimulus.
Morphology
Multinodular goiters are multilobulated,
asymmetrically enlarged glands that can achieve
a weight of more than 2000 gm.
The pattern of enlargement is quite
unpredictable and may involve one lobe far
more than the other, producing lateral pressure
on midline structures, such as the trachea and
esophagus.
The goiter grows behind the sternum and
clavicles to produce the so-called intrathoracic
or plunging goiter.
Nodular goiter. The gland is coarsely nodular and
contains areas of fibrosis and cystic change.
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One nodule may so stand out as to impart the
clinical appearance of a solitary nodule.
On cut section, irregular nodules containing
variable amounts of brown, gelatinous colloid
are present.
Regressive changes occur frequently,
particularly in older lesions, and include areas of
hemorrhage, fibrosis, calcification, and cystic
change.
The microscopic appearance includes colloidrich follicles lined by flattened, inactive
epithelium and areas of follicular epithelial
hypertrophy and hyperplasia, accompanied by
the degenerative changes noted previously.
Clinical Course
The dominant clinical features of goiter are those
caused by the mass effects of the enlarged gland.
Cosmetic effects of a large neck mass, goiters
may cause airway obstruction, dysphagia, and
compression of large vessels in the neck and
upper thorax.
Most patients are euthyroid, but in a substantial
minority of patients, a hyperfunctioning nodule may
develop within a long-standing goiter, resulting in
hyperthyroidism (toxic multinodular goiter).
Hyperfunctioning nodules concentrate radioiodine
and appear "hot.“
Goiters are also of clinical significance because of
their ability to mask or to mimic neoplastic
diseases arising in the thyroid
Thyroid Tumors
Epithelial Tumors-specific types
A-Follicular adenoma
-Hyalinizing trabecular adenoma and related lesions
B-Papillary carcinoma
C-Follicular carcinoma
D-Clear cell tumors
E-Squmaous cell, mucinous, and related tumors
F-Poorly differentiated carcinoma
G-Undiferentiated carcinoma
H-Medullary carcinoma and related NE lesions
Lymphoid tumors and tumorlike conditions
Mesencymal tumors
Other primary tumors and tumorlike conditions
Metastatic tumors
Neoplasms of the Thyroid
Several clinical criteria might provide a clue to the nature
of a given thyroid nodule:
1-Solitary nodules, in general, are more likely to be
neoplastic than are multiple nodules.
2-Nodules in younger patients are more likely to be
neoplastic than are those in older patients.
3-Nodules in males are more likely to be neoplastic than
are those in females.
4-A history of radiation treatment to the head and neck
region is associated with an increased incidence of
thyroid malignancy.
5-Nodules that take up radioactive iodine in imaging
studies (hot nodules) are more likely to be benign than
malignant
ADENOMAS
Adenomas of the thyroid are typically discrete,
solitary masses
Most of these benign tumors are nonfunctional
Simple colloid adenomas (macrofollicular
adenomas), a common form, resemble normal
thyroid tissue;
Others recapitulate stages in the embryogenesis
of the normal thyroid (fetal or microfollicular,
embryonal or trabecular).
Hormone production in functional adenomas
("toxic adenomas") occurs independent of TSH
stimulation and represents another example of
thyroid autonomy, analogous to toxic
multinodular goiters.
Pathogenesis.
The TSH receptor signaling pathway plays an
important role in the pathogenesis of toxic
adenomas.
Activating ("gain of function") somatic mutations
in one of two components of this signaling
system-most often the TSH receptor itself or the
α-subunit of Gs-cause chronic overproduction of
cAMP, generating cells that acquire a growth
advantage
This results in clonal expansion of follicular
epithelial cells that can autonomously produce
thyroid hormone and cause symptoms of thyroid
excess
Morphology
The typical thyroid adenoma is a solitary,
spherical, encapsulated lesion that is well
demarcated from the surrounding thyroid
parenchyma.
Follicular adenomas average about 3 cm in
diameter, but some are smaller and others are
much larger (up to 10 cm in diameter).
The neoplastic cells are demarcated from the
adjacent parenchyma by a well-defined, intact
capsule. These features are important in
making the distinction from multinodular
goiters,
Areas of hemorrhage, fibrosis, calcification, and
cystic change, similar to those encountered in
multinodular goiters, are common in follicular
adenomas, particularly within larger lesions.
Microscopically
The follicular growth pattern within the
adenoma is usually quite distinct from the
adjacent non-neoplastic thyroid.
The epithelial cells composing the follicular
adenoma reveal little variation in cell and
nuclear morphology.
Mitotic figures are rare, and extensive
mitotic activity warrants careful
examination of the capsule to exclude
follicular carcinoma.
Similar to endocrine tumors at other
anatomic sites, even benign follicular
adenomas may, on occasion, exhibit
focal nuclear pleomorphism, atypia,
and prominent nucleoli (endocrine
atypia); this by itself does not
constitute a feature of malignancy.
Follicular adenoma of the thyroid. A solitary, well-circumscribed
nodule is seen.
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Follicular adenoma. The photomicrograph shows well-differentiated
follicles resembling normal thyroid parenchyma.
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Follicular adenoma. A high-power view showing that the tumor is composed
of cells with abundant eosinophilic cytoplasm and small regular nuclei.
(Courtesy of Dr. Mary Sunday, Brigham and Women's Hospital, Boston,
MA.)
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Atypical follicular adenomas:
Increased cellularity, more extensive variation in
cellular size and nuclear morphology, and even
mitotic activity.
The hallmark of all follicular adenomas is the
presence of an intact, well-formed capsule
encircling the tumor.
Careful evaluation of the integrity of the
capsule is therefore critical in distinguishing
follicular adenomas from follicular
carcinomas , which demonstrate capsular
and/or vascular invasion
Clinical Features
unilateral painless mass,
cold nodules relative to the adjacent thyroid
tissue
Owing to the need for evaluating capsular
integrity, the definitive diagnosis of
adenomas can be made only after careful
histologic examination of the resected
specimen.
Suspected adenomas of the thyroid are
therefore removed surgically to exclude
malignancy.
Thyroid adenomas, including atypical
adenomas, have an excellent prognosis and
do not recur or metastasize.
OTHER BENIGN TUMORS
Additional benign lesions include dermoid
cysts, lipomas, hemangiomas, and
teratomas (seen mainly in infants).
CARCINOMAS
1.5% of all cancers(in United States)
Most cases occur in adults, although some forms,
particularly papillary carcinomas, may present in
childhood.
A female predominance
The major subtypes of thyroid carcinoma:
Papillary carcinoma (75% to 85% of cases)
Follicular carcinoma (10% to 20% of cases)
Medullary carcinoma (5% of cases)
Anaplastic carcinoma (<5% of cases)
Most thyroid carcinomas are derived from
the follicular epithelium, except for
medullary carcinomas; the latter are
derived from the parafollicular or C cells
Pathogenesis
There are several factors, genetic and
environmental, implicated in the
pathogenesis of thyroid cancers.
Pathogenesis
Genetic
Follicular Thyroid Carcinomas -Approximately
half of follicular thyroid carcinomas harbor
mutations in the RAS family of oncogenes (HRAS,
NRAS, and KRAS
Papillary Thyroid Carcinomas- One pathway
involves rearrangements of the tyrosine kinase
receptors RET or NTRK1 (neurotrophic tyrosine
kinase receptor 1) and another involves activating
mutations in the BRAF oncogene. A third pathway
involves RAS mutations (10% to 20% of papillary
carcinomas), suggesting that some of these
cancers are related to follicular adenomas
Environmental Factors
The major risk factor-ionizing radiation,
particularly during the first two decades of life.
In the past, radiation therapy was liberally
employed in the treatment of a number of head
and neck lesions in infants and children,
including reactive tonsillar enlargement, acne,
and tinea capitis.
Up to 9% of people-thyroid malignancies
Long-standing multinodular goiter-areas with
iodine deficiency-related endemic goiter have a
higher prevalence of follicular carcinomas
Thyroid lymphomas may arise from pre-existing
Hashimoto thyroiditis.
Papillary Carcinoma
Papillary carcinomas are the most
common form of thyroid cancer
Young-middle age adults.
Morphology
Papillary carcinomas are solitary or multifocal
lesions.
Well-circumscribed and even encapsulated;
others may infiltrate the adjacent parenchyma
with ill-defined margins.
The lesions may contain areas of fibrosis and
calcification and are often cystic.
On the cut surface, they may appear granular
and may sometimes contain grossly discernible
papillary foci. The definitive diagnosis of
papillary carcinoma can be made only after
microscopic examination
Papillary carcinoma of the thyroid. A, The macroscopic appearance of a papillary
carcinoma with grossly discernible papillary structures. This particular example
contains well-formed papillae
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Microscopic examination
Papillary carcinomas can contain branching papillae
having a fibrovascular stalk covered by a single to
multiple layers of cuboidal epithelial cells.
The nuclei of papillary carcinoma cells contain finely
dispersed chromatin, which imparts an optically clear or
empty appearance, giving rise to the designation
ground glass or Orphan Annie eye nuclei.
intranuclear inclusions ("pseudo-inclusions") or
intranuclear grooves.
 Concentrically calcified structures termed psammoma
bodies are often present within the lesion, usually within
the cores of papillae.
 Foci of lymphatic invasion by tumor are often present,
but involvement of blood vessels is relatively uncommon,
particularly in smaller lesions.
 Metastases to adjacent cervical lymph nodes are
estimated to occur in up to half the cases.
Papillary carcinoma of the thyroid. This particular example contains wellformed papillae (B), lined by cells with characteristic empty-appearing
nuclei, sometimes termed "Orphan Annie eye" nuclei
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Papillary carcinoma of the thyroid. lined by cells with characteristic emptyappearing nuclei, sometimes termed "Orphan Annie eye" nuclei (C).
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Papillary carcinoma of the thyroid. D, Cells obtained by fine-needle
aspiration of a papillary carcinoma. Characteristic intranuclear inclusions
are visible in some of the aspirated cells.
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Clinical Course
Most papillary carcinomas present as
asymptomatic thyroid nodules, but the first
manifestation may be a mass in a cervical lymph
node.
In a minority of patients, hematogenous
metastases are present at the time of diagnosis,
most commonly in the lung.
Most papillary lesions are cold masses on
scintiscans.
Cytologic analysis have made fine-needle
aspiration cytology a reliable test for
distinguishing between benign and malignant
nodules.
The nuclear features are often nicely
demonstrable in aspirated specimens.
Follicular Carcinoma
The second most common form of thyroid
cancer, accounting for 10% to 20% of all
thyroid cancers.
They tend to present in women, and at an
older age than do papillary carcinomas,
with a peak incidence in the forties and
fifties.
The incidence of follicular carcinoma is
increased in areas of dietary iodine
deficiency,
Morphology
Follicular carcinomas are single nodules well circumscribed or widely infiltrative
Sharply demarcated lesions may be
exceedingly difficult to distinguish from
follicular adenomas by gross examination.
Degenerative changes, such as central
fibrosis and foci of calcification, are
sometimes present.
Follicular carcinoma. Cut surface of a follicular carcinoma with
substantial replacement of the lobe of the thyroid. The tumor has a
light-tan appearance and contains small foci of hemorrhage.
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Microscopically
Most follicular carcinomas are composed
of fairly uniform cells forming small follicles
containing colloid, quite reminiscent of
normal thyroid
The nuclei lack the features typical of
papillary carcinoma, and psammoma
bodies are not present.
Distinction from follicular adenomas
requires extensive histologic sampling of
the tumor-capsule-thyroid interface to
exclude capsular and/or vascular invasion
Capsular integrity in follicular neoplasms. Evaluating the integrity of the capsule is
critical in distinguishing follicular adenomas from follicular carcinomas. In adenomas
(A), a fibrous capsule, usually thin but occasionally more prominent, circumferentially
surrounds the neoplastic follicles and no capsular invasion is seen (arrowheads);
compressed normal thyroid parenchyma is usually present external to the capsule
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Clinical Course
Follicular carcinomas present as slowly
enlarging painless nodules.
Most frequently, they are cold nodules on
scintigrams
Vascular invasion is common, with spread to
bone, lungs, liver, and elsewhere
The prognosis is largely dependent on the
extent of invasion and stage at presentation.
Most follicular carcinomas are treated with total
thyroidectomy followed by the administration of
radioactive iodine.
Medullary Carcinoma
Medullary carcinomas of the thyroid are
neuroendocrine neoplasms derived from the
parafollicular cells, or C cells, of the thyroid
The cells of medullary carcinomas, similar to
normal C cells, secrete calcitonin,
In some instances, the tumor cells elaborate
other polypeptide hormones, such as
somatostatin, serotonin, and vasoactive
intestinal peptide (VIP).
The tumors arise sporadically in about 80% of
cases. The remainder occurs in the setting of
MEN syndrome 2A or 2B or as familial tumors
without an associated MEN syndrome
Morphology
Medullary carcinomas can arise as a
solitary nodule or may present as multiple
lesions involving both lobes of the thyroid.
The sporadic neoplasms tend to originate
in one lobe
Bilaterality and multicentricity are
common in familial cases.
The tumor tissue is firm, pale gray to tan,
and infiltrative.
Microscopically
Medullary carcinomas are composed of
polygonal to spindle-shaped cells, which may
form nests, trabeculae, and even follicles.
Small, more anaplastic cells are present in some
tumors and may be the predominant cell type.
Acellular amyloid deposits, derived from
altered calcitonin molecules, are present in the
adjacent stroma in many cases .
Calcitonin is readily demonstrable within the
cytoplasm of the tumor cellsimmunohistochemical methods.
Clinical Course
Sporadic cases of medullary carcinoma
come to medical attention most often as a
mass in the neck
In some instances, the initial
manifestations are those of a
paraneoplastic syndrome, caused by the
secretion of a peptide hormone (e.g.,
diarrhea owing to the secretion of VIP).
Anaplastic Carcinoma
Anaplastic carcinomas of the thyroid are
undifferentiated tumors of the thyroid
follicular epithelium
Anaplastic carcinomas are aggressive
tumors, with a mortality rate approaching
100%.
Patients with anaplastic carcinoma are
older than those with other types of thyroid
cancer, with a mean age of 65 years.
Morphology
Microscopically, these neoplasms are composed
of highly anaplastic cells, which may take one of
several histologic patterns:
(1) large, pleomorphic giant cells, including
occasional osteoclast-like multinucleate giant
cells;
(2) spindle cells with a sarcomatous appearance;
(3) mixed spindle and giant cells; and (4) small
cells resembling those seen in small cell
carcinomas arising at other sites.
Clinical Course
Anaplastic carcinomas usually present as
a rapidly enlarging bulky neck mass.
In most cases, spread beyond the thyroid
capsule into adjacent neck structures or
has metastasized to the lungs at the time
of presentation. Compression and invasion
symptoms, such as dyspnea, dysphagia,
hoarseness, and cough, are common.
There is no effective therapy for anaplastic
thyroid carcinoma, and the disease is
almost uniformly fatal.