1 Flashcards
The majority of solitary nodules of the thyroid are either
benign adenomas or localized, non-neoplastic conditions (for example, a dominant nodule in a multinodular goiter, simple cysts, or foci of thyroiditis).
Carcinomas of the thyroid percentage
less than 1% of solitary thyroid nodules.
more likely to be neoplastic
Solitary nodules
very young (<20 years) or very old (>70 years) individuals
Nodules that take up radioactive iodine in imaging studies (hot nodules) are more likely to be
benign
Adenomas of the thyroid are benign neoplasms derived from
follicular epithelium.
Follicular adenomas usually are
solitary
Although the vast majority of adenomas are
nonfunctional
toxic adenoma
produce thyroid hormones, causing clinically apparent thyrotoxicosis
follicular adenomas are not
forerunners to carcinomas
forerunners to carcinomas
follicular adenoma
carcinomas
pathogenesis of toxic adenomas
somatic mutations in tsh receptors allow follicular cells to secrete thyroid hormone independent of TSH stimulation. (thyroid autonomy)
The result is symptomatic hyperthyroidism with a “hot” thyroid nodule seen on imaging studies.
somatic mutations in the TSH receptor signaling pathway are present in slightly
over half of toxic adenomas
minority of nonfunctioning follicular adenomas (<20%) exhibit mutations in
RAS or other other genes, genetic alterations that are shared with follicular carcinomas.
MORPHOLOGY thyroid adenoma
solitary, spherical lesion that compresses the adjacent nonneoplastic thyroid. The neoplastic cells are demarcated from the adjacent parenchyma by a well-defined, intact capsul
microscopic examination thyrohyoid adenoma
constituent cells are arranged in uniform follicles that contain colloid. Occasionally, the neoplastic cells acquire brightly eosinophilic granular cytoplasm (oxyphil or Hürthle cell change)
adenomas occasionally exhibit
focal nuclear pleomorphism, atypia, and prominent
nucleoli (endocrine atypia)
hallmark of all follicular adenomas is the presence of
intact well- formed capsule encircling the tumor.
Most adenomas of the thyroid manifest as
painless nodules, often discovered during a routine physical examination.
Larger masses may produce local symptoms such as
difficulty in swallowing.
Individuals with toxic adenomas may present with features of.
thyrotoxicosis
Essential techniques used in the preoperative evaluation of suspected adenomas are
ultrasonography and fine needle aspiration biopsy.
definitive diagnosis of thyroid adenoma can be made only after careful … because…
careful microscopic examination of the resected specimen
of the need for evaluating capsular integrity,
Suspected adenomas of the thyroid are therefore removed surgically to
exclude malignancy.
Thyroid adenomas carry an excellent
prognosis and do not recur or metastasize.
Most thyroid carcinomas (except medullary carcinomas) are derived from… and thr vast majority are..
thyroid follicular epithelium
well-differentiated lesions.
The major subtypes of thyroid carcinoma and their relative frequencies are
• Papillary carcinoma (accounting for more than 85% of cases)
• Follicular carcinoma (5% to 15% of cases)
• Anaplastic (undifferentiated) carcinoma (<5% of cases)
• Medullary carcinoma (5% of cases)
What are the Different molecular events that play a role in the pathogenesis of the four main variants of thyroid cancer
Genetic changes in three follicular cell-derived malignancies cluster along two oncogenic pathways that run downstream of growth factor receptors and RAS
What are the two oncogenic pathways that run downstream of growth factor receptors and RAS
the mitogen-activated protein (MAP) kinase pathway and the phosphatidylinositol-3- kinase (PI-3K) /AKT pathway.
Gain-of-function mutations in components of these pathways in thyroid carcinomas lead to
constitutive activation even in the absence of growth factors, promoting carcinogenesis.
a feature of most papillary carcinomas
Activation of the MAPkinas e pathway
One-third to one-half of papillary thyroid carcinomas harbor a gain-of-function mutation in
BRAF, the most common driver mutation in this neoplasm.
Follicular thyroid carcinomas. Follicular thyroid carcinomas frequently harbor driver mutations in
RAS or components of the PI3K/AKT signaling pathway
Follicular thyroid carcinomas
gain-of function mutations in PI3K and loss-of-function mutations in PTEN, a negative regulator of PI3K, are seen.
RAS and PI3K mutations also are found in
benign follicular adenomas and anaplastic carcinomas suggesting a shared histogenesis.
These highly aggressive tumors can arise de novo or, more commonly, by the progression of a well-differentiated papillary or follicular carcinoma.
Anaplastic carcinomas
This tumor …contains specific mutations. The most common of these mutations are …
Anaplastic carcinomas
loss- of-function mutations in TP53.
Medullary thyroid carcinomas. These neoplasms arise from
parafollicular C cells, rather than the follicular epithelium.
Familial medullary thyroid carcinomas occur in
And are associated with
multiple endocrine neoplasia type 2 (MEN-2)
germline RET proto-oncogene mutations that lead to constitutive activation of the RET tyrosine kinase receptor
RET mutations are also seen in approximately
half of nonfamilial (sporadic) medullary thyroid cancers.
major risk factor predisposing to thyroid cancer is
exposure to ionizing radiation, particularly during the first 2 decades of life.
deficiency of dietary iodine (and by extension, an association with goiter) is linked with a higher frequency of follicular carcinomas.
there was a marked increase in the incidence of .. carcinomas among children exposed to ionizing radiation after the Chernobyl nuclear disaster in 1986.
papillary
most common form of thyroid cancer
PAPILLARY CARCINOMA
vast majority of thyroid carcinomas associated with previous exposure to ionizing radiation are
PAPILLARY CARCINOMA
MORHOLOGY_ Papillary carcinoma
solitary or multifocal lesions. Some tumors may be well- circumscribed and encapsulated; others infiltrate the adjacent parenchyma and have ill- defined margins. Papillary structures can be seen on the cut surface.
microscopic hallmarks of papillary neoplasms include
epithelium covering the papillae with differentiated, uniform, orderly cuboidal cells
Nuclei with finely dispersed chromatin, which imparts an optically clear or empty appearance,
Concentrically calcified structures termed psammoma bodies are often present within the lesion, usually within the cores of papillae
Branching papillae have
fibrovascular stalk covered by a single to multiple layers of cuboidal epithelial cells.
Nuclei with finely dispersed chromatin gives rise to
designation ground-glass or Orphan Annie eye nuclei
invaginations of the cytoplasm often give the appearance of
intranuclear inclusions (“pseudo-inclusions”) or intranuclear grooves
sufficient for the diagnosis of papillary carcinoma, even in the absence of papillary architecture.
nuclear features a
…..present within the lesion, usually within the cores of papillae. These structures are rarely found in follicular and medullary carcinomas.
Concentrically calcified structures
Lymph of pappilary carcinoma
Foci of lymphatic invasion by tumor are often present,
the involvement of blood vessels is relatively uncommon, particularly in smaller lesions. Metastases to adjacent cervical lymph nodes occur in up to one-half of cases.
Papillary carcinomas are …. lesions, with 10-year survival rates of …. Of interest, the presence of isolated cervical node metastases …. influence on prognosis. In a minority of patients, ….are present at the time of diagnosis, most commonly in …
indolent
over 95%
does not have a significant
hematogenous metastases
the lung.
long-term survival of patients with papillary thyroid cancer is dependent on several factors, including
age (in general, the prognosis is less favorable among patients older than 40 years of age), the presence of extrathyroidal extension, and the presence of distant metastases (stage).
Follicular carcinomas manifest most frequently as
solitary cold thyroid nodules.
Rarely may be hyper-functional
Folecular carcinoma metastasize through
bloodstream (hematogenous dissemination) to the lungs, bone, and liver.
regional nodal metastases
Common in papillary
Uncommon in folicular
Follicular carcinomas are treated with
surgical excision.
Anaplastic carcinomas are
undifferentiated tumors of the thyroid follicular epithelium,
accounting for less than 5% of thyroid tumors
ANAPLASTIC CARCINOMA mortality rate
100%.
Patients with … are older than those with other types of thyroid cancer,
anaplastic carcinoma
65 years.
Approximately one-fourth of patients with anaplastic thyroid carcinomas have a history of ….. and another one-fourth harbor a …..
well-differentiated thyroid carcinoma,
concurrent well-differentiated tumor in the resected specimen.
Anaplastic carcinomas manifest as
bulky masses that typically grow rapidly beyond the thyroid capsule into adjacent neck structures.
Anaplastic carcinomas microscopic examination
composed of highly anaplastic cells, which may be large and pleomorphic or spindle-shaped and in some cases mixture of the two cell types.
…. may be present in some tumors, suggesting an origin from a better-differentiated carcinoma.
Foci of papillary or follicular differentiation
Anaplastic carcinomas are very aggressive despite therapy. Metastases to distant sites are
common
in most cases, death occurs in … as a result of …
less than 1 year as a result of aggressive local growth and compromise of vital structures in the neck.
Medullary carcinomas of the thyroid are
neuroendocrine tumors derived from the parafollicular cells, or C cells, of the thyroid.
Like normal C cells, medullary carcinomas secrete
calcitonin
measurement of which plays an important role in the diagnosis and postoperative follow-up of patients
Calcitonin
some cases, the tumor cells elaborate on other polypeptide hormones such as
somatostatin, serotonin, and vasoactive intestinal peptide.
Medullary carcinomas arise sporadically in about
70% of cases.
The remaining 30% are familial, occurring in the setting of
multiple endocrine neoplasia (MEN) syndrome 2A or 2B, or familial medullary thyroid carcinoma without an associated MEN syndrom
Both familial and sporadic medullary forms are associated with
gain- of-function driver mutations in the RET receptor tyrosine kinase
Sporadic medullary carcinomas, as well as familial cases without an associated MEN syndrome, occur in
adults, with a peak incidence in the fifth and sixth decades. Cases associated with MEN- 2A or MEN-2B, by contrast, tend to occur in younger patients, including children.
Medullary carcinomas may arise as
solitary nodule or may manifest as multiple lesions involving both lobes of the thyroid.
Multicentricity is particularly common in
familial cases
Larger lesions often contain areas of
necrosis and hemorrhage and may extend through the capsule of the thyroid.
microscopic examination, medullary carcinomas are composed of
polygonal to spindle-shaped cells, which may form nests, trabeculae, and even follicles
Amyloid deposits, derived from altered calcitonin molecules, are present in
adjacent stroma in many cases and are a distinctive feature.
Calcitonin is readily demonstrable both
within the cytoplasm of the tumor cells and in the stromal amyloid by immunohistochemical methods.
One of the characteristic features of familial medullary carcinomas is the presence of
multicentric C cell hyperplasia in the surrounding thyroid parenchyma, a feature usually absent in sporadic lesions
Foci of C cell hyperplasia are believed to represent
the precursor lesions from which medullary carcinomas arise.
Clinical Features of medullary carcinoma
sporadic cases, medullary carcinoma manifests most often as a mass in the neck, sometimes associated with compression effects such as dysphagia or hoarseness.
some instances, the initial manifestations are caused by
secretion of a peptide hormone (e.g., diarrhea caused by the secretion of vasoactive intestinal peptide)
Palpable nodules occur in ~..% of the population.
6
Malignancy is present in ~..% of all thyroid nodules and in ~8% of palpable thyroid nodules.
10
Incidence of increases with age and is more frequently present in women than men.
Medullary carcinoma a. This cancer originates from
C cells of the thyroid.
Medullary carcinoma produces
calcitonin, a calcium-lowering hormone.
Histologic characteristics pf medullary include
sheets of tumor cells in an amyloid-containing stroma.
Calcitonin is a tumor marker for
medullary carcinoma of the thyroid
Increased levels of calcitonin may produce
hypocalcemia
Calcitonin can be converted into
amyloid
C-cell hyperplasia is a
precursor lesion for medullary carcinoma.
