Carcinoma Thyroid

Presenter:- Dr Nafizul Faizana

Chair Person :-Dr Prem Kumar A
Relations
Anatomy
Classification of neoplasm of Thyroid neoplasm
Incidence of primary neoplasm
Thyroid Follicular Cell Neoplasia and Oncogenesis

● The two major molecular mechanisms governing thyroid follicular cell

oncogenesis
● 1.mitogen-activated protein kinase (MAPK) signaling
● 2. phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathways
● These mechanisms govern normal thyroid cell survival and function.
● Perturbations at multiple points in these pathways have been directly linked to
the pathogenesis of thyroid cancer.
Papillary thyroid cancer

● Most common -80%

● Female predominance F:M ratio of 3:1
● Peak incidence of age 30-50yrs
● Disseminates primarily via the lymphatic route and affects the cervical
lymph nodes in the central and lateral compartments
● Risk factors:- irradiation ,family history
● PATHOLOGY :gross-PTCs generally are hard and whitish and remain flat on
sectioning with a blade, in contrast to normal tissue or benign nodular lesions
that tend to bulge. Macroscopic calcification, necrosis, or cystic change may be
apparent.
● Histology:- papillary projection,mixed papillary follicular variant,follicular variant
of PTC which are of 2 types encapsulated/noninvasive follicular thyroid
neoplasm with papillary-like nuclear features (NIFTP) and invasive /non
encapsulated.
Clinical features

● Slow growing painless mass in neck.

● Euthyroid state.
● Dysphasia,dyspnea,dysphonia in locally advance invasive disease
● Lymph node metastases are common, especially in children and young adults,
and may be the presenting complaint. “Lateral aberrant thyroid” almost always
denotes a cervical lymph node that has been invaded by metastatic cancer.
● Distant metastases do occur in up to 3% to 5% of patients, typically to lung and
bone.
Prognostic indicator

● PTC have excellent prognosis with >95% having 10yr survival rate.
● Most of the indicators are post operative
● 1.AGES
● 2.MACIS
● 3.AMES
● 4. TNM

Treatment:- Near total /Total thyroidectomy

With or without CND

Follicular thyroid carcinoma
● 2nd most common-10%
● Occur commonly in iodine deficient areas
● Peak incidence of age 40 -60yrs.
● Female predominance ,F:M -3:1
● FTC shows hematogenous spread to lungs and bones ‘osteolytic pulsatile
secondaries’
● Histology:- usually solitary lesion surrounded by capsule,Cytologically, FTC can
range from having virtually normal-appearing follicular cells to those with various
abnormal features, including nuclear atypia, discohesion, hypercellularity, and
microfollicles;FTC cannot be reliably diagnosed by FNA. FTC can only be definitively
diagnosed on histologic examination based on the presence of capsular and vascular
invasion
● Treatment and prognosis:-
● Patients diagnosed by FNAB as having a follicular lesion should undergo thyroid
lobectomy because at least 70% to 80% of these patients will have benign
adenomas
● Total thyroidectomy is done in follicular lesions >4 cm,a family history of thyroid
cancer, or a history of radiation exposure.
● The cumulative mortality from follicular thyroid cancer is approximately 15% at 10
years and 30% at 20 years. Poor long-term prognosis is predicted by age over 50
years old at presentation, tumor size >4 cm, higher tumor grade, marked vascular
invasion, extrathyroidal invasion, and distant metastases at the time of diagnosis.
Hürthle Cell Carcinoma
● account for approximately 3% of all thyroid malignancies.
● considered to be a subtype of follicular thyroid cancer.
● Hürthle cell cancers also are characterized by vascular or capsular invasion and,
therefore, cannot be diagnosed by FNAB
● Histology:-Tumors contain sheets of eosinophilic cells packed with mitochondria,
which are derived from the oxyphilic cells of the thyroid gland
● Hürthle cell tumors differ from follicular carcinomas in that they are more often
multifocal and bilateral (about 30%), usually do not take up RAI (about 5%), are
more likely to metastasize to local nodes (25%) and distant sites, and are
associated with a higher mortality rate (about 20% at 10 years).
Treatment
● lobectomy and isthmusectomy
for unilateral Hürthle cell
adenomas
● total thyroidectomy for inavasive
hurtle cell neoplasm with routine
central neck node dissection
Stratification system to estimate the risk of persistent/recurrent disease

● Low-risk thyroid cancer :- includes those without local tumor invasion, all macroscopic tumor
resected, absence of aggressive histology (e.g., tall cell, columnar cell carcinoma), no known
distant metastases (clinical or on RAI scan if done), no vascular invasion, clinical N0 or ≤5
pathologic N1 micrometastases (<0.2 cm in largest dimension), intrathyroidal, encapsulated
follicular variant of papillary thyroid cancer, intrathyroidal, well differentiated follicular thyroid
cancer with capsular invasion and no or minimal (<4 foci) vascular invasion and intrathyroidal
papillary microcarcinoma (unifocal or multifocal, including BRAFV600E mutated).
● Intermediate-risk tumors :- include those showing microscopic invasion of tumor into
the perithyroidal soft tissues or RAI-avid metastatic foci in the neck on the first
posttreatment whole-body RAI scan. This group also includes tumors with aggressive
histology (e.g., tall cell, columnar cell carcinoma), papillary thyroid cancer with vascular
invasion, clinical N1 or >5 pathologic N1 with all involved lymph nodes <3 cm in largest
dimension and multifocal papillary microcarcinoma with extra-thyroidal extension (ETE)
and BRAFV600E mutated (if known).
● High-risk tumors :- include those demonstrating macroscopic invasion of tumor into the
perithyroidal soft tissues (gross ETE), incomplete tumor resection, and presence of
distant metastases (or postoperative serum thyroglobulin suggestive of distant
metastase) or pathologic N1 with any metastatic lymph node ≥3 cm in largest dimension.
Follicular thyroid cancers with extensive vascular invasion (>4 foci of vascular invasion)
also fall into this category.
Postoperative Management of DTC

● RAI therapy is recommended for high risk disease i.e, those with gross ETE
and M1 disease.
● Consideration of RAI is recommended for patients with intermediate-risk
disease and “generally favored” for patients with microscopic ETE due to the
risk of recurrent disease, large (>2–3 cm) or clinically evident lymph nodes
(central, mediastinal, and lateral neck) or presence of extranodal extension.
● RAI remnant ablation is not routinely recommended after thyroidectomy for
ATA low-risk DTC patients. However, it may be considered in patients with
aggressive histology or vascular invasion.
Follow-Up of Patients With Differentiated Thyroid Cancer

● Thyroglobulin Measurement:-Tg and anti-Tg antibody levels should be

measured initially at 6 to 12 month intervals and more frequently in patients

with high-risk tumors.

● Radioactive iodine I123 scan

● Cervical ultra sound

● FDG -PET scan

Medullary carcinoma
● accounts for about 5% of thyroid malignancies .
● arises from the parafollicular or C cells of the thyroid, which, in turn, are
derived from the ultimobranchial bodies. These cells are concentrated
superolaterally in the thyroid lobes, and this is where MTC usually develops.
C cells secrete calcitonin, a 32-amino-acid polypeptide that functions to lower
serum calcium levels.
● MTCs occur sporadically. However, approximately 25% occur within the
spectrum of several inherited syndromes such as familial MTC, MEN2A, and
MEN2B. All these variants are known to result secondary to germline
mutations in the RET proto-oncogene.
Clinical features :-

● Patients with MTC often present with a neck mass that may be
associated with palpable cervical lymphadenopathy (15% to 20%).
● Pain or aching is more common in patients with these tumors, and local
invasion may produce symptoms of dysphagia, dyspnea, or dysphonia.
● Distant blood-borne metastases to the liver, bone (frequently
osteoblastic), and lung occur later in the disease.
● The female-to-male ratio is 1.5:1.
● Most patients present between 50 and 60 years old, although patients
with familial disease present at a younger age.
● MTC secrete calcitonin and carcinoembryonic antigen (CEA), and other

peptides such as calcitonin gene related peptide, histaminadases,

prostaglandins E2 and F2 α, and serotonin.

● Patients with extensive metastatic disease frequently develop diarrhea, which

may result from increased intestinal motility and impaired intestinal water and

electrolyte flux. About 2% to 4% of patients develop Cushing’s syndrome as a

result of ectopic production of adrenocorticotropic hormone (ACTH).

Pathology:-

● unilateral (80%) in patients with sporadic disease and multicentric in familial

cases, with bilateral tumors occurring in up to 90% of familial patients .

● Microscopically, tumors are composed of sheets of infiltrating neoplastic cells

separated by collagen and amyloid. Marked heterogeneity is present; cells may

be polygonal or spindle shaped. The presence of amyloid is a diagnostic

finding, but immunohistochemistry for calcitonin is more commonly used as a

diagnostic tumor marker. These tumors also stain positively for CEA and
Diagnosis:-

● The diagnosis of MTC is established by history, physical examination, raised

serum calcitonin, or CEA levels, and FNAB cytology of the thyroid mass.
● Calcitonin and CEA are used to identify patients with persistent or recurrent
MTC. Calcitonin is a more sensitive tumor marker, but CEA is a better
predictor of prognosis.
● Attention to family history is important because about 25% of patients with
MTC have familial diseaseand need be screened for RET point mutations,
pheochromocytoma, and HPT.
Treatment :-
● A neck ultrasound is recommended to evaluate the central and lateral neck
compartments and the superior mediastinum.
● Serum calcitonin, CEA, calcium levels should also be measured, and RET
proto-oncogene mutation testing should be performed.
● Pheochromocytomas need to be excluded. If patients are found to have a
pheochromocytoma, operated first.
● Primary hyperparathyroidism, if present, is treated at the time of
thyroidectomy.
● These tumors are generally (>50%) bilateral. Total thyroidectomy is the
treatment of choice for patients with MTC because of the high incidence of
multicentricity, the more aggressive course,with bilateral prophylactic central
neck node dissection due to frequent involvement in early disease.
RET kinase inhibitor

● Sorafenib, sunitinib, lenvatinib, and cabozantinib are some such multikinase

inhibitors, whereas axitinib and pazopanib act only on VEGFR. Vandetanib
inhibits both targets and is also an EGF receptor inhibitor, and cabozantinib
targets c-MET in addition to RET and VEGF receptor. Both drugs are
currently approved by the FDA and EMA for the treatment of advanced and
progressive MTC based on data that they prolong progression-free survival, in
addition to reducing secretion of calcitonin and CEA. They are recommended
as first-line systemic therapy in symptomatic patients with advanced MTC
Postoperative Follow-Up and Prognosis.
● Follow up is done by annual measurements of calcitonin and CEA levels, in
addition to history and physical examination.
● Ultrasound, CT, MRI, and more recently, FDG-PET/CT scans are used to
localise recurrent diseases.
● Prognosis is related to disease stage. The 10-year survival rate is
approximately 80% but decreases to 45% in patients with lymph node
involvement.
● Survival also is significantly influenced by disease type. It is best in patients
with non-MEN familial MTC, followed by those with MEN2A, and then those
with sporadic disease. Prognosis is the worst (survival of 35% at 10 years) in
patients with MEN2B. Performing prophylactic surgery in RET oncogene
mutation carriers not only improves survival rates but also renders most
patients calcitonin free.
Anaplastic Carcinoma

● Anaplastic carcinoma accounts for approximately 1% of all thyroid malignancies.

● F>M
● Commonly presents at 70-80yrs of age
● The typical patient has a long-standing neck mass, which rapidly enlarges and
may be painful. Associated symptoms such as dysphonia, dysphagia, and
dyspnea are common.
● The tumor is large and may be fixed to surrounding structures or may be
ulcerated with areas of necrosis .
● Lymph nodes usually are palpable at presentation. Evidence of metastatic spread
also may be present.
● Pathology:-Grossly firm and whitish in appearance.

● Microscopically, sheets of cells with marked heterogeneity are seen.

The three main histologic growth patterns are spindle cell, squamoid,

and pleomorphic giant cell. Tumors may show a predominance of one

pattern or a mixture of various patterns.

Prognosis:-This tumor is one of the most aggressive thyroid malignancies, with few
patients surviving 6 months beyond diagnosis

Treatment:A total or near-total thyroidectomy with therapeutic lymph node dissection

is recommended for patients with an intrathyroidal mass.

If extrathyroidal extension is present, an en bloc resection should be considered if all

gross disease can be removed (R1)

Cytotoxic chemotherapy (with some combination of a taxane, anthracycline, and

platinum) is typically given concurrently and has been associated with prolonged
survival, although these agents are also being used in a neoadjuvant fashion,
particularly in patients with unresectable disease.
Lymphoma
● Lymphomas account for <1% of thyroid malignancies, and most are of the non-Hodgkin’s B-cell
type
● Usually seen in patients with chronic lymphocytic thyroiditis.Chronic antigenic lymphocyte
stimulation has been suggested to result in lymphocyte transformation.
● symptoms similar to those of patients with anaplastic carcinoma.
● Investigation:-usg
● FNAB
● TREATMENT:-thyroid lymphoma respond rapidly to chemotherapy (CHOP—cyclophosphamide,
doxorubicin, vincristine, and prednisone), which also has been associated with improved survival.
● The overall 5-year survival rate is about 50%; patients with extrathyroidal disease have markedly
lower survival rate.
Reference
● Schwartz’s Principles of Surgery Eleventh Edition.
● SABISTON: TEXTBOOK OF SURGERY: THE BIOLOGICAL BASIS OF MODERN
SURGICAL PRACTICE, TWENTY FIRST EDITION.
● Bailey & Love’s SHORT PRACTICE of SURGERY 27th edition.
● 2015 American Thyroid Association Management Guidelines for Adult Patients
with Thyroid Nodules and Differentiated Thyroid Cancer.
Thank you