Approach to thyroid malignancy

Papillary Carcinoma
• Risk Factors
o Radiation exposure
o Female “2:1”
• Clinical Behavior
o Occurs in iodine-sufficient areas
o Slow growing painless nodule
o Lymph node metastases are common
o mean age at presentation is 30 to 40 years.
o euthyroid and present with a slow-growing painless mass in the neck
o distant metastasis not common but when it happens à lungs, followed by bone,
liver, and brain.

• Pathology
o Macroscopic features
§ hard and whitish and remain flat on sectioning with a blade
§ hard and whitish and remain flat on sectioning with a blade
o Microscopic features
§ papillary projections
§ mixed pattern of papillary and follicular structures, or a pure follicular
pattern (follicular variant).
§ Presence of Orphan Annie nuclei “Diagnostic on FNAB”
§ Psammoma bodies, which are microscopic, calcified deposits
representing clumps of sloughed cells, also may be present.
§ Multifocality is common in papillary carcinoma and may be present in up
to 85% of cases “RISK FOR CERVICAL L.N. METS”
§ Other rare aggressive variants include, tall cell, insular, columnar, diffuse
sclerosing, clear cell, trabecular, and poorly differentiated types.
• Prognostic Indicators
o presence of BRAF V600E mutation, is associated with aggressive tumor
characteristics.
o presence of N-ras and gsp mutations
overexpression of c-myc
and presence of p53 mutations also have
been associated with a worse prognosis.
 • Points to remember
o When PTC is diagnosed by FNAB, the definitive operation can be done without
confirming the diagnosis by frozen section during the operation.
o If intraoperative frozen-section examination of a lymph node or primary tumor
confirms carcinoma, completion total or near-total thyroidectomy is performed.

Follicular Carcinoma
• Risk Factors
o iodine-deficiency
o Female 3:1
• Clinical behavior
o mean age at presentation of 50 years old
o present as solitary thyroid nodules.
o history of rapid size increase, and long-standing goiter.
o Pain is uncommon, unless hemorrhage into the nodule has occurred.
o cervical lymphadenopathy is uncommon at initial presentation.
o FNAB is unable to distinguish benign follicular lesions from follicular carcinomas.
o Large follicular tumors (>4 cm) in older men are more likely to be malignant.
• Pathology
o solitary lesions, and the majority are surrounded by a capsule
o follicles are present, but the lumen may be devoid of colloid.
o Malignancy is defined by the presence of capsular and vascular invasion

Hürthle Cell Carcinoma

o subtype of follicular thyroid cancer
o they are more often multifocal and bilateral (about 30%).
o usually do not take up RAI
o more likely to metastasize to local nodes (25%) and distant sites.
o associated with a higher mortality rate (about 20% at 10 years).
o lobectomy and isthmusectomy being sufficient surgical treatment for unilateral
Hürthle cell adenomas.
o When Hürthle cell neoplasms are found to be invasiveà total thyroidectomy
should be performed. These patients should also undergo routine central neck
node removal, and modified radical neck dissection when lateral neck nodes are
palpable or identified by ultrasonography.
Treatment of Differentiated Thyroid Carcinoma (Papillary and Follicular)

• Guidelines to Surgery Sabiston chapter 36 page 907 + current Page 661

Total thyroidectomy + RAI therapy is indicated in:
o Age less than 15 or older than 45
o Radiation History
o Known distant metastasis
o Bilateral nodularity
o Extrathyroidal extension
o Tumor greater than 4 cm
o Cervical L.N. metastasis
o Aggressive histological variant
Other than that Lobectomy is sufficient
• Point to remember in DTC
o Does not require prophylactic compartmental dissection “for L.N.”
o Only evidence of lymph node macrometastases serves as an indication for
compartmental neck dissection (i.e., central neck dissection or ipsilateral lateral
neck dissection).

Surgical Approach to FNAB result to reach for a Dx:

• suspicious for follicular/Hürthle neoplasm:
o hemithyroidectomy à
§ if Hürthle adenoma, hemi is enough
§ if Hürthle carcinoma à completion thyroidectomy + central
compartment L.N. dissection
o total thyroidectomy is indicated if:
§ significant contralateral lobe nodularity
§ history of head and neck radiation
§ risk with a second anesthesia
• Atypia of undetermined significance/follicular lesion of undetermined significance:
o Repeat FNA
o If repeat Biopsy fails à lobectomy with or without intraoperative frozen section
is warranted to achieve the Diagnosis.

Radioiodine Therapy for DTC

• Screening with RAI is more sensitive than chest x-ray or CT scanning for detecting
metastases
• it is less sensitive than Tg measurements for detecting metastatic disease in most
differentiated thyroid cancers except Hürthle
• RAI indications are similar to Total thyroidectomy indications written previously
• Remnant ablation can be performed in 2 approaches:
 o recombinant TSH (rTSH) stimulation à then ablation, no need to stop Thyroxine
à associated with an improved quality of life.
o If hormone withdrawal is used, T 4 therapy should be discontinued for
approximately 6 weeks before scanning with 131 I.
§ T 3 has a shorter half-life than T 4 (1 day vs. 1 week) and needs to be
discontinued for 2 weeks to allow TSH levels to rise before treatment.
Levels >30 mU/L are considered optimal
§ A low-iodine diet also is recommended during this 2-week period.
• Treatment doses of 30 to 100 mCi are recommended for ablation in low-risk patients.
• higher risk patients (residual microscopic disease suspected or documented; tall cell,
insular, or columnar cell histology), higher doses (100 to 200 mCi) are recommended.
• If patients have an elevated Tg level, but negative RAI scan, some physicians
recommend treating once with 100 mCi of 131 I and repeating the imaging 1 to 2 weeks
later.

External-Beam Radiotherapy
• required to control unresectable, locally invasive or recurrent disease and to treat
metastases in support bones to decrease the risk of fractures.
• control of pain from bony metastases when there is minimal or no RAIU.

Follow up of DTC
• Thyroglobulin Measurement:
o Tg and anti-Tg antibody levels should be measured initially at 6-month intervals.
o In low risk patients who have low Tg level in first yearà you should measure
after T 4 withdrawal or recombinant TSH stimulation approximately 12 months
after ablationà undetectable stimulated Tg levels can be followed annually with
clinical exam.
o Tg level of >2 ng/mL following rTSH stimulation is highly sensitive in identifying
patients with recurrent tumor.
o Tg measurements in FNAB aspirates have also been shown to be useful in the
detection of nodal metastatic disease.
o
• Imaging
o low-risk patients with negative TSH-stimulated Tg and cervical ultrasound do not
require routine diagnostic whole-body radioiodine scans.
o diagnostic whole-body scans 6 to 12 months after remnant ablation may be of
value in the follow-up of patients with high or intermediate risk of persistent
disease.
o cervical ultrasound be performed to evaluate the thyroid bed and central and
lateral cervical nodal compartments at 6 and 12 months after thyroidectomy and
then annually for at least 3 to 5 years.
o suspicious nodes >5 to 8 mm on the smallest diameterà should be biopsied for
cytology as well as Tg measurement in the aspirate washout.
o recurrent or persistent thyroid cancer in patients who have Tg-positive, RAI
scan–negative disease à use FDG-PET and PET-CT scans
o FDG-PET can also be useful for the initial staging of patients with poorly
differentiated thyroid carcinomas or Hürthle cell tumors.
o FDG-PET prognostic tool in patients with metastatic disease and to evaluate the
response to treatment in patients with metastatic or locally advanced disease.
Medullary Carcinoma
• Remember that:
• arises from the parafollicular or C cells of the thyroid, These cells are
concentrated superolaterally in the thyroid lobes, and this is where MTC usually
develops.
• Most MTCs occur sporadically
• 25% occur within the spectrum of several inherited syndromes such as familial
MTC, MEN2A, and MEN2B.
• 2ndry to mutations in the RET proto-oncogene.
• Pain or aching is more common in patients with these tumors.
• Distant blood-borne metastases to the liver, bone (frequently osteoblastic), and
lung
• female-to-male ratio is 1.5:1
• patients present between 50 and 60 years old, while familial present at an early
age.
• They secrete, calcitonin, carcinoembryonic antigen (CEA), histaminadases,
prostaglandins E 2 and F 2 α, and serotonin
• Diarrhea can be an evidence of extensive metastatic disease
• They can produce ectopic ACTH à causing Cushing syndrome (2% to 4%).

• Pathology
o MTCs typically are unilateral (80%) in patients with sporadic disease.
o in familial cases its multicentric, and 90% bilateral.
o presence of amyloid is a diagnostic finding, but immunohistochemistry for
calcitonin is more commonly used as a diagnostic tumor marker.
• Diagnosis
o Family Hx
o Physical Exam
o Raised serum calcitonin or CEA level
o US neck for evaluation of thyroid and L.n. compartments
o FNAB
o New patients with MTC should be screened for RET point mutations,
pheochromocytoma, and HPT.
o Calcitonin and CEA can be used to monitor patient for recurrent disease
o CEA is better predictor of prognosis.
Treatment
• If patient has pheochromocytoma à must be operated on first.
• Total thyroidectomy is the treatment of choice for patients with MTC.
• 131 I therapy usually is not effective.
• bilateral prophylactic central neck node dissection should be routinely performed.
 • Patients with palpable lymph nodes or serum calcitonin greater than 150 to 400 pg/mL
should undergo further imaging (CT scan of neck, chest, abdomen) to evaluate for
distant metastatic disease.
• In patients who have hypercalcemia and an increased PTH at the time of thyroidectomy,
only obviously enlarged parathyroid glands should be removed.
• When a normal parathyroid cannot be maintained on a vascular pedicle, it should be
removed, biopsied to confirm that it is a parathyroid, and then autotransplanted to the
forearm of the nondominant arm, particularly in patients with MEN2A
• In MEN2B and familial MTC à Re-implantation into the sternocleidomastoid muscle is
also acceptable
• Prophylactic thyroidectomy is recommended within the first year of life for children with
MEN 2B and between 3 and 5 years of age in children with MEN 2A, mutations at codon
634, and familial MTC.
• Central neck dissection can be avoided in children who are RET-positive and calcitonin-
negative with a normal ultrasound examination.
• Vandetanib à treatment of advanced and progressive MTC.
Postoperative Follow-Up and Prognosis
• annual measurements of calcitonin and CEA levels
• history and physical examination.
• For recurrent disease à ultrasound, CT, MRI, and more recently, FDG-PET/CT scans.
• Prognosis in MTC is affected by Nodal statusà 10-year survival rate is approximately
80% but decreases to 45% in patients with lymph node involvement.
• Survival is best in non-MEN familial MTC then MEN2A, then sporadic
• Worst survival is associated with MEN2B survival of 35% at 10 yearsàthus prophylactic
thyroidectomy in 1st year of life.
Anaplastic Carcinoma
o Women are more commonly affected
o present in the seventh and eighth decade of life.
o Hx of long-standing neck mass, which rapidly enlarges and may be painful.
o Commonly associated with dysphonia, dysphagia, and dyspnea.
o Tumor maybe larged or fixed, and may be ulcerated with areas of necrosis
o L.N. palpable at presentation
o FNABà characteristic giant and multinucleated cells à diagnostic
o FNAB DDxà lymphomas, medullary carcinomas, direct extension from a laryngeal
carcinoma
o If spindle cell are present à rule out primary and metastatic sarcomas.
o Immunohistochemical markers can aid with excluding other diagnoses.
o If there are necrotic material on FNAB à Core or incisional biopsy

• Pathology
o three main histologic growth patterns are spindle cell, squamoid, and
pleomorphic giant cell.
• Treatment and Prognosis
o Bad prognosis rarely survive beyond 6 months
o Surgery:
o Intrathyroidal à total thyroidectomy + therapeutic L.N. dissection or
lobectomy if vocal cord is at risk
o Extrathyroidalà en bloc resection, only gross disease (R1 resection)
o impending airway lossà Tracheostomy
o Good performance patients and no mets:
o Adjuvant radiation
o Concurrent Cytotoxic chemotherapy can be given

Lymphoma
o most are of the non-Hodgkin’s B-cell type
o most thyroid lymphomas develop in patients with chronic lymphocytic thyroiditis.
o presentation can be confused with anaplastic carcinoma
o Unlike anaplastic à nodule is painless
o If FNAB can’t make the diagnosis “Especially low grade lymphoma”:
o Core needle Bx or open Bx to reach definitive Diagnosis
Treatment:
o CHOP—cyclophosphamide, doxorubicin, vincristine, and prednisone
o Recommended to be combined with radiotherapy
o Thyroidectomy and nodal resection are used to alleviate symptoms of airway
obstruction in patients who do not respond quickly to the above regimens.
• Prognosis is affected by histologic grade and dissemination à overall 5-year survival is 50%
and lower in extrathyroidal disease
Metastatic Carcinoma
o Usually from kidney, breast, lung, and melanoma.
o Resection of the thyroid, usually lobectomy, may be helpful in many patients, depending
on the status of their primary tumor.

Ref.
Shwarts, sabiston, and current.