Thyroid Nodules: Clinical, Pathologic and Pathophysiologic Correlates

Question 1

Disorders that can lead solitary thyroid nodules

Answer 1

• follicular/hurthle cell adenoma
• follicular/hurthle cell carcinoma (5-15%)

Question 2

Characteristics of Hurthle cell adenoma

Answer 2

• Benign neoplasm derived from follicular epithelium
• Solitary nodule with a well formed capsule that compresses the adjacent non-neoplastic thyroid
• Microscopically
  
  • Variable sized follicles lined by follicular cells or Hurthle cells; confined within the capsule
  • Microscopic view of entire capsule is only way to distinguish adenoma from carcinoma

Question 3

Characteristics of Hurthle cell carcinoma

Answer 3

• Very similar to the adenoma except that it may be minimally invasive or widely invasive
• Solitary nodule, made of variable sized follicles, lined by follicular or Hurthle cells
• Again, distinction between adenoma (benign) and carcinoma (malignant) can only be made after a thorough microscopic review of the entire capsule; nuclear atypia or other cytologic features are not helpful in this distinction
• 50% are caused by PPAR ɣ - PAX 8 rearrangment

Question 4

Minimally invavsive vs. Widely invasive Hurthle cell carcinoma

Answer 4

• Minimally invasive carcinoma shows capsular or vascular invasion vs adenoma which is confined
• Widely invasive carcinoma shows extensive invasion, may be even beyond the thyroid capsule into the surrounding soft tissues of the neck

Question 5

Common cause multiple thyroid nodules

Answer 5

• Papillary Thyroid Carcinoma (PTC):
• Anaplastic carcinoma
• Medullary carcinoma
• Thyroid lyphoma

Question 6

Microscopic appearance of Papillary thyroid carcinoma

Answer 6

• Variable
• Classically the architecture shows finger-like structures with fibrovascular cores and epithelial lining → upper right photo
• Characteristic epithelial cell nuclear features:
• Fine nuclear chromatin
• Nuclear clearing = “Orphan Annie”
• Nuclear grooves
• Pseudo-inclusions → ground glass nuclei
• Psammoma bodies, multi-nuc giant cells, and fibrosis may be seen.

Question 7

Causes of papillary thyroid carcinoma (PTC)

Answer 7

• 20% constitutive act RET by rearrangement
• 20% Ras point mutation
• 40% BRAF point mutation

Question 8

Characteristics of papillary thuroid carcinoma

Answer 8

• Most common type (85%) of thyroid malignancy
• Any age, often young adults
• May be multifocal
• Metastasizes via lymphatics to the neck nodes are not ideal but ok
• Slow growth, excellent prognosis

Question 9

Characteristics of Anaplastic carcinoma

Answer 9

• Older age group
• Extremely aggressive, bulky mass with rapid enlargement, invasive into trachea and soft tissues
• Composed of highly anaplastic cells exhibiting three distinct morphologic patterns:
  
  • Spindled
  • Giant cell → photo right
  • Squamoid
• Poor prognosis, death within a year in most cases

Question 10

Characterics of medullary carcinoma

Answer 10

• Middle aged or elderly patients, but also children and young adults (MEN IIA|B)
• Generally high levels of serum calcitonin (no systemic manifestations), hence the MEN link - Endocrine
• Slow growth, metastasizes to local lymph nodes
• Prognosis is poor in MEN cases
  *

Question 11

Microscopic findings/immunostains in medullary carcinoma

Answer 11

• Microscopic:
  
  • Neuroendocrine C cell nests/ribbons/sheets/cords
  • Amyloid or collagen in supporting stroma
• Immunostains → neg TG, + Calcitonin, +Chromogranin

Question 12

Characteristics of thyroid lymphoma

Answer 12

• Primary lymphoma of thyroid is rare but usually arises in the setting of Hashimoto or other autoimmune thyroiditis
• Common type is B-cell lymphoma

Question 13

Basic types of thyroid nodules

Answer 13

• Two basic types of thyroid nodules, hot and cold.
• Cold nodules >> hot nodules.
• Cold nodules are also the group at risk for being malignant.
• Hot nodules concentrate radioiodine and are likely benign.

Question 14

Main tests are helpful to evaluate for thyroid nodule

Answer 14

• Serum thyroid stimulating hormone
• thyroid scan
• thyroid ultrasound
• fine needle aspiration biopsy

Question 15

Characterstics of serum TSH in evaluation of thyroid nodules

Answer 15

• If the TSH is suppressed, the nodule is likely hot → benign
• If the TSH is normal or elevated, the nodule is probably cold → malignant

Question 16

Characterstics of serum thyroid scan in evaluation of thyroid nodules

Answer 16

• Employs radioactive iodine (¹²³I),
• ¹²³I is concentrated in a hot nodule, but relatively excluded from a cold nodule.

Question 17

Characteristics of thyroid ultrasound (US) in evaluation of thyroid nodules

Answer 17

• Accurately defines number of distinct thyroid nodules as well as location and size
• Recent studies: certain ultrasound features are more often associated with malignant nodules
• US characterization of thyroid nodules can target the most suspicious nodules for the most helpful diagnostic tool, the fine needle aspiration biopsy

Question 18

Characteristics of Fine Needle Aspiration Biopsy (FNAB) in evaluation of thyroid nodules

Answer 18

• Way of sampling cells from the thyroid nodule for cytological analysis.
• Normal sample does not have many cells.
• Papillary carcinoma has highly cellular aspirate
• Very reliable way of separating malignant from benign disease.
• 75- 80% of FNAB will be either clearly benign or clearly malignant and should be treated accordingly
• Suspicious or indeterminate cytology, comprises up to 15-20% of FNAB results and is the most difficult to manage.

Question 19

Characteristics of suspicious or indertminate cytology on FNAB

Answer 19

• Up to 20% of these nodules will be malignant, but 80% will, of course, be benign.
• In this group, we consider a thyroid scan → determines if hot or cold nodules
  
  • If hot, low risk for malignancy, treat accordingly.
  • If cold, integrate clinical information to help direct therapy.
• low clinical suspicion ==> followed closely with repeat biopsy in 3-6 months.
• increased clinical suspicion ==> proceed to surgery.

Question 20

Cytologic features of benign FNAB

Answer 20

Flat sheets of cells →

Round uniform nuclei, “honey-comb” appearance

Question 21

Cytologic features of papillary cancer on FNAB

Answer 21

• Papillae/sheets of cells + diagnostic nuclear features
• If architecturally microfollicular, then it is called follicular variant of papillary

Question 22

Cytologic features of follicular neoplasm on FNAB

Answer 22

Abundant cells, often in sheets or forming microfollicles

Question 23

Cytologic features of hurthle cell neoplasm on FNAB

Answer 23

• Large cells with abundant cytoplasm
• Large pleomorphic nuclei
• Can be seen in groups or as single cells

Question 24

Cytologic features of medullary carcinoma on FNAB

Answer 24

• Small, round to oval parafollicular cells with eccentric nuclei and coarse chromatin,
• Usually seen as single cells.
• Stromal amyloid appears as spherical homogeneous material.
• Immunocytochemistry demonstrates calcitonin.

Question 25

Cytologic features of anaplastic carcinoma on FNAB

Answer 25

Large pleomorphic nuclei, malignant-appearing

Question 26

Cytologic features of lymphomas on FNAB

Answer 26

* Cellular aspirate with monotonous population of large lymphocytes. * Additional studies (immunostains and flow cytometry to needed to confirm)

Question 27

Risk of malignancy and usual management of non-diagnostic & benign thyroid tumors

Answer 27

* Non-dx: * risk = unknown risk * tx = Repeat FNA * Benign * risk = 0-3% * tx = Clinical Follow Up

Question 28

Risk of malignancy and usual management of ACUS (indeterminate) thyroid tumors

Answer 28

* risk = 5-15% * tx = repeat FNA

Question 29

Risk of malignancy and usual management of suspicious for follicular neoplasm thyroid tumors

Answer 29

* Susp for Follicular Neoplasm: * risk = 15-30% * tx = lobectomy

Question 30

Risk of malignancy and usual management of suspicous for malignant and malignant thyroid tumors

Answer 30

* suspicious: * risk = 60-75% * tx = thyroidectomy * malignant: * risk = 97-99% * tx = thyroidectomy