Thyroid Nodules: Clinical, Pathologic and Pathophysiologic Correlates Flashcards
Disorders that can lead solitary thyroid nodules
- follicular/hurthle cell adenoma
- follicular/hurthle cell carcinoma (5-15%)
Characteristics of Hurthle cell adenoma
- 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
Characteristics of Hurthle cell carcinoma
- 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
Minimally invavsive vs. Widely invasive Hurthle cell carcinoma
- 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
Common cause multiple thyroid nodules
- Papillary Thyroid Carcinoma (PTC):
- Anaplastic carcinoma
- Medullary carcinoma
- Thyroid lyphoma
Microscopic appearance of Papillary thyroid carcinoma
- 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.
Causes of papillary thyroid carcinoma (PTC)
- 20% constitutive act RET by rearrangement
- 20% Ras point mutation
- 40% BRAF point mutation
Characteristics of papillary thuroid carcinoma
- 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
Characteristics of Anaplastic carcinoma
- 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
Characterics of medullary carcinoma
- 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
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Microscopic findings/immunostains in medullary carcinoma
- Microscopic:
- Neuroendocrine C cell nests/ribbons/sheets/cords
- Amyloid or collagen in supporting stroma
- Immunostains → neg TG, + Calcitonin, +Chromogranin
Characteristics of thyroid lymphoma
- Primary lymphoma of thyroid is rare but usually arises in the setting of Hashimoto or other autoimmune thyroiditis
- Common type is B-cell lymphoma
Basic types of thyroid nodules
- 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.
Main tests are helpful to evaluate for thyroid nodule
- Serum thyroid stimulating hormone
- thyroid scan
- thyroid ultrasound
- fine needle aspiration biopsy
Characterstics of serum TSH in evaluation of thyroid nodules
- If the TSH is suppressed, the nodule is likely hot → benign
- If the TSH is normal or elevated, the nodule is probably cold → malignant
Characterstics of serum thyroid scan in evaluation of thyroid nodules
- Employs radioactive iodine (123I),
- 123I is concentrated in a hot nodule, but relatively excluded from a cold nodule.
Characteristics of thyroid ultrasound (US) in evaluation of thyroid nodules
- 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
Characteristics of Fine Needle Aspiration Biopsy (FNAB) in evaluation of thyroid nodules
- 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.
Characteristics of suspicious or indertminate cytology on FNAB
- 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.
Cytologic features of benign FNAB
Flat sheets of cells →
Round uniform nuclei, “honey-comb” appearance
Cytologic features of papillary cancer on FNAB
- Papillae/sheets of cells + diagnostic nuclear features
- If architecturally microfollicular, then it is called follicular variant of papillary
Cytologic features of follicular neoplasm on FNAB
Abundant cells, often in sheets or forming microfollicles
Cytologic features of hurthle cell neoplasm on FNAB
- Large cells with abundant cytoplasm
- Large pleomorphic nuclei
- Can be seen in groups or as single cells
Cytologic features of medullary carcinoma on FNAB
- 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.
Cytologic features of anaplastic carcinoma on FNAB
Large pleomorphic nuclei, malignant-appearing
Cytologic features of lymphomas on FNAB
- Cellular aspirate with monotonous population of large lymphocytes.
- Additional studies (immunostains and flow cytometry to needed to confirm)
Risk of malignancy and usual management of non-diagnostic & benign thyroid tumors
- Non-dx:
- risk = unknown risk
- tx = Repeat FNA
- Benign
- risk = 0-3%
- tx = Clinical Follow Up
Risk of malignancy and usual management of ACUS (indeterminate) thyroid tumors
- risk = 5-15%
- tx = repeat FNA
Risk of malignancy and usual management of suspicious for follicular neoplasm thyroid tumors
- Susp for Follicular Neoplasm:
- risk = 15-30%
- tx = lobectomy
Risk of malignancy and usual management of suspicous for malignant and malignant thyroid tumors
- suspicious:
- risk = 60-75%
- tx = thyroidectomy
- malignant:
- risk = 97-99%
- tx = thyroidectomy
