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Prepared by Kurt Schaberg

Thyroid Cytology
Adequacy Criteria Must see at least 6 groups of well-visualized follicular
epithelial cells, each consisting of at least 10 cells.
Exceptions:
1) Abundant colloid with radiographic findings compatible
with a colloid nodule
2) Abundant inflammation with a solid nodule
(lymphocytes, granulomas, or neutrophils)
3) Atypia
Ideally, follicular epithelium should be in nice big, flat (“monolayered”) sheets, with evenly
spaced (“Honeycomb-like”) dark, round nuclei with uniformly granular chromatin.

Benign Follicular Nodule Watery Colloid


Histologically represent nodular goiter, adenomatoid
nodules, and colloid nodules.
Variable amounts of: colloid, bland follicular cells,
Hürthle cells, and macrophages.
Should be sparse to moderately cellular with a good
amount of colloid (easiest to see on diff-quick)
Watery colloid – thin, watery, like cellophane
Dense Colloid – thick, hyaline
Cystic degeneration: macrophages, “reparative” stretched cells Dense Colloid

Lymphocytic Thyroiditis
Hypercellular smear with abundant, polymorphic lymphocytes.
Hürthle cell metaplasia common (Large cells with abundant
granular cytoplasm and prominent nucleoli).
Advanced cases may be hypocellular (due to fibrosis).
Often middle-aged women with associated circulating
autoantibodies.

Granulomatous Thyroiditis Aka subacute or de Quervain’s


Self-limited inflammatory condition, usually diagnosed clinically
Clusters of epithelioid histiocytes (i.e., granulomas) and
multinucleated giant cells, often ingesting colloid
Early can have neutrophils and eosinophils. Later have lymphocytes.
Papillary Carcinoma
Most common malignant thyroid neoplasm
Relatively good prognosis. Spreads via
lymphatics.
Classic findings:
-Intranuclear pseudoinclusions
-Powdery, pale chromatin with marginal
micronucleoli
-Enlarged, irregular nuclei
-Longitudinal nuclear grooves
-Dense, squamoid cytoplasm
-Multinucleated giant cells
-Dense, “Bubble gum” colloid
-Septate cytoplasmic vacuoles
-Papillary structures w/ and w/o fibrovascular
cores

Some findings, but “not enough”?


Consider Atypia of Undetermined Significance
(AUS) or Suspicious for Malignancy.

Follicular Neoplasm/Suspicious for Follicular Neoplasm


Cannot differentiate between Follicular Adenoma
and Carcinoma on cytology specimens (need to
see capsular or vascular invasion on resection
specimen!)
Moderately or Markedly cellular
Significant alteration in follicular architecture
→ Repetitive microfollicular pattern or cell
crowding/overlapping in trabeculae
→ Minimal colloid
Minimal cytologic atypia. Microfollicle: less than 15 cells
arranged in a circle that is at
Hürthle Cell Lesions: least 2/3 complete
Look for: 1) nonmacrofollicular
architecture, 2) absence of colloid, 3) Some findings, but “not enough”?
absence of inflammation, and 4) presence Consider Follicular Lesion of Undetermined
of “Transgressing blood vessels” Significance (FLUS)
Medullary Carcinoma
Can be sporadic or inherited (part of MEN 2A&B)
Derived from Parafollicular C cells→ stain with Calcitonin!
Moderate to Marked Cellularity. Often discohesive.
Plasmacytoid, polygonal, to spindled cells.
Mild to moderate pleomorphism.
“Salt and Pepper” chromatin.
Granular cytoplasm with small granules.
Occasional intranuclear pseudoinclusions or amyloid fragments
Undifferentiated (Anaplastic) Carcinoma
Extremely aggressive. Poor prognosis.
Classically older women with rapidly growing, hard
neck mass → trouble breathing
Variable cellularity. Often discohesive.
Epithelioid to Spindled cells.
Enlarged, pleomorphic nuclei.
Often associated necrosis and inflammation.
Can see osteoclast-like giant cells
The Bethesda System and Genetics
With rare exception, FNAs should be classified into one of the Bethesda Categories.
If you have an equivocal AUS/FLUS case, consider sending for molecular testing.
Papillary Thyroid Carcinoma:
MAPK Pathway Diagnostic Category Risk of Management
BRAF (most classic PTC’s) Malignancy
V600E (most common)
I Unsatisfactory Repeat US-guided FNA
RAS (associated with
follicular variant & NIFTP)
II Benign 0-3% Clinical follow-up
Medullary Carcinoma:
RET (think MEN2A&B) III AUS/FLUS ~5-15% Repeat FNA and/or
Molecular testing
Follicular Neoplasms:
RAS most common IV Follicular 15-30% Lobectomy
PAX8/PPARG Neoplasm
PTEN
V Suspicious for 60-75% Near total or total
Poorly Differentiated and Malignancy thyroidectomy
Anaplastic
TP53 VI Malignant 97-99% Thyroidectomy
CTNNB1
(and others mentioned above)

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