richard demay thyroid - K&M Congresskmcongress.com/eloadasok/iap2011/richard_demay_thyroid.pdf ·...
Transcript of richard demay thyroid - K&M Congresskmcongress.com/eloadasok/iap2011/richard_demay_thyroid.pdf ·...
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Richard M. DeMay, MDProfessor of Pathology
Director of Cytopathology
The University of Chicago
Thyroid CytopathologyThyroid Cytopathology
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Thyroid FNA Made Easy
� Granulomatous ThyroiditisGiant cells munching on colloid
� Hashimoto ThyroiditisLymphocytes + Oncocytes
� Papillary CarcinomaPapillae, nuclei, cytoplasm
� Medullary CarcinomaCarcinoid + amyloid
� Anaplastic CarcinomaUgly giant & spindle cells
� Follicular Lesions?Colloid vs Cells
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Granulomatous Thyroiditis
Giant cells munch
on yummy colloid
Epithelioid Histiocytes
See giant cells:
Think PTC!
Postviral syndrome; painful
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Hashimoto Thyroiditis
Lymphocytes
Oncocytes
Clues: Infiltration; Tangles; Plasma cells; LGBs
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Papillary Carcinoma
3 Best Clues
1. Papillae
2. Nuclear grooves
or inclusions
3. Squamoid cytoplasm
1 2 3
Giant CellPsammoma
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Medullary Carcinoma
When you don’t know…think medullary carcinoma!
Carcinoid + Amyloid
ICC: Calcitonin
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Anaplastic Carcinoma
Ugly Giant
& Spindle Cells
“Ugly Cells”
Think Anaplastic CA,
exclude metastasis
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Follicular Lesions…
…the problem diagnosis
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Follicular Lesions
�GoiterNonneoplastic
�Follicular NeoplasmsAdenomaCarcinoma
�Follicular Variant PTC
All more/less encapsulated nodules of follicles
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Goiter vs Neoplasm
~Never Follicular CA Could be Follicular CA
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This is so cool…
FNA biopsy
can predict
follicle size!
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Macronodules
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Micronodules
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Clues to Diagnosis
More colloid
…more likely benign
More cells
…more likely neoplastic
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Colloid vs Cells
Colloid Cellular FollicularNodule Nodule Nodule(BTN) (FLUS) (SFN)
Zone I Zone II Zone III
Colloid Cells
Very low risk
of malignancy
15%-30% risk
of malignancy
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3 Steps: Follicular Lesion Dx
1. Colloid vs Cells
2. Refine distinction
3. Exclude Papillary CA
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1. Colloid vs Cells*
Zone I: Colloid noduleColloid >> Cells
Zone II: Cellular noduleColloid ≈ Cells
Zone III: Follicular noduleCells >> Colloid
*LBC concentrates cells, loses colloid
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Colloid
Watery Colloid
Dense Colloid
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Fun with colloid
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2. Refine distinction
� Clues to goiter
� Clues to neoplasm
� Clues to carcinoma
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Clues to Goiter
� Fewer cells, more colloid
� Degeneration, Regeneration
Hemorrhage, Fibrosis, Cysts (foam cells,
macrophages, cholesterol), Calcification
Atypical epithelium (WARD cells)
� Variable cells and cell types
� Wide range follicle size
� Honeycomb sheets
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Honeycomb
=> Macrofollicles
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Hemorrhage
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Cystic Degeneration
“Nondiagnostic: cyst content”
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Stromal Fibrosis
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Perifollicular Fibrosis
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Calcification
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Paravacuolar Granules
Hemosiderin, Lipofuscin
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Flame Cells, Hurthle Cells, etc
Flame Cells
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Repair/Degeneration: Atypical Epithelium
WARD Cells
often Line Cysts
WARD Cells:Worrisome Atypia in
Reactive/Degenerative Cells
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Clues to Neoplasm
High cellularity/scant colloid
Microfollicular pattern
Nuclei: Uniform, ± enlarged
Chromatin: May be coarse
Nucleoli infrequent
Atypical epithelium (WARD cells)
usually correlates with goiter!
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Clues to Neoplasm
Microfollicles
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Follicular Lesions
Zone I Zone II Zone III
Colloid Cells
Honeycomb Microfollicles
BTN FLUS SFN
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Clues to Follicular CA
Marked…�Architectural Abnormality
Crowded, 3D groups
Irregular microfolliclesIncreased single cells
�Cytologic AtypiaNuclear Enlargement
PleomorphismAbnormal chromatinProminent or multiple nucleoliMitosis (atypical); Necrosis
Increases risk of malignancy!
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Follicular Carcinoma
Distorted Follicles
Cytologic Atypia
Atypia correlates with invasion!
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Follicular Carcinoma
Two Forms…
� Minimally invasive
Minimally atypical
—Minimally malignant
� Frankly invasive
Frankly atypical
—Frankly malignant
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3. Exclude Papillary CA
No matter what zone,
look at nuclei to exclude PTC
(colloid is irrelevant!)
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Nuclear features key:
� Nuclear grooves (extensive)
� Intranuclear Inclusions (even 1)
Other: Powdery chromatin,
Marginated nucleoli
Papillae, squamoid cytoplasm,
psammoma bodies, etc
Oranges vs Potatoes
Follicular Variant PTC
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Oranges vs Potatoes
Follicular Nuclei Papillary Nuclei
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Intranuclear Cytoplasmic Invaginations
NOT Orphan
Annie Eyes !
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Intranuclear Cytoplasmic
Invaginations (INCIs)
Fewer INCIs, stricter criteria
If debatable: Not diagnostic
Often cluster, but if numerous,
probably bubble artifact
Search-> epiphany: Zen of Cytology
99/100 Malignant; 9/10 PTC
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A confusion of
tongues…
The Bethesda System
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Report Format: 6 Tiered System
Diagnosis Cancer Risk Management
I. Nondiagnostic NA Rpt w/ US
II. Benign <3% F-U Clinically
III. AUS
ACUS, FLUS
5%-15% Rpt FNA
IV. Follicular
Neoplasm*
20%-30% Surgery
V. Suspicious 60%-75% Surgery
VI. Malignant 97%-99% Surgery
*Specify if Hürthle Cell type
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I. Non-Diagnostic
Limited cellularity
Poor fixation
Excess blood
Poor cell preservation
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Adequacy
6 groups of ≥10 well prepared,
well visualized follicular cells
Exceptions:
Thick colloid (Benign)
Thyroiditis (Benign)
Any atypia
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II. Benign
Colloid nodular disease
Colloid nodule
Hyperplastic/adenomatoid nodule
Macrofollicular adenoma
Thyroiditis
Acute thyroiditis
Hashimoto thyroiditis
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III. Atypia of Undetermined
Significance (AUS)
Atypical Cells of Undetermined
Significance (ACUS)
Follicular Lesion of Undetermined
Significance (FLUS)
Not convincingly benign, but not
sufficient for more definitive dx
Risk malignancy 5% to 15%
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AUS: Diagnostic Uncertainty
Microfollicles, Hürthle cells, cyst lining
cells, or focal features of PTC
Eg, prominent microfollicles or Hürthle
cells, but low overall cellularity
Compromised specimens common
eg, low cellularity, poor fixation,
obscuring blood, excessive clotting
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AUS due to poor fixation
R/O Papillary Carcinoma
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IV. (Suspicious for) Follicular Neoplasm*
Follicular patterned lesions lacking
nuclear features of PTC
Risk malignancy 15% to 30%
Notes:
1. Up to 35% non-neoplastic
2. Of malignancies, up to 68% = PTC
*Specify if Hürthle cell type
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V. Suspicious for Malignancy
Suspicious for specific cancer, eg, PTC
Patchy/incomplete nuclear features
Suspicious due to lesion necrosis, eg, ATC
Risk malignancy 60% to 75%
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VI. Malignant
Diagnostic of malignancy
Specify type if possible
Risk malignancy 97%-99%
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You’ve got
cancer !!!
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0
5000
10000
15000
20000
25000
30000
35000
40000
45000
50000
1970
1971
1972
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1984
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Thyroid Cancer
Incidence
Mortality
5th most common cancer in women
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True increase?
1. Environmental carcinogens
2. Environmental radiation
3. Other factors, eg, iodine?
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Or something else?
1. Advances in diagnostic imaging
Detects more abnormalities
2. Increased histologic sectioning
Detects incidental micro PTCs
Detects more invasion (FAd→FCA)
3. More liberal diagnostic criteria
Increased diagnosis of cancer
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You’ve got cancer!!!
Up to 100% of adults have thyroid “cancer”
Harach HR et al:
Occult Papillary Carcinoma of the Thyroid
Cancer 56: 531-538, 1985
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You’ve got cancer!!!
Up to 100% of adults have thyroid “cancer”
Harach HR et al:
Occult Papillary Carcinoma of the Thyroid:
A ‘Normal’ Finding in Finland.
Cancer 56: 531-538, 1985
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g{tÇ~ çÉâg{tÇ~ çÉâg{tÇ~ çÉâg{tÇ~ çÉâ
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g{x XÇwg{x XÇwg{x XÇwg{x XÇw
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Advanced Thyroid Cytology
Hürthle cell lesions
Poorly differentiated carcinoma
Hyalinizing trabecular neoplasms
Hematologic malignancies
Metastases
Graves disease
Therapeutic effects
Dyshormonogenetic goiter
Pregnancy
The Bethesda System
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Hürthle Cell Lesions
Can
of
Worms?
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Mixed Bag of Lesions
Metaplastic Change
� Goiters
� Thyroiditis
� Adenomas
� Carcinomas
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Guidelines
Favors benign or
nonneoplastic
Favors neoplastic or
malignant
Colloid Diffuse atypia
Honeycomb sheets Microfollicles
Chronic inflammation High N/C ratios
PTC features
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Cutting the Gordian Knot
If exclusively Hürthle cells:
~75% chance neoplastic
If neoplastic, ~33% malignant
=> ~1 in 4 chance of cancer
Dx: (Suspicious for)
Hürthle cell neoplasm
Recommend: surgery
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Poorly Differentiated Carcinoma
Insular and Non-Insular types
1. Solid/trabecular/
insular growth
2. No PTC nuclear features
3. At least one of:
a. Convoluted nuclei
b. ↑ Mitotic activity
c. Necrosis
TG, TTF-1 (+); Calcitonin (–)
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Hyalinizing Trabecular Neoplasms
Unique entity vs PTC vs Others?
Nuclei: Similar to PTC
Cytoplasm: No NSGs
Background: ± Psammomas
DDx: PTC, Medullary CA
Thyroglobulin (+), Calcitonin (–)
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Hematologic Malignancies
Sudden growth in Hashimoto thyroiditis
� Diffuse large B cell (easier to dx)
� MALTomas (harder to dx)
� Other lymphomas rare
DDx: Florid lymphoid phase Hashimoto
TGFF: Thank god for flow (cytometry)
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Thyroid Sarcomas
Primary sarcomas:
Extremely rare
Examples: Lipo-, leiomyo-, angio- sarcoma
DDx: Most “sarcomas” = anaplastic CA*
*Both TG and CK can be (–) in anaplastic CA
Anaplastic Carcinoma
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Metastases
Not rare, but rarely dx in past
FNA Bx → antemortem dx
Most pts have known history
Grave prognostic sign
Often PD, unlike most 1°’s
Kidney, lung, breast, GI;
melanoma; lymphomaRCC
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Graves Disease
Related to Hashimoto Disease
Clinical and lab findings
FNA biopsy:
High cellularity
Pale watery colloid
Flame and Hürthle cells
Inflammation, granulomas
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Therapeutic Effects
Radiation or antithyroid Rx
→ marked cytologic atypia
Pearl: Random atypia, mitoses rare
Radiation: ↑ risk CA, esp PTC
Radioiodine Rx Antithyroid Rx
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Dyshormonogenetic Goiter
Congenital hypothyroidism
Autosomal recessive
Enzyme defects in hormone
synthesis → goiter
FNA: High cellularity, atypical cells,
microfollicles, scant colloid
Mimics neoplasm, may favor CA
Actual malignant change rare!
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Pregnancy
Iodine lost in urine
→ thyroid hyperplasia
FNA Biopsy:
High cellularity, watery colloid, flame cells
Papillary hyperplasia may suggest PTC
Women of childbearing age at risk of PTC
Look for usual features of PTC to dx:
Nuclear grooves, INCIs, etc, etc
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Mission:
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Things are not what they seem…
snake tree
wall rope
spear
fan
The blind and the elephant
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Seems Malignant
Atypical Adenoma
= Benign !
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Seems Benign
Well Differentiated Follicular Carcinoma
= Malignant !!
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Non-neoplastic !!!
Goiter (Dyshormonogenetic)
Hashimoto Thyroiditis
Radioiodine Rx Antithyroid Rx
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Histologic Diagnosis
Can be difficult & subjective�Capsular invasion vs trapped glands
�Vascular invasion not always easy dx
�Wide invasion vs some other tumoreg, insular carcinoma
�Metastasis vs sequestered goitrous nodule vs lateral aberrant thyroid
�Follicular variant PTC: most common
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Gold Standard Failure
Up to 3/4 of follicular carcinomashistologically misdiagnosed*
*“interobserver variation”
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Conclusion
Differential diagnosis
�Nonneoplastic nodules
�Follicular adenomas
�Carcinomas
…is impossible