Objective

1
Objective

• Common diagnostic terms
• Use and examples of the diagnostic terms
• Features of Indeterminate cytology
• Why use the term indeterminate
• What does Indeterminate mean for my patient
• Tools to help when the cytology is Indeterminate

2
Diagnostic Terminology

• Approximately 70 - 80 of thyroid fine needle
  aspiration biopsies can distinguish benign from
  malignant thyroid nodules.
• Much of the interpretive diagnostic difficulty
  arises with the remaining 20 - 30 of cases.
• These problematic cases have been placed in
  various diagnostic categories, which collectively
  have led to confusion of terminology and
  difficulty in management of patients with
  thyroid nodules.

3
Common Diagnostic Terms

• Unsatisfactory/ Non-diagnostic
• Benign/Reactive
• Suspicious
• Indeterminate
• Positive/Malignant

4
Unsatisfactory

• Insufficient or poor preservation and fixation of
  follicular cells to make a diagnosis.

5
Non-diagnostic

• Insufficient or poor preservation and fixation of
  follicular cells to make a diagnosis.
• Same as Unsatisfactory

6
Benign/Reactive

• Abundant colloid and bland follicular groupings.

7
Suspicious

• Moderate to low cellularity and equivocal
  malignant features for papillary carcinoma
  (includes the follicular variant of papillary
  thyroid carcinoma)

Baloch ZW, LiVolsi VA. Fine-Needle Aspiration of
Thyroid Nodules Past, Present, and Future.
Endocrine Practice 2004 10(3) 234-241.
8
Indeterminate

• High to moderate cellularity possible
  micro-follicular pattern and scant colloid
  (can be follicular or Hürthle cell)

Baloch ZW, LiVolsi VA. Fine-Needle Aspiration of
Thyroid Nodules Past, Present, and Future.
Endocrine Practice 2004 10(3) 234-241.
9
Positive/Malignant

• High cellularity and cytologicaly malignant cells

10
Dx. Unsatisfactory

• No follicular cells
• Pigment laiden macrophages

11
Dx. Benign/Reactive

• Benign Ex
• Nodular goiter
• Thyroiditis
• Colloid nodule

12
Dx. Suspicious

• Suspicious Ex
• Follicular variant of papillary
• Nuclear elongation, chromatin clearing, and
  grooves, but lacks nuclear inclusions.
• Papillary carcinoma
• But lacking some diagnostic criteria

Logani S et al. Thyroid nodules with FNA cytology
suspicious for follicular variant of papillary
thyroid carcinoma follow-up and management.
Diagn Cytopathol. 200023380-385.
13
Dx. Indeterminate

• Indeterminate Ex
• Follicular neoplasm
• Adenoma
• Carcinoma
• Hurthle cell neoplasm
• Adenoma
• Carcinoma

14
Dx. Positive/Malignant

• Malignant Ex
• Papillary carcinoma and variants
• Medullary carcinoma
• Anaplastic carcinoma
• Lymphoma
• Metastatic carcinoma

15
Indeterminate cytology

• Indeterminate lesions comprise 10 to 30 of
  cytopathologic diagnoses.
• 20 of indeterminate lesions are malignant
• Follicular variant of papillary
• Classic papillary
• Follicular carcinoma
• 80 are benign
• Adenomas
• Hyperplasia

16
Benign versus Follicular Neoplasm
Hyperplastic Nodule
Follicular Neoplasm
Grey Zone
Cells
-Overlapping cytologic features make it difficult
at times to separate between hyperplastic nodules
and follicular neoplasms
17
Indeterminate Cytology Criteria

• High cellularity
• Scant colloid
• Prominent microfollicles
• Nuclear overlapping and crowding
• Nuclear enlargement gt2X RBC
• Coarse clumpy chromatin
• Prominent nucleoli
• Lacking features of papillary carcinoma

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Cellular smearScant colloidMicrofollicular
Indeterminate Cytology
19
Microfollicles
20
Indeterminate Cytology

• Cellular
• No colloid
• All Hurthle

21
Indeterminate Cytology
Microfollicular Overlapping Crowding
22
Indeterminate Cytology - Hurthle
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Why Indeterminate and Not Suspicious

• Total FNAs 459
• Indeterminate diagnosis 339
• Suspicious diagnosis 120
• All cases underwent surgery
• Of the 339 Indeterminate cases
• 265 (78) benign histology
• 74 (22) malignant histology
• Of the 120 Suspicious cases
• 34 (28) benign histology
• 86 (72) malignant histology

Baloch ZW et al Fine-needle aspiration of
follicular lesions of the thyroid. Diagnosis and
follow-up. CytoJournal 2006, 39.
24
Why Indeterminate and Not Suspicious
of cases
NG-nodular goiter, FA- follicular adenoma, FVPTC-
follicular variant papillary thyroid carcinoma.
PTC- papillary thyroid carcinoma, FCA-follicular
carcinoma, HCCA- hurthle cell carcinoma
25
Why Indeterminate and Not Suspicious

• The category of follicular neoplasm/lesion can
  further be modified by dividing these cases into
  two lesions with and without subtle nuclear
  features of papillary carcinoma because of marked
  difference in malignancy rates (22 vs 72).

Baloch ZW et al Fine-needle aspiration of
follicular lesions of the thyroid. Diagnosis and
follow-up. CytoJournal 2006, 39.
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28
Protein Expression in Thyroid Cancers
Prasad M et al. Galectin-3, fibronectin-1,CITED-1,
HBME1, and cytokeratin-19 immunohistochemistry
is useful for the diagnosis of thyroid tumors.
Mod Path. 20051848-57.
29
Protein Expression in Non-neoplastic Thyroid
Prasad M et al. Galectin-3, fibronectin-1,CITED-1,
HBME1, and cytokeratin-19 immunohistochemistry
is useful for the diagnosis of thyroid tumors.
Mod Path. 20051848-57.
30
Differential diagnosis of benign and malignant
tumors with follicular architecture
Prasad M et al. Galectin-3, fibronectin-1,CITED-1,
HBME1, and cytokeratin-19 immunohistochemistry
is useful for the diagnosis of thyroid tumors.
Mod Path. 20051848-57.
31
Positive Immunostaining Rate of GAL3 and CD44v6
in Thyroid Follicular Tumors
GAL3
CD44v6
Maryta J. et al. Immunostaining of Galectin-3 and
CD44v6 Using Fine-Needle Aspiration for
Distinguishing Follicular Carcinoma from Adenoma.
Diagn Cytopath.200413(6)392-396
32
Positive Immunostaining Rate of GAL3 and CD44v6
in Thyroid Follicular Tumors
Maryta J. et al. Immunostaining of Galectin-3 and
CD44v6 Using Fine-Needle Aspiration for
Distinguishing Follicular Carcinoma from Adenoma.
Diagn Cytopath.200413(6)392-396
33
Prevalence of PAX8-PPAR in Thyroid Tumors
Nikiforova MN et al. PAX8-PPAR Rearrangement in
Thyroid Tumors. Am J Surg Pathol
26(8)1016-1023.2002.
34
Is there Help

• Currently there are no recommended additional
  studies on FNAB specimens such as
  immunohistochemistry or molecular techniques by
  which to cytologically separate a follicular
  adenoma from a carcinoma.

Tuttle RM et. The American Thyroid Association
Guidelines Taskforce Management Guidelines for
patients with Thyroid Nodules and Differentiated
Thyroid Cancer. Thyroid 161-33.