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thyroid follicular anomalies

Friday 4 March 2005

thyroid follicular patterned lesions, thyroid vesicular lesions; Follicular-patterned Neoplasms of the Thyroid Gland; nodular follicular lesions of thyroid gland; thyroid follicular lesions

Digital case (Digital slides)

- HPC:395 : Thyroid follicular adenoma with papillary epithelial hyperplasia
- JRC:2665 : Follicular carcinoma (with focal Hurthle cell features), minimally invasive type in a 78 y/o male.
- JRC:3332 : High grade follicular carcinoma of the thyroid.

Nodular follicular lesions of thyroid gland comprise benign and malignant neoplasms, as well as some forms of hyperplasia. "Follicular" refers to origin of cells and in the same time to growth pattern - building follicles.

Nodular follicular thyroid lesions have in common many morphological features, therefore attempts were made to define additional criteria for distinction between follicular adenoma, follicular carcinoma and follicular variant of papillary carcinoma.

FNA study

The differential diagnosis of a follicular lesion in thyroid FNA specimens includes:
- hyperplastic nodule/adenomatoid nodule
- follicular adenoma
- follicular carcinoma
- follicular variant of papillary thyroid carcinoma.

Some laboratories separate follicular lesions of thyroid into:
- hyperplastic nodule/adenomatoid nodule (HN),
- follicular neoplasm (FON)
- follicular derived neoplasm with focal nuclear features suspicious for papillary thyroid carcinoma (FDN).

Fine-needle aspiration (FNA) has been widely accepted as an initial step in the management of thyroid nodules. It is relied upon to distinguish benign from neoplastic/malignant thyroid nodules, thus, influencing therapeutic decisions.

However, the diagnostic efficacy of FNA declines sharply in the diagnosis of follicular patterned lesions of thyroid, i.e. separating hyperplastic/adenomatoid nodule, follicular adenoma (FA), follicular carcinoma (FCA) and follicular variant of papillary carcinoma (FVPTC). Most of these cases are diagnosed as follicular lesion/neoplasm and surgical excision is recommended for definite diagnosis on histopathologic examination.

The malignancy rate in cases diagnosed as follicular lesion/neoplasm (FON) is approximately 20%. This high rate of benign lesions undergoing surgery is because FNA cannot distinguish between follicular adenoma and carcinoma on the basis of cyto-morphology. This distinction is made by demonstrating capsular and/or vascular invasion on histopathologic examination.

Similarly the cytologic diagnosis of "follicular variant of papillary carcinoma" can be challenging due to overlapping cytologic features, with both benign and malignant follicular patterned lesions of the thyroid. These cases can be distinguished from those diagnosed as follicular neoplasm on the basis of subtle nuclear changes suggestive of papillary thyroid carcinoma. Such lesions can be classified as "follicular derived neoplasm with features suspicious for papillary carcinoma". The malignancy rate in such lesions is 70–75% i.e. much higher than seen in cases diagnosed as follicular neoplasm.


- hyperplastic goiter

  • dyshormonogenetic goiter (thyroid dyshormonogenesis in inborm errors of thyroid metabolism)
  • hyperthyroidism (Grave disease)
  • trophoblastic disease
  • pituitary diseases

- follicular thyroid nodules

  • nodular goiter (toxic, nontoxic)
  • adenomatous nodule or adenomatoid nodule
  • true follicular adenoma
  • thyroid follicular carcinoma
  • follicular variant of papillary carcinoma
  • follicular variant of medullary carcinoma
  • insular carcinoma
  • mixed follicular carcinoma
  • mixed parafollicular carcinoma


CK19 and HBME-1 are significantly expressed more in papillary carcinoma as compared to follicular carcinoma. (26503236)

Galectin 3 is most sensitive marker for malignancy. (26503236)

Loss of expression of CD56 is very specific for malignancy. (26503236)

Expected co-expression for combination of markers in diagnosis of follicular lesions decreases sensitivity and increases specificity for malignancy. (26503236)

See also

- thyroid lesions

Open references

- Fine-needle aspiration of follicular lesions of the thyroid. Diagnosis and follow-Up. Deveci MS, Deveci G, LiVolsi VA, Baloch ZW. Cytojournal. 2006 Apr 7;3:9. PMID: 16603062 [Free]


- A Proposal for the Classification of Follicular-patterned Neoplasms of the Thyroid Gland. Chetty R. Am J Surg Pathol. 2011 Feb;35(2):313. PMID: 21263257