Thyroid & parathyroid

Benign thyroid neoplasms

Follicular adenoma


Editorial Board Member: Marc Pusztaszeri, M.D.
Deputy Editor-in-Chief: Andrey Bychkov, M.D., Ph.D.
Shipra Agarwal, M.D.

Last author update: 14 August 2023
Last staff update: 14 August 2023

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PubMed search: Thyroid follicular adenoma

Shipra Agarwal, M.D.
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Cite this page: Agarwal S. Follicular adenoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/thyroidfollicularadenoma.html. Accessed May 19th, 2024.
Definition / general
  • Benign, encapsulated tumor that exhibits thyroid follicular cell differentiation
  • Lacks capsular and vascular invasion
  • Absent nuclear features of papillary thyroid carcinoma
Essential features
  • Benign thyroid tumor, lacking infiltrative properties and usually exhibiting follicular architecture
  • Needs to be differentiated from adenomatoid thyroid nodule and other follicular patterned thyroid neoplasms
ICD coding
  • ICD-O: 8330/0 - follicular adenoma
Epidemiology
Sites
  • Either thyroid lobe, isthmus, ectopic thyroid tissue
Etiology
Diagrams / tables

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Diagnostic

Diagnostic capsular invasions

Incomplete (questionable) capsular invasions in uncertain malignant potential

Incomplete / questionable capsular invasions

Clinical features
  • Painless solitary thyroid nodule
  • May be detected incidentally (during palpation or neck ultrasound)
  • Rarely compression symptoms, if large
  • Hyperthyroidism in case of hyperfunctioning adenomas (Plummer adenoma)
  • Reference: Surg Clin North Am 2014;94:499
Diagnosis
  • Diagnostic workup is similar to any thyroid nodule
    • Ultrasound with fine needle aspiration cytology (FNAC)
Laboratory
  • Thyroid function test; usually euthyroid
  • Can be hyperthyroid in case of hyperfunctioning adenoma
Radiology description
Radiology images

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Ultrasound Ultrasound

Ultrasound

Ultrasound

Ultrasound

Color doppler sonogram Color doppler sonogram

Color Doppler sonogram


Color doppler sonogram Color doppler sonogram Color doppler sonogram

Color Doppler sonogram

Prognostic factors
  • Benign tumor
Case reports
Treatment
  • Lobectomy
  • Hyperfunctioning follicular adenomas: lobectomy preferred over radioiodine (Oncologist 2011;16:585)
Gross description
  • Solitary, encapsulated nodule; multiple if familial
  • Variable size (1 - 10 cm)
  • Solid, gray-white, tan to light brown
  • Secondary changes: hemorrhage, cystic change, fibrosis, calcification, infarction; may develop post-fine needle aspiration cytology
  • Rarely black; especially seen with minocycline therapy
Gross images

Contributed by Andrey Bychkov, M.D., Ph.D., Mark R. Wick, M.D. and AFIP

Encapsulated thyroid nodule

Circumscribed thyroid nodule


Encapsulated, homogeneous tan cut surface

Bisected adenoma has fresh hemorrhage

Marked necrosis, hemorrhage and cystic change

Marked cystic degeneration



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Well circumscribed tumor

Well encapsulated

Central scar

Cystic and partially necrotic tumor

Microscopic (histologic) description
  • Architecturally and cytologically different from surrounding gland
  • Compression signs in surrounding thyroid tissue
  • Encapsulated; thin or moderately thick capsule
  • Architectural patterns (can be seen in any combination)
    • Normofollicular (simple): size similar to normal thyroid follicles
    • Microfollicular (fetal): smaller follicles, small amount of intraluminal colloid
    • Macrofollicular (colloid): large follicles, flattened epithelium, abundant colloid
    • Solid / trabecular (embryonal): minimal or no colloid
  • Focal papillary pattern, occasionally; especially in hyperfunctioning adenoma and follicular adenoma with papillary hyperplasia
  • Cuboidal to low columnar cells
  • Small round nuclei, smooth nuclear boundary, uniformly hyperchromatic or euchromatic, dense chromatin, absent nuclear features of papillary thyroid carcinoma, nuclear score 0 or 1 (JAMA Oncol 2016;2:1023)
  • Inconspicuous nucleoli
  • Rarely, lipid filled vacuoles in cytoplasm
  • Mitoses are uncommon
  • Scant stroma
  • Secondary changes: fibrosis, hyalinization, hemorrhage, hemosiderin deposition, edema, cystic degeneration, calcification, osseous or cartilaginous metaplasia
  • Variants
    • Hyperfunctioning adenoma (Plummer adenoma): tall columnar epithelium, papillary infoldings, vacuolated cytoplasm, watery colloid showing scalloping
    • Follicular adenoma with papillary hyperplasia: cystically dilated follicles, intraluminal papillae
    • Lipoadenoma: adipocytic metaplasia of the follicular adenoma
    • Follicular adenoma with bizarre nuclei: may be seen after radiation exposure and in hyperfunctioning adenoma
    • Signet ring cell follicular adenoma: signet ring cell change
    • Clear cell follicular adenoma: follicular adenoma with clear cell change
    • Spindle cell follicular adenoma: spindle cell metaplasia
    • Black follicular adenoma (black pigment in tumor cell cytoplasm; in patients on minocycline therapy)
  • No capsular or vascular invasion after thorough sampling (at least 10 blocks)
Microscopic (histologic) images

Contributed by Shipra Agarwal, M.D., Andrey Bychkov, M.D., Ph.D., Mark R. Wick, M.D., Asmaa Gaber Abdou, M.D. and AFIP
Capsule & compressed thyroid

Capsule & compressed thyroid

Mixed micro and normofollicular pattern

Mixed micro and normofollicular pattern

Hyperchromatic, small round nuclei

Hyperchromatic, small round nuclei

Abundant crystals of calcium oxalate

Abundant crystals of calcium oxalate

Calcium oxalate crystals

Calcium oxalate crystals


Processing artifact with distorted nuclei

Processing artifact with distorted nuclei

Distorted nuclei due to technical / processing artifact

Distorted nuclei due to technical / processing artifact

Tissue degeneration

Tissue degeneration

Circumscribed thyroid nodule

Cellular follicular adenoma

Cellular follicular adenoma


Cellular follicular adenoma

Cellular follicular adenoma

Trabecular type Trabecular type

Trabecular type

Trabecular type Trabecular type

Trabecular type


Thin and uniform fibrous capsule

Thin and uniform fibrous capsule

Marked fibrosis and stromal hyalinization

Marked fibrosis and stromal hyalinization

Marked hyaline thickening of vessel walls

Marked hyaline thickening of vessel walls

Marked fibrosis, hyalinization and calcium deposition

Marked fibrosis, hyalinization and calcium deposition

Marked vascularization

Marked vascularization

Capsular vessel with smooth muscle cells

Capsular vessel with smooth muscle cells


Bizarre nuclei

Bizarre nuclei

Large, extremely irregular nuclei

Large, extremely irregular nuclei

With papillary hyperplasia With papillary hyperplasia

With papillary hyperplasia

With papillary hyperplasia and adipose metaplasia

With papillary hyperplasia and adipose metaplasia

Cartilaginous metaplasia (adenochondroma)

Cartilaginous metaplasia (adenochondroma)


Prominent, clear cell change

Prominent, clear cell change

Squamous metaplasia

Squamous metaplasia

Mucin production

Mucin production

Thyroglobulin+

Thyroglobulin+

Alcian blue+

Alcian blue+



Patterns:
Solid, trabecular, microfollicular, macrofollicular patterns

Solid, trabecular, microfollicular, macrofollicular patterns

Left: macrofollicular, right: solid pattern

Left: macrofollicular, right: solid pattern

Signet ring

Signet ring

Atypical adenomas:
Markedly cellular with irregular growth

Markedly cellular with irregular growth

Well formed follicles merge with solid pattern

Well formed follicles merge with solid pattern

Spindle cells mix with round cells

Spindle cells mix with round cells



Not invasion:
Fine needle induced changes resemble invasion

Fine needle
induced changes
resemble invasion

Cytology description
  • Cellular aspirate (Korean J Pathol 2013;47:61, J Pathol Transl Med 2018;52:110)
  • Cellular crowding
  • Variable number of singly dispersed cells
  • Microfollicular and solid / trabecular variants: numerous microfollicles, may have scant luminal colloid; absent or minimal background colloid
  • Normofollicular and macrofollicular variants: monolayer sheets of follicular cells, abundant colloid; may mimic benign follicular nodule
  • Hyperfunctioning follicular adenoma and follicular adenoma with papillary hyperplasia: monolayer sheets of polygonal cells with abundant cytoplasm, flame cells and occasionally, papillary fragments
  • Uniform small round to ovoid nuclei, smooth nuclear margin, fine nuclear chromatin
  • Absent nuclear features of papillary thyroid carcinoma
  • The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) IV (follicular neoplasm / suspicious for a follicular neoplasm [FN / SFN]), III (atypia of undetermined significance [AUS A]) or II (benign) (Thyroid 2017;27:1341, Clin Endocrinol (Oxf) 2018;88:936)
  • Cannot rule out follicular thyroid carcinoma based on cytologic findings
Cytology images

Contributed by Shipra Agarwal, M.D. and Ayana Suzuki, C.T.
Cellular aspirate

Cellular aspirate

Microfollicles and small round nuclei

Microfollicles and small round nuclei

Microfollicles

Microfollicles



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Microfollicular Microfollicular

Microfollicular

Microfollicular Microfollicular

Microfollicular

Microfollicular

Microfollicular


FNA

FNA

Round hyperchromatic nuclei

Round hyperchromatic nuclei

FNAC

FNAC

Thyroid neoplasms

Thyroid neoplasms

Positive stains
Negative stains
Electron microscopy description
  • Similar to normal thyroid gland and hyperplastic nodules
  • Hyperfunctioning follicular adenomas: organelle rich cytoplasm, especially rough endoplasmic reticulum; numerous, long microvilli on surface (Am J Clin Pathol 1982;78:299)
  • Clear cell follicular adenomas: cytoplasmic vesicles of variable size; these may be dilated cisternae of the rough endoplasmic reticulum or mitochondria, lysosomes or endocytic vesicles (Virchows Arch A Pathol Anat Histol 1978;380:205)
Electron microscopy images

AFIP images

Abundant dilated endoplasmic reticulum

Microvilli project into well developed lumina

Signet ring follicular adenoma

Molecular / cytogenetics description
Molecular / cytogenetics images

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Gene expression analysis

Gene expression analysis

CNV landscape of thyroid tumors

CNV landscape of thyroid tumors

Driver mutations in thyroid tumors

Driver mutations in thyroid tumors

Driver mutations and pathway analyses

Driver mutations and pathway analyses

Microarray and qRT PCR

Microarray and qRT PCR


Expression ratios of CRABP1, FABP4 and HMGA2

Expression ratios of CRABP1, FABP4 and HMGA2

Clinicopathological features and mutation spectrum

Clinicopathological features and mutation spectrum

Hierarchical clustering Hierarchical clustering Hierarchical clustering

Hierarchical clustering

Videos

Solitary thyroid nodule

Thyroid: compare and contrast

Histopathology thyroid: follicular adenoma (microfollicular)

Sample pathology report
  • Thyroid, right lobectomy:
    • Follicular adenoma, right lobe, 3.2 cm
Differential diagnosis
Board review style question #1

Which of the following best describes this thyroid tumor?

  1. Benign, completely encapsulated, lacks nuclear features of papillary thyroid carcinoma, absent capsular and vascular invasion
  2. Benign, partially encapsulated, lacks nuclear features of papillary thyroid carcinoma, absent capsular and vascular invasion
  3. Malignant, encapsulated, lacks nuclear features of papillary thyroid carcinoma, capsular invasion present
  4. Uncertain malignant potential, completely encapsulated, lacks nuclear features of papillary thyroid carcinoma, questionable capsular invasion
  5. Uncertain malignant potential, completely encapsulated, nuclear score 2, lacks capsular and vascular invasion
Board review style answer #1
A. Benign, completely encapsulated, lacks nuclear features of papillary thyroid carcinoma, absent capsular and vascular invasion. Follicular adenoma is a benign encapsulated tumor, which lacks capsular and vascular invasion as well as nuclear features of papillary thyroid carcinoma. Answer B is incorrect because follicular adenoma is completely encapsulated, unlike a case of nodular hyperplasia with a dominant nodule that can be unencapsulated or partially encapsulated. Answer C is incorrect because follicular adenoma lacks capsular invasion and is benign, unlike a case of follicular thyroid carcinoma. Answer D is incorrect because follicular adenoma is completely encapsulated, lacks even doubtful foci of invasion and is benign. This will be a case of a follicular tumor of uncertain malignant potential. Answer E is incorrect because follicular adenoma has a nuclear score of 0 or 1 and is benign. A tumor with a nuclear score of 2 and lacking capsular and vascular invasion will be noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP).

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Reference: Follicular adenoma
Board review style question #2
Which of the following immunohistochemical / molecular profiles best fits with the diagnosis of follicular adenoma?

  1. Galectin3+, HBME-1+, CITED1+
  2. PAX8-, calcitonin+, chromogranin+
  3. TTF1+, CD56+, PAX8+
  4. TTF1+, CK19+, HBME-1+
  5. TTF1-, synaptophysin+, GATA3+
Board review style answer #2
C. TTF1+, CD56+, PAX8+. Follicular adenoma is immunopositive for TTF1, thyroglobulin, PAX8, CK7 and CD56. Answer A is incorrect because follicular adenoma shows immunoreactivity for no more than 1 of the following markers: galectin3, HBME-1 and CITED1. Answer D is incorrect because CK19 is commonly positive in papillary thyroid carcinoma. Answers B and E are incorrect because calcitonin and GATA3 label medullary thyroid carcinoma and parathyroid tissue, respectively.

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Reference: Follicular adenoma
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