Thyroid gland
Other carcinoma
Follicular carcinoma

Author: Shahidul Islam, M.D., Ph.D. (see Authors page)

Revised: 26 October 2016, last major update March 2009

Copyright: (c) 2002-2016,, Inc.

PubMed Search: Follicular carcinoma [title]

Cite this page: Follicular carcinoma. website. Accessed October 28th, 2016.
Definition / General
  • Thyroid carcinoma with follicular differentiation but no papillary nuclear features; excludes Hurthle cell and poorly differentiated carcinoma
  • Historically 5 - 15% of thyroid carcinoma and 25 - 40% in iodide-deficient areas, but these data may include follicular variant of papillary carcinoma
  • Usually solitary, but not occult
  • Usually "cold" on radionuclide scan
  • Extensive sampling of capsule recommended (Am J Surg Pathol 1992;16:392)

  • Follicular tumor of uncertain malignant potential: questionable capsular invasion and no papillary carcinoma nuclear features

  • Rosai and others (Am J Surg Pathol 1986;10:246) recommend classifying definitive follicular carcinomas as follows:
    • Encapsulated
      • With capsular invasion only
      • With limited (< 4 vessels) vascular invasion
      • With extensive (4 or more vessels) vascular invasion
    • Widely invasive

Minimally invasive follicular carcinoma
  • Invasion of small to medium vessels (i.e. those without a continuous muscular layer), capsular invasion of up to full thickness, no parenchymal tumor extension, no tumor necrosis, excludes Hürthle cell tumors
  • Metastases occur in 1% with capsular invasion only compared to 5% with blood vessel invasion
  • 75% women, older age than papillary carcinoma
Clinical Features
  • Risk factors: radiation exposure, iodine deficiency, older age
  • Does not arise from preexisting adenoma

  • Metastases: does not invade lymphatics but does spread to lungs, liver, bone, brain via veins

  • Distant metastases common in grossly invasive disease:
    • 50% if vascular and capsular invasion
    • 75% if local invasion and vascular or capsular invasion
    • Metastases may pulsate because of their vascularity (also metastatic renal cell carcinoma)
Prognostic Factors
Poor prognostic factors
  • Distant metastases, age > 45 years, large size, extensive vascular invasion, extrathyroidal extension, poorly differentiated or widely invasive tumors (World J Surg 2007;31:1417)

Minimally invasive follicular carcinoma
Case Reports
  • T3 / T4 to suppress endogenous TSH, then thyroidectomy and radioactive iodine
  • No need for nodal dissection since tumors don’t metastasize to lymph nodes
Gross Description
  • Gray-tan-pink
  • Usually single encapsulated nodule, focally hemorrhagic
  • Variable fibrosis and calcification
  • Large lesions may often be infiltrative

Minimally invasive follicular carcinoma
  • Well encapsulated solid and fleshy tumor
  • Capsule is usually thicker and more irregular than adenoma
Gross Images

Images hosted on PathOut server:

Indistinguishable from adenoma (AFIP)

Contributed by Mark R. Wick, M.D.

Minimally invasive follicular carcinoma (AFIP)

Fleshy tumor with irregular central scar

Thicker and irregular capsule than adenoma

Images hosted on Flickr:

Focal invasion

47 year old woman

Images hosted on other servers:

Apparently encapsulated

Widely invasive

A: multiple white tan nodules in thyroid tumor
B: scalp metastases show erosion through skull

Micro Description
  • Need convincing evidence of invasion of adjacent thyroid parenchyma, capsule (complete penetration) or blood vessels (medium sized veins or larger vessels in or beyond the capsule)
  • Capsule is typically thick with calcification
  • Common architectural patterns are follicular or solid
  • May have nuclear atypia, Hürthle cells, focal spindled areas, mitotic figures
  • Usually no squamous metaplasia, no nuclear features of papillary carcinoma, no psammoma bodies, no / rare lymphatic invasion

Minimally invasive follicular carcinoma
  • Encapsulated with thicker and more irregular capsule than adenoma, invasion of adjacent tissue or CD31+ vessels of venous caliber in or immediately outside the capsule (not within the tumor), with tumor clusters attached to the wall or protruding into the lumen
  • Capsular invasion must be full thickness, tumor then expands in a mushroom-like fashion into adjacent area
  • May have additional “capsules” in the advancing tumor edge
  • Growth pattern resembles embryonal, fetal or atypical adenoma
  • Often hemorrhage, necrosis, infarction or significant mitotic activity
Micro Images

Scroll to see all images:

Images hosted on PathOut server:

Courtesy of Andrey Bychkov, M.D., Ph.D.

Contributed by Mark R. Wick, M.D.

AFIP images

Incomplete capsular invasion

Small closely packed follicles

Trabecular growth pattern

Moderate to marked pleomorphism

Mucin production in extracellular space

Capsular invasion - with clear cell change (inset)

Minimal capsular invasion

Marked capsular invasion

Metastases to iliac bone are solid or micro-follicular

Vascular invasion images (AFIP)

Vessel is in capsule

Massive vascular invasion

Minimal vascular invasion

Endothelial cells covering tumor thrombus

Factor VIII stains endothelial cells

Minimally invasive follicular carcinoma (AFIP)

Capsular invasion with regressive changes

Tumor is surrounded by thick, irregular capsule

Minimally invasive follicular carcinoma

Capsular invasion

Capsular invasion and mimics

Not vascular invasion

Varying degrees of capsular penetration

Small (A-C), medium (D-E)
and large (F) vessel invasion

Insular pattern

Tumor necrosis

Oxyphilic change with
focal capsular penetration

Images hosted on Flickr:

47 year old woman with enlarged thyroid gland

Images hosted on other servers:

Tumor has distinct border,
but separate foci of invasive
tumor lie beyond the border

Fig A: H&E
B: extensive lymphovascular invasion
C: CD34+ vessels
D: Ki-67 shows minimal cell proliferation

Focally abutting the normal parenchyma

Insular type

Insular type - resembles an endocrine tumor

Follicular tumor capsular invasion penetrating the broad collagenous capsule

Van Gieson stain

Invasive tumor has
penetrated former
capsule and is surrounded
by a new capsule

Equivocal capsular invasion

Not capsular invasion

Vascular invasion

Vascular invasion in tumor capsule

Tumor cells invading capsular vessel


Giant scalp metastases

Scalp metastases show
well differentiated follicular
epithelium that is TTF1+

Fig 1: Incidental renal cysts
Fig 2: occult bony metastasis

Cytology Description
  • Nuclear enlargement, overlapping and crowding
  • Cannot distinguish between follicular adenoma and carcinoma by fine needle aspiration since need evidence of capsular or vascular invasion or invasion of adjacent parenchyma
Cytology Images

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Figures 9A / 9B

Nuclei are larger than in adenoma

Electron Microscopy Images

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Follicular cells
converge toward
central lumen (AFIP)

Molecular / Cytogenetics Description

"Histopathology Thyroid - Follicular carcinoma"
by John R. Minarcik, M.D.

Differential Diagnosis

Minimally invasive follicular carcinoma
Additional References