Thyroid gland
Other thyroid carcinoma
Follicular carcinoma

Author: Shuanzeng Wei, M.D., Ph.D. (see Authors page)

Revised: 15 November 2017, last major update August 2017

Copyright: (c) 2003-2017, PathologyOutlines.com, Inc.

PubMed Search: (Follicular carcinoma [title]) thyroid Review[ptyp]
Cite this page: Wei, S. Follicular carcinoma. PathologyOutlines.com website. http://pathologyoutlines.com/topic/thyroidfollicular.html. Accessed December 15th, 2017.
Definition / general
  • Thyroid carcinoma with follicular differentiation but no papillary nuclear features (Hürthle cell (oncocytic) carcinoma is discussed separately)
  • Comprises 6 - 10% of thyroid carcinomas
  • Insufficient dietary iodine is a risk factor
  • Usually solitary "cold" nodule on radionuclide scan
  • Extensive sampling of capsule is recommended (Am J Surg Pathol 1992;16:392)
  • Three types (Lloyd: WHO Classification of Tumours of Endocrine Organs, 2017):
    • Minimally invasive follicular carcinoma
      • With capsular invasion only
    • Encapsulated angioinvasive:
      • Tumors with limited vascular invasion (< 4) have a better prognosis than those with extensive vascular invasion
    • Widely invasive:
      • Extensive invasion of thyroid and extrathyroidal soft tissue
  • Two types (ARP: Tumors of the Thyroid and Parathyroid Glands, 2016):
    • Minimally invasive follicular carcinoma
      • With capsular invasion (not obvious, need to search)
      • With limited (fewer than 4 vessels) vascular invasion
      • With extensive (4+ vessels) vascular
    • Widely invasive
Essential features
  • Follicular lesion with capsular or vascular invasion but without papillary nuclear features
Epidemiology
  • 75% women
  • Older age than papillary carcinoma, peak age: 40 - 60
  • Rarely in children
Diagrams / tables

Images hosted on other servers:
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Schematic drawing for capsular invasion

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Schematic drawing for vascular invasion

Etiology
  • Iodine deficiency and irradiation exposure, older age
Clinical features
  • Usually "cold" on radionuclide scan
  • May arise from preexisting adenoma
  • Does not metastasize through lymphatics but does spread to lungs, liver, bone, brain via blood vessels
  • Less than 5% with ipsilateral lymphadenopathy
  • Up to 69% distant metastasis: lung and bone (common in widely invasive carcinoma)
Radiology description
  • Ultrasound: solid hypoechoic nodule with a peripheral halo (fibrous capsule); irregular or poorly defined margins may be suggestive of carcinoma
Prognostic factors
  • Minimally invasive follicular carcinoma: very low long term mortality (Cancer 2001;91:505)
  • Widely invasive: 50% long term mortality
  • Poor prognostic factors: tumor size greater than 4 cm, distant metastases, age greater than 45 years, large size, extensive vascular invasion, extrathyroidal extension (World J Surg 2007;31:1417)
Case reports
Treatment
  • T3 / T4 to suppress endogenous TSH, thyroidectomy and radioactive iodine
  • No nodal dissection is needed
Gross description
  • Tan to brown solid cut surface, can have cystic changes and hemorrhage
  • Minimally invasive: usually single encapsulated nodule, with thickened and irregular capsule
  • Widely invasive: extensive permeation of capsule or no capsule
  • All capsule with adjacent tissue needs to be submitted for histological evaluation
Gross images

Images hosted on PathOut server:

Images contributed by Dr. Wafaey Fahmy Badawy Mohamed, Sharurah Armed Forces Hospital (Saudi Arabia)
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Focal invasion

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47 year old woman with follicular thyroid carcinoma and multinodular goiter



Minimally invasive follicular carcinoma (AFIP):

Fleshy tumor with irregular central scar

Thicker and irregular capsule than adenoma



Other:

Indistinguishable from adenoma (AFIP)

Contributed by Mark R. Wick, M.D.




Images hosted on other servers:

Apparently encapsulated

Widely invasive

Fig A: multiple white tan
nodules in thyroid tumor
Fig B: scalp metastases
show erosion through skull
Microscopic (histologic) description
  • Trabecular or solid pattern of follicles (small, normal sized or large - microfollicular, normofollicular or macrofollicular respectively)
  • No nuclear features of papillary thyroid carcinoma
  • Invasion of adjacent thyroid parenchyma, capsule (complete penetration) or blood vessels (in or beyond the capsule)
  • Capsular invasion: capsule is typically thickened and irregular, needs penetration through the capsule (full thickness), may have reactive pseudocapsule around the invasion edge, exclude FNA site
  • Vascular invasion: vessel within or beyond capsule, tumor covered with endothelium, attached to the wall or with thrombus
  • May have nuclear atypia, focal spindled areas, mitotic figures (< 3/10HPF)
  • No necrosis
  • Usually no squamous metaplasia, no psammoma bodies, no / rare lymphatic invasion
  • Metastatic follicular carcinoma can mimic normal thyroid tissue
Microscopic (histologic) images

Scroll to see all images.


Images hosted on PathOut server:

Images contributed by Andrey Bychkov, M.D., Ph.D.:

Capsular vessel with endothelialized tumor deposit

Vascular invasion

Endothelialized tumor embolus in vascular space

Transcapsular penetration

Invasion through tumor capsule


Propagation of tumor embolus

Extensive necrosis

Tumor necrosis

Unusual brisk mitotic activity



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 microfollicular



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



Images contributed by Dr. Wafaey Fahmy Badawy Mohamed, Sharurah Armed Forces Hospital (Saudi Arabia)
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Figs 4 - 13: 47 year old woman with follicular thyroid carcinoma and multinodular goiter



Images contributed by Dr. Mark R. Wick

Metastatic follicular
carcinoma in bone,
TTF1 stain



Images hosted on other servers:

Focally abutting the normal parenchyma

Insular type - resembles an endocrine tumor

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


Follicular tumor capsular invasion penetrating the broad collagenous capsule

Fig A: H&E
B: Extensive lymphovascular invasion
C: CD34+ vessels
D: Ki67 shows minimal cell proliferation


Van Gieson stain

Equivocal capsular invasion

Invasive tumor
penetrated former
capsule

Not capsular invasion



Vascular invasion:

Vascular invasion in tumor capsule



Metastases:

Giant scalp metastases

Scalp metastases
show well differentiated
follicular epithelium
that is TTF1+

Fig 1: Incidental
renal cysts; Fig 2:
Occult bony
metastasis


Minimally invasive follicular carcinoma:

Capsular invasion

Capsular invasion and mimics

Not vascular invasion

Fig 1: Varying degrees of capsular penetration

Fig 2: Small (A - C),
medium (D - E) and
large (F) vessel
invasion

Fig 3: Insular pattern

Fig 4: Oxyphilic
change with focal
capsular penetration

Fig 5: Tumor necrosis

Cytology description
  • Microfollicules (6 - 12 nuclei) with nuclear enlargement, overlapping and crowding
  • No or scant colloid
  • Nuclear atypia is not specific for malignancy
  • Cannot distinguish between follicular adenoma and carcinoma by fine needle aspiration since there needs to be evidence of capsular invasion, vascular invasion or invasion of adjacent parenchyma
Cytology images

Images hosted on PathOut server:

Images contributed by Dr. Jose Mellado, HRU de Malaga - Carlos Haya, Malaga (Spain):

Follicular carcinoma, microfollicules with nuclear enlargement



Images hosted on other servers:

Figs: 9A / 9B

Fig 9: Nuclei are larger than in adenoma

Positive stains
Electron microscopy images

Images hosted on PathOut server:

Follicular cells
converge toward
central lumen (AFIP)

Molecular / cytogenetics description
  • Activated PI3K / AKT or RAS of the receptor tyrosine kinase signaling pathway
  • NRAS and HRAS mutations in 49%, PAX8 and PPAR gamma rearrangements in 36% (J Clin Endocrinol Metab 2003;88:2318)
  • PI3CA and PTEN mutations in 5 - 10%
  • Tumors with rearrangement tend to be overtly invasive versus minimally invasive without this rearrangement (Am J Surg Pathol 2002;26:1016)
  • Widely invasive carcinomas have higher frequency of allelic loss than minimally invasive carcinomas (Hum Pathol 2003;34:375)
Videos

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

Differential diagnosis
Board review question #1
    Which statement for thyroid follicular carcinoma is FALSE?

  1. Cannot have necrosis or increased mitotic figures (≥ 3/10 HPF)
  2. Commonly metastases to bone, lung, not lymph node
  3. Detecting RAS mutations and PPAX8-PPAR gamma rearrangements can be used to distinguish follicular carcinoma from adenoma
  4. Nuclear atypia does not indicate malignancy
  5. Risk factors include iodine deficiency and irradiation exposure
Board review answer #1
C. Detecting RAS mutations and PAX8-PPAR gamma rearrangements can be used to distinguish follicular carcinoma from adenoma. RAS mutations and PAX8-PPAR gamma rearrangements can be found in follicular adenoma.