Definition/General
Introduction:
Follicular adenoma is a benign encapsulated thyroid neoplasm composed of follicular cells
On FNAC, it cannot be definitively distinguished from follicular carcinoma and falls under Bethesda Category IV (Follicular Neoplasm or Suspicious for Follicular Neoplasm)
The distinction requires histological examination of the capsule for invasion
Represents 5-10% of thyroid nodules.
Origin:
Arises from thyroid follicular epithelial cells as a clonal neoplasm
Develops within a complete fibrous capsule
May arise from pre-existing adenomatoid nodules or de novo from normal thyroid tissue.
Classification:
WHO classification includes conventional type and variants: macrofollicular (colloid-rich), microfollicular (cellular), trabecular, solid, and Hurthle cell (oncocytic) adenoma
Bethesda System classifies as Category IV.
Epidemiology:
Accounts for 5-15% of thyroid neoplasms
Female predominance (4:1)
Peak incidence 30-50 years
More common in iodine-deficient regions
Malignant transformation rare (<5%).
Clinical Features
Presentation:
Solitary, slow-growing thyroid nodule
Well-defined margins on palpation
Usually asymptomatic
May be discovered incidentally on imaging
Size typically 1-4 cm.
Symptoms:
Usually asymptomatic unless large
Compressive symptoms possible with large adenomas (>4 cm)
Most patients euthyroid
Toxic adenoma may cause hyperthyroidism (5-10% cases).
Risk Factors:
Iodine deficiency
Female gender
Radiation exposure in childhood
Genetic factors (adenomatous polyposis coli, Carney complex)
TSH elevation.
Screening:
Thyroid ultrasound shows well-defined, hypoechoic nodule with smooth margins
Halo sign (hypoechoic rim) characteristic
Normal thyroid function tests in most cases
Hot nodule on thyroid scintigraphy if toxic.
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Gross Description
Appearance:
Well-encapsulated, round to oval nodule
Cut surface shows homogeneous tan-brown color
Smooth, glistening surface
Complete fibrous capsule surrounds the lesion.
Characteristics:
Solitary nodule with intact capsule
Size ranges 1-10 cm (average 3-4 cm)
May show cystic degeneration in larger lesions
Calcification and hemorrhage possible.
Size Location:
Size typically 1-6 cm diameter
Can occur in any part of thyroid gland
Unifocal lesion by definition
Larger adenomas may cause gland asymmetry.
Multifocality:
Solitary lesion by definition (multifocal = multinodular hyperplasia)
No capsular invasion or vascular invasion
Clear demarcation from surrounding normal thyroid tissue.
Microscopic Description
Histological Features:
Encapsulated neoplasm with intact fibrous capsule
Microfollicular, macrofollicular, or solid growth patterns
Uniform follicular cells without significant atypia
No capsular or vascular invasion.
Cellular Characteristics:
Uniform follicular epithelial cells with round nuclei
Nuclear pleomorphism minimal
Chromatin finely granular
Nucleoli small and inconspicuous
Mitoses rare (<2 per 10 HPF).
Architectural Patterns:
Predominantly microfollicular pattern (small follicles with minimal colloid)
Trabecular and solid areas possible
Macrofollicular areas may be present
Papillary architecture absent.
Grading Criteria:
No established grading system for benign adenomas
Assessment based on cellular uniformity, mitotic activity (low), and architectural preservation
Nuclear atypia minimal by definition.
Immunohistochemistry
Positive Markers:
Thyroglobulin positive (confirms follicular differentiation)
TTF-1 positive
PAX-8 positive
Thyroid peroxidase positive
CK19 may be focally positive.
Negative Markers:
Calcitonin negative (excludes medullary carcinoma)
Chromogranin negative
Synaptophysin negative
CK20 negative
CEA negative.
Diagnostic Utility:
Thyroglobulin and TTF-1 confirm thyroid follicular lineage
Normal immunoprofile excludes other neoplasms
CK19 limited focal staining (unlike papillary carcinoma).
Molecular Subtypes:
No specific molecular subtypes recognized
Normal follicular cell immunophenotype
Absence of markers associated with malignancy
BRAF mutation typically negative.
Molecular/Genetic
Genetic Mutations:
RAS mutations in 10-45% cases (NRAS most common)
TSH receptor mutations in toxic adenomas
PIK3CA mutations rare
PTEN mutations uncommon.
Molecular Markers:
Low Ki-67 proliferation index (<5%)
Normal p53 expression
Cyclin D1 may be overexpressed
Telomerase activity variable.
Prognostic Significance:
Excellent prognosis with complete excision
Very low risk of malignant transformation
Long-term follow-up shows stable behavior
Recurrence rare with complete excision.
Therapeutic Targets:
Surgery (lobectomy) curative
Radioactive iodine for toxic adenomas
TSH suppression therapy not indicated
Ethanol ablation for selected cases.
Differential Diagnosis
Similar Entities:
Follicular carcinoma
Adenomatoid nodule
Papillary thyroid carcinoma (follicular variant)
Hurthle cell neoplasm
Parathyroid adenoma
Medullary thyroid carcinoma.
Distinguishing Features:
Follicular carcinoma: capsular/vascular invasion on histology
Adenomatoid nodule: no true capsule, part of multinodular goiter
Papillary carcinoma: nuclear features, CK19 diffuse
Hurthle cells: oncocytic cytoplasm.
Diagnostic Challenges:
Cannot distinguish from follicular carcinoma on cytology alone
Cellular adenoma may mimic carcinoma
Hurthle cell change may obscure diagnosis
Sampling adequacy crucial.
Rare Variants:
Hurthle cell adenoma with oncocytic cells
Signet ring cell adenoma
Clear cell adenoma
Adenoma with bizarre nuclei
Lipoadenoma with fat component.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Site and Procedure
Site: Thyroid [right/left/isthmus], Procedure: Fine needle aspiration cytology
Adequacy
Adequate for evaluation (>6 groups of follicular cells, each with >10 cells)
Cellularity
High cellularity
Architectural Pattern
Predominantly microfollicular pattern with crowded cell groups
Colloid
Scant to minimal colloid
Cellular Features
Uniform follicular epithelial cells with round nuclei
Nuclear Features
Minimal nuclear atypia, fine chromatin, small nucleoli
Special Features
No Hurthle cells, papillary features, or significant atypia
Cytological Diagnosis
Follicular neoplasm - Bethesda Category IV
Recommendation
Surgical consultation recommended for histopathological evaluation and capsular assessment