Definition/General
Introduction:
Colloid nodule (adenomatoid nodule) is the most common benign thyroid lesion encountered on FNAC
It represents hyperplastic areas within multinodular goiter and is characterized by abundant thick colloid with benign follicular epithelial cells
Falls under Bethesda Category II (Benign) and accounts for 60-70% of thyroid FNAC diagnoses.
Origin:
Develops from thyroid follicular epithelium as part of multinodular goiter
Result of alternating stimulation and regression cycles
TSH stimulation leads to follicular hyperplasia followed by involution with colloid accumulation.
Classification:
Bethesda System for Reporting Thyroid Cytopathology classifies as Category II (Benign)
Subtypes include macrofollicular variant (large follicles with abundant colloid) and microfollicular variant (smaller follicles with less colloid).
Epidemiology:
Most common thyroid lesion globally
Prevalence increases with age, especially >40 years
Female predominance (4:1)
More common in iodine-deficient areas
Indian population shows high prevalence due to endemic goiter.
Clinical Features
Presentation:
Usually asymptomatic thyroid nodules
Part of multinodular goiter in majority of cases
Slow-growing masses
May present as solitary nodule but often multiple nodules on imaging.
Symptoms:
Mostly asymptomatic
Large nodules may cause compressive symptoms (dysphagia, dyspnea)
Cosmetic concerns in visible nodules
Thyroid function usually normal (euthyroid state).
Risk Factors:
Iodine deficiency (most important)
Advanced age >40 years
Female gender
Genetic predisposition
Previous radiation exposure
Dietary goitrogens.
Screening:
Thyroid ultrasound shows well-defined nodules with mixed echogenicity
Coarse calcifications may be present
Normal thyroid function tests in most cases
Elevated TSH in some cases of multinodular goiter.
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Gross Description
Appearance:
Well-demarcated nodule with smooth surface
Cut surface shows glistening appearance due to colloid
Color ranges from yellow to brown
Consistency varies from soft to firm.
Characteristics:
Encapsulated or well-circumscribed nodule
Size varies from few millimeters to several centimeters
Colloid-filled cystic spaces visible
Hemorrhage and calcification possible in large nodules.
Size Location:
Size ranges 0.5-8 cm (average 2-3 cm)
Can occur anywhere in thyroid gland
Multiple nodules common
Cystic degeneration in larger nodules.
Multifocality:
Multifocal disease common (multinodular goiter)
Bilateral involvement frequent
Various stages of nodular development
Heterogeneous appearance on imaging.
Microscopic Description
Histological Features:
Large and small follicles lined by benign follicular epithelium
Abundant intrafollicular colloid with peripheral vacuolization
Flat to low cuboidal epithelium
Minimal inflammatory infiltrate.
Cellular Characteristics:
Benign follicular cells with uniform nuclei and distinct nucleoli
Cells arranged in flat sheets and honeycomb pattern
Nuclear-cytoplasmic ratio low
Chromatin finely granular.
Architectural Patterns:
Macrofollicular architecture predominant
Follicles of varying sizes
Colloid shows peripheral scalloping
Papillary projections absent
No capsular or vascular invasion.
Grading Criteria:
No grading system applicable as benign lesion
Assessment based on cellular atypia (absent), mitotic activity (minimal), and architectural features (preserved follicular pattern).
Immunohistochemistry
Positive Markers:
Thyroglobulin positive (diagnostic)
TTF-1 positive
CK19 may be focally positive
PAX-8 positive
Thyroid peroxidase (TPO) positive.
Negative Markers:
Calcitonin negative (excludes medullary carcinoma)
CK20 negative
CEA negative
Chromogranin negative
Synaptophysin negative.
Diagnostic Utility:
Thyroglobulin confirms thyroid follicular origin
TTF-1 supports thyroid lineage
Normal expression pattern excludes malignancy
CK19 limited focal staining unlike papillary carcinoma.
Molecular Subtypes:
No specific molecular subtypes
Normal thyroid follicular cell immunophenotype
Absence of molecular alterations associated with malignancy
BRAF mutation negative.
Molecular/Genetic
Genetic Mutations:
Usually no significant mutations
Polyclonal proliferation unlike neoplasms
Rare RAS mutations in some adenomatoid nodules
BRAF mutations absent.
Molecular Markers:
Normal p53 expression
Low Ki-67 proliferation index (<2%)
Normal cyclin expression
Absence of molecular markers of malignancy.
Prognostic Significance:
Excellent prognosis with no malignant potential
Risk of malignant transformation extremely low (<1%)
Long-term growth monitoring sufficient.
Therapeutic Targets:
No specific therapy required for benign nodules
TSH suppression therapy controversial
Radioiodine therapy for toxic multinodular goiter
Surgery only for compressive symptoms.
Differential Diagnosis
Similar Entities:
Follicular adenoma
Follicular carcinoma
Papillary thyroid carcinoma (follicular variant)
Hashimoto thyroiditis
Graves disease
Parathyroid adenoma.
Distinguishing Features:
Follicular adenoma: encapsulated neoplasm, microfollicular pattern
Follicular carcinoma: nuclear atypia, capsular invasion
Papillary carcinoma: nuclear features, CK19 diffuse positivity
Hashimoto: lymphocytic infiltrate, Hurthle cells.
Diagnostic Challenges:
Distinction from follicular neoplasm when microfollicular areas present
Cystic degeneration may obscure morphology
Hemorrhage may cause reactive changes
Sampling adequacy important.
Rare Variants:
Colloid nodule with papillary hyperplasia
Nodular goiter with Hurthle cell change
Colloid nodule with oxyphilic metaplasia
Nodular goiter with squamous metaplasia.
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)
Background
Abundant thick, viscous colloid with peripheral scalloping
Cellularity
Low to moderate cellularity relative to colloid
Cellular Pattern
Flat sheets of follicular epithelial cells in honeycomb pattern
Cellular Features
Uniform follicular cells with round nuclei and distinct nucleoli
Nuclear Features
Benign nuclear morphology, no nuclear atypia or pseudo-inclusions
Special Features
No Hurthle cells, lymphocytes, or atypical features
Cytological Diagnosis
Benign follicular nodule (colloid nodule) - Bethesda Category II
Recommendation
Clinical correlation and ultrasound follow-up as clinically indicated