Definition/General
Introduction:
Normal adrenal gland FNAC shows cortical and medullary cells in appropriate proportions
The adrenal cortex comprises 90% of gland mass
FNAC demonstrates three distinct cortical zones
Medullary cells show neuroendocrine morphology
Normal architecture shows no cellular atypia.
Origin:
Adrenal cortex derives from mesoderm (coelomic epithelium)
Adrenal medulla originates from neural crest (chromaffin cells)
Cortical zones: zona glomerulosa (mineralocorticoids)
Zona fasciculata (glucocorticoids)
Zona reticularis (androgens)
Medulla produces catecholamines.
Classification:
Anatomically: cortex (outer 90%) and medulla (inner 10%)
Cortical zones: glomerulosa (15%)
fasciculata (75%)
reticularis (10%)
Functional classification: mineralocorticoid
glucocorticoid
androgen-producing
Catecholamine-producing (medulla).
Epidemiology:
FNAC rarely performed on normal adrenals
Usually done for incidental adrenal masses (incidentalomas)
Bilateral adrenal enlargement workup
Imaging-guided procedures increasing
Age-related changes: cortical nodularity common >50 years
Medullary size relatively stable.
Clinical Features
Presentation:
Asymptomatic in normal adrenals
FNAC usually for incidental masses
Hormonal workup preceding biopsy
Imaging abnormality investigation
Bilateral enlargement evaluation
Staging workup for malignancy
Normal function tests expected.
Symptoms:
No symptoms from normal adrenal tissue
Mass effect if enlarged glands
Hormonal excess symptoms absent
Normal blood pressure
Normal electrolytes
Normal glucose metabolism
Normal sexual development.
Risk Factors:
Age-related changes (nodular hyperplasia)
Stress-related hyperplasia
Medication effects (ACTH stimulation)
Chronic illness (stress response)
Genetic variants (size variation)
No significant risk factors for normal tissue.
Screening:
Hormonal assessment: cortisol, aldosterone, catecholamines
Dexamethasone suppression test
24-hour urine collections
Plasma metanephrines
Imaging correlation: CT, MRI characteristics
Clinical assessment for hormone excess.
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Gross Description
Appearance:
FNAC yields scant to moderate cellular material
Cortical cells predominant (90%)
Clear to eosinophilic cytoplasm
Medullary cells scattered (10%)
Minimal blood and debris
Fat cells from surrounding tissue
No necrosis or atypical cells.
Characteristics:
Mixed cell population
Cortical cells: polygonal, abundant cytoplasm
Clear cytoplasm (lipid-rich) in zona fasciculata
Eosinophilic cytoplasm in zona reticularis
Medullary cells: smaller, granular cytoplasm
Uniform nuclear morphology
Background adipose tissue.
Size Location:
Normal adrenal size: 4-6 cm length
2-3 cm width
Thickness <1 cm
Weight 4-5 grams each
Right adrenal: triangular shape
Left adrenal: semilunar shape
Retroperitoneal location superior to kidneys.
Multifocality:
Bilateral organs normally present
Uniform architecture in each gland
Cortical zonation maintained
Central medulla preserved
No nodular hyperplasia in young patients
Age-related changes may show multiple small nodules.
Microscopic Description
Histological Features:
Cortical cells arranged in cords and nests
Zona glomerulosa: small cells in arcs
Zona fasciculata: large clear cells in cords
Zona reticularis: compact eosinophilic cells
Medullary cells: chromaffin cells with granular cytoplasm
Rich vascular supply.
Cellular Characteristics:
Cortical cells: polygonal with distinct borders
Abundant cytoplasm (clear or eosinophilic)
Central nuclei with fine chromatin
Small nucleoli
Medullary cells: smaller, oval to round
Granular cytoplasm (chromaffin granules)
Salt-and-pepper chromatin.
Architectural Patterns:
Cortical pattern: cords and nests
Sinusoidal arrangement
Zonal organization from outer to inner
Medullary pattern: irregular clusters
Rich capillary network
No compression or distortion
Maintained architecture.
Grading Criteria:
No grading for normal tissue
Assessment based on architectural preservation
Cellular morphology: normal vs hyperplastic
Nuclear features: uniform vs atypical
Mitotic activity: absent vs present
Zonal differentiation: preserved vs lost.
Immunohistochemistry
Positive Markers:
SF-1 (steroidogenic factor-1, cortical cells)
Inhibin (cortical cells)
Melan-A (cortical cells)
Synaptophysin (medullary cells)
Chromogranin A (medullary cells)
PNMT (phenylethanolamine N-methyltransferase, medulla).
Negative Markers:
Cytokeratins (negative in normal adrenal)
EMA (negative)
RCC marker (negative, excludes renal)
Hepatocyte marker (negative, excludes liver)
TTF-1 (negative, excludes lung)
PSA (negative, excludes prostate).
Diagnostic Utility:
Confirms adrenal origin
SF-1, inhibin, melan-A identify cortical cells
Synaptophysin, chromogranin identify medullary cells
Excludes metastases from other organs
Normal expression pattern indicates benign tissue
Hormonal correlation with function.
Molecular Subtypes:
No specific molecular subtypes for normal adrenal
Functional zonation based on enzyme expression
CYP11B2 (zona glomerulosa)
CYP17A1 (zona fasciculata/reticularis)
PNMT (medulla)
Normal gene expression profile.
Molecular/Genetic
Genetic Mutations:
No pathogenic mutations in normal adrenal
Normal chromosomal profile
Physiologic gene expression
Normal DNA repair mechanisms
Stable genome
Age-related changes: telomere shortening, oxidative damage
Hormonal regulation genes intact.
Molecular Markers:
Steroidogenic enzymes: normal expression
ACTH receptor (MC2R) functional
Angiotensin II receptor functional
Growth factors: IGF-1, VEGF normal levels
Apoptosis regulators: balanced expression
Cell cycle genes: normal regulation.
Prognostic Significance:
Normal tissue has no prognostic implications
Age-related changes: benign course
Functional reserve maintained
Response to stress preserved
No malignant potential
Hormonal function typically normal
Life-long stability expected.
Therapeutic Targets:
No treatment needed for normal tissue
Hormone replacement if adrenalectomy performed
Stress dose steroids for surgical procedures
Monitoring if incidentaloma present
Lifestyle factors: stress management
Regular follow-up if bilateral enlargement.
Differential Diagnosis
Similar Entities:
Adrenal adenoma
Adrenal hyperplasia
Adrenal cyst
Myelolipoma
Metastatic disease
Pheochromocytoma
Adrenal cortical carcinoma
Neuroblastoma (pediatric).
Distinguishing Features:
Normal adrenal: mixed cortical/medullary cells, normal morphology, no atypia
Adenoma: monomorphic population, may show atypia
Hyperplasia: increased cell numbers, maintained architecture
Malignancy: cellular atypia, necrosis, high mitotic rate
Pheochromocytoma: pure medullary cells.
Diagnostic Challenges:
Distinguishing normal vs hyperplastic adrenal
Age-related nodularity vs pathologic changes
Sampling adequacy issues
Mixed populations interpretation
Crush artifact from procedure
Clinical correlation essential.
Rare Variants:
Adrenal rest tissue
Accessory adrenal glands
Congenital adrenal hyperplasia
Adrenal hypoplasia
Age-related atrophy
Post-stress hyperplasia
Drug-induced changes.
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.
Clinical Information
Patient with [clinical indication], hormonal studies: [results]
Specimen Adequacy
Adequate with mixed cortical and medullary cells
Cytomorphological Features
Shows [cortical cells] and [medullary cells] with normal morphology
Cortical Cells
Cortical cells show [clear/eosinophilic cytoplasm] with [uniform nuclei]
Medullary Cells
Medullary cells show [granular cytoplasm] with [salt-pepper chromatin]
Background
Background shows [minimal blood, adipose tissue, no necrosis]
Final Cytological Diagnosis
Normal adrenal tissue with cortical and medullary elements
Recommendations
Recommend [clinical correlation, imaging follow-up as indicated]