Definition/General
Introduction:
Reactive lymphadenopathy represents the most common cause of lymph node enlargement in clinical practice
It constitutes 80-90% of all lymph node FNAC cases
The condition involves benign proliferation of lymphoid elements in response to antigenic stimulation
FNAC shows characteristic polymorphous population of lymphoid cells.
Origin:
Results from immune response to infectious agents, inflammatory conditions, or antigenic stimulation
Primary sites of reaction include paracortex (T-cell zones), follicles (B-cell zones), and sinusoids
The response is polyclonal and self-limiting
It demonstrates preservation of normal lymph node architecture.
Classification:
Classified based on predominant pattern: Follicular hyperplasia (B-cell predominant)
Paracortical hyperplasia (T-cell predominant)
Mixed hyperplasia (both B and T cells)
Sinus histiocytosis (macrophage predominant)
Each pattern has distinct FNAC features.
Epidemiology:
Most common in children and young adults (5-30 years)
Peak incidence in pediatric age group
No gender predilection
Common sites include cervical, axillary, and inguinal lymph nodes
Indian population shows higher incidence due to infectious disease burden.
Clinical Features
Presentation:
Painless lymph node enlargement (most common)
Node size typically 1-3 cm
Mobile and non-adherent to surrounding structures
May be associated with fever or malaise
Multiple nodes may be involved
Resolution occurs with treatment of underlying cause.
Symptoms:
Usually asymptomatic
Mild tenderness in acute cases
Constitutional symptoms (fever, malaise) in 30-40% cases
Night sweats rare (helps differentiate from lymphoma)
Weight loss uncommon
Symptoms related to underlying infection or inflammation.
Risk Factors:
Recent viral infections (EBV, CMV, HIV)
Bacterial infections (streptococcal, staphylococcal)
Immunization history
Autoimmune conditions (SLE, rheumatoid arthritis)
Drug reactions (phenytoin, allopurinol)
Malnutrition and immunocompromised states.
Screening:
Clinical examination of all lymph node groups
Complete blood count with differential
ESR and CRP levels
Specific tests for suspected infections (Mantoux test, viral serology)
FNAC is the primary diagnostic tool
Follow-up examination after 2-4 weeks.
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Gross Description
Appearance:
Lymph nodes are typically enlarged but maintain normal oval shape
Surface is smooth and non-adherent
Cut surface shows gray-white appearance
Prominent follicles may be visible on cut surface
No areas of necrosis or hemorrhage
Consistency is firm but not hard.
Characteristics:
FNAC yields abundant cellular material
Aspirate appears grayish-white to slightly turbid
Good cellularity with easily dispersed cells
Background shows proteinaceous material
No necrotic debris or caseous material
May contain tingible body macrophages.
Size Location:
Node size ranges from 1-5 cm in reactive conditions
Cervical nodes most commonly involved (60-70%)
Axillary nodes (15-20%)
Inguinal nodes (10-15%)
Generalized lymphadenopathy in systemic conditions
Size correlates with degree of stimulation.
Multifocality:
Multiple node involvement common in viral infections
Regional distribution suggests local infectious source
Bilateral involvement suggests systemic cause
Matted nodes uncommon (helps differentiate from TB)
Nodes in drainage areas preferentially affected.
Microscopic Description
Histological Features:
FNAC shows polymorphous lymphoid population
Mixture of small mature lymphocytes (60-70%), transformed lymphocytes (15-20%), and immunoblasts (5-10%)
Tingible body macrophages are characteristic
Plasma cells and dendritic cells present
Background is clean without necrosis.
Cellular Characteristics:
Small lymphocytes: Round nuclei with clumped chromatin and scant cytoplasm
Medium lymphocytes: Slightly larger with more cytoplasm
Large transformed lymphocytes: Open chromatin, prominent nucleoli, abundant basophilic cytoplasm
Immunoblasts: Large cells with single prominent nucleolus
Centrocytes and centroblasts in follicular hyperplasia.
Architectural Patterns:
Follicular hyperplasia: Predominance of centrocytes and centroblasts with tingible body macrophages
Paracortical hyperplasia: Increased immunoblasts and transformed lymphocytes
Mixed pattern: Combination of above features
Plasmacytoid differentiation may be seen
Background shows lymphoglandular bodies.
Grading Criteria:
No formal grading system for reactive lymphadenopathy
Assessment based on degree of cellular transformation
Mild: Predominantly small lymphocytes with few transformed cells
Moderate: Increased proportion of medium and large lymphocytes
Marked: Abundant immunoblasts and transformed cells
Degree correlates with intensity of stimulus.
Immunohistochemistry
Positive Markers:
CD20 positive in B-cells (40-60%)
CD3 positive in T-cells (40-60%)
CD68 positive in macrophages/histiocytes
Ki-67 shows moderate proliferation index (20-40% in germinal centers)
Bcl-2 negative in germinal center cells
CD10 positive in germinal center cells.
Negative Markers:
CD15 and CD30 (negative, helps exclude Hodgkin lymphoma)
ALK negative (helps exclude ALCL)
Cyclin D1 negative (excludes mantle cell lymphoma)
CD23 shows normal distribution
TdT negative (excludes lymphoblastic lymphoma)
Cytokeratin negative (excludes carcinoma).
Diagnostic Utility:
IHC rarely required for typical reactive cases
Useful in atypical cases to exclude lymphoma
Flow cytometry shows polyclonal B-cell population
CD4:CD8 ratio may be altered but not extreme
Helps differentiate from monomorphic lymphoid proliferations
Light chain restriction absent.
Molecular Subtypes:
Reactive hyperplasia shows polyclonal pattern
Immunoglobulin gene rearrangement studies show polyclonal pattern
T-cell receptor studies show polyclonal T-cell population
No clonal chromosomal abnormalities
EBV association possible in some cases
Normal p53 expression pattern.
Molecular/Genetic
Genetic Mutations:
No specific genetic mutations associated with reactive hyperplasia
Polyclonal B-cell and T-cell populations maintain normal genetic diversity
Chromosomal translocations absent (helps differentiate from lymphomas)
Point mutations in oncogenes not seen
Tumor suppressor genes function normally.
Molecular Markers:
Polyclonal immunoglobulin production
Cytokine expression appropriate for immune response (IL-2, IL-4, IL-10)
Normal apoptosis pathways
Cell cycle checkpoints intact
No aberrant protein expression
MYC protein expression within normal limits.
Prognostic Significance:
Excellent prognosis with resolution of underlying cause
Self-limiting condition in most cases
No malignant potential per se
Risk of misdiagnosis as lymphoma if not properly evaluated
Chronic stimulation may rarely lead to lymphoma development
Follow-up essential to ensure resolution.
Therapeutic Targets:
Treatment directed at underlying cause
Antimicrobial therapy for infections
Anti-inflammatory medications for inflammatory conditions
Immunosuppression for autoimmune causes
Supportive care with observation
Surgical excision rarely required except for diagnostic purposes.
Differential Diagnosis
Similar Entities:
Lymphoma (Hodgkin and non-Hodgkin types)
Metastatic carcinoma to lymph nodes
Infectious lymphadenitis (TB, atypical mycobacteria)
Autoimmune lymphadenopathy
Sarcoidosis
Kikuchi disease
Castleman disease
Drug-induced lymphadenopathy.
Distinguishing Features:
Lymphoma: Monomorphic population, abnormal lymphoid cells, high Ki-67
Metastatic carcinoma: Epithelial cell clusters, positive cytokeratin
TB lymphadenitis: Epithelioid cells, Langhans giant cells, caseous necrosis
Sarcoidosis: Non-caseating granulomas, negative AFB
Kikuchi disease: Histiocytes with crescentic nuclei, debris, absence of neutrophils.
Diagnostic Challenges:
Distinguishing florid reactive hyperplasia from low-grade lymphoma
Large transformed lymphocytes may mimic Reed-Sternberg cells
Monotypic B-cell populations in early reactive responses
Atypical lymphoid cells in viral infections
Age-related variations in cellular composition
Site-specific variations in lymphoid populations.
Rare Variants:
Progressive transformation of germinal centers
Hyaline-vascular variant (Castleman-like)
Interfollicular hyperplasia
Marginal zone hyperplasia
Plasmacytic hyperplasia
Histiocytic hyperplasia
Paracortical expansion with clear cells.
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.
Specimen Information
Fine needle aspiration cytology of [site] lymph node
Adequacy
Adequate for evaluation - cellular smears with adequate lymphoid tissue
Cellularity
Cellular smears showing abundant lymphoid cells
Background
Clean background with proteinaceous material and lymphoglandular bodies
Cell Population
Polymorphous lymphoid population: Small lymphocytes [X]%, Medium lymphocytes [X]%, Large transformed lymphocytes [X]%
Morphological Features
Small lymphocytes with round nuclei and clumped chromatin. Transformed lymphocytes with open chromatin and basophilic cytoplasm. Tingible body macrophages present. No atypical or Reed-Sternberg-like cells identified
Special Features
Presence of tingible body macrophages. Absence of necrosis. No epithelial cell clusters. No granulomas identified
Cytological Diagnosis
Reactive lymphadenopathy/lymphoid hyperplasia - [specify pattern if identified]
Recommendations
Clinical correlation advised. Treatment of underlying cause. Follow-up to ensure resolution. Consider excision biopsy if nodes persist or increase in size
Comments
The cytological features are consistent with reactive lymphoid hyperplasia. No evidence of malignancy in the present sample. Close clinical follow-up recommended