Definition/General
Introduction:
Lymph node paracortical hyperplasia is a reactive T-cell proliferative response characterized by expansion of the paracortical zone (T-cell dependent area) of lymph nodes
It represents a cell-mediated immune response to various antigenic stimuli
The condition demonstrates T-lymphocyte activation and proliferation with associated immunoblast formation.
Origin:
Results from T-cell mediated immune responses to viral infections, drugs, vaccines, and transplant rejection
Viral infections (EBV, CMV, HIV) commonly cause paracortical expansion
Drug hypersensitivity reactions (phenytoin, allopurinol) characteristic cause
Post-vaccination responses
Autoimmune conditions with T-cell activation
Transplant rejection and graft-versus-host disease.
Classification:
Classified by underlying etiology: Viral-induced paracortical hyperplasia (EBV, CMV, HIV)
Drug-induced paracortical hyperplasia (anticonvulsants, allopurinol)
Post-vaccination paracortical hyperplasia
Autoimmune-associated
By severity: Mild paracortical expansion
Marked paracortical hyperplasia
Immunoblastic hyperplasia.
Epidemiology:
Common reactive pattern in T-cell mediated responses
Age distribution varies with underlying cause
Young adults commonly affected (viral infections, drug reactions)
No gender predilection generally
Seasonal variation with viral epidemics
Geographic variation based on endemic infections
Immunocompromised patients may show atypical patterns.
Clinical Features
Presentation:
Generalized lymphadenopathy often present (distinguishes from follicular hyperplasia)
Bilateral, symmetric involvement common
Firm, mobile lymph nodes
Hepatosplenomegaly may be associated
Skin rash (drug reactions, viral infections)
Fever and constitutional symptoms
Multiple lymph node groups simultaneously affected.
Symptoms:
Fever (common in viral infections and drug reactions)
Skin rash (morbilliform, maculopapular)
Pharyngitis and tonsillar enlargement
Hepatosplenomegaly
Atypical lymphocytes on peripheral blood smear
Eosinophilia (drug reactions)
Malaise and fatigue.
Risk Factors:
Viral infections (EBV, CMV, HIV, hepatitis viruses)
Drug therapy (phenytoin, carbamazepine, allopurinol, sulfonamides)
Recent vaccination
Autoimmune predisposition
Immunocompromised state
Young age (increased viral susceptibility)
Medication allergies or hypersensitivities.
Screening:
Complete blood count with differential (atypical lymphocytes)
Viral serology (EBV, CMV, HIV)
Liver function tests (drug reactions, viral hepatitis)
Drug history and allergy assessment
Autoimmune markers when indicated
Flow cytometry may show T-cell activation
Excisional biopsy for definitive diagnosis.
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Gross Description
Appearance:
Enlarged lymph nodes with smooth, intact capsule
Cut surface shows diffuse gray-white appearance with less prominent follicular pattern
Soft to firm consistency
Homogeneous texture without focal lesions
No necrosis typically present
Vascular prominence may be evident
Multiple lymph nodes similarly affected.
Characteristics:
Less prominent follicular pattern compared to follicular hyperplasia
Diffuse gray appearance due to paracortical expansion
Soft, fleshy consistency
No calcification or fibrosis
Homogeneous cut surface
Bilateral involvement common
Size proportional to degree of T-cell activation.
Size Location:
Variable size from 1-4 cm typically
Generalized lymphadenopathy characteristic
Cervical lymph nodes commonly involved
Axillary and inguinal lymph nodes affected
Mediastinal involvement in systemic conditions
Symmetric, bilateral distribution
Multiple anatomical sites simultaneously involved.
Multifocality:
Generalized lymphadenopathy typical pattern
Bilateral symmetric involvement
Multiple lymph node groups affected simultaneously
Hepatosplenomegaly often associated
Progressive involvement with ongoing stimulation
Gradual resolution with removal of stimulus.
Microscopic Description
Histological Features:
Marked expansion of paracortical zone with increased T-lymphocytes and immunoblasts
Compressed follicular structures due to paracortical expansion
Increased vascularity with prominent high endothelial venules
Immunoblasts scattered throughout paracortex
Mixed inflammatory infiltrate
Preserved sinusoidal architecture generally.
Cellular Characteristics:
Small to medium T-lymphocytes predominant cell type
Immunoblasts (large cells with vesicular nuclei, prominent nucleoli)
Plasma cells may be increased
Eosinophils (drug reactions)
High endothelial venules prominent
Dendritic cells increased
Mitotic activity increased but not atypical.
Architectural Patterns:
Paracortical expansion pattern with T-cell zone enlargement
Compressed follicular structures
Prominent high endothelial venules
Interfollicular expansion
Preserved sinusoidal pattern
Capsular preservation
No significant architectural effacement.
Grading Criteria:
No standard grading system for paracortical hyperplasia
Degree of expansion (mild, moderate, marked)
Immunoblast density
T-cell activation markers
Vascular prominence
Associated inflammatory changes
Follicular compression degree
Resolution potential assessment.
Immunohistochemistry
Positive Markers:
CD3 highlights expanded T-cell population in paracortex
CD4 and CD8 show T-cell subsets
Ki-67 increased in paracortical areas
CD68 positive in histiocytes
CD21 highlights high endothelial venules and compressed FDC networks
CD138 shows plasma cells when increased
PD-1 may highlight T-follicular helper cells.
Negative Markers:
CD20 limited to compressed follicular B-cells
CD30 negative (excludes lymphoma)
ALK-1 negative
CD1a and Langerin negative
EBV/EBER may be positive in viral cases but not in malignant pattern
Cyclin D1 negative
BCL-2 pattern normal.
Diagnostic Utility:
CD3 staining demonstrates paracortical T-cell expansion
Ki-67 shows increased proliferation in paracortex
CD4/CD8 ratio may be altered
CD21 staining shows compressed but intact FDC networks
PD-1 highlights T-follicular helper cells
Flow cytometry shows polyclonal T-cell population
No aberrant T-cell markers.
Molecular Subtypes:
No molecular subtypes for reactive paracortical hyperplasia
Polyclonal T-cell population by flow cytometry
No clonal T-cell receptor rearrangements
Normal chromosomal complement
Activation markers upregulated
Cytokine expression profile shows T-cell activation
No malignant genetic alterations.
Molecular/Genetic
Genetic Mutations:
No specific genetic mutations in reactive paracortical hyperplasia
Normal T-cell receptor rearrangements
Activation-induced gene expression changes
Cytokine receptor upregulation
No oncogene activation
Transient epigenetic changes related to activation
Normal chromosomal complement.
Molecular Markers:
T-cell activation markers (CD25, CD69, CD71)
Cytokine expression (IL-2, IFN-γ, TNF-α)
Chemokine receptors (CCR7, CXCR3)
Proliferation markers (Ki-67, PCNA)
Apoptosis regulation (BCL-2, FAS)
Transcription factors (T-bet, GATA-3)
Cell adhesion molecules.
Prognostic Significance:
Excellent prognosis with removal of inciting stimulus
Self-limiting condition in most cases
Resolution time varies from weeks to months
Drug withdrawal leads to rapid improvement
Viral clearance results in gradual resolution
No malignant transformation risk
Recurrence possible with re-exposure.
Therapeutic Targets:
Removal of inciting agent (drug discontinuation)
Supportive care for viral infections
Corticosteroids for severe drug reactions
Antihistamines for allergic reactions
Symptomatic treatment of underlying viral infection
Observation appropriate in most cases
No specific immunosuppression needed.
Differential Diagnosis
Similar Entities:
T-cell lymphoma (peripheral T-cell lymphoma, angioimmunoblastic)
Infectious mononucleosis (EBV, CMV)
Drug-induced lymphadenopathy
Autoimmune lymphadenopathy
Dermatopathic lymphadenopathy
Interferon-alpha induced lymphadenopathy
Post-transplant lymphoproliferative disorder.
Distinguishing Features:
Paracortical hyperplasia: polyclonal T-cells, preserved architecture, resolution with stimulus removal
T-cell lymphoma: monoclonal T-cells, architectural effacement, progressive course
AITL: aberrant T-cell phenotype, high endothelial venule proliferation, EBV+ B-cells
Infectious mononucleosis: atypical lymphocytes, specific serology positive
Drug reaction: temporal relationship, eosinophilia, resolution with withdrawal.
Diagnostic Challenges:
Distinguishing from T-cell lymphoma requires immunophenotyping and molecular studies
Immunoblastic hyperplasia may be concerning for malignancy
EBV-associated cases may show atypical features
Chronic stimulation may lead to architectural distortion
Flow cytometry essential for clonality assessment
Clinical correlation crucial.
Rare Variants:
Immunoblastic hyperplasia (prominent immunoblasts)
Eosinophil-rich paracortical hyperplasia (drug reactions)
Plasma cell-rich variant
Post-vaccination hyperplasia
Interferon-induced hyperplasia
Autoimmune-associated hyperplasia
Dermatopathic pattern (with melanin deposition).
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
Lymph node biopsy from [anatomical location], measuring [X.X] cm in greatest dimension
Diagnosis
Lymph node paracortical hyperplasia, reactive T-cell proliferation
Pattern Classification
Pattern: [paracortical expansion/immunoblastic hyperplasia], degree: [mild/moderate/marked]
Histological Features
Shows [marked paracortical expansion] with [increased T-lymphocytes and immunoblasts] and [compressed follicles]
Size and Architecture
Size: [X.X] cm, paracortex: [expanded/prominent], follicles: [compressed/preserved]
Cellular Composition
Contains [mixed T-lymphocytes/immunoblasts/plasma cells] with [high endothelial venules] without malignant features
Special Studies
IHC: CD3 [expanded T-cells], CD4/CD8 [T-cell subsets], Ki-67 [increased paracortical proliferation], CD30 [negative]
Flow cytometry: [if performed] polyclonal T-cell population, no aberrant expression
Clinical correlation: [drug history/viral serology/symptoms]
Final Diagnosis
Lymph node paracortical hyperplasia, reactive T-cell proliferation, clinical correlation recommended for underlying etiology