Chronic Nonspecific Lymphadenitis

Slide 1 · Chronic Nonspecific

Lymphadenitis

Reactive patterns in lymph nodes and extranodal immune tissues

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Describe how chronic immune stimulation changes lymph-node architecture.

Recognize three major reactive patterns and their dominant compartments.

Identify morphologic features that favor reactive follicular hyperplasia.

Link nodal morphology to clinical context and tertiary lymphoid structures.

Slide 3 · Chronic lymphadenitis is a pattern of immune reactivity

Multiple long-standing antigenic stimuli can produce nonspecific nodal enlargement.

“Nonspecific” denotes stereotyped reactive changes rather than one unique etiology.

Morphologic patterns may coexist within an individual lymph node.

Interpret the pattern alongside the clinical distribution and history.

Slide 4 · Secondary lymphoid tissue has distinct functional zones

Cortex / B-cell follicles

Paracortex / T-cell zone

Lymphatic sinuses

Native editable anatomical schematic • not histology

Compartments explain why stimuli produce different histologic patterns.

Slide 5 · B-cell follicles are sites of humoral response

Resident B-cell follicles can develop reactive germinal centers after antigenic stimulation.

Secondary follicles contain actively responding B cells.

A peripheral mantle zone surrounds the germinal center.

Follicular enlargement creates the follicular hyperplasia pattern.

Slide 6 · The paracortex is the T-cell–rich compartment

Cortex / B-cell follicles

Paracortex / T-cell zone

Lymphatic sinuses

Native editable anatomical schematic • not histology

Expansion of T-cell zones defines a different response pattern.

Slide 7 · Lymphatic sinuses form another reactive compartment

Cortex / B-cell follicles

Paracortex / T-cell zone

Lymphatic sinuses

Native editable anatomical schematic • not histology

Sinuses contain lining cells and transit-associated phagocytes.

Slide 8 · Antigenic exposure produces architectural change

Antigenic

Stimulation

Lymphocyte

Activation

Compartmental

Expansion

Reactive

Node

The distribution of activated cells determines the dominant morphologic pattern.

Slide 9 · Lymph nodes respond dynamically to repeated exposure

Resting compartments

Initial activation

Germinal center response

Persistent / repeated stimuli

That adult lymph nodes frequently reflect prior immune exposures.

Slide 10 · Acute and chronic nonspecific lymphadenitis

Acute reaction

Often associated with microbial drainage or systemic infection

Can show neutrophils and tissue damage

May be painful or suppurative

Chronic reaction

Many persistent immunologic triggers

Follicular, paracortical and sinus patterns

Typically slow enlargement and nontender nodes

Distinguish response pattern and tempo; The two are not mutually exclusive.

Slide 11 · Three reproducible reactive morphologies

Follicular hyperplasia

Germinal-center / B-cell compartment predominates

Paracortical hyperplasia

T-cell zones expand with activated immunoblasts

Sinus histiocytosis

Sinuses enlarge with lining cells and macrophages

Slide 12 · One node can show several reactive processes

A mixed pattern is expected, not a contradiction.

Follicles, paracortex and sinuses respond to distinct immune inputs.

Different compartments may expand simultaneously.

Describe the dominant pattern without ignoring the others.

Slide 13 · Assess the entire nodal architecture before naming a pattern

Cortex / B-cell follicles

Paracortex / T-cell zone

Lymphatic sinuses

Native editable anatomical schematic • not histology

Architecture is as important as the appearance of individual cells.

Slide 14 · Patterns track the dominant immune compartment

Humoral reaction

Secondary follicles enlarge

Germinal-center polarity appears

T-cell reaction

Paracortex expands

Immunoblasts become conspicuous

Sinus response

Sinuses dilate and distort

Phagocytic macrophages accumulate

Interpret these as morphologic patterns, not etiologic diagnoses.

Slide 15 · Follicular hyperplasia: The defining finding

Prominent large, oblong secondary follicles containing germinal centers.

Each germinal center is surrounded by a mantle of small resting naive B cells.

Germinal centers show distinct light and dark zones.

The architecture outside the follicles remains important to interpretation.

Slide 16 · The mantle zone surrounds the reactive germinal center

Mantle zone

Dark zone

Light zone

Native editable schematic • not histology

The rim contains small resting naive B cells.

Slide 17 · Dark and light zones reveal germinal-center polarity

Mantle zone

Dark zone

Light zone

Native editable schematic • not histology

Polarity reflects different cellular populations and processes.

Slide 18 · Dark zones contain proliferating centroblasts

The dark zone is enriched in blast-like dividing B cells.

Proliferation explains frequent mitotic figures.

Prominent mitoses do not by themselves establish malignancy.

Assess mitoses together with macrophages, polarity and architecture.

Slide 19 · Light zones contain centrocytes

Centrocytes are B cells with irregular or cleaved nuclear contours.

The light zone is morphologically distinct from the proliferative dark zone.

Preserved light–dark zoning supports a reactive follicular process.

The dark and light areas must be interpreted within an intact follicle.

Slide 20 · Germinal-center B-cell selection and apoptosis

B-cell

Responses

Affinity-dependent

Selection

Failure to make

High-affinity antibody

Apoptosis and

Clearance

Failure pathway shown: Unsuccessful B cells undergo apoptosis and macrophage clearance.

Slide 21 · Tingible-body macrophages reflect cellular turnover

Macrophages contain phagocytosed nuclear debris of apoptotic B cells.

They are interspersed among responding germinal-center B cells.

They provide a practical clue to reactive follicular activity.

Interpret macrophages together with variable follicles and polarity.

Slide 22 · Follicular dendritic cells form a subtle supporting network

Antigen-presenting follicular dendritic cells reside within germinal centers.

They support the microenvironment of the follicular immune response.

This network is relatively inconspicuous by routine morphology.

Their presence should not be confused with tingible-body macrophages.

Slide 23 · Integrated morphology of a reactive secondary follicle

Mantle zone

Dark zone

Light zone

Native editable schematic • not histology

Mantle, polarized germinal center, mitoses and macrophages are complementary clues.

Slide 24 · Reactive follicle versus neoplastic follicle: Architecture

Reactive follicular hyperplasia

Interfollicular T-cell zones remain

Lymphatic sinusoids remain recognizable

Follicles vary markedly in shape and size

Follicular lymphoma: Caution

May resemble reactive follicles morphologically

Loss of the typical reactive features raises concern

Architecture alone is not an absolute diagnostic test

The source identifies reactive features favoring benignity; Ambiguous cases need additional studies.

Slide 25 · Variation among follicles supports a reactive process

Reactive follicles show substantial differences in both size and shape.

A nonuniform population of follicles fits changing immune responses.

Assess the follicle population at low magnification.

Combine size variation with preservation of other nodal compartments.

Slide 26 · Preserved interfollicular structures support reactivity

Cortex / B-cell follicles

Paracortex / T-cell zone

Lymphatic sinuses

Native editable anatomical schematic • not histology

Look for intact T-cell zones and sinuses between follicles.

Slide 27 · Morphologic evidence for reactive follicular hyperplasia

Feature

Reactive interpretation

Why it matters

Variable follicle sizes

Heterogeneity across the node

Reactive follicles do not have to be uniform

Recognizable light / dark zones

Germinal-center polarity

Distinct functional compartments persist

Frequent mitoses

Active centroblast proliferation

High turnover can be physiologic

Tingible-body macrophages

Clearance of apoptotic cells

Supports active germinal-center selection

Preserved T zones / sinuses

Retained overall architecture

Argues against diffuse replacement

Slide 28 · Contexts associated with follicular hyperplasia

Rheumatoid arthritis

A chronic inflammatory autoimmune stimulus

Toxoplasmosis

An infectious trigger of immune activation

Early HIV infection

An early viral immune response

Slide 29 · A reactive follicle can resemble follicular lymphoma

Histologic resemblance is the key diagnostic pitfall.

Preserved compartments, follicle variability and germinal-center polarization favor reactivity.

Reactive follicles typically show mitoses and tingible-body macrophages.

If the pattern is ambiguous, morphology alone may not exclude neoplasia.

Slide 30 · Practical review of follicle-rich lymph nodes

Survey whole

Node architecture

Assess follicle

Size and shape

Examine polarity,

Mitoses, macrophages

Integrate atypia

And clinical context

This is an educational morphology workflow, not a validated stand-alone diagnostic algorithm.

Slide 31 · Paracortical hyperplasia reflects T-cell activation

Stimuli activating T-cell–mediated immunity expand the paracortex.

Acute viral infections are a characteristic context.

Infectious mononucleosis is a classic example.

The expanded compartment lies between or around B-cell follicles.

Slide 32 · Paracortical expansion changes the balance of compartments

Cortex / B-cell follicles

Paracortex / T-cell zone

Lymphatic sinuses

Native editable anatomical schematic • not histology

T-cell-rich tissue expands inward and toward follicles.

Slide 33 · Immunoblasts are enlarged activated T cells

The paracortex can contain strikingly large reactive immunoblasts.

Approximately three- to fourfold larger than resting lymphocytes.

Round nuclei with open chromatin and prominent nucleoli.

Moderate amounts of pale cytoplasm complete the described phenotype.

Slide 34 · Resting lymphocytes versus reactive immunoblasts

Resting lymphocyte

Small cell size

Condensed chromatin

Inconspicuous nucleolus

Activated T-cell immunoblast

Markedly larger size

Open chromatin; Prominent nucleoli

Moderate pale cytoplasm

Activated morphology can be alarming without implying a clonal tumor.

Slide 35 · Why the paracortex becomes expanded

Viral / T-cell

Immune stimulus

T-cell

Activation

Immunoblast

Accumulation

Paracortical

Hyperplasia

This schematic summarizes the source-described cellular pattern.

Slide 36 · Exuberant paracortical reactions may obscure follicles

Expanded T-cell zones can encroach upon—and sometimes efface—B-cell follicles.

Degree of expansion varies with the intensity of activation.

Follicular effacement does not automatically imply malignancy.

Evaluate the cytology and clinical stimulus as well as architecture.

Slide 37 · Sinusoidal and vascular endothelium may hypertrophy

Paracortical reactions often include endothelial activation.

Activated lining cells become more conspicuous.

Changes may involve both sinuses and blood vessels.

Interpret vascular change within the overall reactive process.

Slide 38 · Reactive paracortices can contain accessory inflammatory cells

Macrophages and eosinophils may accompany T-cell zone expansion.

They are secondary components rather than the defining population.

The dominant pattern remains reactive T-cell activation.

Cellular mixtures should be evaluated across the full node.

Slide 39 · When immunoblasts mimic lymphoid neoplasia

Features supporting a reaction

Recognizable infectious / immunologic context

Mixture of activated and background immune cells

Pattern centered in T-cell zones

Reason to investigate further

Marked immunoblast-rich expansion

Architectural effacement in exuberant cases

Source notes special studies may be necessary

Avoid claiming that a large immunoblast is neoplastic solely because it is atypical.

Slide 40 · Paracortical pattern: Three linked findings

Stimulus

T-cell–mediated activation, often viral

Cell population

Immunoblast-rich expansion of T-cell zones

Architectural effect

Follicles compressed or obscured in marked cases

Slide 41 · Sinus histiocytosis is also called reticular hyperplasia

The characteristic change is expansion and distortion of lymphatic sinuses.

Increased number and size of sinus-lining cells.

Increased numbers of macrophages within sinuses.

These changes can be substantial in nodes draining tumors.

Slide 42 · Enlarged sinus-lining cells contribute to sinus expansion

Enlarged sinus-lining cells

Intrasinusoidal macrophages

Native editable schematic • not histology

The lining-cell component accompanies macrophage accumulation.

Slide 43 · Intrasinusoidal macrophages drive the histiocytic appearance

Accumulating macrophages enlarge the sinus compartments.

They are found inside lymphatic sinuses.

Together with enlarged lining cells, they distort sinus outlines.

The word “histiocytosis” here denotes a reactive pattern.

Slide 44 · Sinus histiocytosis preserves a recognizable sinus-based topology

Enlarged sinus-lining cells

Intrasinusoidal macrophages

Native editable schematic • not histology

Identify the expanded sinus spaces rather than assuming a diffuse infiltrate.

Slide 45 · Cancer-draining lymph nodes may show sinus histiocytosis

Tumor-containing

Tissue drainage

Regional lymph

Node exposure

Sinus macrophage /

Lining-cell response

Sinus

Histiocytosis

Breast carcinoma is Robbins’ example of a setting with conspicuous sinus histiocytosis.

Slide 46 · Sinus histiocytosis does not by itself mean metastasis

A reactive nodal pattern may accompany lymphatic drainage from a carcinoma.

The described sinus change consists of macrophages and lining-cell enlargement.

Presence of this pattern alone does not demonstrate tumor cells in a node.

Tumor status requires assessment for actual neoplastic involvement.

Slide 47 · Three-pattern diagnostic comparison

Pattern

Main compartment

Leading morphologic clues

Follicular hyperplasia

B-cell follicles

Oblong polarized germinal centers; Mantle; Tingible-body macrophages

Paracortical hyperplasia

T-cell paracortex

Immunoblast-rich expansion; Can obscure follicles

Sinus histiocytosis

Lymphatic sinuses

Enlarged lining cells and intrasinusoidal macrophages

Slide 48 · Slow enlargement usually explains the absence of pain

Chronic lymphadenitis is characteristically nontender.

Nodal growth usually occurs gradually.

Acute tissue injury and associated inflammation are absent or limited.

Tenderness is a clinical clue, not an absolute histologic classifier.

Slide 49 · Why axillary and inguinal nodes often show chronic reactions

Drain large skin /

Extremity territories

Repeated trivial injury

Or infection

Ongoing antigenic

Exposure

Reactive nodal

Enlargement

The source specifically emphasizes axillary and inguinal distributions.

Slide 50 · Link a nodal site to its immune-drainage territory

Axillary / inguinal groups

Large drainage territories

Repeated low-grade peripheral immune challenges

Common sites of chronic lymphadenitis

Other patterns of presentation

Localized or generalized nodes require context

Nodal distribution does not identify a single cause

Morphology should be correlated with clinical findings

Compartment- and distribution-aware interpretation.

Slide 51 · Case 1 · Persistent axillary lymphadenopathy

An axillary node enlarges slowly and is not tender. The region has experienced repeated minor skin injuries.

Interpret the tempo and likely nodal process.

The presentation is compatible with chronic reactive lymphadenitis; Histologic pattern still requires evaluation.

Slide 52 · Case 2 · Immunoblast-rich node

Following an acute viral illness, a lymph node shows extensive expansion of its T-cell zones. Many large cells have open chromatin and prominent nucleoli.

What is the likely reactive pattern?

Paracortical hyperplasia. Numerous immunoblasts can necessitate further studies to exclude neoplasia.

Slide 53 · Case 3 · Numerous enlarged germinal centers

A lymph node contains follicles of diverse sizes, identifiable mantle zones and polarized germinal centers. Many tingible-body macrophages are present.

Which process does this morphology favor?

Reactive follicular hyperplasia rather than a uniform neoplastic follicular proliferation.

Slide 54 · Case 4 · A carcinoma-draining node

A lymph node draining a breast carcinoma has markedly expanded lymphatic sinuses, enlarged lining cells and abundant macrophages.

Name the reactive pattern; Does it prove nodal metastasis?

Sinus histiocytosis. No: Tumor cells must be demonstrated separately.

Slide 55 · Tertiary lymphoid structures form outside normal lymphoid organs

Chronic immune reactions can organize lymphoid cell collections within nonlymphoid tissue.

These structures are sometimes called tertiary lymphoid structures.

They resemble aspects of secondary lymphoid organization.

They arise in the setting of chronic local inflammatory stimulation.

Slide 56 · Chronic gastritis may create mucosal lymphoid aggregates

Helicobacter pylori

Gastritis

Persistent mucosal

Immune stimulation

Organized lymphocyte

Aggregates

Peyer patch–like

Architecture

This is an extranodal example—not a lymph node.

Slide 57 · Rheumatoid synovium may contain organized B-cell follicles

Rheumatoid

Inflammation

Prolonged synovial

Immune activation

Organized B-cell

Follicles

Tertiary lymphoid

Architecture

Anatomical location distinguishes these collections from nodal follicles.

Slide 58 · Lymphotoxin is a proposed organizer of ectopic lymphoid tissue

Lymphotoxin as probably contributing to tertiary-structure formation.

Lymphotoxin is required for normal secondary lymphoid-organ development.

Its role in extranodal chronic inflammatory collections is presented as probable.

Do not convert a proposed mechanism into an obligatory diagnostic criterion.

Slide 59 · Secondary lymph nodes versus tertiary lymphoid structures

Lymph node

Pre-existing, encapsulated secondary lymphoid organ

Defined B-cell / T-cell compartments and sinuses

Changes its morphology during immune responses

Tertiary lymphoid structure

Immune collection developing in nonlymphoid tissue

Appears with sustained local inflammation

May organize follicle-like B-cell areas

Both illustrate structural organization of adaptive immune responses.

Slide 60 · How to interpret a reactive lymph-node biopsy

Question

Observation to make

Inference supported

What expanded?

Follicles, paracortex or sinuses

Describe the dominant reaction

Is architecture preserved?

T-cell zones and sinuses between follicles

Helpful evidence for reactivity

What cells predominate?

Centroblasts, immunoblasts, macrophages

Links cytology to compartment

Is clinical context compatible?

Infection, autoimmunity, drainage territory

Refines interpretation—not proof of cause

Does a mimicker remain possible?

Extreme atypia or architectural disruption

Consider additional diagnostic investigation

Slide 61 · Morphologic reactivity and malignancy are not simple opposites

Some reactive patterns resemble lymphoid neoplasia.

Follicular hyperplasia may resemble follicular lymphoma.

Immunoblast-rich paracortical reactions may suggest neoplasia.

The source advises special studies in difficult paracortical reactions.

Slide 62 · Integrated review · Mixed patterns in one node

A lymph node contains large reactive follicles, conspicuous paracortical immunoblasts, and dilated sinuses filled with macrophages.

Must one compartment exclude the others?

No. Chronic nonspecific lymphadenitis may show multiple reactive patterns in a single node.

Slide 63 · Final synthesis: Interpret the compartment, not only cell size

B-cell follicle

Polarized germinal centers; Tingible-body macrophages

T-cell paracortex

Activated immunoblasts; Expanding T-cell zones

Sinus compartment

Sinus-lining cells and macrophages; Enlarged sinuses

Slide 64 · Reference and scope

Robbins, Cotran & Kumar: Pathologic Basis of Disease

11th edition (2026). Reactive proliferations of white cells and lymph nodes; chronic nonspecific lymphadenitis.

Morphologic drawings are original teaching schematics, not diagnostic photomicrographs.