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Hematopathology

LYMPHADENITIS

Prof. Pier Paolo Piccaluga

Department of Experimental, Diagnostic and Specialty Medicine, Bologna University

Department of Pathology JKUAT, Nairobi

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Lymph node structure

• Capsule

• Fibroblasts and

reticular fibers

• Macrophages

• Dendritic cells

• T-lymphocytes

• B-lymphocytes

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Classification

• Acute Lymphadenitis

• Chronic Lymphadenitis

– Specific (35%)

– Non-specific (65%)

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Main causes of reactive lymphadenitis

• Infections

• Autoimmune diseases

• Hyper-sensitivity

• Iatrogenic

• Idiopathic

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Occipital: scalp infections (bacterial, fungal),

insect bites

Posterior Auricolar: Rubella

Anterior Auricolar: ocular and conjunctival

infections

Submandibular/submental: dental

infections, metastasis

Anterior Cervical: nasofaringeal infections,

TBC, EBV, metastasis

Posterior Cervical : Toxoplasma, scalp

infections, Cat scratch disease, EBV

Main causes of lymphadenitis by site

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Acute Non-specific Lymphadenitis

• Fast volume increase

• Painful

• Mobile beneath the skin

• Reddish-grey, congested

• Abscess:

– “floating”

– flushed skin

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Lymph nodes

• Cervical /sub/supramandibular/submental:

– Draining of infections from teeths and tonsils

• Axillary or inguinal

– Limb infections/inflammations

• Mesenteric

– Acute appendicitis

– Mesenteritis

Acute Non-specific Lymphadenitis

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Possible evolution

• Suppuration: floating consistency at palpation, flushing/red skin

• Fistula

• Soft tissue abscess

– Staphylococcus aureus, Streptococcus pyogenes, Haemophilus influenzae, Fusobacterium necrophorum, Str intermedius, Str Agalactiae (new borns)

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Chronic Non-specific Lymphadenitis

• Chronic immunological stimulation can

determine different lymph node reactions:

– Slow volume increase

– Painless (more often, not always!)

– Hard consistency

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Chronic Non-specific Lymphadenitis

- Follicular hyperplasia

- Paracortical hyperplasia

- Mixed follicular-paracortical hyperplasia

- Sinuses histiocytosis

- Granulomas

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FOLLICULAR HYPERPLASIA

• HIV-related lymphadenitis• Aspecific follicular hyperplasia• Reumatoid lymphadenitis• Syphilis • Toxoplasmosis• Kimura disease (extremely rare)• Mycosis• Progressively transformed

germinal centres• Castleman disease

SINUS ENLARGEMENT

• Rosai-Dorfman disease (sinus histiocytosis with massive adenopathy)

• Langerhans cells histiocytosis• Lipogranulomatous reaction• Silicon induced lymphadenopathy

PARACORTEX EXPANSION

• Dermatopathic lymphadenitis• Kikuchi-Fujimoto disease• SLE• Viral lymphadenitis (including

infectious mononucleosis)• Drug induced lymphadenitis

GRANULOMATOUS LYMPHADENOPATHY

• Suppurative (Cat scratch disease, pestis, listeriosis, lymphogranuloma venereum)

• Granulomatous

– Necrotizing (TBC, mycotic, leprosy)

– Non-necrotizing (sarcoidosis, berilliosis, cancer etc)

• Foreign body reaction

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Follicular hyperplasia

• Reumatoid arthritis

• Follicular hyperplasia in HIV

• Luetic lymphadenitis

• Kimura disease (extremely rare)

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Reactive follicular hyperplasia

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Reactive follicular hyperplasia• Humoral immunity reaction• Enlarged germinal centers

– Variable in size

• Evident mantle zone• Morpho-functional polarization• Tingible body macrophage

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Follicular lymphoma

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Paracortical hyperplasia

T-dependent immune response

- Viral lymphadenitis (EBV, CMV, Herpes

simplex, Herpes Zoster)

- Hypersensitivity drug reactions

- Lymphadenitis following vaccination

- Dermatopathic lymphadenitis

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Paracortical/interfollicular hyperplasia

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Paracortical/interfollicular hyperplasia

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Dermatopathic lymphadenitis

• Lymph nodes draining from skin• Dermatitis vs. mycosis fungoides• Accessory cells expansion

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S100

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S100 protein

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Infectious mononucleosis

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29CD3

30CD20

31CD4

32CD8

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ki67

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Ibridazione in situ EBV: sonde EBER

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Granulomatous lymphadenitis

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Granulomatous lymphadenitis

• Infections: TBC, fungi, Brucellosis…

• Sarcoidosis

• Hypersensitivity/immune reactions

• Cancer associated

• Idiopathic

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Granulomatous lymphadenitis

• Without necrosis (sarcoidosis)

• With necrosis:

– Suppurative: fungal infection, cat scratch disease,

lymphogranuloma venereum, Yersinia, atypical

Mycobacteria

– Non suppurative: Mycobacteria tuberculosis

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Sarcoidosis

Necrosis absent

Single (isolated) giant cells

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Granulomatous lymphadenitis

• Without necrosis (sarcoidosis)

• With necrosis:

– Suppurative: fungal infection, cat scratch disease,

lymphogranuloma venereum, Yersinia, atypical

Mycobacteria

– Non suppurative: Mycobacteria tuberculosis

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Suppurative granulomatous lymphadenitis

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Cat scratch disease

- Bartonella Henselae (gram-negative)

- Pleomorphic bacteria, highlighted by

Warthin-Starry* o immunohistochemistry

- Unilateral lymphadenopathy

*Silver nitrate-based staining method: Spirochetes, Helicobacter pylori, Lawsonia intracellularis, Microsporidia, Bartonella henselae

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Warthin-Starry

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Toxoplasmosis

• Primary infection caused by Toxoplasma gondii– Infection occurs when a person ingests oocysts from

contaminated hands or food, or sarcocysts fromundercooked meat and vegetables

• Classic Triad:1. Follicular hyperplasia2. Microgranulomas (epithelioid cells aggregates)

within and outside germinal centers3. Monocytoid B-cells aggragates

• Sometimes, Toxoplasma within cystic structureswithin cortical senuses

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Classical triad• Follicular hyperplasia• Microgranulomas (within and outside the follicles) (arrow,

yellow)• Monocytoid B-cell aggregates (arrow, red)

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Lymphadenitis caused byHistoplasma capsulatum

PAS

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Lymph node pathology &HIV infection

• Reactive – hyperplasic lymphadenopathy

• Metastatic tumors

• Lymphomas

– Non-Hodgkin

– Hodgkin

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HIV-related lymphadenitis

• HIV infects mononuclear peripheral blood cells → lymph nodes → reactive acute adenitis

• In the lymph node, macrophages and dendritic cells (DC) represent the reservoir, while peripheral T-cell are responsible for virus spread

• Consequences:

– T-cell death;

– DC involution in the LN

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Disease evolution

• Florid follicular hyperplasia

• Follicular hyperplasia / follicular

involution

• Follicular involution

• Lymphocyte depletion

Tim

e

Acute

Chronic

52Giant follicle with bizarre morphology

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Abundant plasma cells

54FDC at various differentiative stages: involuted in red, normal in yellow

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Involuted GC; arrow: giant cell

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• FLORID FOLLICULAR HYPERPLASIA (Acute phase)– Irregular hyperplastic follicles

– Reduced/abolished mantle zone

– Monocytoid hyperplasia

– Warthin-Finkeldey giant cells

• FOLLICLE INVOLUTION (Subacute/chronic phase)– Involuted GC with hyaline deposition

– Paracortical lymphocyte depletion

– Plasma cells accumulation in the paracortex

– Paracortical vascular priliferation

• LYMPHOCYTE DEPLETION (BURNOUT) – Atrofic/absent follicles

– Hyalinized GC with endothelial enlargement and PAS+ material

– Paracortical lymphocyte depletion

– Vascular proliferation and fibrosis

HIV-related lymphadenitisPathology

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• Fever, weight loss, diarrhea,

hypergammaglobulinemia

• Recurrent infections

• Palpable lymph nodes

• Peripheral blood CD+ cells

• CD4+/CD8+ inversion

• HIV test: positive

HIV-related lymphadenitisClinical picture

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Mycobacterium Tubercolosis lymphadenitis

• High (increasing) incidence worldwide

• Correlated with HIV infection

– Commonest extra-pulmonary complication (TBC history)

– Tubercolin +

– Multiple lymphadenopathies

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Necrotizing granulomatous lymphadenitis (non-abscessual) (mycobacterium tubercolosis)

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Ziehl-Neelsen

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Fusiform cells pseudo tumor (intracellular Mycobacterium avium)

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Ziehl-Neelsen

THANKS YOU

Q/A

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