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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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