Non-neoplastic disorders of myeloid and lymphoid system

A) Non-neoplastic disorders of the myeloid system

1. Leukopenia

Leukopenia = decreased total WBC count.

Lymphopenia is less common and can be congenital or acquired (HIV, high-dose corticosteroids).

Neutropenia / agranulocytosis

• Neutropenia: decreased granulocytes in blood
• Severe neutropenia = agranulocytosis
• Major risk: severe bacterial and fungal infections

Pathogenesis

1. Decreased production

• Bone marrow failure (e.g., aplastic anemia)
• Marrow replacement/infiltration (e.g., leukemias)
• Chemotherapy → transient marrow aplasia

2. Increased destruction / removal

• Immune-mediated injury
• Overwhelming infections
• Splenomegaly → sequestration and increased removal

Morphology

• Marrow hypercellularity can be seen if destruction is increased or granulopoiesis is ineffective (e.g., megaloblastic anemia)
• Decreased granulocytic precursors in drug-induced suppression

Clinical

• Malaise, chills, fever, weakness, fatigue
• Oral ulcerations/necrosis (“agranulocytic angina”)

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2. Reactive leukocytosis

• Increased granulocytes in peripheral blood due to reactive causes (infection/inflammation).
• Leukemoid reaction: marked leukocytosis that can mimic leukemia.
• Left shift: immature forms present (bands, metamyelocytes, myelocytes, promyelocytes, myeloblasts).

By lineage pattern

• Neutrophilia: acute bacterial infection, sterile inflammation (tissue necrosis)
• Eosinophilia: allergy, drug reactions
• Basophilia: rare; may suggest myeloproliferative disease
• Monocytosis: chronic infections (TB, bacterial endocarditis)
• Lymphocytosis: viral and some bacterial infections

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B) Non-neoplastic disorders of the lymphoid system

1. Infectious mononucleosis (“kissing disease”)

• Caused by EBV
• Epidemiology: early childhood in developing settings; adolescence/young adults in developed settings.

Pathogenesis

• Saliva transmission
• EBV infects oropharynx → lymph nodes → infects mature B cells via CD21
• Polyclonal B-cell activation → antibodies against EBV
• Circulating virus-specific CD8+ T cells → atypical lymphocytes

Morphology

• Peripheral leukocytosis with atypical lymphocytes (often CD8+)
• Lymph nodes: paracortical expansion by atypical lymphocytes
• Spleen/liver: infiltrates

Clinical

• Fever, sore throat, generalized lymphadenopathy
• Recovery in ~4–6 weeks
• Can be severe/lethal in T-cell immunodeficiency

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2. Non-specific lymphadenitis (reactive patterns)

Lymphadenitis = enlarged lymph nodes, usually due to infection/inflammation.

1. Follicular hyperplasia

• GC hyperplasia due to B-cell activation
• Causes: bacterial infection, RA, toxoplasmosis, early HIV

2. Paracortical hyperplasia

• T-zone hyperplasia with immunoblasts; GC size reduced
• Causes: viral infections, post-vaccination, drug reactions

3. Sinus histiocytosis

• Sinus distention by endothelial cells and macrophages
• Often in bronchial nodes (anthracosis)
• Can be associated with nodes draining cancers

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3. Cat scratch disease

• Self-limited lymphadenitis due to Bartonella henselae
• Regional lymphadenopathy (axilla/neck) ~2 weeks after scratch/splinter
• Histology: necrotizing granuloma with central neutrophils

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4. Toxoplasma lymphadenitis

• Infection with Toxoplasma gondii
• Transmission: undercooked meat, contaminated food/water, cat feces (oral–fecal)
• Reactive pattern described as small epithelioid cell lymphadenitis

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C) Bridge to neoplasia (for the next topics)

Myeloid neoplasms arise from hematopoietic stem cells → monoclonal proliferation replacing normal marrow.

• AML: maturation block early → myeloblast accumulation
• MDS: ineffective hematopoiesis + cytopenias
• MPN: proliferation of mature myeloid elements (CML, ET, PMF, PV)

💡 High-yield: Leukemoid reaction = reactive leukocytosis + left shift. EBV mono: CD21 infection of B cells + atypical CD8+ lymphocytes. Reactive node patterns: follicular hyperplasia (B), paracortical hyperplasia (T), sinus histiocytosis (macrophages).