Identify reactive leukocytosis, leukopenia, and qualitative WBC disorders using lab findings for ASCP hematology.

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Chapter 18 โ€” NONMALIGNANT LEUKOCYTE DISORDERS

ASCP Board Exam ยท Lab-Focused Study Guide
Pelger-Huรซt (True vs Pseudo) ยท Hypersegmentation ยท Alder-Reilly ยท Chรฉdiak-Higashi ยท May-Hegglin ยท CGD (NBT, DHR) ยท LAD Iโ€“III ยท MPO Deficiency ยท Lysosomal Storage (MPS, Gaucher, Niemann-Pick) ยท DiGeorge, XLA, SCID, Wiskott-Aldrich ยท Neutrophilia/Neutropenia ยท Leukemoid vs CML ยท Eosinophils, Basophils, Monocytes, Lymphocytes ยท Toxic Changes ยท Reactive Lymphocytes ยท Infectious Mononucleosis ยท Practice Questions

1 ยท Priority Table & Quick Foundation

Topic Priority Why It’s Tested
Inherited morphologic anomalies: Pelger-Huรซt, Alder-Reilly, Chรฉdiak-Higashi, May-Hegglin (Box 29-1) HIGH Film identification + genes (Rodak Q1โ€“Q3)
True vs pseudo-Pelger-Huรซt; PHA mistaken for left shift HIGH Differential counting error
Toxic granulation vs Alder-Reilly; Dรถhle bodies vs May-Hegglin inclusions HIGH Classic look-alikes (Rodak Q8)
Chronic granulomatous disease: NADPH oxidase, NBT/DHR tests, X-linked HIGH Case study 1; Rodak Q5
Absolute count thresholds: neutrophilia, neutropenia, lymphocytosis, monocytosis, eosinophilia, basophilia HIGH Always use absolute counts
Leukemoid reaction vs CML (Box 29-4); leukoerythroblastic reaction HIGH LAP score, basophils, dysplasia
Reactive lymphocytes and infectious mononucleosis (heterophile, EBV serology) HIGH Rodak Q7, Q10
Gaucher vs Niemann-Pick cells (Box 29-3) HIGH Marrow macrophage morphology (Rodak Q4)
LAD I, II, III MEDIUM Integrin/fucose/kindlin defects; bombay-like H-negative in LAD II
Immunodeficiencies: DiGeorge, XLA (BTK), SCID (ADA, IL-2Rฮณ), Wiskott-Aldrich MEDIUM Rodak Q6
Congenital neutropenias: Kostmann, cyclic (ELANE, 21 days), Shwachman-Diamond MEDIUM Cause matching
Ehrlichia/Anaplasma morulae, vacuoles, pyknotic vs necrotic nuclei MEDIUM Case study 2
MPS enzyme table (Table 29-1), MPO deficiency, WHIM/myelokathexis LOW Recognition
๐ŸŽฏ KEY POINT โ€” Where to spend your time

Focus: the four inherited morphologic anomalies (what, where, gene, function), CGD and the NBT test, absolute-count definitions, leukemoid vs CML, reactive changes (toxic granulation, Dรถhle bodies, vacuoles), reactive lymphocytes and IM testing, Gaucher vs Niemann-Pick cells. Skim: drug lists for neutropenia, individual MPS subtypes, Gaucher ethnic data.

Quick Foundation โ€” from zero

  • White cells can go wrong in two ways: their appearance or function (qualitative) or their number (quantitative). This chapter covers the nonmalignant (non-cancer) causes.
  • Some changes are inherited (a gene defect present from birth) and some are reactive โ€” a normal response to infection, inflammation, stress or drugs.
  • The lab’s job is to recognize look-alikes: an inherited anomaly can mimic an infection-related change (Alder-Reilly vs toxic granulation), and a benign reaction can mimic leukemia (leukemoid reaction vs CML).
  • Numbers must be judged as absolute counts (WBC ร— %), not percentages alone.
๐Ÿ’ก Analogy

Think of neutrophils as firefighters. Inherited anomalies are firefighters born with odd uniforms โ€” Pelger-Huรซt looks like a trainee (few lobes) but works fine. CGD firefighters look perfect but their hoses have no water (no respiratory burst). LAD firefighters can’t get out of the truck (can’t stick to vessel walls), so they pile up in the blood. Toxic granulation and Dรถhle bodies are soot and sweat on firefighters actively fighting a blaze โ€” reactive, not a birth defect.

๐Ÿฅ Why this matters clinically

Misreading Pelger-Huรซt cells as bands creates a false ‘left shift’ and an unnecessary infection workup. Missing a leukemoid reaction vs CML changes everything. Recognizing morulae in monocytes can make an early diagnosis of ehrlichiosis, which is treatable with doxycycline. The NBT or DHR test diagnoses CGD before fatal infections occur.

Concept Plain-English Explanation
Left shift More immature neutrophils (bands, metamyelocytes, myelocytes) in the blood
Absolute count WBC ร— percentage of that cell type
Neutrophilia / neutropenia Too many / too few neutrophils
Agranulocytosis Neutrophils below 0.5 ร— 10โน/L
Leukemoid reaction Reactive WBC >50 ร— 10โน/L with marked left shift โ€” mimics leukemia
Leukoerythroblastic reaction Immature neutrophils + nRBCs + teardrop cells โ€” suggests a marrow space-occupying lesion
Respiratory burst Oxygen-radical production by phagocytes to kill microbes
Reactive (variant) lymphocyte Lymphocyte transformed by antigen stimulation โ€” large, basophilic cytoplasm

2 ยท Core Content Tables

2.1 Morphologic Abnormalities of Neutrophils (Rodak Box 29-1)

Anomaly Morphology Inheritance / Gene Clinical Findings
Pelger-Huรซt anomaly Decreased segmentation (bilobed ‘pince-nez’, unilobed round/peanut); coarse, clumped chromatin; may affect all WBCs Autosomal dominant; lamin B receptor gene Asymptomatic; normal function
Pseudo-Pelger-Huรซt Same shapes; usually neutrophils only; often hypogranular Acquired Depends on underlying condition (MDS, AML, MPN, HIV, TB, drugs)
Hypersegmentation >5 lobes Acquired (megaloblastic, MDS) or hereditary Depends on cause; hereditary form asymptomatic
Alder-Reilly anomaly Large, darkly staining metachromatic granules (partially digested mucopolysaccharides) in granulocytes; also in lymphocytes and monocytes Recessive Normal function; associated with Hurler, Hunter, Maroteaux-Lamy
Chรฉdiak-Higashi Giant lysosomal granules (fused) in granulocytes, monocytes, lymphocytes Autosomal recessive; CHS1/LYST (1q42.1-2) Rare, fatal: recurrent pyogenic infections; bleeding (abnormal platelet dense granules); hair, skin, nerves affected
May-Hegglin Large Dรถhle bodyโ€“like inclusions (precipitated myosin heavy chains) in neutrophils, eosinophils, basophils, monocytes + giant platelets + thrombocytopenia Autosomal dominant; MYH9 (22q12-13), myosin heavy chain IIA Usually asymptomatic; mild bleeding with thrombocytopenia

2.2 Pelger-Huรซt โ€” Details & Lab Issues

Feature Details
Prevalence ~1 in 4785 in the U.S.
Zygosity Homozygous: all neutrophils round nuclei ยท heterozygous: 55โ€“93% of neutrophils affected, mixed shapes
Pseudo-PHA causes MDS, AML, chronic MPNs; HIV, TB, M. pneumoniae, severe bacterial infection; drugs โ€” mycophenolate, valproate, sulfisoxazole, ganciclovir, ibuprofen, paclitaxel, docetaxel
True vs pseudo (1) True: 63โ€“93% of cells vs pseudo <38% ยท (2) true: all lineages possible vs pseudo neutrophils only (except some MDS) ยท (3) check family members ยท (4) pseudo in MDS often hypogranular; true PHA normal granulation
Counting pitfall Round/peanut nuclei โ†’ miscounted as myelocytes, metamyelocytes or bands โ†’ false left shift. Clues: mature, clumped chromatin; nearly colorless cytoplasm (immature cells have basophilia)
Reporting Suggested: count as ‘others’ and define others as Pelger-Huรซt neutrophils

2.3 Hypersegmentation & Myelokathexis

Feature Details
Hypersegmented neutrophil >5 lobes (normal 3โ€“5); most often megaloblastic anemia (cell also larger); MDS (dysplasia); rare hereditary neutrophil hypersegmentation (asymptomatic)
Myelokathexis Normal production but impaired release โ†’ neutropenia; hypermature neutrophils: hypersegmentation, hypercondensed pyknotic chromatin, vacuoles
WHIM syndrome Warts, Hypogammaglobulinemia, Infections, Myelokathexis; CXCR4 gain-of-function mutation

2.4 Normal Morphology with Functional Abnormalities (Rodak Box 29-2)

Disorder Cause Clinical Findings
Chronic granulomatous disease (CGD) Mutations in NADPH oxidase genes โ†’ no respiratory burst after phagocytosis Recurrent bacterial and fungal infections; granulomas may obstruct organs
LAD I Mutation in ฮฒโ‚‚ integrin (CD18) subunits (exons 5โ€“9) โ†’ โ†“ or truncated ฮฒโ‚‚ integrin Recurrent infections, neutrophilia, lymphadenopathy, splenomegaly, skin lesions; severity depends on ฮฒโ‚‚ amount
LAD II SLC35C1 (fucose transporter) mutation โ†’ โ†“ fucosylated selectin ligands Growth retardation, coarse face, neurologic defects, infections, absent blood group H antigen; normal ฮฒโ‚‚ integrins
LAD III Kindlin-3 mutation โ†’ ฮฒ integrin activation fails (integrins normally expressed) Milder LAD Iโ€“like infections + bleeding (โ†“ platelet GPIIb/IIIa activation, like Glanzmann)

2.5 Chronic Granulomatous Disease (CGD)

Feature Details
Normal burst Phagocytosis โ†’ phosphorylation of cytosolic p47phox and p67phox; granules bring cytochrome complex gp91phox + gp22phox to the phagolysosome; with p40phox and RAC2 โ†’ active NADPH oxidase โ†’ electron from NADPH to Oโ‚‚ โ†’ superoxide โ†’ other oxidants
Defect Mostly gp91phox or p47phox mutations
Inheritance ~60โ€“65% X-linked recessive (gp91phox); 35โ€“40% autosomal recessive
Clinical Bacterial and fungal infections of lung, skin, lymph nodes, liver; macrophage granulomas (liver, spleen) may obstruct intestine, urinary tract. With antifungals, >90% survive into adulthood
Morphology Normal; phagocytosis and chemotaxis normal โ€” killing fails
NBT test Stimulated normal neutrophils reduce yellow, water-soluble nitroblue tetrazolium to dark blue insoluble formazan; CGD neutrophils cannot
Flow cytometry Dihydrorhodamine-123 (DHR) fluorescent probe measures intracellular reactive oxygen species

2.6 Leukocyte Adhesion & MPO Deficiency

Feature Details
Normal recruitment Capture and rolling via selectins and their ligands โ†’ high-affinity integrin binding to endothelium โ†’ spreading โ†’ transmigration
LADs Rare autosomal recessive; neutrophils/monocytes can’t adhere and migrate โ†’ potentially lethal bacterial infections; neutrophils accumulate in blood
MPO deficiency โ†“ MPO in primary granules (neutrophils) and lysosomes (monocytes); MPO normally makes hypochlorite/hypochlorous acid. Autosomal dominant*, ~1 in 2000, MPO gene chromosome 17; usually no significant infections (compensatory pathways). Acquired with hematologic neoplasms and lead poisoning
Lab detection Easily detected on analyzers using peroxidase for the automated differential (e.g., Siemens Advia)

*Rodak states autosomal dominant; many references describe MPO deficiency as autosomal recessive โ€” know your exam source’s answer.

2.7 Monocyte/Macrophage Lysosomal Storage Disorders (Rodak Table 29-1)

Type Name Deficient Enzyme Substance Stored
MPS I โ€” severe Hurler syndrome ฮฑ-L-iduronidase Dermatan sulfate, heparan sulfate
MPS I โ€” attenuated Scheie syndrome ฮฑ-L-iduronidase Dermatan sulfate, heparan sulfate
MPS II โ€” severe Hunter syndrome Iduronate sulfatase Dermatan sulfate, heparan sulfate
MPS III A/B/C Sanfilippo syndrome Heparan N-sulfatase / ฮฑ-N-acetylglucosaminidase / acetyl-CoA:ฮฑ-glucosaminide N-acetyltransferase Heparan sulfate
MPS IV A/B Morquio syndrome Galactose-6-sulfatase / ฮฒ-galactosidase Keratan sulfate (ยฑ chondroitin-6-sulfate)
Lipid Gaucher disease ฮฒ-Glucocerebrosidase Glucocerebroside
Lipid Niemann-Pick disease Sphingomyelinase Sphingomyelin
Lipid Fabry disease ฮฑ-Galactosidase Ceramide trihexoside
Lipid Tay-Sachs, Sandhoff disease Hexosaminidase A GM2 ganglioside

2.8 Mucopolysaccharidoses (MPS)

Feature Details
Defect Inherited deficiency of an enzyme degrading GAGs (dermatan, heparan, keratan, chondroitin sulfate) โ†’ buildup in lysosomes โ†’ physical abnormality, sometimes mental retardation
Blood May look normal; metachromatic Reilly bodies in neutrophils, monocytes, lymphocytes
Marrow Macrophages with large amounts of metachromatic material
Diagnosis / treatment Specific enzyme assays; enzyme replacement or HSCT

2.9 Gaucher Disease

Feature Details
Frequency Most common lysosomal lipid storage disease; โ‰ฅ1 in 17 Ashkenazi Jews are carriers; >300 mutations
Genetics Autosomal recessive; ฮฒ-glucocerebrosidase gene at 1q21
Pathology Glucocerebroside accumulates in macrophages throughout the body (osteoclasts, microglia)
Diagnostic triad Hepatosplenomegaly, Gaucher cells in marrow, โ†‘ serum acid phosphatase*
Gaucher cell Macrophage with abundant fibrillar blue-gray cytoplasm, striated/wrinkled (‘onion skin’, crumpled tissue paper); PAS positive
Hematologic Anemia and thrombocytopenia (hypersplenism, marrow replacement); 15ร— โ†‘ risk of plasma cell neoplasm, CLL, lymphoma, acute leukemia
Tests Chitotriosidase (storage level, monitoring); PAS; PCR screen in Ashkenazi Jews; gene sequencing to confirm
Treatment Enzyme replacement (recombinant glucocerebrosidase); substrate reduction agents; HSCT (high mortality); pharmacologic chaperones
Pseudo-Gaucher cells Thalassemia, CML, ALL โ€” excess cell turnover overwhelms a normal enzyme; EM shows no tubular inclusions

*Rodak prints ‘increase in serum phosphatase’; the classic marker is tartrate-resistant acid phosphatase.

2.10 Clinical Subtypes of Gaucher Disease (Rodak Table 29-2)

Feature Type I: Nonneuropathic Type II: Acute Neuropathic Type III: Subacute Neuropathic
Onset Childhood/adulthood Infancy Childhood
Hepatosplenomegaly + + +
Skeletal abnormality + โˆ’ +
Neurodegeneration โˆ’ +++ ++
Death Variable By 2 years 2ndโ€“4th decade
Ethnic predilection Ashkenazi Jews Panethnic Swedes

2.11 Niemann-Pick Disease & Box 29-3 Comparison

Disease Morphology Clinical Lab Test
Gaucher Blue-gray, striated/wrinkled cytoplasm (‘onion skin’) Neurologic symptoms (types II/III), hypersplenism, anemia, thrombocytopenia Chitotriosidase; PAS; PCR and sequencing
Niemann-Pick A Foamy macrophages packed with lipid-filled lysosomes (vacuoles/bubbles), eccentric nucleus Infancy: failure to thrive, hepatosplenomegaly, rapid neurodegeneration โ†’ death by 3 years; <5% ASM activity Acid sphingomyelinase activity distinguishes A vs B
Niemann-Pick B Same First decadeโ€“adulthood; hepatosplenomegaly, heart disease, pulmonary insufficiency; little/no neurologic disease; 10โ€“20% ASM ASM activity
Niemann-Pick C Same Defective cholesterol efflux from endosome/lysosome (NPC1/NPC2); systemic, neurologic, psychiatric; most die before 25 Sequencing: NPC1 (95%), NPC2 (5%)

Types A and B: autosomal recessive SMPD1 mutations โ†’ acid sphingomyelinase (ASM) deficiency โ†’ sphingomyelin in liver, kidney, lungs (brain in A).

2.12 Genetic B and T Lymphocyte Abnormalities

Disorder Lineage Defect Key Features
DiGeorge syndrome T Absent/underdeveloped thymus; microdeletion 22q11.2 (most common chromosome deletion, ~1 in 3500) โ†“ T cells; parathyroid defects (hypocalcemia), cardiac anomalies, abnormal face, neurologic. <1% athymic (‘complete’) โ†’ thymus transplant (~75% survival)
X-linked agammaglobulinemia (XLA) B Bruton tyrosine kinase (BTK) mutation โ†’ B cells fail to mature Symptoms after 1โ€“2 months when maternal antibodies clear; recurrent life-threatening bacterial infections
SCID โ€” ADA deficiency T, B, NK Adenosine deaminase deficiency โ†’ toxic adenosine and 2โ€ฒ-deoxyadenosine Depletion of T, B and NK cells
X-linked SCID T, B, NK IL-2 receptor ฮณ chain (common ฮณ chain shared by several interleukins) More common SCID; T lymphopenia, dysfunctional B cells, no NK cells
Wiskott-Aldrich syndrome T, B, NK X-linked; WASp protein absent/low Triad: immunodeficiency, eczema, thrombocytopenia

2.13 Quantitative Definitions (Absolute Counts)

Term Definition Notes
Neutrophilia >7.0 ร— 10โน/L adults; >8.5 ร— 10โน/L children ANC = segs + bands (some labs add metas/myelos)
Neutropenia <2.0 ร— 10โน/L (white adults); <1.3 ร— 10โน/L (black adults) Infection risk rises below 1.0; severe <0.5
Agranulocytosis <0.5 ร— 10โน/L
Leukemoid reaction Reactive WBC >50 ร— 10โน/L with neutrophilia and marked left shift Usually neutrophilic; can involve other cells
Eosinophilia >0.4 ร— 10โน/L >1.5 ร— 10โน/L for >6 months with no cause โ†’ hypereosinophilic syndrome (MPN)
Eosinopenia <0.09 ร— 10โน/L
Basophilia >0.15 ร— 10โน/L Most common cause: MPN such as CML
Monocytosis >1.0 ร— 10โน/L adults; >3.5 ร— 10โน/L neonates
Monocytopenia <0.2 ร— 10โน/L Rare alone; steroids, hemodialysis, sepsis, EBV
Lymphocytosis >4.5 ร— 10โน/L adults; >10.0 ร— 10โน/L young children Relative 20โ€“40% shouldn’t define it
Lymphocytopenia <1.0 ร— 10โน/L adults; <2.0 ร— 10โน/L young children

2.14 Neutrophilia โ€” Mechanisms & Causes (Table 29-3)

Feature Details
Demargination Shift from marginal to circulating pool โ€” catecholamines/epinephrine: strenuous exercise, emotional stress, shock, burns, trauma, labor (no left shift)
Marrow release/production Shift from marrow storage pool or โ†‘ production โ€” almost always with a left shift
Causes Emotional, exercise, trauma, labor/postpartum, postsurgery, acute hemorrhage, bacterial (some viral) infections, burns, MI, pancreatitis, vasculitis, colitis, autoimmune disease, acute hemolysis, steroids, lithium, G-CSF, smoking, chronic blood loss, metabolic ketoacidosis, uremia, eclampsia, malignancy, LAD, familial cold urticaria, hereditary neutrophilia

2.15 CML vs Leukemoid Reaction (Rodak Box 29-4)

Feature Chronic Myelogenous Leukemia (Malignant) Leukemoid Reaction (Reactive)
Cells increased All granulocytes, including eosinophils and basophils; occasional blasts Neutrophils including immature forms; blasts rarely
Morphology Dyspoietic: mixed eos/baso granulation, pseudo-Pelger-Huรซt cells Reactive: toxic granulation, Dรถhle bodies, vacuoles
Platelets May be โ†‘; giant, hypogranular, bizarre forms Normal number and morphology
LAP score Markedly decreased Increased

2.16 Leukoerythroblastic Reaction

Feature Details
Definition Immature neutrophils + nRBCs + teardrop RBCs in the same sample (ยฑ neutrophilia)
Meaning Possible space-occupying lesion in the marrow: metastatic tumor, fibrosis, lymphoma, leukemia, or marked hyperplasia (e.g., erythroid in hemolytic anemia)
Strong association Primary myelofibrosis

2.17 Neutropenia โ€” Acquired Causes

Feature Details
Mechanisms โ†‘ removal/destruction; โ†“ production or ineffective hematopoiesis; shift to marginal pool; combinations
Alloimmune neonatal Maternal IgG crosses placenta against paternal neutrophil antigens (FcฮณRIIIb, NB1, HLA); ~1 in 2000 births; resolves after a few months
Autoimmune (children) Primary; antibodies to HNA-1; self-limiting, resolves 7โ€“24 months
Secondary autoimmune RA and Felty syndrome, SLE, Sjรถgren; immune complexes, cytokines, splenomegaly
Drugs >100 drugs; 3โ€“12 per million/year; dose-dependent toxicity or immunologic. Examples: acetaminophen, ibuprofen, cephalosporins, chloramphenicol, penicillin, vancomycin, carbamazepine, phenytoin, cimetidine, chloroquine, quinine, methyldopa, clozapine, allopurinol, chlorpromazine
Other acquired Radiation, toxins, viral infection of progenitors, overwhelming infection, splenomegaly, hemodialysis, copper deficiency, alcoholism, babies of hypertensive mothers

2.18 Intrinsic (Congenital) Neutropenias

Disorder Genetics Key Features
Shwachman-Diamond syndrome Autosomal recessive Marrow failure + pancreatic insufficiency + skeletal abnormalities; intermittent neutropenia (88โ€“100%); anemia and reticulocytopenia (~80%); thrombocytopenia; โ†‘ MDS/AML risk
Kostmann syndrome (severe congenital neutropenia) Autosomal recessive Neutrophils often <0.2 ร— 10โน/L shortly after birth; marrow maturation arrest at the promyelocyte stage
Cyclic neutropenia ~50% ELANE/ELA2 (neutrophil elastase) Severe neutropenia every 21 days: fever, mouth ulcers, infections; G-CSF helps; monocytosis inverse to neutropenia
Chronic idiopathic neutropenia (adults) โ€” Women 18โ€“35; more immature than mature neutrophils in marrow; G-CSF useful
Fanconi anemia AR or X-linked Marrow failure, cytopenias, โ†‘ cancer risk
Dyskeratosis congenita X-linked recessive, AD or AR Mucocutaneous abnormalities, skin pigmentation, nail dystrophy, leukoplakia, marrow failure
Note All congenital neutropenias โ†‘ risk of hematologic neoplasms; G-CSF linked to โ†‘ secondary leukemia

2.19 Eosinophils & Basophils

Feature Details
Eosinophilia causes Cytokines IL-3 and IL-5. Underdeveloped areas: parasites (helminths, protozoa). Developed countries: allergic (asthma, hay fever, urticaria, atopic dermatitis); also scarlet fever, HIV, fungal infections, autoimmune disorders, drug hypersensitivity; reactive in ALL t(5;14) and some solid tumors
Eosinopenia causes Marrow hypoplasia; infection/inflammation with neutrophilia; autoimmune disease, steroids, stress, sepsis, acute inflammation
Basophilia causes Most common: malignant MPN (CML). Nonmalignant: allergic rhinitis, drug/food hypersensitivity, chronic infections, hypothyroidism, chronic inflammation, radiation, bee stings

2.20 Monocytes โ€” Reactive Monocytosis (Table 29-4)

Feature Details
Infection Tuberculosis, viral, malaria, brucellosis, leishmaniasis, fungal, subacute bacterial endocarditis, syphilis, protozoa
Recovery From acute infection or neutropenia (often first sign of recovery after chemotherapy) โ€” a positive sign
Immunologic SLE, RA, autoimmune neutropenia, IBD, myositis, sarcoidosis
Hematologic Acute/chronic, cyclic, drug-induced neutropenia; Wiskott-Aldrich; hemolysis; ITP
Drugs G-CSF/GM-CSF, olanzapine, carbamazepine, phenytoin, phenobarbital, valproic acid
Other Carcinoma, sarcoma, plasma cell dyscrasias, lymphoma; stress (trauma, MI, exercise); splenectomy; alcoholic liver disease, sprue

2.21 Nonmalignant Lymphocytosis & Lymphocytopenia (Table 29-5)

Category Causes
Lymphocytosis โ€” reactive morphology Infectious mononucleosis, CMV, hepatitis, acute HIV, adenovirus, chickenpox, herpes, influenza, mumps, rubella, roseola, ฮฒ-hemolytic strep, brucellosis, toxoplasmosis, typhoid/paratyphoid, Listeria, Mycoplasma, syphilis; drug reactions, postvaccination, stress (MI), allergy, hyperthyroidism, malnutrition
Lymphocytosis โ€” nonreactive morphology Bordetella pertussis (whooping cough), acute infectious lymphocytosis, polyclonal B-lymphocytosis
Lymphocytopenia โ€” inherited SCID, common variable immunodeficiency, ataxia-telangiectasia, Wiskott-Aldrich
Lymphocytopenia โ€” acquired Aplastic anemia; AIDS, SARS, West Nile, hepatitis, TB, sepsis, malaria and others; immunosuppressants, chemotherapy, radiation, surgery; autoimmune disease, Hodgkin lymphoma, carcinoma, myelofibrosis, protein-losing enteropathy, renal failure; ethanol, zinc deficiency

2.22 Reactive Morphologic Changes in Neutrophils (Box 29-5A)

Change Morphology Associated With
Toxic granulation Dark, blue-black granules (peroxidase +; โ†‘ acid mucosubstance in primary granules) in segs, bands, metas; not all neutrophils equally affected Inflammation, infection, G-CSF; correlates with CRP
Dรถhle bodies Pale blue round/elongated bodies 1โ€“5 ยตm, near the membrane; lamellar rows of rough ER โ€” ribosomal RNA; grayer with EDTA delay Nonspecific: bacterial infections, sepsis, normal pregnancy
Cytoplasmic vacuoles Autophagocytic: small (~2 ยตm), scattered ยท phagocytic: large (up to 6 ยตm), with toxic granulation Septicemia; drugs (sulfonamides, chloroquine), EDTA storage >2 h (artifact), autoantibodies, acute alcoholism, high-dose radiation
Pyknotic nucleus Dehydrated, very dense chromatin; filaments still visible Imminent cell death (vs necrotic: rounded fragments, no filaments)
Degranulation Granules emptied (neutrophils, eosinophils); eosinophils fragile on smearing Activation
Cytoplasmic swelling Neutrophil anisocytosis Osmotic swelling or adhesion to glass
Left shift Mild (bands, metas) โ†’ moderate (metas, myelos, occasional promyelocyte) โ†’ marked (+ occasional blast) Infection, inflammation, stress, CSF therapy

2.23 Ehrlichia & Anaplasma

Feature Details
Organisms Small, obligate intracellular tick-borne bacteria; grow as clusters (morulae)
Location Neutrophils: Anaplasma phagocytophilum, Ehrlichia ewingii ยท monocytes: Ehrlichia chaffeensis (human monocytic ehrlichiosis)
Labs Leukopenia, thrombocytopenia, โ†‘ liver enzymes; anemia in ~half of HME
Detection Morulae on Wright-Giemsa film or buffy coat preparation in the first week; confirm with immunofluorescent antibody titers or PCR
Treatment Early doxycycline

2.24 Reactive Monocytes (Box 29-5B) & Lymphocytes (Box 29-5C)

Feature Details
Monocytes Thin, band-like or segmenting nucleus; โ†‘ cytoplasm and granules; phagocytic activity (vacuoles, debris, irregular borders). Infection, marrow recovery, GM-CSF. Many immature monocytes โ†’ think neoplasm
Lymphocyte names Variant, reactive, effector, transformed, Turk, Downey cells, immunoblasts, atypical (‘atypical’ least suitable โ€” implies abnormal)
Reactive lymphocyte features Heterogeneous shapes and sizes; โ†‘ variably basophilic cytoplasm; variable N:C ratio; mostly clumped chromatin (some less mature); nucleoli may be visible; cytoplasm indented by RBCs
Plasmacytoid lymphocyte Reactive lymphocyte with plasma cell features โ€” a morphologic term, not a lineage

2.25 Infectious Mononucleosis (IM)

Feature Details
Agent Epstein-Barr virus; primary childhood infection usually silent; IM = symptomatic infection in adolescents/adults
Incubation 3โ€“7 weeks
Pathogenesis Virus infects B lymphocytes via envelope glycoprotein 350/220 binding CD21 (C3d receptor); oropharyngeal epithelium also infected. Response: NK cells, CD4โบ T cells, CD8โบ cytotoxic T cells โ€” most circulating reactive lymphocytes are activated T cells
Epidemiology ~500 per 100,000/year in the U.S.; peak age 15โ€“24 (3 monthsโ€“70 years reported)
Common symptoms Sore throat, dysphagia, fever, chills, cervical lymphadenopathy, fatigue, headache
Less common Hepatomegaly, โ†‘ transaminases, splenomegaly, hemolytic anemia, thrombocytopenia; rare: aplastic anemia, DIC, TTP, HUS, Guillain-Barrรฉ
CBC WBC 10โ€“30 ร— 10โน/L with absolute lymphocytosis; up to โ‰ฅ50% reactive lymphocytes
Screening Rapid heterophile antibody tests (cross-react with sheep and horse RBC antigens). Not everyone produces them โ€” especially children
Definitive EBV-specific panel: VCA, EBNA, IgG/IgM against VCA and EBNA
Mimic Cytomegalovirus causes a similar mononucleosis syndrome

3 ยท Visual Memory Hooks

๐Ÿง  Pelger-Huรซt
โ€œPelger = Pince-nez, Perfectly functional, Lamin Bโ€.
๐Ÿง  True vs pseudo PHA
โ€œTrue = Tons (63โ€“93%) and the whole family; Pseudo = Poorly granular, few (<38%)โ€.
๐Ÿง  Alder-Reilly
โ€œAlder-Reilly = Really big purple granules in ALL cells (even lymphs) โ€” Hurler/Hunterโ€.
๐Ÿง  Toxic vs Alder-Reilly
โ€œToxic = only some neutrophils + Dรถhle + left shift; Alder = every cell, no infectionโ€.
๐Ÿง  Chรฉdiak-Higashi
โ€œChรฉdiak = Chunky giant granules, Chronic infections, Can’t clot well (dense granules)โ€.
๐Ÿง  May-Hegglin
โ€œMay-Hegglin = MYH9, Mega platelets, Myosin inclusionsโ€.
๐Ÿง  Dรถhle body
โ€œDรถhle = Dough of RNA (ribosomes)โ€.
๐Ÿง  CGD
โ€œCGD can’t Go Dark on NBTโ€ โ€” no blue formazan; X-linked gp91phox.
๐Ÿง  LAD
โ€œLAD I = Integrin (CD18); LAD II = fucose (no H antigen); LAD III = kindlin (bleeds)โ€.
๐Ÿง  Gaucher
โ€œGaucher = Glucocerebroside, crumpled tissue paper (onion skin)โ€.
๐Ÿง  Niemann-Pick
โ€œNiemann-Pick = Nice foamy bubbles (Sphingomyelin)โ€.
๐Ÿง  DiGeorge
โ€œCATCH-22*โ€ โ€” Cardiac, Abnormal face, Thymic aplasia, Cleft palate, Hypocalcemia, 22q11.
๐Ÿง  XLA
โ€œBruton = B cells Broken, Boys, after maternal Ab fade (1โ€“2 months)โ€.
๐Ÿง  SCID
โ€œX-SCID = IL-2Rฮณ; ADA = toxic Adenosineโ€.
๐Ÿง  Wiskott-Aldrich
โ€œWATER: Wiskott-Aldrich = Thrombocytopenia, Eczema, Recurrent infectionsโ€*.
๐Ÿง  Leukemoid vs CML
โ€œLAP is High in Leukemoid (reactive), Low in CMLโ€; CML brings eos + basos.
๐Ÿง  Leukoerythroblastic
โ€œYoung whites + Young reds + Teardrops = something is crowding the marrowโ€.
๐Ÿง  Cyclic neutropenia
โ€œCyclic every 21 days โ€” ELANEโ€.
๐Ÿง  Kostmann
โ€œKostmann stops at the Promyelocyteโ€.
๐Ÿง  Eosinophilia
โ€œNAACP*โ€ โ€” Neoplasm, Asthma/Allergy, Addison, Collagen vascular, Parasites.
๐Ÿง  IM
โ€œEBV Enters B cells via CD21, but T cells React (CD8)โ€.
๐Ÿง  Heterophile
โ€œHeterophile loves Horse and sheep RBCs โ€” often absent in kidsโ€.

*CATCH-22, WATER and NAACP are general mnemonics; hypocalcemia/cardiac/facial features and the WAS triad are from Rodak, the extra letters are general references.

Pattern Triggers

If you seeโ€ฆ Thinkโ€ฆ Becauseโ€ฆ
Most neutrophils bilobed with dense chromatin, healthy patient, same in parent Pelger-Huรซt anomaly Lamin B receptor, AD
Bilobed hypogranular neutrophils + cytopenias in elderly Pseudo-Pelger-Huรซt (MDS) Dysplasia
Hypersegmented neutrophils + macrocytic anemia Megaloblastic anemia Bโ‚โ‚‚/folate deficiency
Dark granules in all granulocytes AND lymphocytes, coarse facies Alder-Reilly (MPS: Hurler/Hunter) Undigested mucopolysaccharides
Giant granules in all granulated cells, albinism*, recurrent infections Chรฉdiak-Higashi LYST fused lysosomes
Blue inclusions in neutrophils + giant platelets + low count May-Hegglin (MYH9) Myosin precipitates
Recurrent staph/fungal infections, normal film, NBT negative Chronic granulomatous disease No respiratory burst
Persistent neutrophilia, recurrent infections, no pus, delayed cord separation* LAD I No CD18
Recurrent infections + bleeding + normal integrin expression LAD III (kindlin-3) Integrin activation failure
Marrow macrophages with crinkled blue-gray cytoplasm, Ashkenazi, splenomegaly Gaucher disease Glucocerebroside
Foamy bubbly marrow macrophages, infant, neurodegeneration Niemann-Pick A Sphingomyelin
WBC 60, left shift, toxic granulation, โ†‘ LAP, pneumonia Leukemoid reaction Reactive
WBC 90, โ†‘ basophils/eosinophils, โ†“ LAP CML Malignant MPN
nRBCs + immature neutrophils + teardrops Leukoerythroblastic reaction (myelofibrosis, metastases) Marrow infiltration
Neutropenia every 21 days with fever and mouth ulcers Cyclic neutropenia (ELANE)
Child with pancreatic insufficiency + neutropenia Shwachman-Diamond
Clusters of organisms in monocytes, tick bite, leukopenia Human monocytic ehrlichiosis E. chaffeensis morulae
Teen with sore throat, lymphadenopathy, 40% reactive lymphs Infectious mononucleosis EBV
Marked lymphocytosis of small normal-looking lymphocytes, child with cough Pertussis Nonreactive lymphocytosis

*Partial albinism in Chรฉdiak-Higashi and delayed umbilical cord separation in LAD I are general references (Rodak mentions hair/skin involvement and skin lesions).

Commonly Confused Pairs

Feature A B
Pelger-Huรซt vs left shift Mature clumped chromatin, pale cytoplasm Finer chromatin, basophilic cytoplasm
True vs pseudo-PHA 63โ€“93% affected, all lineages, family <38%, neutrophils, hypogranular (MDS)
Toxic granulation vs Alder-Reilly Some neutrophils only; infection clues All granulocytes + lymphs/monos; normal function
Dรถhle body vs May-Hegglin inclusion Rough ER/RNA; normal platelets Myosin; giant platelets + thrombocytopenia
Chรฉdiak-Higashi vs toxic granulation Giant fused granules, all granulated cells Fine dark granules, neutrophils
CGD vs LAD Can’t kill; normal count Can’t migrate; neutrophilia
Gaucher vs Niemann-Pick cell Striated, crumpled, blue-gray Foamy, bubbly vacuoles
Gaucher vs pseudo-Gaucher Enzyme deficiency; tubular inclusions on EM High turnover (CML, thal, ALL); no tubules
XLA vs DiGeorge No B cells (BTK) No T cells (thymus, 22q11)
Leukemoid vs CML โ†‘ LAP, toxic changes, normal platelets โ†“ LAP, โ†‘ eos/basos, dysplasia
Pyknotic vs necrotic nucleus Dense, filaments present Rounded fragments, no filaments
Autophagic vs phagocytic vacuoles Small ~2 ยตm; drugs, EDTA artifact Large up to 6 ยตm; sepsis, with toxic granulation
Reactive lymphocyte vs blast Heterogeneous, clumped chromatin Monotonous, fine chromatin*

*Rodak notes blasts can also show RBC indentation; the monotonous vs heterogeneous contrast is standard teaching.

Timeline Table

Event Timing Key Point Best Exam Use
XLA symptoms After 1โ€“2 months of age Maternal IgG gone Onset clue
Alloimmune neonatal neutropenia Resolves in a few months Maternal IgG half-life Self-limited
Autoimmune neutropenia of childhood Resolves 7โ€“24 months Anti-HNA-1 Self-limited
Cyclic neutropenia Every 21 days ELANE Periodic infections
Gaucher type II death By 2 years Acute neuropathic Subtype
Niemann-Pick A death By 3 years <5% ASM Subtype
Niemann-Pick C death Before 25 years NPC1/NPC2 Subtype
EBV incubation 3โ€“7 weeks IM onset History
Morulae visible First week of infection Ehrlichia/Anaplasma Early diagnosis
EDTA vacuole artifact Storage >2 hours Compare collection vs smear time Pre-analytical
Hypereosinophilic syndrome >1.5 ร— 10โน/L for >6 months No identifiable cause Definition

4 ยท Diagnostic Flowcharts

Flowchart 1 โ€” Hyposegmented neutrophils on the film

Bilobed/round nuclei with coarse, clumped chromatin โ†’ Mature cell โ€” not a band or myelocyte
63โ€“93% of neutrophils, normal granulation, other lineages too โ†’ True Pelger-Huรซt (check family)
<38%, hypogranular, cytopenias โ†’ Pseudo-Pelger-Huรซt โ†’ MDS/AML/MPN workup
Recent drug (valproate, mycophenolate, taxanes) or infection (HIV, TB) โ†’ Acquired pseudo-PHA
Reporting โ†’ Count as ‘others’ = Pelger-Huรซt neutrophils, not as left shift
โš ๏ธ Common mistake: reporting a left shift and triggering an infection workup.

Flowchart 2 โ€” Abnormal granules or inclusions in neutrophils

Dark granules in some neutrophils + Dรถhle bodies + left shift โ†’ Toxic granulation (reactive)
Dark metachromatic granules in all granulocytes + lymphs/monos โ†’ Alder-Reilly โ†’ MPS workup
Giant granules in all granulated cells, infections, bleeding โ†’ Chรฉdiak-Higashi
Large pale blue inclusions + giant platelets + thrombocytopenia โ†’ May-Hegglin
Small pale blue patch near membrane, normal platelets โ†’ Dรถhle body (infection, pregnancy)
Clusters of organisms โ†’ Morulae โ†’ Anaplasma/Ehrlichia
โš ๏ธ Common mistake: calling Alder-Reilly granules toxic granulation โ€” look at lymphocytes and the clinical picture.

Flowchart 3 โ€” Recurrent infections with a normal-looking film

Recurrent bacterial/fungal infections, granulomas โ†’ NBT test or DHR flow
NBT not reduced / DHR no fluorescence โ†’ Chronic granulomatous disease (NADPH oxidase)
Neutrophilia, no pus formation โ†’ CD18 (ฮฒโ‚‚ integrin) flow โ†’ LAD I
Growth retardation, H-negative โ†’ LAD II (fucose)
Infections + bleeding, normal integrins โ†’ LAD III (kindlin-3)
Low immunoglobulins, male infant after 2 months โ†’ XLA (BTK)
โš ๏ธ Common mistake: trusting a normal film to exclude a phagocyte defect โ€” CGD and LAD have normal morphology.

Flowchart 4 โ€” Marked neutrophilia: reactive or leukemia?

WBC >50 ร— 10โน/L with left shift โ†’ Examine morphology and platelets
Toxic granulation, Dรถhle bodies, vacuoles; blasts rare; normal platelets โ†’ Leukemoid reaction
โ†‘ Eosinophils and basophils, dysplasia, bizarre platelets โ†’ Suspect CML
LAP score โ†’ โ†‘ = leukemoid ยท โ†“ = CML
Confirm CML โ†’ BCR-ABL1 / Philadelphia chromosome*
nRBCs + teardrops + immature neutrophils โ†’ Leukoerythroblastic โ†’ marrow infiltration/myelofibrosis
โš ๏ธ Common mistake: diagnosing leukemia from the WBC count alone.

*Covered in the CML chapter.

Flowchart 5 โ€” Absolute lymphocytosis

Adult lymphocytes >4.5 ร— 10โน/L (child >10) โ†’ Look at morphology
Heterogeneous reactive lymphocytes โ†’ Viral (IM, CMV, hepatitis), toxoplasmosis, drug reaction
Young adult + sore throat + lymphadenopathy โ†’ Heterophile test โ†’ EBV panel (VCA, EBNA) if negative
Small, normal-looking lymphocytes, child with cough โ†’ Pertussis
Monotonous atypical cells, older adult โ†’ Consider lymphoid neoplasm (flow cytometry)*
โš ๏ธ Common mistake: using the relative % instead of the absolute count.

*Neoplasm pathway from general practice.

Flowchart 6 โ€” Case 2: fever of unknown origin with monocytosis

Fever, weight loss, cultures and O&P negative, 28% monocytes, vacuolated monocytes, toxic neutrophils, ESR 70 โ†’ Look for intracellular organisms in monocytes/neutrophils
Where โ†’ Feathered edge โ€” large cells (monocytes) accumulate there*
Morulae in monocytes โ†’ Human monocytic ehrlichiosis (E. chaffeensis) โ†’ doxycycline
Better yield โ†’ Buffy coat preparation concentrates WBCs
Confirm โ†’ Immunofluorescent antibody titers or PCR
โš ๏ธ Common mistake: stopping at ‘reactive monocytosis’ without searching for organisms.

*The Case 2 answers (organism, feathered edge) are my interpretation โ€” the answer key isn’t in the upload.

5 ยท 25 High-Yield Facts

# Fact
1 Pelger-Huรซt anomaly is autosomal dominant and caused by a lamin B receptor mutation.
2 Pelger-Huรซt neutrophils have bilobed or round nuclei with coarse chromatin but function normally.
3 Pelger-Huรซt cells can be miscounted as bands or metamyelocytes, creating a false left shift.
4 Pseudo-Pelger-Huรซt cells are acquired, affect fewer cells and are often hypogranular in MDS.
5 Hypersegmented neutrophils (>5 lobes) are most often seen in megaloblastic anemia.
6 Alder-Reilly anomaly shows large metachromatic granules and is associated with Hurler and Hunter syndromes.
7 Chรฉdiak-Higashi syndrome is autosomal recessive (LYST) with giant lysosomal granules and recurrent infections.
8 May-Hegglin anomaly is an MYH9 disorder with Dรถhle-like inclusions, giant platelets and thrombocytopenia.
9 Chronic granulomatous disease neutrophils cannot produce superoxide (NADPH oxidase defect).
10 CGD is detected by failure to reduce NBT to formazan or by DHR-123 flow cytometry.
11 About 60โ€“65% of CGD is X-linked (gp91phox).
12 LAD I is a ฮฒโ‚‚ integrin (CD18) defect; LAD II a fucose transporter defect; LAD III a kindlin-3 defect.
13 Gaucher disease is ฮฒ-glucocerebrosidase deficiency; Gaucher cells have striated blue-gray cytoplasm.
14 Niemann-Pick disease is sphingomyelinase deficiency; Niemann-Pick cells have foamy cytoplasm.
15 X-linked SCID is caused by a mutation in the IL-2 receptor ฮณ chain.
16 XLA is caused by a BTK mutation and presents after maternal antibodies disappear (1โ€“2 months).
17 Neutrophilia is an absolute neutrophil count above 7.0 ร— 10โน/L in adults.
18 Agranulocytosis is an absolute neutrophil count below 0.5 ร— 10โน/L.
19 A leukemoid reaction has an increased LAP score; CML has a markedly decreased LAP score.
20 A leukoerythroblastic reaction suggests a space-occupying marrow lesion and is associated with myelofibrosis.
21 Cyclic neutropenia recurs about every 21 days and is linked to ELANE mutations.
22 Dรถhle bodies are composed of ribosomal RNA (rough endoplasmic reticulum).
23 Women in active labor usually have a high WBC count with a slight left shift.
24 Reactive lymphocytes are heterogeneous with increased, variably basophilic cytoplasm, suggesting viral infection.
25 EBV infects B cells via CD21; most reactive lymphocytes in IM are activated T cells.
โญ EXAM TIP โ€” The single most testable pattern

Match the inclusion to the disorder: pince-nez nuclei = Pelger-Huรซt (lamin B receptor) ยท dark granules in all WBCs = Alder-Reilly (MPS) ยท giant granules = Chรฉdiak-Higashi (LYST) ยท blue inclusions + giant platelets = May-Hegglin (MYH9). A normal-looking neutrophil that can’t kill = CGD (NBT negative). LAP high = leukemoid; LAP low = CML.

Quick Interpretation Table

Lab Finding Clinical Interpretation
5-year-old: recurrent staph infections, liver abscess, normal CBC/morphology, normal chemotaxis and phagocytosis, NBT not reduced Chronic granulomatous disease (Rodak Case 1) โ€” most likely X-linked gp91phox; antifungal/antibiotic prophylaxis โ†’ >90% reach adulthood
66-year-old: fever, weight loss, WBC 4.0, platelets 130, 28% monocytes, vacuolated monocytes, toxic neutrophils, ESR 70 Search for intracellular organisms (morulae) โ€” feathered edge, buffy coat (Rodak Case 2)*
Healthy donor, 80% bilobed neutrophils, dense chromatin Pelger-Huรซt anomaly
WBC 55, toxic granulation, LAP โ†‘, basophils normal Leukemoid reaction
Platelets 60 (giant), blue neutrophil inclusions, asymptomatic May-Hegglin anomaly
Eosinophils 2.5 ร— 10โน/L, traveler with diarrhea Parasitic infection (helminths)
Heterophile negative, EBV VCA IgM positive, 8-year-old EBV infectious mononucleosis (children often heterophile-negative)

๐ŸŽด Flashcards โ€” Active Recall Practice

How it works: tap the card to flip it. Then mark it โœ“ Knew It or โœ— Review Again (buttons unlock after flipping). Use ๐Ÿ”€ Shuffle to randomize and ๐Ÿ Finish anytime โ€” your summary appears at the end, and you can drill only the cards you missed.

๐Ÿ“ Practice Quiz โ€” Test Your Knowledge

How it works: tap an answer for each case. You’ll get instant feedback with the full explanation and the examiner’s trap. Your final score appears once all 10 are answered.

๐Ÿชค Trap Questions โ€” Beat the Examiner

Harder on purpose. Each question targets a real misconception. After answering you’ll see the correct reasoning, the trap explained, why the examiner wrote it, and the wrong answer most students choose.

8 ยท Rapid Revision Sheet

๐Ÿ“– READ THIS 2 HOURS BEFORE YOUR EXAM

Inherited Morphology

  • PHA: AD, lamin B receptor, pince-nez, normal function
  • Alder-Reilly: AR, metachromatic granules all WBCs, MPS
  • Chรฉdiak-Higashi: AR, LYST, giant granules, infections + bleeding
  • May-Hegglin: AD, MYH9, inclusions + giant platelets
  • Hypersegmentation >5 lobes: megaloblastic

PHA Pitfalls

  • True: 63โ€“93%, all lineages, family
  • Pseudo: <38%, hypogranular, MDS/AML/drugs
  • Don’t count as bands (false left shift)
  • Mature clumped chromatin, pale cytoplasm
  • Report as ‘others’

Functional Defects

  • CGD: NADPH oxidase, no superoxide
  • NBT โ†’ no formazan; DHR flow
  • 60โ€“65% X-linked gp91phox
  • LAD I CD18 ยท II fucose (Hโˆ’) ยท III kindlin-3 (bleeds)
  • MPO deficiency: usually asymptomatic

Storage Diseases

  • Gaucher: ฮฒ-glucocerebrosidase, 1q21, AR
  • Striated blue-gray macrophages; chitotriosidase
  • Types I (Ashkenazi) ยท II (death by 2) ยท III (Swedes)
  • Niemann-Pick: sphingomyelinase (SMPD1), foamy cells
  • Pseudo-Gaucher: CML, thal, ALL

Lymphocyte Genetics

  • DiGeorge: 22q11.2, no thymus, โ†“ T, hypocalcemia
  • XLA: BTK, no B cells, 1โ€“2 months
  • SCID: ADA or X-linked IL-2Rฮณ
  • Wiskott-Aldrich: WASp, eczema + โ†“ plts + infections

Absolute Counts

  • Neutrophilia >7.0 (child 8.5)
  • Neutropenia <2.0 (black 1.3) ยท agranulocytosis <0.5
  • Eos >0.4 ยท baso >0.15 ยท mono >1.0
  • Lymphocytosis >4.5 (child 10)
  • Lymphopenia <1.0 (child 2.0)

Neutrophilia vs CML

  • Leukemoid: WBC >50, left shift, toxic, โ†‘ LAP
  • CML: โ†‘ eos/basos, dysplasia, โ†“ LAP
  • Leukoerythroblastic: nRBC + teardrops + immature
  • โ†’ marrow infiltration, myelofibrosis
  • Demargination: stress, exercise, labor

Neutropenias

  • Alloimmune neonatal (maternal IgG)
  • Autoimmune childhood anti-HNA-1 (7โ€“24 mo)
  • Felty, SLE, drugs (clozapineโ€ฆ)
  • Kostmann: promyelocyte arrest
  • Cyclic 21 d (ELANE) ยท Shwachman-Diamond (pancreas)

Reactive Changes

  • Toxic granulation: some neutrophils; CRP
  • Dรถhle: RNA, 1โ€“5 ยตm; infection, pregnancy
  • Vacuoles: small autophagic vs large phagocytic
  • EDTA >2 h โ†’ vacuole artifact
  • Morulae: Anaplasma (neut), E. chaffeensis (mono)

Lymphs & IM

  • Reactive: heterogeneous, basophilic, RBC indentation
  • EBV โ†’ B cells via CD21; T cells react
  • IM: 15โ€“24 yr, WBC 10โ€“30, โ‰ฅ50% reactive
  • Heterophile (sheep/horse RBCs); kids often โˆ’
  • Confirm VCA, EBNA; CMV mimics

9 ยท Final Memory Map

  • โšช NONMALIGNANT LEUKOCYTE DISORDERS
    • Qualitative โ€” Morphologic
      • Pelger-Huรซt (true/pseudo) ยท hypersegmentation ยท myelokathexis/WHIM
      • Alder-Reilly ยท Chรฉdiak-Higashi ยท May-Hegglin
    • Qualitative โ€” Functional
      • CGD (NBT, DHR)
      • LAD I, II, III ยท MPO deficiency
    • Storage Diseases
      • MPS (Hurler, Hunter, Sanfilippo, Morquio)
      • Gaucher ยท Niemann-Pick A/B/C ยท Fabry ยท Tay-Sachs
    • Lymphocyte Genetics
      • DiGeorge ยท XLA ยท SCID (ADA, IL-2Rฮณ) ยท Wiskott-Aldrich
    • Quantitative
      • Neutrophilia ยท leukemoid vs CML ยท leukoerythroblastic
      • Neutropenia: acquired and congenital
      • Eosinophils ยท basophils ยท monocytes ยท lymphocytes
    • Reactive Morphology
      • Toxic granulation ยท Dรถhle ยท vacuoles ยท pyknosis
      • Reactive monocytes ยท reactive lymphocytes
      • Ehrlichia/Anaplasma morulae
    • Infectious Mononucleosis
      • EBV โ†’ CD21 ยท T-cell response
      • Heterophile ยท VCA/EBNA ยท CMV mimic



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