WBC, LN disorders Flashcards
Chediak Higashi
LYST
Large granules in neutrophils
Associated with albinism, bleeding, and HLH-like EBV infection
May-Hegglin anomaly
MYH9 abnormality
Dohle-like granulocyte inclusions
Macrothrombocytopenia
Associated with deafness, cataracts, nephritis
Alder-Reilly phenomenon
PAS+ granules in ALL WBCs.
Associated with mucopolysaccharidoses.
Normal granulocyte function.
Pelger-Huet anomaly
Lamin B receptor abnormality.
Hypolobated neutrophils.
No clinical significance.
Niemann-Pick
Sphingomyelinase deficiency.
Foamy vacuolated macrophages. “Sea-blue”? Mucin negative.
Gaucher cells
Glucocerebrosidase deficiency
Tissue paper wrinkled macrophages. Mucin-negative.
Hematogones
Blast-like B-cell precursors.
CD34+, TdT+. CD10+, which fades as CD20 is acquired.
Blast morphologies and markers
Monoblasts: Grey-blue cytoplasm, irregular and prominent nuclear folds. CD4/CD16
Megakaryoblasts: Blebbing. CD41/42/61
Erythroblasts: Dark, with vacuoles. CD71/E-Cad/GlycophorinA
Myeloblasts generally: MPO, CD13, CD15, CD33
“Block PAS positivity”
Buzzword for ALL
Cytochemistry, generally
Alpha-naphthyl esterase (non-specific) - Monocytes
Chloroacetate esterase (CAE) - Granulocytes
*Both of above in Combined esterase
MPO, Sudan Black - Myeloid
Acute monocytic leukemia
Pure erythroid leukemia
Megkaryoblastic leukemia
Need >80% of each respective blast morphology and phenotype. Rule out other specific diagnoses (eg, for Megakaryoblastic, must rule out inv(3), t(1;22))
APL
t(15;17) PML-RARa ; variant translocations often confer resistance to ATRA therapy
Hypergranular or hypogranular (butterfly lobed nuclei, higher count).
CD33+, CD117+, CD34 dim, HLA-DR -
t(9;11) AML
MLL rearrangement
Usually seen in children. Intermediate prognosis.
Monocytic morphology
t(6;9) AML
DEK-NUP.
Basophilia. Poor prognosis.
inv(3) or t(3;3) AML
MECOM
Megakaryoblasts
Hypolobation, dysplasia
t(1;22) AML
RMB15-MLK1
Megakaryoblastic.
Associated with t21.
Chemotherapy types and t-MN
Alkylating agents: MDS-like AML with -5, -7, etc. Dismal prognosis. Slow onset.
Topoisomerase inhibitors: MLL-rearrangement, monocytic. Still poor prognosis. Fast onset.
AML with normal karyotypes
FLT3 ITD - Poor px (especially D835 - Confers resistance to FLT3 inhibitors)
Biallelic CEBPA - Good px
NPM1 - Good px
IDH - ???
B-ALL - Molecular profiles
t(12;21) ETV6-RUNX1 - Good
Hyperdiploidy (>52chr) - Good
(Age 1-10 good)
Hypodiploidy (<40chr) - Bad t(9;22) or BCR-ABL1-like - Bad MLL-rearranged - Bad. Infants. RUNX1 amplified - Bad Complex karyotype - Bad
Features of MPNs
Extramedullary hematopoiesis Organomegaly NO DYSPLASIA Basophilia Progression to fibrosis and leukemia
MPN genetics
JAK2 (V617F > Exon 12 mut)
CALR
MPL
BCR-ABL
CSF3R in CNL
CML
Basophilia, marked left shift. Diagnosable on smear and molecular (but get BMBx for blast count)
Low LAP score. Pseudo-Gaucher cells. Dwarf megakaryocytes
Phases: Chronic, accelerated (10-19% blasts), blast crisis (+Ph, i17q, +8, +19)
p210 transcripts
MDS genetics
Good: -Y, del(5q), del(20q)
Poor: -7, -17p, complex karyotypes
MDS class flowchart
- Excess blasts
- Mildilineage dysplasia
- Ringed sideroblasts
- Isolated del(5q)
5q minus syndrome
Usually seen in older women. MDS with isolated del(5q)
Presents with macrocytosis and THROMBOCYTOSIS
BMBx shows small megakaryocytes
Associated with RPS14 abnormalities. Treatable with lenalidomide
CMML
Need >1M monocytes to diagnose.
ASXL1 mutations
PDC clusters (CD123+)
JMML
RAS-opathy. Associated with Noonan, NF1
Elevated HbF. -7.
Sensitive to GM-CSF, but poor prognosis
Atypical CML
BCR-ABL1-negative overlap syndrome. SETBP1 mutations. Has nothing to do with CML.
Castleman disease
Hyaline-vascular: Onion-skinning, lollipops, increased FDC meshwork
Plasma-cell: HHV-8 associated. Increased IL-6. Associated with POEMS. May progress to DLBCL
POEMS
Polyneuropathy Organomegaly Endocrinopathy Monogammaglobulinemia Skin lesions
Associated with plasma-cell multicentric castleman
HIV lymphadenopathy
Evolution of follicular hyperplasia, to involution, to depletion
Toxoplasmosis
Triad of follicular hyperplasia, monocytoid B cells, and epithelioid granulomas
Infectious mononucleosis
Sinusoidal monocytoid B cells.
Paracortical immunoblasts, RS_like cells.
Necrosis and apoptosis OK
Dermatopathic lymphadenopathy
Pigment incontinence with increased interdigitating dendritic cells (IDCs): S100+, Fascin+, CD1a-
Kikuchi-Fujimoto lymphadenitis
Asian patients
Proliferative phase (Crescentic histiocytes, PDCs)»_space; Necrotic phase (no granulocytes)
Self-limiting
Cat scratch lymphadenitis
Palisading / stellate necrotizing granuloma
HLH - Primary, secondary, criteria
Primary: PRF1»_space; STX11, UNC13D (AutRec)
Secondary: 5 of 8 - Fever, splenomegaly, cytopenias, hyperferritinemia, hypertriglyceridemia, decreased NK cell activity, HLH visualized, elevated sCD25
CLL
CD20+. CD5+/CD23+. CD200+, LEF1+.
Need 5k lymphs, else call MBL.
Proliferation foci. Paraimmunoblasts.
Cytogenetics: del(13q) good. t12, -11q, -17p bad.
CD38, ZAP70, CD49d, IGHV unmut bad.
Follicular lymphoma
CD20+. CD10+, BCL2+. Tends also to express BCL6, HGAL, LMO2
Back-to-back follicles. Buttock cells.
Grading: <15 centroblasts per hpf (Gr 1-2), any residual centrocytes 3a, purely centroblasts 3b.
Follicular lymphoma - Subtypes
Cutaneous: Neither BCL2+ nor fusion+.
Pediatric: BCL2+, but no fusion.
Duodenal: BCL2+, fusion+.
Mantle cell lymphoma
CD20+. BCL1/CycD+. SOX11+. CD5+/CD23-.
Histiocytes present. Recall LyPolyp.
FISH is preferable to PCR for CyclinD1 rearr.
Aggressive variants: Pleomorphic, blastoid.
Marginal zone lymphomas
General: Dutcher/russell bodies.
NMZL: Associated with IRTA abnormalities
EMZL: Often t(11;18) API2-MALT1
SMZL: Bipolar villous projections.
Associated with autoimmune disorders, H. Pylori, Chlamydia
LPL/WM
Open sinuses, increased mast cells in BM. IgM paraprotein.
MYD898 L265P (nonspecific)
Burkitt
3 types: Endemic (EBV+, jaw), sporadic (abdomen), immunosupp (EBV++).
Starry sky histology. Vacuolated cells on smear. EXTRANODAL!
CD10+, MYC+. Also BCL6+. Ki67 100%
t(8;14) > t(2;8) (kappa) or t(8;22) (lambda)
Hans classifier
CD10+»_space; GCB
BCL6-»_space; ABC
MUM+»_space; ABC
None of above true (ie, only BCL6+?)»_space; GCB
THRLBCL
LBCL that resembles NLP (normal B cell phenotype, maybe CD30). NO ROSETTES.
DLBCL, Leg-type
Cutaneous DLBCL with poor prognosis.
CD10-, BCL2+, MUM1+ (both poor markers in LBCLs)
PMBL
Young women, mediastinum
Compartmentalizing fibrosis
B-cell phenotype, often CD30+.
IRF4 rearranged DLBCL
As name suggests.
CD10+, BCL6+, MUM1+ (all 3!)
High proliferation rate
NLPHL
Popcorn cells: CD45+, CD20+, often EMA+.
Rosettes of PD1+ helper T-cells
Expanded FDC meshworks
Associated with PTGC
CHL types
Nodular sclerosing - Mediastinal, often women
Mixed cellularity - Eosinophils, most EBV+
Lymphocyte rich - Good px, few germinal centers
Lymphocyte depleted - Retroperitoneal, poor px
AITL
Fh T-cells: CD3+, CD4+, CD8- ; CD10+, PD1+, ICOS+, BCL6+, CXCL+
Arborizing vessels in LN with PAS+ material.
Polyclonal hypergammaglobulinemia (rheumatoid factors, ASMA, cryoglobulins)
Expanded FDC meshworks
May have incidental EBV+ B cells
ALCL
Sinusoidal involvement by CD30+ Hallmark/Wreath cells. Granule markers more reliable than CD30?
EMA+, ALK variable. t(2;5) has nuclear and cytoplasmic expression.
Perivascular rosettes
ALK- often DUSP22, IRF4, TP63 rearranged (poor px)
ATLL
T-regs: CD3+, CD4+, CD25+, FOXP3+, CCR4+. CD8-.
Flower cells. Associated with HTLV (+TSP)
Hypercalcemia, lytic bone lesions
T-LGLL
Need at least 2B/mL?
Associated with RA. Presents with cytopenias.
CD4-, CD8+, toxic markers+.
STAT3 mutations.
EATL
Celiac disease, europeans
Large cells, usually CD8-.
MEITL
Asians. Non-mass forming?
Smaller cells. CD8+, CD56+?
Hepatosplenic T-cell lymphoma
Young men. Common in post-transplant setting.
Usually gamma-delta cells: cCD3, 4-/8-, CD56+.
-7q.
Subcuteanous panniculitis-like TCL
Lymphoma of gamma-delta T-cells. No involvement of overlying epidermis or dermis.
Note fat rimming by neoplastic T-cells.
Mycosis fungoides
Patch / Plaque / Tumor stages. Indolent course, but poor overall prognosis?
Epidermotropism, Pautrier microabscesses, cerebriform nuclei.
CD4+, CD8-. Often loss of CD5, CD7. TCR rearrangements.
HCL
Leukemic disorder of B-cells: CD20+, CD11c+, CD13+, CD103+, TRAP+, Annexin A1+. CYCLIN D1?
BRAF V600E, sometimes MAP2K1.
Monocytopenia, marrow fibrosis with interstitial infiltration. Blood lakes in spleen. Fried eggs. No LN involvement.
Circumferential projections.
vHCL
Resembles hairy cell leukemia, but…
CD25-, no BRAF mutations.
ETP-ALL
Must express CD7, be CD1a- and CD8-.
Cytoplasmic CD3. TdT.
ALK+ LBCL
Often CD20, PAX5-negative
ALK+, CD138+, often IgA.
T-PLL
Nuclear irregularity, cytoplasmic blebbing
inv(14) TCL1 abnormalities
NK, gamma-delta phenotypes
NK: CD4+, CD64+. No CD3.
Gamma-delta: CD3+, 4-/8-.
AMLs with megakaryoblastic features
t21
t(1;21) RMB-MLK1 - Kids
inv(3) GATA-MECOM - Adults
Sezary syndrome
Erythrodermic TCL. Loss of epidermotropism.
CD3+, CD4+, CD5/7 often lost, CD8-. Same as MF.
Leukemic, but no BM involvement. Poor survival.
DLBCL gene rearrangements
BCL6 - Most common (30%). Good Px alone.
BCL2 - 25%. Bad.
MUM-1 - Bad.
Generally, GCB preferable to ABC.
WHIM / Myelokathexis
CXCR4 mutations, delaying neutrophil maturation & release
Neutropenia, aberrant segmentation, accelerated apoptosis
Severe congenital neutropenias
HAX1: SCN3 (Kostmann syndrome). Affects mitochondria/apoptosis
ELAN: SCN1. AutDom, Elastase misfolds, mistrafficks.
HRS phenotype
CD20- (but PAX5 weakly positive)
CD15+, CD30+
CD45-
LMP1+?
Arise from follicle center B-cells
Mast cell disorders
(Rule out other hematolymphoid malignancy first)
Must show clustering, abnormal spindling
CD2, 25 are abnormal. CD117 is expected.
KIT mutational analysis (817).
Increased mast cell tryptase.
Plasma cell myeloma - Genetics
t(11;14) Cyclin D1 favorable, confers lymphoid morphology
Hyperdiploidy: Odd chromosomes, favorable.
-13 bad, -17 bad. Complex bad. Other IGH translocations bad.
Plasma cell paraprotein trivia
Flame cells suggest IgA
Plasma cell leukemia often IgD, IgE, or light chain only
Lambda free light chain is more amyloidogenic than kappa
Rosai Dorfman
Self-limiting histiocytosis of especially cervical and occipital lymph nodes.
Emperipolesis. S100+. CD1a-.
Often has increased plasma cells and polyclonal hypergammaglobulinemia.
Rule out hemophagocytosis.
PMF diagnostic criteria
Major: Atypical megakaryocytes, clonality, no other better diagnosis
Minor: Leukoerythroblastosis, anemia, LDH++, splenomegaly
Need all 3 major and 2 minor.
Duncan disease
X-linked lymphoproliferative syndrome
Associated with SLAM, XIAP gene abnormalities.
Hypogammaglobulinemia. Exaggerated response to EBV infection.
TAM
Develops in 25% of t21 infants, with acquired GATA-1 mutation
Increased circulating blasts (10%?) up to a few months out from birth.
Resolves spontaneously, but predicts later AML.
Core binding factor AMLs
t(8;21) RUNX1-RUNX1T1 - Salmon-colored granules. CD19.
inv(16) CBFB-MYH11 - Abnormal eosinophils
Both are definable by translocation (do not need 20% blasts)
Both are worsened with co-occurrence of KIT mutation
BPDCN
CD4+, CD123+ (normal PDC markers)
CD56+, TdT+ (aberrant)
MLNeo
PDGFRA/B
FGFR1
NPM-JAK
Responsive to TKIs
Most common plasmacytoma sites
2 (extraosseous): Upper respiratory tract
Bone #1
