Glossary of Path-WBC disorders
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- Describe AML FAB 1
- Acute Myeloblastic leukemia without differentiation
*minimal maturation >90% type I and II blasts in the marrow
*very few auer rods
* Immuno: variable:positive for CD13, CD14, CD11b, CD33, and HLA-DR.
*Chromo: t(9;22) Philadelphia chromosome, 8+, -5, and -7.
*Pheno: minimum of 3% show + MPO stain, negative for others
- Describe AML FAB 2
- Acute myeloblastic leukemia with maturation
*Most common AML (20-40%)
*Type II blasts and Auer rods present
*Largely MPO +, others -
* Variable positivity for CD13, CD33, and HLA-DR, but are negative for CD14 and CD11b.
*Chromosome Abnormalities: t(8;21), 8+, -5, and -7.
*Morph: some with basophilic and some granules, if >10% of cells then M2
- Describe AML FAB 3
- Acute promyelocytic leukemia (APL)
*Maturation: In the classic M3 the majority of the proliferating cells are abnormal promyelocytes with numerous primary type granules. Auer rods are frequent and often multiple.
*Staining: The cells are MPO and chloroacetate esterase (CAE) positive, but generally negative for NSE (NSE positive in 25%).
*Immuno: Positivity for CD13 and CD33, but are usually negative for HLA-DR.
*Chromosome Abnormalities: The t(15;17) is unique to promyelocytic leukemia.
*t(15;17) assoc. with Retinoic Acid Receptor and so can be treated with retinoic acid
- Describe AML FAB 4
- Acute myelomonocytic leukemia (AMML)
*Maturation: Differentiation along both myeloid and monocytic lines. Monocytes and promonocytes represent > 20%, but < 80% of the marrow differential.
*Staining: More than 20% of the blasts should be MPO + and more than 20% should be NSE +
1. High serum lysozyme (3x normal)
2. A peripheral monocytosis of > 5x10/L in an otherwise M2 marrow and increased lysozyme
3. A peripheral monocytosis of >5 x10/L in M2 marrow and >20% NSE + marrow blasts. *Chromosome Abnormalities: t(4;11), t(9;11), 8+ and -7.
*Variant: M4e variant in which eosinophils (> 5%) are increased in number and abnormal associated with abnormalities of chromosome 16.
- Describe AML FAB 4e variant
- *Variant: M4e variant in which eosinophils (> 5%) are increased in number and abnormal associated with abnormalities of chromosome 16.
*Staining of Variant: CAE, usually negative in eosinophils, is frequently positive in the abnormal eosinophils of M4e.
- Describe AML FAB 3v variant
- *Microgranular Variant: the leukemic cells have a monocytic appearance with clefted angel-wing nuclei and abundant cytoplasm having at best indistinct cytoplasmic granulation.
*cytochemical, immunophenotypic and chromosomal features are indentical to the classic M3.
*Both forms of acute promyelocytic leukemia are associated with a high incidence of
*****disseminated intravascular coagulation (DIC) and hemorrhage.
- Describe AML FAB 5
- Acute monocytic leukemia
*Differentiatiation: Monocytic. Two subtypes:* M5a is the poorly differentiated form * M5b is the well-differentiated form
*Chromo: t(9;11), 8+, -5, and -7. Chromosome abnormalities of 11q are closely associated with M5a
*Morph: Note the nuclear folds and the relatively large nucleoli typical of monoblasts at right. fewer granules,
occasionally will see slight nuclear fold, few, large nucleoli
- Describe AML FAB 6
- Acute erythroleukemia (erythroblastic)
*Maturation: rare and difficult to diagnose. More than 50%* of the nucleated marrow cells are abnormal nucleated red blood cells.
*Morph: The leukemic red cells are frequently bizarre with extreme dysplastic features including: giant forms, multinucleation, cytoplasmic vacuolization, cytoplasmic buds, and megaloblastoid changes.* 30% considered adequate by some
*Staining: The blasts are MPO negative, but often positive for NSE. The malignant red cells are PAS positive, (forming PAS positive lakes or containing coarse chunks of PAS positive material).
*Immuno: Positive for glycophorin A.
*Chromo: 8+, -5, del(5q), and -7.
*DDX: Congenital dyserythropoietic anemia, myelodysplastic syndrome, sideroblastic anemia, and megaloblastic anemia.
- Describe AML FAB 7
- Acute Megakaryocytic leukemia
*M7 blasts are often resemble lymphoblasts, although M7 leukemias may be accompanied by atypical megakaryocytes. The marrow is often fibrotic.
*Staining: M7 blasts are MPO negative and variably positive for PAS and NSE.
*Diagnosis: Determination of an M7 subtype is dependent on immunologic evidence or electron microscopic ultracytochemical identification of platelet peroxidase (PPO).
*Immuno studies of M7 are positive for glycoproteins GP Ib andGP IIb/IIIa.
*Factor VIII related protein is usually found in the megakaryoblast cytoplasm.
*Chromo: t(1;22), have been associated with M7 in infants.
- Describe ALL-L1
- *Morphology: L1 blasts are small and homogeneous. The nuclei are round and regular with little clefting and inconspicuous nucleoli. Cytoplasm is scanty and usually without vacuoles.
*Staining: MPO is always negative.
*Maturation: Most L1 ALLs are of pro B or pre B lineage.
85% of ALL
- Describe ALL-L2
- *Morphology: L2 blasts are large and heterogeneous. The nuclei are irregular and often clefted. One or more, usually large nucleoli are present. The volume of cytoplasm is variable, but often abundant and may contain vacuoles.
*Maturation: L2 ALLs may be of pro B or pre B lineage, but cases of T cell ALL are more likely to have an L2 than L1 morphology.
*Staining: L2 blasts may have granular or "chunky" PAS positivity with a negative cytoplasmic background. NSE is usually negative. MPO is always negative.
- Describe ALL-L3
- Burkitt's Lymphoma
*Morphology: L3 blasts are moderate-large in size and homogeneous. The nuclei are regular and round-oval in shape. One or more prominent nucleoli are present. The volume of cytoplasm is moderate and contains prominent vacuoles.
*Staining: MPO is always negative. NSE is negative, but may show focal cytoplasmic positivity. The vacuoles are PAS negative (center), but are classically positive for the neutral lipid stain Oil Red O (right).
***All L3 leukemias are surface immunoglobulin (SIg) positive and are of B cell lineage.
- M2-acute myeloblastic leukemia
- M3- Promyelocytic leukemia APL
- inv, del, t (16q)
- M4- Myelomonocytic leukemia
- M5-Monocytic leukemia
- ALL-pre B cell
- ALL- T cell
- t(8;14), t(2;8) t(8;22)
- L3- Burkitt's lymphoma
- Describe CML
- *Def: 15%, is a malignant disorder of multipotent stem cells with predominance of mature granulocytes and their precursors accumulating in excess in the marrow and blood.
*Clinic: The initial phase of CML is stable or indolent (usually lasting 2-4 years), but is followed by an acclerated stage (6-12 months), and finally an acute phase or blast crisis (2-4 months) similar to acute leukemia.
*Gene: Philadelphia chromosome (Ph') or t(9;22)(q34;q11) -stops apoptosis
*CBC: WBC count typically elevated from 20 x 109/L, and is often >100 x109/L. PBS:Segmented neutrophils, myelocytes, and metamyelocytes predominate, but eosinophilia and basophilia. <2% blasts &/or myelodysplasia. +/-anemia, plate-nl or inc.
*LAP:low or absent
*BM: hypercellular (100%),inc. M:E ratio;left shifted myeloid, and inc. eosinophils. Megakary-Nl or inc, small
*Dz: Accel=inc. baso/eso and inc. blast #. The blast phase is reached when the number of blasts exceeds 30% in PB or BM. usually myeloid (>60%), lymphoid (30%)
*CML differentiated from leukemoid reactions= marked increase in myeloid elements secondary to infection, chronic inflammation and other causes. Dist. blast from AML
*Genetics: accelerated or blast phase a double Ph' or other chromosomes abnormality, ie. trisomy 8, may be encountered.
*Clinic: 45 yrs (rare in children). The incidence is ≈1/100,000/year with M=F.
- Describe PV
- polycythemia vera
*Def: erythroid hyperplasia, absolute increase RBC. Myeloid +Megakaryo also.
*Path: unknown. One respond to unusually low levels of erythropoietin. Supresses epo and Nls not stimulated. Myeloid and megakaryocytic dysregulated
*BM: hypercellular, all three major cell lines, erythroid elements predominate, M:E ratios of 1:1 or lower.
*CBC: inc. Hct, Hgb,RBC(nl) 50% mild - moderate leukocytosis and thrombocytosis. Basophils are frequently increased.
*DDX: 1) Relative increases in red cell concentration (hemoconcentration,ie. dehydration) and 2) secondary forms of absolute increases in red cell number (increased erythropoietin, ie. smoking & sleep apnea).
*Clinic: age of 40-60 years with symptoms secondary to the increased blood volume and viscosity - including plethora, hypertension, headache, dizziness and hematemesis. Pruritis is a frequent symptom.
- Describe Myelofibrosis
- *Def: Primary, also know as agnogenic (idiopathic) myeloid metaplasia or myeloid metaplasia with myelofibrosis is malignancy of red, white and megakaryocytic cells - a panmyelosis. Marrow fibrosis with either increased or decreased cellularity. fibrosis secondary to the production of PDGF by malignant megakaryocytes. PDGF is a known mitogenic stimulus of fibroblasts.
*BM: 1'MF hypocellular 2nd extensive fibrosis Megakaryocytes, appear morphologically abnormal. Osteosclerosis is a common finding.
*MF worsens then extramedullary myeloid metaplasia increases. spleen is the primary site of myeloid metaplasia, any site can be involved liver, lymph nodes, and kidneys.
*Clinic: 1MF one-third less common than CML and is seen primarily >50 years Splenomegaly, increasing anemia presenting findings (symptoms). Bone pain, fever and night sweats common.
*PBS: Moderate to severe anemia; anisocytosis &poikilocytosis- teardrop shapes (dacryocytes). Nucleated red cells. leukocytosis with immature forms. The LAP score normal or high. Abnormally large platelets and sometimes megakaryocyte nuclei are found.
*DDX: Metastatic neoplasia;inflammation;
*Dz: Survival 5 years after two year period of asymptomatic disease. Death secondary to infection, hemorrhagic episodes or acute leukemia.
*Tx: chemotherapy (dec plate and WBC) or PRBC or platelets PRN.
- Describe Essential Thrombocytopenia
- *Def: UNK etio
*PBS: platelet > one million/mL, R/O reactive. Plat. not nl funct.
*Dx: R/O other chronic myeloproliferative disorders CML, PV and 1'MF
*BM: hypercellular excessive megakaryocytes similar PV.
*Clinica: thrombosis or hemorrhage often involving the microvasculature with resultant neurologic symptoms. Can lead to bleeding and bruising. 50% splenomegaly. *Tx: Myelosuppressive chemotherapy, platelet pheresis or platelet inhibitors
1. platelets >600 x10 /L
2. hemoglobin <130g/L
3. marrow iron stores or failed Fe trial
4. Philadelphia chromosome negative
5. no collagenous fibrosis of marrow or fibrosis <1/3 examined area with no splenomegaly and no leukoerythroblastic reaction
6. no known cause of reactive thrombocytosis
- Describe CLL
- *Epid: most common chronic lymphoproliferative disorders, representing about 30% of all leukemia.
*adults. > 60 years of age and asymptomatic
*Def: proliferation mature appearing, functionally incompetent lymphocytes, in BM, PBS, other organs.
*PBS= absolute lymphocytosis (>5.0 x109/L, but usually >15.0 x109/L and sometimes > 100.0 x109/L).
*Clinic: LAD and splenomegaly are common late in the disease
*Hypogammaglobulinemia common late in the disease course, associated increased infection. 10% IgM mono. *Anemia and thrombocytosis may indicate marrow replacement or autoimmune destruction.
*Morp: smaller than normal and appear to be more fragile resulting in characteristic "smudge" cells.
*Immuno: B cells (98%). 2% are of T cells. CLL-B: weakly express surface immunoglobulin IgM or IgM & IgD. light chain is monoclonal. CD19, CD20, and CD21 and the T-associated antigen CD5.
*The coexpression of CD19 and CD5, (seen on <1% of normal B cells), is also seen in mantle cell lymphoma, and some prolymphocytic leukemias.
*Chromo: trisomy 12 associated with CLL; 14q+ chromosome abnormality with prolymphocytic leukemia (see below). When trisomy 12 + abnormalities of chromosomes 11 or 14 the prognosis is worsened.
*Marrow: diffuse small lymphocytes. Other patterns: interstitial or nodular infiltration usually seen earlier in the disease. The diffuse infiltration suggests a worse prognosis and correlates with a Rai stage III or IV.
*Disease Complic: change into a more aggressive disease.
* Prolymphocytic transformation occurs when increasing numbers of prolymphocytes. refractory to therapy and the prognosis worsens.
* Richter's syndrome" development of a large cell lymphoma, usually immunoblastic. 5% of the CLL and an ominous occurence.
- Describe Chronic Prolymphocytic leukemia
- *Morp: morph variant CLL. cell is a prolymphocyte, larger than the lymphocytes of CLL (10-15m), resembles activated lymphocytes with fine almost blastic chromatin, a single large nucleolus, and pale blue cytoplasm.
*Immuno: similar to CLL (CD19+; CD5+), but surface Ig is strongly expressed.
*Clinic: WBC count is high (usually >100.0 x10 /L). Splenomegaly common, but lymphadenopathy unusual. Patients with prolymphocytic leukemia tend to be older (70 years) than patients with CLL (64 years) and have an aggressive clinical course. Surviv: prolymphocytic leukemia is 3 years versus the 8 years of CLL.
*About 20% of prolymphocytic leukemias T cell origin. prognosis poor, survival is only 6 months. T cell: involves the skin causing a papular nonpruritic nonscaling rash.
- Describe Hairy Cell leukemia
- *Def: low grade B cell leukemia of moderately large mononuclear cells having distinctive "hairy" cytoplasmic projections (upper right).
*Morph: abundant cytoplasm "fried egg" appearance to each cell in tissue sections producing a characteristic "honeycomb" appearance on biopsy of BM
*BM: "dry" because of a network of increased recticulin.
*Dx: PBS or marrow aspirate, positive tartrate resistant acid phosphatase stain ( TRAP positive) and CD19+; CD5-; CD11c+; CD25+ are diagnostic.
*Clinic: Splenic involvement usu. red pulp; 4:1 male to female predominance (compared to a 2:1 ratio in CLL).
*Sx: pancytopenia (fatigue, infection, easy bruising) or splenomegaly, but with little lymphadenopathy.
hx dz: variable survival of 5 years before current interferon or adenosine deaminase (ADA) inhibitor therapy. The most common cause of death infection.
*Tx: In the past splenectomy (curing pancytopenia caused by the hypersplenism) was the only effective form of therapy for HCL.**Today treatment with alpha-2-interferon, deoxycoformycin (Pentostatin) and 2-chlorodeoxyadenosine approaching a normal age-matched life expectancy.
- Describe T-cell chronic lymphoproliferative dz
- *heterogeneous iphenotype and clinical behavior. Most are post-thymic T cells expressing either CD4 or CD8. Some cells express natural killer (NK) antigens. Aberrant pan T antigen expression is frequent
*T cell Chronic Lymphoid Proliferations
* T cell chronic lymphocytic leukemia
* T prolymphocytic leukemia
* T g lymphocytosis syndrome
Relatively rare and some may not even be malignant.
*Sezary syndrome and ATLL are post-thymic T cell malignancies must be distinguished from the T-cell chronic lymphoproliferative disorders.
*Sezary syndrome is a proliferation of malignant cerebriform T cells that circulate in the peripheral blood but present primarily in the skin.
*ATLL is an aggressive proliferation of highly atypical T lymphocytes associated with HTLV-1, involving the peripheral blood, skin, liver, spleen, etc.
- Describe T-cell chronic leukemia
- *exceptionally rare and must be distinguished from the various subtypes of the T g lymphocytosis syndrome and from T prolymphocytic leukemia. The T lymph of T-cell CLL morphologically resemble the cells of B-cell CLL. Nearly all have a CD4 T-helper phenotype.
*No known clinical course.
**T prolymphocytic leukemia (20% of prolymphocytic leukemias) is an aggressive malignant proliferation of T cells with a median survival of only 6 months. Skin involvement (a papular nonpruritic nonscaling rash) and lymphadenopathy are common.
*PBS: lymphocyte counts are exceptionally high (frequently >100.0x109/L).
***T g lymphocytosis syndrome most important of the T-cell chronic lymphoproliferative disorders. T g lymphocytosis is a proliferation of large granular lymphocytes (LGL) in the peripheral blood and bone marrow often accompanied by neutropenia, less often by anemia.
*Clinic: At presentation people with T g lymphocytosis 55-65 years of age. Recurrent infections are the most common presentation. Rheumatoid arthritis is found in one-third of patients. The spleen is enlarged in 50 to 70 percent. Lymphadenopathy is uncommon.
*dz: Although the course is usually indolent it may be quite variable. About one-quarter slowly progress to death due to infection secondary to neutropenia. Chemotherapy is not very effective. Control of the neutropenia by growth factors may play a significant role in treatment of T g lymphocytosis.
*Immuno: Clonal rearrangements of various T cell receptor genes has been found in some, but not all cases of the T g lymphocytosis syndrome. majority are monoclonal and low grade malignancy, others could be reactive proliferations.
- What is PAS?
- *Weak-Neg: Myeloid/monocytic
*Pos: Erythroid line
The periodic acid Schiff stain demonstrates glycogen and related mucopolysaccharides. Myeloid or monocytic blasts are typically weakly positive or negative. A granular (may be fine, coarse, or block) PAS pattern with a negative background is characteristic of lymphoblastic leukemia. PAS staining is positive in the erythroid population in erythroblastic leukemias.
- What is NSE?
- **Only strong in monocytes
Nonspecific esterase (NSE) - Alpha naphthyl acetate esterase is an enzyme found in large amounts in monocytic cells, but in only minor concentrations in myeloid or lymphoid cells. Useful to identify monocytes.
- What is MPO?
- ***Myeloid and Monocytes only
Myeloperoxidase (MPO)- Myeloperoxidase is an enzyme located in the granules of myeloid and monocytic cells. Myeloperoxidase is never found in lymphoid cells. If positive, is the most important marker distinguishing myeloid from lymphoid blasts.
- what is AP?
- **Dot pattern in T-lymphocytes and lymphoblasts
Acid phosphatase (AP) - Although the acid phosphatase enzyme is ubiquitous, T-lymphocytes and lymphoblasts have a characteristic "dot-like" focus of intense positivity, whereas the activity in most other cells is diffuse.
- What is TRAP?
- **Only Hairy Cell Leukemia
Tartrate-resistant acid phosphatase (TRAP), one of the AP isoenzymes, is an important diagnostic feature of hairy cell leukemia.
- Characteristics of Hodgkins Lymphoma
- *Reed-Sturnberg cells
*young adults but can be old
*contingious spread by lymph
*fever,night sweats,weight loss
*usus. always B-cell lineage
- Describe Nodular Sclerosis Hodgkins Lymphoma
- "Lacunar" R-S variants and sclerosing bands of collagenous fibrosis forming a nodular pattern are characteristic features.
*The fibrosis thickens the capsule and divides the proliferating process into "nodules" or islands.
*Classic Reed-Sternberg cells are generally infrequent, but there may be numerous "lacunar" variants.
*Nodular sclerosis classical Hodgkin Lymphoma is the most common type of Hodgkin lymphoma (70%).
*Nodular sclerosing Hodgkin lymphoma is more common in women than other forms of Hodgkin lymphoma. Most cases (80%) have mediastinal involvement present with stage II disease.
- Describe Mixed Cellularity Hodgkins lymphoma
- *Mixed cellularity Hodgkin Lymphoma has numerous R-S cells in a mixed inflammatory background that obliterates the normal architecture.
*Plasma cells and eosinophils are frequent. Only small amounts of fibrosis and occasional necrosis may be present.
*Patients with MC Hodgkin lymphoma frequently have systemic manifestations.
*Mixed cellularity Hodgkin Lymphoma is less common (20-25%) than NS,HD. Most patients are men (70%) an present with late stage (III-IV) disease and B-symptoms.
- Describe Lymphocyte depletion Hodgkin's lymphoma
- *Lymphocyte-depleted classical Hodgkin lymphoma is characterized by many Reed-Sternberg cells and variants (small lymphocytes are virtually absent) or by extensive fibrosis. There are two subtypes, a sarcomatous subtype with numerous bizarre Reed-Sternberg cells and a "diffuse fibrosis" variant, with extensive fibrosis and rare Reed-Sternberg cells.
*Rare (5%), this subtype is often associated with HIV infection.
*Clinical features: Abdominal organs, retroperitoneal lymph nodes, and bone marrow are often involved. Peripheral lymph node involvement is less common. Approximately 70% of patients present at an advanced stage and most (80%) have B symptoms.
- Describe Lymphocyte Predominance Hodgkin's lymphoma
- *Classic R-S cells are rare and difficult to find, but mononuclear "L&H" Hodgkin cells with "popcorn" shaped nuclei and inconspicuous nucleoli are present against a background of small lymphocytes. HD,LP may be diffuse (shown here) or vaguely nodular.
- Reed-sternberg cell expression
- Reed-Sternberg cells and most Hodgkin variants express the monoclonal antigens CD15 (Leu M-1) and CD30 (Ki-l), but are CD45 (LCA-leukocyte common antigen) negative.
The exception is the Hodgkin cell of LP,HD - the "L&H" or "popcorn" cell, which is CD45 positive; CD15 negative, CD20 (L26) positive, and light-chain restricted (monoclonal). Therefore HD,LP is immunologically distinct from the other types of HD.
- B-cell NHL Types
- *Follicular Lymphoma
*Low grade B-cell lymphoma of MALT
*Diffuse Large B-cell Lymphoma
- T-cell NHL types
- *Precursor T-lymphoblastic lymphoma
*Peripheral T-cell Lymphoma
- Follicular Lymphoma
- *Most common type of NHL
*peripheral and retroperitoneal adenopathy
*B follicular center cell origin
*effacement of the nodular arch.
*small cleaved cells (GI) or mixtures of small cleaved and large transformed cells (GII) but rare large cells (GIII)
*Immuno: CD20+,10+, monotypic surface Ig
*Chromo: t(14;18) 90% of FL
- B-small Lymphocytic Lymphoma
- *older adults
*adenopathy, leukemic blood picture
*diffuse effacement by small lymphocytes with round nuclei and dense chromatin
*low grade neoplasm
*weak CD20,5,23 and weak surface Ig
- Low-grade B-cell lymphoma of MALT
- *usu. low grade and in extranodal tissue, GI and lung
*assoc. with H.pylori and autoimmune
- Diffuse large B-cell lymphoma
- *common NHL in adults
*diffuse prolif of neoplastic B-lymphoid cells.
*CD20 and surface IG
- Burkitt's Lymphoma
- *highly aggressive
*kids and adults, extranodal-jaws, distal ileum, ovaries
*diffuse prolif or small non-cleaved cells with "starry night" pattern.
*Assoc. with EBV
*CD 20, 10, and surface IG
*t(8;14) all cases
- Precursor T-lymphoblastic lymphoma
- *Rapidly growing A mediastinal mass in young pts, us. male.
*disseminate rapidly to marrow, PBS, regional lympoh
*blastic appearance with high N:C ration, fine chromatin and nucleoli
*thymic tissue effaced by diffuse groth for monomorphic tumor cells with high mitotic rate
*markers of immature T-cells
- Mycosis Fungoides
- *tumor of small, skin-based T-cells with CD4 subset in adults
*band-like superficial dermal infiltrate adjacent to and invading epidermis with small collections of lympocytes in the epidermis
*lymph-small and folded cerebriform nuclei
- Peripheral T-cell lymphoma
- *nodal disease of adults
*advanced systemic dz c, eosinophilia, and hemophagocytosis
*loss or abberant expression of pan T-cell antigens
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