CHRONIC LEUKEMIAS Flashcards by Sab Manlapaz

-Increased MATURE rather than immature cells in the lymphoid or myeloid lines
-The basic defect in growth control presumably affects [precursor/progenitor] cells, but in these disorders most ________ cells differentiate
-Progression is [slower/faster]; can be [weeks or months] up to years

CHRONIC LEUKEMIAS
progenitor
neoplastic cells
slower
months

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2 TYPES OF CHRONIC LEUKEMIAS

MYELOPROLIFERATIVE NEOPLASMS [MPN]
LYMPHOPROLIFERATIVE DISORDERS/ MATURE LYMPHOID NEOPLASMS.

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-are clonal hematopoietic disorders caused by
genetic mutations in the hematopoietic stem cells (HSCs) that result in expansion, excessive production, and accumulation of mature erythrocytes, granulocytes, platelets, and mast cells

MYELOPROLIFERATIVE NEOPLASMS

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MYELOPROLIFERATIVE NEOPLASMS
Each has a chronic course that may terminate as ________ ________, ____________, or a ___________.

Acute leukemia
Myelofibrosis
Coagulopathy

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MYELOPROLIFERATIVE NEOPLASMS
Mutation in_________; this discovery allowed for refinement of the classification of MPNs.

Myeloproliferation largely is due to [hyposensitivity or hypersensitivity] or [dependence or independence] of normal cytokine regulation resulting from genetic mutations that reduces ______ levels through _______ _________ systems normally induced by mature cells

JAK2/Janus Kinase 2 [JAK2V617F mutation]

hypersensitivity
independence
cytokine
negative feedback

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it is a [pluripotent/multipotent] HSC ______where all of the MPNs involve dysregulation

multipotent hematopoietic stem cell (CD34)

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WHO CLASSIFICATION OF MPNs
● ________ MUTATION
-CHRONIC MYELOID LEUKEMIA (CML)
● ________ MUTATION
-POLYCYTHEMIA VERA (PV)
-ESSENTIAL (PRIMARY) THROMBOCYTHEMIA (ET)
-PRIMARY MYELOFIBROSIS (PMF)

BCR-ABL1

JAK2V617F

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is an MPN arising from a [single/multiple] genetic translocation in a pluripotential HSC producing a clonal overproduction of the myeloid cell line, specifically __________.
-occurs at _____ ages but is seen predominantly in those aged 46 to 53 years.

CHRONIC MYELOID LEUKEMIA
single
Granulocytes

all ages

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it represents about 20% of all cases of leukemia, is slightly more common in men than in women

CHRONIC MYELOID LEUKEMIA

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CML begins with a chronic clinical phase and, if untreated, progresses to an accelerated phase in ___ to ____ years and often terminates as _____ leukemia (_____ crisis phase).

3-4
acute, blast

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CML
CYTOGENETIC ABNORMALITY:
-Presence of the _______ gene (_________/_____)
-Reciprocal translocation between the [short-p/long-q] of chromosomes___and _____ t(__;__)
-This acquired somatic mutation specifically reflects the translocation of an _____ proto-oncogene from band _____ of chromosome ____ to the ___________ of band q11 of chromosome ____ (___;q11)
-The _______ protein has constitutive kinase activity that deregulates _____ transduction pathways, causing abnormal cell ______, inhibition of _______, and increased proliferation of cells
-Also found in FAB ___ (3-5%) and FAB ___ and ____(10-25%)

BCR-ABL1
Philadelphia Chromosome/Ph’
long, q arms
9 and 22, t[9;22]
ABR- q34 -9
Breakpoint Cluster Region [BCR]- q11-22
[q34;q11]

BCR-ABL: signal, cycling, apoptosis
M1, L1, L2

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_______

Most cases (____%) are diagnosed in this phase -Frequent ______, ______ secondary to massive massive pathologic accumulation of myeloid progenitor cells in bone marrow, peripheral blood, and extramedullary tissues
-_________ WITH ALL MATURATIONAL STAGES PRESENT, _________, __________
-Progressive fatigue and malaise, low-grade fever, anorexia, weight loss, and bone pain
-Night _______ and _____, associated with an increased metabolism caused by granulocytic cell turnover
-EM: ______; _______ infarction is common because of the abnormal overproduction and accumulation of granulocyte precursors in the bone marrow, _____, and blood
-On fresh incision, extramyeloid masses appear [color] (_______), presumably because of the presence of the myeloid enzyme _________.

CML
85%
Infection, anemia
Neutrophilia, Basophilia, Eosinophilia
sweat, fever
Splenomegaly, splenic, spleen
green [Chloromas]
myeloperoxidase

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________
ACCELERATED PHASE:
-[Increased/Decreased] splenomegaly
-Worsening ______ and _______.
-Gradual failure of response to treatment
-[+/=] cytogenetic abnormalities
-___-___% blasts

______ CRISIS (______):
-involves the peripheral blood, bone marrow, and extramedullary tissues
-Based on AL definitions, blasts constitute more than ___% of total BM cellularity, and the peripheral blood exhibits increased [matured cells or blasts]

-Clinical symptoms of blast crisis mimic those of AL, including severe anemia, leukopenia of all WBCs except _____, and __________.

CML
Increased
anemia, thrombocytopenia
+
10-19% blasts

Blast Crisis [Acute]
20%
blasts

blasts, thrombocytopenia

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-referred to as a latter of extramedullary growth may occur as lymphocytic or myeloid cell proliferations.

Granulocytic sarcoma

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CML
LABORATORY FINDINGS:
BLOOD:
-Marked expansion of the ________ pool
-Anemia and thrombocytopenia (variable)
-[left/right] shift with few blasts in the peripheral blood
-Extramedullary hematopoiesis (_____, _____)

OTHER LABORATORY FINDINGS:
-_________ and _________ (from cell turnover)
-Detection of t(9;22) translocation (cytogenetic analysis, _______,________)
-[DECREASED/INCREASED] ____ SCORE (is used to differentiate CML from leukemoid reaction)

granulocytic pool
left shift
spleen, liver

Hyperuricemia, uricosuria
FISH, RT-PCR
DECREASED, LAP

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CML
LABORATORY FINDINGS:

BONE MARROW:
-Intense [hypocellularity/hypercellularity]
-_______ fibers are increased in approximately 20% of patients
-Increased _________ density is associated with an increase in myelofibrosis
-Presence of _____________ cells

hypercellularity
Reticulin
megakaryocyte
Pseudo-Gaucher cells

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__________
-Is a clonal stem cell proliferation affecting primarily the _______ series, characterized by excessive proliferation of it and also usually granulocytic and megakaryocytic elements in the marrow
-The very slow evolution of the malignant erythroid clone leads to overexpansion of the [red/white] cell mass, [hypovolemia/hypervolemia], and splenomegalic red cell pooling
-These consequences eventually cause generalized _______ _______ with subsequent increases in the quantity of all three cell lines.

Polycythemia Vera
erythroid
red
hypervolemia
marrow hyperplasia

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PV
Associated with the _____ mutation; is detected in more than 95% of patients with PV and is found on chromosome band __p___ ; also associated with ______________[another type]

-__________ phosphorylates signal transducers and activators of transcription______ proteins, eventually generating transcription proteins that bind promotor regions and signal gene expression
-Controls transphosphorylation through conformational _________.
-Constitutive ______ _______ activity of the mutated causes [continous/non-continuous] activation of several signal transduction pathways— that are normally activated after erythropoietin stimulation via the erythropoietic receptor.
-Mutated is active and will phosphorylate ____ proteins in the absence of ________ or will overphosphorylate in its presence

JAK2V617F
9p24
JAK2 exon 12 mutation

JAK2 protein– Tyrosine kinase
STAT
inhibition

tyrosine kinase
continous

STAT
EPO

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________ POLYCYTHEMIA VERA
>Increased Hct: increase BM production
>Types: Primary, secondary with appropriate EPO production, inappropriate production of EPO

> PRIMARY
-_________
-Increased BM production of erythrocytes, leukocytes, and thrombocytes
-EPO: [increased/decreased]

> SECONDARY WITH APPOPRIATE EPO PRODUCTION
-Occurs in response to ______
-Patients with _______disease
-Increased BM production of erythrocytes, leukocytes, and thrombocytes
-EPO: [increased/decreased]

> SECONDARY WITH INAPPROPRIATE EPO PRODUCTION
-_____ of kidneys, liver, brain, adrenals
-Increased erythrocytes, leukocytes, and thrombocytes
-EPO: [increased/decreased]

ABSOLUTE

Panmyelosis
Decreased

hypoxia
cardiac/pulmonary
Increased

Tumors
Increased

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> RELATIVE POLYCYTHEMIA VERA
Increase ______; Decrease ______ volume
Dehydration, stress, spurious polycythemia, anxiety
_________ ________: spurious polycythemia

Hct, Plasma
Gaisbock’s syndrome

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CLINICAL FINDINGS:
>PV often presents with a history of [mild/severe] symptoms occurring for several [months/years]
- Increased RCM produces blood [hypoviscosity/hyperviscosity] , often resulting in __________ disease

In the early stages of the disease, before treatment, extended periods of high HCT (60%) and hyperviscosity produce ________ in about 50% of patients with PV
Hyperviscosity and hyperproliferation and include headache, weakness, [a skin condition], weight loss, and fatigue
About half of PV patients have ________ and 1/3 experience ______ or ________ episodes

mild
years
hyperviscosity– cardiovascular disease

hypertension

pruritis

thrombocytosis
hemorrhagic and thrombotic episodes

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> PV patients older than __ years of age or those associated with a history of thrombosis are considered high risk for thrombotic or hemorrhagic events

> The stable phase of PV can progress to a ____ phase in a few patients, usually within ____ years from diagnosis
- Splenomegaly (palpable spleen)
- Hypersplenism
- BM hyperplasia
- ________ [low RBC, WBC. PLT]

___________: Triad of ________, _________, and _______ with [abnormal RBC morphology] and develops in about 30% of PV patients within 20 years

Spent phase
10 years
Cytopenia

Postpolycythemic myeloid metaplasia
myelofibrosis, splenomegaly, anemia
teardrop-shaped poikilocytes

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_______________

LABORATORY FINDINDS:
>Common morphologic patterns in peripheral blood and BM _______ and cellular changes
>BM normoblasts may collect in large clusters, __________ are enlarged and exhibit lobulated nuclei, and BM ______ are enlarged without fibrosis
>Pseudo-Gaucher cells are rare

> 80% of patients manifest BM ________.

PV
morphologic
megakaryocytes
sinuses

panmyelosis

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_____________:AKA [name three]

-a clonal MPN with increased megakaryopoiesis and thrombocytosis, usually with a count greater than _____ x 109/L ; sometimes with a count greater than ______ x 109/L
-However, WHO criteria require a sustained thrombocytosis with a platelet count of ______ x 109/L –

Associated with mutations in:
_____ (64.1%) ____ (4.3%) ____ (15.5)

ESSENTIAL THROMBOCYTHEMIA
Primary thrombocytosis, Idopathic thrombocytosis, Hemorrhagic thrombocythaemia

600
1000

400

JAK2, MPL, CALR [calreticulin]

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____ CLINICAL FINDINGS: -_______ ______ [increased clots] are often the result of microvascular thromboses in the digits or thromboses in major arteries and veins that occur in a variety of organ systems, including splenic or hepatic veins, as in __________ syndrome -Repeated splenic infarcts can result in ______ _______. -Thrombosis can result in ______ emboli and ______ complications like headache, paresthesis of the extremities, visual impairments, and tinnitus -[Venous/Arterial] thrombi can cause _________ infarction, transient ischemic attack, and cerebral vascular accident -_______ occurs most often from mucous membranes in the gastrointestinal, skin, urinary, and upper respiratory tracts.

ET Vascular occlusions Budd-Chiari syndrome splenic atrophy pulmonary emboli and neurologic complications Arterial thrombi-- myocardial Bleeding

In ET, platelets often appear normal, [4] but ___ _____ platelets, platelet _______, ___________, and megakaryocyte ________ can also be observed. Platelets are present in clusters and tend to [be depleted/accumulate] [far/near] the thin edge of the blood film ; abnormal platelet function testing can occur. BM has marked megakaryocytic [hypocellularity/hypercellularity] , clustering of megakaryocytes, and increased megakaryocyte diameter with nuclear hyperlobulation and density

giant bizarre platelets platelet aggregates micromegakaryocytes megakaryocyte fragments near accumulate near hypercellularity

DIAGNOSIS OF ESSENTIAL THROMBOCYTHEMIA (ET) WHO CRITERIA FOR DIAGNOSIS OF ET: MAJOR CRITERIA: Megakaryocyte [depletion/proliferation] with large and mature morphology, [little to no/many] granulocyte or erythroid proliferation] [Major/Minor] increase in reticulin fibers MINOR CRITERIA: presence of a ____ marker or absence of evidence of reactive ________. Based on WHO standards, a diagnosis of ET requires meeting all _____ major criteria or the first _____ major criteria and one minor criteria

proliferation little to no Minor clonal marker reactive thrombocytosis four, three

___________:AKA [NAME THREE] -associated with areas of marrow hypercellularity (______________), extramedullary hematopoiesis, fibrosis, and increased ________; it is the least common but most aggressive form of MPN. -Can form __ ____ or as an evolutionary consequence of PV or ET - ASSOCIATED MUTATIONS: ____ (V617F) – 60% ; _____ - 30% ; _____ – 5% MYELOFIBROSIS -Fibroblasts produce ____ to provide structural support for HSCs -In PMF a reactive process causes overproduction of _____ that eventually disrupts the normal architecture of the BM and replaces hematopoietic tissue resulting in _________. EXTRAMEDULLARY HEMATOPOIESIS -recognized as __________ or _________, seems to originate from release of clonal stem cells into the circulation -The cells accumulate in the spleen, liver, or other organs, including adrenals, kidneys, lymph nodes, bowel, breasts, lungs, mediastinum, mesentery, skin, synovium, thymus, and lower urinary tract

Primary Myelofibrosis Chronic Idopathic Myelofibrosis, Agnogenic Myelofibrosis, Myelofibrosis with myeloid metaplasia leukoerythroblastosis megakaryocytes de novo JAK2, CALR, MPL collagen collagen Pancytopenia hepatomegaly, splenomegaly

is an uncommon disease with an incidence one-third that of CML

Chronic Idiopathic Myelofibrosis [CIM]

-The disease may be asymptomatic and usually progresses as a slow, chronic condition Symptoms result from anemia, myeloproliferation, or splenomegaly and include fatigue, weakness, shortness of breath, palpitations, loss of appetite, weight loss, night sweats, pruritis, pain in the extremities and bones, bleeding, and discomfort or pain in the left upper quadrant associated with splenomegaly

PMF

-Major _______ _______ occur in 15% of PMF patients during the course of their disease and 10% of patients demonstrate _________ and decreased blood _________ levels suggesting _________ hemolysis -Some patients develop ________ ________resulting from a combination of thrombocytopenia, abnormal platelet function, and hemostatic abnormalities suggestive of chronic_______ [disease]

hemolytic episodes hemosiderinuria haptoglobin =intravascular hemolysis bleeding diathesis DIC

PMF LABORATORY FINDINGS: In the EARLY STAGES, anemia, _______ with a ____ shift, and _________ are identified that are consistent with a MPN. [ALL INC but immature] As the fibrosis DEVELOPS in the BONE MARROW, blood cell counts fall and _______ eventually develops, along with leukoerythroblastosis, _______, and _________. Examination of the ___ ______specimen provides most of the information for diagnosis ____Abnormal cell morphology

leukocytosis, thrombocytosis, left shift pancytopenia poikilocytosis anisocytosis BM Biopsy Dacryocytes

Are a diverse collection of disease entities with varying clinical presentations and natural histories; however, common to all is identification with a particular lineage Disease states in large part can be identified with a normal counterpart in the ______, _______ or_______. Neoplastic transformation of these cells results in abnormal changes in growth and differentiation patterns, resulting in disease. Lymphoproliferative disorders in which the primary site of disease is the blood or bone marrow are classified as ________; disorders in which the localization of disease is in the lymph nodes and spleen are considered _______.

MATURE LYMPHOID NEOPLASMS blood, BM, lymph nodes leukemias lymphoma

is the most common leukemia in adults in Western countries

Chronic Lymphocytic Leukemia

is a clonal proliferation of small B lymphocytes [CALLED AS:__________] involving BM, blood, and lymph nodes -generally a disease of the older adult; median age of diagnosis is approximately ___ years which is common in _____.

Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma 72, males

Most patients are asymptomatic on presentation, and the disease is often detected by an abnormality in a routine CBC

Chronic Lymphocytic Leukemia

In CLL, The (IWCLL) requires the presence of at least __ x 109 cells/L of circulating B lymphocytes for more than ___ months to establish the diagnosis of CLL, with confirmation of clonality performed by ____ ________.

5 3 flow cytometry

CLL CYTOGENETIC ABNORMALITIES: [5]

13q14.3 --> DLEU2/MIR15A/MIR16A 6q21 Trisomy 12 ATM gene --> 11q23del TP53 gene --> 17p13del

Typical CLL presents with ____% of the lymphocytes appearing small and mature with ____ cytoplasm and a dense nucleus with a condensed chromatin pattern without a defined nucleolus. This characteristic chromatin pattern has been labeled as _______ or likened to a [basket/soccer] ball.

85% scant cobblestone soccer

________ _____ -Seen in 20% of patients -_________ or ______ lymphoid cells represent less than 10% or less than 15% of circulating lymphocytes -Associated with biologic markers indicating more aggressive disease >Subtypes: -___/___>10% but <55% of total lymphocytes (>55% is associated with _____________) -_______/atypical CLL >15% large atypical lymphoid cells

ATYPICAL CLL Prolympochytes Atypical CLL/PLL Prolymphocytic leukemia Mixed-type

are a common finding on peripheral blood film review in CLL

SMUDGED LYMPHOCYTES

CLL POSITIVE MARKERS: [6] CD__, CD__, CD__, CD__, CD__, ___ surface Ig (single light chain with IgM or IgM/IgD) NEGATIVE: CD__, _____, _____. >This pattern is very useful in distinguishing CLL/SLL from mantle cell, follicular, and marginal zone lymphomas BUT ANTIGEN EXPRESSION IS VARIABLE.

5, 19, 20, 23, 79a, dim surface Ig 10, BCL-6, Cyclin D1

________this scoring system has been developed to account for this variability and differentiate CLL from related B cell neoplasms. >Each criterion is given 1 point, and the total score is cumulative: [5 criterion] 4 or more: _________________ 1 or 2: ______________ 3 (Intermediate): remains _______, and these cases may require _______ of a node or _________ data to establish the diagnosis

Catovsky-Matutes Scoring Weak expression of surface Ig Expression of CD5 Expression of CD 23 NO expression of FMC7 NO or WEAK expression of CD79B or CD22 Chronic Lymphocytic Leukemia Non-Hodgkin's Lymphoma problematic, biopsy, molecular

__________ ________important prognostic determinants for CLL and are used to guide clinical management. >The _____ and ______ ________ systems have been used for this purpose. >Both systems divide patients into risk categories reflecting the degree of ________ and ________ or compromise of __________ function

Staging systems Rai and Binet Staging System organomegaly, lymphadenopathy, BM

CLL PROGNOSTIC INDICATORS: presence indicate worse prognosis [3]

del [17q] [TP53] IGHv mutational status [unmutated] Testing for CD38, ZAP [70 kDa]

RAI CLASSIFICATION [revised] Low Risk: Intermediate Risk: High Risk: BINET CLASSIFICATION Stage A: Stage B: Stage C:

Lymphocytosis >5 x 10 9/μL Lymphocytes >5 x 10 9/μL + EM [liver,spleen] Lymphocytes >5 x 10 9/μL + EM [liver,spleen] + Hgb <11 g/dl Hgb >10 g/dl, Plt >100 x 10 9/μL + <3 enlarged nodules Hgb >10 g/dl, Plt >100 x 10 9/μL + >3 enlarged nodules Hgb <10 g/dl, Plt <100 x 10 9/μL + any number of enlarged nodules

Originally described as a variant of CLL

PROLYMPHOCYTIC LEUKEMIA [PLL]

PLL is characterized by a very marked _________ (usually greater than _____ × 103/μL), massive splenomegaly, moderate hepatomegaly, and inconspicuous lymphadenopathy The malignant lymphoid cells have a large vesicular nucleolus, condensed nuclear chromatin, and a moderate amount of cytoplasm. More than ___% blood leukemic cells are prolymphocytes

lymphocytosis 100 x 10 3/uL 55%

PLL IMMUNOPHENOTYPING: POSITIVE: [3] NEGATIVE: [2]

CD 19, CD 20, FMC 7, bright surface Ig CD5, CD23

is an indolent disease of B cell lineage most commonly found in middle age (median age, 50 years) ; more common in males.

HAIRY CELL LEUKEMIA

Major focus of disease is in the spleen, blood, and bone marrow

HAIRY CELL LEUKEMIA

________. Have round to ovoid nuclei, lack nucleoli, and have relatively abundant cytoplasm with ragged projections that extend circumferentially around the entire cell.

HAIRY CELLS

HCL CYTOGENETIC ABNORMALITY: _________ IMMUNOPHENOTYPING: >_______ ____ is specific to HCL and helps to differentiate HCL from related B cell disorders CLINICAL FINDINGS: >Fatigue >Anemia, leukocytopenia, thrombocytopenia, _______ (most predominant finding), and _________ (bone marrow aspirates frequently are unsuccessful) >Bleeding and infection can be present

BRAF[V600e] CD 11c, CD 20, CD 22, CD25, CD79a, CD103 Annexin A splenomegaly marrow fibrosis

-Is the most familiar form of cutaneous T cell lymphoma is the more common disorder, making up approximately 60% to 70% of the cutaneous T cell lymphoma cases

MYCOSES FUNGOIDES AND SEZARY SYNDROME

-is largely confined to the skin, although in the later stages of the disease, dissemination to lymph nodes, organs, and blood can be seen -is generally an indolent disease with a slow progressive course; ___ is defined as a systemic

Mycoses Fungoides and Sezary Syndrome Sezary Syndrome

MF/SS has abnormal appearance with scant cytoplasm and a _______, _______ nucleus, variably condensed chromatin,and inconspicuous nucleoli in its cells. In MF/SS, Biopsies of the skin reveal _____ lymphocytic infiltrates in the dermis often with admixed ______ and occasional _______. -T cells with irregular nuclei show single-cell infiltration of the epidermis and often form clusters known as _________. -Presence of _______ cells.

cerebriform, folded Pautrier's abscesses sezary

MYCOSIS FUNGIODES -______-like skin lesions requiring repeated biopsy before a definitive diagnosis is made. -Skin biopsy can show a characteristic localization of atypical cells in ______ ________ in the epidermis, but this occurs in only a minority of cases SEZARY SYNDROME -Characterized by erythroderma, generalized lymphadenopathy, and the presence of clonal __ cells in skin, lymph nodes, and peripheral blood -An absolute Sézary cell count greater than __ X109/L.

psoriasis-like Pautrier's microabscesses T-cells 1

MF/SS IMMNUNOPHENOTYPING:

CD2, CD3, CD4, CD5

are malignant disorders of terminally differentiated B cells (plasma cells) Associated with rouleaux formation and elevated ESR

PLASMA CELL NEOPLASMS/ MYELOMAS/DYSCRASIAS

PLASMA CELL NEOPLASMS/MYELOMAS Also known

Plasma Dyscrasias

Although they constitute approximately __% to __% of cancers, PCNs are the _______ most common hematologic malignancy

1%-2% SECOND

Plasma cells to secrete [monoclonal/polyclonal] immunoglobulin (________) is an essential characteristic of this.

monoclonal Ig [paraproteins]

MYELOMAS TYPES:

Monoclonal Gammopathy of Uncertain Significance [MGUS] Multiple [Plamsa] Cell Myeloma Waldenstrom's Macroglobulinemia

>Benign monoclonal proliferation of plasma cells that is usually considered with the plasma cell neoplasms because it represents a precursor state for myeloma >Detections relies on detection of paraproteins in serum or urine

monoclonal gammopathy of uncertain significance

>Presence of circulating monoclonal protein WITHOUT ASSOCIATED PLASMA CELL DYSCASIA or other neoplasm

monoclonal gammopathy of uncertai significance

-Malignant bone marrow–based, plasma cell neoplasm associated with abnormal protein production Rouleaux formation and elevated ESR

Multiple [Plasma] Cell Myeloma

is an increased number of plasma cells in the peripheral blood and should be considered a form of multiple myeloma and not a separate entity

Plasma Cell Leukemia

MCM IMMUNOPHENOTYPING: [2]

cd38, cd138 [kappa or lambda clonal excess]

MCM CLINICAL FINDINGS: -Include ___ pain (typically in the back or chest) -Weight loss and night sweats are not prominent until the disease is advanced -Abnormal bleeding may be a prominent feature -In some patients, the major symptoms result from acute infection, _____ insufficiency, __________, or _________. -Approximately 90% of patients suffer from broadly disseminated destruction of the _____ ; bone marrow failure -Major cause of death are ______ and _____ _________

bone renal insufficiency, hypocalcemia, amyloidosis infection, renal insufficiency

MCM LABORATORY FINDINGS: Bone marrow plasma cells _____%. Increased _____ volume caused by monoclonal protein commonly produces -________. Serum electrophoresis: >Overproduction of ___; “___-spike” -Presence of monoclonal serum protein (mostly ____, can be Ig_ OR Ig_) -Presence ________ proteins (free light chains—kappa or lambda) found in the urine

30% plasma hypervolemia IgM M-spike IgG IgA or IgD Bence Jones

-B-cell neoplasm characterized by lymphoplasmoproliferative disorder with infiltration of the bone excessive Ig__ (macroglobulin) and decreased production of the other immunoglobulins -High levels of Ig__ can result in a _______ syndrome

Waldenstrom's Macrglobulinemia [Lymphoplasmacytic Lymphoma] -IgM IgM hyperviscosity syndrome

-CYTOGENETIC ABNORMALITY:

Myeloid differentiation factor 88 gene mutation

CLINICAL FINDINGS: -Symptoms of WM are due to the extent of _____ ______ and to elevated. -Weakness, fatigue attributable to anemia, and bleeding -Bone pain is virtually [existent/nonexistent]; HYPERVISCOCITY SYNDROME -Lymphadenopathy and Hepatosplenomegaly

tumor infiltration existent

LABORATORY FINDINGS: -______ B-lineage cells at different stages of maturation, such as [small/medium] lymphocytes, __________ cells. (abundant basophilic cytoplasm but lymphocyte-like nuclei), and _____ cells

pleomorphic b-lineage cells small lymphoplasmacytic cells plasma

IMMUNOPHENOTYPING: CD___ -Absolute lymphocytosis -IgM levels in the blood circulation (IgM >__ g/dL) ; “__-spike”serum electrophoresis

CD154 3 M

VARIANTS OF RS CELLS: [3]

hodgkin cells mummified lacunar cells

-Large mononuclear lymphoid cells with an oval nucleus, thick nuclear membrane, distinct eosinophilic nucleolus, and abundant cytoplasm

hodgkin cells

-Degenerated or apoptotic cells with a pyknotic nucleus and condensed cytoplasm

mummified cells

-Lobated nucleus and _____ retraction of cytoplasm secondary to ______ fixation -Occurs predominantly in the nodular sclerosis variant of Classical ______ _______ -Appear to be situated in a clear space

artefactual formalin Hodgkin's Lymphoma

HODGKIN’S LYMPHOMA is primarily a lymph node-based disease, distinct from NHL that involves the lymph nodes -DIAGNOSIS involves _____ biopsy, _______, cytogenetics, [DNA/RNA] analysis CLASSICAL HODGKIN’S LYMPHOMA -Comprises a heterogenous group of lymphoid neoplasm derived from the germinal center; can be associated with EBV infections -Presence of Reed-Sternberg cells (a usual pathognomonic sign for Classical Hodgkin’s Lymphoma) -IMMUNOPHENOTYPING: CD15, CD30, CD45 -SUBTYPES: Nodular sclerosis, Mixed cellularity, Lymphocyte depleted, Lymphocyte-rich

Hodgkin's Lymphoma

-The hallmark of classical H, which is a large binucleated, multinucleated, or mononuclear (Hodgkin) cell with each nucleus bearing a very large inclusion-like nucleolus

Reed-Sternberg cells

-Is a B-cell neoplasm composed relatively rare neoplastic cells called “_______ cells” or _____ _____ cell (L&H cell) -_____ cells are large lymphoid cells with abundant cytoplasm and vesicular multi-lobated nuclei (_______ nuclei)

NODULAR LYMPHOCYTE-PREDOMINANT HL popcorn cells lymphocytic histiocytic cells popcorn popcorn

NODULAR LYMPHOCYTE-PREDOMINANT HL IMMUNOPHENOTYPING

CD20, CD45, BCL-6

-Comprises a heterogenous group of lymphoid neoplasm derived from the germinal center; can be associated with _____ infections -Presence of Reed-Sternberg cells (a usual pathognomonic sign for it)

Classical Hodgkin's Lymphoma EBV

CLASSIC HL IMMUNOPHENOTYPING:

CD 15, CD30, CD45

Classical HL SUBTYPES:

Nodular necrosis, Mixed cellularity, Lymphocyte-depleted, Lymphocyte-rich

broad bands of collagen, nodules of lymphoid tissue w/ aggregates of HRS cells/lacunar cells, multinucleated variants EBV 1-40%

nodular sclerosis

HRS cells, lymphocytes, plasma cells, eosinophils, histiocytes EBV 75%

mixed cellularity

HRS cells, paucity of background lymphocytes, pleomorphic HRS cells mimic sarcoma HIV infected

lymphocyte depletion

scattered HRS cells, numerous small lymphocytes, nodular growth pattern

lymphocyte-rich classical

HL STAGING [2] [I,II,III,IV]

Ann Arbor Lugano

1 node involved or single extranodal site

Ann Arbor [1:Limited]

2 or more nodes/groups or lymphatic structures on SAME SIDE of diaphragm. involvement of Limited Contiguous Extralymphatic organ or tissue [IIIE]

Ann Arbor [II]

1 node or group of nodes. single extranodal lesion w/o nodal involvement

Lugano [I]

2 or more nodes or nodal groups on SAME SIDE OF DIAPHRAGM; stage I or II by nodal extent w/ LIMITED contiguous extranodal involvement

Lugano [II]

Nodes on BOTH SIDES OF DIAPHRAGM [III] w/ involvement of spleen [III_] or limited contiguous extralymphatic organ or tissue involvement [III_] or both [III_]

Ann Arbor [III] S E ES

Nodes on BOTH SIDES OF DIAPHRAGM Nodes on ABOVE DIAPHRAGM w/ SPLEEN INVOLVEMENT

Lugano [III]

Diffuse or disseminated foci of involvement of 1 or more extralymphatic organs or tissues w/ or w/o associated lymphatic involvement.

Ann Arbor [IV]

Additional noncontiguous extralymphatic involvement

Lugano [IV]

-its most frequent type of is diffuse large B-cell lymphoma, which accounts for approximately 40% of new cases of lymphoma -More than half of patients with diffuse large B-cell lymphoma are older than 60 years of age

Non-Hodgkin's Lymphoma

expresses high levels of genes characteristic of germinal center, B-cell–like lymal germinal center B cells

Germinal center, B cell-like lymphoma [NHL]

expresses genes characteristic of mitogenically activated blood B cells

Activated B cell-like lymphoma [NHL]

a heterogeneous gene expression that suggests it includes more than one subtype of lymphoma

Type 3 diffuse large, B-cell lymphoma

-FAB classification of myelodysplastic syndromes based on the presence of dysmyelopoiesis and the quantification of myeloblasts (Type I and Type II) or erythroblasts:

REFRACTORY ANEMIA [RA] REFRACTORY ANEMIA WITH RINGED SIDEROBLASTS [RARS] REFRACTORY ANEMIA WITH EXCESS BLASTS [RAEB] REFRACTORY ANEMIA [RA] WITH EXCESS BLASTS IN TRANSFORMATION [RAEB-T] CHRONIC MYELOMONOCYTIC LEUKEMIA [CMML]

CHRONIC LEUKEMIAS Flashcards

(105 cards)