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Flashcards in CANCER Deck (38):
3

Angioimmunoblastic T-cell Lymphoma Presentation and Morphology

Clinical Presentation: rapidly progressive critical illness, diffuse lymphadenopathy, hepatosplenomegaly, skin rash, cold autoimmune hemolytic anemia, evidence of immunocompromise

-Normal Counterpart: Follicular T-helper cells (involved sites: lymph nodes, spleen, liver, BM and skin)

-Morphology: will see enlarged lymph node b/c of expanded paracortex

-Reactive will see expansion of small paracortical vessels and immunoblast, microscopic examination is not always helpful

 

 

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Angioimmunoblastic T-cell Lymphoma: Immunophenotyping

-CD3+, CD4+ and CD10+

-CD10: usally a marker of B-cells in germinal center, presence in paracortex on these T cells can lead toward diagnosis

-CD21: residual FDC network, should be absent if there is not a germinal center, but with this lymphoma they are present and staining for CD21+ can help diagnose

Picture: L-CD3 and R-CD10

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Angioimmunoblastic T-cell Lymphoma: Genetics and Clinical Course

-Complex Karyotypes: mult chromo loss/gain, mult deletions, no pattern has emerged

-Clinical Course: Aggressive, median survival >3yrs

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Periperipheral T-cell Lymphoma Not otherwise specified (NOS): Clincal presentation and features

~30% T cell lymphomas

-Clinical presentation: (1) Diffuse lymphadenopathy (2) B symptoms (fever, night sweats, weight loss) (3) paraneoplastic features (eosinophilia, pruritis, hemolytic anemia)

-Normal counter part: unclear

-Involved sites: any where, except usually NOT blood stream

Usual Themes: expanded paracortex, effacement of normal architecture

Variations: Distinct subsets of atypical cells or clusters of "epitheloid histocytes" usually near the cortex (paracortical, picture)

 

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Periperipheral T-cell Lymphoma Not otherwise specified (NOS): Immunophenotype and Clinical Course

Immunophenotype:

-expected; CD3, 5, 7, and 4 or 8/

-Usually see; loss of one or more of the above

-Variants: "double +" (CD4+, CD8+)

--Unexpected markers: CD20 (B-cell marker), CD56 (macrophage/monocyte marker), CD30 (R/S cell marker)

-Genetics: no pattern has emerged

-Clinical Course: aggressive 5 yr survival 20-30%

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Typical Organ Distribution of CLL

-Chronic lymphocytic leukemia

See mostly in the PB and some in the BM and lymph nodes

-If blood is primary site use: leukemia

-If not use lymphoma

-If there is more lymph node involvement it could be called a SLL (small lymphocytic LYMPHOMA)

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CLL Facts/Presentation

-Presentation: lymphocytosis in older males (high familial incidence)

-Malignancy of Memory B-cells, see more PB (CLL) involvment and see small lymphocytes with little cytoplasm and "SMUDGE CELLS"

-Cells have already been through a germinal center rxn/class switching and express IgG

-Pseudofollicular:  looks like germinal center (reactive) in germinal center, but is actually a proliferative center, Ki67 should be over expressed in these

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CLL: Genetics and Markers

Genetics: 80%: del13q14.3>trisomay 12>del11q (MLL gene), del17p (p53)

Immunophenotype: Light chain restricted (kappa or lambda) CD20-weak, CD5+ and CD23+

Key clinical predictors: immunopheno; ZAP-70+ (bad), CD38+ (bad), markers of somatic hypermutation state (means more or les differ)

Genetics: 17p deletion (p53/bad) and 13q deletion (good)

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Plasma Cell Neoplasms, Types

Monoclonal gammaopathy of uncertain significant (MGUS), mild form, usally asymptomatic can progress to myeloma

-Myeloma: more severe form associated with multiple lytic bone lesions

Involved sites: BM>>>PB

-See Rouleaux (row of coins) on peripheral smear from protein production

-Almost always presents in elderly (aquired mutations)

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Diagnosis of Plasma Cell Neoplasms

Serum Protein Electrophoresis (SPEP): can show abundence of Igs (not light chain only)

-Immunofixation electrophoresis (IFE): can determine if monoclonal and will show light chain restrictive

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Plasma Cell Neo Morphology

-See a lot of cytoplasm and an eccentric nucleus, usually have clumpy chromatin and prominent golgi apparatus

-Will look like bone is being eaten away in places (osteoclasts)

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General Plasma Cell Neoplasms

-Immunophenotype: CD38++++, CD138++++, CD19-, CD20-; light chain restricted

-Genetics: Translocation of IgH (chromo 14) in about 2/3 of cases, Trisomes of ODD # chromo are common

-MGUS: 1%/yr progress to mult myeloma

-Mult Myeloma: median survival 3-4 years

Predictors of worse outcome: t(4;14)-FGFR3, t(14;16)-C-MAF, t(14;20)-MAFB, del17p (p53 region) and Serum beta 2 microglobulin (all these are usually not found but when they are it is a poor prognosis

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Follicular Lymphoma

-Presentation: lymphadenopathy in older individuals, can involve BM and PB

-Results from failure of germinal B-cells to apoptose (b/c of Bcl-2 over expression-anti-apoptotic)

-t(14;18)-Bcl-2 w/ IgH promoter

-Immunopheno: CD19+, CD10+ (germ cen), Bcl-2 (90%), BCL-6 (85%)

--BCL-2 staining will not be seen in a reactive center reaction

-Will like a germinal center but will lack: polarity (Iarge cells at one end and smaller cells at the other end) and tingible body macrosphages (sign of rapid turn over, no cells are apoptosing)

-Clinical Course: (1)30% will progress to diffuse large B-cell lymphoma (2) Quite variable, depends on stage, grade, cytogenetics

--Grade 1 will have mostly centrocytes (small dark cells) and Grade 3 will have mostly Centroblasts (larger cells)

PICTURE: Darker staining center is abnormal and the lighter stained center is normal

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Grade 1 Follicular Lymphoma

-Most centrocytes, smaller than centroblasts

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GRADE 3 FOLLICULAR LYMPHOMA

MOSTLY CENTROBLASTS (LARGER)

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DIFFUSE LARGE B-CELL LYMPHOMA

-"garabage" category of B-cell lymphomas

-Clinical presentation: Rapidly growing adenopathy, ELDERLY, 40% present with extranodal disease (GI, BM, other)

-IMMUNOPHENO: CD19+, CD20+, CD10+ (30-60%)

-Genetics: t(v, 3q27)(v, BCL-6) ~30%, t(14;18) (BCL-2)~20-30% and others may occur

-Clinical course: depends on stage, generally have a more acute course

-KEY PREDICTORS: BM involvement and BM appearnace (concordant vs discordant), can see follicles w/o germinal centers, big cells with mitotic figures, generally

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Hodkin Lymphoma Pathophysiology

-Cannot be killed (NFkB or EBV or other anti-apoptotic mutation), similar to Follicular lymphoma, B-cells which went into germinal centers and did not die.

-Classical: do have Ig rearrangement, but do not express Ig w/n cell or on their surface (cripple Ig promoter/transcription factor mutation) (strom-it has a "shaved head")

-Nodular: express surface Igs and other B-cell markers

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AML with AUER RODs

t(8;21) Runx-1-Run1T1 Mutation

Clinical Presentation: younger patients/kids

Auer rods: crystalization of granule contents (excess myeloperoxidase production)

Immunophenotype: CD34+, CD13+, CD33weak

Prognosis: good response to chemo

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APL: PML-RARA

t(15;17) fusion of PML (trans factor) with RARA (retinoic acid receptor)

-Class II mutation: Inhibits granulocyte differentiation

-TREATMENT: All Trans Retinoic Acid (ATRA), induces cell differentiation of the blasts to granulocytes (CLINICAL REMISSION)

-CLINICAL PRESENTATION: DIC, SEVERE THROMBOCYTOPENIA***

-Morphology: AUER RODS in stacks (faggot cells)*** sometimes see Bi-nuclear appearance

Immunophenotype: Weak/absent: CD34, HLA-DR, CD13+, CD33+

Prognosis: good if diagnosis is made

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AML: CBFB-MYH11

inv(16) or t(16;16)

-Class II mutant, clinical presentation: younger patients/kids

-Morphology: Myelomonocytic* (mixed granulocyte-monocyte feats), Increased Eosinophils in blood and marrow (not known why)

-Immunophenotype: CD34+, CD117+ (blasts); CD13+, CD33+ (granulocytes); CD14+, CD11b+ (monocytes)

Prognosis: GOOD; optimal with high dose CYTARABINE

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AML w/ Normal Cytogenetics 

40-50% of AML cases

-Any age group

Morphology: undifferentiated or variable granulocytic or monocytic/monoblastic

-Immunophenotype: blast markers (CD34, CD117)+, can show any lineage markers

-Prognosis: have to look at molecular genetics, pairing of mutation will determine 

-For some BM transplant doesnt help (NPMN! or CEBPA+, FLT3-ITD-, 60% 4-yr survival)

-for other it will (FLT3-ITD+ or NPM1-, CEBPA-, FLT3-ITD-, ~29% 4-yr survival)

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ALL (Acute Lymphoblastic Leukemias)

TdT: important for VDJ recombination and marker of B and T cells

-CD19,CD10 and uCD20 are markers of B cells, can also express myeloid markers (CD13, CD33)

-Can also express CD34 (GENERAL BLAST MARKER*****)

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ALL: BCR-ABL1

-t(9;22), proliferation activator (class I), diff from the mutation found in CML which is a class II mutation and prevents maturation of the cell, and have similar cytogenetics

-Clinical Presentation: Older adults (25% of all cases)

Morphology: Big agranular blasts, hard to tell ir myeloid or lymphoid

Immunophenotype CD10+, CD19+, TdT+

Prognosis: Poor

 

 

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ALL: MLL rearranged

t(v;11q23), or t(11;19) Class II mutation, also found in AML

Clinical Presentation: most common leukemia in kids

Morphology: big agranular blasts

Immunophenotype: CD10-, CD19+, TdT+

Prognosis: Poor

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ALL, Mutations that made St. Jude Famous

-t(12;21); TEL-AML1 (ETV6-RUNX1), class II (inhibits differentition)

-Clinical Presentation: Kids, 25% of pediatric B-ALL

Morphology: big agranular blasts

Immunophenotype: TdT+, CD34+, CD20-

Prognosis: 90% cure rate

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ALL: T-ALL

-Common motif for lymphoid malignancies: oncogene>>>>Ig or TCR promoter

-Clinical Presentation: Kids 25% of pediatric T-ALL, often wih thymic mass**

Morphology: Big agranular blasts

Immunophenotype: TdT+, CD3+, CD5+, can express myeloid or B-cell antigens as well

Prognosis: High Risk: more intense chemotherapy regime, pretty good survival rate

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Myeloproliferative Disease

Definition: Chronically proliferating clones which differentiate to circulating blood cells

Chronic Myelogenous Leukemia (CML): shows blast profile

CMML (myelodysplastic/myelomonocytic): hybrid b/t myelocytes and granulocytes

-Can also see Chronic: eosinophilic, neutrophilic or mastocytosis leukemia. Need to differentiate from a Reactive condition

--Best indicator if prominence of mature to immature cells is out of order, "Myeloid Bulge" (more blasts than more mature cells)

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Myeloproliferative Diseases of Erythroid and Megs Lineages

Polycythemia Vera, elevated RBC count (erythroid lineage)

-Essential thromboythaemia/Primary myelofibrosis: elevated platelet count (meg lineage)

-Can progress to AML

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CML that is Undectable

Cryptic Translocation, Cannot see with Routine Cytogenetics

-Will progress to AML (can be myeloid or lymphoid)

PHASES: chronic, accelerated, acute

-Can also confuse with sepsis, get a BM

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Mastocytosis

--Usually presents as benign cutaneous lesions in kids (itchy) that goes away by itself

-Release of histamine can cause systemic symptoms that confuse clinician

Morphology: Aggregates of blank looking cells, round or spindle shapes, s/t with eosinophils

Immunophenotype: Tryptase+, CD117+, CD25+

Treatment: Imatinib

Prognosis: highly variable

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Polycythemia Vera

-Jak2 mutation in >95% of cases-detectable in PB leukocytes

-Clinical presentation: Thromboisis?hypertension/stroke or MI. increased RBC # 

Morphology: hypercellular marrow, erythroid hyperplasia, increased Megs

-Immunophenotype: no known features

Prognosis: >10yr survival is common, can progress to myelofibrosis MDS, acute leukemia

Epo will usually be low, one way to differ between neoplastic and reactive

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Essential Thrombocythemia

Jak2 mutation in ~50% of cases-detectable in PB

-Clinical Presentation: Thrombosis, increased platelets, can also be due to Fe deficiancy, infecion or chronic inflammation, can also have bleeding and splenomegaly

Morphology: Increased Megs (very abnormal and tend to cluster)

Immunopheno: not known, can not put Meg through flow cytometry (too fragile)

-Prognosis: >10yr survival is common, can progress to myelofibrosis MDS, acute leukema

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Primary Myelofibrosis

Jak2 mutation ~50%, disputed diagnostic criteria

-Morphology: increased Megs, bizarre shapes, clusting and fibrosis (TEAR DROPS?)

No known immunopheno

Prognosis: usually shorter survival than ET, can progress to marrow failure, acute leukemia

-Cells of bone marrow will relocate to spleen and liver: Extra-medullary hematopoiesis

Treatment: supportive care, blood transfusions, splenectomy are dangerous (pts too old, will bleed) and HSCT is curative but high mortality rate b/c pts are old as hell

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Myelodyisplasias

-Usually present as unexplained cytopenia, bicytopenia or pancytopenia

-see poorly functioning clones, mostly in elderly (>70)

5 major adult forms (best to worst prognosis): (1) Refractory cytopenia with unilineage dysplasia (2) refractory anemia with ring sideroblasts (3) myelodysplastic syndrome with isolated del(5q) (4) refractory cytopenia with multilineage dysplasia (5) refractory anemia with excess blasts

-Accumulation of several mutations over time in different mutations

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Refractory Cytopenia with Unilineage Dysplasia

Clinical pres: unexplanined cytopenai

Morphology: weird looking precursors: binucleation or irregular nuclei, can show fibrosism high or low cellularity, megaloblastoid features

Prognosis: surival unclear, rarely progresses to AML

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Refractory Anemia with Ring Sideroblasts

-Nonspecific cytogenetic abnormalities (trisomes, monosomes) may be present

-Morphology: ring sideroblasts usually with dyspoietic feats (in red cell series only)

--Iron granules form ring around nucleus 

-Prognosis: rarely progresses to AML

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MDS with Isolated del(5q)

-All the Megakaryocytes are MONOCUCLEAR

-Clinical pres: Anemia often severe, usually elderly

-Morph: megs are mononuclear

-Prognosis: good median survival; treatable with LENALIDOMIDE, 10% progress to AML

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Refractory Cytopenia with multilineage dysplasia

-Two or more lineages show dysplastic changes

-Clinical pres: Anemia often severe: usually elderly

-Morph: Granulocytes dont granulate normally (if affected), nuclei dont lobulate normally

Prognosis: Median survival 30 months, 10% progress to AML in 2 years

 

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