3.27 STROM Hematologic Malignancies II: B cells Flashcards Preview

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Flashcards in 3.27 STROM Hematologic Malignancies II: B cells Deck (28):
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Tingible Bodies

Macrophages that are located in the lymph node that take up apoptosed B cells in the germinal center reaction

-Tend to take up hematoxyin 

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B Cell Markers

-TdT: Expressed during early B cell development

-CD10: Early dev and when B cell is in Germinal center

-CD19, CD20: B cell marker throughout (can target with Rituximab)

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CD20 Immunohistostaining 

Stains B-cells, in germinal centers and in the mantle zones

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CD10 Immunohistostain

Some B cells, mostly ones in the germinal center

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CD5 or 3 Immunohistostain

T-cell Stain, mostly in the paracortex

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Translocations and Oncogenesis

Common motif is for an prooncogene to translocate next to an Ig promoter to form an oncogene

-Common Ig Promoters: IgH (14q32)**, Ig lambda (22q11) and Ig kappa (2p12)

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Common Oncogene Associations in B cells

Cyclin-D and Myc: over expressed in malignancies of naive B cells (worse)

-Bcl-2 and Bcl-6: B cells derived from germinal centers

-C-Maf, Cyclin D3 and Pax-5: B memory cells/myelomas

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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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Mantle Cell Lymphoma

-Mantle cells: reserve of naive cells that encirlcle the germinal center

-Often misdiagnosed as CLL (less common than CLL)

-Differ in morphology of lymph node do not have proliferative centers, have a starry sky from macros w/ cll remnents

-all have t(11;14) (IgH;Cyclin D1) is ALWAYS present (FISH)

-More aggressive than CLL

Immunopheno markers: CD5+ (t cell marker), CD20 strong, CD23-

-Also have light chain restriction

-can also stain with Ki-67

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Follicular Lymphoma

Presents mainly in the Lymph nodes, also found in BM and PB, finding outside of normal distribution usually means an increase in aggressiveness

 

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Burkitt's Lymphoma

Found Mainly in GI tract and Lymph nodes, also found some in PB

Genetics: t(2;8), t(8;14) or t(8;22) rearrangement of c-MYC

Immunology: Surface IgM+, CD10, 19, 20, 22, 79a all pos and Ki67 (85%)

-Occurs more often in children

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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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Hodgkin Lymphoma (clasical)

Clinical Presentation

-Sub-categories: (1) Classical Hodgkin 

-Clinical Presentation: males 30-50, localized or diffuse adenopathy, often w/ involvement of cervical, mediastinal or abdominal lymph nodes and/or spleen

 

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Classical Hodgkins: Morphology

-Morphology: Reed/Sternberg cells (large lymphoid w/ mono-/bi-nucleated appearance, huge eosinophilic nucleoli and overall horseshoe shape likely) and Diverse background cells: small lymphocytes, plasma cells, eosinophils, neutrophils, histocytes

--Lymph node architecture: wholly or partially effected; can be criss-crossed by fibrous bands

-will not see germinal centers

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Classical Hodgkins: Immunophenotyping and Prognosis

R/S cells: too fragile cannot flow, have to use stains

-CD30+(90%), CD15+, Pax5+ (Bcell transcription factor), CD20/wk (KNOW THESE)

-Genetics: not useful

-Clinical Course: Curable w/ chemo/RT (97% 10yr survival)

-Predictors: stage, histologic type

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Hodgkin Lymphoma: Nodular Lymphocyte MORPHOLOGY

-Reed/Sternberg cells: large lymphoid cells with mono-/bi-nucleated appearance, huge eosinophilic nucleoli 

-Diverse background cells: small lymphocytes, plasma cells, eosinophils, neutrophils and histocytes

-"popcorn" cells (lympho-histocytic L&H cells) in place of classic RS cells

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Nodular Lymphocyte Predominant Hodgkin Lymphoma: Immunophenotype and Clinical Course

 

Also cannot use flow

CD30- (~80%)

CD15- (~100%)

-Pax5+

CD20+ (>95%)

T cells surround the R/S cells

Clincal Course: 80% 10 yrs survival, treatment at stage 1 may not be needed, 3-5% progress to diffuse large B-cell lymphoma

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CD3 Stain for Nodular Hodgkin

Stain for T cells, can see them surrounds the R/S cells

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