CANCER Flashcards
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
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
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
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)
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%
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)
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
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)
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)
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
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)
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
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
Grade 1 Follicular Lymphoma
-Most centrocytes, smaller than centroblasts
GRADE 3 FOLLICULAR LYMPHOMA
MOSTLY CENTROBLASTS (LARGER)
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
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
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
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
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
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)
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
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
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
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
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
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
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
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
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
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
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
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
