Lymphoid & Myeloid Neoplasms

Question 1

Follicular lymphoma

Answer 1

t(14;18), translocations involving BCL2

-overexpression of BCL2

Question 2

IgH locus chr

Answer 2

Chr 14

Question 3

BCL2 chr

Answer 3

Chr 18

Question 4

follicular lymphoma morph

Answer 4

centrocytes & centroblast
BM involvement = paratrabecular lymphoid aggregates
BCL6 is normal, BCL2 is not normal

Question 5

Follicular lymphoma clinical

Answer 5

most common indolent lymphoma of adults

painless, generalized LAD, extranodal site involvement, indolent NHL, anti-CD20 Ab, can transform to DLBCL

Question 6

DLBCL

Answer 6

most common form of NHL/most common lymphoma of adults

Males, 60 yrs, can also occur in young adults and children

Question 7

DLBCL path

Answer 7

dysregulaton of BCL6- needed for norm germinal center formation
-express CD19, CD20, CD10, BCL6, surface Ig

Question 8

primary effusion lymphom

Answer 8

DLCBL subtype
pleural effusion in HIV or older pts
tumor cells infx with KSHV/HHV8

Question 9

immunodeficiency-associated large B-cell lymphoma

Answer 9

DLBCL subtype
severe T cell immunodef
neoplastic B cells infx with EBV

Question 10

DLBCL clinical

Answer 10

rapidly enlarging mass at a nodal or extranodal site
waldeyer ring involved- oropharyngeal tissue that includes tonsils & adenoids
No BM involvement
-aggressive tumors, rapidly fatal without tx
-anti-CD20 antibody therapy

Question 11

Burkitt lymphoma translocation

Answer 11

MYC gene on chr 8 -> lead to incr MYC protein levels

• incr expressions of genes required for aerobic glycolysis= warburg effect
• translocation partner usually IgH locus t(8;14)

Question 12

endemic Burkitt lymphoma

Answer 12

latently infx with EBV
-predilection for mandible, may involve abdominal visceral organs -> kidneys, ovaries, adrenal glands

-25% HIV-associated tumors also infx w/ EBV
15-20% sporadic cases- EBV infx

Question 13

Burkitt lymphoma morph

Answer 13

tumor exhibits high mitotic index and contains numerous apoptotic cells & tumor cells have multiple small nucleoli

• starry sky pattern- phagocytes w/ abundant clear cytoplasm (numerous pale tingible body M0s)
• tumor cells in BM aspirate -> royal blue cytoplasm containing clear cytoplasmic vacuoles

Question 14

Burkitt lymphoma immunophenotype

Answer 14

CD19, CD20, CD10, BCL2, IgM

Question 15

Burkitt lymphoma- clinical

Answer 15

found mainly in children or young adults
30% of childhood NHLs in US
Tumors manifest at extranodal sites
-involvement of BM and PB is uncommon
-Sporadic= mass involving the ileocecum & peritoneum
very aggressive, responds well to chemo

Question 16

ALL

Answer 16

most common type of cancer in kids

precursor B & T cels

Question 17

CLL/SLL

Answer 17

most common leukemia of adults 
tumor of mature B cells
manifests w/ BM or LN involvement
indolent course, incr suspectibility to infx and autoimmune disorders 
-prolymphocytes

Question 18

Multiple Myeloma (MM)

Answer 18

plasma cell neoplasm
associated with lytic bone lesions, hypercalcemia, renal failure, acquired immune abnormalities
CD138, syndecan-1, CD56
-sharply punched out bone lesions
-set up for recurrent bacterial infxs
-renal insufficiency
-Most myelomas are associated with more than 3gm/Dl of serum Ig or more than 6mg/dL of urinary Bence-Jones protein –> most common monoclonal Ig is IgG then IgA
-60-70% of pts have free light chains and a serum M protein

Question 19

MM diagnosis

Answer 19

requires a BM exam
-marrow involvement often gives rise to a normocytic normochromic anemia, & sometimes mod leukopenia & thrombocytopenia

Question 20

smoldering myeloma

Answer 20

serum M protein > 3gm/dL
pt asymptomatic
75% progress to MM in 15 yr period

Question 21

solitary myeloma

Answer 21

solitary lesion of bone or soft tissue
extraosseous lesions= lung, oronasopharynx, nasal sinuses –> resected
osseous lesions= progress to MM w/in 10 to 20 yrs

Question 22

MGUS

Answer 22

most common plasma cell dyscrasia

elderly, asymptomatic, serum M protein

Question 23

Multiple Myeloma translocation and dysregulation

Answer 23

diverse translocations involving IgH locus

frequent dysregulation and overexpression of D cyclins

Question 24

Lymphoplasmacytic lymphoma

Answer 24

B cell lymphoma that exhibits plasmacytic differentiation
clinical sx dominated by hyperviscosity syndrome from excess IgM
MYD88 mutation

Question 25

hairy cell leukemia

Answer 25

``` BRAF mutations 55 y/o M indolent course TRAP stain, dry tap massive splenomegaly incr incidence of atypical mycobacterial infx ```

Question 26

peripheral T cell lymphoma, unspecified

Answer 26

present with LAD, eosinophilia, pruritis, wt loss worse prognosis tumors efface LNs diffusely, typically composed of a pleomorphic mix of variable sized malig T cells

Question 27

Anaplastic Large-cell Lymphoma

Answer 27

ALK positive -> chr 2p23 hallmark cells= large anaplastic cells some containing horse-shoe shaped nuclei & voluminous cytoplasm children or young adults, freq present as soft tissue masses very good prognosis CD30+ infiltrate lymphoid sinuses

Question 28

Adult T-cell Leukemia/Lymphoma

Answer 28

CD4+ T cells only adults infected with HTLV1 Japan, W Africa, Caribbean Skin lesions, gen LAD, hepatosplenomegaly, PB lymphocytosis, hypercalcemia Tumor cells = multilobated nuclei "cloverleaf" or "flower"cells

Question 29

Mycosis Fungoides/Sezary syndrome

Answer 29

tumor of CD4+ helper T cells that home to the skin (epidermis & upper dermis are infiltrated by neoplastic T cells -> cerebriform appearance) Sezary syndrome - skin involvement= generalized exfoliative erythroderma, cerebriform nuclei tumor cells express CLA, CCR4, CCR10 indolent tumor

Question 30

large granular lymphocytic leukemia

Answer 30

T cell & NK cell variants Mainly adults T cell dz -> present with mild to mod lymphocytosis and splenomegaly. CD3+ NK cell dz -> present in subtle fashion w/ little or no lymphocytosis or splenomegaly. CD3- & CD56+ Mutations of the TF STAT3 tumor cells are large lymphocytes with abundant blue cytoplasm & a few coarse azurophilic granules on PB smear -marrow usually contains sparse interstitial lymphocytic infiltrates

Question 31

large granular lymphocytic leukemia- clinical

Answer 31

Neutropenia and anemia dominate clinical picture increased incidence of rheumatologic disorders Felty syndrome: triad of rheumatoid arthritis, splenomegaly, and neutropenia tumors of T cells origin have more indolent course NK-cell tumors behave more aggressively

Question 32

extranodal NK/T Cell Lymphoma

Answer 32

3% of NHL in Asia Presents most commonly as a destructive nasopharyngeal mass tumor cell infiltrate typically surrounds and invades small vessels --> extensive ischemic necrosis large azurophilic granules seen in cytoplasm Highly associated with EBV Most tumors are CD3- highly aggressive, respond to radiation, not chemo poor prognosis in advanced dz

Question 33

Nodular Sclerosis HL

Answer 33

most common form of HL Lacunar variant RS cells Deposition of collagen in bands that divide involved LNs into circumscribed nodules -> fibrosis RS cells are found in a polymorphous background of T cells, eosinophils, plasma cells, M0s PAX5, CD15, CD30 uncommonly associated with EBV involve the lower cervical, supraclavicular, & mediastinal LNs of adolescents and young adults excellent prognosis

Question 34

Mixed Cellularity HL

Answer 34

LNs are diffusely effaced by heterogenous cellular infiltrate Diagnostic RS cells and mononuclear variants are usually plentiful RS cells are infx with EBV in 70% of cases PAX5, CD15, CD30 associated with older age, night sweats, wt loss, advanced tumor stage prognosis is very good

Question 35

Lymphocyte-Rich Type HL

Answer 35

uncommon reactive lymphocytes make up the vast majority of the cellular infiltrate involved LNs are diffusely efface, but some vague nodularity mononuclear variants and diagnostic RS cells EBV associated in 40% excellent prognosis

Question 36

Lymphocyte-Depleted Type HL

Answer 36

least common form of HL lack of lymphocytes and relative abundance of RS cells or their variants RS cell infx with EBV in 90% cases older adults, HIV+, developing countries advanced stage & systemic sx are freq less favorable outcome

Question 37

Lymphocyte Predominance Type HL

Answer 37

uncommon "nonclassical" variant -involved nodes are effaced by a nodular infiltrate of small lymphocytes admixed w/ variable #s of M0s -few RS cells, more L&H cells (popcorn cells - multilobated nucleus) -L&H variants express B cell markers- CD20, BCL6, CD30- & CD15- EBV not associated -Males,

Question 38

Nodular Sclerosis HL-Clinical

Answer 38

usually Stage 1 or 2 (free of systemic manifestations), frequent mediastinal involvement, F=M, most pts young adults

Question 39

Mixed Cellularity HL- Clinical

Answer 39

more than 50% present as S3 or 4 dz(disseminated dz- shows constitutional sx: fever, night sweats, wt loss); Males, biphasic incidence, peaking in young adults and again in adults older than 55

Question 40

Lymphocyte rich HL- CLinical

Answer 40

uncommon, M, older adults

Question 41

Lymphocyte Depletion HL- Clinical

Answer 41

uncommon; more common in older males, HIV+, developing countries; often presents as advanced dz

Question 42

Lymphocyte predominance

Answer 42

uncommon; young males with cervical or axillary LAD; mediastinal

Question 43

HL Clinical

Answer 43

commonly presents as painless LAD suppressed Th1 immune responses Spread of HL: nodal -> spleen -> liver -> marrow & other tissue high cure rate radiotherapy tx -> higher incidence of lung cancer, melanoma, breast cancer chemo tx w/ alkylating agents -> 2ndary tumors (AML) Anti-CD30 Ab