Lymphoid & Myeloid Neoplasms Flashcards
Follicular lymphoma
t(14;18), translocations involving BCL2
-overexpression of BCL2
IgH locus chr
Chr 14
BCL2 chr
Chr 18
follicular lymphoma morph
centrocytes & centroblast
BM involvement = paratrabecular lymphoid aggregates
BCL6 is normal, BCL2 is not normal
Follicular lymphoma clinical
most common indolent lymphoma of adults
painless, generalized LAD, extranodal site involvement, indolent NHL, anti-CD20 Ab, can transform to DLBCL
DLBCL
most common form of NHL/most common lymphoma of adults
Males, 60 yrs, can also occur in young adults and children
DLBCL path
dysregulaton of BCL6- needed for norm germinal center formation
-express CD19, CD20, CD10, BCL6, surface Ig
primary effusion lymphom
DLCBL subtype
pleural effusion in HIV or older pts
tumor cells infx with KSHV/HHV8
immunodeficiency-associated large B-cell lymphoma
DLBCL subtype
severe T cell immunodef
neoplastic B cells infx with EBV
DLBCL clinical
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
Burkitt lymphoma translocation
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)
endemic Burkitt lymphoma
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
Burkitt lymphoma morph
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
Burkitt lymphoma immunophenotype
CD19, CD20, CD10, BCL2, IgM
Burkitt lymphoma- clinical
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
ALL
most common type of cancer in kids
precursor B & T cels
CLL/SLL
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
Multiple Myeloma (MM)
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
MM diagnosis
requires a BM exam
-marrow involvement often gives rise to a normocytic normochromic anemia, & sometimes mod leukopenia & thrombocytopenia
smoldering myeloma
serum M protein > 3gm/dL
pt asymptomatic
75% progress to MM in 15 yr period
solitary myeloma
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
MGUS
most common plasma cell dyscrasia
elderly, asymptomatic, serum M protein
Multiple Myeloma translocation and dysregulation
diverse translocations involving IgH locus
frequent dysregulation and overexpression of D cyclins
Lymphoplasmacytic lymphoma
B cell lymphoma that exhibits plasmacytic differentiation
clinical sx dominated by hyperviscosity syndrome from excess IgM
MYD88 mutation
hairy cell leukemia
BRAF mutations 55 y/o M indolent course TRAP stain, dry tap massive splenomegaly incr incidence of atypical mycobacterial infx
peripheral T cell lymphoma, unspecified
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
Anaplastic Large-cell Lymphoma
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
Adult T-cell Leukemia/Lymphoma
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
Mycosis Fungoides/Sezary syndrome
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
large granular lymphocytic leukemia
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
large granular lymphocytic leukemia- clinical
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
extranodal NK/T Cell Lymphoma
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
Nodular Sclerosis HL
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
Mixed Cellularity HL
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
Lymphocyte-Rich Type HL
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
Lymphocyte-Depleted Type HL
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
Lymphocyte Predominance Type HL
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,
Nodular Sclerosis HL-Clinical
usually Stage 1 or 2 (free of systemic manifestations), frequent mediastinal involvement, F=M, most pts young adults
Mixed Cellularity HL- Clinical
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
Lymphocyte rich HL- CLinical
uncommon, M, older adults
Lymphocyte Depletion HL- Clinical
uncommon; more common in older males, HIV+, developing countries; often presents as advanced dz
Lymphocyte predominance
uncommon; young males with cervical or axillary LAD; mediastinal
HL Clinical
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
