1/10 Lymphoma - Corbett Flashcards
lymphoma classification
- nonHodgkin lymphoma 90% new cases
- B cell 90%
- indolent/slow-growing
- follicular lymphoma [germinal center B cell]
- extranodal marginal cell lymphoma (MALT) [marginal zone B cell]
- mantle cell lymphoma [mature B cell - follicle]
- small lymphocytic lymphoma/CLL
- rapid-growing
- Burkitt lymphoma [germinal center B cell]
- diffuse large B cell lymphoma [germinal center B cell]
- indolent/slow-growing
- T cell 10%
- mycoses fungoides
- Hodgkin lymphoma 10% new cases [ALL GERMINAL CENTER B CELLS!!!]
- classic
- nodular sclerosing
- mixed cellularity
- lymphocyte-rich
- lymphocyte-depleted
- non-classic
B cells: devpt stages
B cell/T cell interaction and activation
[corbett slides really good pictorial summary]
B cell lymphomas by cell of origin
general features of lymphoma
- painless lymph node enlargement
- dx: LN biopsy
- clonal tumor cells
- common: immune dysfx → incr risk of infection, devpt of auto-antibodies
follicular lymphoma
most common INDOLENT lymphoma
90% have t(14;18) arising in germinal center B cells
- BCL2_IgH promoter
- overexpression of Bcl2 → protects cells from apoptosis → lymphadenopathy and marrow infiltration as cell numbers increase
age at dx: 65
- painless lymphadenopathy (waxing/waning)
- 20% pts with “B symptoms” (fever, weight loss, fatigue)
-
nodular growth pattern with cells expressing CD 10, 19, 20, surface Ig, BCL6 and BCL2!
- centrocytes: small
- centroblasts: large with nucleoli
no cure, but sx alleviation with rituximab
extranodal marginal zone B cell lymphoma of MALT type
conditions assoc with…gastric/salivary/thyroid/ocular/cutaneous MALTs
cell of origin: POSTgerminal center (“memory B cells”)
associated with chronic inflammation
- continued stimulation drives B lymphocytes to pick up mutation → malignancy
- Heliobacter gastritis → gastric MALT
- Sjogren’s syndrome → salivary gland MALT
- Hashimoto’s thyroiditis → thyroid MALT
- C. psittaci conjunctivitis → ocular MALT
- Borrelia skin infection → cutaneous MALT
many are gastric (salivary glands, ocular, thyroid, lung)
- peptic ulcer disease, abd sx
- associated autoimmune disease
t(11;18) → API2-MALT1 fusion protein
pathogenesis
- v early stage MALT dependent on presence of H. pylori
- significant tx implications
- usually stays localized
- can progress to diffuse large B cell lymphoma if left untreated
mantle cell lymphoma
cell of origin: naive preGC B cell of mantle zone
75% male, mean age 68
t(11;14) → incr cyclinD
- promotion of cell cycle progression
- impaired DNA damage repair
- impaired cell death
not nodular growth (kind of hard to tell from histopath), but does stain positive for cyclinD1
- advanced stage at dx
- poor prognosis (no effective tx)
- nodal disease in 75%
- spleen GI tract, bone marrow
- lymphomatous polyposis
- 35% with systemic B sx
clinical presentation of rapid growth NHL
aggressive
- present acutely with rapidly growing mass
- systemic B sx: fever, night sweats, weight loss
- elevated levels of serum LDH and uric acid
ex. diffuse large B cell lymphoma, Burkitt lymphoma, anaplastic large T cell lymphoma
diffuse large B cell lymphoma
most common lymphoma overall
- predominantely male, 64
- occurs de novo, transformation from low grade tumor
- assoc with HIV
90% assoc with overexpression of BCL6
- encodes transcriptional repressor protein that downregs p53, p27Kip1, cyclinD2 →→→
- genetic instability
- differentiation arrest
- continuous cell prolif
- survival
30% have BCL2 overexpression
- v aggressive: rapidly enlarging symptomatic mass
- lymph node expansion is common
- 35% extranodal (most common: stomach)
- 30% systemic B symptoms
histo: disruption of original architecture (large size, prominent nucleoli, basophilic cytoplasm)
- diffuse growth pattern
- high proliferation fraction
Burkitt lymphoma
origin: mature germinal center B cells
three forms: all assoc with c-MYC
myc_IgH translocation (8;14)
- starry sky pattern: macrophages engulfing apoptotic cells
- endemic/African
- age 4-7, M>F
- jaw 50-60%
- 90% assoc with EBV
- sporadic (US incidence)
- 30% of pediatric lymphoma, age 11
- abdomen: massive disease/ascites (distal ileum, stomach, cecum, mesentary; kidneys/testis/bone marrow/CNS)
- HIV-assoc
mycoses fungoides
cutaneous T cell lymphoma
males, over 50
HIV -
indolent disease associated with eczematous dermatitis
anaplastic large T cell lymphoma
uncommon tumor of young adults (30)
male predom (70%)
translocation (2;5) → overexpression of ALK
hallmark cells: large anaplastic cells, some containing horseshoe nuclei and lots of cytoplasm
express CD30 (TNF family receptor)
Hodgkin lymphoma basics
10% of all lymphomas
bimodal age dist
variation in subtype with socioeconomics
risk factors:
- EBV
- childhood illnesses
- immunosuppression
cell of origin: germinal center B cell BUT DO NOT EXPRESS B CELL MARKERS!!!
- REED-STERNBERG CELLS
- contiguous pattern of spread
- most cells in tumor are NOT neoplastic
strong constitutive activation of NF-kB is characteristic
- all express CD30 → can self-oligomerize to activate NFkB pathway
HL keys
key concepts
- Reed Sternberg cells
- mixed cell infiltrate
- RS cells produce tons chemokines/cytokines → tissue rxn with mixed infiltrate
- CD15: adhesion molecule typical of myeloid cells
- CD30: TNF receptor family member
most common clinical pres: nontender, palpable LAD
- neck/supraclavicula, axilla
- mediastinal adenopathy (nodular sclerosis)
- ar presentation, 2/3 of NS type have mediastinal adenopathy
- often young women
- 1/3 have fevers, night sweats, weight loss (B sx)
other subtypes
