Pathology of Non-Hodgkins Lymphomas Flashcards
B cell lymphoblastic leukemia/lymphoma (B-LBL or B-ALL) - clinical features
*children > adults
*abrupt stormy onset; days-weeks of first symtpoms
*predominantly leukemic:
-peripheral blood/bone marrow involvement
-sx related to marrow dysfunction: fatigue, infections, bruising
-bone pain: marrow/subperiosteum infiltration
*extramedullary involvement frequent:
-CNS: headache, vomiting, and nerve palsies resulting from meningeal spread
-organomegaly: lymph nodes, spleen, liver, gonads
B cell lymphoblastic leukemia/lymphoma (B-LBL or B-ALL) - clinical course
*typically aggressive
*prognosis depends on cytogenetics
*80% cure rate in children
B cell lymphoblastic leukemia/lymphoma (B-LBL or B-ALL) - morphology
*primitive lymphoblasts replace tissue (Tdt+)
-no auer rods
-sites: peripheral blood/bone marrow; nodes and extranodal sites
B cell lymphoblastic leukemia/lymphoma (B-LBL or B-ALL) - phenotype
*IMMATURE B cells:
-Tdt, CD34 (markers of maturity)
-CD19, CD10 (markers of B lineage)
-negative for CD20, Sig kappa/lambda
-Ki-67 proliferation > 90%
B cell lymphoblastic leukemia/lymphoma (B-LBL or B-ALL) - genotype
t(9;22) - BCR/ABL = favorable
t(4;11) AF4/MLL = unfavorable
hyperdiploidy > 50 = favorable
hypodiploidy < 44 = unfavorable
T cell lymphoblastic leukemia/lymphoma (T-LBL or T-ALL) - clinical features
*adolescents
*predominantly lymphomatous:
-mediastinal mass: compression of large vessels and airways; pleural effusions
-CNS: headache, vomiting, and nerve palsies resulting from meningeal spread
-organomegaly: lymph nodes, spleen, liver, gonads
*peripheral blood/bone marrow frequent:
-symptoms related to marrow dysfunction: fatigue, infections, bruising
-bone pain: marrow/subperiosteum infiltration
note - aggressive clinical course; good prognosis
T cell lymphoblastic leukemia/lymphoma (T-LBL or T-ALL) - morphology
*primitive lymphoblasts replace tissue
*no auer rods
*sites:
-anterior mediastinum/nodes
-peripheral blood/bone marrow
*thymus replaced by lymphoblasts
note - morphologically indistinguishable from B-ALL
T cell lymphoblastic leukemia/lymphoma (T-LBL or T-ALL) - phenotype
*IMMATURE T cells
-Tdt, CD34 (markers of immaturity)
-CD7, CD3
-CD4/8 CO-EXPRESSION (b/c immature)
-Ki-67 proliferation > 90%
T cell lymphoblastic leukemia/lymphoma (T-LBL or T-ALL) - genotype
*TCR genes rearranged
*30% cases translocations TCR loci
chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) - clinical features
*90% of chronic lymphoid leukemias
*adults > 40 years; M>F
*USUALLY ASYMPTOMATIC
*lymphadenopathy +/- organomegaly
chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) - indolent course
*prognosis generally very good:
-asymptomatic pt: median survival > 10 years, even without treatment
-symptomatic patients are treated
note - “Richter transformation” = aggressive tumor progression, low median survival
chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) - bone marrow
*diffuse interstitial lymphoid infiltrate or nodular lymphoid infiltrate
chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) - lymph nodes
*diffuse effacement:
-monotonous round small lymphocytes
-clumpy “soccer ball” chromatin
*“pseudofollicular” proliferation centers
chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) - phenotype
*MATURE B cells
-CD19, CD20, sIg kappa/lambda
-CD5+ (IMPORTANT - this is a T cell marker)
*Ki-67 proliferation < 20%
chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) - genotype
*IGH, IGL genes clonally rearranged
*karyotypic/genetic abnormalities prognostic:
-TP53 mutations = worse prognosis
follicular lymphoma - clinical features
*most common indolent NHL in US (25-30% of NHL; adults)
*often ASYMPTOMATIC
*“waxing/waning” lymph nodes - painless, generalized lymphadenopathy
*usually higher stage:
-multiple lymph node sites (III,IV)
-bone marrow involved
-may be extranodal: spleen, liver, GI, skin
follicular lymphoma - clinical course
*indolent, INCURABLE course
*prognosis generally good:
-“gentle” chemo
-median survival 7-9 years
*up to 30% progress to a more aggressive tumor
follicular lymphoma - morphology
*nodular growth pattern:
-effacing node
-“back-to-back” follicles
-extracapsular extension
*mixed cell composition:
-small “rasinoid” centrocytes with cleaved nuclei
-larger centroblasts
follicular lymphoma - phenotype
*MATURE B cells:
-CD19, CD20, sIg kappa/lambda
-CD10 (germinal center marker)
-BCL2 protein!!
-Ki-67% proliferation < 20%
follicular lymphoma - genotype
*IGH, IGL genes clonally rearranged
*t(14;18) BCL2/IgH genotype
diffuse large B-cell lymphoma - clinical features
*most common lymphoma in US
*all ages, more common in adults > 50 years
*RAPIDLY ENLARGING, SYMPTOMATIC MASS:
-nodal
-extranodal common
*may be de novo or secondary to other B-NHL
diffuse large B-cell lymphoma - clinical course
*aggressive, CURABLE course
*different distinct molecular subtypes have differing clinical outcomes
*intensive combination chemo & anti-CD20 immunotherapy
diffuse large B-cell lymphoma - morphology
*diffuse, destructive growth
*LARGE LYMPHOID (B) CELLS:
-pleomorphism
-irregular nuclear contours
-may have prominent nucleoli
*mitoses and necrosis common
diffuse large B-cell lymphoma - phenotype
*MATURE B cells:
-CD19, CD20, sIg kappa/lambda
-other variable expressions (CD5, CD10, BCL2, etc)
-Ki-67 proliferation 50-100%
*MAY BE EBV ASSOCIATED
diffuse large B-cell lymphoma - genotype
*IgH, IgL genes clonally rearranged
*non specific chromosomal or genetic abnormalities
anaplastic large cell lymphoma - clinical features
*children and young adults
*rapidly enlarging, symptomatic mass
-nodal, extranodal common (skin, bone, soft tissue, liver, lung)
*may be advanced stage with B-symptoms (but it is a T cell lymphoma)
anaplastic large cell lymphoma - clinical course
*aggressive, curable course
*>80% survival
anaplastic large cell lymphoma - morphology
*complete to partial nodal effacement
*sinusoidal infiltrate
*large pleomorphic cells:
-“Hallmark” cells = reniform nuclei
-multi-nucleated “wreath” cells
-“donut” cells
-Reed-Sternberg cells
anaplastic large cell lymphoma - phenotype
*MATURE T cells
*T-cell or “null” phenotype:
+/- CD3, CD4
+CD30
+/- ALK-1 protein
anaplastic large cell lymphoma - genotype
*TCR genes clonally rearranged
*t(2;5) → ALK/NPM fusion protein
*genotype is important for distinguishing from Hodgkin’s Lymphoma: anaplastic large cell lymphoma has a 2;5 TRANSLOCATION; Hodgkin’s does NOT
-AND Hodgkin’s is B-cell; anaplastic is T-cell
Classic Hodgkin Lymphoma (CHL) - clinical features
*bimodal age distribution: young adults (2nd and 3rd decade); elderly (>60 years)
*PAINLESS LYMPHADENOPATHY: mediastinal, cervical, para-aortic
*typically low stage I/II
*may have B-symptoms
*may be EBV associated
Classic Hodgkin Lymphoma (CHL) - clinical course
*indolent, CURABLE course
*tumor stage most important prognostic factor
-stages I/IIA cure > 90%
Classic Hodgkin Lymphoma (CHL) - morphology
1. REED-STERNBERG CELLS: distinctive tumor giant cells; bilobed nuceus with the 2 halves as mirror images (“owl eyes”)
-CD15+ and CD30+, B cell origin
2. inflammatory background: eosinophils, neutrophils, lymphocytes, plasma cells
3. collagen fibrous bands (+/- nodular growth pattern); lymph node capsular fibrosis
Classic Hodgkin Lymphoma (CHL) - genotype
*IgH, IgL genes clonally rearranged
*no specific chromosomal/genetic abnormalities
plasma cell myeloma (multiple myeloma) - clinical features
*bone marrow involvement (bone fractures, pain):
-radiographically: multiple PUNCHED-OUT, LYTIC BONE LESIONS (spine, ribs, and skull especially)
*immunoglobulin protein secretion:
-MONOCLONAL SERUM GAMMOPATHY
-Bence Jones proteins found in the urine:
~monoclonal immunoglobulin kappa/lambda light chains
plasma cell myeloma (multiple myeloma) - peripheral blood
*normochromic, normocytic anemia
*ROULEAUX FORMATION - correlates with magnitude of gammopathy
*occasional plasma cells
*leukopenia
*thrombocytopenia
plasma cell myeloma (multiple myeloma) - bone marrow
*plasmacytosis with atypia (hypercellular marrow with replacement by plasma cells - see image):
-patchy, interstitial, focal, or diffuse
-multinucleation
-nucleoli
-cytoplasmic or nuclear inclusions
> 10% plasma cells for multiple myeloma (<10% for MGUS)
plasma cell myeloma (multiple myeloma) - phenotype
*unique “post-mature” B cells in bone marrow:
-CD38, CD138, cytoplasmic Ig kappa/lambda
-CD56
-negative for BD19, CD20, sIg kappa/lambda
plasma cell myeloma (multiple myeloma) - genotype
*IGH, IGL genes clonally rearranged
*IGH TRANSLOCATIONS [ex. t(11;14)]
Burkitt Lymphoma - morphology
*“starry sky” histiocytes with apoptotic debris on biopsy of tumor and/or bone marrow
*effacing (destroying) underlying tissue architectures
Burkitt Lymphoma - phenotype
*MATURE B-cells:
-CD19, CD20, sIg kappa/lambda
-CD10
*Ki-67 proliferation ~100%
*may be EBV-associated
note - negative for CD34, TdT
Burkitt Lymphoma - genotype
*c-MYC (8q24) REARRANGEMENT is required
*most commonly: t(8;14) MYC/IGH rearrangement
Burkitt Lymphoma - prognosis
*potentially curable with intensive chemo
*treatment begins ASAP due to rapid doubling time or tumor
*include CNS prophylaxis
hairy cell leukemia (HCL) - clinical features
*rare distinctive B-cell non-Hodgkin Lymphoma in which cells have filamentous, hair-like projections
*classically presents with:
1. PANCYTOPENIA (weakness/fatigue, easy bruising, recurrent opportunistic infections)
2. massive SPLENOMEGALY
3. fibrosis of bone marrow -> dry tap on aspiration
hairy cell leukemia (HCL) - clinical course
*indolent, CURABLE course
*sensitive to alpha-interferon, purine analogs 2-cda
*BRAF inhibitors
hairy cell leukemia (HCL) - peripheral blood
*lymphocytosis:
-large, round, oval, reniform nuclei
-moderate/abundant pale cytoplasm with “hairy” or “villous” projections
*cytopenias: anemia, neutropenia, monocytopenia, thrombocytopenia
hairy cell leukemia (HCL) - bone marrow
*lymphocytic infiltrate: “fried egg” cells in bone marrow (round cells with pale cytoplasm and distinct cell borders)
*“dry tap” on marrow aspiration:
-increased reticulin fibrosis
-inaspirable
hairy cell leukemia (HCL) - phenotype
*MATURE B cells
-CD19, CD20, sIg kappa/lambda
-HCL markers: CD11c, Cd103, CD25
*stains TRAP positive
hairy cell leukemia (HCL) - genotype
associated with BRAF MUTATIONS !!!
mycosis fungoides - clinical featuers
*rare, mainly affects adults/elderly
*CUTANEOUS INVOLVEMENT:
-widespread distribution +/- ulceration
-plaques/patches/papules
-tumors
note - it is a T cell lymphoma of the skin
mycosis fungoides - clinical course
*indolent, INCURABLE course:
*long natural history:
-slow dissemination & long-term survival
-median survival 8-9 years
*prognosis depends on clinical stage: small may transform to more aggressive subtype
mycosis fungoides - morphology
*dermal infiltration of medium-sized “cerebriform” cells
*epidermotropism with Pautrier microabscess
Sezary Syndrome - clinical features
*systemic generalized disease
*LEUKEMIC FORM OF MYCOSIS FUNGOIDES (peripheral blood with sparing of bone marrow)
*generalized exfoliative erythroderma (pruritis, alopecia, etc)
Sezary Syndrome - morphology
*peripheral blood:
-atypical lymphocytosis
-circulating Sezary cells and variants
*skin/other tissues:
-skin: histology similar to mycosis fungoides
-lymph nodes: paracortical expansion with atypical cerebriform cells
Sezary Syndrome - phenotype
*MATURE T cells:
-CD3, CD4, also CD2, CD5
-loss of pan T-cell antigen: CD7
-CCR4, CCR10
Classic Hodgkin Lymphoma (CHL) - phenotype
*“broken” mature B cells
*“null” lineage phenotype (negative: CD19, CD20, sIg kappa/lambda)
*positive for CD30, CD15 (Reed Sternberg cells)
*+/- EBV
chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) - peripheral blood
*absolute lymphocytosis > 5K
*small mature cells (scant cytoplasm, condensed, clumped “soccer ball” chromatin)
*“SMUDGE CELLS” (arrows on image)
*prolymphocytes < 55%
*anemia
*thrombocytopenia
