Lymph Noes 2 Flashcards
Burkitt Lymphoma - 3 Clinical variants
Endemic, sporadic, immunosupressed
ENDEMIC BURKITT LYMPHOMA
Africa
Children 4-7 y/o
Male
Malaria
Jaw/facial bones
95% EBV +
Sporadic Burkitt lymphoma
- adult median 30 y.o.
- 30-50% of childhood lymphomas
- EBV positive cells in 30% of cases
Burkitt - Immunophenotype, molecular
• Immuno -Positive for CD20, CD10 & bcl-6 -Ki-67 100% of cells -Neg for bcl-2, or weakly+ in 20% • Molecular -T(8;14) IgH/myc -T(2;8) myc/kappa -T(8;22) myc/lambda
Burkitt - Factsoids
• Translocation involving MYC is highly characteristic but
not specific for Burkitt lymphoma
• No single parameter alone (ie morphology, genetics, IHC)
can be used as the gold standard for the diagnosis of
Burkitt lymphoma
• A combination of several techniques is required for dx.
• The 2008 WHO does not recognize atypical Burkitt
lymphoma as a distinct entity.
• Instead, it acknowledges that there are cases of Burkitt
lymphoma with nuclear pleomorphism, which previously
would have been called atypical Burkitt
DLBCL - Diffuse Large B-Cell Lymphoma
• Common morphologic variant -Centroblastic -Immunoblastic -Anaplastic • Molecular subgroups -Germinal centre B cell like -Activated B cell like • IHC subgroups -CD5+ DLBCL -Germinal centre B cell like -Non germinal centre B cell like • Subtypes -T cell/histiocyte-rich large B ‘ cell lymphoma -Primary DLBCL of the CNS -Primary cutaneous DLBCL, leg type -EBV + DLBCL of the elderly
• Other lymphomas of large B cells -Primary mediastinal (thymic) large B cell lymphoma -Intravascular large B cell lymphoma -DLBCL associated w chronic inflammation -Lymphomatoid granulomatosis -ALK-positive LBCL -Plasmablastic lymphoma -LBCL arising in HHV8+ `multicentric Castlemans -Primary effusion lymphoma • Borderline cases Discussed later
Subtypes of DLBCL
– T cell/histiocyte-rich large B cell lymphoma
– Primary DLBCL of the CNS
– Primary cutaneous DLBCL, leg type
– EBV + DLBCL of the elderly
T cell/histiocyte-rich large B cell lymphoma
Large cells
<10% of total cellularity
Can look like centroblasts, immunoblasts, L&H cells, RS cells
CD20+, LCA+, CD30+/-, rare CD15+, bcl-6+, bcl2+/-
DLBCL, leg type
• Old diagnosis for E.O.R.T.C. • New diagnosis from WHO • elderly females • Aggressive • Tx, combination chemotherapy • 5 year survival 55% (Blood, 2005) • Histology – Immunoblastic – Round cell morphology
Immunos
- Strong bcl-2+, unlike cutaneous follicular lymphoma
- MUM1/IRF+, FOXP1, CD10 usually -, BCL-6+,
Other lymphomas of large B cells
- Primary mediastinal (thymic) LBC lymphoma
- Intravascular large B cell lymphoma
- DLBCL associated w chronic inflammation
- Lymphomatoid granulomatosis
- ALK-positive LBCL
- Plasmablastic lymphoma
- LBCL arising in HHV8+ multicentric Castlemans
- Primary effusion lymphoma
Mediastinal (thymic) Large B-cell Lymphoma
Clinical
B cell lymphoma in mediastinum
May have superior vena cava syndrome
20-40 year old women
Immunos/molecular Lack of surface immunoglobulin by flow But IgH rearrangement by PCR B-cell markers + Bcl-2 and bcl-6 can be + CD30 + (80%), but weak CD15 only rarely + MAL protein +
compartmentalizing fibrosis
B cells w clear cytoplasm
Lymphomatoid granulomatosis
- Angiocentric and angiodiestructive lymphoproliferative dz of extranodal sites, composed of EBV+ B cells and reactive T cells.
- Used to be thought of as a T cell lymphoma
- Lung, brain, liver, kidney skin
Hodgkin lymphoma
• WHO classification: –Nodular lymphocyte predominant – Classical • Nodular sclerosis • Mixed cellularity • Lymphocyte-rich • Lymphocyte-depleted
Nodular Lymphocyte Predominant Hodgkin lymphoma
L & H cells with 1 large folded nucleus, and scant cytoplasm (popcorn cells)
Absence of PMNs and eosinophils
Progressive transformation of germinal centers (PTGC) is associated
Nodular Lymphocyte Predominant Hodgkin lymphoma - Immunophenotype
– CD45+, CD20+, J-chain and EMA+
– CD3+ and CD57+ T-cells in background ring malignant cells
– Nearly all cases are CD15 & CD30 neg
– Oct2 and BOB.1 consistently present whereas in
classic HL one or both will be absent
Hodgkins- PROGRESSIVE TRANSFORMATION OF GERMINAL CENTERS
- Large follicles (3-4 times normal)
- inward migration of perifollicular small B cells and
activated T cells into the germinal centers - Absent L and H cells
- May proceed, follow or accompany NLPHD
Classic Hodgkin lymphoma
- 95% of HL with bimodal age with 15-35 year peak and 2nd peak late life
- Mediastinal
Nodular Sclerosis Hodgkin lymphoma
CD30+, CD15+ (75-85%);
CD45 neg, LMP-1 and EBER variable,
BSAP(PAX5)+
Reed Sternburg cells in up to 40% of cases
Mixed cellularity Hodgkin lymphoma (MCHL)
- Interfollicular growth pattern may be seen
- May have interstitial fibrosis but no capsular thickening or
broad bands of collagen fibrosis - EBV-LMP- highest frequently-75%
- Mediastinal involvement uncommon
Lymphocyte rich Hodgkin lymphoma
nodular growth pattern
Regressed germinal centers
RS cells in mantle zone
No eos + PMNs in background
T CELL LYMPHOMA BY LOCATION
Lymph node:
Peripheral T-cell lymphoma, NOS
Angioimmunoblastic T-cell lymphoma
Anaplastic large cell lymphoma
Leukemia/bone marrow: Adult T-cell leukemia/lymphoma T-cell prolymphocytic leukemia T-cell large granular lymphocytic leukemia Aggressive NK-cell leukemia T cell lymphoblastic lymphoma
Extranodal Enteropathy-type T cell lymphoma Hepatosplenic T-cell lymphoma Extranodal NK/T-cell lymphoma, Nasal type Subcutaneous panniculitis-like T cell lymphoma Γδ cutaneous T cell lymphoma Mycosis fungoides Primary cutaneous CD30+ T cell LPD
PERIPHERAL T-CELL LYMPHOMA, NOS
• T cell lymphoma in which cases do not better fit into a different category
• H&E
– clear cytoplasm
– Inflammatory background of eosinophils and epithelioid histiocytes
– Lymphoepithelioid variant (Lennert lymphoma)
Angioimmunoblastic T-cell lymphoma
Signs and Symptoms B symptoms 68-85 Generalized lymphadenopathy 94-97 Splenomegaly 70-73 Hepatomegaly 52-72 Rash 48-58 Arthritis 18 Ascites/effusions 23-37
Lab Results: Anemia 40-47 Other cytopenias 20 Eosinophilia 39 Hypergammaglobulinemia 50-83 Hypogammaglobulinemia 9-27 Autoantibodies 66-77 LDH 70 ESR 45
AILT - Histology
Arborizing blood vessels w PAS material
Follicular dendritic cells CD23+ surround vessels
Anaplastic large cell lymphoma
- Large cells with marked atypia
- Hallmark cells are large kidney shaped nucleus with eosinophilic paranuclear area
- Reed-Sternberg like cells, wreath-like
- Multinucleate
- Sinusoidal growth pattern
- Show perivascular rosetting, but does not destroy blood vessels.
Translocations and fusion proteins involving ALK
slide 2110 - this is an image slide that I need to transcribe
ALCL - response to therapy
ALCL is one of the T cell lymphomas that has the best responses to therapy.
Alk+ has better px.
•Except with the small cell variant. In small cell variant, ALK positivity does not lead to a better prognosis.
ATLL Clinical syndrome
• Caused by HTLV1
• Japan, Caribbean, central Africa,
• Lymphocytosis (62%), lymphadenopathy (61%), lytic bone lesions (36%) HSM (61%), skin lesions (61%) hypercalcemia (73%),
• Large polylobated “flower” cells
• Skin, epidermotropism w Pautrier-like microabscesses
• Bone marrow, tumor cells + osteoclasts
• Dilated lymph node sinuses with tumor cells.
• Variants
1. Acute–leukemic
2. Lymphomatous variant—lymphadenopathy
3. Chronic variant—skin lesions
4. Smoldering variant–WBC normal
ATLL Phenotype
- T cell markers, CD4+, CD5+
- HTLV1+, FoxP3+, CD25
- EBV-
- Cytotoxic markers -
Enteropathy - type T- cell lymphoma
Associated with gluten-sensitive enteropathy
(celiac disease); but occurs less commonly
without gluten-sensitive enteropathy
Jejunal involvement; perforation common
Stomach and colon not commonly affected
Aggressive, death from multiple perforations.
ETTCL-Morphology
1. T cell lymphoma part Mixture of small and large lymphocytes A mass of lymphocytes 2. Gluten sensitive enteropathy part Intraepithelial T-cells in adjacent mucosa Villous atrophy
ETTCL - Phenotype
- T cell markers
- CD8+, but can also be negative
- CD103+
- CD5-
- CD30+/-, CD56+/-
- Cytotoxic markers
Hepatosplenic T cell lymphoma
- Young men
- Hepatosplenomegaly
- Often no lymphadenopathy
- Aggressive
- T cells in sinusoids of liver and spleen.
- Spares portal triads & white pulp
- Most commonly Γδ cells– TCRδ1+, βF1-, Usually CD4-/CD8-, but can be CD4-/CD8+, CD5-, Tia+, but perforin –
- Iso 7q, trisomy 8
Extranodal NK/T-cell lymphoma, Nasal type
- AKA polymorphic reticulosis, lethal midline granuloma, angiocentric lymphoma.
- Young/Asian
- Big midline facial tumor, but can be seen in other locations
- Angiocentric with necrosis
- Plasma cells, eos, macs
- Hemophagocytosis
- T cell markers, Surface CD3-, cytoplasmic CD3έ+
- CD56+, CD57, cytotoxic markers, EBV+
Subcutaneous panniculitis-like T cell lymphoma
- Aggressive T cell lymphoma
- WHO distinguishes between αβ and γδ
- Αβ are included in SPLTCL
- Γδ are called cutaneous γδ T cell lymphoma
- Lesions are confined to subcutis
- Lymphocytes encircle fat lobules
- Septum involvement is mild
- Karyorrhexis and fat necrosis almost always present
Mycosis Fungoides
- Clinical-Scaly erythematous rash that progresses from patches/plaques and may form a solid skin tumor
- Disease has a long natural history, so patients may have nonspecific infiltrates in the skin and rashes for years before diagnostic histology develops.
- Morphology-lymphocytes w cerebriform nuclei in dermis with extension to epidermis (epidermotropism)
- Pautrier abscesses are collections of malignant T cells in the epidermis
- Halos
- Dermal infiltrate—non specific
- Usually CD4+, rarely CD8+
- USUALLY NO CYTOTOXIC FEATURES
Sezary Sydrome
- Exfoliative erythroderma, generalized lymphadeopathy and malignant (Sezary cells in the peripheral blood
- Spares bm
T cell lymphoma molecular abnormalities
PTCL - ITK/SYK translocations AILT - Trisomies ALCL - ALK translocations T-PLL - TCL1A translocations ETTCL - 9q34 amplifications HSTCL - Isochromosome 7q
LYMPHOBLASTIC LYMPHOMA
VS. MANTLE CELL LYMPHOMA
slide 2147 image slide to transcribe
LBL VS BURKITT
slide 2148 - slide has tables need to transcribe
TCRLB vs. Nodular LP Hodgkins
slide 2149 - slide has tables need to be transcribed
