Lecture 48/49 - Lymphomas and Myelomas Flashcards
what is a luekemia vs lymphoma vs myeloma? where do they abnormalities present
L eukemia vs Lymphoma vs Myleoma
○ Leukemia – abnormal proliferation of immature lymphoid/myeloid cells (blasts; ALL)
§ Bone marrow
○ Lymphoma -- Mature B cells growing out of control § Lymph Nodes ○ Myeloma -- plasma cell growing out of control § Bone marrow
what are the layers of a normal reactive LN from inner to outer?
Follicle
Mantle Zone
Marginal Zone
Describe the Ann Arbor Tumor staging for Lymphomas
Stage 1 – Single Location
Stage 2 – Multiple sites; same side of the diaphragm
Stage 1,2 – Localized disease; consider radiation therapy
Stage 3 – both sides of the diaphragm
Stage 4 – diffuse involvement of non lymphoid organs
Wide spread
Consider chemotherapy
Hodgkin Lymphoma –
what is it?
Localized single group of Nodes; contiguous spread
Extra nodal involvement is rare
Better Prognosis than Non-Hodgkin Lymphoma
Strongly associated with EBV
What is the classical morphology associated with Hodgkin Lymphoma
Reed Sternberg Cells
+Reactive benign Infiltrate
What are the 4 classical subtypes of Hodgkin Lymphoma?
What is the immunophenotype in general?
which are associated with EBV
CD15, 30+) and are EBV associated but to varying degrees
Nodular sclerosing (most common) Rare EBV association
Lymphocyte-rich
(do not confuse with lymphocyte-predominant)
40% EBV+
Mixed cellularity
70% EBV+
Lymphocyte depleted
90% EBV+
Immunophenotype of nonclassical HL subtype
CD15, CD30 and EBV Negative
Common Presentation + symptoms of HL
Enlarged LN in the neck, mediastinum, axilla
○ Often positive for EBV
○ 40% have B symptoms: night sweats, fevers, weight loss;
○ Itch
Sensitivity to alcohol
Treatment of HL:
(ABVD) +/- radiation therapy
□ Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine
Outcomes/prognosis of HL
○ Limited stage – 85% disease free 10 years later
○ Wide spread - 70% disease free 10 years later
What are the NHL - B Cell Lymphomas?
Which are aggressive(more treatable)?
Which are indolent (less treatable)?
CLL/SLL
Diffuse Large B Cell Lymphoma — aggressive
Burkitts Lymphoma —- (some are EBV ASSOCIATED) — aggressive
Follicular Lymphoma – indolent
Marginal Zone – indolent
(H. Pylori associated)
NHL B Cell: DLBCL: - what is it/presentation - what are the causes? - - -
- Fast growing, large Bcell tumor mass; Disease may extend beyond LNs
Causes not well understood. Very Heterogeneous Origins
- what are the virally associated subtypes of DLBCL?
- what is are some possible genetic makers (translocation?
Immunodeficiency associated LBCL (eg such as with acquired immunodef or HIV)
Primary Effusion Lymphoma
HHV8 (Kaposis’ Sarcoma) Associated
Potential translocations: BCL6
t(14:18)
Treatment of DLBCL
+ what drug is used for CNS prophylaxis
treatment: RCHOP
Rituximab (anti CD20); Cyclophosphamide, Doxorubicin, Vincristine, Prednisone +/- Radiation
CNS prophylaxis: Methotrexate
NHL B Cell: Burkitt’s Lymphoma
- what is it/presentation?
an aggressive B cell tumor: extremely fast growing. Medical emergency
- NHL B Cell: Burkitt’s Lymphoma
what causes it?
- is there a viral association?
cMYC Translocations with an Ig – proto-oncogene that gets activated when attached to an Ig Loci and becomes constitutively activated
t(8:14) translocation
Viral association for some of
subtypes:
- African – all EBV associated
Sporadic and HIV – few are EBV associated
What is the morphology of Burkitts?
“starry sky” – Sheets of lymphocytes with interspersed macrophages
High apoptotic rate: Macrophages in the background full of dead lymphoma cells
NHL - B Cell – Follicular Lymphoma
- what is it?
an indolent, slow growing B cell Lymphoma
Presentation: stage 3,4 disease; usually does not grow out of the Lymph Nodes
Can gradually transform to DLBCL
NHL - B Cell – Follicular Lymphoma
- what is the genetic origin?
- how can this help with diagnosis (immunophenotype)
T(14:18): Translocations of BCL2 with IgH
Immunophenotype:
Test: Over expression of BCL2
A normal follicular center is BCL2 negative
NHL - B Cell – Follicular Lymphoma
- what is the standard of care?
- when do you treat?
§ Current standard of Care:
□ Advanced Disease – Close surveillnace; treatment is not worth it
Treatment when the patient is symptomatic due to the lymphoma (eg the mass is compressing an important nerve or organ)
- Rituximab + Chemo
- Rituximab + Targetted therapy
NHL - B Cell – Marginal Zone Lymphoma (MALToma)
- what is it?
- What bacteria is it associated with?
- treatment
Indolent B cell Lymphoma that involves the mucosa;
— no enlarged LNs
– (H. Pylori)
– Treatment: if in the setting of H. pylor
® Triple therapy – 2 abx + PPI; followed by Surveillance Endoscopy
Name of the Mature T Or NK-Cell Lymphomas:
Adult T Cell Lymphoma:
Anaplastic Large Cell Lymphoma (ALCL)
Extranodal NK/T Cell Lymphoma
Mycosis Fungoides/Sezary Syndrome:
Peripheral T Cell Lymphoma – Not Otherwise Specified
Adult T Cell Lymphoma: What is the viral association?
Human T Lymphotrophic Virus 1: HTLV 1
○ Anaplastic Large Cell Lymphoma (ALCL)
what is the Constitutively Activated protein
ALK
Extranodal NK/T Cell Lymphoma
- where does it commonly occur? What structures are invaded?
- what is the viral association?
§ Very destructive tumor often involving the nasopharynx
§ Invades into blood vessels —> ischemic necrosis
§ Strongly associated with EBV
Mycosis Fungoides vs Sezary Syndrome:
- what is it? what is the difference between the two?
- Treatment for the two:
Mycosis Fungoides: Malignant T Helper cells infiltrate the skin, eventually form discrete plaques and tumors; can progress to Sezary — treat topically
Sezary Syndrome: Typically associated with a leukemia
treat with chemotherapy
Describe the progression of Plasma Cell Neoplasms
- what is the common finding of all of these ?
1) MGUS: Monoclonal Gammopathy of Uncertain Significance
2) Smoldering Myeloma
3) Plasma Cell Myeloma – Plasmacytoma
4) Multiple Myeloma: Multiple Plasmacytomas
Common finding: Elevated M (monoclonal para) protein
1) MGUS: Monoclonal Gammopathy of Uncertain Significance –
Presentation
what % become multiple myeloma
Clinical Findings:
what is notably absent
No masses; Asymptomatic
§ 1% will develop multiple myeloma
Clinical Findings: M protein
no CRAB findings
Smoldering Myeloma:
- presentation
- clinical findings
§ No Masses
§ Asymptomatic
M protein elevated
Elevated Marrow Plasma Cells (>10%)
Plasma Cell Myeloma – Plasmacytoma
§ a single Marrow based Tumors
§ Increased marrow plasma cells
• Elevated monoclonal Component
§ Solitary marrow mass; (if multiple, then its called Multiple Myeloma)
Mutlitple Myeloma:
- what is it?
- how do patients commonly present?
proliferation of plasma cells (in the marrow at multiple sites) – fully developed B cell that makes Ig
§ Excess Monoclonal Ig — M Protein;
§ Patient often presents with bony pain; new renal failure; new anemia
What are the criteria for diagnosis of a Multiple Myeloma?
§ Dx – Bone marrow aspirate and biopsy
Criteria for Multiple Myeloma Diagnosis:
> 10% plasma cells in the bone marrow
An M protein (monoclonal protein, Ig) – -quantitative Ig Levels; serum, urine and electrophoresis
End organ Damage: CRAB findings
What are the CRAB findings?
What symptoms can they cause?
what causes the renal damage?
◊ Calcium: hypercalcemia — can lead to dehydration and mental status changes (confusion)
◊ Renal failure — some of the M proteins can damage the kidneys
◊ Anemia
◊ Bone Lesions – skeletal survey — get every part of the body X-ray
Findings: Punched out lytic bone lesions;
How is serum protein electrophoresis used in Multiple Myeloma?
Used to classify the type of Ig that being abnormally produced (IgG, IgA, or IgM ) and whether it is kappa or lambda light chain
treatment of multiple myeloma?
treatment:
§ Multi-agent
Bisphosphonate therapy to stabilize bones
