Unit 3: Lymphomas and Plasma Cell Disorders Flashcards
What region of the lymph node focus of B-cell proliferation (germinal centers)
Cortex
-Cortical nodules (arranged in circles in outer cortex)
Lymph node medulla has medullary cords (____ lymphs and plamsa cells)
B
What area of the lymph nodes contains T cells and macrophages?
Paracortex (between the medulla and cortex)
Naïve B lymphs express what CD markers?
CD 19, 20, and 5
T cells express what CD markers?
(CD3,5,2,7) w/ CD4
and CD8
CD 10 is found in…
mature B-cells
All CD 20 except…
T-cells?
Lymph node functions:
- Role in the formation of new ___ lymphocytes from germinal centers
- Involved in the processing of specific immunoglobulins
- Involved in the filtration of matter, debris, and bacteria
B
Lymph Node Processing:
- Specimen is transported to Pathology laboratory…..kept moist
- Sliced into ___mm-thick sections
- Touch imprints are made
- Thin sections are sliced and preserved
- Portion is sent to flow cytometry, and the rest in frozen in -70°C for further
studies
3
True or Flase:
Most lymphomas develop in previously healthy people.
true
strongest risk factor for developing lymphoma
altered immune function
-Also a link to chemical exposure
Lymphomas subtypes are distinguished based on…
morphology,
immunophenotype, molecular characteristics, and clinical characteristics – all are mandatory for
comprehensive lymphoma diagnosis
General characteristics of lymphomas:
Hallmark signs…
histology is abnormal, destructive lymph
node enlargement
True or false:
lymphoma diagnosis requires lymph node biopsy
True!
-Typically no abnormal cells seen in p.b. until late in disease course (progression to a leukemia)
What is it called when lymphoma progress to the p. b.?
peripheralization stage (going towards leukemia)
Lymphomas can be divided into what two categories?
- Mature B cell lymphomas
- Mature T cell lymphomas
What are the two major types of lymphomas?
-Hodgkin’s Lymphoma (HL)
-Non-Hodgkin’s Lymphoma (NHL)
Two Major Types of Lymphomas:
Which is more common?
Which is more common in kids?
Non-Hodgkin’s Lymphoma (NHL)
-especially in autoimmune pts
Hodgkin’s Lymphoma (HL) more common in kids
Two Major Types of Lymphomas:
Which has a leukemic phase (cleaved lymphocytic nuclei)?
Non-Hodgkin’s Lymphoma (NHL)
Two Major Types of Lymphomas:
Pleomorphic cells, some normal, some malignant
Hodgkin’s Lymphoma (HL)
Two Major Types of Lymphomas:
Uniform, malignant cells
Non-Hodgkin’s Lymphoma (NHL)
Two Major Types of Lymphomas:
Accurate staging crucial to treatment!
Hodgkin’s Lymphoma (HL)
-Unifocal origin with predictable spread along lymph node chain
Two Major Types of Lymphomas:
Multifocal origin with unpredictable spread
Non-Hodgkin’s Lymphoma (NHL)
Hodgkin’s Lymphoma (HL):
Malignant cell =
Reed-Sternberg cell (distinctive, multi-nucleated, & giant-sized; called “owl-eyes”) or a variant of this cell
Non-Hodgkin’s Lymphoma (NHL):
Malignant cell =
B lymph in 95% of cases; T lymph in remaining cases, & rarely, even NK cell
Two Major Types of Lymphomas:
Which has good prognosis if still localized (>90% cure)?
Which is worse prognosis?
Hodgkin’s Lymphoma (HL)
Non-Hodgkin’s Lymphoma (NHL)
What are the symptoms of Hodgkin Lymphoma?
- Painless, enlarged cervical lymph nodes
- Sometimes mediastinal mass between lungs.
- “B symptoms” = fever, weight loss, night sweats (poor prognostic indicator)
Hodgkin lymphoma and Non-Hodgkin’s Lymphoma (NHL) are _______-geneous group of disorders
hetero-
Hodgkins lymphoma:
Untreated patients die ____ years after onset due to recurrent infections & organ failure.
1-2
Hodgkin lymphoma can be divided into what two groups?
- Nodular Lymphocyte-Predominant Hodgkin Lymphoma
- Classical Hodgkin Lymphoma
Hodgkin lymphoma group:
B cell neoplasm w/ rare neoplastic cells (popcorn cells)
Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL)
Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL) cells are positive for CD___ and CD___.
20, 45
Reed Sternberg (RS) cells are also known as…
owl eyes
Characteristic Reed-Sternberg (RS) cell (or variant) found in lymph nodes, but virtually never found in p.b.
Classical Hodgkin Lymphoma***
What must be seen with Hodgkin’s lymphoma to establish diagnosis?
Reed-Sternberg (RS) cells!
-Huge! 4-8X size of normal lymph
- Typical large, eosinophilic dual nucleus (“binucleated”), with distinctive surrounding halo (“owl-eyed”).
Reed-Sternberg (RS) cells are ***CD ___+ in all cases, CD___+ in 80% of cases.
30
15
Why is it important to stage HL?
Essential to accurately stage disease to determine treatment & prognosis! Numerous diagnostic tests used: bone scans, thoracic CT scans, immunophenotyping, routine labs, & both lymph node & liver biopsies.
HL treatment?
Radiation & chemo. can effect 90% cure rate if disease is localized! Treatment success judged by degree of reversal of
lymph node dysplasia. However, therapy can cause secondary cancer later on!
How does NHL present?
with painless cervical lymph node enlargement, but typically at a more advanced stage.*
Pre-existing NHL causes ↑ risk of developing…
a combined B & T Cell disorder by 10,000X
What are the 3 combined B & T cell disorders?
Wiskott-Aldrich, SCID, & ataxia telangiectasia (AT)
NHL overall has strong association with _____ proto-oncogene rearrangement on chromosome ___
cmyc, 8
_____ is a transcription factor for cell growth found to be over-expressed
in many different kinds of malignancies
cmyc
NHL lab findings:
Mostly N. p.b. cell morphology, but may see…
cleaved nuclei in lymphs
Ture or false:
NHL typically does have a leukemic presentation at the end stage of the disease.
true
________ Grade NHL - affects 45-60 yrs. old; slow-growing, survival with treatment 5 - 7 yrs
Low
_____________ grade NHL - affects 45-60 yrs. old; more rapid enlargement & more common extra-nodal disease. (FYI: frequently the Diffuse Large B Cell Lymphoma subtype.)
Intermediate
_______ grade NHL - rapidly growing nodes; often rapidly
fatal even with therapy.
High
NHL treatment?
Similar to that of HL:
Radiation
Chemotherapy
Mature B cell lymphomas:
- Derived from various stages of B cell differentiation
- All produce ____________
immunoglobulins, clonal immunoglobulin gene
rearrangements, or both
monoclonal light chain***
Mature B cell lymphomas:
Most cases are _________-based and occur in elderly individuals
lymph node
What are the types of Mature B cell lymphomas?
- CLL/SLL (small lymphocyte lymphoma)
- Mantle cell lymphoma
- Follicular lymphoma
- Diffuse large B cell lymphoma
- Burkitt lymphoma
Small Lymphocytic Lymphoma/CLL:
-Diffuse proliferation of small hypermature (“soccer-ball”) lymphoid cells and smudge cells
-Derived from what circulating cells?
IgM, IgD, B-cells
Small Lymphocytic Lymphoma/CLL:
Both types (naïve B and memory B cells) are positive for CD,,,
D19, CD 20, and CD23 (+/- CD5)
Median survival for Small Lymphocytic Lymphoma/CLL?
10 years
- Diffuse proliferation of medium-sized cells w/ irregular nuclear
outlines - Peripheral blood can mimic PLL
Mantle Cell Lymphoma
Mantle Cells are positive for CD…
CD5, CD19, CD20; but negative for CD23**
Mantle cell Lymphoma is linked to t(_____) defect
t(11;14)
Median survival for Mantle Cell Lymphoma?
3 to 5 years
Nodular proliferation replaces N. architecture
Follicular Lymphoma
Follicular Lymphoma:
Originates in ________ and involves neoplastic proliferation of medium-sized cells, mixed w/ large lymphoid cells.
germinal centers
How is Follicular Lymphoma graded?
3 grades = graded by counting the average number of large cells observed per hpf
True or false:
Follicular Lymphoma cells have an increased sensitivity to apoptosis?
False, decreased
Follicular Lymphoma cells are positive for CD…
CD19 and CD20
Follicular lymphoma is linked to t(_____) and (______)
t(14:18) and (q32;q21)
> 95%. Follicular Lymphoma Express ______ protein – decreased apoptosis sensitivity.
BCL-2
Follicular Lymphoma:
____% of cases see bone marrow involvement
50
- Diffuse proliferation of large lymphocytes (twice the size of normal lymphs)
- Most common lymphoma (30-40%)
Diffuse Large B Cell Lymphoma
(DLBCL)
Diffuse Large B Cell Lymphoma (DLBCL) cells are positive for CD…
D5, CD10, CD30, and CD138
- Rarely observed in children
- Rarely extends to bone marrow
- Survival rate is increasing – varies upon severity
Diffuse Large B Cell Lymphoma (DLBCL)
What pattern can be observed with macrophages in Burkitt Lymphoma?
“starry sky”
Mass proliferation of medium-sized cells with basophilic vacuolated cytoplasm
Burkitt Lymphoma
Burkitt Lymphoma:
Cells are positive for CD…
CD10, CD19, and CD20
Burkitt Lymphoma:
Linked to MYC gene t(____), t(_____), and t(_____) causing varying degrees of severity
(t[8;14], t[2;8], t[8;22])
- Diagnosis is considered a medical emergency
- Treatment is highly aggressive and helps keep cure rates high
Burkitt Lymphoma
Mycosis Fungoides & Sezary Syndrome:
Both are _____________ (just different stages of the same neoplasia!)***
cutaneous T-cell lymphomas
- Mature T-helper cell (CD4+) lymphoma.
- Cells produced in lymphatic tissues, then migrate to skin!
- Highly aggressive.***
Mycosis Fungoides & Sezary Syndrome
Mycosis Fungoides & Sezary Syndrome pts are usually…
middle-aged males.
What is the most common cutaneous lymphoma?
Mycosis fungoides*
What is the skin presentation stage of Mycosis fungoides?
- Typically see pruritus, followed by weepy erythroderma.
- Then whitish plaques form
- Finally, nodular tumors occur (very indolent course until end of the disease).
- Disease progresses from skin to organ involvement.
- After organ involvement, survival is just a few months if treatment is not instituted.
What is the prognosis for Sezary syndrome with p.b. presentation stage?
bad prognosis by now
Are “butt cells” highly specific for just Sezary?
no, seen in other lymphoid neoplasms
What are the lymphocytes in Sezary syndrome?
Lymphocyte here called Sezary cell:
* Larger lymph than N.
* Scant cytoplasm
* Large, uniquely cleaved nucleus:
* May be cleaved (“butt cell”)
Mycosis Fungoides & Sezary Syndrome treatment?
- Topical chemo. & superficial radiation for mycosis fungoides.
- Regular radiation & chemo. if disease has progressed to organ involvement.
HIV infection increases general lymphoma risk (by ~____X).
* Many types (NHL, HL, Burkitt’s, etc.) may occur, especially late in AIDS.
* Usually very aggressive.
* Usually EBV negative.
60
HIV-Related Lymphoma:
What therapy increases CD4 counts, unfortunately does not ↓ rate of incidence of HIV-related lymphomas?
Highly Active Anti-Retroviral Therapy
occurs when a tumor of malignant plasma cells overgrows in the bone marrow
* Causes overproduction of a single Ig (synthesis of normal Igs is suppressed).
Multiple Myeloma (MM)
_____ is the most common malignant disease of plasma cells!***
MM
Pts. generally > 40 yrs. old.
SPE & urine elp show characteristic monoclonal “spike”, Bence-Jones
proteinuria, and ↑ ESR
MM
MM lab findings?
*Characteristic mod. rouleaux & few abnormal plasma cells in p.b. smear.
* FYI: ↑ [plasma protein] can depress plt. function.
What type of anemia do MM pts have?
Normo- normo- anemia due to Myelophthisic Anemia
MM:
Lytic bone disease seen on bone scans. Patients also can develop amyloidosis: condition in which…
amyloid (starch-like protein deposits) are deposited throughout body, causing multiple organ defects*
Bone marrow findings with MM?
plasma cells that contain Russell bodies (rounded accumulations of Ig in rER), are called Mott cells/grape cells/morula cells.
MM:
Plasma cell seen in Ig___ myeloma is called a Flame Cell
A
MM Clinical Symptoms?
- Painful bone lesions*
- Pathologic fractures*
- FYI: These occur bc. plasma cells secrete an osteoclast-activating factor.
- Weakness & fatigue
- Renal failure*
What is the prognosis for MM?
Not curable, but treatable (but poor prognosis
overall)*
MM treatment:
what meds are used in various combinations?
- Steroids
- Chemo. & radiation before stem cell transplant.
- Aredia – new drug; strengthens bones.
- Newest med. for MM: Velcade – used for relapsed & refractory MM only.
- First in new drug class of IV proteasome inhibitors
-For unknown reason, proteasome inhibition causes more apoptosis
in malignant cells than in N. cells!
-Occurs when absolute # of circulating plasma cells exceeds cutoff (> 2000/uL)
* May occur as end-stage sequela of MM, or by itself.
* Usually found in pts. younger than middle age.
Plasma Cell Leukemia (PCL)
- Malignant plasmacytoid lymphocytes
- Pt. typically male, over 50 yoa.
- Rarer condition than MM.
Waldenstrom’s Macroglobulinemia (WM)
Waldenstrom’s Macroglobulinemia (WM):
Abnormally increased CD___ cell surface markers.
20***
Waldenstrom’s Macroglobulinemia (WM):
- Oversecretion of Ig___
M
Malignant plasmacytoid lymphocytes
Waldenstrom’s Macroglobulinemia (WM)
Waldenstrom’s Lab Findings:
* P.b. smear looks similar to ______
MM
Waldenstrom’s Lab Findings:
___+ increased ESR
-Slt. Bence-Jones proteinuria
4
Waldenstrom’s Lab Findings characteristic marked __________ in p.b. smear.
rouleaux
Automated Heme instrumentation may give spuriously high WBC & plt. counts due to the cryoglobulin activity of IgM – it forms gels & precipitates upon refrigeration!
Waldenstrom’s Macroglobulinemia (WM)
increased [plasma protein] can ↓ plt. function, same as MM.
Waldenstrom’s Macroglobulinemia (WM)
Waldenstrom’s Clinical Findings:
- Gradual onset of following as IgM levels increase:
- Weakness & fatigue
- Weight loss
- Epistaxis
- But no bone lesions – organomegaly instead
Waldenstrom’s Treatment:
- Steroids
- Plasmapheresis and/or chemo.
- Rituximab, an I.V. monoclonal Ab binds CD20 antigens, & thus flags malignant plasmacytoid lymphs for death!
Waldenstrom’s Macroglobulinemia (WM):
Why are CD20 Ags important here?
Because they are so highly overexpressed in this disease.
Ig produced with MM?
with Macroglobulinemia?
IgG > A > D > E
IgM
