Lymphoproliferative Neoplasms

ONCOL 255 - Intro to Oncology. University of Alberta

What is the common ancestors of the lymphocytes

the common lymphoid progenitor: gives rise to all lymphocytes

what type of cells is CLL made of

Small lymphocytes: B and T lymphocytes

what type of cell is ALL made of

common myeloid progenitor cells

what type of cell is multiple myeloma made of

Plasma cells

what are lymphoprolifertive neoplasms (LPNs)

a heterogenous group of diseases characterized by the infiltration of lymph nodes, spleen, bone marrow, and other tissues by abnormal clonal proliferation of lymphoid cells

malignant lymphoid cells exhibit uncontrolled ______ and failure to undergo _____

proliferation, apoptosis

Lymphomas involve ____, and Leukemias involve ____

lymph nodes, blood

where do normal lymphocytes develop

in the bone marrow or thymus (primary lymphoid tissues)

what secondary lymphoid tissues to lymphocytes migrate to?

• lymph nodes

• spleen

• tonsils

• appendix

• peyer’s patches

what do abnormaly lymph nodes look like

• increased in number and size

• hard/swollen

• unusal location

• infiltration of abnormal cells

• alteration in architecture

what are the three main causes of lymphadenopathy

M.I.A

• Malignancy

• Infection

• Autoimmune

Malignant causes of lymphadenopathy

lymphoma, metastasis

infection causes of lymphadenopathy

• TB (bacterial)

• Mono!!! (Viral)

• histoplasmosis (fungal)

• parasites

Autoimmune causes of lymphadenopathy

• sarcdoidosis

• Lupus

• Sjogren’s

• Kawasakis

what does a physical examination for abnormal lymph nodes look like

• inspect for asymmetry, erythema and tenderness

• palpate for location size, tenderness, etc

Fixed/Firm/Matter lymph nodes =

bad

tender lymph nodes =

reactive (most likely)

what clinical tests can be done for abnormal lymph nodes

imaging may be used to see all areas involved that aren’t palpable (appendix)

blood tests can help rule out infections or autoimmune

if we have a suspicion of lymphoma, what clinical test is done

LN biopsy

why are excisional biopsies preferred for potential lymphoma

better to see the architecture of the lymph ndoes

3 different types of biopsies

• Fine Needle Aspiration

• Core Biopsies

• Excisional (best)

what type of biopsy should never be done to diagnose lymphoma

fine needle aspiration (FNA)

• does not provide architecture of lymph nodes, lymphoma cells look a lot like normal lymphocytes when seen individually

what does an altered spleen look like>

too large, altered architecture, prescence of nodules

5 diagnosies that may cause splenomegaly

• lymphoproliferative neoplasms

• infections

• inflammation

• cirrhosis with portal hypertension

• extramedually hematopoeisis

what type of imaging is used to see an abnormal spleen

ultrasound or CT

if the cause of an abnormal spleen is suspected to be LPN, what else should be done?

A bone marrow or LN biopsy should be performed to confirm the diagnosis and assess for lymphoproliferative disease.

are there more T cells or B cells bine marrow

more T cells

if LPN is suspected, are there more B cells or T cells in bone marrow

abnormal ratio of B cells to T cells

what is a bone marrow biopsy

A procedure to obtain a sample of bone marrow for examination, typically used to diagnose blood disorders or malignancies.

what is a CBCD

a complete blood count that includes the complete break down of types of white blood cells

what CBCD levels increase in LPNs

The levels of atypical lymphocytes, particularly B cell counts, typically increase in lymphoproliferative neoplasms.

what are the only two pathologies that increase lymphocyte count

Chronic lymphocytic leukemia

Mononucleolis Virus

why is flow cytometry used to identify different types of lymphocytes

under a microscope, B and T cells look nearly identical, however they have different surface antigens that can be used to detect the type of lymphocyte

what type of cell surface markers are consister with B cells

CD19 and CD 20 (high numbers)

what type of cell surface markers are consistent with T cells

CD3, CD4, CD8 (low numbers)

what leukemia is the most frequent cause of persistent blood lymphocytosis

Chronic Lymphocytic Leukemia (CLL)

what 3 tests are used to confirm CLL diagnosis

• Blood smear with MATURE lymphocytes

• Flow cytometry profile

• bone marrow biopsy or aspiration

3 constituinal (B) symptoms

• weight loss of 15-20 pounds

• fever of over 100

• sustained DRENCHING night sweats

What lab tests should be done for lymphoma

• CBCD

• electrolytes

• creatinine (kidney)

• Uric acid

what is biopsied for lymphoma diagnosis

Lymph node or involved organs

what viral studies are used for lymphoma

Test for HIV and HEP B/C which increase risk of lymphomas

What genetic tests can be done for lymphoma

• Karyotype

• FISH

• oncogene testing

three types of LPN/Lymphoma

• B cell Non-Hodgkins

• T cell Non-Hodgkins

• Hodgkins

two types of of Non-Hodgkins

• Indolent

• agressive

what is the most aggressive lymphoma

Burkitt’s

• HIV subtype: true next day emergency

second most agressive lymphoma

DLBCL

• diffuse large B cell lympgoma

most indolent aggressive lymphoma

Chronic Lymphocytic Leukemia (CLL)

• watch and see treatment

do lymphomas have good or bad prognosis

typically decent prognosis: lots of stage 4 ones are manageable

what staging system is used for lyphomas, how is it different than solid tumors

The Ann Arbor staging system is used for lymphomas

• solid tumors use TMN, but lymphoma has no primary tumor, so you can’t use it

Ann Arbor Stage 1

one site

Ann Arbor Stage 2

multiple sides on one side of the diaphragm

Ann Arbor Stage 3

multiple sites on both sides of the diaphragm

Ann Arbor Stage 4

Diffuse involvement of extra-lymphatic organs

what is the most common treatment modality for lymphoma

chemotherapy or immunotherapy

is radiation therapy used often for lymphoma

it is fairly rare to treat lymphoma with radiation

what can corticosteroids (prednisone) used for in lymphoma treatment

reduce tumors and relieve symptoms

• but must be used after biopsy to ensure proper diagnosis

difference between Non-Hodgkins and Hodgkin’s Lymphoma

Non-Hodgkin's lymphoma is characterized by the absence of Reed-Sternberg cells, while Hodgkin's lymphoma includes these cells and typically has a better prognosis.

which lymphoma is more common, NHL or HL

Non-Hodgkin's lymphoma (NHL) is more common than Hodgkin's lymphoma (HL), making up the majority of lymphoma cases.

age range of Hodkin’s lymphoma

bimodal: peak 20-30, then 70-80

• NHL more common above 65 (and more common in men)

is there more LN spread in HL or NHL

Non-Hodgkin's lymphoma generally demonstrates more extensive lymphatic spread compared to Hodgkin's lymphoma, which usually spreads in a more predictable manner.

what intent is treatment of HL

alway curative

why is radiation not used in treatment of Hodgkin lymphoma

• increases CV disease

• secondary malignancies

• thyroid dysfunction

what is the Chemotherapy standard for HL

ABVD regimen, which includes Adriamycin, Bleomycin, Vinblastine, and Dacarbazine.

what are the two cell origins of NHL

• B-cell

• T-cell

Agressive NHL example

Diffuse Large B-Cell lymphoma (DLBCL)

• TLS syndrome possible

• fatal in months

Indolent NHL example

Follicular lymphoma

• no TLS

• watch and wait treatment

what is tumor lysis syndrome

rapid death (lysis) of tumor cells, resulting in intracellular contents dumped into blood stream

effects of TLS (PUCCK)`

PUCCK

• increased PO4

• increased Urate

• decrease Ca (as it binds to PO4)

• increased creatinine

• increased potassium

how does renal damage occur due to TLS

when calcium binds to PO4, it enters the kidnets where it causes calcium crystals to form = damage

prophylactic treatment of TLS

allopurinol

• prevents metabolism of uric acid

Treatment of TLS

Rasburicase

• metabolises uric acid to allantoin, a more soluble compound to be excreted by kidneys

when is radiation therapy used for aggressive NHL

if disease is bulky

when do you treat aggressive NHL, when do you treat indolent?

aggressive: treat immediatly with CHOP

indolent: treat when symptomatic

what type of NHL is CLL

indolent NHL

Staging of CLL (LLSAT)

LLSAT

• Stage 0: lymphocytosis

• Stage 1: lymphadenopathy

• Stage 2: splenomegaly

• Stage 3: anemia

• Stage 4: thrombocytopenia

Does not use Ann Arbor!

is CLL curable?

no

what anti-CD20 IgG is used to treat CLL (when patient is symptomatic)

Rituximab is used to treat symptomatic CLL patients.

Side effects of Rituximab

may include infusion reactions, fever, chills, hypotension, and increased risk of infections.

• normal for all antibodies

• treat with acetominophen and corticosteroids

Leukemia = ____ malignancy

peripheral blood

Lyphoma = ____ malignancy

solid lymph node

do NOT do an _____ to diagnose a lymphoma

Fine needle aspiration

Lymphadenopathy Differential

M.I.A

• malignancy

• infection

• autoimmune