Lymphoma Flashcards
What is Lymphoma?
cancers that begin by the “malignant transformation” of a lymphocyte in the lymphatic system
What are many lymphomas due to?
Whats an example?
specific genetic mutations
Follicular lymphoma due to overexpression of BCL-2 (gene that blocks programmed cell death)
Where does lymphoma start?
Leukemia is a cancer of what?
cancer that starts in the lymph nodes or lymphatic system
a tumor or cancer of white blood cells or bone marrow
How does lymphoma spread?
How does leukemia spread?
invades other organs by unnecessary and uncontrollable growth of lymphoid tissue
produces abnormal white blood cells which inhibits the function of the immune system and platelet function
(reduced, abnormal white cells and lack of fucntion of other cells)
How will lymphomas present?
How will leukemia present?
present with signs of swollen lymph nodes in the neck, armpits or groin which are frequently painful
patients have symptoms typical of other cancers and may have no early telling symptoms, especially if chronic (fatigue, malaise, blah)
How to classify lymphoma?
3
- Based on the grade or “aggressiveness”
- Divided into Hodgkin’s lymphoma and NHL
- NHL divided into B and T cell
HOw is Hodgkin’s lymphoma characterized?
Who does it affect mostly?
How does it spread? and what cells does it involve?
reed-sternberg cells (look like an owl)
Bimodel incidence: young adults and elderly
Spreads in an ordely fashion and throughtout the lymphatic system and involves abnormal B cells
What are all other lymphomas called?
Who is it most often seen in?
How does it spread?
What cells are involved?
Non-Hodgkins lymphoma
affects adults, average age of 60
disordly fashion (plays hide and seek with the physician)
Abnormal B cells (most common) or T cells
What are the types of HL?
4
What is the most common?
What is the one that responds best to treatment?
What is the best that repsonds worst to treatment?
Nodular sclerosis (most common)
Mixed cellularity
Lymphocyte rich
Lymphocyte depeletion
What are the categories of the special kinds of NHL that are different from the others?
2 categories
2 and 3
Describe them
Indolent
- follicular lymphoma
- MALT lymphoma (tumors in gut that are muscosal associated)
Slow growing, varies sites, disorderly
Aggressive
- diffuse large B cell lymphoma (most common)
- AIDS associated lymphoma
- Burkitt’s lymphoma
Symtpoms of HL Lymphoma
6
- painless enlargemntt of lymph nose usually in the neck armpits or groin
- swelling from edema in legs or feet
- shortness of breath, fatigue
- weight loss, muscle weakness
- Pel-Ebstein fever (very very variable fever), night sweats!!!
- increased susceptibility to infections
Why are these masses painless?
Slow growth, pain comes from the strecthing of the tissue so its not painful. Its painful if its acute
-capsule of the liver as the pain fibers and if the liver enlarges rapidly he will present with pain
What are the two ways that swelling happens in HL lymphoma?
(lymphatics might be blocked or decreased albumin = fluid goes into tissue)
decrease in oncotic pressure or increased hydrostatic pressure
Symtpoms of NHL?
10
- Rapid, painless (however pain is more common than in HL) enlargment of of lymph nodes
- Progressive swellling of legs, swelling of face
- Pale skin or dark itchy patches of skin
- Difficulty breathing, chest pain
- Pleural effusion, causing persistant cough
- bloating, cramping, diahhrea, flatuence
- abdominal pain or distention, constipation
- unexpplained appetite loss, weight loss
- fever, causing excessive night sweating
- increased susceptibility to infections
How does staging of lymphoma classify tumors?
What system do we use?
What is this helpful with?
Staging classifies tumors into categories based on where the tumor is present
Ann Arbor system (AAS)
Useful in determining specific treatments, prognosis
Name the steps in the staging process?
7
CXR CT scans Bone marrow aspiration/biopsy PET scan Gallium scan (will see hot spots) MRI Lumbar puncture (see if it has spread to brain or spinal fluid)
Name the site involvement for the floowing stages: Stage 1 Stage 2 Stage 3 Stage 4
- Single LN region or extralymphatic organ or site
- Cancer in 2 or more groups of LN on same side of diaphragm (above or below)
- Cancer in groups of LN both above and below diaphragm
- Cancer has spread to one or more organ or tissue sites
Describe the substaging of lymphoma: A B E (extranodal) S (spleen)
So what does 1B mean?
What does 3E mean?
A. No systemic symptoms present at diagnosis (B-Symptoms absent)
B. B-Symptoms present (fever, night sweats, weight loss)
E. Cancer in an area or organ other than LN or spread to tissues outside lymphatic system
S. Cancer spread present in the spleen
How does grading of lymphoma describe and what kind of lymphoma is it used for?
What are the grades?
Used in NHL, which describes how quickly cancer is growing
Low, Intermediate, or high grade
Other grading: indolent or aggressive
Describe Low, Intermediate, and High grades of NHL.
- (slow growing, incurable)
therapy really wont help, but good because slow - (rapid growing, potentially curable) respnd very rapidly to treatment
- (fastest growing, potentially curable)
What are the diseases associated with low grade? 3
What are the disease associated with intermediate grade? 3
What are diseases associated with high grade? 4
Follicular, small lymphocytic, Waldenstrom’s
Diffuse large B cell, mantle cell, anaplastic large (T cell) NHL
Burkitt’s lymphoma
lymphoblastic lymphoma
What kind fo tumors have the best response to therapy?
faster growing (but tend to reoccur after treatment)
What does indolent grade mean?
Grow very slowly, need little or no treatment until symptoms appear. Tend to reoccur after treatment.
What does aggressive grade mean?
Grow quickly, symptomatic and treatment required immediately. Can be treated with intense chemotherapy
Risk factors for HL?
in young people
- diagnostic history of mononucleosis increaes young adult HL
- Sibling diagnosed with HL
Risk factors for NHL?
5
- toxic compounds in atmosphere
- Epstein-Barr Virus after organ transplant
- H. pylori causing MALT lymphoma
- Hep C
- Genetic
Risk factors for both HL and NHL?
4
- HIV
- AIDS
- Human T lymphocyte virus
- suppressed immune function
Where do peak incidences occur in HL?
Bimodal distribution with peaks at 20 yrs and > 50 yrs
Up to 50% of cases are associated with what?
Association with EBV (up to 50% of the cases)
Clincial Features of HL?
5
- Asymptomatic lymphadenopathy (70%)
- Splenomegaly
- Systemic symptoms: B symptoms – fever, pruritus, night sweats
- Non-specific: alcohol induced pain in nodes, nephrotic syndrome
- Disease spread in contiguity with lymphatic system
What labs should we order for HL to test out other things and confirm HL?
6
- CBC: anemia, eosinophilia, leukocytosis, platelets N or increased then decreased in advanced disease.
- LFTs, ESR (high), LDH
- CXR, CT
- Cardiac function assessment
- Excisional Lymph biopsy confirms diagnosis
- Bone marrow bx: if B symptoms present ( stage III/IV)
If what symtpoms are present should we order a bone marrow biopsy?
B
Describe stage 1 HL?
Lymphocyte rich classical Hodgkin lymphoma: localized , good prognosis; 5%
Describe stage 2 HL?
Nodular sclerosis: young, stage I or II , relatively favorable prognosis; 55%
Describe stage 3 of HL?
Mixed cellular: tendency of dissemination, relatively poor prognosis; 25%
Describe stage 4 of HL?
Cancer has spread to one or more organ or tissue sites
What is a worse prognosis?
NHL
What does Reed Sternberg cell cell look like?
a bi-nucleate cell with large “owl’s eyes” eosinophilic nuclei
Treatment methods for HL treatment?
5
Surgery Radiation Chemotherapy Biotherapy Peripheral blood stem cell transplant (PBSCT)
Treatment for stage I-II of HL?
Chemotherapy followed by XRT
Treatment for stage III-IV HL?
Chemo with XRT for bulky disease
Treatment for relapse after treatment?
High dose chemo, bone marrow transplant – PET to follow-up treatment response.
Treatment complications for HL?
4
- Cardiac disease and hypothyroidism post XRT
- Pulmonary disease
- Infertility
- Secondary malignancy e.g MDS, AML, non-Hodgkin’s Lymphoma
Stage 1A and IIA treatment for HL?
Extended radiation(mantle form or inverted Y form)
Stage IB、IIB、IIIA、IIIB、IV
HL treatment?
Combined chemotherapy+localized radiation
Important factors in how the treatment will work?
10
Sub-type of lymphoma Age >=45 yrs Male Stage IV disease Extra-nodal disease LDH Performance status Hemoglobin level (
Whats the most common hematological cancer?
Its also the second fastest growing cancer in the US.
NHL
How is NHL differentiated from HL?
Distinguished from HL by proliferation of only malignant B-cells (rarely, T-cells)
What is the highly aggresssive lymphoma?
Burkitt’s lymphoma
What are the two kinds of NHL B cell neoplasms?
T cell?
Precursor B-cell Neoplasms
Mature B-cell Neoplasms
Precursor T-cell Neoplasms
Mature T-cell Neoplasms
Risk factors for adult NHL?
9
- Being older, male
- Autoimmune disease
- HIV/AIDS
- Other viruses (EBV, HTLV-1)
- Helicobacter pylori infection (in stomach)
- Long term use of immunosuppressant drugs
- Pesticides
- Past treatment for Hodgkin’s lymphoma or with radiation
- Other unknown environmental factors ?
NHL Clinical features?
7
- Painless superficial LAD
- Widespread disease
- Constitutional symptoms uncommon
- Cytopenia (anemia, neutro, thrombocytopenia) with bone marrow involvement
- Abdominal signs: hepatosplenomegaly, retroperitoneal and mesenteric involvement
- Sore throat and obstructive apnea (tonsilar enlargement)
- CNS involvement in HIV patients
NHL diagnostic process?
4
Mandatory lymph node biopsy
Blood tests
CXR, CT chest, abdomen, pelvis for staging
Gallium scan to monitor response to treatment
What kind of biopsy would you do for NHL?
3
Excisional biopsy preferred
Core biopsy
Needle aspiration/biopsy
What things would you be looking for in the blood tests that you order?
4
CBC: normocytic normochromic anemia, autoimmune hemolytic anemia, thrombocytopenia, neutropenia
Elevated Uric acid, LDH-poor prognosis, abnormal LFTs.
Treatment for low grade group of NHL?
What if the disease progresses?
If all of this fails and the patient shows signs of a very large tumor waht is our option?
- requently follow up, postpone chemotherapy
- -Single drug :CB1348 (Leukeran) 2mg b.i.d ~t.i.d
- -cyclophosphamide: 100mg/d
Disease progressing —-combined chemotherapy
-Fludarabin
-Pentostatine
CD20(Rituximab)
Autologous or allogeneic transplantation
Total nodal irradiation, first
What CD20(Rituximab)? 3 (go into the process)
- Rituxan, a therapeutic antibody, binds to the CD-20 protein found on normal and cancerous B-cells in vitro
- Rituxan recruits components of the body’s immune system (phagocytes etc) to destroy B cells
- Once Rituxan has cleared the body, normal B-cells can begin to grow again
NHL complications?
5
- Hypersplenism (causes red cells to be destroyed)
- Infection
- Autoimmune hemolytic anemia and thrombocytopenia
- Vascular obstructions
- Tumor lysis syndrome (aggressive lymphoma)
IF you have a Diffuse B cell lymphoma: age>60, AAS III-IV, elevated LDH, >1 extranodal site?
mean 5 year survival 25-73%
- Which of the following viruses is a member of the herpes family, infects B cells and epithelial cells of the oropharynx, and causes a positive heterophil reaction?
EBV
- A 7-year old boy living in central Africa presents with a rapidly enlarging mass that involves his mandible. A histologic section from this mass reveals a diffuse proliferation of small non-cleaved lymphocytes. In the background are numerous tingible-body macrophages that have a “starry-sky” appearance when viewed under low magnification. Which of the following is the most likely diagnosis?
Burkitt lymphoma
- A twenty-five year old man comes to you complaining of a lump in his right neck. The lump has not changed since he first noticed it about six weeks ago. Lately he has been losing weight - 10 lbs. in the last month. His only medication is Tylenol for fever (101 ).
You obtain a chest X-ray and perform a lymph node and a bone marrow biopsy and touch prep of the marrow core.
With the results of this information you determine that this young man has:
E. stage IVb, HD, nodular sclerosis type
To diagnose lymphoma what is needed?
lymph node biopsy is required
How is HL distinguished from NHL?
the presence of Reed-Sternberg cells
What are the classical represenations of HL?
painless, non-tender, firm, rubbery enlargement of superficial LN, most often in cervical nodes.
NHL associated conditions?
3
Immunodeficiency (e.g. HIV), Autoimmune disease (e.g. SLE), infections (e.g. EBV)
Treatment of HL depends on what?
stage
Treatment of NHL depends on what?
sub type and stage
What is Burkitt lymphoma?
What part of the body does it often involve?
an aggressive, high-grade B-cell lymphoma that is associated with infection by EBV
Maxilla or mandible, more common in children
