Non-Hodgkin Lymphoma Flashcards
What are the two main hematologic malignancies?
- Leukemia
2. Lymphoma
What is leukemia?
- Malignancy of hematopoetic cells
- Starts in bone marrow, can spread to blood, nodes
- Myeloid or lymphoid
- Acute or chronic
What is lymphoma?
- Malignancy of hematopoietic cells
- Starts in lymph nodes, can spread to blood, marrow
- Lymphoid only (stem cell and lymphocyte)
- Hodgkin or non-Hodgkin
With Non-hodgkin lymphoma, what usually brings people into the doctor?
Lymphadenopathy
What should you remember about the causes of lymphadenopathy??
- Most common cause overall: benign reaction to infection
- Most common malignant cause: metastatic carcinoma
What is the most common malignancy in lymph nodes?
Metastatic carcinoma (CA)
Anatomy of lymph node:
- Follicles = contain B cells (germinal center + mantle)
- Inner part/Paracortex = contains T cells
- Germinal center = lighter circle
- Mantle zone = darker cells surrounding germinal center
What can be found in follicles?
-Tingible body macrophages and dark mantle outside
What are tingible body macrophages?
- Found in follicles
- Cell are all different
- A lot of mitotic activity
What is Follicular Hyperplasia?
- Benign condition where the lymph nodes has been stimulated (usually due to infection)
- See follicles of varying shapes and sizes
- Normal
What things must you know about Follicular Hyperplasia?
- Large, irregular follicles
- Mixture of cells in germinal centers
- Tingible body macrophages
- B-cell response to some immune stimulus
What does benign follicular hyperplasia look like in a lymph node?
-Normally the lymph nodes are soft and reddish but these have follicles/white round things too scattered throughout
What does a lymphoma lymph node look/feel like?
- Fleshy color with little red
- Very firm, fish-flesh feel - like sushi
- Not very firm like you see with metastatic hyperplasia
- Lymphoma is more squishy
- No normal lymph node tissue left
What do you see in a slide of follicular hyperplasia?
- All different sizes of follicles
- Space in-between them
- In constrast to, Lymphomas = cookie-cutter follicles
What things must you know about Interfollicular hyperplasia?
HARD TO DIAGNOSE
- Expanded area between follicles
- Mixture of cells
- Partial effacement (little bit of follicle left - lymphoma usually doesn’t have any follicle left) – Benign things partially efface
- T-cell response to some immune stimulus (usually infection)
What is the difference between follicular hyperplasia and follicular lymphoma?
Hyperplasia - benign, round germinal centers, surrounded by dark mantle zone, circles come in many shapes and sizes
Lymphoma - cancerous, no mantle zone, circles tend to be same size and are more ‘packed in’ but have less distinct/dark boarder
What does a benign follicle look like in comparison to a lymphoma nodule?
Benign - tangible body macrophages seen - see large gaps of white
Lymphoma - all small cells, tightly packed, follicle = nodule
What things must you know about Non-Hodgkin Lymphoma?
- Malignant proliferation of lymphoid cells (blasts or mature cells) in lymph nodes
- Skips around (ex: in inguinal area, then bone marrow, then liver)
- Many subtypes
- Most are B cell
What are three symptoms of NHL?
- Painless, firm lymphadenopathy (will not be soft and will not hurt - infected lymph node is painful and soft)
- Extranodal manifestations (can show up in the bone marrow - if very severe they could be getting anemic - could show up in CNS, skin, etc.)
- “B” symptoms: weight loss (like 20 lb. weight loss over 2 months without dieting), night sweats (you wake up drenched every hour or so where you have to change your clothes), fever (nothing to do with B lymphocytes) – patients with these symptoms tend to do worse than patients without these symptoms
What are the features of low grade (chronic) NHL?
- Older patients
- Indolent (incurable! - can go unnoticed for years)
- Small, mature cells
- Non-destructive
What are the features of high grade NHL?
- Need to treat aggressively
- Children, sometimes
- Aggressive (curable?)
- Big, ugly cells (could be pleomorphic - different shapes, mitoses all over)
- Destructive (invade everything around them)
How is NHL classified?
Working formulation --Low-grade --Intermediate-grade --High-grade REAL/WHO -Divides it: --B cell disorders --T cell disorders
What cancers are low grade NHL?
- Small lymphocytic lymphoma
- Malt lymphoma
- Follicular lymphoma
- Mycosis fungoides
What cancers are high grade NHL?
- Large cell lymphoma
- Lymphoblastic lymphoma
- Burkitt Lymphoma
What things MUST you know about small lymphocytic lymphoma?
- Small, mature lymphocytes
- Same thing as CLL
- B-cell lesion, but CD5+ (weird!)
- Long course; death from infection
- Can be in lymph nodes OR bone marrow
What does SLL/CLL look like on a slide?
Lymph Node:
-Big group of small, dark lymphocytes, along with areas that are cloudy/pale looking - when you look closer, the cells/areas look pale and tend to show up in clusters (proliferation center)
What does SLL/CLL look like in the blood?
-Mature lymphocytes that all look very similar, B cell in nature with CD5 positivity - (monomorphic - all look the same)
What can happen to cells in SLL/CLL?
Richter’s transformation: bigger/gigantic, uglier, blocky cells
What must you know about marginal zone lymphoma?
- Actually a bunch of lymphomas
- Marginal zone pattern
- MALT lymphoma (MALT = mucosa associated lymphoid tissue - associated with H. pylori which can cause stomach cancer and/or ulcers)
- Helicobacter pylori
What does marginal zone lymphoma look like on a slide?
- Marginal zone pattern
- Benign follicles - lymphoma forming zones that will eventually blend together and disappear as disease progresses
What is the difference between marginal zone cells and small lymphocytes?
Marginal zone - more cytoplasm so nuclei are pushed apart more - looks paler –> sometimes these cells get into blood
Small lymphocytes - less cytoplasm, look darker
What can you see in MALT lymphoma?
- Tumors/growths in GI tract (seen with endoscopy)
- Lymphoepithelial lesions (lymphocytes start invading/chewing into the epithelium - malignant!!)
What happens if you treat MALT lymphoma at an early stage with antibiotics?
Lymphoma goes away - one of the only neoplasms associated with a bacteria!
What things MUST you know about mantle cell lymphoma?(EXAM)
- BORING
- Mantle zone pattern
- Small angulated lymphocytes
- t(11;14)-EXAM!! - bcl-1 and IgH
- More aggressive
What translocation is associated with AML-M3?
t(15;17)
What is bcl-1?
Same thing as cyclin D1.It allows cell to get through the cel cycle. If you put this by an Ig heavy chain gene, you can get an over proliferation!
Where is mantle cell lymphoma in a slide? What do mantle zone lymphoma cells tend to look like?
- It’s the mantle surrounding a benign germinal center
- Small, irregular, dark with very little cytoplasm (tend to be angulated
What MUST you know about follicular lymphoma?
- Follicular pattern (later diffuse)
- Small cleaved cell, mixed or large cell (because of the development through the germinal center)
- Grade 1, 2, 3
- t(14;18) - IgH and bcl-2
- Will see small cells with deep cleft in the middle =
What will you see in grade 3 follicular lymphoma?
Small cells with a deep cleft in the middle
What does follicular lymphoma look like: in lymph nodes, on slide, in spleen?
Lymph Node -Fish-flesh appearance & feeling -Has round white areas = lymphoma follicles on node Slide -Many follicles, about the same size -Very close together Spleen -Can see some reddish/splenic tissue -Follicular pattern still seen
What do you see in the blood of follicular lymphoma (EXAM!!)?
“Butt cells” - must investigate if you ever see these!
Where does follicular lymphoma aggregate in the bone marrow?
Right next to the trabecule, cells are closer together (paratrabecular aggregates)
-Many CD20/B cells
What are B symptoms?
Weight loss, night sweats, fever
What MUST you know about mycosis fungicides/Sezary Syndrome? (EXAM!!)
Sezary = leukemia type!
- Skin lesions
- Blood involvement
- Cerebriform lymphocytes (look like little brains)
- T-cell immunophenotype
What is the disease progression for Mycosis fungicides/Sezary syndrome?
- It starts as flat, localized lesions
- Then can progress to Erythroderma = skin very red, scaly, involves entire body
- Then, it can raise into a plaque and then a nodule (this is where the mushroom related name comes from) - red, violacius, purple in color
- Can cause very rarely = lionie faces
What two things will you see in a stain of mycosis fungicides?
- Pautrier microabscess - lymphocytes in weird, irregular shape
- Sezary cells - have deep cleft, two hemispheres, outside of cytoplasm is irregular (not smooth), cerebriform appearance of the nucleus
What things MUST you know about Diffuse Large-Cell Lymphoma?
- Large B cells - almost always B cell in nature
- Extranodal involvement (move around quickly!)
- Grows rapidly - more aggressive this way
- Bad prognosis!
What does Diffuse Large-Cell Lymphoma look like on a slide?
- No follicles, completely effaced, has gone through capsule, diffuse pattern, icky-looking, large cells
- Cell type doesn’t change prognosis
What MUST you know about lymphoblastic lymphoma?
- Two types: B and T
- Lymphoblasts in diffuse pattern
- Same as ALL!
- T-lymphoblastic lymphoma often in teenage male with mediastinal mass (relating to thymus!) - THINK T’S
- Mass shows up on chest x-ray
- T-lymphoblastic lymphoma = T-cell ALL
What does Lymphoblastic Lymphoma look like on a slide?
- Goes through capsule out into fat (diffuse)
- Chromatin pattern is open, dark, smudgy
- In T-cell you see two populations of cells
- In B-cell you see one population of cells (all cells look pretty similar)
What things MUST you know about Burkitt Lymphoma (EXAM!!)?
- Child with fast-growing, extra nodal mass
- Starry-sky pattern - NEED TO KNOW FOR EXAM
- t(8;14)
- Same as Burkitt Leukemia
- African type (jaw) and non-african type (abdominal mass) - grows so fast you can see the growth day to day
What is happening in the starry-sky pattern with Burkitt Lymphoma?
- Cells turning over really fast, making a lot of ‘junk’
- Tingible body macrophages then eat the debris/leftovers
What do odd cells look like in Burkitt Leukemia/Lymphoma?
- Always perfectly round, cobalt blue cytoplasm
- Very discrete, punched out vacuoles in cytoplasm
- Dark, purple nucleus
What things must you know about Adult T-Cell Leukemia/Lymphoma?
- Japan/Caribbean basin
- HTLV-1 (present in almost all cases)
- Skin lesions, hypercalcemia (may or may not have bone marrow involvement - may get kidney stones)
- Very aggressive
What do the nuclei look like in T-cell leukemia/lymphoma?
-Flower-shape nuclei, deep clefts that go in and reach to the middle of the nucleus
