Lymphomas Flashcards
What is a lymphoma?
A malignancy of lymphoid cells based in lymphoid tissues such as the lymph nodes, spleen, thymus, or MALT. It may involve the marrow and blood secondarily.
B-ALL clinical presentation
Acute Several weeks of fatigue due to anemia Easy bruising due to thrombocytopenia Fever, signs of infection due to neutropenia May have pain in a single long bone, skin involvement
B-ALL workup
Peripheral blood smear: lymphoblasts CBC: anemia, thrombocytopenia, granulocytopenia Bone marrow: lymphoblasts are >20% of marrow cellularity
B-ALL flow cytometry
TdT+ CD19+ CD34+
B-ALL age of peak incidence
3 (FYI this is the time of peak B cell production in the bone marrow)
Does the presence of t(9;22) produce a good or bad prognosis?
Bad
T-ALL peak incidence
15
T-ALL clinical presentation
cough, shortness of breath, superior vena cava
T-ALL clinical presentation
usually presents as a large thymus mass with cough, shortness of breath, superior vena cava syndrome (swelling and redness of face and upper extremities)
T-ALL flow cytometry markers
TdT+ CD 2-8
Are ALLs agressive tumors?
Yup! Treat early, treat fast!
What are B symptoms?
fever night sweats weight loss
Relative to T or NK cells, why are germinal center B cells most likely to give rise to neoplasms?
B cells rely on somatic hypermutation and class switching to function properly. Since their genomes are designed to be able to change, they are also most likely to mutate in a malignant way.
What infections are associated with lymphoid neoplasms?
EBV HHV8 (kaposi sarcoma herpesvirus) HTLV-1 HIV H. pylori
CLL/SLL pathogenesis
Not entirely understood but thought to involve deletions
CLL workup (blood smear, bone marrow, etc)
Blood smear: increased numbers of small round lymphocytes, smudge cells
Bone marrow: aggregates of similar appearing tumor cells
Lymph nodes: diffusely infiltrated by small lymphocytes and patchy collections of larger, mitotically active cells known as proliferation centers.
CBC: lymphocytosis (lymphs > 5000)
CLL clinical presentation
Often asymptomatic
May present with weight loss, fatigue, anorexia, diffuse LAD, or hepatosplenomegaly
CLL flow cytometry
CD 5+
CD 10-
CD 20 +, CD 19+, CD23+
What does this CBC suggest?
CLL
lymphocytosis with everything else fairly normal
CLL
smudge cells
Does CLL always require treatment?
No, approx. 60% of patients with CLL never require treatment.
High lymphocyte count alone is not an indication to start treatment
What’s the significance of chromosome 17 in CLL?
Chromosome 17 is home to the p53 tumor suppressor gene. This is a common target for chemotherapy so CLL with deletions of this gene cannot be treated effectively with conventional chemo. They have a very poor prognosis.
Hairy cell
Hairy cell leukemia
- A tumor of mature B cells expressing CD20 but not CD5 of CD10
- Associated with BRAF mutations
- Often presents with splenomegaly and cytopenia, especially monocytopenia, and infections (especially with mycoplasma)
- Peripheral blood shows “hairy cells”
What’s this?
A healthy lymph node germinal center
What’s this? (Note: this is a low power view)
Lymph node germinal center in diffuse large B cell lymphoma
What’s this? (Note: this is high power)
Lymph node germinal center in diffuse large B cell lymphoma
- large cells with prominent nucleoli
DLBCL pathogenesis
Mutations involving BCL6 which codes for a transcription factor required for the maturation of germinal center B cells.
- lead to survival and continued proliferation of B cells.
- thought to be due to errors in class switching or somatic hypermutation
DLBCL presentation
Can present with B symptoms and LAD or a rapidly enlarging mass
Does DLBCL have an elevated LDH?
Yup.
DLBCL flow cytometry
CD20+
may also express CD10 and surface Ig
Burkitt Lymphoma
- Endemic (Africa): EBV+, jaw mass
- Sporadic (US): may be EBV+, abdominal mass, spreads to the CNS
- Associated with HIV
- Associated with c- MYC gene mutations - t(8;14)
- Express CD20, CD10, BCL6, but not usually BCL2 (distinguishes from DLBCL)
- tissue histology shows “starry sky”
Starry sky
- Pale macrophages in the Burkitt’s lymphoma
Follicular lymphoma pathogenesis
- t(14;18) (plus other mutations)
- causes overexpression of BCL2 which inhibits apoptosis.
- FYI: Normal B cells downregulate BCL2, resulting in the death of cells that don’t produce high affinity Abs. With the overexpression of BCL2, these cells do not die.
Follicular lymphoma lymph node
Nodular growth pattern
Follicular lymphoma peripheral blood
small to intermediate sized cells with cleaved nuclear contours and clumped chromatin
What is a Non-Hodgkin’s Lymphoma anyway?
Any lymphoma that isn’t a Hodgkin’s lymphoma.
What’s going on in Hodgkin’s lymphoma?
Neoplastic cells are in the minority. They secrete cytokines and chemokines that attract inflammatory cells, which make up most of the tumor mass.
Hodgkin Lymphoma subtypes
Classical vs nodular lymphocyte predominant
Classical subtypes:
- Nodular sclerosis
- Mixed cellularity
- Lymphocyte rich
- Lymphocyte depleted
Reed-Sternberg cells
The neoplastic cells of Hodgkin’s lymphoma. They are derived from germinal center B cells and have clonal rearranged immunoglobulin heavy chains that have undergone somatic hypermutation. They express PDL-1 (programmed death ligand 1), inhibiting immune response.
- express CD 15 and CD 30
- Do not express CD20
- “owl eyes”
Nodular sclerosis HL
Reed-Sternberg cell
Characteristic of Hodgkin’s lymphoma
Large highly atypical cells with abundant cytoplasm, one or 2 nuclear lobes, vesicular chromatin, prominent eosinophilic nucleoli
HL clinical presentation
Painless LAD
- In nodular sclerosis subtype, may be in the mediastinum resulting in chest discomfort, cough, dypsnea, and/or SVC syndrome
May have B symptoms
May have itching
HL workup
CBC: leukocytosis, eosinophilia
- may show anemia in chronic state
Lymph node biopsy: Reed Sternberg cell (owl eyes)
Classical HL flow cytometry
CD 20-
CD 15+
CD 30+
