Non-Hodgkins Lymphoma Pathology Flashcards
Normal lymph node
What is the “dark zone” of the lymph node?
area that is reacting to Ag → centroblasts are undergoing proliferation, somatic mutation & isotype switching
Centrocytes
small cleaved lymphocytes exhibiting surface Ab in the light zone
(centroblasts are in the dark zone)
mantle zone of lymph node contains _____
naive b-cells
Marginal zone (just outside mantle zone) contains ______ (2)
- naive B-cell
- memory B-cells
(they’re just chillin’)
Ki67 role in dx
proliferation marker for lymph follicle
(proliferation may be normal, but it can aid in dx)
Non-Hodgkin’s Lymphoma (malignant lymphoma) arises within the _____.
lymph nodes, not in bone marrow (can metastasize there though)
(or other organs rich in lymphoid tissue; leukemias arise in bone marrow and metastasize to lymph nodes. “leukemia/lymphoma” used when we aren’t sure where it started first)
Neoplastic cells are monoclonal, how can we tell if the cells (T cell or B cells) are monoclonal?
- B cells: light chain restriction
- T cells: TCR arrangement
CD5+ is a good dx marker for which 2 N-H lymphomas?
- SLL/CLL
- Mantle
(Rules out follicular and marginal zone)
Hodgkin’s Lymphoma (malignant lymphoma) risk factors (3)
- Immunodeficiency
- Chronic autoimmune diz
- Chronic infections
(immune system being overly stimulated)
2 Clinical findings of Non-Hodgkin’s Lymphoma (malignant lymphoma)
- painless lymphadenopathy
- B-type sx: fatigue, fever, wt. loss, night sweats
(may have extranodal sx if metastasized: abdominal pain, rash, sensorimotor, chest pain)
Low-grade lymphoma is well differentiated tumor; High-grade is a poorly differentiated tumor. Which has the better prognosis?
Low-grade
(low grade: painless lymphadenopathy, no B-symptoms; high-grade is the opposite)
Hodgkin’s lymphoma staging is the similar as leukemia. What is the general staging?
1: 1 lymph node involved or single extranodal site
1B: + systemic sx (B-sx)
2: 2+ lymph nodes on same side of diaphragm
3: both sides of diaphragm
4: extranodal involvement, both sides of diaphragm
How do you tell the difference between benign and malignant lymph node changes?
- malignant: painful
- benign: gets better, goes down
(bx to confirm)
What is the main finding that indicates a benign reactive changes (hyperplastic) of lymph nodes?
interfollicular area (spaces btwn follicles)
(mantle zone, dark/light zones present)
What is the most important immunophenotypic finding of benign changes to the lymph node?
bcl-2 negative (anti-apoptotic protein) in the follicle
(CD3+, CD20+ cells present)
Why is this a neoplastic follicle (2)?
- loss of zonal definition w/absent mantle zone (loss of polarity)
- No tingible body MF
MC form of adult indolent NHL?
follicular lymphoma
Mutation in follicular lymphoma (type of NHL)
t(14;18) → BCL-IgH fusion gene
(anti-apoptotic effect)
Key terms of histopathology that indicate follicular lymphoma?
- atypical lymphocyte
- cleaved v. non-cleaved
(more importantly, look for cytogenetics and immunophenotype)
MC type of NHL?
diffuse large B-cell lymphoma (also MC adult NHL)
Diffuse Large B-Cell lymphoma may arise from which two hematologic cancers?
- Follicular lymphoma
- CLL→Richter transformation
dx?
(left: intermediate power; right: high power)
Diffuse B-cell Lymphoma (high grade tumor)
(any lymph node may be affected)
What does this tell you?
CD10 is a malignant marker
(found in Burkitt lymphoma, follicular & diffuse large b-cell. Next you need to determine cytogenetics)
CD10+, CD19+, CD20+ w/Surface Ig + (light chain restriction) and a BCL6 rearrangement of 3q27 indicates which hematologic cancer?
diffuse large B cell lymphoma
(bcl-2 t(11;14) is 2nd MC)
Diffuse B cell Lymphoma is most common in which demographic?
~ 60 y/o men
Diffuse B-cell Lymphoma typically appears w/ a rapidly growing ______.
mass (nodal or extra nodal)
Waldeyer ring, liver/spleen or skin are common locations of _____ in diffuse b-cell lymphoma
rapidly growing mass that appears
Untreated, diffuse B-cell lymphoma prognosis
- ~55% survive 5 years w/treatment (rituximab)
- rapidly fatal w/o treatment (<1 year) → intensive chemo
What is a dangerous side effect of chemotherapy when treating aggressive cancer?
tumor lysis syndrome: electrolyte dump from the dying cells
(hypercalcemia, hyperkalemia)
Why is this follicular lymphoma (2)?
- follicular enlargement of different sizes and shapes
- decreased interfollicular spacing
Follicular lymphoma is a ______-grade tumor
low
The majority of follicular lymphoma have extranodal involvement, such as ______(4)
- bone marrow
- spleen
- liver, GI
- CNS
(note DLBCL does NOT involve bone marrow until late course)
Bone marrow bx in follicular lymphoma will show ______
paratrabecular lymphoid aggregates
Any time there is a B-cell malignancy you may see _____ (3).
- Autoimmune hemolytic anemia
- thrombocytopenia
- M-spike
(paraproteins from clonal cells → hemolytic anemia or M-spike)
Both follicular lymphoma, DLBCL, and Mantle Cell lymphoma present at _____ stage
III/IV
_______ presents as waxing and waning with painless lymphadenopathy in older adults.
Follicular lymphoma
How can you tell a follicular lymphoma apart from benign changes in the lymph node?
benign changes will be CD5(-)
(and CD43(-); both may be nodular)
_______ are the only 3 lymphomas that are CD5+.
- Mantle cell
- CLL/SLL
- Hairy cell
(mantle cell is CD23(-); CLL/SLL are CD23+)
Both DLBCL, FL & Mantle Cell Lymphoma have SIg+ with light chain restriction. Which has IgM w/or w/o IgD?
FL
Mantle cell (NHL) is CD23(-); CLL/SLL are CD23+. What is one other distinguishing factor between them?
Mantle cell has NO proliferation centers
(lymphoblastic lymphomas have homogenous proliferation cells)
CD5+, CD10- distinguishes Mantle Cell Lymphoma from ______
follicular (which is CD10+)
CD5+, CD10- distinguishes Mantle Cell Lymphoma from ______
follicular
Mutation t(11;14) → cylinD1-IgH fusion indicates ______
Mantle Cell Lymphoma
(this allows bypass of normal G1-S phase regulation)
Mantle cell lymphoma has a good short-term prognosis, but poor long-term without _____
bone marrow transplant
(usually causes organ failure)
What is a “blastoid variant” of mantle cell lymphoma?
proliferative profile (even worse prognosis)
Mantle cell lymphoma involves _____ cells, this is the reason why there is no somatic hypermutation.
naive B cells
(in contrast to Marginal Zone Lymphoma, which involves mature B cells)
_______ presents as a disseminated disease in older males.
(hint: may also involve GI polyps)
Mantle cell lymphoma
t(11;18) mutation, MALTomas (80% of cases) & chronic inflammation are diagnostic features of ______.
marginal zone lymphoma
(mature B cells; also lack of other markers you would expect to see)
Chronic inflammation of _______3 glands can lead to Marginal zone lymphoma.
- stomach (H.pylori or celiac)
- salivary (Sjogren’s)
- thyroid (Hashimoto’s)
(may regress if this inflammation is cured, i.e. abx)
(stomach tissue)
MALToma: effacement by malignant lymphocytes
(will produce GI sx: nausea, anorexia, pain)
(stomach
effacement by malignant lymphocytes
CD19/20/10+, BL6, “starry sky” histology and failure to express BCL-2 is diagnostic of ______
Burkitt lymphoma (the fastest growing human tumor)
(also EBV association)
“starry sky” describes _____
histology of burkitt lymphoma: tingible MF phagocytizing apoptotic debris
“tingible body” macrophage
Burkitt lymphoma: vacuoles + deep blue cytoplasm
t(___;___) → _____ fusion is present in the majority of Burkitt lymphoma cases
t(8;14) → MYC-IgH
(this leads to the Warburg effect)
All cases of African/endemic Burkitt lymphoma are from a _____ and primarily affect the _____.
- latent EBV infection
- mandible or small intestine
(very aggressive, mass can appear w/in weeks; fastest growing human tumor)
Sporadic Burkitt lymphoma is a common childhood cancer that is NOT associated with ______ and is commonly located in the _____.
- EBV
- distal ileum and cecum
(African/endemic burkitt is assoc. w/EBV)
EBV & HTLV-1 are associated with which malignancy?
Peripheral T cell Lymphoma
(mature T cells)
CD3+, CD4+ w/diffusely effaced LN & B-symptoms is diagnostic of _______
nodal cell lymphoma
(note: it is CD8(-))