WBC & Lymph nodes, Part 5: Lymphomas Flashcards
lymphomas are classified into what 2 types?
- Non- Hodgkin Lymphoma (NHL)
- Hodgkin Lymphoma (HL)
what are the B-cell lymphomas found in the non-Hodgkin Lymphoma ?
- Follicular Lymphoma
- Diffuse Large B-cell Lymphoma (DLBCL)
- Burkitt Lymphoma
- Mantle cell Lymphoma
- Marginal zone Lymphoma
what are the T-cell lymphomas found in the non-Hodgkin Lymphoma ?
Anaplastic Large-cell Lymphoma
What are the sub-types found in Hodgkin Lymphoma?
- Nodular sclerosis
- Mixed cellularity
- Lymphocyte rich
- Lymphocyte depletion
- Lymphocyte predominant
Follicular Lymphoma
- how common is it?
- what is its incidence?
- what is its pathogenesis?
- common type of lymphoma
- middle aged, males and females
- Pathogenesis:
- t(14;18) causing overexpression of BCL-2 so it causes inhibition of apoptosis, therefore these cells keep proliferating
Follicular lymphoma Labs
- CBC?
- Lymph node biopsy?
- What organ is mainly involved?
- What other organs are involved?
- Immunophenotype of tumor?
- What other investiagion can be used?
- normal
- loss of cell architecture, there is follicle-like pattern, stains positive for BCL-2
- Bone Marrow
- Liver and Spleen
- tumor expresses CD10, CD19, CD20,
- CT scan
what is this?
Follicular lymphoma
what will you notice about a microscopy of a lymph node with follicular lymphoma?
- numerous follicle-like structures
- absence of germinal centers
- absence of tingible body macrophages
what is this?
follicular hyperplasia
Follicular Lymphoma
what are the clinical features?
is it curable?
what is the median survival rate?
- painless generalized lymphadenopathy
- about 10% of patients present with B symptoms (fever, drenching night sweats, or loss of 10% of the body weight)
- disease usually is widespread at presentation, with involvement of multiple lymph node, liver, and spleen
- bone marrow is involvement seen
- incurable, but has an indolent course
- median survival: 7 to 9 years
Follicular Lymphoma
into what can follicular lymphoma transform?
what is the prognosis after transformation?
to “diffuse large B cell lymphoma”
poor prognosis with transformation
Diffuse large B cell lymphoma
- on who is it seen?
- how aggresive is it?
- what may it involve?
- what are its special sub-types?
- what are the molecular genetics at play here?
- any age group, but mostly middle-age
- aggressive
- may involve ‘extra-nodal’ sites (example: GIT, liver, brain)
- Special subtypes:
Immunodeficiency associated (bone marrow transplantation/advanced HIV infection)
Primary Effusion Lymphoma (PEL). Seen mostly in advanced HIV infection
- dysregulation of BCL-6 (this is normally required for the formation of normal germinal centers)
Diffuse large B cell lymphoma
CBC?
Bone Marrow?
Serology?
LDH?
CT scan?
flow cytometry?
CBC= normal
Bone Marrow = involved in late disease
Serology = HIV
LDH = increased due to increased tumor burden
CT scan = abdominal lymph nodes
flow cytometry = Diagnosis is based on tissue biopsy:
- Lymph node/tissue morphology
- presence of large lymphoid cells
- immunophenotype: CD19, CD20
- surface Ig is seen
- negative for TdT
what is this?
Diffuse large B-cell lymphoma: lymph node contains large cells with enlarged nuclei, open chromatin, and prominent nucleoli
what does this aspiration cytology reveal?
does this stain positive for? what will it stain negative for?
Primary Effusion Lymphoma (PEL) with large pleomorphic cell
stain positive for immunoglobulin
stain negative for cytokeratin
Diffuse Large B cell Lymphoma
what is the clinical presentation?
what do you use for therapy?
where can nodes arise as well?
when is bone marrow involved?
- rapidly enlarging lymph nodes at single nodal site or extra nodal site where aggressive tumors appear
- adjuvant therapy with anti-CD20 antibody
- extra nodal: GIT, skin, brain
- bone marrow involvement is late
Burkitt Lymphoma
what are the 3 types?
with what diseases are each associated?
- African (endemic): malaria or EBV
- Sporadic (non endemic): large abdominal masses
- Aggressive form: associated with HIV
Burkitt Lymphoma
African (endemic) type:
- in what age group do we see it?
- what are the clinical features we find in it?
- what immunophenotype do we see in the tumor?
- what translocation do we see here?
- children, young adult
- Clinical features:
- extra-nodal
- common location: mandible, abdominal viscera (kidney, ovaries, adrenal)
- aggressive, but responds to chemotherapy - CD19, CD20, B-cell expression of IgM
- t(8; 14): myc gene on chromosome 8. The myc (transcriptional promoter) is relocated adjacent to strong Ig promoter and enhancer which drive increased myc expression
what is this?
Burkitt’s lymphoma African (endemic) type
Burkitts Lymphoma
CBC?
Bone Marrow?
The diagnosis for this disease is based on what 2 things?
CBC = normal
B. marrow = barely involved
1) tissue biopsy
2) karyotyping
Burkitts Lymphoma
African (endemic) type:
How do you see it under the microscope?
involved tissues will show what?
as starry sky pattern
diffuse infiltrate of intermediate-sized lymphoid cells
what is this?
burkitts lymphoma - starry sky pattern
what is this?
Mantle Cell Lymphoma
In mantle cell lyphoma, tumors will resemble what?
what can be expected in a lab report for mantle cell lymphoma:
CBC
Bone Marrow
Lymph node biopsy
Immunophenotype
the mantle zone B lymphocytes
CBC = normal
Bone Marrow = involved
Lymph node biopsy = loss of arquitecture, few reactive germinal centers, surrounded by tumor cells
Immunophenotype =
- CD 19/20/5 positive
- CD 23 negative
- cyclin D1 expressed
why is it important that CD23 be tested for in Mantle cell lymphoma?
What are the clinical features of Mantle cell Lymphoma?
how curable is it?
because if negative, we know it is not CLL or SLL
C/F:
- painless lymphadenopathy
- splenomegaly
- Extranodal: Waldeyer ring, and GIT
- GIT = lymphmatoid polyp
by the time the pt seeks treatment it is stage 4 (rarely curable)
what is this?
what can be noted here?
Mantle Cell Lymphoma
LN Biopsy: note the distribution of cyclin D1 positivity around germinal centers.
what is this?
what can be noted here?
Mantle Cell lymphoma
Lymphmatoid polyp: Cyclin D1 positivity (dark brown).
what is Marginal zone lymphoma?
what are the clinical findings for marginal zone lymphoma?
- a distinct B-cell neoplasms with variable clinical features
C/F:
- extra nodal marginal zone MALToma
* stomach, orbit, intestine, lung, thyroid, salivary gland, bladder, CNS - nodal marginal zone lymphoma
- splenic marginal zone lymphoma
Extranodal involvement in Marginal Zone Lymphoma is seen when?
extranodal area involvement will remain involved for how long?
what is the immunophenotype markers that we look for in marginal zone lymphoma?
- in areas involved in chronic inflammation by autoimmune or infectious etiology
- (Sjörgen syndrome, Hashimoto’s thyroiditis, Helicobacter pylori)
- long time
- B cell markers: CD19, CD20
how do MALTomas begin as in Marginal Zone Lymphoma?
MALTomas begin as polyclonal immune reactions and later acquire an initiating mutation in the B-cell clone
- as these cells divide more mutations are gained which will make these cells autonomous
- NF-kB activation promotes growth and survival
what is this?
Marginal Zone Lymphoma
eradication of Helicobacter pylori in Marginal Zone Lymphoma will results in what?
tumor regression in gastric MALTomas
what is this?
what immunostain is being used here?
H. pylori infection from gastric MALToma
CD19
Anaplastic Large-cell Lymphoma is what type of lymphoma?
why does it happen?
it is a T cell lymphoma
re-arrangement in ALK gene (2p23) leading to JAK/STAT pathway activation
what can we expect in a skin biopsy in Anaplastic Large-cell lypmhoma?
what can we expect in a Lymph Node biopsy in Anaplastic Large-cell lypmhoma?
why is the prognosis good?
- infiltrates of large anaplastic cells with horseshoe nuclei (hallmark cells)
- loss of architecture, large anaplastic cells, “hallmark” or “doughnut” cells positive for CD30 (Ki-1)
- because it is a T-cell malignancy
what is this?
Anaplastic Large-cell Lymphoma in Lymph node: loss of architecture, note giant cells (hallmark cells)
what is this?
Lymph node Anaplastic Large-cell Lymphoma
what characterizes Hodgkins lymphoma?
on who does it happen more oftenly?
how do you describe the Reed-Sternberg cell?
Reed-Sternberg cell: residing in a mixed infiltrate of non-neoplastic cells
mostly young adults
Reed-Sternberg cell has a bilobed nucleus with prominent eosinophilic nucleoli separated by a clear space from the thickened nuclear membrane
what is the pathogenesis of Hodgkin’s Lymphoma?
- IgG genes of Reed Sternberg cells have undergo V(D)J recombination and somatic hypermutation in germinal/post-germinal center in B cells
- RS cell fail to express most B-cell specific markers
- NF-kB activation is seen
- helps these abnormal RS from being removed through apoptosis
- NF-kB activation is seen
- RS cells produces cytokines (IL-5, IL-10, 1L-13, & TGF-β),
- which creates a reactive response in the surrounding cells
what are the classifications of Hodgkins lymphoma?
what is the prognosis for each?
- Nodular sclerosis (good prognosis)
- Mixed cellularity
- Lymphocyte rich (good prognosis)
- Lymphocyte depletion (poor prognosis)
- Lymphocyte predominant
what is the most common form of Hodgkin’s lymphoma?
nodular sclerosis Hodgkin’s lymphoma
nodular sclerosis hodgkin lymphoma involves usually what areas?
what Reed Steinberg cell variant do we see here?
How does nodular sclerosis hodgkin lymphoma look like?
- frequent involvement of the lower cervical, supraclavicular, and mediastinal lymph nodes
- ‘lacunar cell’
- fibrous bands, going around the lymph node into nodular areas, ‘lacunar RS cells’ are seen in a reactive background composed of T-cells, eosinophils, plasma cells, macrophages
what can we see if we do immunophenotyping in nodular sclerosis hodgkin lymphoma?
what areas are the most commonly involved in nodular sclerosis hodgkin lymphoma?
CD15, CD30 positive
lower cervical, supra clavicular and mediastinal lymph nodes
what is this?
Hodgkin lymphoma Lymph Node Biopsy: Lacunar variant cells (arrow) are seen within spaces created by tearing away of the wispy cytoplasm during tissue sectioning
what is the clinical course of hodgkin lymphoma?
Clinical course:
- painless lymph node enlargement of neck, supraclavicular, axilla, mediastinal lymph nodes in 50% at the time of diagnosis
- fevers, night sweats, and/or weight loss
- fever: Pel-Epstein fever
- fevers persist for days to weeks, followed by afebrile intervals and then recurrence
- fever: Pel-Epstein fever
Hodgkin Lymphoma long term survivors of chemotherapy, and radiotherapy have an increased risk for whatsecond malignancy?
AML in the setting of MDS, lung cancers, and breast cancers
