Lymphoid Histology and B Cell Lymphomas Flashcards by Jing Ji

What are the architectural/functional compartments of the lymph node?

<ul>
<li>Follicle
<ul>
<li>Mantle zone: naive cells meet antigen</li>
<li>Germinal center:
<ul>
<li>proliferating cells (centroblasts) differentiate into antigen-specific B cells (centrocytes)</li>
</ul>
</li>
</ul>
</li>
<li>Marginal Zone
<ul>
<li>memory B cells</li>
</ul>
</li>
<li>Medulla
<ul>
<li>B cell area: accumulation of plasma cells</li>
<li>Mainly T cell area</li>
</ul>
</li>
<li>Paracortex
<ul>
<li>site of entrance to all lymphoid cells and of accessory cells - T/B cell interaction</li>
</ul>
</li>
<li>Sinus
<ul>
<li>Macrophage area - "seive" functions</li>
</ul>
</li>
</ul>

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What does Ig (kappa/gamma) a marker for?

B cells (surface) and plasma cells (cytoplasmic)

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What is CD20 a marker for?

most B cells

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What is PAX5 a marker for?

most B cells

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What is CD3 a marker for?

all T cells

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What are some characteristics of benign follicles?

variable follicles, polarized, mantle zone intact

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What are some characteristics of neoplastic follicles?

follicles crowded, loss of polarity, mantle zone attenuated

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What are some important immunohistochemical marker patterns in neoplastic cells?

<ul>
<li>Abnormal immunoarchitecture

<ul>
<li>CD20 outside of follicles</li>
</ul>
</li>
<li>Aberrant expression of proteins
<ul>
<li>expression of BCL-2 in neoplastic germinal centers in follicular lymphoma with t(14;18)</li>
</ul>
</li>
</ul>

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In CLL, what is a characteristic finding on flow cytometry?

kappa light chain restriction (high predominance of kappa cells)

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In neoplastic B cell proliferation what is a key findings on PCR in terms of IgH rearrangement?

<ul>
<li>IgH rearrangement is a random event in normal cells, and there are fragments of random sizes</li>
<li>In B cel lymphoma, will see a single band beause of common progenitor</li>
</ul>

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What is the WHO classification of lymphomas?

<ul>
<li>Non-Hodgkin Lymphomas - classified based on cell of origin and stage of development

<ul>
<li>B cell type (precursor, mature)</li>
<li>T/NK cell type (precursor, mature)</li>
</ul>
</li>
<li>Hodgkin Lymphoma
<ul>
<li>nodular lymphocyte predominant</li>
<li>classical</li>
</ul>
</li>
</ul>

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What are the most common adult Non-Hodgkin lymphomas?

<ul>
<li>SLL/CLL</li>
<li>Mantle</li>
<li>Follicular lymphoma</li>
<li>Marginal zone/MALT</li>
<li>Diffuse large B cell (most common)</li>
<li>Peripheral T Cell, NOS</li>
</ul>

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What are the most common Non-Hodgkin lymphomas found in children?

<ul>
<li>Burkitt (40%)</li>
<li>Lymphoblastic T or B (30%)</li>
</ul>

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What is the pathological presentation of large cell B cell lymphomas?

<ul>
<li>Large, atypical, aggressive</li>
<li>Large cells tend to proliferate locally</li>
<li>Results in distinct nodules/masses</li>
</ul>

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What is the pathological presentation of small cell B cell lymphoma?

<ul>
<li>Small, bland cells - indolent</li>
<li>Small cells tend to disseminate widely</li>
</ul>

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Describe the diagnostic process of malignant lymphomas.

<ul>
<li>Non-invasive

<ul>
<li>physical exam</li>
<li>radiographic studies: x-rays, CT-scans, MRI</li>
</ul>
</li>
<li>Invasive
<ul>
<li>bone marrow biopsy</li>
<li>biopsies of suspected involvement</li>
</ul>
</li>
<li>Surgical
<ul>
<li>laparotomy/splenectomy</li>
</ul>
</li>
</ul>

What is the Ann Arbor staging system for lymphomas?

<ul>
<li>Stage I

<ul>
<li>Single lymph node region or extranodal site (IE) </li>
</ul>
</li>
<li>Stage II
<ul>
<li>Two or more lymph node regions (or one extra-nodal site and one or more lymph node regions; IIE), on the same side of diaphragm</li>
</ul>
</li>
<li>Stage III
<ul>
<li>Lymph node regions (or extranodal sites and lymph nodes; IIIE) on both sides of the diaphragm</li>
</ul>
</li>
<li>Stage IV
<ul>
<li>Any previous with additional extranodal site or two or more extranodal sites with lymph nodes</li>
</ul>
</li>
<li>A = no symptoms, B = symptoms</li>
</ul>

What are the clinical characteristics of follicular lymphomas

<ul>
<li>Older individuals; rare in children</li>
<li>Lymphadenopathy and disseminated disease (80% with stage III-IV disease), but asymptomatic</li>
<li>Most grade I or II (low grade) - indolent
<ul>
<li>10-60% transform to diffuse large cell lymphoma</li>
</ul>
</li>
<li>Long survival (grade 1-2), but not curable</li>
</ul>

What is the grading of follicular lymphomas?

<ul>
<li>Grade I: Mostly centrocytes </li>
<li>Grade II: Mixed centrocytes and centroblasts </li>
<li>Grade III: Mostly centroblasts</li>
</ul>

What are the histological findings of follicular lymphomas?

<ul>
<li>Follicular growth pattern: recapitulates normal reactive follicles</li>
<li>Phenotype
<ul>
<li>recapitulates normal GC cells
<ul>
<li>B antigens +</li>
<li>CD10+</li>
<li>BCL6+</li>
<li>CD21+</li>
<li>FDC meshworks</li>
</ul>
</li>
</ul>
</li>
</ul>

What are some common genetic findings of follicular lymphomas?

t(14;18) in 80% of grade 1-2 follicular lymphoma BCL6 rearrangements in 5-15% of FL, most commonly in grade 3

What are the clinical findings of diffuse large B cell lymphomas?

<ul>
<li>Occurs in any age group (even children)</li>
<li>Presents in nodal and extra-nodal sites</li>
<li>Often localized disease</li>
<li>Aggressive</li>
</ul>

What are the histological findings of diffuse large B cell lymphomas?

Diffuse growth pattern Different cell origins - any large transformed

B cell Monotypic s/c Ig

High mitotic activity

What are the important determinants of prognosis for diffuse large cell lymphoma?

GC vs non-GC (Prior to Rituxan)

GC better

Non-GC: NFkB/Rel pathway inhibitors

GC: BCL6 inhibitors

Ongoing clinical trials to evaluate DLBCL , COO, response to different therapies

What are the clinical findings of chronic lymphocytic leukemia/small lymphocytic lymphoma?

Most common leukemia of adults in western countries ~7% of non-Hodgkin lymphomas
Sites of involvement: Blood, BM, Lymph node
In the absence of EM/tissue involvement, must be >5x109/L monoclonal lymphocytes

What is the immunohistochemical phenotype of chronic CLL/SLL?

Kappa-restricted, CD5+, CD23+, dim CD79b, dimCD20+, FMC7-

What are the genetics of CLL/SLL?

Has the highest family predisposition among all hematopoietic neoplasms (5-10%)
IGH mutation:
- Mutated (post-GC; memory)
- Unmutated (pre-GC, ?naive) - worse prognosis
Surrogate markers:
- ZAP-70: 20% discordant, independent prognostic factor CD38
Chromosomal abnormalities (FISH)
- Most common:
  - 13q deletion
- Favorable prognosis:
  - 13q deletion (?miRNA)
- Poor prognosis:
  - Del (11q22): ATM
  - Del (17p13): p53

What types of lymphoma can CLL/SLL transform into?

DLBCL and Hodgkin lymphoma

What are the clinical findings of mantle cell lymphoma?

Example of single distinct entity based on characteristic immunophenotype and genotype
Considered an “indolent” lymphoma, but has an aggressive clinical behavior
Most people present with stage III or IV disease (lymphadenopathy, PB or BM involvement)

What are the histologic findings and immunohistochemical markers of mantle cell lymphoma?

Patterns:
- Mantle zone pattern
- Nodular pattern
- Diffuse pattern