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Heme/Onc > Lymphoid Histology and B Cell Lymphomas > Flashcards

Lymphoid Histology and B Cell Lymphomas Flashcards

1. Describe normal lymph node structure including primary location of the major cell types (MKS 1) 2. Describe how normal lymph node structure/architecture relates to neoplastic lymphoid proliferations (MKS 1) 3. Differentiate the relationship and differences between normal and neoplastic lymphoid cells (MKS 1) 4. Understand that lymphoma is a clinicopathologic entity – describe the morphology, phenotype, genotype and clinical features that are required to correctly classify the disease (SA

1
Q

<p>What are the architectural/functional compartments of the lymph node?</p>

A

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

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2
Q

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

A

<p>B cells (surface) and plasma cells (cytoplasmic)</p>

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3
Q

<p>What is CD20 a marker for?</p>

A

<p>most B cells</p>

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4
Q

<p>What is PAX5 a marker for?</p>

A

<p>most B cells</p>

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5
Q

<p>What is CD3 a marker for?</p>

A

<p>all T cells</p>

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6
Q

<p>What are some characteristics of benign follicles?</p>

A

<p>variable follicles, polarized, mantle zone intact</p>

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7
Q

<p>What are some characteristics of neoplastic follicles?</p>

A

<p>follicles crowded, loss of polarity, mantle zone attenuated</p>

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8
Q

<p>What are some important immunohistochemical marker patterns in neoplastic cells?</p>

A

<ul>
<li><strong>Abnormal&nbsp;immunoarchitecture</strong>

<ul>
<li>CD20 outside of follicles</li>
</ul>
</li>
<li><strong>Aberrant&nbsp;expression of proteins</strong>
<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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9
Q

<p>In CLL, what is a characteristic finding on flow cytometry?</p>

A

<p>kappa light chain restriction (high predominance of kappa cells)</p>

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10
Q

<p>In neoplastic B cell proliferation what is a key&nbsp;findings on PCR in terms of IgH rearrangement?</p>

A

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

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11
Q

<p>What is the WHO classification of lymphomas?</p>

A

<ul>
<li><strong>Non-Hodgkin Lymphomas</strong>&nbsp;- 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><strong>Hodgkin Lymphoma</strong>
<ul>
<li>nodular lymphocyte predominant</li>
<li>classical</li>
</ul>
</li>
</ul>

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12
Q

<p>What are the most common adult Non-Hodgkin&nbsp;lymphomas?</p>

A

<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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13
Q

<p>What are the most common Non-Hodgkin lymphomas found in children?</p>

A

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

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14
Q

<p>What is the pathological presentation of large cell B cell lymphomas?</p>

A

<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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15
Q

<p>What is the pathological presentation of small cell B cell lymphoma?</p>

A

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

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16
Q

<p>Describe the diagnostic process&nbsp;of malignant lymphomas.</p>

A

<ul>
<li><strong>Non-invasive</strong>

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

17
Q

<p>What is the Ann Arbor staging system for lymphomas?</p>

A

<ul>
<li><strong>Stage I</strong>

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

18
Q

<p>What are the clinical characteristics of follicular lymphomas</p>

A

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

19
Q

<p>What is the grading of follicular lymphomas?</p>

A

<ul>
<li><strong>Grade I</strong>:&nbsp;Mostly centrocytes&nbsp;</li>
<li><strong>Grade II</strong>:&nbsp;Mixed centrocytes and centroblasts&nbsp;</li>
<li><strong>Grade III</strong>:&nbsp;Mostly centroblasts</li>
</ul>

20
Q

<p>What are the histological findings of follicular lymphomas?</p>

A

<ul>
<li><strong>Follicular growth pattern</strong>: recapitulates normal reactive follicles</li>
<li><strong>Phenotype</strong>
<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>

21
Q

<p>What are some common genetic findings of follicular lymphomas?</p>

A

<p><strong>t(14;18)</strong> in 80% of grade 1-2 follicular lymphoma BCL6 rearrangements in 5-15% of FL,&nbsp;most&nbsp;commonly in <strong>grade 3</strong></p>

22
Q

<p>What are the clinical findings of diffuse large&nbsp;B cell lymphomas?</p>

A

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

23
Q

<p>What are the histological findings of diffuse&nbsp;large B cell lymphomas?</p>

A

<p>Diffuse growth pattern Different cell origins -&nbsp;any large transformed</p>

<p>B cell&nbsp;Monotypic s/c Ig</p>

<p>High mitotic activity&nbsp;</p>

24
Q

<p>What are the important determinants of prognosis for diffuse large cell lymphoma?</p>

A

<p>GC vs non-GC (Prior to Rituxan)&nbsp;</p>

<p>GC better&nbsp;</p>

<p>Non-GC:&nbsp;NFkB/Rel pathway inhibitors</p>

<p>GC:&nbsp;BCL6 inhibitors</p>

<p>Ongoing clinical trials to evaluate DLBCL , COO, response to different therapies</p>

25
Q

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

A

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

26
Q

<p>What is the immunohistochemical phenotype of chronic CLL/SLL?</p>

A

<p>Kappa-restricted, <strong>CD5+</strong>, <strong>CD23+</strong>, dim CD79b, dimCD20+, <strong>FMC7-</strong></p>

27
Q

<p>What are the genetics of CLL/SLL?</p>

A

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

28
Q

<p>What types of lymphoma can CLL/SLL transform into?</p>

A

<p>DLBCL and Hodgkin lymphoma</p>

29
Q

<p>What are the clinical findings of mantle cell lymphoma?</p>

A

<ul>
<li>Example of <strong>single distinct entity</strong> based on characteristic immunophenotype and genotype</li>
<li>Considered an <strong>&ldquo;indolent&rdquo; lymphoma</strong>,&nbsp;but has an aggressive clinical behavior</li>
<li>Most people present with <strong>stage III or IV disease</strong> (lymphadenopathy, PB or BM involvement)</li>
</ul>

30
Q

<p>What are the histologic findings and immunohistochemical markers&nbsp;of mantle cell lymphoma?</p>

A

<ul>
<li><strong>Patterns</strong>:

<ul>
<li>Mantle zone pattern</li>
<li>Nodular pattern</li>
<li>Diffuse pattern</li>
</ul>
</li>
</ul>

Heme/Onc (50 decks)

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