Lymphoid Histology and B Cell Lymphomas Flashcards Preview

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Flashcards in Lymphoid Histology and B Cell Lymphomas Deck (30):
1

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

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

2

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

B cells (surface) and plasma cells (cytoplasmic)

3

What is CD20 a marker for?

most B cells

4

What is PAX5 a marker for?

most B cells

5

What is CD3 a marker for?

all T cells

6

What are some characteristics of benign follicles?

variable follicles, polarized, mantle zone intact

7

What are some characteristics of neoplastic follicles?

follicles crowded, loss of polarity, mantle zone attenuated

8

What are some important immunohistochemical marker patterns in neoplastic cells?

  • Abnormal immunoarchitecture
    • CD20 outside of follicles
  • Aberrant expression of proteins
    • expression of BCL-2 in neoplastic germinal centers in follicular lymphoma with t(14;18)

9

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

kappa light chain restriction (high predominance of kappa cells)

10

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

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

11

What is the WHO classification of lymphomas?

  • Non-Hodgkin Lymphomas - classified based on cell of origin and stage of development
    • B cell type (precursor, mature)
    • T/NK cell type (precursor, mature)
  • Hodgkin Lymphoma
    • nodular lymphocyte predominant
    • classical

12

What are the most common adult Non-Hodgkin lymphomas?

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

13

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

  • Burkitt (40%)
  • Lymphoblastic T or B (30%)

14

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

  • Large, atypical, aggressive
  • Large cells tend to proliferate locally
  • Results in distinct nodules/masses

15

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

  • Small, bland cells - indolent
  • Small cells tend to disseminate widely

16

Describe the diagnostic process of malignant lymphomas.

  • Non-invasive
    • physical exam
    • radiographic studies: x-rays, CT-scans, MRI
  • Invasive
    • bone marrow biopsy
    • biopsies of suspected involvement
  • Surgical
    • laparotomy/splenectomy

17

What is the Ann Arbor staging system for lymphomas?

  • Stage I
    • Single lymph node region or extranodal site (IE) 
  • Stage II
    • 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
  • Stage III
    • Lymph node regions (or extranodal sites and lymph nodes; IIIE) on both sides of the diaphragm
  • Stage IV
    • Any previous with additional extranodal site or two or more extranodal sites with lymph nodes
  • A = no symptoms, B = symptoms

18

What are the clinical characteristics of follicular lymphomas

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

19

What is the grading of follicular lymphomas?

  • Grade I: Mostly centrocytes 
  • Grade II: Mixed centrocytes and centroblasts 
  • Grade III: Mostly centroblasts

20

What are the histological findings of follicular lymphomas?

  • Follicular growth pattern: recapitulates normal reactive follicles
  • Phenotype
    • recapitulates normal GC cells
      • B antigens +
      • CD10+
      • BCL6+
      • CD21+
      • FDC meshworks

21

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

22

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

  • Occurs in any age group (even children)
  • Presents in nodal and extra-nodal sites
  • Often localized disease
  • Aggressive

23

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 

24

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

25

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

26

What is the immunohistochemical phenotype of chronic CLL/SLL?

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

27

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 

28

What types of lymphoma can CLL/SLL transform into?

DLBCL and Hodgkin lymphoma

29

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)

30

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

  • Patterns:
    • Mantle zone pattern
    • Nodular pattern
    • Diffuse pattern