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follicular lymphoma

Monday 24 June 2013

follicular lymphomas; follicular center cell lymphoma

PO

Microscopy

- Nodal architecture effacement by closely packed follicles containing small cleaved cells without nucleoli (centrocytes) and larger non-cleaved cells with moderate cytoplasm, open chromatin and multiple nucleoli (centroblasts)
- Minimal or no apoptotic cells or tingible body macrophages
- Attenuated or absent mantle zones
- Often is interfollicular involvement or capsular infiltration
- Rarely large areas of necrosis, dense fibrous bands

Immunochemistry

- Positive:

  • B-cell markers: CD20+ (strong), CD79a+, CD19+
  • Germinal center phenotype: CD10+, bcl6 (Am J Surg Pathol 2000;24:846)
  • BCL2 surexpression by gene rearrangement: bcl2+ within follicles and nodules

- CD30+ cells in 30% (Arch Pathol Lab Med 2001;125:1036)
- Variable surface immunoglobulin (intense in bone marrow)

- CD0+/-

  • CD10 frequently is weak/negative in interfollicular infiltrates and in grade III follicular lymphomas (Am J Clin Pathol 2001;115:862)
  • CD10 is sensitive and specific for follicular lymphoma among small B cell lymphomas in multiparameter flow cytometry (Am J Clin Pathol 2002;117:291)

Patterns

- Diffuse pattern

  • defined as complete absence of CD21/CD23 positive follicular dendritic cells;
  • usually centrocyte-type cells;
  • follicular areas present in larger biopsy specimens;
  • same staining and molecular patterns as classic follicular lymphoma, but histologically may resemble mantle cell lymphoma

- Floral pattern (not a diagnostic term)

  • nodules are surrounded and infiltrated by small lymphocytes of the follicular mantle, resulting in an unusual serrated configuration that resembles progressive transformation of germinal centers and lymphocyte predominance Hodgkin lymphoma;
  • occasionally CD5 positive, but usually CD10 positive with bcl2 rearrangement (Am J Clin Pathol 2000;114:912)

- Incipient

  • monoclonal proliferation of germinal center cells within a lymph node follicle that is also immunoreactive for B cell antigens, CD10, bcl6 and bcl2 with IgH rearrangement (Hum Pathol 2001;32:1410)

- With marginal zone differentiation

  • tumors are primary follicular cell (not primary marginal zone) since bcl2 immunoreactive, have t(14;18) and are same clone as follicular center cell (Mod Pathol 2001;14:191)

Bone marrow

- Usually paratrabecular involvement by CD20+ CD10+ bcl2+ cells;
- rarely (5%) has follicular pattern (Am J Clin Pathol 2002;118:780);
- may recapitulate neoplastic follicle or have “reverse germinal center” pattern with transforming cells on periphery of lymphoid cluster; may have foci of transformation resembling Reed-Sternberg cells with cleaved nuclei

Grading

- graded as 1, 2 or 3 based on average number of intrafollicular centroblasts per field, by counting ten 40x (0.159 mm2) fields (WHO);
- important to differentiate grades 1/2 (low-grade follicular lymphoma) vs. grade 3 (hogh-grade follicular lymphoma):

  • grade 1: 0-5
  • grade 2: 6-15
  • grade 3: >15 centroblasts/HPF
    • grade 3A – centrocytes present
    • grade 3B – solid sheets of centroblasts
    • grade 3 with diffuse areas should be reported as Diffuse large B cell lymphoma with follicular lymphoma

WHO recommends reporting as follicular (>75% follicular architecture), follicular and diffuse (25-75% follicular), focally follicular/predominantly diffuse ( < 25% follicular) or diffuse (0% follicular), although this may not have clinical significance (Leuk Lymphoma 2009;50:900)

Prognostic

- high-risk follicular lymphoma