nodal follicular 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)

Differential diagnosis

 lymphoid nodular hyperplasia
 hyalin vascular Castleman disease

• https://twitter.com/KyleBradleyMD/status/732685499714940938

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