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Follicular dendritic cell in lymphomas of follicular origin

Written2018-06Antonino Carbone, Annunziata Gloghini
Department of Pathology Centro di Riferimento Oncologico Aviano (CRO), Istituto Nazionale Tumori, IRCCS, Aviano, Italy; acarbone@cro.it (AC); Department of Diagnostic Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy; annunziata.gloghini@istitutotumori.mi.it (AG)

Abstract B-cell lymphomas of presumed follicular origin include follicular lymphoma (FL), mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL). Within the microenvironment of all these follicle-derived lymphomas tumor cells show a strict topographical and functional relationship with FDCs, together with reactive lymphoid and stromal cells. The FDC patterns, as described for FL and MCL, are reminiscent of the distribution pattern of FDC meshwork seen in the GC or the mantle zone of the secondary lymphoid follicle, respectively.

Keywords Lymphomas; Follicular lymphoma; Mantle cell lymphoma; Marginal zone Lymphoma; Follicular dendritic cells

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Identity

ICD-Topo C420,C421,C424
ICD-Morpho 9690/3 Follicular lymphoma; Paediatric follicular lymphoma
ICD-Morpho 9673/3 Mantle cell lymphoma
ICD-Morpho 9699/3 Extranodal marginal zone lymphoma of mucosa- associated lymphoid tissue (MALT lymphoma); Nodal marginal zone lymphoma; Paediatric nodal marginal zone lymphoma
Atlas_Id 1783
Other namesFollicular dendritic cell patterns in the microenvironment of b-cell lymphomas of follicular origin

Clinics and Pathology

Note Follicular dendritic cell: main features and functions
Follicular dendritic cells (FDCs) are stromal cells of mesenchymal origin, located in the peripheral lymphoid tissues, particularly in the B-cell-dependent areas, i.e. in lymphoid primary follicles (primary FDCs) or in secondary follicles (secondary FDCs) (Allen et al., 2008; Rezk et al., 2013). The lymphoid follicle is a structure made of B and T lymphoid cells within a meshwork of FDCs. In the secondary lymphoid follicle, rounded collections of cohesive FDCs are seen in the germinal center (GC), whereas irregularly shaped meshworks of poorly cohesive FDCs are evident in the mantle zone (Tsunoda et al., 1999). Therefore, the patterns of FDC distribution, usually recognizable in secondary lymphoid follicles, include a tight/dense meshwork pattern with a polarized FDC meshwork pattern in the GC, and an expanded FDC meshwork with extension into the mantle zones (Rezk et al., 2013).
Classic FDC immunophenotype includes the expression of CD21, CD23, and CD35. Other markers reported to be highly sensitive but not specific to FDCs include S-100 protein (Carbone et al., 1986), clusterin (Grogg et al., 2004) and podoplanin (Yu et al. 2007). FDC's main functions comprise: histoarchitecture organization of lymphoid follicles, antigen trapping and presentation, organization of apoptotic "waste" removing, and self-immunity prevention. Organizing functions of FDCs are chemokine dependent (Carbone and Gloghini 2014).
B-cell lymphomas of follicular origin: classification
B-cell lymphomas of presumed follicular origin include follicular lymphoma (FL), mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL). Within the microenvironment of all these follicle-derived lymphomas tumor cells show a strict topographical and functional relationship with FDCs, together with reactive lymphoid and stromal cells (Carbone et al. 2009; Rezk et al., 2013). The FDCs are thought to represent newly generated cells arising during lymphoma growth and progression, although they remain non-neoplastic bystander cells (Jin et al., 2011). The FDC patterns, as described for FL and MCL, (Manconi et al., 1988; Gloghini and Carbone 1993) are reminiscent of the distribution pattern of FDC meshwork seen in the GC or the mantle zone of the secondary lymphoid follicle, respectively (Carbone et al., 1988). The FDC patterns shown by FL and the other lymphomas of follicular origin have recently been reviewed (Rek et al., 2013).
Disease Follicular Lymphoma
FLs are derived from GC B cells and usually express BCL2 as a result of the characteristic t(14;18)(q32;q21) IGH/ BCL2 translocation. A pathologic diagnosis requires immunohistologic detection of neoplastic B cells that show positive staining for BCL2 and CD10. The FDC meshwork usually form a well-developed "spherical" dendritic meshwork with a sharp outline highlighting an attenuated mantle zone (Figure 1). Other patterns that can be seen include contracted/distorted/disintegrated FDC meshworks (Rezk et al., 2013; Carbone and Gloghini 2014).
 
Figure 1. Follicular lymphoma. In this figure a follicular lymphoma shows a nodular pattern. Within the nodules, follicular dendritic cells form a spherical meshwork stained by CD21 and CD23.

Disease Mantle Cell Lymphoma
MCL is a B-cell neoplasm that usually carries the characteristic t(11;14)(q13;q32) translocation that juxtaposes the protooncogene CCND1, which encodes cyclin D1, at chromosome 11q13, to the Ig heavy-chain gene at chromosome 14q32.25 The typical antigen profile in this lymphoma includes the coexpression of CD5 and CD20 in the absence of CD3, CD10, and CD23 expresssion. Several growth patterns may be observed in MCL. They include a nodular growth pattern with residual GCs, a nodular growth pattern without residual GCs, a nodular growth pattern due to the colonization of reactive GCs, and a diffuse pattern with or without residual GCs (Campo et al., 2011). The t(11;14) translocation is the primary event of the B lymphocyte transformation that is followed by colonization and expansion of the mantle cell area of the lymphoid follicles (Figure 2). When there is a nodular growth pattern with residual GCs, obviously the reactive GCs have preserved tight FDC meshworks, whereas neoplastic zones show a disrupted and fragmented FDC meshwork. Conversely, as the expansion of the neoplastic mantle zones continue outward, MCL neoplastic nodules with absent FDC meshworks and negative staining for CD21 and CD23 are formed (Carbone and Gloghini 2014).
 
Figure 2. Mantle cell lymphoma (MCL) with mantle zone pattern. In this MCL, cyclin D1+ tumor cells involve the mantle zone of a secondary follicle where the CD23+ follicular dendritic cell meshwork is fragmented.

Disease Marginal Zone Lymphoma
MZL is a B-cell lymphoma that is supposed to derive from the marginal zone. It encompasses 3 distinct entities known as mucosa-associated lymphatic tissue (MALT) lymphoma, nodal MZL (NMZL), and splenic MZL (SMZL) (Cook et al., 2017; Campo et al, 2017). Among these B-cell lymphomas, early lesions may be observed within the subsets of NMZL and SMZL with tumor cells growing inside an attenuated mantle zone and often around a residual GC. Immunohistochemical studies show that in all MZL entities neoplastic B cells express CD20, CD43, and BCL2, but not CD3, CD5, CD10, and CD23 (Carbone et al. 1986; Rezk et al., 2013). The FDC meshwork is variably distorted and disintegrated when there is a follicular colonization (Rez et al., 2013; Carbone and Gloghini, 2014; Cook et al., 2017; Campo et al., 2017). The presence of remnants of FDC meshwork suggests colonized follicles (Rez et al., 2013; Carbone and Gloghini, 2014).The FDC meshwork is more evident in cases with a nodular/follicular pattern (Figure 3).
 
Figure 3. Marginal zone lymphoma with follicular colonization. The CD20+ neoplastic cells invade and colonize the germinal center. These neoplastic cells show a low proliferative index by MIB1/Ki67. The germinal center is still recognizable, but the CD23+ follicular dendritic cell meshwork is fragmented and disrupted.

To be noted

Conclusions: The microenvironmental FDC patterns seen in the CD21 and CD23 stains contribute to the definition of the early stages of B-cell lymphomas of follicular origin. The FDC patterns recognizable include a "spherical" pattern in FLs, a "mantle zone" pattern in MCL and a "centrifugal" pattern in MZL. These FDC patterns are easily recognizable the lymphoma is in its early stage and still maintains a follicular/nodular pattern of growth.

Bibliography

Characterizing follicular dendritic cells: A progress report
Aguzzi A, Krautler NJ
Eur J Immunol 2010 Aug;40(8):2134-8
PMID 20853499
 
Follicular dendritic cell networks of primary follicles and germinal centers: phenotype and function
Allen CD, Cyster JG
Semin Immunol 2008 Feb;20(1):14-25
PMID 18261920
 
The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications
Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES
Blood 2011 May 12;117(19):5019-32
PMID 21300984
 
Follicular dendritic cell pattern in early lymphomas involving follicles
Carbone A, Gloghini A
Adv Anat Pathol 2014 Jul;21(4):260-9
PMID 24911251
 
S-100 protein, fibronectin, and laminin immunostaining in lymphomas of follicular center cell origin
Carbone A, Manconi R, Poletti A, Colombatti A, Tirelli U, Volpe R
Cancer 1986 Nov 15;58(10):2169-76
PMID 3530426
 
The nonlymphoid microenvironment of reactive follicles and lymphomas of follicular origin as defined by immunohistology on paraffin-embedded tissues
Gloghini A, Carbone A
Hum Pathol 1993 Jan;24(1):67-76
PMID 8418015
 
Clusterin expression distinguishes follicular dendritic cell tumors from other dendritic cell neoplasms: report of a novel follicular dendritic cell marker and clinicopathologic data on 12 additional follicular dendritic cell tumors and 6 additional interdigitating dendritic cell tumors
Grogg KL, Lae ME, Kurtin PJ, Macon WR
Am J Surg Pathol 2004 Aug;28(8):988-98
PMID 15252304
 
Follicular dendritic cells in follicular lymphoma and types of non-Hodgkin lymphoma show reduced expression of CD23, CD35 and CD54 but no association with clinical outcome
Jin MK, Hoster E, Dreyling M, Unterhalt M, Hiddemann W, Klapper W
Histopathology 2011 Mar;58(4):586-92
PMID 21401698
 
Dendritic reticulum cell pattern as a microenvironmental indicator for a distinct origin of lymphoma of follicular mantle cells
Manconi R, Poletti A, Volpe R, Sulfaro S, Carbone A
Br J Haematol 1988 Feb;68(2):213-8
PMID 3280004
 
Follicular dendritic cells: origin, function, and different disease-associated patterns
Rezk SA, Nathwani BN, Zhao X, Weiss LM
Hum Pathol 2013 Jun;44(6):937-50
PMID 23332930
 
Differential expression of Ca(2+)-binding proteins on follicular dendritic cells in non-neoplastic and neoplastic lymphoid follicles
Tsunoda T, Yamakawa M, Takahashi T
Am J Pathol 1999 Sep;155(3):805-14
PMID 10487838
 
Podoplanin (D2-40) is a novel marker for follicular dendritic cell tumors
Yu H, Gibson JA, Pinkus GS, Hornick JL
Am J Clin Pathol 2007 Nov;128(5):776-82
PMID 17951199
 

Citation

This paper should be referenced as such :
Carbone A, Gloghini A
Follicular dendritic cell in lymphomas of follicular origin;
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Anomalies/FollDendriticCellID1783.html


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