Nodular lymphocyte-predominant Hodgkin lymphoma

2016-04-01   Antonino Carbone , Annunziata Gloghini 

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

Abstract

Diagnostic characteristics of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL): nodular or nodular and diffuse proliferation of scattered lymphocyte predominant (LP) tumour cells within a background reminiscent of primary or secondary lymphoid follicles.

Clinics and Pathology

Disease

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a distinct subtype of Hodgkin lymphoma (HL), usually associated with an indolent course and presenting in the early stages of the disease (Anagnostopoulos et al., 2000).

Phenotype stem cell origin

Cell origin
Tumour cells are antigen-selected mutating germinal center (GC) B cells. This origin is supported by
The expression of BCL6 and CD40 by tumour cells (Carbone et al., 1995; Liso et al., 2006).
The presence of CD4+, CD57+, PD1+ T cells surrounding the tumour cells (Poppema et al., 2008).
The presence of a follicular dendritic cell meshowork within the tumour nodules (Mason et al., 1994 ; Carbone and Gloghini, 2012)
The gene expression profile (Brune et al., 2008).
Rearranged, clonal and mutated (ongoing) Ig genes of tumour cells (Marafioti et al., 1997; Küppers, 2011).
Phenotype
LP cells profile: CD45+, CD20+, CD40+, CD79a+, CD75+, BCL6+, IRF4/MUM1+, and OCT2+, BOB1+, PAX5+, PU.1+, epithelial membrane antigen+. CD15 and CD30 are usually negative (Poppema et al., 2008).
Nodules compositon: CD20+ and IgD+ small B cells, CD3+ and CD4+ T cells and histiocytes.
The background of the nodules also includes an increase in GC-derived CD57+, IRF4/MUM1+, and PD-1+ T-cells populations which form a rim around LP cells (Carbone and Gloghini, 2012).

Epidemiology

About 5% of all HL cases are classified as NLPHL. Males are more commonly affected than females (male-female ratio, 3:1). The median age at presentation is about 40 years.

Clinics

NLPHL is a neoplasm usually associated with a favourable clinical course despite a tendency for local recurrences.

Cytology

NLPHL tumour cells are termed lymphocyte predominant (LP) cells. LP cells are large cells with multilobated nuclei and scant cytoplasm. They contain multiple, not prominent, nucleoli in contrast with typical Reed Sternberg cells of classical HL that contain huge eosinophilic nucleoli.

Pathology

LP tumour cells proliferate within a nodular or nodular and diffuse background (Anagnostopoulos et al., 2000). The tumour nodules are reminiscent of a primary follicle containing spherical meshworks of follicular dendritic cells (FDCs) admixed with inflammatory cells (Mason et al., 1994).
On morphologic and immunohistologic grounds, six patterns are recognizable in NLPHL (Fan et al., 2003): A) classical nodular, B) serpiginous/interconnected nodular, C) nodular with prominent extra-nodular LP cells, D) T-cell-rich nodular, E) diffuse with a T-cell-rich background, and F) diffuse, B-cell-rich pattern.
Typical histopathologic patterns in NLPHL include patterns A and B. Both of these patterns show a predominantly nodular growth, with LP cells located within the nodules. So called "histopathologic variants" include patterns from C to F and are associated to prominent extranodular LP cells or to B-cell depletion of the microenvironment (Hartmann et al. Blood, 2013).
An additional nodular pattern in which LP cells proliferate within a background reminiscent of a secondary follicle without invasion of the extranodular space has been recognized (Carbone and Gloghini, 2012; Gloghini et al., 2015).
Atlas Image

Other features

Virology
The neoplastic cells are usually EBV negative (Anagnostopoulos et al., 2000).

Treatment

Early stage disease: treatment with local radiation provides disease control and good overall survival (Advani and Hoppe, 2015).
Locally extensive or advanced stages: paradigms used for classical HL with similar outcomes (Advani and Hoppe, 2015). Excellent response rates (but increased relapse rates) observed with single agent rituximab. Promising data observed with R-CHOP (Advani and Hoppe, 2013; Younes et al., 2014).
Relapsed disease: single agent rituximab is a reasonable choice because of excellent tolerability (Advani and Hoppe, 2015).

Prognosis

Favourable clinical course despite a tendency for local recurrences (Advani and Hoppe, 2013).
Compared with "typical NLPHL", "histopathologic variants" are associated with more advanced disease and a higher relapse rate (Hartmann et al. Blood, 2013).

Note

Translocation involving the BCL6 protooncogene (Liso et al., 2006).
Strong NFKB activity (Küppers, 2011).
Aberrant somatic hypermutation of multiple proto-oncogenes (PIM1, RHOH (TTF), MYC, and PAX5) in a fraction of cases. Most of mutations are on the 5 untranslated regions of the genes (Liso et al, 2006).
Mutation in SOCS1 (Küppers, 2011).
BAG6 (BAT3), HIGD1A, and UBD (FAT10) gene espression (Hartmann et al. PlosOne, 2013).

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Citation

Antonino Carbone ; Annunziata Gloghini

Nodular lymphocyte-predominant Hodgkin lymphoma

Atlas Genet Cytogenet Oncol Haematol. 2016-04-01

Online version: http://atlasgeneticsoncology.org/haematological/1570/nodular-lymphocyte-predominant-hodgkin-lymphoma

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