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Hodgkin's Lymphomas: A Tumor Recognized by Its Microenvironment.

Montes-Moreno S - Adv Hematol (2010)

Bottom Line: Thomas Hodgkin's and Samuel Wilks first recognized Hodgkin disease in the first half of the 19th century.Initially described as lymphogranulomatosis, it was later recognized to be a lymphoid neoplasm derived from B cells and was classified on the basis of its histopathological features.This paper focuses on the current knowledge about the biological features that characterize both NLPHL and CHL, highlighting those relevant to correct pathological diagnosis and those that might be associated with patient outcome.

View Article: PubMed Central - PubMed

Affiliation: Lymphoma Group, Spanish National Cancer Centre (CNIO), E-28029, Madrid, Spain.

ABSTRACT
Thomas Hodgkin's and Samuel Wilks first recognized Hodgkin disease in the first half of the 19th century. Initially described as lymphogranulomatosis, it was later recognized to be a lymphoid neoplasm derived from B cells and was classified on the basis of its histopathological features. Hodgkin lymphomas are now regarded as encompassing two clearly defined entities according to the WHO classification: nodular lymphocyte-predominant Hodgkin Lymphoma (NLPHL) and classical Hodgkin Lymphoma (CHL). This paper focuses on the current knowledge about the biological features that characterize both NLPHL and CHL, highlighting those relevant to correct pathological diagnosis and those that might be associated with patient outcome.

No MeSH data available.


Related in: MedlinePlus

NLP-HL: HE section of a case of Nodular lymphocyte-predominant Hodgkin lymphoma, showing a typical lymphocyte-Predominant (LP) cell positive for CD20 (NLP-CD20) and surrounded by a rim of PD1-positive T cells (NLP-PD1). LR-CHL: HE section of a case of lymphocyte-Rich Classical Hodgkin lymphoma that highlights a typical Reed-Sternberg (R-S) cell with the characteristic phenotype (CD30+, LR-CD30) and surrounded by a rim of PD1-positive T cells (LR-PD1). The pattern is reminiscent of that found in the outer part of the germinal centre where PD1-positive cells surround large B blasts (see arrows in the immunofluorescence capture region of the outer zone of a reactive germinal centre).
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fig1: NLP-HL: HE section of a case of Nodular lymphocyte-predominant Hodgkin lymphoma, showing a typical lymphocyte-Predominant (LP) cell positive for CD20 (NLP-CD20) and surrounded by a rim of PD1-positive T cells (NLP-PD1). LR-CHL: HE section of a case of lymphocyte-Rich Classical Hodgkin lymphoma that highlights a typical Reed-Sternberg (R-S) cell with the characteristic phenotype (CD30+, LR-CD30) and surrounded by a rim of PD1-positive T cells (LR-PD1). The pattern is reminiscent of that found in the outer part of the germinal centre where PD1-positive cells surround large B blasts (see arrows in the immunofluorescence capture region of the outer zone of a reactive germinal centre).

Mentions: Biologically, NLPHL is a Germinal Centre-(GC-)derived B cell neoplasm [17, 18] that retains an almost complete B Cell program at the transcriptional [19] and phenotypic [8, 20] levels. The characteristic lymphocyte-Predominant (LP) cells exhibit a GC phenotypic profile with expression of GC markers such as BCL6 [11, 21], GCET1 [22] and LMO2 [23], together with expression of transcription factors related to a sustained B cell program such as Oct-2 and BOB.1. Interestingly, the GC-related profile is seen not only in LP cells but also in the surrounding T cells, which characteristically create a rosette-like pattern typical of NLPHL (Figure 1). These rosetting T cells have a Follicular T cell phenotype with expression of CD3/CD4/CD57 [24], bcl6 [21], PD1 [20, 25] and, interestingly, CXCL13, a chemokine that is known to induce B cell homing to lymphoid follicles and that plays a role in the T cell-dependent B cell affinity maturation process [26]. These observations suggest that NLPHL is characterized by a GC phenotype in both LP and T cells. This combination is not found in classical HL (CHL), with the exception of lymphocyte-Rich CHL. In fact, this particular subtype of CHL has a profile intermediate between those of NLPHL and CHL with overexpression of B cell transcription program markers and the presence of a follicular T cell background in a substantial proportion of cases [27] (Figure 1). This is not the case for the other types of CHL in which the B cell program and the germinal centre microenvironment are lost. It is remarkable that this previously described immunohistological pattern (i.e., rosettes of Follicular T cells surrounding large B cells) can also be exploited in the differential diagnosis of NLPHL and T/HRBCL, especially in cases whose morphological features overlap [11, 20, 28].


Hodgkin's Lymphomas: A Tumor Recognized by Its Microenvironment.

Montes-Moreno S - Adv Hematol (2010)

NLP-HL: HE section of a case of Nodular lymphocyte-predominant Hodgkin lymphoma, showing a typical lymphocyte-Predominant (LP) cell positive for CD20 (NLP-CD20) and surrounded by a rim of PD1-positive T cells (NLP-PD1). LR-CHL: HE section of a case of lymphocyte-Rich Classical Hodgkin lymphoma that highlights a typical Reed-Sternberg (R-S) cell with the characteristic phenotype (CD30+, LR-CD30) and surrounded by a rim of PD1-positive T cells (LR-PD1). The pattern is reminiscent of that found in the outer part of the germinal centre where PD1-positive cells surround large B blasts (see arrows in the immunofluorescence capture region of the outer zone of a reactive germinal centre).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2963118&req=5

fig1: NLP-HL: HE section of a case of Nodular lymphocyte-predominant Hodgkin lymphoma, showing a typical lymphocyte-Predominant (LP) cell positive for CD20 (NLP-CD20) and surrounded by a rim of PD1-positive T cells (NLP-PD1). LR-CHL: HE section of a case of lymphocyte-Rich Classical Hodgkin lymphoma that highlights a typical Reed-Sternberg (R-S) cell with the characteristic phenotype (CD30+, LR-CD30) and surrounded by a rim of PD1-positive T cells (LR-PD1). The pattern is reminiscent of that found in the outer part of the germinal centre where PD1-positive cells surround large B blasts (see arrows in the immunofluorescence capture region of the outer zone of a reactive germinal centre).
Mentions: Biologically, NLPHL is a Germinal Centre-(GC-)derived B cell neoplasm [17, 18] that retains an almost complete B Cell program at the transcriptional [19] and phenotypic [8, 20] levels. The characteristic lymphocyte-Predominant (LP) cells exhibit a GC phenotypic profile with expression of GC markers such as BCL6 [11, 21], GCET1 [22] and LMO2 [23], together with expression of transcription factors related to a sustained B cell program such as Oct-2 and BOB.1. Interestingly, the GC-related profile is seen not only in LP cells but also in the surrounding T cells, which characteristically create a rosette-like pattern typical of NLPHL (Figure 1). These rosetting T cells have a Follicular T cell phenotype with expression of CD3/CD4/CD57 [24], bcl6 [21], PD1 [20, 25] and, interestingly, CXCL13, a chemokine that is known to induce B cell homing to lymphoid follicles and that plays a role in the T cell-dependent B cell affinity maturation process [26]. These observations suggest that NLPHL is characterized by a GC phenotype in both LP and T cells. This combination is not found in classical HL (CHL), with the exception of lymphocyte-Rich CHL. In fact, this particular subtype of CHL has a profile intermediate between those of NLPHL and CHL with overexpression of B cell transcription program markers and the presence of a follicular T cell background in a substantial proportion of cases [27] (Figure 1). This is not the case for the other types of CHL in which the B cell program and the germinal centre microenvironment are lost. It is remarkable that this previously described immunohistological pattern (i.e., rosettes of Follicular T cells surrounding large B cells) can also be exploited in the differential diagnosis of NLPHL and T/HRBCL, especially in cases whose morphological features overlap [11, 20, 28].

Bottom Line: Thomas Hodgkin's and Samuel Wilks first recognized Hodgkin disease in the first half of the 19th century.Initially described as lymphogranulomatosis, it was later recognized to be a lymphoid neoplasm derived from B cells and was classified on the basis of its histopathological features.This paper focuses on the current knowledge about the biological features that characterize both NLPHL and CHL, highlighting those relevant to correct pathological diagnosis and those that might be associated with patient outcome.

View Article: PubMed Central - PubMed

Affiliation: Lymphoma Group, Spanish National Cancer Centre (CNIO), E-28029, Madrid, Spain.

ABSTRACT
Thomas Hodgkin's and Samuel Wilks first recognized Hodgkin disease in the first half of the 19th century. Initially described as lymphogranulomatosis, it was later recognized to be a lymphoid neoplasm derived from B cells and was classified on the basis of its histopathological features. Hodgkin lymphomas are now regarded as encompassing two clearly defined entities according to the WHO classification: nodular lymphocyte-predominant Hodgkin Lymphoma (NLPHL) and classical Hodgkin Lymphoma (CHL). This paper focuses on the current knowledge about the biological features that characterize both NLPHL and CHL, highlighting those relevant to correct pathological diagnosis and those that might be associated with patient outcome.

No MeSH data available.


Related in: MedlinePlus