Intranodular clusters of activated cells with T follicular helper phenotype in nodular lymphocyte predominant Hodgkin lymphoma: a pilot study of 32 cases from Finland

• Published in: Human pathology Vol. 44; no. 9; pp. 1737 - 1746
• Main Authors: Nathwani, Bharat N., MD, Vornanen, Martine, MD, Winkelmann, Ria, MD, Kansal, Rina, MD, Doering, Claudia, MD, Hartmann, Sylvia, MD, Hansmann, Martin L., MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2013; Elsevier Limited
• Subjects: Activated T cells; Adolescent; Adult; Aged; Biomarkers, Tumor - metabolism; Child; Chromatin; CXCL13; Cytoplasm; Female; Finland; Genotype & phenotype; Hodgkin Disease - complications; Hodgkin Disease - metabolism; Hodgkin Disease - pathology; Hodgkin lymphoma; Humans; Immunophenotyping; In Vitro Techniques; Intranodular clusters of activated cells; Lymph Nodes - metabolism; Lymph Nodes - pathology; Lymphatic Diseases - etiology; Lymphatic Diseases - metabolism; Lymphatic Diseases - pathology; Lymphocyte Activation; Lymphocytes; Male; Middle Aged; Neoplasm Staging; Nodular lymphocyte predominant Hodgkin lymphoma; Pathology; PD1; Pilot Projects; Recurrence; Remission Induction; Rosette Formation; Rosettes; T follicular helper cells (TFH); T-Lymphocytes, Helper-Inducer - metabolism; T-Lymphocytes, Helper-Inducer - pathology; Young Adult; Finland; Activated T cells; Intranodular clusters of activated cells; Rosettes; Nodular lymphocyte predominant Hodgkin lymphoma; PD1; CXCL13; T follicular helper cells (T FH); Hodgkin lymphoma; T follicular helper cells (TFH); T follicular helper cells (T(FH))
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2013.02.010

Summary In nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), little is known about the presence of intranodular clusters of cytologically activated lymphoid cells producing a moth-eaten pattern histologically. This pilot study of 32 NLPHL cases from Finland ascertained (1) the frequency of the intranodular clusters of activated lymphoid cells, (2) the immunophenotype of the activated cells, (3) the size and immunophenotype of the rosetting cells, and (4) the clinical significance of the activated cells. Histologically, intranodular clusters of activated cells produced a moth-eaten pattern in 100% (32 cases; subtle in 62.5%, overt in 37.5%). In immunostains, activated cells in subtle clusters (20 cases) were very difficult to identify. Twelve cases had overt clusters of activated cells, which were positive with CD3, CD4, PD1, CXCL13 (T follicular helper [TFH ] phenotype), but rarely with Ki-67 and BCL2. Most activated rosetting cells had the same immunophenotype as the nonrosetting cells, except for CXCL13. Clinical presentation for all 32 Finnish patients was distinctive: 97% men, 97% with peripheral lymphadenopathy and 35.5% with stage III/IV disease. Only 22% relapsed; 97% were in remission. There was no significant clinical difference between cases with overt and subtle clusters. Intranodular activated TFH cells in NLPHL appeared to be nonproliferating and not long-living, and they were not associated with any adverse clinical outcome. Although most activated cells were TFH cells, it seemed that they were unable to increase the number of malignant cells. The pathogenetic role of the intranodular activated TFH and the small T cells in NLPHL needs further investigation.