Table 7

Diagnostic approach and advice for assessing lymphoid lesions with a T cell-rich infiltrate and minor large B cell component

S/no.Diagnostic approach and advice
1.Generous sampling and processing of the entire specimen/lesion (where practical) is advisable as some of the features can be focal but critical to diagnosis (eg, a focal nodular component in NLPHL).
2.Perform immunohistochemistry for FDC meshworks (eg, CD21, CD23) to visualise the topography and overall architecture, as well as to highlight inconspicuous lymphoid follicles. The appearance and distribution of FDC meshworks may be pathognomic of some conditions (eg, AITL).
3.Immunohistochemistry for CD30 and in situ hybridisation for EBER should be done as part of an initial assessment panel. However, close attention should be given to the type of cells that express them.
4.It is often useful to have a sensitive reference marker to identify and assess the pattern and distribution of the large B cells, eg, Oct-2 for lymphocyte-predominant cells of NLPHL and MUM1 for Hodgkin/Reed-Sternberg cells of CHL, and help to gauge expression of other immunohistochemical markers in this minority cell population.
5.The existence and distribution of the small B cells in an otherwise T cell-rich infiltrate can be valuable (eg, NLPHL vs TCHRLBCL).
6.As many lineage-specific immunohistochemical markers as practicable should be performed (eg, CD2, CD3, CD5, CD7 as pan-T-cell markers; CD21 and CD23 for FDC; PD-1, CD10, iCOS and CXCL13 for TFH cells) as sensitivity and specificity differs across the various markers for different conditions. It should be noted that many of the markers may not be exclusive to specific cell types (eg, TFH markers).
7.For immunohistochemical markers normally expressed in non-neoplastic tissue, it is advisable to use reactive lymphoid tissue as a control (eg, tonsil or appendix) to appreciate the pattern and intensity of their normal expression. This will provide a reference point, eg, PD-1 must be at least equivalent in intensity to TFH cells in the reactive germinal centres to be significant. Attention should also be paid to internal positive controls (if present) as some markers are sensitive to fixation.
8.Be cautious in making a definitive diagnosis on a lymphoid lesion with a small T cell-rich infiltrate and minor large B cell component in a limited sample (eg, narrow core biopsies, tiny fragmented biopsies) in view of the importance of architectural assessment. Deferral to excision lymph node biopsy is advisable if in doubt.
9.Always have a high index of suspicion for neoplasia in a ‘reactive’-appearing lymph node of an older adult/elderly person, especially in persistent and/or multiple lymphadenopathy with constitutional symptoms (eg, fever, night sweats, weight loss). Conversely, the elderly also suffer from senescence-related conditions that can mimic neoplasia (eg, EBV-positive mucocutaneous ulcer).
  • AITL, angioimmunoblastic T cell lymphoma; CHL, classical Hodgkin lymphoma; EBV, Epstein-Barr virus; FDC, follicular dendritic cell; NLPHL, nodular lymphocyte-predominant Hodgkin lymphoma; TCHRLBCL, T cell/histiocyte-rich large B cell lymphoma; TFH, follicular helper T cell.