Orris

Write a short note on RS Cells

Reading File
Finding Sources
Searching PubMed

Reed-Sternberg cells Hodgkin lymphoma

Finding Sources
Reading File
Finding Sources
Reading File
Reading File
Finding Sources
Reading File
Loading Image
Here is a comprehensive note on Reed-Sternberg (RS) cells, sourced from Robbins, Cotran & Kumar Pathologic Basis of Disease and Robbins & Kumar Basic Pathology:

Reed-Sternberg (RS) Cells

Definition

RS cells are the large, neoplastic giant cells that are pathognomonic of Hodgkin lymphoma (HL). Their identification in a background of non-neoplastic inflammatory cells is mandatory for the diagnosis of HL.

Morphology

The diagnostic (classic) RS cell is:
  • Very large (~45 µm in diameter)
  • Binucleated or multinucleated (or a single nucleus with multiple lobes)
  • Each nucleus/lobe contains a large, prominent, inclusion-like nucleolus (~5-7 µm) - the size of a small lymphocyte, giving the classic "owl-eye" appearance
  • Surrounded by abundant pale cytoplasm
Reed-Sternberg cells and variants: (A) Classic binucleated RS cell with owl-eye nucleoli; (B) Mononuclear variant; (C) Lacunar variant; (D) Lymphohistiocytic (popcorn) variant
Fig. 13.25 RS cells and variants (A-D). - Robbins, Cotran & Kumar Pathologic Basis of Disease

RS Cell Variants

VariantFeaturesAssociated Subtype
Classic (diagnostic) RS cellBinucleate, owl-eye nucleoli, abundant cytoplasmAll classic HL subtypes
Mononuclear (Hodgkin cell)Single nucleus with large inclusion-like nucleolusAll classic subtypes
Lacunar cellFolded/multilobated nucleus, pale cytoplasm; sits in a clear space (artifact of formalin fixation)Nodular sclerosis
Lymphohistiocytic (L&H / "Popcorn" cell)Multiple infolded nuclear membranes, small nucleoli, fine chromatin, abundant pale cytoplasmNodular lymphocyte predominant HL

Cell of Origin

RS cells originate from germinal center (or post-germinal center) B cells. This was established by molecular studies on single microdissected RS cells, which showed:
  • Clonal IGH gene rearrangements
  • Evidence of somatic hypermutation of immunoglobulin genes
Despite this B-cell origin, classic RS cells paradoxically fail to express most B-cell genes, including immunoglobulin genes - likely due to widespread epigenetic reprogramming.

Immunophenotype

MarkerClassic RS cellL&H (Popcorn) cell
CD30+-
CD15+-
PAX5+ (weak)+
CD20-+
CD45 (LCA)-+
EBV (LMP-1)Variable-

Pathogenesis

The key molecular event in classic HL is activation of NF-κB, which promotes RS cell growth and survival. This occurs via:
  1. EBV infection - LMP-1 (a viral latent membrane protein) directly activates NF-κB. EBV is found in RS cells in ~70% of mixed-cellularity HL and a smaller fraction of other classic subtypes.
  2. Loss-of-function mutations in IκB or TNF-α-induced protein 3 (negative regulators of NF-κB) - in EBV-negative tumors.
  3. REL proto-oncogene copy number gains on chromosome 2p.
RS cells are aneuploid with diverse chromosomal aberrations.

Immune Evasion

RS cells actively suppress anti-tumor immunity:
  • Overexpression of PD-L1 and PD-L2 (encoded on chromosome 9p) - these immune checkpoint ligands antagonize cytotoxic T-cell responses.
  • Loss of β2-microglobulin function - prevents expression of MHC class I molecules, so RS cells are invisible to cytotoxic T cells.
  • Despite generating a florid reactive inflammatory infiltrate (via cytokines such as IL-5, IL-10, eotaxin, TGF-β), the host immune response is entirely ineffective.

Reactive Background & Cytokine Environment

RS cells secrete cytokines that attract a reactive background infiltrate, which in turn feeds RS cell survival:
  • IL-5 - attracts eosinophils
  • TGF-β - fibrogenic (responsible for sclerosis in nodular sclerosis HL)
  • IL-13 - may stimulate RS cell growth via autocrine signaling
  • Eotaxin - chemotactic for eosinophils
Eosinophils and T cells in the background express CD30L and CD40L, which activate CD30/CD40 on RS cells and further upregulate NF-κB - a positive feedback loop.

RS-like Cells in Other Conditions

Classic RS-like cells are not exclusive to Hodgkin lymphoma. Similar-appearing cells may be seen in:
  • Infectious mononucleosis
  • Certain non-Hodgkin lymphomas
  • Solid tissue cancers
Diagnosis of HL therefore requires RS cells in the correct morphologic and immunophenotypic context, confirmed by immunohistochemistry (CD15+, CD30+, CD45-).
Sources: Robbins, Cotran & Kumar Pathologic Basis of Disease, pp. 573-575; Robbins & Kumar Basic Pathology, pp. 417-418
This is a shared conversation. Sign in to Orris to start your own chat.