Case 108 – Summary!

Thank you for everybody’s contributions throughout the week!

We focused upon a 32 year old man who presented with asymptomatic unilateral cervical lymphadenopathy and was subsequently diagnosed with limited stage nodular lymphocyte predominant hodgkin lymphoma (NLPHL). He was treated with radiotherapy alone. As is classical of this disease he had a late relapse at 5 years with stage III disease involving splenomegaly and was treated with R-CHOP. 18 months after this he developed transformed T cell/histiocyte rich B cell lymphoma and was treated with salvage regime and ASCT with TLS prophylaxis and CNS prophylaxis due to the extent of disease. Below is a summary of NLPHL.

 Nodular Lymphocyte Predominant Hodgkin Lymphoma 

NLPHL is a rare subtype of Hodgkin Lymphoma (~5%) but is clinically and pathologically distinct from classical Hodgkin Lymphoma. Indeed it is often considered to have been misclassified originally due to the marked differences between the two diseases).

It is associated with an excellent OS (similar to normal-age matched controls) it is important to reduce long-term toxicity with therapies.

Clinical features

  • Bimodal age distribution – childhood (median age 13 years) and adults (median age 30-40 years)
  • Male preponderance
  • Typically present with early stage disease with peripheral lymphadenopathy (predominantly cervical lymph nodes)
  • Mediastinal disease, B symptoms and bulky disease is uncommon
  • Typically has an indolent clinical course with an overall favourable prognosis. However multiple, often late, relapses are characteristic and there is a risk of transformation to high-grade disease. Long-term follow-up is key.
  • PET avid and should be assessed by PETCT.

Morphology

  • Lymphocyte predominant cells (‘popcorn cell’ – multilobulated nucleoli) surrounded by rosette of small lymphocytes (follicular helper T cells). All within nodules of small B lymphocytes and histiocytes.
  • Plasma cells and eosinophlis are uncommon as opposed to classical Hodgkin lymphoma.
  • There are 6 histopathological variant patterns
    • Pattern A + B – LP cells embedded within B cell nodules
    • Pattern C-F – variation of location in relation to nodules, diffuse, pattern, T cell rich backgrounds.

Immunohistochemistry

Lymphocyte Predominant cells – CD20+, CD45+, CD79a, PAX5+, epithelial membrane antigen expressed. CD15-, EBV-, rarely express CD30.

Follicular helper T cells – CD4+CD57+PD1+

Differential diagnosis

  • Lymphocyte rich classical Hodgkin lymphoma
    • Reed-sternberg cells, CD30+, CD15+, CD20-
  • Progressive transformation of germinal centres
    • Don’t contain lymphocyte predominant cells, no T cell rosettes, BCL2+.
    • Rarely exist within the same lymph node as NLPHL
  • T cell/histiocyte rich B cell lymphoma
    • Difficult to distinguish but absence of follicular dendritic cell meshwork and loss of background of small B cells.

Prognostic factors

Inferior PFS / OS associated with:

  • Advanced stage
  • Albumin <40g/l
  • Anaemia (Hb <105g/l)
  • Histiopathological variant C-F
  • Lymphopenia (<8% of WCC)
  • Male sex

 

Management

Early Stage Disease Guidelines:

  • ESMO guidance
    • Stage IA and no clinical risk factors: Radiotherapy alone (IFRT 30Gy)
    • Stage IIA and no clinical risk factors: 2#R-ABVD + 20Gy RT
    • Early stage and unfavourable risk factors: 4-6# ABVD + 30Gy IFRT
  • NCCN guidance:
    • Stage I-IIA and no clinical risk factors: Radiotherapy alone (IFRT 30-36Gy)
    • Early stage and unfavourable risk factors: 4-6# ABVD + 30Gy IFRT

Early stage Disease Info:

  • Associated with overall survival >90%
  • Observation
    • Can be considered in selected patients – asymptomatic, fully resected stage IA without unfavourable features.
  • RT alone for stage IA associated with 10yr PFS/OS 89%/96% (Chen et al)
  • No prospective data comparing combined modality treatment versus radiotherapy and most regimens extrapolated from classical Hodgkin lymphoma.
  • Single agent rituximab not appropriate (responses are not durable)

 

Advanced Stage Disease

 ESMO / NCCN Guidance

  • Offer option of R-CHOP and R-chemo (treatment regimes identical to treatment for classical HL with addition of anti-CD20 antibody)

 Advanced Stage Disease Info:

  • ~20% present with advanced stage disease
  • Associated poorer prognosis
  • Ensure biopsy from appropriate site as advanced stage is significant risk factor for transformation
  • R-CHOP associated with better PFS vs R-ABVD

Relapsed Disease

  • Late relapses are characteristic of NLPHL
  • Re-biopsy essential to exclude transformation

Limited Stage Relapse

  • Single agent rituximab (greater benefit also if had long disease free interval)
  • Radiotherapy (ISRT)

Advanced Stage Relapse (or short disease free interval)

  • High dose chemotherapy and ASCT (e.g R-CHOP)

 

Transformed Disease

  • ~15% transformed to an aggressive large B cell NHL by 10 yrs
  • Typically transforms to T cell/histiocyte rich B cell lymphoma
  • Risk factors for transformed disease:
    • Advanced stage disease
    • Infradiaphramatic involvement
    • Splenic involvement
    • Histopathological variant patterns C-F
  • Always important to re-biopsy ‘relapsed’ disease to ensure no transformation
  • No standard treatment
  • NCCN / ESMO guidance: as per standard treatment regime for de novo DLBCL
  • Associated with prognosis similar to de novo DLBCL

 

References

  1. Spinner et al. Modern Principles in the management of NLPHL. British Journal of Haematology. 2019. 17-29.
  2. Eichenauer et al. Hodgkin Lymphoma: ESMO Clinical Practice Guidelines. 2018. https://oncologypro.esmo.org/Guidelines/Clinical-Practice-Guidelines/Haematological-Malignancies/Hodgkin-Lymphoma
  3. Advani et al. How I treat NLPHL. Blood. 2013. 122:4182-4188

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