Lymphoma

Section: Surgical Oncology Curriculum: Curriculum, page 66

Definition

• Neoplastic disease lymphoid tissue and the Lymphatic system and form discrete masses (leukaemia – involve BM & peripheral blood)

Broad categorisation of lymphoma

• Hodgkin’s lymphoma (5 different types) – considered curable          
  • develops from a specific abnormal B lymphocyte lineage
  • characterised by Reed-Sternberg cells
• Non-Hodgkin’s = NHL (30 types)
  • Classified as low-grade of high-grade
  • may derive from either abnormal B or T cells -  distinguished by unique genetic markers
    • E.g
      • Diffuse Large cell B cell Lymphoma (DCBCL) = 30% of all lymphoma
      • MALT (B cell) = 5% of all lymphoma

Non-Hodgkins lymphoma

• 90% of lymphoma

• B or T cells

• Affects multiple nodes

• 80% B-cells

  • 40% follicles
  • 40% Diffuse

• 20% T-cells

  • Always diffuse

Aggressive features

• Factors associated with increased proliferation
  • Non cleaved vs cleaved
  • Large vs small
  • Immature vs mature
  • Diffuse vs follicles

Hodgkins lymphoma

• Only B cells
• Single group of lymph nodes
  • Contagious spread
• Reed-Sternberg cells

Aetiology

• Hodgkin’s: Unknown
  • Familial clustering
  • ?oncogenic virus? EBV
• NHL risk factors
  • Congenital disorders: coeliac disease, Ataxia Telangiectasia, Wiskott-Aldrich syndrome
  • Prior chemo or radiotherapy / immunosuppressive therapy
  • BV, HIV, Helicobacter infection
  • Hashimoto’s thyroiditis
  • Sjogrens syndrome

Clinical

• Most pts present with enlarged, painless LNs
• Hodgkin’s
  • Mediastinal masses → cough, dyspnoea
  • 25% have systemic B Symptoms: weight loss, fever, night sweats
• NHL
  • 1/3 of cases originate outside the LN’s – eg mucosa, BM, skin
  • GI tract is the most common location

Pathology

• Reed-Sternberg large multinucleated (or bilobed nucleus) cells express large numbers of the surface antigen CD30 & CD15; usually negative for CD20
• NHL
  • can originate from B cells (CD20), T cells or histiocytes
• NB most are B cell lymphomas (major exception = T cell lymphoma associated with Coeliacs disease)

Investigations

Imaging

• CT chest abdo pelvis

Biopsy

•  Diagnosis
  • Need adequate tissue for histologic, immunologic, and molecular biologic assessment.
    • Excisional or incisional biopsy
    • Multiple core needle
  • FNA
    • FNΑ is neither adequate to exclude a diagnosis of lymphοma (eg, due to limited diagnostic material, sampling issues, loss of fragile cells during processing) nor does it enable definitive classification (because it disrupts the nodal architecture)
• Send
  • Fixed in Formalin
    • Histology
    • Can also do if required
      • Immunohistochemistry - can get information that you get form flow cytometry
      • Fluorescence in situ hybridization (FIЅH) - can get information detected by conventional karyotype
  • Fresh
    • Flow cytometry
    • Conventional Karyotyping

Stage

• Ann-Arbor staging

Management

• Hodgkin’s:
  • Stage I / II → RTx
  • Stage III / IV → RTx & chemotherapy ± BM transplant
• NHL
  • High grade:
    • Stage I / II → radiotherapy ± chemo (Doxyrubacin)
    • Stage II-IV → CHOP (cyclophosphamide, doxyrubicin, vincristine, prednisone)
  • Low grade: radiotherapy, if localised ± chemo

Prognosis / Natural Hx:

• Hodgkin’s lymphoma → 70% cured with modern therapy
  • Relapse rates 20-30%
• NHL
  • Low grade: difficult to cure; most pts die of their disease
  • High grade: more aggressive, but often curable
• Relapse → poor prognosis (10% long-term survival)

Intestinal lymphoma

• Primary intestinal lymphoma = (HNL) lymphoma affecting intestine, which exhibits no evidence of liver, spleen or BM involvement at time of Dx (but regional LN may be present)
• Incidence:
  • accounts for 30% of GI lymphoma
• Classification
  • Western type – seen in Europe & North America: sporadic discrete lesion arises from B cells in MALT in small intestine that was previously normal
  • Mediterranean type – B cell lymphoma that arises in association with diffuse plasma-cell infiltration of the small intestine mucosa (the plasma cells synthesize an abN IgA heavy chain)
  • Primary lymphoma is also associated with
    • Coeliac disease / Tropical Sprue- associated lymphoma → T cell lymphoma
      • Occurs after 10-20 year history of symptomatic malabsorption
    • HIV / AIDS → tends to be NHL of B-cell type
    • Pts with congenital / therapy-induced immunodeficiency states
    • lymphoid nodular hyperplasia
• Aetiology
  • Primary small bowel lymphoma (10%) – most commonly in the ileum
  • Mostly (90%) secondary involvement of small bowel – ie secondary manifestations of nodal lymphoma
• Clinical
  • May be asymptomatic
  • May cause
    • Obstruction
    • Blood loss
    • Perforation – in 10% of presentations
      • (due to lack of stromal support; chemo can also reduce tumour bulk leading to perforation)
• Pathology
  • Overall, most gut lymphomas are B-cell type (>95%); the rare T-cell tumours almost always occur in pts with pre-existing Coeliacs disease
• Ix
  • CT
  • Endoscopy
  • Excisional Bx
• Mx
  • Primary/ isolated / localised small intestinal lymphoma: surgery
  • Diffuse / secondary lymphoma: Combination chemo
• Prognosis / Natural Hx:
  • Primary GI lymphomas better prognosis than those arising in other sites
  • 85% 10YS