Non-Hodgkin's Lymphoma

 

• Background

  

  
  

  Definition

  • Lymphoma is a malignant proliferation of mature lymphocytes that accumulate in lymph nodes ± other tissue, often as a solid tumour. Differs from leukaemia, which arises in the bone marrow and is present in the blood.
  • Non-Hodgkin's lymphomas (NHL) represent 80% of all lymphomas, and are distinguished from Hodgkin's lymphoma by the absence of Reed-Sternberg cells on light microscopy.
  • NHL are a diverse group of conditions, with proliferating cells potentially accumulating in various sites, including lymph nodes, mucosa-associated lymphoid tissue (MALT), CNS, and skin.
  • 90% are B cell proliferations, 10% T cell.

  Types

  Low-grade lymphoma:

  • Slow growing, good prognosis, but hard to cure.
  • Follicular lymphoma. CD20 +ve.
  • Marginal zone lymphoma. Various types including MALT, which can occur in stomach, lung, thyroid, or salivary/tear glands. Generally remain localised to original organ so good prognosis.
  • Lymphocytic lymphoma. Similar to CLL.
  • Waldenström's macroglobulinaemia (aka lymphoplasmacytoid lymphoma). ↑IgM production.

  High-grade lymphoma:

  • More acute but easier to cure.
  • Diffuse large B-cell lymphoma (DLBCL). CD20 +ve.
  • Mantle cell lymphoma. ↑Cyclin D1, CD5 and CD19-22 +ve. Usually incurable.
  • Peripheral T-cell lymphoma (PTCL).
  • Burkitt's lymphoma. Commoner in kids. Characteristic jaw lymphadenopathy.
  • Lymphoblastic lymphoma. Similar to ALL.

  Epidemiology

  Lifetime risk: 1/50.

  Commoner types, in order of frequency:

  1. DLBCL
  2. Follicular lymphoma.
  3. MALT lymphoma.
  4. Mantle cell lymphoma.

• Signs and symptoms

  Lymphadenopathy:

  • Presenting complaint in ⅔.
  • In high-grade, short history of rapid growth.
  • Splenomegaly often accompanies lymphadenopathy. Especially common in marginal zone lymphoma. Hepatomegaly is less common.

  Extranodal manifestations:

  • Presenting complaint in ⅓.
  • Can be anywhere, meaning almost any symptom.
  • Gut e.g. MALT: abdo pain, weight loss, dyspepsia.
  • Skin e.g. T cell lymphoma: rash, discolouration.
  • Oropharynx e.g. Waldeyer's lymphatic ring (MALT) lymphoma: sore throat, obstructed breathing.
  • Others: nervous system (↑ICP, CN palsy), bone, lung.

  Other features:

  • B symptoms: less common that in Hodgkin's lymphoma, but quite frequent in high-grade.
  • CNS and eye symptoms in Waldenström's.
  • Pancytopenia. Commoner than in Hodgkin's lymphoma.

• Risk factors

  Immunodeficiency:

  • Congenital e.g. Wiskott-Aldrich.
  • Drugs
  • HIV: usually high-grade lymphomas.

  Infection:

  • HTLV-1
  • EBV: Burkitt's, CNS lymphoma in HIV.
  • Hep C: DLBCL, marginal zone lymphoma.
  • H. pylori: gastric MALT.

  Autoimmune:

  • Hashimoto's: thyroid MALT lymphoma.
  • Sjogren's: salivary MALT lymphoma.

• Investigations

  Bloods:

  • FBC: pancytopaenia in bone marrow infiltration.
  • Blood film.
  • ↑LDH, ↑ESR.
  • LFT, U+E.
  • Protein electrophoresis: IgM monoclonal paraprotein in Waldenström's.
  • β2 microglobulin may be useful for prognostic information and follow up.

  Biopsy for diagnosis:

  • Obtain sample via lymph node excision and/or bone marrow biopsy. Biopsy other tissues if indicated, including skin, or gut for gastric MALT (via endoscopy).
  • Cytogenetics: t(14;18) in follicular, t(14;8) in Burkitt's, t(11;14) in mantle cell. Also microscopy, immunohistochemistry, and flow cytometry.

  Imaging for staging:

  • CT or PET-CT.

  Use Ann Arbor staging system.

• Management

  Low-grade:

  • Treatment may not be needed if asymptomatic e.g. in follicular lymphoma.
  • Otherwise, chemo ± radiotherapy.
  • Maintain remission with α-interferon or rituximab (especially if CD20 +ve).
  • H. pylori eradication can sometimes cure gastric MALT.

  High-grade:

  • Chemotherapy e.g. R-CHOP (Rituximab, Cyclophosphamide, doxorubicin [Hydroxydaunomycin], vincristine [Oncovin], Prednisolone).
  • Autologous or allogenic stem cell transplant in refractory cases.

• Complications and prognosis

  Disease complications:

  • Pancytopaenia
  • Pleural or pericardial effusion from mets.
  • Compression from primary or mets: SVC obstruction, spinal cord.
  • GI obstruction and perforation.

  Chemo complications:

  • Tumour lysis syndrome, especially in Burkitt's.
  • Nausea, fatigue, immunosuppression.

  Prognosis:

  • 5 year survival: 60%.
  • Poor prognosis if: >60 years old, B symptoms, bulky or disseminated disease, ↑LDH.