14. Indolent non-Hodgkin’s lymphomas

Indolent non-Hodgkin lymphoma

The indolent non-Hodgkin lymphomas can be considered “low-grade”. The life expectancy for patients with indolent NHLs is measured in years, even if untreated. They’re rarely curable. Most cases present in stage III and IV.

The indolent NHLs are:

  • B cell neoplasms
    • Chronic lymphocytic leukaemia (see topic 15)
    • Marginal zone lymphoma
      • MALT lymphoma
      • Nodal marginal zone lymphoma
    • Follicular lymphoma
    • Mantle cell lymphoma
    • Hairy cell leukaemia
  • T cell neoplasms
    • Primary cutaneous peripheral T cell lymphoma
      • Mycosis fungoides
      • Sézary syndrome

Source: https://www.uptodate.com/contents/image?imageKey=HEME%2F59978

Presentation:

Indolent NHLs usually present with slow-growing lymphadenopathy, hepatomegaly, splenomegaly or cytopaenias.

Treatment:

There are many treatment options for indolent NHLs. The vast majority will have an initial response to therapy by most of these patients will ultimately experience histological transformation to a more aggressive lymphoma (like DLBCL) or relapse.

Stage I NHLs can be cured with just radiotherapy, if all disease-involved sites are contained within one radiation field.

Stage II, III, IV NHLs, and stage I NHLs which cannot be treated with only radiotherapy should only be treated if any of these indications are present:

  • The disease causes B symptoms
  • The disease is rapidly progressing
  • The patient has cytopaenia
  • The disease compromises normal organ function

If any of these indications are present the patient should be treated with rituximab + bendamustine, which is superior to R-CHOP for indolent NHLs. If none of these indications are present the “watch and wait” approach is best, where the patient is closely observed for any changes.

A new anti-CD20 antibody called obinutuzumab is potentially more effective but more expensive and more toxic than rituximab.

Relapse:

Most patients treated for NHL will experience relapse. When a patient experiences relapse after initial treatment of an indolent NHLs, biopsy should be performed to rule out histological transformation of the cancer. If there is none, and there are no indications for treatment (see above), the “watch and wait” approach is best.

If there is indication for treatment, there are multiple treatment options:

  • Haematopoietic stem cell transplantation
  • Chemoimmunotherapy
  • Radioimmunotherapy
  • Novel agents
Follicular lymphoma

Etiology:

t(14;18). This translocation involves the antiapoptotic protein Bcl-2 and the immunoglobulin heavy chain gene (IgH). IgH is highly active, so this translocation significantly increases production of Bcl-2.

Epidemiology:

Most common indolent lymphoma. Most common in middle-aged adults.

Clinical features:

Often presents with asymptomatic generalized lymphadenopathy.

Prognosis:

25 – 35% of cases will progress into DLBCL, a process called Richter’s transformation.

Mantle cell lymphoma

There are two forms of MCL:

  • Classical (cytic) mantle cell lymphoma
  • Aggressive (blastic) mantle cell lymphoma

Etiology:

t(11;14). This translocation involves the cell cycle checkpoint protein cyclin D1 and the immunoglobulin heavy chain gene (IgH). Increased production of cyclin D1 increases proliferation by driving the cells through the cyclin D1-dependent cell cycle checkpoint.

Epidemiology:

Most common in older men.

Clinical features:

Often presents with asymptomatic lymphadenopathy. The bone marrow is frequently involved. It can occasionally present as GI polyposis.

Diagnosis:

Staining tissue biopsies with immunohistochemistry for cyclin D1 confirms the diagnosis in most cases. FISH can detect the t(11;14) translocation, but it is not specific for MCL. Tumor cells are often CD5+.

Prognosis:

Very bad prognosis among the indolent NHLs. The aggressive type has worse prognosis than the classical type.

Marginal zone lymphoma

There are three types of marginal zone lymphoma (MZL):

  • Extranodal marginal zone lymphoma (= MALT lymphoma)
  • Nodal marginal zone lymphoma
  • Splenic marginal zone lymphoma

Etiology:

Extranodal MZLs originate in the MALT. This occurs most frequently in the mucosa of the stomach, but also in the intestines, thyroid and salivary glands. These lymphomas are most commonly seen in association with chronic infectious or inflammatory conditions, like:

  • H. pylori infection – gastric MALT lymphoma
  • C. jejuni infection – intestinal MALT lymphoma
  • Hashimoto thyroiditis – thyroid MALT lymphoma
  • Sjögren syndrome – MALT lymphoma in the salivary glands
  • Chlamydia psittaci – MALT lymphoma in the ocular adnexa

Epidemiology:

The extranodal variant is the most common.

Clinical features:

The clinical features depend on the tissue involved.

Treatment:

If caught early, extranodal MZLs can be treated by treating the causative infection or inflammation. For example, gastric MALT lymphoma often undergoes complete remission after antibiotic therapy against H. pylori.

Mycosis fungoides

Mycosis fungoides is the most common type of primary cutaneous peripheral T cell lymphoma.

Etiology:

Mycosis fungoides originates from CD4+ T cells which have affinity for the skin. The tumor cells infiltrate the epidermis, forming so-called Pautrier microabscesses.

Epidemiology:

Older adults.

Clinical features:

Usually presents with pruritic erythematous patches and plaques.

Treatment:

The exact treatment depends on stage. Options include:

  • Topical steroids
  • Topical alkylating agents
  • Localized electron beam therapy
  • Ultraviolet light therapy
  • Chemotherapy

Systemic chemotherapy is only used in advanced stages.

Prognosis:

Mycosis fungoides may progress into Sézary syndrome, but Sézary can also develop de novo. Sézary syndrome is characterised by malignant CD4+ T cells in the peripheral blood and local lymph nodes.


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13. Aggressive non-Hodgkin’s lymphomas

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28. Haematopoietic Stem Cell Transplantation

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