Makindo Medical Notes

Related Subjects: |Hodgkin Lymphoma |Non Hodgkin Lymphoma |Diffuse large B-cell lymphoma |Intravascular large B-cell lymphoma |Mantle cell lymphoma |Marginal Zone Lymphoma |Gastric (MALT) Lymphoma |Primary CNS Lymphoma (PCNSL) |Burkitt's lymphoma |Follicular Lymphoma

Most are B cell lineage and so Rituximab an antibody against B cells CD20 can be used. High lactate dehydrogenase (LDH) are associated with fast-growing lymphomas

About

• Malignant disorder of lymphoid cells in lymphoid tissue
• 10% of lymphomas are HL and 90% NHL
• Peak incidence Age 20-40
• Viral infections or Immunosuppression

Non-Hodgkin Lymphoma (NHL) is a diverse group of blood cancers that include any type of lymphoma except Hodgkin Lymphoma. NHL typically originates in the lymphatic system, which is part of the body’s immune system. The disease can develop in lymph nodes and lymphatic tissue throughout the body. NHL is categorized based on the type of lymphocyte it affects (B cells or T cells) and its growth rate (indolent or aggressive).

Types of Non-Hodgkin Lymphoma

• B-Cell Lymphomas: The most common type of NHL, accounting for about 85% of cases. Subtypes include:
  • Diffuse Large B-Cell Lymphoma (DLBCL): The most common aggressive NHL subtype.
  • Follicular Lymphoma: A common indolent (slow-growing) subtype.
  • Chronic Lymphocytic Leukaemia (CLL)/Small Lymphocytic Lymphoma (SLL): An indolent lymphoma that affects both blood and lymph nodes.
  • Mantle Cell Lymphoma: A rarer and more aggressive B-cell lymphoma.
  • Burkitt Lymphoma: A highly aggressive form often associated with EBV infection and commonly seen in children.
• T-Cell Lymphomas: Less common than B-cell lymphomas, these include:
  • Peripheral T-Cell Lymphoma (PTCL): A group of aggressive T-cell lymphomas that originate in mature T cells.
  • Cutaneous T-Cell Lymphoma (CTCL): A group of T-cell lymphomas that primarily affect the skin, such as Mycosis Fungoides and Sézary Syndrome.
  • Angioimmunoblastic T-Cell Lymphoma (AITL): An aggressive subtype associated with immune system dysregulation.
  • Anaplastic Large Cell Lymphoma (ALCL): A rare T-cell lymphoma that can be systemic or primarily cutaneous.

Aetiology

• Usually a B or T or NK cell lineage

Risk factors

• Immunodeficiency - hypogammaglobulinaemia or Wiskott-Aldrich syndrome) or HIV
• Autoimmune disease (Crohn disease, RA, SLE, Sjogren syndrome, or psoriasis)
• Treatment for autoimmune diseases, especially with methotrexate and tumour necrosis factor (TNF)-inhibitor therapy as immunosuppression therapies
• Treatment with certain drugs used after solid organ transplantation
• Infections
  • HTLV-1 (Adult T cell lymphoma)
  • HCV (Splenic marginal zone lymphoma)
  • H. pylori (Gastric MALT)
  • EBV Hodgkin's lymphoma, Burkitt's lymphoma, Primary CNS lymphoma, post-transplant lymphoproliferative disorders
  • HIV - primary CNS lymphoma x 17 times expected
  • Borrelia burgdorferi - cutaneous marginal zone lymphoma
  • Campylobacter jejuni - small bowel marginal zone lymphoma
  • HHV8 - Castleman's disease, primary effusion lymphoma, body cavity lymphoma in HIV
• Genetic
  • Burkitt's lymphoma t(8;14) and c-myc gene on chromosome 8 translocations
  • Follicular lymphoma t(14;180
  • Mantle cell lymphoma t(11;14)
  • Anaplastic large cell lymphoma (t(2;5)
  • Diffuse large cell lymphoma mutations/translocation on bcl-6 on 3q27
• Family history of lymphoma
• Age - commoner in adults older than 60, although NHL also occurs in children and younger adults)
• Male sex
• Exposure to certain chemicals, such as certain herbicides (for example, Agent Orange) and pesticides, and some chemotherapy drugs used to treat other cancers or autoimmune diseases
• Treatment with radiation therapy for other cancers, including NHL

Clinical: NHL is often widely disseminated at presentation, including in extranodal sites.

• B symptoms: fever, unexplained weight loss, drenching sweats
• Lymphadenopathy - peripheral, painless, persistent
• Neurological symptoms suggest brain or spine lesions
• Abdominal pain, nausea, vomiting, decreased appetite, or feeling full.
• Hepatosplenomegaly, ascites may be seen
• Rash or itchy red or purple lumps or nodules under the skin
• Anaemia, Thrombocytopenia, lymphocytosis,

Clinical Classification

• Indolent NHL: slow progressions, low proliferation fraction
  • Chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL)
  • Follicular lymphoma (FL) : the second most common type of NHL diagnosed often age 60 with enlarged nodes. Follicular lymphoma is graded from 1 to 3 depending on the number and pattern of certain large cells called centroblasts seen in biopsy samples. Usually presents with peripheral painless nodes and B symptoms. Median age is 55. t(14;18) leads to overexpression of bcl-2.
  • Lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (WM): uncommon B-cell lymphoma with high levels IgM and increased plasma viscosity
  • Marginal zone lymphoma (MZL): B-cell lymphoma that accounts aged 60. One form is mucosa-associated lymphoid tissue [MALT]) occurs outside the lymphatic system
  • Mycosis fungoides (MF): Cutaneous T-cell lymphoma (CTCL) is a general term for a group of T-cell lymphomas that originate in the skin. Mycosis fungoides is the most common type of CTCL. This type of lymphoma is indolent and usually progresses very slowly. Patients with mycosis fungoides may have various types of lesions, including Patches, which are usually flat, possibly scaly, and look like a rash or plaques, which are thicker, raised, usually itchy lesions that are often mistaken for eczema, psoriasis, or dermatitis
• Aggressive NHL: rapidly progressive, less differentiation, higher proliferation factor
  • Anaplastic large cell lymphoma (ALCL) Angioimmunoblastic T-cell lymphoma (AITL)
  • Burkitt/Burkitt-like lymphomas: a rare, highly aggressive B-cell NHL. There are three main types. Associated with EBV.
  • Diffuse large B-cell lymphoma (DLBCL): Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma. Rapid swelling in the neck, underarms, or groin or abdominal pain and swelling caused by enlarged lymph nodes. Other symptoms include night sweats, chills, unexplained fevers, and weight loss, a cluster of symptoms called B symptoms.
  • Lymphoblastic leukaemia/lymphoma
  • Mantle cell lymphoma (MCL)
  • Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS)
  • Primary mediastinal large B-cell lymphoma (PMBL) (a subtype of DLBCL): arises in the thymus gland and is usually limited to the mediastinum
  • Sezary syndrome (an advanced subtype of cutaneous T-cell lymphoma): a rare, aggressive form of CTCL that affects both the skin and the blood. Most cases occur in adults older than 60. The most common symptoms are swollen lymph nodes and a red, very itchy rash that covers large portions of the body.

Staging NHL

Investigations

• FBC, LFT, U&E, ALP, LDH, ESR, CT TAP
• Incisional Lymph node biopsy
• Bone marrow aspiration and trephine.
• Immunophenotyping of surface antigens to distinguish T- and B-cell tumour s.
• Immunohistochemistry
• Cytogenetic analysis for translocations.
• Urate levels - can cause renal failure during treatment.
• Lumbar puncture if CNS disease suspected
• MRI/CT spine if cord compression suspected
• MUGA cardiac scan before cardiac toxic medications
• HIV testing - if risk factors are present.
• PET scans can help identify response to disease
• Hypergammaglobulinaemia not produced as B cells inactive

Assess Performance Status Grade Description

• 0: Fully active and able to carry on all pre-disease activities without restriction
• 1: Cannot perform taxing physical activities, but can move around (ambulatory) and carry out light work (such as light housework) or do things that can be done while seated (such as office work)
• 2: Can move around and take care of oneself, but unable to do any work; up and about for more than half of awake hours
• 3: Can only partially take care of oneself; confined to a bed or chair for more than half of awake hours
• 4: Completely disabled; cannot take care of oneself; completely confined to a bed or chair

Management

• Indolent (Low Grade) tumour (Slow course. Median survival 10 years)
  • Limited disease Stage IA/IIA: radiation therapy
  • Advanced disease (IIB/III/IV): CVPR chemotherapy Cyclophosphamide, Vincristine, Prednisone, Rituximab x 8 cycles then rituximab for 2 years. If relapse further second line agents. Consider stem cell transplants in fit individuals.
• Aggressive (High Grade)Tumours (Potentially curable with aggressive treatment)
  • Commonest form is diffuse large B-cell NHL which responds to following.
  • Limited disease Stage IA/IIA: CHOPR (Cyclophosphamide, doxorubicin, vincristine and prednisolone with rituximab) x 3 cycles. Repeat cycle if complete remission otherwise advanced field radiation
  • Advanced disease (IIB/III/IV): CHOPR x 6 cycles. PET scan and if only local disease then radiotherapy. Radiotherapy for debulking or cord compression. May need intrathecal chemotherapy to prevent leptomeningeal disease. If diffuse residual disease then Salvage with GDPR (Gemcitabine, Dexamethasone, Cisplatin, Rituximab) or RICE (rituximab, ifosamide, carboplatin, etoposide) and autologous stem cell transplant
• Highly Aggressive Tumours
  • Burkitt's lymphoma
  • Acute Lymphoblastic lymphoma

References