Lymphoma Prognosis and Life Expectancy

• Group of diseases caused by malignant lymphocytes the accumulate in the lymph nodes
• Occasionally they may spill into the blood – leukaemic phase or infiltrate other organs
• Major subdivision is into Hodgkins and non-Hodgkins lymphoma based on the histological appearance of Reed-Sternberg cells in Hodgkins lymphoma

Hodgkin’s lymphoma

• B cell lineage
• Less common that Hodgkins and more generally treatable
• There are 4 subtypes of HL;
  • Lymphocyte dominant
  • Lymphocyte depleted
  • Mixed cellulrity
  • Nodular sclerosis
  • (Nodular lymphocyte predominant can also be classed as a subset but there are no RS cells and has features of NH lymphoma so may be treated as such)
• RS cells are clonal B cells and can be associated with EBV infection
• They are a minor population in the tumour

Epidemiology

 In developing countries there is a bimodal distribution, in young adulthood and aged over 50

• 2:1 male predominance

Clinical features

• Painless lymphadenopathy – cervical nodes (70%), axillary nodes (15%), inguinal nodes (10%)
• Generally disease occurs in one node and spreads to others within the lymphatic system
• Splenomegaly – 50% of patients
• Mediastinal involvement – particularly in sclerosing type. May cause pleural effusions and vena cava obstruction
• B cell symptoms
• Alcohol induced pain
• Puritis
• Pel-Ebstein fever – cyclical over period of 7-10 days. Fever spikes can reach 40 degrees
• T cell mediated immune deficiency associated with infections e.g. herpes, fungal, mycobacterial

Biochemical findings

• Normocytic normochromic anaemia – rarely BM is involved
• 1/3 of patients have a neutrophilia or eosinophilia
• Advanced disease is associated with lymphopenia
• ESR is raised
• Serum LDH can be raised

Classification

• Diagnosis is by histological examination of excised lymph node
• Nodular sclerosis and mixed cellularity are the most common
• Lymphocyte predominant has the most favourable prognosis

Clinical staging – Ann Arbor staging

• Stage 1 node involvement in one lymph node area
• Stage 2 2 or more nodal areas confined to one side of the diaphragm
• Stage 3 indicates nodal involvement on both sides of the diaphragm. Splenic disease is included by is designated as IIIs
• Stage 4  involvement outside the lymph node areas e.g. BM, liver
• The clinical stage is followed by a letter A or B indicating the absence of presence respectively of one of more aspects of the B cell symptoms
• Local extranodal extension from a mass of nodes does not advance the stage of the disease but is indicated by the subscript E

Prognosis

• Decreased by;
  • Age < 45
  • Male sex
  • Albumin <40
  • Lymphocytes <8%
  • Stage IV
  • Hb <10.5
  • WCC >15

Treatment

• With chemotherapy, radiotherapy or combination of both
• Gold standard for early disease is 2-4 cycles of ABVD – doxorubicin, bleomycin, vincristin and dacarbazine) with involved field radiotherapy

Prognosis

• 5 year survival rate ranges from 50% to 90% depending on age, stage and histology

Late effects of Hodgkins’s lymphoma and its treatment

• Second malignancies
  • Lung cancer (due to radiotherapy treatment)
  • Acute myeloid leukaemia (associated with alkylating agents)
  • Breast cancer (associated with radiation)
• Cardiac disease (mediastinal radiation)
• Endocrine dysfunction
  • Hypothyroidism
  • Infertility

Non-Hodgkin’s lymphoma

• 6^th most common cause of cancer death
• The types of NHL represent different stages in lymphocyte differentiation
• 85% are of B cell origin, the rest are T cell or null cell

Types of NHL

• Low grade (indolent)
  • Long life expectancy if left untreated
  • 85-90% present at stage III or IV disease
  • Incurable
• Intermediate
• High grade (aggressive)
  • Life expectancy in weeks if not treated
  • Potentially curable

Most common NHL subtypes;

• Diffuse B cell lymphoma
• Follicular lymphoma
• MALT Marginal B cell lymphoma
• Peripheral T cell lymphoma

Aetiology

• Immune suppression
  • Congenital
  • Age
  • Organ transplantation e.g. cyclosporine
  • AIDS
• DNA repair defects – ataxia telangiectasia
• Chronic inflammation and antigen stimulation
  • H. pylori
  • Chlamydia psittaci
  • Sjorgen’s syndrome
• Viral causes
  • EBV- Burkett’s lymphoma
  • HTLV-I – T cell leukemia-lymphoma
  • HTLV-V – cutaneous T cell lymphoma
  • Hepatitis C

Clinical features

• Lymphadenopathy – may fluctuate or spontaneously remit especially in low grade lymphomas
• Constitutional B cell symptoms – fever, night sweats and weight loss. Occur less commonly than in HL and are associated with disseminated high grade disease
• Oropharyngeal involvement – Waldeyer’s ring lymphoid structures – sore throat or obstructed breathing
• Cytopenia – anaemia, neutropenia, thrombocytopenia
• Abdominal disease – hetaposplenomegaly
• Classic lymphoma arises in a lymph node
• Extra-nodal primary more common in high grade disease

• Spread of disease is haematological with no predictable pattern

Diagnosis

• Excision biopsy
• Immunohistochemistry to confirm cells are of lymphoid origin – CLA
• Flow cytometry
  • B cell – CD19, CD20, CD72a
  • T cell – CD3, CD4, CD8
• Biochemical findings
  • Normochromic, normocytic is normal, autoimmune haemolytic anaemia
  • If BM is involved there may be neutropenia and thrombocytopenia
  • Lymphoma cells with variable nuclear abnormalities may be found in the peripheral blood
  • Trephine biopsy is important – BM involvement is more likely in low grade lymphomas
  • Serum LDH is raised the more rapidly proliferating and extensive the disease and can be used as a prognostic marker
• Cytogenetics
  • Follicular lymphoma – t(14:18) – bcl-2 oncogene constitutive expression
  • Burkett’s lymphoma – t(8:14) – c-myc oncogene
  • Mantle cell lymphoma – t(11:14) – cyclin D1

Staging is via the Ann Arbor scheme the same as HL

Specific subtypes of Non-Hodgkin’s lymphoma

Follicular lymphoma

• Most common form of NHL
• Generally low grade
• Follicular lymphoma international prognostic index (FLIPI)
  • Nodal regions > 4
  • Elevated LDH
  • Age > 60
  • Stage III/IV
  • Haemoglobin < 12 g/dl
• If 1 or less, associated with very good prognosis – 90% five year survival rate
• If 2, intermediate prognosis – around 80% five year survival rate
• If 3 to 5, poor prognosis – around 50% five year survival
• 10-15% Stage I or II
  • Potentially curable
  • Local radiotherapy
• 85-90% Stage III or IV
  • Incurable
  • Treatment may prolong survival

Treatment options

• Observation
• Radiotherapy
• Chemotherapy e.g. CHOP
• Antibody against CD20 – rituximab
• Stem cell or bone marrow transplant

Diffuse Large B cell lymphoma

• Generally a high grade lymphoma
• Treated with CHOP – cyclophosphamide, hydroxydaudorubicin, vincristin and prednisolone
• Prognosis is improved with the addition of rituximab

Lymphoblastic lymphoma

• T cell malignancy
• Male adolescents
• Mediastinal mass
• T cell variant of T cell acute lymphoblastic leukemia (ALL)
• Prognosis improving with intensive ALL regimens

Burkitt’s lymphoma

• Occurs in endemic and sporadic forms
• Endemic or African Burkitt’s lymphoma is associated with EBV infection
• In virtually all cases the c-myc oncogene is overexpressed as it is translocated to a heavy chain Ig gene t(8:14)
• Typically the patient (generally a child) presents with a massive lymphadenopathy of the jaw
• In other areas it may present as an abdominal mass
• Most rapidly growing human tumour

Mycsis fungoides

• Malignancy of helper T cells
• Presents with severe puritus and psoriasis like lesions
• Can be treated with electron beam radiation, ultraviolet light or topical alkylating agents

MALT lymphoma

• Type of marginal zone lymphoma
• Due to chronic inflammation and antigenic stimulation
• In the stomach is due to chronic infection by H. pylori
• Eradication with PPI, Amoxycillin or Metronidazole + Clarithromycin