Hodgkin’s Lymphoma

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Hodgkins Lymphoma

• Dr Mohamed Iqbal Musani

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Overview of the lymphoid immune system

• A. Lymphocytes evolve from pluripotent stem cells
  located in the bone marrow, and differentiate
  into two major functional cell types
• 1. B lymphocytes, comprising the humoral immune
  system, whose ultimate function is the production
  of antibodies
• 2. T lymphocytes, comprising the cellular immune
  system, whose functions include
• a. Direct killing of foreign or intracellularly
  infected cells, cytotoxic T cells
• b. Fine control of the immune response through
  the secretion of cytokines, helper and suppressor
  T cells.

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The anatomical organization of the lymphoid
immune system

• The anatomical organization of the lymphoid
  immune system can also be divided into two major
  functional groups
• 1. The primary immune organs, which are the sites
  of initial maturation from immature precursors
  into immune competent cells
• a. B cells- bone marrow
• b. T cells- thymus
• 2. The secondary immune organs, which are the
  sites of antigen driven replication and
  differentiation into committed effector cells
• a. Lymph nodes
• b. Spleen
• c. Mucosal Associated Lymphoid System
  (MALT)-lymphoid cells lining the respiratory and
  gastrointestinal tracts
• d. Everywhere else
• C. The lymph nodes, in their totality, are the
  largest of the secondary immune organs, and the
  site of the majority of lymphoid pathology.

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Lymph node anatomy
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Sub divisions

• A. The lymph node has 7 major subdivisions.
• 1. The lymph node capsule, which surrounds the
  lymph node
• 2. The subcapsular sinus- the initial entryway of
  lymphatic fluid into the node via afferent
  lymphatics
• 3. The lymph node cortex- beneath the subcortical
  sinus-the location of primary and secondary
  lymphoid follicles

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• a. In the absence of immune stimulation, the
  cortical lymphoid follicles are primary follices,
  composed of small B lymphocytes which may be
  virgin B lymphocytes or recirculating memory B
  cells. There is also a fine meshwork or dendritic
  reticulin cell cytoplasm, which is invisible
  without special immunolabelling techniques
• b. With antigenic stimulation, antigen
  recognizing B cells are stimulated to replication
  and differentiation. This converts the primary
  follicle into a secondary follicle or germinal
  center, surrounded by a mantle zone of transient
  small lymphocytes, and a central area containing
  replicating "follicular center cells" and their
  differentiating progeny- see below.

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Sub divisions

• 4. The paracortex- the region surrounding and
  beneath the germinal centers
• 5. The medulla- deep to the cortex/paracortex,
  and composed of medullary cords and medullary
  sinuses
• 6. Medullary vessels- artery and vein
• 7. Afferent and efferent lymphatic vessels

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lymphoma

• The term lymphoma describes any neoplastic
  disorder of lymphoid tissue. Malignant lymphomas
  fall into two groups
• Hodgkin's disease or Hodgkin's lymphoma
• non-Hodgkin's lymphoma

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Major differences exist between the two

• age - bimodal distribution in Hodgkin's, many are
  young median age of 50 in non-Hodgkin's,
  increasing with age
• mode of spread - predictable in Hodgkin's, spread
  is step-by-step to contiguous lymph nodes,
  usually starting in the neck spread is random in
  Non-Hodgkin's
• histology - polymorphic in Hodgkin's, with
  diagnostic Reed-Sternberg cells often outnumbered
  by reactive cells, especially eosinophils
  Non-Hodgkin's is monomorphic, with malignant
  cells most numerous
• prognosis - up to 80 of Hodgkin's lymphomas are
  potentially curable this proportion is much less
  for Non-Hodgkin's patients taken as a whole

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Hodgkin's disease

• aetiology
• Hodgkin's disease is of unknown aetiology.
• Because of the origin of the tumour from immune
  cells there has been put forward the theory that
  Hodgkin's disease may be immunologically
  mediated.
• The mechanism for development of the tumour may
  be the result of a continuous antigen challenge
  mechanism or by failure of the innate
  immunological surveillance system.
• However, at present this theory remains unproven.
  
• It seems likely that there is a multifactorial
  mechanism for the development of Hodgkin's
  lymphoma.

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epidemiology

• In adults aged 15 years in England and Wales in
  1992 - there were 1,188 new cases of Hodgkin's
  lymphoma the number per annum per 2000
  population was 0.05 (1).
• The disease has a bi-modal age incidence. The
  first peak occurs between 15 and 34 years and the
  second peak occurs after 50 years.
• Ninety-five per cent of patients present with
  lymph gland involvement

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histology

• Hodgkin's disease is divided by the Rye
  classification into four types
• lymphocyte predominant
• thought to be a clinically distinct B cell
  lymphoma
• often only affects a single lymph node
• nodular sclerosis
• accounts for 70-80 of Hodgkin's disease
• classically a disease of young women
• presents with cervical and mediastinal
  lymphadenopathy
• mixed cellularity
• commonly found in elderly people
• often widespread at presentation
• lymphocyte depleted
• a rare disease
• The classical cell seen on histological
  examination is the Reed-Sternberg cell, which is
  a necessary, but not sufficient element, for a
  diagnosis of Hodgkin's disease. Other cells seen
  in diseased tissue include histiocytes,
  lymphocytes, plasma cells, eosinophils and
  fibroblasts.

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clinical features

• The majority of patients present with
  lymphadenopathy.Other features include
• generalised pruritus
• anaemia
• immune dysfunction
• B symptoms
• fever
• night sweats
• weight loss
• In advanced disease there may be infiltration of
  any organ often presenting with
  hepatosplenomegaly. Other sites for tumour
  localisation include bone, bone marrow, lung,
  kidneys.The Ann Arbor system is used to stage
  Hodgkin's

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differential diagnosis

• In a young patient the differential includes
• infection
• EBV
• CMV
• HIV
• toxoplasmosis
• brucellosis
• ongoing regional sepsis
• cat scratch disease
• tuberculosis
• sarcoidosis
• lymphadenopathy associated with collagen vascular
  diseases
• chronic lymphocytic leukemia
• non-Hodgkin's lymphoma
• In older patients, secondary carcinoma must be
  included in the differential diagnosis of any
  localised lymphadenopathy.

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investigations

• Investigative procedures include
• lymph node biopsy
• FBC
• ESR
• liver function tests
• renal function tests e.g. renal clearance
• chest radiography
• CT scan and ultrasound - to demonstrate
  abnormalities of the upper Para-aortic and
  mesenteric nodes
• lymphography - rarely used
• Splenectomy has been used in the past as a
  diagnostic and therapeutic procedure. Althought
  the spleen is involved in 30 of cases of
  Hodgkin's disease there is no prognostic
  advantage for patients who undergo splenectomy.
•  

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prognosis

• In localised disease treated with irradiation
  there is a 5-year survival rate of at least
  80.In disseminated disease treated with
  cytotoxic chemotherapy ---
• the 5-year survival falls to 50.Overall, a 5
  year survival of gt70 should be achieved.
• Prognostic indicators include
• age - better prognosis in younger patients
• histology - lymphocytic predominant gt nodular
  sclerosis gt mixed cellularity gt lymphocytic
  depletion
• stage - lower has better prognosis
• symptoms - generalised symptomatic disease has
  worst prognosis