l A. Lymphocytes evolve from pluripotent stem cells located in the bone marrow, and differentiate into two major functional cell types:
l 1. B lymphocytes, comprising the humoral immune system, whose ultimate function is the production of antibodies
l 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.
The anatomical organization of the lymphoid immune system
l The anatomical organization of the lymphoid immune system can also be divided into two major functional groups:
l 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
l 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
l C. The lymph nodes, in their totality, are the largest of the secondary immune organs, and the site of the majority of lymphoid pathology.
Sub divisions
l A. The lymph node has 7 major subdivisions.
l 1. The lymph node capsule, which surrounds the lymph node
l 2. The subcapsular sinus- the initial entryway of lymphatic fluid into the node via afferent lymphatics
l 3. The lymph node cortex- beneath the subcortical sinus-the location of primary and secondary lymphoid follicles
l a. In the absence of immune stimulation, the cortical lymphoid follicles areprimary 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
l b. With antigenic stimulation, antigen recognizing B cells are stimulated to replication and differentiation. This converts the primary follicle into asecondary 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.
l 4. The paracortex- the region surrounding and beneath the germinal centers
l 5. The medulla- deep to the cortex/paracortex, and composed of medullary cords and medullary sinuses
l 6. Medullary vessels- artery and vein
l 7. Afferent and efferent lymphatic vessels
lymphoma
l The term lymphoma describes any neoplastic disorder of lymphoid tissue. Malignant lymphomas fall into two groups:
l Hodgkin's disease or Hodgkin's lymphoma
l non-Hodgkin's lymphoma
Major differences exist between the two:
l age - bimodal distribution in Hodgkin's, many are young; median age of 50 in non-Hodgkin's, increasing with age
l 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
l 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
l 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
Hodgkin's disease
l aetiology
l Hodgkin's disease is of unknown aetiology.
l 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.
l 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.
l However, at present this theory remains unproven.
l It seems likely that there is a multifactorial mechanism for the development of Hodgkin's lymphoma.
epidemiology
l 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).
l 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.
l Ninety-five per cent of patients present with lymph gland involvement
histology
l Hodgkin's disease is divided by the Rye classification into four types:
l lymphocyte predominant:
– thought to be a clinically distinct B cell lymphoma
– often only affects a single lymph node
l nodular sclerosis:
– accounts for 70-80% of Hodgkin's disease
– classically a disease of young women
– presents with cervical and mediastinal lymphadenopathy
l mixed cellularity:
– commonly found in elderly people
– often widespread at presentation
l lymphocyte depleted:
– a rare disease
l 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.
clinical features
l The majority of patients present with lymphadenopathy.Other features include:
l generalised pruritus
l anaemia
l immune dysfunction
l B symptoms:
– fever
– night sweats
– weight loss
l 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
differential diagnosis
l In a young patient the differential includes:
l infection:
– EBV
– CMV
–
– HIV
– toxoplasmosis
– brucellosis
l ongoing regional sepsis:
– cat scratch disease
– tuberculosis
l sarcoidosis
l lymphadenopathy associated with collagen vascular diseases
l chronic lymphocytic leukemia
l non-Hodgkin's lymphoma
l In older patients, secondary carcinoma must be included in the differential diagnosis of any localised lymphadenopathy.
investigations
l Investigative procedures include:
l lymph node biopsy
l FBC
l ESR
l liver function tests
l renal function tests e.g. renal clearance
l chest radiography
l CT scan and ultrasound - to demonstrate abnormalities of the upper Para-aortic and mesenteric nodes
l lymphography - rarely used
l 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.
l
prognosis
l 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 >70% should be achieved.
l Prognostic indicators include:
l age - better prognosis in younger patients
l histology - lymphocytic predominant > nodular sclerosis > mixed cellularity > lymphocytic depletion
l stage - lower has better prognosis
l symptoms - generalised symptomatic disease has worst prognosis
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