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Stages of Non-Hodgkin’s lymphoma

PET scan shows multiple black hot spots due to widely disseminated multifocal disease.  The PET scan has become an important staging tool.
PET scan shows multiple black hot spots due to widely disseminated multifocal disease. The PET scan has become an important staging tool.
After the diagnosis of NHL has been made, the doctor is interested to know from his pathologist as to whether the NHL is of high grade or low grade and whether it is of T or B cell origin. The first is assessed by the pathologist by microscopic analysis of the biopsy specimen; in low grade tumours the cells often resemble normal small lymphocytes in many regards but will show some characteristics that are diagnostic of NHL and others which help the pathologist to further subtype the NHL.


For example the pathologist may say that the tumour is a follicular, low grade NHL, which means that he has seen the typical small round lymphocyte NHL population but also that this is enveloped within groupings/follicles; this is a common type of low grade NHL.


In high grade lymphomas, the pathologist often encounters large bizarre looking malignant lymphocytes, often with many in cell division (mitosis); this is a more aggressive/faster growing cancer. The distinction between T and B cells is made by a process called immunophenotyoping, and there nowadays further subdivisions within the lineages made other immunological tests. For example there are now available a battery of antibodies directed at surface immunoglobulin light chains and the presence of some of these on B cell lineage NHL can be used to subtype (e.g. CD numbering).


Recently, genetic analysis of NHL cells has become a recent science in itself; gene re-arrangement is found in many NHL and engenders excitement in the profession who believe that it is getting closer to the exact genetic defect in this cancer. Recently, the technique of PCR (polmerase chain reaction) technology has been used in gene re-arrangement analysis to detect clonal populations at incredibly low levels and is therefore of extreme interest in the establishment of cure (i.e. that there is no NHL left in the body at the end of a therapy programme).


The above histopathological analysis of the biopsy specimen is the first and a critical first step in the assessment of the type of disease from which the patient suffers. The next question is “how far has it spread and where else may the disease be?”


All patients will have complete body scanning (at least by CT scan and usually nowadays by PET scanning) as well as blood tests, bone marrow and perhaps CSF (for high grade disease). 


Thus staging of the patient is achieved (according to a system that was originally evolved at a conference at Ann Arbor so called the Ann Arbor system):


Stage 1: NHL affecting one group of lymph nodes only (e.g. node swelling/involvement only affecting the lymph node chain down the left side of the neck).


Stage 2: Two or more lymph node groups affected on one side of the diaphragm (e.g. neck and armpit groups of nodes).


Stage 3: Lymph nodes (and in this nomenclature the spleen is counted as a lymph node organ) affected on both sides of the diaphragm (e.g. neck nodal and groin nodal involvement).


 Stage 4: Lymph nodes and other organs involved (e.g. bone marrow, CSF or liver).


The overall outlook for the patient presenting with NHL is worse the higher the stage at presentation. A poorer perceived prognosis can be nowadays reversed by the more aggressive therapies that are given to higher stage patients. 


 There is one small addendum: After these staging groupings, the doctor will often place a suffix A or B. If the patient has a suffix B after his staging then he has been observed to exhibit sweating (sufficient to wake him from sleep), more than 10% body weight loss and/or persistent fever at the time of presentation and this suffix B denotes a slightly worse outlook - stage for stage. Stage suffix A patients do not exhibit any of these clinical features at presentation. In general, patients with B symptoms have a higher bulk of disease and are treated as more extensive disease, than their Ann Arbor stage might suggest.


A special category is recognised where there is only one extranodal site of lymphoma and no lymph node involvement per se: this is referred to as stage 1E.


For some small, isolated skin or conjunctival (MALT) lymphomas presenting as stage 1E disease, the results of local therapy alone (radiotherapy) are excellent,  indicating that these particular forms of lymphoma have a lesser and later tendency to spread.

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