clonal, uncontrollably expanding, destructive proliferations of lymphoid cells.
Although 25-40% of NHLs arise extra-nodally, lymphoma cells are most at home in lymph
nodes or other primary lymphoid organs, such as the spleen, thymus, Waldeyer's
ring, or mucosa-associated lymphoid tissue. Lymphoid neoplasms
that predominantly involve the bone marrow and peripheral blood are usually
Like carcinomas and sarcomas,
NHLs more or less resemble
the normal tissue from which they derive. What makes life for the diagnostician
more difficult is that normal lymphocytes go through many stages as they
develop from small, resting, inexperienced cells to larger,
atypical-appearing, proliferating cells. The stimulus for this change, of course, is exposure to antigen. Malignancies may arise from lymphoid cells arrested at any of these stages. Morphologically, immunophenotypically, and genetically, the NHLs
fall into categories with important therapeutic
and prognostic associations.
Both cytologically and architecturally, lymphoid proliferations may lack some of the morphological complexity seen in more highly structured organs. In some cases, ancillary laboratory studies are necessary to determine if a lymphoid proliferation is benign or malignant or to identify its lymphoma subtype. These studies include:
In its goal of teasing actual biologic diseases with immunologic and genetic qualities out of the confusing mass of lymphoid malignancies, the REAL/WHO classification has replaced the Working Formulation, which is now some 20 years old. This classifcation was devised by examining 2 types of morphologic features of lymphomas: 1) the cytologic appearance of individual cells and 2) the follicular or diffuse nature of the proliferation. NHLs were named and then categorized as low grade, intermediate grade, or high grade. These categories have clinical significance that was demonstrated in an initial study of over a thousand cases.
Many clinicians are accustomed to this classification and like the fact that each type of lymphoma is placed in a category with prognostic and therapeutic significance. Nonetheless the classification is limited because it is based only on morphologic findings. It is like diagnosing someone with "red-face disease", when the patient may have erythroderma, SVC compression, carcinoid syndrome, or sunburn.
For the patient and clinician the most important distinction is between low grade NHLs on the one hand and intermediate and high grade ones on the other. These 2 groups of NHLs have morphological, biological, and clinical differences that are discussed later.