Lymphomas represent the third most frequent neoplasia on a worldwide scale and constitute 3% of malignant tumors. Their prevalence progressively grows at the annual rate of 3%.
The WHO classification of tumors, which result from the hematopoietic tissues and the lymphoid tissues, allows to distinguish lymphoid neoplasias, according to the cell line and the differentiation, into:
peripheral B-cell neoplasia;
B-cell proliferations of uncertain malignant potential;
Peripheral T/NK-cell neoplasia;
T-cell proliferations of uncertain malignant potential [1–3].
The main histopathologic feature of Hodgkin's lymphoma is the presence of Reed-Stenberg cells (binucleated or multinucleated, with big and clear nuclei and intensely colored "owl's eyes" nucleoli).
The above-mentioned Reed-Stenberg cells are not found in the so-called non-Hodgkin's lymphoma, a category that include all the other histopathologic entities that are not related to Hodgkin's disease . The considerable histological variety of non-Hodgkin's lymphomas involves significant classification problems, although from a morphological point of view, we can identify two main forms of NHL:
• Nodular (or follicular) forms, characterized by a regular nodular pattern. They affect the whole lymph node or the extranodal area;
• Widespread forms, in which neoplastic cells are uniformly distributed on the affected tissue .
From a clinical point of view and in almost all cases, Hodgkin's lymphoma is a nodular lesion that rarely involves the extranodal areas, whereas NHL frequently have an extranodal onset.
In addition, whereas Hodgkin's disease spreads in the nodal groups in a contiguous fashion, in NHL the nodal evolution proceeds randomly; this means that it does not proceed in a contiguous fashion, but is instead unforeseeable (obviously, this aspect has important repercussions on the therapeutic protocol).
It is interesting to notice a geographic variability between the North and the South of Italy, with a ratio of 2:1 in favor of northern regions.
Apart from age, there are several risk factors associated to NHL:
1) Primary or acquired immunodeficiency [6, 7];
2) Autoimmune diseases (Sjögren's Syndrome, LES, AR, Coeliac disease) , especially if treated with immunosuppressant drugs[8, 9];
3) Infective agents, such as:
- Herpetic viruses (EBV, associated to the African form of Burkitt's lymphoma [8, 9], HHV8, associated to Kaposi's Sarcoma and found in some forms of NHL in HIV-positive subjects);
- HCV, whose association with non-Hodgkin's lymphoma is considered to be very high in several European countries with a high prevalence of this infection) [6–9];
-H. Pylori, associated to peptic ulcer and gastric MALT lymphoma [6–9];
4) Professional exposure to noxious chemical agents [6–8];
5) Hereditary factors [6–8].
Chromosomal translocations play a crucial role in the pathogenesis of NHL, determining oncogenes activation or the inactivation of oncosuppressor genes, with the consequent malfunction of the mechanism of genomic rearrangement in the lymphoid cells .
The primary sites most frequently affected are:
Sovraclevear and laterocervical lymph nodes (regarding nodal sites)
Extranodal sites (20-30% of cases) such as Waldeyer's ring, the gastroenteric tract, the skin and the subcutaneous tissue.
In the successive stages, there is the frequent involvement of the bone marrow and spleen, causing splenomegaly, which is almost constant in the immunoblastic form. A severe splenomegaly usually indicates a leukemic progression .
At the level of the oral cavity, they can originate from the lymphoid tissue associated to mucosa (Waldeyer's ring) or can be infiltrations of non-lymphoid tissue.
The most affected sites are tonsils (55% of oral cases), palate (30% of cases), genial mucosa (2% of cases). There are, instead, sporadic manifestations affecting the tongue (2% of cases), the buccal floor (2% of cases) and the retromolar trigone (2% of cases) .
From a clinical point of view, they manifest themselves with an asymptomatic tumefaction, often associated to mucosa ulceration.
The most common type in the head-neck area is the big cells type [6, 11].