Clinical case

A 25-year-old male smoker of 20 cigarettes/day presented with a history of appendectomy in childhood. For the previous month and a half he had a lump in the right side of the face, in the lower genian region. During this period the patient used amoxicillin-clavulanic acid, though the lesion failed to disappear. Clinical examination revealed a hard-elastic tumor in the zone of the masseter muscle. The lesion was rounded in shape, with a diameter of about 3 cm. It was not adhered to layers and was painless. The overlying skin appeared normal. The intraoral soft tissues exploration proved normal. A panoramic X-ray study revealed extensive caries with pulp involvement and an apical radiotransparency in tooth 4.6. The lesion was punctured via the intraoral route with a trocar, without obtaining either blood or purulent material. The tooth in question was removed, and laboratory tests were requested together with an MRI study and a biopsy. The laboratory test findings were within normal limits. MRI showed a very well delimited lesion measuring 21x31x34 mm in size, located in the right-side Bichat fatty tissue space in contact with the ascending mandibular ramus. There was no periosteal reaction, evidence of infiltration or osteolytic lesions. The lesion was seen to grow towards the right masseter muscle, compressing rather than infiltrating the latter, since clear delimitation of the muscle was seen. The lesion was hyperintense, with heterogeneous internal zones. Following contrast injection, uptake was seen to be heterogeneous, with a hypointense center producing a ring-like appearance in sagittal sections. Right lateral neck adenopathies were also seen, some measuring over 10 mm in diameter. Adenopathies were likewise located around the jugular-carotid vascular bundle and in the submental region.
Under general anesthesia, a lateral cervicotomy was performed to access the tumor. A biopsy of the lesion was obtained, together with several satellite adenopathies. The pathology report indicated the presence of a compact mass of small cells with scant cytoplasm, with immunohistochemical positivity for CD-20, CD-79a, CD-10 and bcl-6, and accompanying CD-45Ro+ T cells. CD-3, EMA, S-100, CD-15 and CD-30 proved negative. The Ki-67 cell proliferation index showed positivity in 10-15% of the cell population. The diagnosis was HIGH-GRADE FOLLICULAR B-CELL LYMPHOMA.

Discussion

Lymphomas constitute a large and heterogeneous group of lymphatic system malignancies. Since the first description of these lesions by Hodgkin in 1832 (1), the classification of lymphomas has generated controversy and confusion. With the purpose of establishing uniform diagnostic criteria to facilitate our understanding of these processes, a consensus classification was proposed, known as the REAL (Revised European-American Classification of Lymphoid Neoplasms)(1994). This classification was posteriorly adopted by the World Health Organization (WHO), with some modifications (2). The REAL does not group these neoplasms into similar clinical behavior categories. Rather, the classification identifies them according to their morphological, immunophenotypic and molecular characteristics, and each tumor is associated to the corresponding normal precursor or non-precursor cell (3). Three large categories are established: non-Hodgkin B cell lymphomas, non-Hodgkin T/NK cell lymphomas, and Hodgkin lymphomas. The latter in turn are defined by the presence of Reed-Sternberg cells, which are giant cells with two large nuclei and a thick nuclear membrane.
Non-Hodgkin lymphomas (NHLs) have a less predictive clinical behavior than Hodgkin lymphomas. The common form of presentation in the region of the neck and face is an often painless and rapidly growing mass (4,5).
In the oral cavity, these lesions can manifest as a possibly painful mass, in the form of an ulcer, or with diffuse involvement of structures such as the gums (6).
Approximately two-thirds of all NHLs correspond to proliferations derived from B lymphocytes, while the rest originate from T/NK cells or represent other lymphomas.
The histological diagnosis must be completed with staging of the disease. This requires a thoracoabdominal and pelvic CAT study, as well as a bone marrow biopsy and full hematological evaluation. The Ann Arbor classification is used in this context (7), with the definition of four stages: I.- Adenopathies in a single lymph node chain; II.- Adenopathies in two or more lymph node chains on the same side of the diaphragm; III.- Adenopathies in two or more lymph node chains on both sides of the diaphragm; IV.- Disseminated presentations. In turn, the letter E after the stage indicates extra-lymph node involvement, while the letter A or B expresses the absence or presence of characteristic symptoms of the disease: weight loss of over 10% in the previous 6 months; profuse nocturnal perspiration; and fever of 38ºC or higher, with no justifying cause.
In the present case, follicular lymphoma is a mature B cell neoplasm representing follicular center lymphoma. It is the second most common lymphoma, after diffuse large-cell NHL. The disease tends to manifest in patients over 30 years of age, and affects both males and females equally. The risk factors underlying the disease comprise exposure to pesticides, chemo- and radiotherapy, viral infections, and congenital and acquired immune deficiencies. The risk is multiplied 6-fold in transplant patients (8).
In most cases (up to 80%) the condition manifests as disseminated disease with lymph node and bone marrow involvement. The tumor is indolent rather than aggressive and is non-curable, though prolonged remissions can be achieved in the low-grade presentations. In a considerable number of cases (13% after 10 years) transformation into large-cell lymphoma can occur (9).
Depending on the observed proportion of centroblasts, the tumor can be classified as follows: I.- Centrocytic predominance; II.- Fewer than 15 centroblasts per high-power field; and III.- More than 15 centroblasts per high-power field.
Categories I and II are considered to correspond to low-grade forms, while category III corresponds to high-grade disease (10).
The most common cytogenetic anomaly of reticular lymphoma is chromosomal translocation t(14;15) (q32;q21), detected in 70-75% of all cases. This induces rearrangement of the bcl-2 gene, with over-expression of the encoded protein and constant cell proliferation (11).
The immunohistochemical characteristics in turn include positivity for B cell markers such as CD-19, CD-20, CD-22 and CD-79a. Accompanying T cells (CD-45Ro+) are commonly seen, as in our patient (10).
An index has been developed to establish the prognosis, involving a one-point score for each of the following factors: age (over 60 years); stages III and IV of the Ann Arbor classification; hemoglobin under 120 g/l; more than four affected lymph node locations; and serum lactate dehydrogenase (LDH) levels above normal. This index is known as the IPI (International Prognostic Index)(12). An IPI score of 0-1 implies a low risk, and patient survival reaches 88% after 5 years. In contrast, scores of 4-5 correspond to high risk, with a survival rate of 43% after 5 years.
The treatment of these neoplasms has not been fully standardized. Field radiotherapy is recommended in stage I and IIa disease, including chemotherapy in the presence of over two affected lymph node locations or if there are symptoms. Complete remission is achieved in 89% of the cases, though 46% relapse after 10 years (9).
Stages III and IV are subjected to chemotherapy that reduces the symptoms but fails to avoid relapse. The introduction of rituximab (an anti-CD-20 monoclonal antibody) has radically changed the treatment of follicular lymphomas. The drug is usually used in combination with chemotherapy, and a number of studies have for the first time reported an increase in survival with this type of therapy (13,14).
Other management strategies include interferon, autologous peripheral blood transplantation, allogenic transplants, radioimmunotherapy, other monoclonal antibodies, or the generation of immunotoxins (12,13).

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