Paper # 001

Versión en Español

Adenocarcinoma of the Stomach after Therapy for Lymph Nodes Low Grade Lymphoma

Marcial Garcia-Rojo, Jesús González, Ana Morillo, Jesus Martín

[Title] [Introduction] [Materials and Methods] [Results] [Pictures] [Bibliography]

DISCUSSION

Incidence

The studies from the registry of tumors find an incidence of second tumors of about a 20 per thousand in patients with leukemia or lymphoma (16). In a series of 2,340 patients with lymphoma, Moertel and Hagedorn found 68 patients with a second malignant neoplasm, 25 diagnosed simultaneously, 23 tumors preceded the diagnosis of lymphoma, and 17 appeared after the lymphoma. They concluded that the incidence was not greater than the observed in the general population (10).

In the ample series of NHL a greater incidence of cutaneous and pulmonary neoplasms and acute leukemia has been detected (14). However, the presence of a gastric adenocarcinoma as a secondary tumor is a less frequent phenomenon (13,14).

The incidence of a gastric adenocarcinoma after treatment for a gastric NHL is between 4 % and 14 % (9).

In Hodgkin's disease the incidence of solid tumors is 3.9 %. Breast cancer is the most common solid tumor in some series (8).

Synchronous vs. Metachronous

We have collected 14 cases from the literature in which a nodal non Hodgkin lymphoma (NHL) and an adenocarcinoma of the stomach presented in the same patient (table 1). Most of these cases belong to statistical studies (10,14), and in only 4 cases there was at least some information about the two neoplasms (13,15,17,18). In 3 of these 4 cases the adenocarcinoma of the stomach presented simultaneously with the lymphoma. In one case the gastric adenocarcinoma presented 8 months after remission of the lymphoma. In our case the interval between the diagnosis of lymphoma and the appearance of the adenocarcinoma is of only six months. Besides, the gastric tumor probably had been present for a long period of time because of its extension.

The coincidence of gastric adenocarcinoma with a NHL of thyroid (19) or the brain (20) has also been describe. In these two cases the tumors were also simultaneous

This contrasts sharply with the studies of Hodgkin lymphoma and gastric adenocarcinoma (table 2). We have collected 10 patients in the literature that suffered from these two neoplasms (3,7,8,10). In 6 cases there was enough information about the tumors. Of these, in only one case the Hodgkin lymphoma and the gastric adenocarcinoma presented simultaneously (21). In the other five cases, the interval between the Hodgkin lymphoma and the gastric neoplasm varied between 10 and 2 years (average 7 years) (3,7,22,23).

The type of lymphoma

The type of NHL was stated in very few studies. Furthermore, the description and classification of these tumor don't allow a uniform comparison between the cases (table 1). However, it is easy to observe that diffuse lymphomas are the rule, small B-cell types predominate, that is, low grade or intermediate grade lymphomas predominate.

Some studies propose the hypothesis that patients with low grade B cells neoplasms have a greater susceptibility to suffer from second tumors (12,16), specially those NHL with monoclonality in /kappa immunoglobulin (9,24). Our patient had a cell B diffuse low grade lymphoma type immunocytoma with monoclonality in kappa light chains. No clinical sign of hypersecretion of IgM was found.

The type of gastric tumor

The adenocarcinoma of the stomach in these patients diagnosed of lymphoma is usually aggressive, in contrast with the low or intermediate grades of the lymphomas (7). The adenocarcinoma of the stomach in our patient was also an aggressive tumor.

Although the non-Hodgkin lymphoma of the stomach only comprises an 1 - 5 % of the malignant gastric pathology (9), the coincidence of an adenocarcinoma and a NHL in the stomach has been described in about 80 cases, 70 % of them presenting simultaneously (9,12). In these cases of collision of an adenocarcinoma and a lymphoma in the stomach, the adenocarcinoma is usually a well differentiated early tumor, whereas the NHL generally affects extensively the gastric wall (9).

Risk factors

The causes for the second neoplasms in patients with lymphomas are still unknown. Due to the rarity of these associations, some authors think that it is a mere coincidence and no causal relationship exists between them (9). It is possible that both the lymph node lymphoma and the gastric adenocarcinoma appear as independent responses to the same carcinogens or predisposing factor in the patient. But there are some evidences that manifest the presence of possible factors like lymphoma associated immunosuppression (9).

A greater incidence of gastric adenocarcinoma has been found in patients with combined variable immunodeficiency, probably due to associated autoimmune mechanisms that produce an atrophic gastritis (1,25). In ataxia-telangiectasia, an DNA repair defect, also associated with immunodeficiency, a greater frequency of gastric carcinomas has also been detected (25).

Some factors that are considered in the association of gastric lymphoma and adenocarcinoma, like chronic irritation of the mucosa by the lymphoma or gastrectomy (9), local radiation (7), or the Helicobacter pylori (26), seem to play no rule in patients with nodal lymphomas. However, the Epstein-Barr virus, clearly involved in lymphocytes type B neoplasms, has also been detected with polymerase chain reaction in 16 % of typical gastric adenocarcinomas, mainly in males (27).

The greater frequency of secondary tumors may be due to a longer survival of cancer patients (16). Patient with a extragastric NHL and a gastric adenocarcinoma preset at an advanced age, with an interval of 63 to 87 years and an average of 73.5 years. Our patient was 72 years old.

Since most of the gastric adenocarcinoma appear at the same time that the nodal NHL, treatment of the lymphoma, with ionizing radiation's or chemotherapy, is not an etiologic factor in the gastric tumor, as it has been suspected in metachronous secondary tumors (9).

In those cases in which the interval between the lymphoma and gastric adenocarcinoma was long enough, like Hodgkin lymphoma (average interval: 7 years) and a 30 % of gastric lymphoma (average 5 years), a possible association between the combined radiotherapy and chemotherapy these patients underwent and the subsequent gastric carcinoma has been suggested (3,7,23,28).

In Hodgkin's disease patients a synergetic effect has been noted in those exposed to intense radiotherapy and chemotherapy, resulting a risk 18-20 times greater of myeloid leukemia (23,29,30). Treatment with alkilating agents, older age at the diagnosis of Hodgkin disease, recurrence of Hodgkin's disease, and late stage of disease at diagnosis were recently considered by Bhatia et al as risk factors for leukemia (8).

In treated non-Hodgkin lymphomas a 10 fold increase of myeloid leukemia has been observed, with no increase in the incidence of secondary solid tumors (14,28).

Combined chemotherapy with MOPP regimen (Nitrogen Mustard, Vincristine, Prednisone, and Procarbazine) associated with radiotherapy seem to play a significant role in the development of secondary acute myeloid leukemia (7). However, radiotherapy alone appears to have a more significant role in the development of solid tumors (3,7).

In fact, some chemotherapeutic agents like procarbazine are administered orally, and, subsequently we cannot exclude a direct local carcinogenic effect on gastric mucosa (7).

TABLES

TABLE 1. NON HODKIN EXTRAGASTRIC LIMPHOMA AND GASTRIC ADENOCARCINOMA

TABLE 2. HODGKIN´S DISEASE AND GASTRIC ADENOCARCINOMA

• Title
• Introduction
• Materials and Methods
• Results
• Pictures
• Bibliography