b cell lymphoma prognosis | "Gastric Lymphoma" malt "-what's new?

"Gastric Lymphoma" malt "-what's new?





All primitive gastrointestinal lymphomas are from malt (mucosa associated lymphoid tissue) after dinner. Among these, the gastric lymphomas are most frequent [1]. "" "" "By abuse of language, one tends to restrict the term of gastric lymphomas' malt ' to small cell lymphomas ' centrocyte-like" type MALT of low malignancy described by Isaacson in his ' classification ' digestive lymphomas [2]. These are defined according to the new classification of who in 2001 as to lymphomas in the marginal area of the MALT from which they originate [3]. These are lymphomas of low degree of malignancy, indolent evolution, generally located and that can turn into high degree of malignancy Lymphoma when appears one or several contingents of large cells.

In almost 80% of gastric lymphomas of the marginal zone of the MALT, the link with a chronic Helicobacter pylori infection has been established. This brings to offer in first treatment eradication of the bacteria [4]. The first cases were published 10 years ago. We still hurt the future of these lymphomas and their pathophysiology, although advances in molecular biology provide new data on the lymphomagenese each year. This explains the need to study and follow these patients through protocols such as the GELD (digestive lymphoma study group) current /FFCD. However the diagnosis, treatment and follow-up of these lymphomas are now well codified by international teams involved in this field.

Although rare, any gastroenterologist is likely to have to take over a gastric MALT lymphoma.

The diagnosis
The endoscopic appearance at diagnosis is aspecific and can range from the simple Erythema, erosions or ulceration creusante surrounded by big folds, more evocative. Although not confirmed, some studies have suggested that the importance of ulceration and the exophytique aspect could make fear a transformation in high malignancy [5, 6]. Biopsies should be many and wear on the lesion (10 in total) and distance. The levies fixed in Bouin's fluid allow a morphological analysis of good quality but fixed in formalin at 10%, they allow more often and immuno-Histochemical studies of molecular biology, in particular techniques amplification. To the extent possible, samples should be frozen for formal studies as well.

The histological characters of the edge zone of MALT lymphomas are stereotyped, associating an infiltration of the chorion by small lymphoid cells,"centrocyte-like", lymphoepitheliales damage defined by infiltration and» destruction of the epithelium of the glands or Crypts by these cells and lymphoid follicular hyperplasia. The blast, to type of centroblasts or immunoblastes cells are often present in small numbers. The Immunohistochemistry study shows the phenotype B (CD20 +, + CD79a) of the tumor population, more often expressing an IgM (more rarely IgA or IgG) Monoclonal, found in pododermatitis population, as well as the lack of expression of Some antibodies (RMI, CD5 CD10, CD23), useful for differential diagnosis with any other B lymphomas in small cells.

The techniques of molecular biology with gene amplification (PCR) can allow the quick highlight of a clonal rearrangement of immunoglobulin heavy chain gene. Cytogenetic more frequently found in these marginal area of MALT lymphomas, are Trisomy 3 (50 to 60% of cases) and a translocation t (11;18) (30% of cases). For now, these molecular studies are not common practice and have no impact on the therapeutic decision.

Research of Helicobacter pylori is systematic. She gets on the biopsies in histology (coloring Giemsa improved the sensitivity). Culture on the Middle Portagerm is sometimes permissible for antibiogram in case of resistance to treatment. Serology should be systematic in the absence of Helicobacter pylori in histology. The positive Helicobacter pylori status, to establish a likely link between the bacteria and the lymphoma, is defined as a histology and/or positive serology [4].
Apart from Helicobacter pylori serology, biology does no help in the diagnosis. However, we'll check the negativity of the normality of liver biology, HIV serology and the absence of high level of LDH.

The MTR extension
Gastric echo-endoscopy is essential in the initial assessment of the lymphoma regional extension and will help the monitoring of lymphoma after medical treatment. Its results have a value prognostic and predictive of response to the eradication of Helicobacter pylori (see below).

The rest of the MTR extension will confirm the usually localized nature of gastric MALT lymphoma. It should include research of peripheral and abdominal or thoracic ganglion damage by CT; an ENT examination with endoscopy or CT of the cavum and spinal cord biopsy. Of the upper and lower digestive endoscopies with systematic biopsies, in particular, at ileal level will seek a breach at the level of the rest of the digestive tract.

The treatment
Once the diagnosis of lymphoma of the marginal zone of the MALT and its localized nature confirmed, as well as its relationship with Helicobacter pylori established (positive status), the eradication of the bacteria treatment is undertaken. The seven days usually recommended in the duodenal ulcerative disease enough initially, but is often used in protocols for lymphoma in 14 days of treatment. This attitude resulted in the latest study of the GELD a rate of eradication of first intention of 96% and 100% on the second line [4].

After antibiotic therapy, it is usually the antisecretoires gastric who were arrested a few days before the next endoscopic control.

Monitoring (Fig 1)
One month after the end of the treatment of Helicobacter pylori eradication endoscopic control should be carried out to verify the effective eradication of the bacteria and the absence of extension of the lesion.

The patient will then followed every 4 months by endoscopy and echo-endoscopy stomach associated with biopsies. The remission of the lymphoma is defined as the disappearance of the endoscopic and histological lesions. It must be confirmed on at least two successive controls [4]. It can be observed from the sixth month and up to 18 months after the end of the treatment. Usually the echo-endoscopy also normalizes. Once remission is affirmed, controls will be carried out all six months the first year and every years later. In the literature, the maximum reduction in the follow-up of patients in remission is six years [7]. True relapses are classically early and rare and are mainly associated with the persistence of a monoclonal population in the gastric mucosa after histological regression of lymphoma [7-9].

Predictors of regression of the lymphoma after eradication of Helicobacter pylori
The positive Helicobacter pylori status, the absence of pathological lymph node to the initial echo-endoscopy are good prognostic factors and give us hope a rate of remission from Lymphoma to 80% [4]. Regardless of the ganglionic achievement, the chances of regression of the lymphoma drop significantly when the initial achievement objectified in echo-endoscopy extends beyond the mucosa. The large tumor masses with massive parietal infiltration let alone the endoscopic appearance does not have partially regressed to the first endoscopic control after treatment, need to suspect a transformation in high malignancy. Usually superficial endoscopic biopsies can ignore areas infiltrated by the large cells.

A European study recently reported the criteria histological and immunohistochemical for predicting the evolution of lymphoma after antibiotic therapy [10]. Recent studies of molecular biology have also shown the link between the presence of translocation t (11;18) in the lymphoma cells and the resistance of the lymphoma to the eradication of the bacteria [11]. It will however wait for the results on the most important series to validate this biological marker that could have an interest in the care of patients.

What to do if the lymphoma does not regress after eradication of Helicobacter pylori?

In case of persistence of lymphoma or for cases negative Helicobacter pylori status, should be considered either surgery or radiation therapy, or even sometimes a chemotherapy.

Radical surgery results according to series 88-100% 5-year survival (with a decline of 40 to 96 months follow-up) [6: 12-20]. Surgery seems so the reference of gastric lymphomas of low malignancy treatment but the need for a total gastrectomy (multifocal lymphomas and endoscopic explorations and echo-endoscopy not sensitive enough to judge of his [21] extension) must consider other therapeutic alternatives.

The results of exclusive radiotherapy failure of antibiotic treatment are being assessed. Two randomised and recently published series still have limited staff or an insufficient decline, forbidding any firm conclusions [22, 23]. However, they give excellent results (100% survival at 5 years without relapse) with the radiation therapy at low doses. Those usually recommended are 30 Gy in conventional fractionation (5 X 1, 8Gy per week) on the gastric volume and perigastriques lymph node areas.

As the results of chemotherapy, they are long term disappointing to ganglion low malignancy small cell lymphomas; they have that's rarely been evaluated in localized gastric lymphomas. Rare (less than 20 patients) studies report of initial remissions ranging from 34 to 75% on a follow-up is still too short given the natural history of love [6: 24]. There is currently no argument to recommend it. No therapeutic trial is currently underway.

The choice between these options will therefore depend on for now the patient (age and the ground) and the clinical presentation of lymphoma. Indeed, for the important stomach masses, the choice of a total gastrectomy will, in addition to healing, verify the lack of transformation in high malignancy. For the persistent lymphoid infiltrates without gastric parietal significant extension, less invasive radiation therapy will be proposed yet to evaluate it under protocols-looking. For these forms, oral monochimiotherapie by a (chlorambucil or cyclophosphamide) alkylating agent may also be considered in light of evolution indolent Lymphoma, particularly in the elderly and in the case of contraindication to treatment loco-regional.

In the case of conservation of the stomach, regular endoscopic surveillance should continue, not only to check the non recurrence of lymphoma, but also the subsequent lack of occurrence of gastric adenocarcinoma as it has been recently reported.

REFERENCES

1 Zucca E, David Pileri S e. - B-cell lymphoma of MALT type: a review with special emphasis on diagnosis and management problems of low-grade gastric tumours. BR J Haematol 1998; 100: 3-14.

2 Isaacson PG, Spencer J Wright DH. -Classifying primary gut lymphomas. Lancet 1988; 2: 1148-1149.

3 jaffe are, Harris NL, Stein H Vardiman JW. -World Health Organization Classification of tumours. In: P. Kleinhues and L. H. Sobin. Pathology and genetics of the haematopoietic and lymphoid tissues. Lyon: IARC press, 2001.

4 Ruskone-Fourmestraux A, Lee A, Aegerter PH, Megraud F, Palazzo L, of Mascarel, et al. -Predictive factors for regression of gastric MALT lymphoma after anti - Helicobacter pylori treatment. Gut 2001; 48: 297-303.

5 Taal BG, Boot H, van Heerde P, Jong D, Hart AA JM Burgers. -Primary non-Hodgkin lymphoma of the stomach: endoscopic pattern and prognosis in low versus high grade malignancy in relationship to the MALT concept. Gut 1996; 39: 556-561.

6 C, Castrillo JM, Abraira V, Serrano Montalban M, Bellas C, Piris MA, et al. -Gastric B-cell mucosa-associated lymphoid tissue (MALT) lymphoma. Clinicopathological study and evaluation of the prognosis factors in 143 patients. Ann histopathology 1995; 6: 355-362.

7 Isaacson PG, Diss TC, Wotherspoon AC, Barbazza R, Boni M Doglioni C. - Long term follow-up of gastric MALT lymphoma treated by eradication of h. pylori with antibodies. Gastroenterology 1999; 117: 750-751.

8 Morgner A, Thiede C, Bayerdorffer E, Alpen B, Wundisch T, Neubauer, et al. Long term Follow-up of Gastric MALT Lymphoma After H. pylori Eradication. Curr Gastroenterol Rep 2001; 3: 516-22.

9 Thiede C, Wundisch T, Alpen B, A B, Morgner Neubauer, Schmitz M, et al. -Long-term persistence of monoclonal B cells after cure of Helicobacter pylori infection and complete histologic remission in gastric mucosa-associated lymphoid tissue B-cell lymphoma. J blink histopathology 2001; 19: 1600-1609.

10. de Jong, Vyth-Dreese F, Dellemijn T, see N, Ruskone-Fourmestraux A, Lavergne-Slove A, and al. -Histological and immunological parameters to predict outcome of Helicobacter pylori eradication treatment in low-grade gastric MALT lymphoma. J Edition 2001; 193: 318-324.

11 has Liu H, Ruskone-Fourmestraux, Lavergne to Slove A, H, Molina Ye T, Bouhnik, et al. -Resistance of t (11;18) positive gastric mucosa-associated lymphoid tissue lymphoma to Helicobacter pylori eradication therapy.) Lancet 2001; 357: 39-40.

12. valiant JC, Ruskone-Fourmestraux A, P, Gayet Aegerter B, Rambaud JC, Valleur P, et al. -Management and long-term results of surgery for localized gastric lymphomas. Am J Surg 2000; 179: 216-222.

13 Roher HD, okay PR, Wormer O, Müller FP, Ohmann C Fischbach W. - Helicobacter pylori in the upper gastrointestinal tract: medical or surgical treatment of gastric lymphoma? [In Process Citation]. Langenbecks Arch Surg 2000; 385: 97-105.

14 Fischbach W, Dragosics B, Kolve-Goebeler ME, Ohmann C, Greiner has, Yang Q, et al. -Primary gastric B-cell lymphoma: results of a prospective multicenter study. The German-Austrian Gastrointestinal Lymphoma Study Group. Gastroenterology 2000; 119: 1191-1202.

15 Fung CY, ML, Linggood RM, Younger J, Flieder Grossbard A, Harris NL, et al. -Mucosa-associated lymphoid tissue lymphoma of the stomach: long term outcome after local treatment. Cancer 1999; 85: 9-17.

16 Zinzani PL, Magagnoli M, G, Bendandi Pagliani M, Gherlinzoni F, Merla E, et al. -Primary intestinal lymphoma: clinical and therapeutic features of 32 patients. Haematologica 1997; 82: 305-308.

17 Lybeert ML, W, LW, Coen Vrints Neve V Coebergh JW. -Primary gastric non-Hodgkin's lymphoma stage IE and IIE. EUR J Cancer 1996; 32A: 2306-2311.

18 Zinzani PL, Frezza G, M, Barbieri Bendandi E, Gherlinzoni F, Neri S, et al. -Primary gastric lymphoma: a clinical and therapeutic assessment of 82 patients. Leuk Lymphoma 1995; 19: 461-466.

19 Durr ED, Bonner JA, Strickler JG, Martenson JA, Chen MG, Habermann TM, et al. -Management of training IE primary gastric lymphoma. ACTA Haematol 1995; 94: 59-68.

20 Jelic S, Kovcin V, Jovanovic V, Opric M Milanovic N. - Primary gastric non-Hodgkin's lymphoma localized to the gastric wall: No. adjuvant treatment following radical surgery. Oncology 1994; 51: 270-272.

21 Palazzo L, G, Ruskone-Fourmestraux Reed has, Rougier P, Chambers S, Rambaud JC, et al. -Endoscopic ultrasonography in the local staging of primary gastric lymphoma. Endoscopy 1993; 25: 502-508.

22 Tsang RW, Gospodarowicz MK, Pintilie M, Bezjak A, W, Hodgson DC, Wells et al. -Stage I and II MALT lymphoma: results of treatment with radiotherapy. Int J Radiat histopathology Biol Phys 2001; 50: 1258-1264.

23. NR Yahalom j. Schechter - Low-grade MALT lymphoma of the stomach: a review of treatment options. Int J Radiat histopathology Biol Phys 2000; 46: 1093-1103.

24 Hammel P, Haioun C, Chaumette MT, P, Divine M, Reyes Gaulard F, et al. -Efficacy of single-agent chemotherapy in low-grade B-cell mucosa-associated lymphoid tissue lymphoma with prominent gastric expression. J blink histopathology 1995; 13: 2524-2529.