East and Central African Journal of Surgery Association of Surgeons of East Africa and College of Surgeons of East Central and Southern Africa ISSN: 1024-297X EISSN: 2073-9990 Vol. 12, Num. 2, 2007, pp. 99-104

East and Central African Journal of Surgery, Vol. 12, No. 2, November/December 2006, pp. 99-104

Primary Gastrointestinal Lymphoma In Immunocompromised Patient. Case Report And Literature Review

E.V. Ussiri, L.E.K. Lema, N.N.A. Mbembati, J.L. Magandi
Muhimbili University College of Health Sciences, Muhimbili National Hospital. Department of Surgery, P. O. Box 65000, Dar es Salaam, Tanzania- East Africa.
Correspondence to: Dr. Ussiri EV, E-mail: eussiri@yahoo.com

Code Number: js07049

Primary gastrointestinal lymphoma is a rare disease with no specific clinical presentation. Early diagnosis is usually based on suspicious index, otherwise majority of patients present at late with very advanced disease with complications. The incidence of primary gastrointestinal lymphoma is increasing with HIV disease. There are several classification and staging systems with different treatment options varying from one center to another. Prognosis depends on the stage at presentation, degree of differentiation and age. It was concluded that early diagnosis depends on degree of suspicious index with good treatment response. Late presentation is accompanied by marked immunosuppresion. Future research needs to determine whether single or combined modalities of treatment have good treatment outcomes. A case of primary gastrointestinal lymphoma in immunocompromised patient is reported with literature review.

Introduction

Primary gastrointestinal lymphoma is a rare condition accounting for 0.8-1.2 cases per 100,000. Gastrointestinal tract is the most frequent extra-nodal site of primary lymphoma^1,2,3,4 .

The incidence of primary gastrointestinal or hepatic lymphoma is increasingly being seen with human immunodeficiency disease^5,6,7,8 . Non-Hodgkin’s lymphoma (NHL) is the second most frequent malignancy associated with Human Immunodeficiency virus (HIV) following Kaposi’s sarcoma. Other malignancies include carcinoma of cervix, anal canal carcinoma, ocular carcinoma and childhood malignancies^5,6,9 . When evaluating AIDS-associated cancers in Sub-Saharan Africa it was found that among patients with HIV/AIDS; 5.6% have NHL in South Africa, 2.8% in autopsy study at Ivory Coast, 8.5% and 12.4% in 1981 – 1990 and 1991 – 1998 in Ibadan respectively² .

Majority of patients with primary gastrointestinal lymphoma present with late advanced disease and complication(s) before diagnosis is made. Diagnosis of gastrointestinal lymphoma is mainly based on suspicious index as there is no specific symptom or sign1^0,11,12 . There are several different histological classifications, staging systems and controversies in the treatment options^1,2,3,4,5 . This prompted the authors to report on this case as well as literature review on primary gastrointestinal lymphoma.

Case Report

T.M aged 48 male, driver, known seropositive on Anti-Retro Viral therapy (ARV)- Trioimune⁴⁰ for four months, presented with gradual onset of epigastric pain for two months. Initially pain was dull in nature and localized but later on became generalized and colicky in nature. He also experienced postprandial fullness with little feeds, on and off episodes of diarrhoea (3 loose motions per day, not bloody or foul smelling) and vomiting of recently taken food and occasionally bilious vomitus. He reported a significant body weight loss with no history of haematemesis or maelena. His micturition habits were normal and there was no history of fever.

He had been admitted twice at District Hospital and twice in Medical Department at Muhimbili National Hospital for the same complaints with no improvement. He had completed a 9-months course treatment for pulmonary tuberculosis therapy in 2001. He was married with three children all alive and doing well. He took alcohol occasionally but he was a non smoker.

Physical examination revealed middle-aged man, very weak and dehydrated. He was not pale, had no oral thrush and no palpable peripheral lymph nodes. Pulse rate was 80/minute regular and of normal volume. Blood pressure was 120/70 mmHg. Abdominal examination revealed a full abdomen, moving with respiration, visible peristalsis from left to right and soft. There was a palpable firm, tender, ill defined mass in the left hypochondrium. Succussion splash was negative. Bowel sounds were normal and digital rectal examination revealed normal findings. Other systems were found to be normal. A provisional diagnosis of Partial intestinal obstruction. The cause was uncertain

Investigations done during this illness included:

• Chest X-ray, which was normal. A repeat after one month was normal too.
• Haemoglobin was 14.2 g/dl, WBC count = 8,800cells/cmm, ESR=30mm/hr.
• Serology for H. pylori was negative.
• Stool analysis revealed E. coli.
• Urinalysis was normal.
• Oesophagogastroduodenoscopy (OGD) revealed oesophageal candidiasis, severe reflux oesophagitis and gastritis.
• Double ELISA test for HIV was positive.
• CD4 count was 180-cells/ µl. Repeat CD4 after one month was 284-cells/ µl.
• Abdominal Ultrasonography was normal. Repeat after one month was normal too.
• .CT-scan revealed a mass in the right hypochondrium (opposite from clinical examination) with undetermined origin.

Treatment given during this period included Fluconazole, Omeprazole, Metronidazole, Trioimune⁴⁰, Septrin, Metochlorpramide, Multivitamin, Intravenous fluids.

Because of persistent colicky abdominal pain, it was decided to take the patient for exploratory laparotomy. The findings included multiple purple nodules involving the stomach and small bowel wall. There was one big mass (6 x 4cm) causing jejunal obstruction. There were no mesenteric or paraortic lymph node enlargement and the rest of the abdominal viscera were normal. Resection of the mass causing obstruction, end to end anastomosis was done with uneventful postoperative recovery.

Histology of biopsy specimen revealed “diffuse large cell lymphoma, high grade”. The patient was then referred to Ocean Road Cancer Institute (ORCI) where he was planned for six cycles of second line chemotherapy (Doxorubicin, Cyclophosphamide, Bleomycinand and Prednisolone).He received the first cycle then he was discharged home.

He was planned to go back for the second cycle after three weeks but he died suddenly on the same day of discharge just after arrival at home. The cause of death was attributed to treatment complications due to advanced disease.

Clinical features of gastrointestinal lymphoma are often vague and non-specific leading to delay in diagnosis with poor treatment outcome^13,14,15. Its presentation depends on the tumor size and its location. It may present with a single lesion, multiple fungating masses or diffuse lesions affecting any region from the oral mucosa to the rectum. The most frequent location is the stomach accounting for 74.7% to be followed by small bowel (8.6%) then ileo-caecal region (7.0%) and multiple sites (6.5%). The rest of regions constitute 3.2 %⁴. Our patient presented with multiple sites involving stomach, duodenum, jejunum and ileum.

The commonest symptoms include vague abdominal pain, nausea, weight loss, vomiting and abdominal fullness^16,17,18. These may mimic other abdominal pathologies such as peptic ulcer, pancreatitis, cholecystitis or malignancies. Our patient had all these symptoms with diarrhoea in addition. Pain is the main diagnostic symptom to be followed by nausea in both gastric and intestinal lymphoma accounting for 78% in gastric and 53.3% in multiple involvements⁴. Less frequent symptoms include body weakness, sweating, jaundice, pyrexia of unknown origin and dysphagia^16,19,20. Rare symptoms include haematemesis or malaena, gastric outlet obstruction, and bowel perforation^15,16.

Physical examination is normal in 55-60% of patients¹⁶. Common signs include epigastric or generalized tenderness and palpable mass(es) accounting for 20-35% and 17-25% respectively^17,20,21. Other uncommon findings include pyrexia, hepatosplenomegaly, jaundice and lymphadenopathy. Our patient had a palpable tender mass.

Diagnostic investigations include barium swallow or meal depending on presentation, upper or lower gastrointestinal endoscopy + step multiple biopsies depending on presentation, abdominal ultrasonography, abdominal CT scan, Magnetic Resonant Imaging (MRI) and Fine Needle Aspiration Cytology (FNAC) if present with a mass. Barium swallow or meal may show a filling defect, atypical ulcer deformities, obstruction, mass effect and gastric wall thickening suggestive of gastric lymphoma but not specific^12,16,17,22. Upper GI’ endoscopy (OGD) may reveal a range of features which vary from subtle mucosal changes to gross lesions which include mucosal oedema, friability, patchy redness, irregular patchy gray or whitish granular easily bleeding, irregular erosions and ulcerations^12,23. Powtz et al¹ when evaluating seropositive patients with abdominal pain found that out of 93 endoscopies 7.5% had Non Hodgkin’s lymphoma.

Abdominal ultrasonography is helpful in evaluating hepatic lesion(s) or in staging purposes by identifying involvement of intraabdominal lymph node. CT scan of abdomen revealed gastric wall thickening or mass lesions. It may show mural (horizontal) thickening compared to vertical growth in carcinoma at early stages of the disease. It also reveals peri-gastric, porta-hepatis and para-aortic lymph node enlargement, which is useful in staging purposes^24,25.

Endoscopic ultrasonography may differentiate infiltrative carcinomas from lymphoma whereby, carcinoma reveal a vertical growth compared to horizontal growth in early stages as well as perigastric lymph nodes in staging purposes^26,27. MRI reveals irregularly thickening mucosa, irregularly submucosal infiltration, annular constricting lesion, exophytic tumor growth, mesenteric masses and mesenteric/retroperitoneal lymphadenopathy²⁸. Bone marrow is used for staging purposes and indirect laryngoscopy is used in assessing Waldeyer’s ring, which is common in lymphoma. FNAC by experienced Cytologist is helpful in hepatic lesion or lymph node²³. The above diagnostic methods avoid unnecessary exploratory laparotomy to confirm the diagnosis and staging purposes.

There are several classification systems for staging gastrointestinal lymphoma based on Ann Arbor Classification. Treatment for gastrointestinal NHL depends on the stage and grade of the disease as follows^4,30,31:

(i) Low- grade lymphoma, stage IE and IIE Surgical resection then extended field radiotherapy with total abdominal irradiation with 30 Gy. In case of residual tumor, then an additional boost (10 Gy) In addition to patient with stage IIE, six cycles of (COP)- Cyclophosphamide 500mg/m² on days 1-5, Vincristine 1.4 mg/m² on day 1 and Prednisone 100mg/m² on days 1-5 preceeding radiotherapy.

(ii) Low grade lymphoma, stage IIIE and IVE receive COP six cycles only.

(iii) High grade lymphoma stage IE Four cycles of second line chemotherapy, which include (CHOP)-Cyclophosphamide 750 mg/m2, Doxorubicin50mg/m², Vincristine 1.4mg/m2, Prednisone 100mg on days 1-5 followed by extended field radiotherapy (30Gy + 10 Gy boost) on tumor bed.

(iv) High grade lymphoma stage IIE – IVE Six cycles of CHOP and additional involved field radiotherapy (40 Gy)

Table 1.Staging Classification for gastric lymphoma according to Musshof’s criteria²⁹:

E = Extra-nodal, S = Splenic, A=Asymptomatic, B = Symptomatic.

Table 2. Modified Black-ledge staging system for gastrointestinal lymphomas²⁹:

When evaluating prognosis and cause of death it was found that gastrointestinal lymphoma is associated with late manifestation of HIV/AIDS with marked immunosuppresion and poor prognosis². Gastric and ileocaecal lymphoma had better prognosis than small bowel (P=0.04323) and when multiple sites involved (P=0.0177). Another study revealed that 13 out 20 (65%) deaths were related treatment or late presentation⁴. Surgical resection in early stages of disease has good outcome with a 5year survival rate of 80-93%^32,33. Aggressive surgery is not indicated due to increased morbidity and this does not influence the survival^34,35.

Operative mortality was between 3 to 25 % with higher rates for palliative resection, which were performed for symptomatic relief or tumor debulking³⁶. Combination of surgery and chemotherapy have shown the survival rate of 60-100% for early disease³⁷.Good prognosis was associated with low Grade disease, age below 65 years, free surgical margins in case of complete resection and achievement of initial complete remission^38,39,40. Five-year survival rates were reported to be 91%for low grade, 73% for secondary high grade and 56% for primary high-grade tumors⁴¹.

Early diagnosis of gastrointestinal lymphoma is mainly based on a high suspicious index and has good treatment outcome. Late presentation is associated with marked immunosuppression and poor prognosis. Randomized trials are needed to clarify whether conservative (radiotherapy), surgical or combination treatment is more appropriate for localized gastric lymphoma.

1. Ducrex M, Boutron MC, Piard F. A 15-year series of gastrointestinal Non-Hodgkin’s lymphoma: A population-based study. Br J Cancer 1998; 77: 511-514.
2. Morton JE, Leyland MJ, Vaughan HG. Primary gastrointestinal Non-Hodgkin’slymphoma: A review of 175 British National Lymphoma Investigation cases. Br J Cancer 1993; 67: 776782
3. Amer MH, el Akkada S. Gastrointestinal lymphoma in adults: Clinical features andmanagement of 300 cases. Gastroenterol. 1994; 106: 846-858.
4. Barlett DL, Karpeh MS (Jr), Fillipa DA. Longterm follow-up after curative surgery for early gastric lymphoma. Ann Surg 1996; 223: 53-62.
5. Powtz F, Bogner JR, Sandor P, Zietz C, Goebel FD, Zolter WG. Gastrointestinal lymphomas in patients with AIDS. Z Gastroenterol 1997; 35: 179-15.
6. Anisa Mosam. AIDS-associated cancers in Africa. Seminars in Oncology 2001; 28: 198-206.
7. Ziegler JL, Beckstead JA, Volberding PA. Non-Hodgkin’s lymphoma in 90 homosexual men: Relation to generalized lymphadenopathy and the AIDS. N Engl J Med. 1984; 311: 565-570.
8. Koch P, del Valle F, Berdel WE, Willich NA, Reers B, Hiddemann W et al. PrimaryGastrointestinal Non-Hodgkin’s Lymphoma: I. Anatomic and Histologic Distribution, Clinical features and Survival Data of 371 patients registered in the GermanMulticenter Study GIT NHL 01/92. J Clin Oncol 2001; 19: 3861-3873.
9. Szelenyi H, Armbrecht C, Becher K, Manegold C, Mauss S, Vogt C. HIV-related NHL of the GIT. AIDS Nov. 1994 no.8.
10. Cogliatti SB, Schmid U, Schnmacher U. Primary B- cell gastric lymphoma: A clinicopathological study of 145 patients. Gastroenterol 1991; 101: 1159-1170.
11. Rackner VL,Thirlby RC, Ryan JA. Role of Surgery in multimodality therapy for gastrointestinal lymphoma. Am J Surg 1991; 161: 570- 575.
12. Al-Mofleh IA. Complications of primary gastrointestinal lymphoma. Ann Saudi Med 1992; 12: 297-299.
13. Koch P, de Valle F, Berdel WE, Willich NA, Reers B, Hiddemann W et al. Primarygastrointestinal Non-Hodgkin’s lymphoma: II. Combined Surgical and Conservative or Conservative Management only in localized gastric lymphoma. Results of the prospective German Multicenter Study GIT NHL 01/92. J Clin Oncol 2001; 19:3874-3883.
14. Ono H, Kondo H, Saito D, Yoshida S, Shiroa K, Yamaguchi H, Yokota T, Hozokawa K, Fukuda H, Hayashi S. Rapid diagnosis of gastric malignant lymphoma frombiopsy specimens: Detection of immunoglobulin heavy chain reaction. Jpn J Cancer Res 1993; 84: 813-817.
15. Isaacson PG. Recent developments in our understanding of gastric lymphomas. Am J Surg Pathol. 1996; 20: 1-7
16. Brooks JJ, Enterline HT. Primary gastric lymphomas: a clinicopathologic study of 58 cases with long-term follow-up and literature review. Cancer 1983; 51: 701-711.
17. Sutherland AG, Kennedy M, Anderson DN, Park KGM, Keenan RA, Davidson AI.Gastric lymphoma in Grampian region: presentation, treatment and outcome. J R Coll Surg Edinb 1996; 41: 143-147.
18. El Saghir NS, Jessen K, Al-Mofleh IA, Ajarim DS, Fawzy E, Al Faleh FZ, Dahaba N, Qteishat W. Primary gastrointestinal lymphoma in the Middle East: Analysis of 23 cases from Riyadh, Saudi Arabia. Saudi Med J 1990; 11: 133-152.
19. Chandran RR, Raj EH, Chaturvedi HK. Primary gastrointestinal lymphoma: 30-year experience at the Cancer Institute, Madras, India. J Surg Oncol 1995; 60: 41-49.
20. Radaszkiewicz T, Dragosics B, Baner P. Gastrointestinal malignant lymphomas of the mucosa-associated lymphoid tissue: Factors relevant to prognosis. Gastroenterol 1992; 102: 1628-163.
21. Kitamwa K, Yamaguechi T, Okamoto K, Ichikawa D, Hohima M, Taniguchi H, Takahashi T. Early gastric lymphoma: a clinicopathological study of ten patients, literature review and comparison with early gastric carcinoma. Cancer 1996; 77: 850-857.
22. Kodera Y, Yamanura Y, Nakamura S, Shimizu Y, Torii A, Hirai T, Yasui K, Morimoto T, Kato T, Kito T. The role of radical gastrectomy with systemic lymphadenectomy for the diagnosis and treatment of primary gastric lymphoma. Ann Surg 1998; 227: 45-50.
23. Bottles K, Mc Phaul LW, Volberrding P. Fineneedle aspiration biopsy of patients with AIDS: Experience in an outpatient clinic. Ann Intern Med 1988; 108: 42-45.
24. Park SH, Han JK, Kim TK, Lee JW, Kim SH, Kim YJ, Choi BI, Yeon KN, Han MC. Unusual gastric tumors: Radiographics 1999; 19: 14351446.
25. Brown JA, Carson BW, Gascoyne RD, Cooperbeng PL, Connors JM, Mason AC. Lowgrade gastric MALT lymphoma: Radiographic findings. Clin Radiol 2000; 55: 384-389.
26. YucelC, Ozdemir H, Isk S. Role of endosonography in the evaluation of gastric malignancy. J Ultrasound Med 1999; 18: 283-288.
27. Caletti G, Fusaroli P, Togliani T, Bocuo P, Roda E. Endosonography in gastric lymphoma and large gastric folds. Eur J Ultrasound 2000; 11: 31-40.
28. Chou CK, Chen LT, Shen RS, Yang CW, Wang MC, Jaw TS, Liu GC. MRI manifestations of gastrointestinal lymphoma. Abdom Imaging 1994; 19: 495- 500.
29. Ahmad M, Al-Akwaa, Neelam S, Al-Mofleh IA. Primary gastric lymphoma. World J Gastroenterol 2004; 10: 5-11.
30. Stole M. Helicobacter pylori gastritis and gastric MALT-lymphoma. Lancet1992; 339; 745- 746.
31. Isaacson P, Wright DH. Extra-nodal malignant lymphoma arising from mucosa associated lymphoid tissue. Cancer 1984; 53: 2515-1524.
32. Fung CY, Grossbard ML, Liggood RM, Younger J, Flieder A, Harris NL, Gaeme-Cook F. Mucosa-associated lymphoid tissue lymphoma of the stomach: Long term outcome after local treatment. Cancer 1999; 85: 9-17.
33. Salvagano L, Soraru M, Busetto M, Puccettic C, Sava C, Endrizzik L, Gusto M, et al. Gastric Non-Hodgkin lymphoma : analysis of 252 patients from a multicenter study. Tumori 1999; 85: 113-121.
34. Popescu RA, Wotherspoon AC, Cunningham D, Norman A, Prendiville J, Hill ME. Surgery plus chemotherapy or chemotherapy alone for primary intermediate and high-grade gastric Non-Hodgkin’s lymphoma: The Royal Marsden Hospital experience. Eur J Cancer 1999; 35: 928-934.
35. Cooper DI, Doria R, Sallom E. Primary gastrointestinal lymphomas. Gastroenterol 1996; 4: 54-64.
36. Law MM, Willmas SB, Wong JH. Role of surgery in the management of primary lymphoma of the gastrointestinal tract Surg Oncol 1996;61:199-204.
37. Ruskone –Fourmestraux A, Aegertes P, Dehmer A, Brousse N, Rambad JC. Primary digestive tract lymphoma: a prosepective multicentric study of 91 patients. Gastroenterol 1993; 105: 1662-1671.
38. Rohatiner A, d’Amore F, Coiffier B, Crowther D, Gospodarowicz M, Isaacson P, Lister TA, Norton A, Salem P, Shipp M. Report on a workshop convened to discuss the pathological and staging of Gastrointestinal tract lymphomas. Ann Oncol 1994; 5: 397-400
39. Azab MB, Henry-Amar M, Rougier P, Bognel C, Theodore C, Carde P, Lasser P, Cosset JM, Caillon B, Oroz JP, Marcel H. Prognostic factors in primary gastrointestinal Non-Hodgkin’s lymphoma. Cancer 1989; 64: 1208-1217.
40. Liang R, Todd D, ChanTK, Chiu E, Lie A, Kwong YL, Choy D, Ho FC. Prognostic factors for primary gastrointestinal lymphoma. Haemtol 1995; 13: 153-163.
41. Cogliatti SB, Schmid U, Schumacher URS, Eckert F, Hausmann ML, Hedderic J, Takahashi H, Lennert K. Primary B-cell gastric lymphoma: A clinicopathological study of 145 patients. Gastrenterol 1991; 101: 1159-1170

© 2007 East and Central African Journal of Surgery

The following images related to this document are available:

Photo images