|LYMPHOMA: ORIGINAL ARTICLE
|Year : 2014 | Volume
| Issue : 3 | Page : 290-292
Primary gastrointestinal lymphomas - A study of 81 Cases from a Tertiary Healthcare Centre
HS Shirsat, K Vaiphei
Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
|Date of Web Publication||10-Dec-2014|
Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh
Source of Support: None, Conflict of Interest: None
Purpose: Retrospective analysis of 81 routinely diagnosed gastrointestinal (GI) lymphoma to illustrate clinicopathological and immunohistochemical characteristics with predisposing condition. Materials and Methods: Age, sex, site, tumour stage, associated pathological features like lympho-epithelial lesion (LEL), atrophic gastritis (AG), intestinal metaplasia (IM) and enteropathy changes were analysed. Requisite immunohistochemical panel was applied wherever needed. Results: There were 55 male and 26 female patients with median age of 54.5 years. Site wise distributions were stomach 40, small intestine 22, colon 4, cecum 2, ileocecum 3, esophagus 1 and multiple sites 9. Histological subtypes were mucosa associated lymphoid tissue lymphoma (MALTOMA) 48, diffuse large B cell lymphoma (DLBL) 21, T cell lymphoma 9 [5 anaplastic large cell lymphoma (ALCL) and 4 enteropathy associated T cell lymphoma (EATL)], immunoproliferative small intestinal disease (IPSID) 2 and follicular lymphoma 1. LEL was present in 31 cases. Of the 19 AG, 8 had associated IM, and 1 case each had associated H Pylori infection and neuroendocrine tumor. Enteropathy was observed in 4 EATL, and one case each of DLBL and high grade MALTOMA. Giardia infection was present in 1 low grade duodenal MALTOMA. Of the 24 resected specimens, 16 were stage IE, 7 stage IIE and 1 stage IV (Mushoff's staging). Conclusion: Primary GI lymphoma was frequently observed in 6 th decade of life with male preponderance. Stomach was the commonest site and high grade MALTOMA being the commonest histological variant. Isolated colonic involvement and intestinal perforations were not infrequent. Rare variants like ALCL and follicular lymphomas were also observed.
Keywords: Gastrointestinal Lymphoma, Lympho-epithelial lesion, MALTOMA, enteropathy associated T cell lymphoma
|How to cite this article:|
Shirsat H S, Vaiphei K. Primary gastrointestinal lymphomas - A study of 81 Cases from a Tertiary Healthcare Centre
. Indian J Cancer 2014;51:290-2
| » Introduction|| |
Gastrointestinal (GI) lymphomas are the commonest site of primary extra nodal lymphoma observed in 30-50% of all lymphomas. , Stomach is the commonest site followed by small intestine  while colon, rectum and esophagus account for a minority of cases.  Majority are non-hodgkin lymphomas, B cell dominating over T cell type. 
B cell lymphomas are classified into MALT (mucosa associated lymphoid tissue) lymphoma, DLBL (diffuse large B cell Lymphoma) with/without a MALT component, IPSID (immunoproliferative small intestinal disease), follicular lymphoma, mantle cell lymphoma, Burkitt lymphoma, lymphomas and lympho proliferations associated with immunodeficiency; while T cell lymphomas are the enteropathy associated T cell lymphoma (EATL), and other types unassociated with enteropathy and nasal type NK cell lymphoma (WHO classification)  . The present study was undertaken to evaluate incidence, distribution, morphological and immunological characteristics of primary GI lymphomas with co-existing predisposing factor.
| » Materials and Methods|| |
The study was retrospective in 81 cases of newly diagnosed untreated primary GI lymphomas diagnosed routinely over a period of 5 and half years (Jan 2006 - Jun 2011). Nodal lymphomas with secondary involvement of GI system or GI lymphoma with dominant nodal involvement and GI lymphomas that had received treatment at the time of diagnosis were excluded from the study. Age, sex, site and depth of involvement, regional nodal status and changes in adjoining mucosa were noted. Associated pathological findings like LEL, AG with IM and enteropathy associated changes in intestinal mucosa were also documented. Requisite immunohistochemical panel that had been done included i.e. CD20, CD79a, CD3, LCA, CD138, Kappa, Lambda, CD30, CK, EBNA, Ki67, Mic2, bcl2, CD5, CD68, Chromogranin, Synaptophysin and NSE (Dako, Glostrup, Denmark) Paraffin sections were stained by standard staining protocol for peroxidase anti-peroxidase technique with prior antigen retrieval. For clinical staging of the tumour, Mushoff's modification of Ann-Arbor system was used. 
| » Results|| |
Out of 81 cases 76 were in-house cases while 5 were referral blocks from outside. The in-house cases included 54 endoscopic biopsies and 22 resected specimens, and the 5 referral cases included 3 biopsies and 2 resection specimens. There were 55 males and 26 females, ages ranged from 5 to 83 years with median age being 54.5 years. There were 3 pediatric patients, 1 case of IPSID involving the jejunum in a 5 year old boy and 2 cases of DLBL involving the duodenum in 8 year old boy and ileocecum in a 10 year old boy. Site-wise distribution showed a preponderance of gastric lymphoma in 40 (49.38%) followed by small intestine 22 (27.16%). There were 6 cases which involved both stomach and duodenum (7.4%). There were 3 cases that had involved ileo-cecal region, 2 cecum and 4 colon, and another 3 cases had involvement of both large and small intestine. There was 1 case involving the esophagus exclusively. Commonest histological subtype was MALTOMA observed in 48 cases; of these 44 (54.32%) were high grade MALTOMA, 1 (1.2%) intermediate grade while 3 (3.7%) were low grade. On immunohistochemical staining, all MALTOMAs showed distinct membranous CD20 positivity except in 1 case which was negative for both CD20 and CD138. CD3 was also found to be expressed by 20-30% of the neoplastic lymphoid cells.
There were 21 cases of DLBL which showed membranous CD20 positivity, of which 20-30% neoplastic lymphoid cells also showed CD3 positivity. There were 2 cases of high grade IPSID. The case of jejunal IPSID had clinically palpable liver and spleen with multiple enlarged regional lymph nodes, biopsies of which showed tumor infiltration into portal and peri portal liver parenchyma and splenic sinusoids along with contiguous nodal and peri nodal involvement. Bone marrow trephine biopsy was free. Both IPSID cases showed prominent LELs and nodular aggregates of CD20 positive bcl2 negative neoplastic cells. There was one case of high grade follicular lymphoma positive for CD20 and bcl2. There were 9 cases of primary intestinal T cell lymphomas, of which 4 were EATL and 5 were anaplastic large cell lymphoma (ALCL). Of the 4 EATL cases, 2 were small intestine resection specimens with transmural infiltration and perforations with no nodal involvement. All EATL cases showed large areas of mucosal ulcerations, diffuse infiltration wiping out the crypt and villous architecture. Infiltrating cells were dominantly small sized lymphocytes intermixed with scattered intermediate sized lymphocytes having convoluted and hyper chromatic nuclei and visible nucleoli. Many atypical mitosis and scattered eosinophils were also present. Neoplastic cells showed strong cytoplasmic CD3 positivity interspersed with CD20 positive reactive B cells in the background. The adjoining mucosa in all 4 cases of EATL showed variable degree of villous atrophy, heavy mucosal inflammation, marked mucin depletion and grossly increased intra-epithelial lymphocytes. Of the 5 cases of ALCL, one was a subtotal gastrectomy with serosal extension involving 10/17 perigastric and 2/5 mesenteric lymph nodes. Four of the cases were biopsy specimens, one involving ileocaecal region in HIV positive patient, 2 involving small intestine and 1 involving stomach. All 5 ALCL cases showed grossly thicken mucosa with ulceration. The infiltrating cells were highly pleomorphic with many large anaplastic cells intermixed with scattered eosinophils and mature looking lymphocytes in the background. Variably sized lymphoid cells showed cytoplasmic CD3 positivity including the pleomorphic and anaplastic cells. Membranous CD30 positivity was exhibited mainly by the large pleomorphic and anaplastic cells. One case of ALCL also showed EMA positivity by the anaplastic cells. All the 5 ALCL did not associated enteropathy changes in adjoining intestinal mucosa.
Amongst the gastric MALTOMAS, 19 cases showed features of AG, 8 with IM. One case of high grade gastric MALTOMA was associated with malignant neuroendocrine tumor. Characteristic LEL was seen in 31 cases inclusive of 16 high grade and 1 intermediate grade gastric MALTOMAS. Three of the high grade MALTOMA involved both stomach and duodenum. High grade MALTOMAS were also seen involving small intestine in 2 and colon in 1. There was one case of low grade MALTOMA involving duodenum. In addition, LEL was also noted in 1 case each of gastric, ileal and colonic DLBL and 1 involving both large and small intestine, 1 case each of ileal and duodenal ALCL, and 1 case of jejunal EATL. Besides EATL, enteropathy associated mucosal changes were also seen in 1 case each of DLBL and high grade MALTOMA. H pylori could be demonstrated in gastric mucosa in one high grade gastric MALTOMA. An associated Giardia Lamblia infection was also demonstrated in a low grade duodenal MALTOMA.
Depth of the tumor invasion was evaluated in the 22 resected specimens from in-house specimens and 2 referral cases. And 20/24 (83.33%) cases showed transmural invasion upto serosa. Small intestinal perforation was observed in 5 cases (20.83%), 3 cases of DLBL and 2 cases of EATL. Contiguous regional mesenteric lymph nodal involvement was also documented in 2 cases each of ileal DLBL and gastric high grade MALTOMAs, 1 case each of ileal high grade MALTOMA, gastric ALCL and colonic follicular lymphoma. One jejunal IPSID had involvement of liver portal tract, spleenic sinusoids and contiguous lymph nodes. None of our cases had evidence of bone marrow involvement. According to Mushoff's staging, 16 cases belonged to stage IE, 7 to stage IIE and 1 to stage IV. All the cases with higher clinical staging had a high grade lymphoma.
| » Discussion|| |
The median age in our patients was 54.4 years, similar to other reports in the literature. , However, Arora et al., reported a decade younger in their study in south Indian population.  This could possibly be related to geographical variation and incidence of H pylori infection . [ 9], Similar to previous studies, we also observed male preponderance accounting for 68% of the cases. ,, Stomach was the commonest site of involvement followed by ileum in our cases. Number of cases involving large intestine were relatively few while just one case of DLBL involved the esophagus. Similar distribution was also reported by another group. , Ghimire et al.  reported incidence of primary esophageal lymphoma in less than 1% of all GI lymphomas with a predominant histological phenotype of DLBL. The commonest histological subtype observed in the present study was MALTOMA followed by DLBL, similar to the Japanese study which also reported higher incidence of MALTOMA (51%) over DLBL (41%). , However, Radic-Kristo et al.,  reported much higher incidence of DLBL in 71% and MALTOMA only in 20% of their cases similar Arora et a., T cell lymphoma accounted for 11% of our cases, similar to the findings by Nakamura et al.,  who reported 9% of T cell lymphoma in their series. H pylori infection and atrophic gastritis are proven precursor lesions of gastric lymphoma.  We could demonstrate H pylori only in 1 case and most of our cases had progressed to AG with variable degree of IM. One case of gastric MALTOMA showed co-existing malignant neuroendocrine tumor in the background of AG. There are two case reports of gastric MALTOMA with carcinoid of the duodenum. , However there is no report of synchronous gastric MALTOMA with gastric neuro-endocrine tumor in the English literature. The underlying pathogenesis for the development both malignancies in both conditions is thought to be the same by excessive stimulation of the G cells in an atrophic gastric mucosa. Celiac disease (CD) is also a known forerunner of EATL.  Enteropathy associated mucosal changes were seen in 4 of EATL but none of these patients had history of long standing diarrheal diseases and serological markers for CD were non-contributory. Distribution of the histological staging observed in our cases were similar to studies done by Nakamura et al.,  and Papaxoinis et al.,  where most of their cases also belonged to stage I. There was 1 case (4.5%) of jejunal IPSID infiltrating the liver, spleen and adjacent lymphnodes, hence Mushoff's stage IV. Though contiguous nodal involvement is common in IPSID, spread to other abdominal organs is rare. Haghighi also reported secondary infiltration of liver by IPSID in just one of their case series. 
| » Conclusion|| |
Primary gastrointestinal lymphoma was observed frequently in the 6 th decade with a male preponderance. Stomach was the commonest site and high grade MALTOMA being the commonest histological variant. Isolated colonic involvement and intestinal perforations at presentation were not infrequent. A few rare variants like ALCL and follicular lymphomas were also observed. Atrophic gastritis and enteropathy associated changes are predisposing conditions.
| » References|| |
Freeman C, Berg JW, Cutler SJ. Occurrence and prognosis of extra nodal lymphomas. Cancer 1972;29:252-60.
Otter R, Bieger R, Kluin PM, Hermans J, Willemze R. Primary gastrointestinal non-Hodgkin's lymphoma in a population based registry. Br J Cancer 1989;60:745-50.
Mihaljeviæ B, Nedeljkov-Janciæ R, Vujiciæ V, Antiæ D, Jankoviæ S, Coloviæ N. Primary extra nodal lymphomas of gastrointestinal locations: A single institutions'' 5-yr experience. Med Oncol 2006;23:225-35.
Ghimire P, Wu GY, Zhu L. Primary gastrointestinal lymphoma. World J Gastroenterol 2011;17:697-707.
Jaffe ES, Harris NL, Stein H, Vardiman JW, editors. World Health Organization Classifications of tumors: Pathology and genetics of tumors of hematopoietic and lymphoid tissues. Lyon, France: IARC Press; 2001.
Mushoff K, Schmidt -Volmer H. Prognosis of non-Hodgkin's lymphomas with special emphasis on the staging classification. Z Krebsforsch, 1975, 83: 323-41.
Papoxinis G, Papageorgiou S, Rontogianni D, Kaloutsi V, Fountzilas G, Pavlidis N, et al.
Primary gastrointestinal non-Hodgkin's lymphoma: A clinicopathologic study of 128 cases in Greece. A Hellenic Cooperative Oncology Group study (HeCOG). Leuk Lymphoma 2006;47:2140-6.
Radiæ-Kristo D, Planinc-Peraica A, Ostojiæ S, Vrhovac R, Kardum Skelin I, Jasic B. Primary Gastrointestinal non-Hodgkin Lymphoma in Adults. Clinicopathologic and Survival Characteristics. Coll Antropol 2010;34:413-7.
Arora N, Manipadam MT, Pulimood A, Ramakrishna BS, Chacko A, Kurian SS et al.
Gastrointestinal lymphomas: Pattern of distribution and histological subtypes: 10 years experience in a tertiary centre in South India. Indian J Pathol Microbiol 2011;343:712-9.
Singh V, Trikha B, Nain C, Singh K, Vaiphei K. Epidemiology of Helicobacter pylori
and peptic ulcer in India. J Gastroenterol Hepatol 2002;17:659-65.
Kate V, Ananthakrishnan N, Ratnakar C, Badrinath S. Anti-H. pylori IgG seroprevalence rates in asymptomatic children and adults from South India. Indian J Med Microbiol 2001;19:20-5.
Koch P, Valle F, Berdel WE, Willich NA, Reers B, Hiddemann W et al.
Primary Gastrointestinal non-hodgkin's lymphoma: I.anatomic and histologic distribution, clinical features, and survival data of 371 patients registered in the German Multicenter Study. GIT NHL 01/92. J Clin Oncol 2001;19:3861-73.
Nakamura S, Matsumoto T, Iida M, Yao T, Tsuneyoshi M. Primary gastrointestinal lymphoma in japan A clinicopathologic analysis of 455 patients with special reference to its time trends Cancer 2003;97:2462-73.
Hussell T, Issacson P, Crabtree J, Spencer J. Helicobacter pylori
specific tumor infiltrating T cells provide contact dependant help for the growth of malignant B cells in low grade gastric lymphoma of mucosa associated lymphoid tissue. J Pathol 1996;178:122-7.
Agarwal T, Jain M, Dhameja N, Prasad TL, Saxena R, Gupta RK. Malignant lymphoma of stomach associated with duodenal carcinoid. Indian J Gastroenterol 2006;25:213-4.
Benharroch D, Peiser J. Malignant lymphoma of the stomach associated with carcinoid tumor of the duodenum. J Clin Gastroenterol 1992;14:90-1.
Ko YH, Karnan S, Kim KM, Park CK, Kang ES, Kim YH, et al.
Enteropathy-associated T cell Lymphoma--a clinicopathological and array comparative genomic hybridization study. Hum Pathol 2010;41:1231-7.
Haghighi P, Kharazmi A, Gerami C, Haghshenass M, Abadi P, Omidi H et al.
Primary upper small-intestinal lymphoma and alpha-chain disease. Report of 10 cases emphasizing pathological aspects. Am J Surg Pathol 1978;2:147-57.
|This article has been cited by|
||Intraepithelial lymphocytes, scores, mimickers and challenges in diagnosing gluten-sensitive enteropathy (celiac disease)
| ||Consolato Sergi,Fan Shen,Gerd Bouma |
| ||World Journal of Gastroenterology. 2017; 23(4): 573 |
|[Pubmed] | [DOI]|
||Primary rare anaplastic large cell lymphoma, ALK positive in small intestine: case report and review of the literature
| ||Qinghua Cao,Fang Liu,Shurong Li,Ni Liu,Lihui Li,Changzhao Li,Tingsheng Peng |
| ||Diagnostic Pathology. 2016; 11(1) |
|[Pubmed] | [DOI]|