Characterization of primary small intestinal lymphoma: a retrospective study based on double balloon endoscopy.

BACKGROUND: The diagnosis of primary small intestinal lymphoma (PSIL) is difficult. This study aimed to evaluate the clinical, radiological and endoscopic characteristics of PSIL and provide clue for diagnosis. METHODS: A total of 30 patients diagnosed with PSIL who underwent double balloon endoscopy (DBE) in the First Affiliated Hospital of Zhejiang University were retrospectively analyzed. Clinical, radiological and endoscopic data were collected. Univariate analysis was used to determine significant indicators for differentiating three main subtypes of PSIL. Cox regression analysis was performed to assess the risk factors for survival. RESULTS: In this study, 10 patients were pathologically diagnosed as diffuse large B-cell lymphoma (DLBCL), 11 were indolent B-cell lymphoma (BCL) and 9 were T-cell lymphoma (TCL). Compared with DLBCL patients, the body mass index (BMI) of TCL patients was significantly lower (p = 0.004). Meanwhile, compared with patients with DLBCL, the patients with indolent BCL had lower levels of C-reactive protein, lactate dehydrogenase (LDH), fibrinogen and D-Dimer (p = 0.004, p = 0.004, p = 0.006, and p = 0.002, respectively), and lower proportion of thicker intestinal wall and aneurysmal dilation in CT scan (p = 0.003 and p = 0.020, respectively). In terms of ulcer morphology, patients with DLBCL had significantly higher proportion of deep ulcers than patients with indolent BCL (p = 0.020, respectively). Cox regression analysis showed that drink (p = 0.034), concomitant colonic ulcers (p = 0.034) and elevated LDH (p = 0.043) are risk factors for mortality in patients with PSIL. CONCLUSIONS: This study provides clinical characteristics of patients with PSIL. Thicker intestinal wall and aneurismal dilation detected on CT scan and deeper ulcer on DBE examination helps to establish a diagnosis of DLBCL.

Oncogenetic landscape of lymphomagenesis in coeliac disease.

OBJECTIVE: Enteropathy-associated T-cell lymphoma (EATL) is a rare but severe complication of coeliac disease (CeD), often preceded by low-grade clonal intraepithelial lymphoproliferation, referred to as type II refractory CeD (RCDII). Knowledge on underlying oncogenic mechanisms remains scarce. Here, we analysed and compared the mutational landscape of RCDII and EATL in order to identify genetic drivers of CeD-associated lymphomagenesis. DESIGN: Pure populations of RCDII-cells derived from intestinal biopsies (n=9) or sorted from blood (n=2) were analysed by whole exome sequencing, comparative genomic hybridisation and RNA sequencing. Biopsies from RCDII (n=50), EATL (n=19), type I refractory CeD (n=7) and uncomplicated CeD (n=18) were analysed by targeted next-generation sequencing. Moreover, functional in vitro studies and drug testing were performed in RCDII-derived cell lines. RESULTS: 80% of RCDII and 90% of EATL displayed somatic gain-of-functions mutations in the JAK1-STAT3 pathway, including a remarkable p.G1097 hotspot mutation in the JAK1 kinase domain in approximately 50% of cases. Other recurrent somatic events were deleterious mutations in nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) regulators TNFAIP3 and TNIP3 and potentially oncogenic mutations in TET2, KMT2D and DDX3X. JAK1 inhibitors, and the proteasome inhibitor bortezomib could block survival and proliferation of malignant RCDII-cell lines. CONCLUSION: Mutations activating the JAK1-STAT3 pathway appear to be the main drivers of CeD-associated lymphomagenesis. In concert with mutations in negative regulators of NF-κB, they may favour the clonal emergence of malignant lymphocytes in the cytokine-rich coeliac intestine. The identified mutations are attractive therapeutic targets to treat RCDII and block progression towards EATL.

Unusual presentation of extra-nodal double-hit follicular lymphoma: a case report.

BACKGROUND: To the best of our knowledge, this case represents the first report of an extranodal double-hit follicular lymphoma (DH-FL) as an intestinal polypoid lesion. CASE PRESENTATION: A 72-year-old woman presents with constipation. Colonoscopy reveals a sessile polypoid lesion of the colon bearing morphological, immunohistochemical and molecular hallmarks of DH-FL. Complete clinical staging and bone marrow biopsy showed no signs of disseminated disease. The patient, after two years of follow-up is still free of disease confirming the indolent behaviour of this limited lesion. CONCLUSIONS: A synoptic view at all the features of the patient and not merely at the molecular hallmarks of a disease are essential to establish the correct clinical approach.

Ascites as First Atypical and Only Clinical Manifestation of De Novo Follicular Lymphoma.

Follicular lymphoma is the most common indolent non-Hodgkin's lymphoma and is usually initially detected in lymph nodes. Primary extranodal NHL is most commonly primarily localized in the gastrointestinal tract. We present one unusual case of ileum FL with ascites as the first clinical sign. The 73-year-old female patient was presented to the emergency department for evaluation of mild abdominal pain and abdominal swelling that had been going on for three days followed by bloating and occasional pain in the spine. The abdominal contrast-enhanced CT revealed the contrast stagnation in the distal part of the ileum. The ileum wall about 11 cm in length was thickened up to 2.9 cm and the tumor mass infiltrated all layers of ileum mesenteric lymphadenopathy up to 2 cm in diameter and significant ascites. On the upper ileum wall, the vegetative mass was described 3 cm in diameter. The patient had an emergent laparotomy with the ileocolic resection and latero-lateral ileocolic anastomosis. The microscopy finding of terminal ileum and the regional lymph nodes showed domination of cleaved cells with irregular nuclei which correspond to centrocytes. There were 0-15 large non-cleaved cells corresponding to centroblast in the microscopy high-power field. The final diagnosis was follicular lymphoma, the clinical stage 2E and histological grade by Berard and Mann criteria 1-2.

Clinical features and outcomes of bowel perforation in primary pediatric gastrointestinal lymphoma.

BACKGROUND: Whether surgery can improve the prognosis of patients with primary pediatric gastrointestinal lymphoma (PPGL) who experienced bowel perforation remains controversial. This study aimed to evaluate the prognosis of such patients. METHODS: Nine patients pathologically diagnosed with PPGL who experienced perforation at our center between January 2010 and December 2020 were enrolled and divided into two groups: those with perforation during (n = 4) and before (n = 5) chemotherapy. Their medical records were reviewed, and long-term follow-up was conducted by telephone in February 2021. RESULTS: All patients with perforation during chemotherapy were diagnosed with PPGL in the outpatient department. The mean time from outpatient visit to chemotherapy was 17.3 ± 6.1 days. Two patients experienced perforation during the first chemotherapy regimen and received conservative treatment, while the others developed perforation after multiple chemotherapy regimens and underwent surgery. All of the patients received regular chemotherapy and survived for a mean follow-up time of 3.8 ± 1.9 years. No patient with perforation before chemotherapy had a definite diagnosis in the outpatient department. Among these patients, 4 experienced perforation and underwent surgery, of whom 3 developed perforation-related complications and died; the other recurred after chemotherapy. Only the patient who received conservative treatment was diagnosed with PPGL before chemotherapy, received regular chemotherapy, and survived without a recurrence for 1.0 year. CONCLUSION: Prompt diagnosis and chemotherapy improve the prognosis of PPGL. Surgery does not affect the prognosis of patients with perforation during chemotherapy but may accelerate disease progression in patients with perforation before chemotherapy.

Gastrointestinal lymphoproliferative lesions: a practical diagnostic approach.

The gastrointestinal tract (GI) is the primary site of lymphoproliferative lesions, spanning from reactive lymphoid hyperplasia to overt lymphoma. The diagnosis of these diseases is challenging and an integrated approach based on clinical, morphological, immunohistochemical and molecular data is needed. To reach to confident conclusions, a stepwise approach is highly recommended. Histological evaluation should first assess the benign versus neoplastic nature of a given lymphoid infiltrate. Morphological and phenotypic analyses should then be applied to get to a definite diagnosis.This review addresses the key histological features and diagnostic workup of the most common GI non-Hodgkin lymphomas (NHLs). Differential diagnoses and possible pitfalls are discussed by considering distinct groups of lesions (i.e. small to medium B-cell NHLs; medium to large B-cell NHLs; T-cell NHLs; and mimickers of Hodgkin lymphoma). The key clinical and epidemiological features of each entity are also described.

NKp46 is a diagnostic biomarker and may be a therapeutic target in gastrointestinal T-cell lymphoproliferative diseases: a CELAC study.

OBJECTIVES: Primary GI T-cell lymphoproliferative diseases (T-LPD) are heterogeneous entities, which raise difficult diagnosis and therapeutic challenges. We have recently provided evidences that lymphomas complicating coeliac disease (CD) arise from innate-like lymphocytes, which may carry NK receptors (NKRs). DESIGN: NKRs expression was compared by flow cytometry in intraepithelial lymphocytes (IEL) from CD, type I or type II refractory CD (RCD). NKp46 was next assessed by immunohistochemistry in paraffin-embedded biopsies from 204 patients with CD, RCDI, RCDII or GI T-cell lymphomas and from a validation cohort of 61 patients. The cytotoxic properties of an anti-NKp46 monoclonal antibody conjugated to pyrrolobenzodiazepine (PBD) was tested ex vivo in human primary tumour cells isolated from fresh duodenal biopsies. RESULTS: NKp46 (but not CD94, NKG2A, NKG2C, NKG2D) was significantly more expressed by malignant RCDII IEL than by normal IEL in CD and RCDI. In paraffin biopsies, detection of >25 NKp46+ IEL per 100 epithelial cells discriminated RCDII from CD and RCDI. NKp46 was also detected in enteropathy-associated T-cell lymphomas (EATL, 24/29) and in monomorphic epitheliotropic intestinal T-cell lymphomas (MEITL, 4/4) but not in indolent T-LPD (0/15). Treatment with anti-NKp46-PBD could efficiently and selectively kill human NKp46+ primary IEL ex vivo. CONCLUSION: NKp46 is a novel biomarker useful for diagnosis and therapeutic stratification of GI T-LPD. Strong preclinical rationale identifies anti-NKp46-PBD as a promising therapy for RCDII, EATL and MEITL.

Extranodal lymphomas in the public health system in Chile: Analysis of 1251 patients from the National Adult Cancer Program.

The aim of the study was to describe the clinical and epidemiological characteristics, anatomic and histologic distribution, and treatment results of extranodal lymphomas (ENLs), diagnosed and treated in the public health system in Chile. We included patients with ENL diagnosed from 1998 to 2014, in 17 cancer centers, registered prospectively in the database of the National Adult Cancer Program (PANDA) of the Ministry of Health. Treatment was based on the local protocols for each lymphoma subtype. Extranodal lymphoma was documented in 1215 of 4907 non-Hodgkin lymphomas diagnosed in that period (25%). Median age was 59 years (range, 16-95), and 55% were female. The gastrointestinal (GI) tract was the most common location (38%), followed by the head and neck (24%) and the skin (15%). B-cell lymphomas accounted for 78% of cases, diffuse large B-cell lymphoma being the most common histologic subtype (68%). Mycosis fungoides/Sezary syndrome was the most frequent T-cell subtype (36%), followed by NK/T-cell lymphomanasal type (24%). In comparison with western countries, Chile showed a significantly high prevalence of NK/T-cell lymphoma nasal type, while the frequency of B-cell ENL and the anatomic distribution appeared similar, being GI the most commonly involved site.

Surgical management of primary colonic lymphoma: Big data for a rare problem.

BACKGROUND AND OBJECTIVES: Primary colonic lymphoma (PCL) is rare, heterogeneous, and presents a therapeutic challenge for surgeons. Optimal treatment strategies are difficult to standardize, leading to variation in therapy. Our objective was to describe the patient characteristics, short-term outcomes, and five-year survival of patients undergoing nonpalliative surgery for PCL. METHODS: We performed a retrospective cohort analysis in the National Cancer Database. Included patients underwent surgery for PCL between 2004 to 2014. Patients with metastases and palliative operations were excluded. Univariate predictors of overall survival were analyzed using multivariable Cox proportional hazard analysis. RESULTS: We identified 2153 patients. Median patient age was 68. Diffuse large B-cell lymphoma accounted for 57% of tumors. 30- and 90-Day mortality were high (5.6% and 11.1%, respectively). Thirty-nine percent of patients received adjuvant chemotherapy. For patients surviving 90 days, 5-year survival was 71.8%. Chemotherapy improved survival (surgery+chemo, 75.4% vs surgery, 68.6%; P = .01). Adjuvant chemotherapy was associated with overall survival after controlling for age, comorbidity, and lymphoma subtype (HR 1.27; 95% CI, 1.07-1.51; P = .01). CONCLUSIONS: Patients undergoing surgery for PCL have high rates of margin positivity and high short-term mortality. Chemotherapy improves survival, but <50% receive it. These data suggest the opportunity for improvement of care in patients with PCL.

Development and internal validation of a risk scoring system for gastrointestinal events requiring surgery in gastrointestinal lymphoma patients.

BACKGROUND AND AIM: The predictors of severe gastrointestinal (GI) events in GI lymphoma patients are unclear. We aimed to develop a risk scoring system for GI events requiring surgery. METHODS: In this retrospective study of 192 patients with GI lymphoma, the state of lymphoma, macroscopic findings, examination results, and International Prognostic Index were assessed. We developed a risk score for GI events that required surgery and assessed its accuracy by calculating the area under the receiver operating characteristic curve (AUC). Internal validation was performed using bootstrap resampling. RESULTS: Severe GI events occurred in 21 (11%) patients. We developed a 4-point scoring system (the FLASH score) comprising the following three independent predictors (weighted by regression coefficients): (i) focal appearance and large size (≥ 40 mm), 1 point; (ii) aggressive lymphoma of the small bowel, 2 points; and (iii) high (18)F-fluorodeoxyglucose positron emission tomography uptake, 1 point. The score predicted severe GI events with an AUC value of 0.91 (internal validation; AUC, 0.86). Risk was classified into three categories: the GI event rate was 0% in the low-risk group (0 points), 9% in the intermediate-risk group (1-2 points), and 61% in the high-risk group (3-4 points) (AUC, 0.89). CONCLUSIONS: We developed and internally validated a risk scoring system (the FLASH score) that included macroscopic findings to predict severe GI events in GI lymphoma patients. Patients with high scores are candidates for elective surgery to prevent GI events.

CLINICAL CHARACTERISTICS OF PRIMARY EXTRANODAL VERSUS NODAL DIFFUSE LARGE B-CELL LYMPHOMA: A RETROSPECTIVE COHORT STUDY IN A CANCER CENTER.

BACKGROUND: The outcome of patients with primary extranodal diffuse large B-cell lymphoma (PE-DLBCL) varies according to the primary site involved. Primary gastrointestinal, breast, bone, craniofacial, and testicular DLBCL are rare extranodal manifestations of DLBCL. OBJECTIVE: The objective of the study was to describe the clinical course of patients with PE-DLBCL disease in a referral cancer center. RESULTS: From 637 patients, 51 (8.77%) were considered as having PE-DLBCL (25 gastrointestinal, 12 craniofacial, 6 breast, 5 bone, and 3 with primary testicular DLBCL). Complete remission was higher in all PE-DLBCL sites (100% in testicular, 92.6% craniofacial, 83.3% breast, 80% bone, and 80% gastrointestinal) compared with 73.3% in nodal DLBCL. Although 2 cases with breast PE-DLBC relapsed, they achieved a complete response with chemotherapy. The overall survival at 5 years was 100%, 80%, 78%, 58%, 58%, and 62% for patients with primary breast, primary bone, gastrointestinal, primary craniofacial, primary testicular, and nodal DLBCL, respectively. CONCLUSIONS: PE-DLBCLs constitute rare, primary sites of lymphoproliferative disorders in most cases, with localized disease and good prognosis. They require a combined chemoimmunotherapy with radiotherapy in most cases to improve local and systemic disease.

Primary Gastric Lymphoma, Epidemiology, Clinical Diagnosis, and Treatment.

Primary gastric lymphoma (PGL) is the most common extranodal non-Hodgkin lymphoma and represents a wide spectrum of disease, ranging from indolent low-grade marginal zone lymphoma or mucosa-associated lymphoid tissue (MALT) lymphoma to aggressive diffuse large B-cell lymphoma. The PGL is a relatively rare cancer and easily misdiagnosed due to its unspecific symptoms of the digestive tract. The medical literature and ongoing clinical trials were reviewed on the clinical presentation, diagnosis, prognosis, prevention, and treatment of PGL. Primary gastric lymphoma is an event in the course of cancer with a variable clinical presentation and a wide differential diagnosis. Chronic gastritis secondary to Helicobacter pylori ( H pylori) infection has been considered a major predisposing factor for MALT lymphoma. Magnetic resonance imaging and endoscopic ultrasonography have helped in staging of these cancers. The clinical course and prognosis of this disease are dependent on histopathological subtype and stage at the time of diagnosis. A global therapeutic approach to the cure of PGL has completely changed over the past 10 years, including innovative and conservative options to reduce treatment toxicity. Due to the rarity of PGL, many aspects of this neoplasm are still controversial. The incidence of this disease is increasing, making it necessary for clinicians to understand the clinical symptoms, workup, and treatment of these lymphomas.

The value of EUS in combination with cytological, flow cytometry, and gene rearrangement in the diagnosis of gastrointestinal lymphoma.

Endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) have a great value in clinical practice of gastrointestinal lymphoma (GIL). Auxiliary methods such as flow cytometry (FCM) and gene rearrangement provide additional information for the diagnosis. Current study aims to explore the diagnostic value of EUS-FNA combined with FCM and gene rearrangement for GIL in our single institution. Suspected GIL cases, which were referred to EUS, FNA, FCM, or gene rearrangement examination, were retrospectively reviewed from January 2011 to May 2014. Definitive final diagnosis was included based on the pathological and immunostaining evidence. The gene scan analysis was applied for fragment detection in gene rearrangement. The sensitivity, specificity, and accuracy were considered and calculated. Fifty-three EUS cases were identified, including 38 GIL, 10 inflammations, 4 linitis plastica, and one multiple myeloma. EUS-FNA was successfully conducted in 39 out of 53 cases. After combined with FCM, the sensitivity, specificity, and accuracy were increased from 60.7% to 76.9%, 90.9% to 100%, and from 69.2% to 81.8% respectively. Among 33 cases for FCM, 11 of them gained positive B or T non-Hodgkin lymphoma diagnosis, and 28 out of 53 specimens were delivered for gene rearrangement. The sensitivity, specificity, and accuracy of gene rearrangement were 68.2%, 100%, and 75% respectively. EUS-FNA is a possible technique for the diagnosis of GIL, With additional FCM examination may further improve the diagnostic efficiency and facilitate subclassification. Moreover, gene rearrangement assay by gene scan is also a considerable method in the specimens from GIL. Copyright © 2016 John Wiley & Sons, Ltd.

Anatomic distribution, clinical features, and survival data of 87 cases primary gastrointestinal lymphoma.

BACKGROUND: The purpose of this study is to analyze the anatomic distribution, clinical features, therapeutic methods, and prognosis factors of primary gastrointestinal lymphoma (PGIL). METHODS: Clinical data of 87 cases PGIL in the First Affiliated Hospital of Dalian Medical University from January 1999 to December 2010 were collected. Follow-ups were made according to the clinical feature, pathological pattern, clinical stage, and therapeutic method. Kapan Meier method was used for the survival analysis. Log-rank test was used to perform univariate survival analysis. COX multivariate analysis was carried out to analyze factors of P < 0.05 in univariate survival analysis. RESULTS: The incidence of PGIL significantly increased in patients more than 40 years old (87.4%). Clinical symptoms of PGIL were indistinguishable from other digestive system diseases, which included abdominal pain or discomfort (72.4%), lack of appetite (16.3%), gastrointestinal hemorrhage (14.9%), and diarrhea (12.8%). Some patients presented with systemic symptoms or complications, such as weight loss (35.6%) and digestive tract obstruction (13.8%). Primary gastric lymphoma (PGL) was the most common, followed by primary intestine lymphoma (PIL). The majority of PGIL were single lesion, which included 40 cases (87%) PGL and 35 cases (94.5%) PIL. The most frequent site of PGL was antrum of the stomach (43.5%), as to PIL, the small intestine (90.2%) was the most frequent site, especially within 100 cm far away from ileocecal valve. Most of PGIL were derived from B cell (93.1%). The most common pathological type was mucosa-associated lymphoid tissue (MALT) (67.4%) in the PGL group and diffuse large B cell lymphoma (DLBCL) (46.3%) in the PIL group. Surgical treatment had been performed in most of PGIL, which included 32 cases in the PGL group and 38 cases in the PIL group. The 1-year overall survival (OS) and the 3-year OS were 82 and 77%, respectively. Analysis of single factor affecting prognosis showed that lesion location, sources of cells, and clinical stage were associated with OS. PGL group had better OS than that of PIL group (1-year 89 vs 62%, 3-year 84 vs 50%, P = 0.03). B cell-originated group had better OS than that of T cell-originated group (1-year 89 vs 36%, 3-year 85 vs 0 %, P = 0.008). Stage I + II group had better OS than that of stage III + IV group (1-year 89 vs 38%, 3-year 87 vs 0 %, P = 0.007). Multivariate analysis showed that clinical stage and sources of cells were the significant independent prognostic factors. CONCLUSIONS: It was more common to find location of PGIL in the stomach than that in the intestine. The most common pathological type was MALT in the PGL and DLBCL in the PIL. The treatment of PGL was focused on chemotherapy. It was noting that since PIL was not only difficult to make confirmed diagnosis but also likely to develop with complications, so it was usually needed surgical excision. Clinical stage and pathological pattern were related to prognosis of PGIL.

[Extranodal lymphomas in adults in Szabolcs-Szatmár-Bereg county, Hungary. Analysis of 30 years' epidemiologic data]. / Extranodalis lymphomák Szabolcs-Szatmár-Bereg megye felnott lakossága körében. 30 év adatainak elemzése.

INTRODUCTION: In their previous work, the authors reported 27-year' findings on the epidemiology of extranodal lymphomas in Szabolcs-Szatmár-Bereg county, Hungary. There are no other studies on this topic available in Hungary. AIM: The aim of this study was to analyse in detail the epidemiologic data of patients with non-Hodgkin's lymphoma who were recorded in the leukaemia/lymphoma registry of Szabolcs-Szatmár-Bereg county during a 30-year period, to compare the main epidemiologic features of the extranodal and nodal forms, and compare the results with data reported in the international literature. METHOD: Between January 1, 1983 and December 31, 2012, 1123 adult patients with newly diagnosed non-Hodgkin's lymphoma were recorded in the leukaemia/lymphoma registry of Szabolcs-Szatmár-Bereg county. Of those, 347 patients suffered from extranodal, and 776 patients from nodal form of non-Hodgkin's lymphoma. The authors compared the incidence of the extranodal and nodal forms, the age and sex distribution of patients, the ratio of B- and T-cell, as well as the indolent and aggressive forms, the geographic distribution and the association with carcinomas. In addition, they studied the occurrence of familial appearance and the localisation of extranodal forms. RESULTS: The occurrence of non-Hodgkin's lymphomas indicated an increasing tendency in their county. This tendency was true for both the extranodal and nodal forms, but it was more remarkable in the extranodal form of lymphomas. They found no substantial difference between the main epidemiologic features of the two forms. The gastrointestinal tract was the most frequent site of presentation for extranodal lymphomas. CONCLUSIONS: These observations are in line with data reported in the international literature. The data are essentially similar to those published in populations from Western European countries and the United States.

Diagnostic accuracy of endoscopic biopsies for the diagnosis of gastrointestinal follicular lymphoma: a clinicopathologic study of 48 patients.

The purpose of this study was to reveal the diagnostic accuracy of initial pathologic assessment of biopsied samples in patients with gastrointestinal follicular lymphoma lesions. A total of 48 patients with follicular lymphoma (Lugano system stage I: n = 30; II1: n = 4; II2: n = 4; IV: n = 10) with gastrointestinal involvement who underwent endoscopic biopsy were enrolled and retrospectively reviewed. Nine (18.8%) of the 48 patients were not appropriately diagnosed as having follicular lymphoma at the initial biopsy. The initial pathological diagnosis included extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (n = 4), necrotic tissue (n = 2), duodenitis (n = 1), or suspected lymphoma of unspecified subtype (n = 2). The reasons for these inappropriate diagnoses were insufficient histopathologic analysis lacking CD10 and BCL2 staining (n = 7) and unsuitable biopsy samples taken from erosions or ulcers that contained scanty lymphoma cells or no lymphoid follicles (n = 2). In conclusion, incomplete histopathologic analysis and unsuitable biopsy samples are pitfalls in the diagnosis of gastrointestinal follicular lymphoma.