Primary Gastrointestinal Lymphoma Research Articles

S3015 Primary Gastrointestinal T-cell Lymphoma Presenting as Spontaneous Perforation Peritonitis: A Case Report

S3015 Primary Gastrointestinal T-cell Lymphoma Presenting as Spontaneous Perforation Peritonitis: A Case Report

828MO Exonic mutation profile of primary gastrointestinal diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma, and about 10% of DLBCL cases primarily occur in the gastrointestinal tract. Previous reports have revealed that primary gastrointestinal-DLBCL (pGI-DLBCL) harbors different genetic mutations from other nodal or extranodal DLBCL. However, the exonic mutation profile of pGI-DLBCL has not been fully addressed.

Increased MALAT1 expression predicts poor prognosis in primary gastrointestinal diffuse large B-cell lymphoma.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is involved in the pathogenesis and progression of several cancers. However, the potential effect of MALAT1 in primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) has not been elucidated. This study aimed to explore the prognostic value of MALAT1 in patients with PGI-DLBCL. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine the expression of MALAT1 in 90 patients with PGI-DLBCL. MALAT1 was remarkably upregulated in PGI-DLBCL tissues compared to paired adjacent non-tumor tissues (P < 0.001), and the area under the receiver operating characteristic (ROC) curve (AUC) was 0.838. MALAT1 expression was further increased in the non-germinal center B-cell-like (non-GCB), advanced stage (stages IIE-IV) and International Prognostic Index (IPI) score (3-5) groups (P = 0.01, P < 0.001 and P < 0.001, respectively). Furthermore, Kaplan-Meier analysis showed that elevated MALAT1 expression correlated with inferior overall survival (OS) and progression-free survival in PGI-DLBCL patients (P < 0.001 and P < 0.001, respectively), and our multivariate analysis results suggested that upregulation of MALAT1 and high IPI score (3-5) were two unfavorable prognostic factors for PGI-DLBCL. In conclusion, our results demonstrate that MALAT1 may serve as a novel prognostic biomarker and an ideal therapeutic target for patients with PGI-DLBCL.

Ibritumomab Tiuxetan Radioimmunotherapy for Primary Gastrointestinal Follicular Lymphoma.

Primary gastrointestinal follicular lymphoma (PGIFL) is characterized by localized involvement of the gastrointestinal (GI) tract. PGIFL usually runs an indolent course. External beam radiation therapy is curative in a substantial proportion of localized follicular lymphomas, but GI toxicities may discourage its use in PGIFL. Ibritumomab tiuxetan radioimmunotherapy (RIT) is a radioimmunoconjugate of anti-CD20 monoclonal antibody linked to chelator tiuxetan and radioisotope. RIT delivers confined high-intensity radiation with short path length specifically targeting lymphoma cells and sparing normal tissue. In this case series report, we included six cases of PGIFL treated with RIT. All patients had low-risk, localized, and nonbulky disease. All patients responded completely and were relapse-free for the duration of follow-up. Hematologic toxicities were seen, but none were serious. RIT is a potentially curative treatment option in PGIFL with a tolerable toxicity profile.

HISTOPATHOLOGICAL ANALYSIS OF GASTROINTESTINAL LYMPHOMAS AT A TERTIARY CARE CENTRE WITH REVIEW OF LITERATURE

BACKGROUND: Primary gastrointestinal lymphoma is the most common extranodal non-Hodgkin lymphoma representing a wide spectrum of disease . It constitutes 10–15% of all non-Hodgkin's lymphoma and about 30–40% of extra-nodal lymphomas. The incidence of GI lymphomas varies across the globe . It can involve any site from the esophagus to the anal canal. AIM: This study aims to analyse the clinical features , anatomic distribution, histological subtypes and sites of all GIT lymphomas presenting to a tertiary care centre . STUDY DESIGN : MATERIALS AND METHODS: Descriptive study. The histological material in 21 patients over a period of 8 years (2011–2019), with a histopathological diagnosis of lymphoma involving the GIT was analyzed retrospectively. All lymphomas were reclassified according to the World Health Organization 2019 classification. RESULTS: There were 21 cases of GI lymphomas. 11 males and 10 females with a male to female ratio of 1.1:1. Predominantly middle aged and elderly range from 41-79years is involved. The commonest clinical presentation was abdominal discomfort and abdominal pain. The commonest site involved is ileum and Diffuse large B cell lymphoma is the commonest subtype (71.42%). Only one case of T cell lymphoma was recognized.

Multicentric Study of Clinicopathological Features of Primary Gastrointestinal Lymphoma of Iran: from 2011 - 2016

Background: Gastrointestinal (GI) tract is the most common site for extranodal lymphoma. The primary GI lymphoma pattern in Iran is different from western countries and has been changed during the past 40 years. Objectives: This study was done to determine the clinical and pathological characteristics of primary GI lymphoma in Tehran, Hamedan, and Mashhad regions in Iran. Methods: In this cross-sectional comparative-descriptive study, 200 patients with primary GI lymphoma in Tehran, Hamadan, and Mashhad regions from 2011 to 2016 were enrolled in a consecutive manner, where the clinical and pathological characteristics of cases were determined. Results: Among 200 patients, 141 (70.5%) subjects were male and 59 (29.5%) subjects were female. The mean age at diagnosis was 54.3 ± 19.3 years. Also, 84%, 8.5%, and 7.5% of the patients’ specimens were from Tehran, Hamedan, and Mashhad, respectively. The stomach was the principal involved location in approximately half of the cases. Diffuse large B-cell lymphoma (DLBCL), was the main subtype that was observed in 64% of the cases. Treatment in 72% of cases was a combination of surgery and chemotherapy. The 5-year survival was assessed in 147 patients with a rate of 68%. Conclusions: Primary GI lymphoma is seen more in male subjects younger than 60 years of age with non-specific symptoms. Also, DLBCL and MALToma are the main histologic types, and the 5-year survival for all cases is 68.0%. The clinical symptoms showed no specific pattern and accordingly, patients with weight loss and abdominal pain should be considered in in differential diagnosis of malignant lymphoma.

Analysis of the Predictive Value of EZH2 Expression Level on the Clinical Efficacy and Long-term Prognosis of Patients with Primary Gastrointestinal Diffuse Large B-cell Lymphoma

To investigate the predictive value of methyltransferase EZH2 expression level on the clinical efficacy and long-term prognosis of patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL). 161 patients with newly treated PGI-DLBCL in our hospital from August 2013 to July 2019 were selected. The expression level of EZH2 protein was detected by immunohistochemistry, and the short-term efficacy and long-term survival differences of patients with different levels of EZH2 were compared. The predictive values of EZH2 expression level on the short-term efficacy and long-term prognosis of PGI-DLBCL patients were analyzed by Log-rank test and COX risk proportional regression model. Chi-square test and Logistic regression analysis were used to analyze the influencing factors of EZH2 expression level. The complete response (CR) and overal response(OR) rates of those with high EZH2 expression were significantly lower than those with low EZH2 expression (P<0.001). The median OS and PFS of EZH2 high-level and low-level expression group was 37, 31 months and 49, 42 months, respectively. The cumulative OS and PFS rates of the high-level expression group were significantly lower than those of the low-level expression group, and the differences were statistically significant (P<0.05). The high expression levels of H3K27me3, EZH2, BCL-2, BCL-6, c-MYC were closely related to the shortening of OS and PFS, while the high expression level of Ki-67 was closely related to the shortening of OS (P<0.05), of which the high expression levels of H3K27me3, EZH2, BCL-2, and BCL-6 were independent risk factors for shortening of OS and PFS. The expression level of EZH2 was positively correlated with the expression level of H3K27me3, BCL-6, c-MYC and Ki-67 (r=0.741, r=0.837, r=0.809, r=0.772), and the high expression levels of H3K27me3, BCL-6 and Ki-67 were independent factors influencing the high expression of EZH2. In patients with PGI-DLBCL, the high expression of EZH2 significantly reduces the short-term CR and OR rates, which is an independent risk factor for the shortening of long-term OS and PFS rates, and it is independently related to the high expression of H3K27me3 and BCL6.

Role of MUM-1 immunohistochemistry in prognosis of primary gastrointestinal diffuse large cell lymphoma

: Diffuse large B-cell lymphoma (DLBCL) is the most common type of primary gastrointestinal lymphomas. It is a clinically heterogenous disease as most patients respond well to therapy, however a significant proportion of these patients become refractory or eventually relapse. Different prognostic factors for response and survival have been described for DLBCL. Immunophenotypic algorithms with small panels of biomarkers have been developed to translate the robust information from molecular studies into a routine clinical.platform. One of these biomarkers is MUM-1 which is used as a marker for classification of diffuse large B cell lymphoma into ABC type and its expression is associated with poorer overall survival as stated by various studies. We aim to study the expression pattern of MUM-1 IHC in primary gastrointestinal diffuse large B cell lymphomas and its role in prognosis and survival outcome. It was a five-year retrospective study where 40 cases of primary gastrointestinal DLBCL were identified, and MUM-1 IHC was done in 29 cases. Follow up and subsequent survival analysis was done.MUM-1 was positive in 7 (24%) and negative in 22 (76%) cases of primary gastrointestinal DLBCL. The overall survival of patients with DLBCL with MUM-1 expression (42.9%) was shorter than those without MUM-1 expression (72.7%). This suggested that MUM-1 expression in cases with DLBCL is associated with poorer prognosis.Multicentre large studies are warranted to study the role of MUM-1 IHC in prognosis of primary gastrointestinal DLBCL.

Molecular Pathogenesis of Primary Gastrointestinal Tract Lymphomas.

Primary gastrointestinal lymphomas are rare though the incidence is significantly increased among adult patients in recent years. The majority of the patients present with symptoms overlapping with other gastrointestinal disorders and imaging findings are not specific. Therefore, histologic examination is necessary to establish the diagnosis. Insight into etiologies, molecular pathogenesis and critical signaling pathways in lymphomas including gastrointestinal lymphomas has significantly expanded within the last 3 decades. Given the increasing demand for incorporation of genetic data, the appropriate handling and processing of small endoscopic gastrointestinal biopsy samples of suspected lymphoma is becoming extremely crucial and at times challenging. The use of next generation sequencing with analysis of genes relevant to diagnosis, prognosis, and therapeutic targets continues to have a significant promising impact on management of patients in lymphoid malignancies. In particular, the identification of constitutively activated pathways and the emergence of novel targeted medications predict that more effective therapies will be identified for these disorders in the coming years.

Gastrointestinal Tract Lymphomas.

The gastrointestinal (GI) tract is the most common site of extranodal non-Hodgkin lymphoma, accounting for 20% to 40% of all extranodal lymphomas. The majority of these are systemic processes secondarily involving the GI tract. Primary GI lymphomas are less common, accounting for approximately 10% to 15% of all non-Hodgkin lymphomas. Most non-Hodgkin lymphomas involving the GI tract are of B-cell lineage, of which diffuse large B-cell lymphoma is the most common subtype, irrespective of location. To review the lymphoproliferative neoplasms of B-cell and T-cell lineage involving the luminal GI tract according to the most prevalent subtypes at each anatomic site. Systematic search of the PubMed database for updated literature on GI lymphoma epidemiology, subtypes, clinical, endoscopic, and genetic findings. Histologic images are derived from our collection of clinical cases. The GI tract is the most common site of extranodal lymphoproliferative neoplasms. Recognition of the most frequently encountered GI lymphomas is imperative for patient management and treatment.

Primary Gastro-Intestinal Lymphoma and Gastro-Intestinal Adenocarcinoma: An Initial Study of CT Texture Analysis as Quantitative Biomarkers for Differentiation.

Background: To explore the potential role of computed tomography (CT) texture analysis and an imaging biomarker in differentiating primary gastro-intestinal lymphoma (PGIL) from gastro-intestinal adenocarcinoma (GIAC). Methods: A total of 131 patients with surgical pathologically PGIL and GIAC were enrolled in this study. Histogram parameters of arterial and venous phases extracted from contrast enhanced modified discrete cosine transform (MDCT) images were compared between PGIL and GIAC by Mann–Whitney U tests. The optimal parameters for differentiating these two groups were obtained through receiver operating characteristic (ROC) curves and the area under the curve (AUC) was calculated. Results: Compared with GIAC, in arterial phase, PGIL had statistically higher 5th, 10th percentiles (p = 0.003 and 0.011) and statistically lower entropy (p = 0.001). In the venous phase, PGIL had statistically lower mean, median, 75th, 90th, 95th percentiles, and entropy (p = 0.036, 0.029, 0.007, 0.001 and 0.001, respectively). For differentiating PGIL from GIAC, V-median + A-5th percentile was an optimal parameter for combined diagnosis (AUC = 0.746, p < 0.0001), and the corresponding sensitivity and specificity were 81.7 and 64.8%, respectively. Conclusion: CT texture analysis could be useful for differential diagnosis of PGIL and GIAC.

Genomic Mutation Profile of Primary Gastrointestinal Diffuse Large B-Cell Lymphoma.

Primary gastrointestinal diffuse large B-cell lymphoma (GI-DLBCL) is the most common gastrointestinal lymphoma, but its genetic features are poorly understood. We performed whole-exome sequencing of 25 primary tumor samples from patients with GI-DLBCL and 23 matched normal tissue samples. Oncogenic mutations were screened, and the correlations between genetic mutations and clinicopathological characteristics were analyzed. Twenty-five patients with GI-DLBCL were enrolled in the genetic mutation analysis with a median of 184 (range 79–382) protein-altering variants per patient. We identified recurrent oncogenic mutations in GI-DLBCL, including those in TP53, MUC16, B2M, CCND3, HIST1H1C, NEB, and ID3. Compared with nodal DLBCL, GI-DLBCL exhibited an increased mutation frequency of TP53 and reduced mutation frequencies of PIM1, CREBBP, BCL2, KMT2D, and EZH2. Moreover, GI-DLBCL exhibited fewer MYD88 and CD79B mutations than DLBCL in the testis and central nervous system. GI-DLBCLs with HLA-B, MEF2A, RHOA, and NAV3 mutations exhibited a tendency toward a high proliferation index. MUC16 and ETV6 mutations often occurred in tumors with early clinical staging. Our data provide a comprehensive understanding of the landscape of mutations in a small subset of GI-DLBCLs. The genetic mutation profiles of GI-DLBCL differ from those of nodal DLBCL and DLBCL in immune-privileged sites. The different mutated genes are related to the NF-κB and JAK-STAT pathways, and the different pathogenetic mechanisms leading to the development of DLBCL may be influenced by the tissue microenvironment. Differences in genetic alterations might influence the clinicopathological characteristics of GI-DLBCL.

Undifferentiated large cell/rhabdoid carcinoma presenting in the intestines of patients with concurrent or recent non-small cell lung cancer (NSCLC): clinicopathologic and molecular analysis of 14 cases indicates an unusual pattern of dedifferentiated metastases

Undifferentiated carcinoma metastatic to the bowel is uncommon in surgical pathology practice and might be confused with primary gastrointestinal carcinoma, melanoma, lymphoma, and others. We present 14 cases of uni- (n = 9) or multifocal (n = 5) undifferentiated large cell/rhabdoid carcinoma presenting in the bowel of patients with concurrent (n = 9) or recent (diagnosed 1 to 25 months earlier; median, 4) non-small cell lung cancer (NSCLC). Patients were 6 females and 8 males, aged 52 to 85 years. Primary NSCLC was verified histologically in 10 cases and by imaging in 4. The undifferentiated histology was present in the lung biopsy in 4/10 patients (as sole pattern in 3 and combined with adenocarcinoma in 1) and was limited to the intestinal metastases in the remainder. PDL1 was strongly expressed in 7/9 cases (CPS: 41 to 100). Loss of at least one SWI/SNF subunit was detected in 7/13 cases (54%). SMARCA2 loss (n = 6) was most frequent and was combined with SMARCA4 loss in one case. PBRM1 loss was observed in one tumor. Successful molecular testing of 11 cases revealed BRAF mutations in 4 (3 were non-V600E variants), KRAS mutations in 3, and wildtype in 4. None had EGFR mutations. Analysis of 4 paired samples revealed concordant KRAS (2) and BRAF (1) mutations or wildtype (1). Our study indicates that undifferentiated carcinoma within the intestines of patients with concurrent/recent NSCLC represents dedifferentiated metastasis from the NSCLC. Recognition of this unusual presentation is cardinal to avoid misdiagnosis with inappropriate therapeutic and prognostic implications.

Clinicopathological Study of Primary Pediatric Gastrointestinal Lymphomas.

Background:Primary gastrointestinal lymphomas (PGIL) are uncommon in children and account for <5% of all pediatric malignancies. The objective of our study was to analyze the prognostic factors of pediatric PGILs with reference to its histological subtypes, stage, and outcomes using immunohistochemistry.Materials and Methods:Twenty cases were studied over 11 years. Clinicopathological profiles, histological details, and immunohistochemical (IHC) profiles were analyzed.Results:The mean age at the presentation was 6 years. Using IHC stains (CD CD10, CD19, CD20, CD3, terminal deoxynucleotidyl transferase, BCL 2 and 6, PAX 5, and MUM1), diffuse large B-cell lymphoma (DLBCL) was most prevalent (45%), followed by Burkitt lymphoma (35%) and lymphoblastic lymphoma (20%). DLBCLs (9) were classified using the Han's algorithm. Six were activated B-cell and 3 were germinal center B-cell subtypes. The cases of lymphoblastic lymphoma and those in Stage I disease had the best prognosis.Conclusion:Pediatric PGILs have variable presentation, outcomes, and diverse treatment modalities depending on the histological subtypes. A panel of IHC stains can be a useful adjunct for the categorization and prognosis of pediatric PGILs.

A 10-year cohort study of 175 primary gastrointestinal lymphoma cases in Thailand: clinical features and outcomes in the immunochemotherapy era

ABSTRACT Background Primary gastrointestinal lymphoma (PGIL), an uncommon subtype of lymphoma, accounts for 1%–4% of gastrointestinal cancers. This study, therefore, aimed to investigate the current 10-year epidemiology and outcomes of PGIL. Methods This retrospective study involved a hospital-based chart review to analyze the epidemiology, clinical features, predisposing factors, and clinical outcomes of patients diagnosed with, and treated for, PGIL. Data covering 10 years was collected of Thai patients aged ≥ 15 years who had been diagnosed as PGIL with pathological confirmation and treated at Siriraj Hospital, Thailand. Results A total of 175 PGIL patients were enrolled. Their median age was 60 years (range, 20–98), with a male predominance. The stomach was the most common site of gastrointestinal (GI) organ involvement by lymphoma (38.9%), followed by the small intestine (23.4%) and multiple sites of GI involvement (23.4%). Diffuse large B-cell lymphoma (DLBCL) had the highest proportion of PGIL, accounting for 61.1%. The median patient follow-up time was 13.9 months (range: 0–104.9 months). The median overall survival (OS) of PGIL patients was not reached during the 10 years, with a 5-year OS of 64.4%. The probability of having a better OS was demonstrated in patients with a good performance status who received a rituximab-containing regimen. Conclusions The stomach was the most common site of lymphoma involvement in the GI tract, with DLBCL accounting for the highest proportion of those patients. The long-term survival outcome was significantly improved in patients with good performance status and rituximab exposure. Trial registrationNot applicable.

Clinical characteristics and outcomes of primary versus secondary gastrointestinal mantle cell lymphoma

Primary gastrointestinal (GI) mantle cell lymphoma (MCL) is rare and the optimal management is unknown. We reviewed 800 newly diagnosed MCL cases and found 22 primary (2.8%) and 79 (9.9%) secondary GI MCL cases. Age, sex, and performance status were similar between primary and secondary cases. Secondary cases had more elevations in lactate dehydrogenase (28% vs 0%, P = 0.03) and a trend for a higher MCL international prognostic index (P = 0.07). Observation or local therapy was more common for primary GI MCL (29% vs 8%, P < 0.01), and autologous stem-cell transplant was more common for secondary GI MCL (35% vs 14%, P < 0.05). The median follow-up was 85 months. Primary and secondary GI MCL had similar 5-year progression-free survival (PFS) (30% vs 28%, P = 0.59) and overall survival (OS) (65% vs 66%, P = 0.83). The extent of GI involvement in primary GI MCL affected treatment selection but not outcome, with a 5-year PFS of 43% vs 14% vs 31% (P = 0.48) and OS of 57% vs 71% vs 69% (P = 0.54) in cases with single lesion vs multiple lesions in 1 organ vs multiple lesions in ≥2 organs. Less aggressive frontline treatment for primary GI MCL is reasonable. It is unknown whether more aggressive treatment can result in improved outcomes.

Primary Gastrointestinal Lymphomas in Adults: An Institutional Experience of 15 Years from Northern India

Primary Gastrointestinal Lymphomas in Adults: An Institutional Experience of 15 Years from Northern India

Assessment of cases of primary cutaneous lymphomas- A clinical study

Background: Primary cutaneous lymphomas represent the second most common group of extranodal non-Hodgkin lymphoma after primary gastrointestinal lymphomas. The present study was conducted to assess cases of primary cutaneous lymphomas. Materials and methods: 82 cases of primary cutaneous lymphomas both genders were recruited. Duration of illness, presence of pruritus, family history, and occupational history was recorded. Results: Out of 82 patients, males were 48 and females were 34. Type of lesions were mycosis fungoides in 42, adult T-cell lymphoma/leukemia in 30 and peripheral T-cell lymphoma in 10 patients. Type of lesions were macules in 16, papules in 20, plaques in 22, macules & papules in 10, papules & plaques in 4, pustules and nodules in 6, plaques and nodules in 4 cases. The difference was significant (P< 0.05). Conclusion: Type of lesions were mycosis fungoides, adult T-cell lymphoma/leukemia and peripheral T-cell lymphoma in 10 patients. Type of lesions were macules, papules, plaques, macules & papules.

Progress in Diagnosis and Treatment of Primary Gastrointestinal Lymphoma

胃肠道；淋巴瘤；病理；诊断；临床表现；治疗

A rare case report of large B cell lymphoma in adult presentation as intussusception.

Adult intussusception represents 5% of all intussusceptions. Primary gastro-intestinal lymphoma comprises 1%-4% of all gastro- intestinal malignancies 90% of them are B-cell non-Hodgkin’s lymphoma (NHL). Most common NHL is diffuse large B-cell lymphoma accounts for 30-40%. Most common lymphoma causing intussusception is diffuse large B-cell lymphoma (DLBCL). We herein report a rare case of ileo-colic intussusception due to DLBCL in a 50- years-old male. Computed tomography showed ileo-colic intussusception with possibility of neoplastic etiology as a lead point. Hemicolectomy with ileo-colic anastomosis was done laparoscopically with post-operative chemotherapy. Subsequently, whole body positron emission tomography-computed tomography verified complete resolution of the malignancy. This study aims to present a rare case of ileo-colic intussusception due to non- Hodgkin’s B-cell lymphoma in a patient with unusual clinical course and highlight the importance of not only the timely surgical intervention but also the significance of strict adherence to follow up and chemotherapy will completely eradicate the malignancy.