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Rezkalla A, Rajab I, Orhun N, Musallam A, Villegas K, Nouri A. A large colonic polyp: an atypical presentation of follicular lymphoma. J Surg Case Rep 2025; 2025:rjaf058. [PMID: 39989727 PMCID: PMC11844243 DOI: 10.1093/jscr/rjaf058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Accepted: 01/29/2025] [Indexed: 02/25/2025] Open
Abstract
Follicular lymphoma of the gastrointestinal tract is a rare entity accounting for <7% of all non-Hodgkin lymphomas and is more common in the small intestine, whereas colorectal manifestations account for only 1%-2% of the cases. Most patients have limited disease with promising overall survival in comparison to nodal lymphoma although the morphologic, immunophenotypic, and genetic aspects of nodal follicular lymphomas remain the same. Despite the lack of randomized clinical trials, chemotherapy is frequently used to treat NCCN grade III and IV colonic follicular lymphomas with favorable prognosis. We hereby present a case of follicular lymphoma of the colon that was treated conservatively with a successful outcome.
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Affiliation(s)
- Abraam Rezkalla
- Internal Medicine Department, Saint Joseph’s University Medical Center, 703 Main Street, Paterson, NJ 07503, United States
| | - Islam Rajab
- Internal Medicine Department, Saint Joseph’s University Medical Center, 703 Main Street, Paterson, NJ 07503, United States
| | - Nagihan Orhun
- Internal Medicine Department, Saint Joseph’s University Medical Center, 703 Main Street, Paterson, NJ 07503, United States
| | - Alaa Musallam
- Internal Medicine Department, Saint Joseph’s University Medical Center, 703 Main Street, Paterson, NJ 07503, United States
| | - Katrina Villegas
- Internal Medicine Department, Saint Joseph’s University Medical Center, 703 Main Street, Paterson, NJ 07503, United States
| | - Ahmad Nouri
- Department of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus 44839, Palestine
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2
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Li X, Gao F, Meng X, Zhang X, Sun C, Liu H, Yu J, Liu X, Han X, Li L, Qiu L, Qian Z, Zhou S, Gong W, Golchehre Z, Chavoshzadeh Z, Ren X, Wang X, Zhang H. Epidemiological features and prognosis for primary gastrointestinal follicular lymphoma. Br J Haematol 2024; 204:1771-1779. [PMID: 38447995 DOI: 10.1111/bjh.19393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2023] [Revised: 02/26/2024] [Accepted: 02/27/2024] [Indexed: 03/08/2024]
Abstract
Primary gastrointestinal follicular lymphoma (PGI-FL) is a rare extra-nodal lymphoma. Its epidemiology and prognosis remain unclear. We performed a retrospective analysis of eligible patients with 1648 PGI-FL and 34 892 nodal FL (N-FL) in the Surveillance, Epidemiology and End Results (SEER) database. The age-adjusted average annual incidence of PGI-FL was 0.111/100000. The median overall survival (OS) for PGI-FL and N-FL patients was 207 and 165 months respectively. The 5-year diffuse large B-cell lymphoma (DLBCL) transformation rates were 2.1% and 2.6% respectively. Age, sex, grade, Ann Arbor stage, primary site and radiation were independent prognostic factors (p < 0.05). Nomograms were constructed to predict 1-, 5- and 10-year OS and disease-specific survival (DSS). The receiver operating characteristic curves and calibration plots showed the established nomograms had robust and accurate performance. Patients were classified into three risk groups according to nomogram score. In conclusion, the incidence of PGI-FL has increased over the past 40 years, and PGI-FL has a better prognosis and a lower DLBCL transformation rate than N-FL. The nomograms were developed and validated as an individualized tool to predict survival. Patients were divided into three risk groups to assist clinicians in identifying high-risk patients and choosing the optimal individualized treatments.
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MESH Headings
- Humans
- Lymphoma, Follicular/mortality
- Lymphoma, Follicular/epidemiology
- Lymphoma, Follicular/therapy
- Lymphoma, Follicular/diagnosis
- Female
- Male
- Middle Aged
- Aged
- Gastrointestinal Neoplasms/epidemiology
- Gastrointestinal Neoplasms/mortality
- Gastrointestinal Neoplasms/diagnosis
- Gastrointestinal Neoplasms/therapy
- Adult
- Retrospective Studies
- Prognosis
- SEER Program
- Aged, 80 and over
- Nomograms
- Incidence
- Lymphoma, Large B-Cell, Diffuse/epidemiology
- Lymphoma, Large B-Cell, Diffuse/mortality
- Lymphoma, Large B-Cell, Diffuse/diagnosis
- Lymphoma, Large B-Cell, Diffuse/therapy
- Adolescent
- Young Adult
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Affiliation(s)
- Xuelei Li
- Department of Lymphoma and National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, The Sino-US Center for Lymphoma and Leukemia Research, Tianjin, China
| | - Fenghua Gao
- Department of Lymphoma and National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, The Sino-US Center for Lymphoma and Leukemia Research, Tianjin, China
| | - Xiangrui Meng
- Department of Lymphoma and National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, The Sino-US Center for Lymphoma and Leukemia Research, Tianjin, China
| | - Xiaoyan Zhang
- State Key Laboratory of Experimental Hematology and Division of Pediatric Blood Diseases Center, Institute of Hematology and Blood Diseases Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Tianjin, China
| | - Cong Sun
- Department of Lymphoma and National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, The Sino-US Center for Lymphoma and Leukemia Research, Tianjin, China
| | - Hengqi Liu
- Department of Lymphoma and National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, The Sino-US Center for Lymphoma and Leukemia Research, Tianjin, China
| | - Jingwei Yu
- Department of Lymphoma and National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, The Sino-US Center for Lymphoma and Leukemia Research, Tianjin, China
| | - Xia Liu
- Department of Lymphoma and National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, The Sino-US Center for Lymphoma and Leukemia Research, Tianjin, China
| | - Xue Han
- Department of Lymphoma and National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, The Sino-US Center for Lymphoma and Leukemia Research, Tianjin, China
| | - Lanfang Li
- Department of Lymphoma and National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, The Sino-US Center for Lymphoma and Leukemia Research, Tianjin, China
| | - Lihua Qiu
- Department of Lymphoma and National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, The Sino-US Center for Lymphoma and Leukemia Research, Tianjin, China
| | - Zhengzi Qian
- Department of Lymphoma and National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, The Sino-US Center for Lymphoma and Leukemia Research, Tianjin, China
| | - Shiyong Zhou
- Department of Lymphoma and National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, The Sino-US Center for Lymphoma and Leukemia Research, Tianjin, China
| | - Wenchen Gong
- Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Zahra Golchehre
- Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Zahra Chavoshzadeh
- Department of Immunology/Allergy, Pediatric Infections Research Center, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Xiubao Ren
- Department of Immunology/Biotherapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Xianhuo Wang
- Department of Lymphoma and National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, The Sino-US Center for Lymphoma and Leukemia Research, Tianjin, China
| | - Huilai Zhang
- Department of Lymphoma and National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, The Sino-US Center for Lymphoma and Leukemia Research, Tianjin, China
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3
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Du YR, Li J, Li SX, Guan CY, Li HL, Gao ZF, Li X, Dong GH. [Studies on clinicopathological features of duodenal-type follicular lymphoma of 18 patients]. ZHONGHUA XUE YE XUE ZA ZHI = ZHONGHUA XUEYEXUE ZAZHI 2024; 45:94-97. [PMID: 38527846 PMCID: PMC10951120 DOI: 10.3760/cma.j.cn121090-20230915-00125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Indexed: 03/27/2024]
Abstract
To investigate the clinical and pathological characteristics of duodenal-type follicular lymphoma (D-FL), and to deepen the understanding of Duodenal-type follicular lymphoma. The clinical symptoms, endoscopic features, pathologic features, immunophenotype, molecular pathological features and treatment follow-up of 18 D-FL patients diagnosed in Department of Pathology, Beijing Tiantan Hospital affiliated to Capital Medical University between January 2020 and July 2023 were summarized. A total of 18 patients with D-FL were included, including 10 males and 8 females. The median age was 49 (32-69) years respectively. Most of the patients were found during gastroenteroscopy or presented with the common gastrointestinal symptoms of stomach pain, acid reflux, vomiting and diarrhea. Most endoscopic findings were multiple small gray and white polyposis. In the pathological morphology, the mucous layer and submucous layer showed lymphoid follicular structures with full and strained follicles. The immunophenotype showed that the tumor cells strongly expressed CD20 and BCL2 and had low proliferation activity. Immunoglobulin clonal analysis of 1 case showed IgK monoclonal rearrangement (1/1). FISH showed 1 case of BCL2 gene rearrangement (1/3). All patients did not receive targeted chemotherapy and adopted a wait-and-see strategy. Median follow-up was 12 (2-34) months. This study shows that D-FL is an indolent lymphoma, which tends to occur in the duodenum and has a good prognosis.
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Affiliation(s)
- Y R Du
- Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
| | - J Li
- Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
| | - S X Li
- Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
| | - C Y Guan
- Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
| | - H L Li
- Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
| | - Z F Gao
- Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
| | - X Li
- Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
| | - G H Dong
- Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
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Kim H, Shin D, Son SM, Cho J, Kim JE, Kim Y, Jeon TS, Ko YH. Clinicopathological and molecular genetic characteristics of primary gastric follicular lymphoma ☆,☆☆,☆☆☆. Hum Pathol 2023; 136:114-122. [PMID: 37054783 DOI: 10.1016/j.humpath.2023.04.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 04/07/2023] [Accepted: 04/07/2023] [Indexed: 04/15/2023]
Abstract
Primary gastric follicular lymphomas (FLs) have been rarely reported and little is known about their characteristics. In the present study, we report five cases of primary gastric FL and describe their clinicopathological and molecular genetic features. A total of seven samples from five patients were investigated for clinicopathological characteristics and somatic mutations by the targeted sequencing of 50 lymphoma-related genes. Two cases were identified as slightly elevated submucosal tumors and three cases as polypoid tumors. Histologically, all cases were low-grade FLs. The immuno-profile was CD20+/CD10+/BCL2+ in four cases and CD20+/CD10+/BCL2- in one case. Immunostaining pattern for CD21 was similar to that of classic FL. BCL2 rearrangement was not identified in fluorescence in situ hybridization studies in any of the five cases. NGS analysis showed mutations in genes involved in epigenetic modifications (KMT2D, ARID1A, EP300, CREBBP), NK-kB pathway (CARD11), and JAK-STAT pathway as found in classic follicular lymphoma. All cases presented with clinical I without the involvement of regional or systemic lymph nodes. Four patients were well, whereas one patient who received endoscopic mucosal resection of tumor without additional chemotherapy or radiotherapy experienced three relapses. In conclusion, primary gastric FL is characterized by a low-grade neoplasm with infrequent BCL2 rearrangement. After resection of the lesion, additional treatment such as radiation therapy or chemotherapy is required as there is a possibility of recurrence.
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Affiliation(s)
- Hyunsung Kim
- Department of Pathology, Seoul Hospital, Hanyang University College of Medicine, Seoul 04763, South Korea
| | - Donghoon Shin
- Department of Pathology, Yangsan Hospital, Pusan National University College of Medicine, Yangsan 50612, South Korea
| | - Seng-Myoung Son
- Department of Pathology, Chungbuk National University College of Medicine, Cheongju 28644, South Korea
| | - Junhun Cho
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University College of Medicine, Seoul 06351, South Korea
| | - Ji Eun Kim
- Department of Pathology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul 07061, South Korea
| | - Yeseul Kim
- Department of Pathology, Anam Hospital, Korea University College of Medicine, Seoul 02841, South Korea
| | - Tae-Sung Jeon
- Department of Pathology, Guro Hospital, Korea University College of Medicine, Seoul 08308, South Korea
| | - Young Hyeh Ko
- Department of Pathology, Guro Hospital, Korea University College of Medicine, Seoul 08308, South Korea; Department of Pathology, Cheju Halla General Hospital, Jeju 63127, South Korea.
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5
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Follicular Lymphoma in the 5th Edition of the WHO-Classification of Haematolymphoid Neoplasms-Updated Classification and New Biological Data. Cancers (Basel) 2023; 15:cancers15030785. [PMID: 36765742 PMCID: PMC9913816 DOI: 10.3390/cancers15030785] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 01/23/2023] [Accepted: 01/24/2023] [Indexed: 01/31/2023] Open
Abstract
The conceptual description of Follicular lymphoma (FL) in the 5th edition of the World Health Organization (WHO) classification of haematolymphoid tumors (WHO-HAEM5) has undergone significant revision. The vast majority of FL (85%) with a follicular growth pattern are composed of centrocytes and centroblasts, harbor the t(14;18)(q32;q21) translocation and are now termed classic FL (cFL). They are set apart from three related subtypes, FL with predominantly follicular growth pattern, FL with unusual cytological features (uFL) and follicular large B-cell lymphoma (FLBCL). In contrast to the revised 4th edition of the WHO classification of haematolymphoid tumors (WHO-HAEM4R), grading of cFL is no longer mandatory. FL with a predominantly diffuse growth pattern had been previously recognized in WHO-HAEM4R. It frequently occurs as a large tumor in the inguinal region and is associated with CD23 expression. An absence of the IGH::BCL2 fusion and frequent STAT6 mutations along with 1p36 deletion or TNFRSF14 mutation is typical. The newly introduced subtype of uFL includes two subsets that significantly diverge from cFL: one with "blastoid" and one with "large centrocyte" variant cytological features. uFL more frequently displays variant immunophenotypic and genotypic features. FLBCL is largely identical to WHO-HAEM4R FL grade 3B and renaming was done for reasons of consistency throughout the classification. In-situ follicular B-cell neoplasm, pediatric-type FL, duodenal-type FL and primary cutaneous follicle center lymphoma are categorized as discrete entities. In addition, novel findings concerning underlying biological mechanisms in the pathogenesis of early and systemic follicular lymphoma will be presented.
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6
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Sumioka A, Oka S, Hirata I, Iio S, Tsuboi A, Takigawa H, Yuge R, Urabe Y, Boda K, Kohno T, Okanobu H, Kitadai Y, Arihiro K, Tanaka S. Predictive factors for the progression of primary localized stage small-bowel follicular lymphoma. J Gastroenterol 2022; 57:667-675. [PMID: 35831477 DOI: 10.1007/s00535-022-01897-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Accepted: 06/14/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND Primary small-bowel follicular lymphoma (FL) is mainly diagnosed as a duodenal lesion during esophagogastroduodenoscopy. Recently, with the widespread use of small-bowel endoscopy, FL in the jejunum and ileum has been detected. Most patients with small-bowel FL are diagnosed at the localized stage, and a watch-and-wait policy is used. However, the predictive factors for the progression of small-bowel FL have not been clarified. This study retrospectively examined the predictive factors for the progression of primary localized stage small-bowel FL based on clinicopathological and endoscopic findings. METHODS We enrolled 60 consecutive patients with primary small-bowel FL diagnosed at two tertiary hospitals between January 2005 and December 2020, with localized stage, low grade, and low tumor burden with the watch-and-wait policy. We examined the predictive factors for progression according to the clinicopathological and endoscopic findings. Endoscopic findings were focused on the color tone, circumferential location of follicular lesions (circumference ≥ 1/2 or < 1/2), fusion of follicular lesions (fusion [ +] or [ -]), and protruded lesions (≥ 6 mm or < 6 mm). RESULTS Progressive disease was observed in 12 (20%) patients (mean observation period, 76.4 ± 55.4 months). In the multivariate analysis, "circumference ≥ 1/2" and "fusion (+)" were significant predictive factors for progression. According to the Kaplan-Meier analysis, progression-free survival was significantly shorter in the "circumference ≥ 1/2" and/or "fusion (+)" group than in the "circumference < 1/2" and "fusion ( -)" group. CONCLUSIONS Endoscopic findings of "circumference ≥ 1/2" and "fusion (+)" were significant predictive factors for the progression of primary localized stage small-bowel FL.
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Affiliation(s)
- Akihiko Sumioka
- Department of Gastroenterology and Metabolism, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Shiro Oka
- Department of Gastroenterology and Metabolism, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
| | - Issei Hirata
- Department of Gastroenterology and Metabolism, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Sumio Iio
- Department of Gastroenterology and Metabolism, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Akiyoshi Tsuboi
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan
| | - Hidehiko Takigawa
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan
| | - Ryo Yuge
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan
| | - Yuji Urabe
- Department of Gastroenterology and Metabolism, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Kazuki Boda
- Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, Hiroshima, Japan
| | - Tomohiko Kohno
- Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, Hiroshima, Japan
| | - Hideharu Okanobu
- Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, Hiroshima, Japan
| | - Yasuhiko Kitadai
- Department of Health and Science, Prefectural University of Hiroshima, Hiroshima, Japan
| | - Koji Arihiro
- Department of Anatomical Pathology, Hiroshima University Hospital, Hiroshima, Japan
| | - Shinji Tanaka
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan
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Saito M, Mori A, Tsukamoto S, Ishio T, Yokoyama E, Izumiyama K, Morioka M, Kondo T, Sugino H. Duodenal-type follicular lymphoma more than 10 years after treatment intervention: A retrospective single-center analysis. World J Gastrointest Oncol 2022; 14:1552-1561. [PMID: 36160741 PMCID: PMC9412938 DOI: 10.4251/wjgo.v14.i8.1552] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2021] [Revised: 01/19/2022] [Accepted: 07/26/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Duodenal-type follicular lymphoma (D-FL) has been recognized as a rare entity that accounts for approximately 4% of primary gastrointestinal lymphomas. D-FL follows an indolent clinical course compared with common nodal FL and is generally considered to have a better prognosis. Therefore, the "watch and wait" approach is frequently adopted as the treatment method. Alternatively, there is an option to actively intervene in D-FL. However, the long-term outcomes of such cases are poorly understood. AIM To clarify the clinical outcomes after long-term follow-up in cases of D-FL with treatment intervention. METHODS We retrospectively analyzed patients who met the following criteria: the lesion was confirmed by endoscopy, the diagnosis of D-FL was confirmed histopathologically, and the patient was followed-up for more than 10 years after the intervention at our center. RESULTS We identified 5 cases of D-FL. Two patients showed a small amount of bone marrow involvement (Stage IV). Rituximab was used as a treatment for remission in all 5 patients. It was also used in combination with chemotherapy in 2 Stage IV patients as well as for maintenance treatment. Radiation therapy was performed in 2 cases, which was followed by complete remission (CR). Eventually, all 5 patients achieved CR and survived for more than 10 years. However, 3 patients experienced recurrence. One patient achieved a second CR by retreatment, and in another case, the lesion showed spontaneous disappearance. The remaining patient had systemic widespread recurrence 13 years after the first CR. Biopsy results suggested that the FL lesions were transformed into diffuse large B-cell lymphoma. The patient died 4 years later despite receiving various chemotherapies. CONCLUSION In this study, the treatment for patients of D-FL in Stage IV was successful. In the future, criteria for how to treat "advanced" D-FL should be established based on additional cases. This study of patients with D-FL indicates that whole-body follow-up examinations should continue for a long time due to a fatal recurrence 13 years after reaching CR.
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Affiliation(s)
- Makoto Saito
- Blood Disorders Center, Aiiku Hospital, Sapporo 064-0804, Japan
| | - Akio Mori
- Blood Disorders Center, Aiiku Hospital, Sapporo 064-0804, Japan
| | | | - Takashi Ishio
- Blood Disorders Center, Aiiku Hospital, Sapporo 064-0804, Japan
| | - Emi Yokoyama
- Blood Disorders Center, Aiiku Hospital, Sapporo 064-0804, Japan
| | - Koh Izumiyama
- Blood Disorders Center, Aiiku Hospital, Sapporo 064-0804, Japan
| | | | - Takeshi Kondo
- Blood Disorders Center, Aiiku Hospital, Sapporo 064-0804, Japan
| | - Hirokazu Sugino
- Department of Cancer Pathology, Hokkaido University, Faculty of Medicine, Sapporo 060-8638, Japan
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8
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Matysiak-Budnik T, Jamet P, Chapelle N, Fabiani B, Coppo P, Ruskoné-Fourmestraux A. Primary Gastrointestinal Follicular Lymphomas: A Prospective Study of 31 Patients with Long-term Follow-up Registered in the French Gastrointestinal Lymphoma Study Group (GELD) of the French Federation of Digestive Oncology (FFCD). Gut Liver 2022; 16:207-215. [PMID: 35249892 PMCID: PMC8924797 DOI: 10.5009/gnl210300] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 10/22/2021] [Accepted: 10/29/2021] [Indexed: 11/04/2022] Open
Abstract
Background/Aims Methods Results Conclusions
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Affiliation(s)
- Tamara Matysiak-Budnik
- IMAD, Department of Gastroenterology and Digestive Oncology, Hotel Dieu Hospital, Nantes, France
- UMR Inserm 1235, Nantes, France
| | - Philippe Jamet
- IMAD, Department of Gastroenterology and Digestive Oncology, Hotel Dieu Hospital, Nantes, France
| | - Nicolas Chapelle
- IMAD, Department of Gastroenterology and Digestive Oncology, Hotel Dieu Hospital, Nantes, France
- INSERM UMR 1064, University of Nantes, Nantes, France
| | - Bettina Fabiani
- Department of Pathology, Saint Antoine Hospital AP-HP, Paris, France
| | - Paul Coppo
- Department of Hematology, Saint Antoine Hospital AP-HP, Paris, France
| | - Agnès Ruskoné-Fourmestraux
- Gastroenterology, Saint Antoine Hospital AP-HP, Paris, France
- French Federation of Digestive Oncology, Dijon, France
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9
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Khanlari M, Chapman JR. Follicular lymphoma: updates for pathologists. J Pathol Transl Med 2021; 56:1-15. [PMID: 34942689 PMCID: PMC8743801 DOI: 10.4132/jptm.2021.09.29] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Accepted: 09/29/2021] [Indexed: 11/17/2022] Open
Abstract
Follicular lymphoma (FL) is the most common indolent B-cell lymphoma and originates from germinal center B-cells (centrocytes and centroblasts) of the lymphoid follicle. Tumorigenesis is believed to initiate early in precursor B-cells in the bone marrow (BM) that acquire the t(14;18)(q32;q21). These cells later migrate to lymph nodes to continue their maturation through the germinal center reaction, at which time they acquire additional genetic and epigeneticabnormalities that promote lymphomagenesis. FLs are heterogeneous in terms of their clinicopathologic features. Most FLs are indolent and clinically characterized by peripheral lymphadenopathy with involvement of the spleen, BM, and peripheral blood in a substantial subset of patients, sometimes accompanied by constitutional symptoms and laboratory abnormalities. Diagnosis is established by the histopathologic identification of a B-cell proliferation usually distributed in an at least partially follicular pattern, typically, but not always, in a lymph node biopsy. The B-cell proliferation is biologically of germinal center cell origin, thus shows an expression of germinal center-associated antigens as detected by immunophenotyping. Although many cases of FLs are typical and histopathologic features are straightforward, the biologic and histopathologic variability of FL is wide, and an accurate diagnosis of FL over this disease spectrum requires knowledge of morphologic variants that can mimic other lymphomas, and rarely non-hematologic malignancies, clinically unique variants, and pitfalls in the interpretation of ancillary studies. The overall survival for most patients is prolonged, but relapses are frequent. The treatment landscape in FL now includes the application of immunotherapy and targeted therapy in addition to chemotherapy.
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Affiliation(s)
- Mahsa Khanlari
- Department of Pathology and Hematopathology, St. Jude Children's Research Hospital, Memphis, TN, USA
- Corresponding Author: Mahsa Khanlari, MD, Department of Pathology and Hematopathology, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA Tel: +1-901-595-0394, Fax: +1-901-595-3100, E-mail:
| | - Jennifer R. Chapman
- Department of Pathology, Division of Hematopathology, University of Miami, Sylvester Comprehensive Cancer Center, and Jackson Memorial Hospitals, Miami, FL, USA
- Corresponding Author: Jennifer R. Chapman, MD, Department of Pathology, University of Miami Hospital, 4th floor, room 4076, 1400 NW 12th Ave., Miami, FL 33138, USA Tel: +1-305-689-1332, E-mail:
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10
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Foukas PG, Bisig B, de Leval L. Recent advances upper gastrointestinal lymphomas: molecular updates and diagnostic implications. Histopathology 2020; 78:187-214. [PMID: 33382495 DOI: 10.1111/his.14289] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Revised: 10/21/2020] [Accepted: 10/22/2020] [Indexed: 12/14/2022]
Abstract
Approximately one-third of extranodal non-Hodgkin lymphomas involve the gastrointestinal (GI) tract, with the vast majority being diagnosed in the stomach, duodenum, or proximal small intestine. A few entities, especially diffuse large B-cell lymphoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, represent the majority of cases. In addition, there are diseases specific to or characteristic of the GI tract, and any type of systemic lymphoma can present in or disseminate to these organs. The recent advances in the genetic and molecular characterisation of lymphoid neoplasms have translated into notable changes in the classification of primary GI T-cell neoplasms and the recommended diagnostic approach to aggressive B-cell tumours. In many instances, diagnoses rely on morphology and immunophenotype, but there is an increasing need to incorporate molecular genetic markers. Moreover, it is also important to take into consideration the endoscopic and clinical presentations. This review gives an update on the most recent developments in the pathology and molecular pathology of upper GI lymphoproliferative diseases.
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Affiliation(s)
- Periklis G Foukas
- Second Department of Pathology, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
| | - Bettina Bisig
- Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and Lausanne University, Lausanne, Switzerland
| | - Laurence de Leval
- Second Department of Pathology, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
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11
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Li HN, Wang RC, Chen JP, Chang ST, Chuang SS. Density and size of lymphoid follicles are useful clues in differentiating primary intestinal follicular lymphoma from intestinal reactive lymphoid hyperplasia. Diagn Pathol 2020; 15:82. [PMID: 32635930 PMCID: PMC7341590 DOI: 10.1186/s13000-020-00991-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Accepted: 06/17/2020] [Indexed: 12/27/2022] Open
Abstract
Background Primary intestinal follicular lymphoma (PI-FL) is a rare and indolent lymphoma and is challenging for diagnosis with endoscopic biopsy specimens. Whole slide imaging (WSI) has been increasingly used for assisting pathologic diagnosis, but not for lymphoma yet, probably because there are usually too many immunostained sections in a single case. In this study we attempted to identify morphological clues of PI-FL in the endoscopic biopsy specimens by measuring various parameters using WSI. Methods We retrospectively investigated 21 PI-FL cases, and scanned the HE sections from 17 of these cases with endoscopic biopsy specimens. Sections from 17 intestinal biopsies showing reactive lymphoid hyperplasia were scanned for comparison. The density and diameter of lymphoid follicles and the shortest distance of these follicles to the surface epithelia were measured on WSI. Comparisons of the aforementioned parameters were made between the neoplastic and reactive follicles. Results The density of follicles was significantly higher in PI-FL than that of reactive hyperplasia (median 0.5 vs. 0.2/mm2; p < 0.01). Furthermore, the neoplastic follicles were significantly larger (median diameter 756.9 vs. 479.7 μm; p < 0.01). The shortest distance of follicles to the surface epithelia tended to be closer in PI-FL (104.7 vs. 177.8 μm, p = 0.056), but not statistically significant. Conclusions In this study we found that in PI-FL the density and diameter of lymphoid follicles as measured from WSI were significantly different from that of intestinal reactive lymphoid hyperplasia. When facing the diagnostic challenge between these two entities in routine practice, pathologists might be alerted by these morphological clues and request for immunohistochemistry for differential diagnosis.
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Affiliation(s)
- Hsin-Ni Li
- Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Ren Ching Wang
- Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.,Department of Nursing, HungKuang University, Taichung, Taiwan
| | - Jun-Peng Chen
- Biostatistics Task Force, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Sheng-Tsung Chang
- Department of Pathology, Chi-Mei Medical Center, 901 Chung-Hwa Road, Yong-Kang District, Tainan, 71004, Taiwan.,Department of Nursing, National Tainan Institute of Nursing, Tainan, Taiwan
| | - Shih-Sung Chuang
- Department of Pathology, Chi-Mei Medical Center, 901 Chung-Hwa Road, Yong-Kang District, Tainan, 71004, Taiwan. .,Department of Pathology, School of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
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12
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Scientific Advances and the Evolution of Diagnosis, Subclassification and Treatment of Lymphoma. Arch Med Res 2020; 51:749-764. [PMID: 32553461 DOI: 10.1016/j.arcmed.2020.05.022] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 05/26/2020] [Indexed: 12/11/2022]
Abstract
The diagnosis of lymphoma has evolved tremendously over time. Initially, diagnosis of lymphoma was largely based on morphology alone. Over time, immunophenotyping using flow cytometry and immunohistochemistry, and then in situ hybridization, have contributed dramatically to the pathologist's ability to recognize, diagnose and subclassify lymphomas more precisely. In recent years, cytogenetic and molecular genetic techniques have developed that allow evaluation of abnormalities in lymphomas, leading to an understanding of their pathogenesis and opening the door to targeted therapies that will lead to better outcomes for lymphoma patients.
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13
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Duffles Amarante G, Collins G, Rocha V. What do we know about duodenal-type follicular lymphoma? From pathological definition to treatment options. Br J Haematol 2019; 188:831-837. [PMID: 31880329 DOI: 10.1111/bjh.16348] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Duodenal-type follicular lymphoma (DFL) is a newly recognised variant of follicular lymphoma (FL), although little is known about its biology and clinical evolution. In general, patients tend to have mild symptoms and do not require therapy, comparable with other forms of low-tumour burden asymptomatic FL. Specific pathological features, such as a dendritic cell meshwork, low expression of CD10 and upregulation of activation-induced cytidine deaminase can help the diagnosis. The molecular landscape of DFL is similar to the classical nodal presentation of FL, although studies using gene expression profiling demonstrate a close relation with MALT lymphomas. Markers associated with inflammation have suggested that the microenvironment plays a likely role in the pathogenesis of DFL and its low progression rate. Clinical series published vary between 20-63 patients with an estimated overall survival between 92-100% and a median follow-up ranging between 20 and 107 months. Treatment options include a watch and wait strategy, rituximab monotherapy and radiotherapy. In this review, we summarise current pathological data and treatment studies in DFL.
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Affiliation(s)
- Guilherme Duffles Amarante
- Hematology Service, Instituto do Câncer do Estado de São Paulo (ICESP), Universidade de São Paulo, São Paulo, SP, Brazil.,Hematology Service, Hospital Sírio-Libanês, São Paulo, SP, Brazil
| | - Graham Collins
- Department of Clinical Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Vanderson Rocha
- Hematology Service, Instituto do Câncer do Estado de São Paulo (ICESP), Universidade de São Paulo, São Paulo, SP, Brazil.,Hematology Service, Hospital Sírio-Libanês, São Paulo, SP, Brazil.,Department of Haematology, University of Oxford, Oxford, UK
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14
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15
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Abstract
Technical advances in diagnostic modalities have led to the characterization of indolent lymphoid disorders similar to the in situ lesions described in epithelial malignancies. These early and indolent lymphoid lesions share clinicopathologic characteristics with well-characterized lymphoid malignancies such as chronic lymphocytic leukemia and follicular lymphoma. The in situ lesions have an indolent clinical course with only a minor subset shown to progress to frank malignancies. In addition to the in situ lesions, new indolent lymphoproliferative disorders have been recently characterized. Diagnosis and characterization of these indolent lesions is necessary to prevent overtreatment with aggressive therapeutic regimens.
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Affiliation(s)
- Sudhir Perincheri
- Department of Pathology, Yale School of Medicine, 310 Cedar Street, Suite LB20, New Haven, CT 06510, USA.
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16
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Abstract
Duodenal-type follicular lymphoma (D-FL) is a newly recognized entity in the 2016 World Health Organization classification update. It has an immunophenotype similar to that of other FLs and usually carries the typical t(14;18)(q32;q21) translocation. However, unlike other FLs, D-FL is almost always diagnosed at a low stage and stays localized to the small intestine, most commonly the second portion of the duodenum, whereas the vast majority of other FLs are diagnosed at an advanced stage. Additionally, D-FL gene expression and pathogenesis appear to be more closely related to extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue than to other types of FL. Therefore, many oncologists have opted to treat this variant of FL in a "watch and wait" manner because of its excellent prognosis and the rarity of D-FL to progress even when no treatments are attempted.
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Affiliation(s)
| | - Yang Shi
- From the Department of Pathology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York
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17
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Yoshino T, Takata K, Tanaka T, Sato Y, Tari A, Okada H. Recent progress in follicular lymphoma in Japan and characteristics of the duodenal type. Pathol Int 2018; 68:665-676. [DOI: 10.1111/pin.12733] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Accepted: 10/05/2018] [Indexed: 12/13/2022]
Affiliation(s)
- Tadashi Yoshino
- Department of Pathology; Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Science; Okayama Japan
| | - Katsuyoshi Takata
- Department of Pathology; Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Science; Okayama Japan
| | - Takehiro Tanaka
- Department of Pathology; Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Science; Okayama Japan
| | - Yasuharu Sato
- Division of Pathophysiology; Okayama University Graduate School of Health Science; Okayama Japan
| | - Akira Tari
- Division of Gastroenterology; Hiroshima Red Cross Hospital & Atomic-bomb Survivor Hospital; Hiroshima Japan
| | - Hiroyuki Okada
- Department of Gastroenterology and Hepatology; Okayama University Graduate School of Medicine; Dentistry and Pharmaceutical Science; Okayama Japan
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18
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Choi SM, Betz BL, Perry AM. Follicular Lymphoma Diagnostic Caveats and Updates. Arch Pathol Lab Med 2018; 142:1330-1340. [PMID: 30221980 DOI: 10.5858/arpa.2018-0217-ra] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
CONTEXT.— Follicular lymphoma is a common small B-cell lymphoma, likely to be encountered by any practicing pathologist, regardless of specialty. Although the features of typical follicular lymphoma are well known and in most instances easily identifiable, there are lesser-appreciated morphologic appearances that can raise alternative diagnostic possibilities. The limited tissue available in core needle biopsies can make it additionally challenging to thoroughly evaluate those features in the context of architecture. Furthermore, ancillary testing including immunohistochemistry and molecular/genetic analysis do not always show classic findings and may pose additional challenges to interpretation. OBJECTIVES.— To review the morphologic features of follicular lymphoma with a discussion of morphologic variants and mimics; to discuss pitfalls of ancillary testing and provide the practicing pathologist with an appropriate context for interpretation of immunohistochemical and molecular/genetic studies when follicular lymphoma is part of the differential diagnosis; and to propose diagnostic strategies when there is limited tissue for evaluation. DATA SOURCES.— We used examples of follicular lymphoma from our institution as well as a review of the literature, with a focus on the diagnostic aspects that are broadly relevant to a general pathology practice. CONCLUSIONS.— Follicular lymphoma can occasionally present with atypical morphologic, immunohistochemical, or molecular/genetic features. In particular, those findings can be difficult to interpret in the setting of a limited tissue sample. Awareness of those possibilities will help guide the pathologist to a more accurate and precise diagnosis.
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Affiliation(s)
- Sarah M Choi
- From the Department of Pathology, University of Michigan, Ann Arbor
| | - Bryan L Betz
- From the Department of Pathology, University of Michigan, Ann Arbor
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19
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Kiesewetter B, Dolak W, Mayerhoefer ME, Simonitsch-Klupp I, Raderer M. Successful Clarithromycin Monotherapy in a Patient with Primary Follicular Lymphoma of the Duodenum. Case Rep Oncol 2018; 11:239-245. [PMID: 29805375 PMCID: PMC5968239 DOI: 10.1159/000488388] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Accepted: 03/13/2018] [Indexed: 01/30/2023] Open
Abstract
Primary follicular lymphoma of the duodenum (FL-D) constitutes a rare subtype of extranodal follicular lymphoma with a usually indolent course. To date, no distinct treatment recommendations have been defined for those patients. We report the case of a 58-year-old male patient presenting with endoscopically assessed, symptomatic FL-D who was treated with clarithromycin monotherapy in analogy to recent data for mucosa-associated lymphoid tissue lymphoma. Each treatment cycle consisted of clarithromycin 500 mg twice daily for 3 weeks followed by a 2-week break. After four cycles of treatment, the patient showed a very good response with normal macroscopic findings confirmed by endosonographic examination and only focal minimal residual disease of lymphoma persisting in the histological assessment. The patient is currently asymptomatic and without treatment for 24+ months. As clarithromycin combines antimicrobial and direct antiproliferative effects mediated through a variety of pleiotropic mechanisms, this appears to be an interesting treatment approach for indolent lymphoma, particularly in those where a chronic infectious background cannot be completely ruled out, i.e., gastrointestinal manifestations. We suggest further investigation of this treatment approach.
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Affiliation(s)
- Barbara Kiesewetter
- Clinical Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
| | - Werner Dolak
- Clinical Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Marius E Mayerhoefer
- Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria
| | | | - Markus Raderer
- Clinical Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
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20
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Takata K, Miyata-Takata T, Sato Y, Iwamuro M, Okada H, Tari A, Yoshino T. Gastrointestinal follicular lymphoma: Current knowledge and future challenges. Pathol Int 2018; 68:1-6. [PMID: 29292593 DOI: 10.1111/pin.12621] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2017] [Accepted: 11/21/2017] [Indexed: 12/14/2022]
Abstract
The gastrointestinal (GI) tract is the most commonly involved site of extranodal follicular lymphoma (FL). GI-FL shows very indolent clinical behavior and localized at GI tract without any progression or transformation compared to nodal FL. The most frequently involved site of the GI tract was the duodenum followed by the jejunum and ileum, and only 15% of FL arising in the second part of the duodenum were localized there without scattered very small daughter lesions in other GI tract examined by double-balloon endoscopy. The typical macroscopic appearance of GI-FL was multiple white nodules. Microscopically, neoplastic cells were small- to medium-sized lymphoid cells and formed neoplastic follicles. Most of the cases (>95%) were histologically Grade 1 to 2 (low grade). Several pathological and molecular characteristics were seen in GI-FL (especially duodenal FL) compared with nodal FL: immunoglobulin heavy chain deviation to VH4 and VH5; memory B-cell immunophenotype; and molecular features shared by mucosa-associated lymphoid tissue lymphoma. Considering the pathological and molecular uniqueness of this disease, GI-FL should be separately managed from nodal FL.
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Affiliation(s)
- Katsuyoshi Takata
- Department of Lymphoid Cancer Research, British Columbia Cancer Research Centre, Vancouver, Canada
- Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Tomoko Miyata-Takata
- Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Yasuharu Sato
- Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Masaya Iwamuro
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Hiroyuki Okada
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Akira Tari
- Department of Internal Medicine, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Tadashi Yoshino
- Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
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21
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Chouhan J, Batra S, Gupta R, Guha S. Gastrointestinal follicular lymphoma: using primary site as a predictor of survival. Cancer Med 2016; 5:2669-2677. [PMID: 27696758 PMCID: PMC5083718 DOI: 10.1002/cam4.763] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2015] [Revised: 04/06/2016] [Accepted: 04/15/2016] [Indexed: 12/22/2022] Open
Abstract
Gastrointestinal follicular lymphoma (GI-FL) is a rare extranodal variant of follicular lymphoma (FL) that has been increasingly reported in the literature. An especially indolent course is linked to the disease after a lack of observed patient death in past studies. However, overall survival (OS) and associated prognostic factors remain unclear. A large population-based database was utilized to identify demographic and clinicopathologic characteristics of GI-FL, along with survival differences among primary sites. The Surveillance, Epidemiology, and End Results Registry was used to identify GI-FL cases between the years of 1973 and 2012. Kaplan-Meier curves compared OS differences and Cox proportional hazard models analyzed prognostic factors. Final analysis included 1109 cases. Small intestinal cases, which included those with single-site and multi-segment involvement, were most common (63.6%) followed by gastric (18.2%) and colorectal cases (18.2%). Small intestinal GI-FL presented more frequently with grade I histology, and less often with grade III histology (P < 0.001 and P < 0.001, respectively). Small intestinal cases had better outcomes (5-year OS = 80.9%, P < 0.001) compared to cases involving the stomach (5-year OS = 52.7%) and colorectum (5-year OS = 71.5%). On multivariate analysis for predictors of mortality, small intestinal involvement predicted for better survival; hazard ratio (HR) 0.66 (95% CI: 0.51-0.85). Advanced age (≥66), grade (grade III), and stage (Ann Arbor Stage III/IV) predicted for mortality with HR 5.46 (95% CI: 3.80-7.84), 1.42 (95% CI: 1.10-1.83), 1.57 (95% CI: 1.15-2.16), respectively. GI-FL has poorer outcomes than previously suggested. Small intestinal involvement has a better prognosis. A possible biological basis for this will require further investigations in the future.
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Affiliation(s)
- Jay Chouhan
- Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, Texas
| | - Sachin Batra
- Department of Gastroenterology, Hepatology and Nutrition, The University of Texas Health Science Center at Houston, Houston, Texas
| | - Rohan Gupta
- Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, Texas
| | - Sushovan Guha
- Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, Texas.
- Department of Gastroenterology, Hepatology and Nutrition, The University of Texas Health Science Center at Houston, Houston, Texas.
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22
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García-Muñoz R, Panizo C. Follicular lymphoma (FL): Immunological tolerance theory in FL. Hum Immunol 2016; 78:138-145. [PMID: 27693433 DOI: 10.1016/j.humimm.2016.09.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2014] [Revised: 09/27/2016] [Accepted: 09/28/2016] [Indexed: 11/19/2022]
Abstract
The ultimate cause of follicular lymphoma (FL) remains unknown. Remarkably, almost nothing is known about immunological tolerance mechanisms that might contribute to FL development. Immunological tolerance mechanisms, like other stimuli, also induce persistent changes of B cell receptors that induce genetic instability and molecular aberrations promoting the development of a neoplasm. Using the same method as Burnet, we provide a new perspective taking advantage of the comparison of a normal linear B cell differentiation process and FL development within the framework of clonal selection theory. We propose that FL is a malignancy of cells that acquire both translocation t(14;18) and self-BCR, inducing them to proliferate and mature, resistant to negative selection. Additional genetic damage induced by non-apoptotic tolerance mechanisms, such as receptor editing, may transform a self-reactive B cell with t(14;18) into an FL. The result of tolerogenic mechanisms and genetic aberrations is the survival of FL B cell clones with similar markers and homogenous gene expression signatures despite the different stages of maturation at which the molecular damage occurs. To antagonize further growth advantage due to self-antigen recognition and chronic activation of tolerance mechanisms in the apoptosis-resistant background of FL B cells, inhibitors of BCR signaling may be promising therapeutic options.
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Affiliation(s)
| | - Carlos Panizo
- Hematology Department, Clínica Universidad de Navarra, Pamplona, Spain
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23
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Harada A, Oguchi M, Terui Y, Takeuchi K, Igarashi M, Kozuka T, Harada K, Uno T, Hatake K. Radiation therapy for localized duodenal low-grade follicular lymphoma. JOURNAL OF RADIATION RESEARCH 2016; 57:412-417. [PMID: 27009323 PMCID: PMC4973641 DOI: 10.1093/jrr/rrw011] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/29/2015] [Revised: 01/12/2016] [Accepted: 01/15/2016] [Indexed: 06/05/2023]
Abstract
The aim of this study was to evaluate the initial treatment results and toxicities of radiation therapy for patients with early stage low-grade follicular lymphoma (FL) arising from the duodenum. We reviewed 21 consecutive patients with early stage duodenal FL treated with radiation therapy between January 2005 and December 2013 at the Cancer Institute Hospital, Tokyo. The characteristics of patients were: median age 62 years (range, 46-79 years), gender (male, 6; female, 15), clinical stage (I, 20; II1, 1), histological grade (I, 17; II, 4). All patients were treated with radiation therapy alone. The median radiation dose was 30.6 Gy (range, 30.6-39.6) in 17 fractions. The involved-site radiation therapy was delivered to the whole duodenum. The median follow-up time was 43.2 months (range 21.4-109.3). The 3-year overall survival (OS), relapse-free survival (RFS) and local control (LC) rates were 94.7%, 79.3% and 100%, respectively. There were four relapses documented outside the treated volumes: two in the gastrointestinal tract (jejunum, terminal ileum), one in an abdominal lymph node (mesenteric lymph node) and one in the bone marrow. None died of the disease; one death was due to acute myeloid leukemia. No toxicities greater than Grade 1 were observed during treatment and over the follow-up time. The 30.6 Gy of involved-site radiation therapy provided excellent local control with very low toxicities. Radiation therapy could be an effective and safe treatment option for patients with localized low grade FL arising from the duodenum.
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Affiliation(s)
- Arisa Harada
- Radiation Oncology Department, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Kouto-ku, Tokyo 135-8550, Japan
| | - Masahiko Oguchi
- Radiation Oncology Department, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Kouto-ku, Tokyo 135-8550, Japan
| | - Yasuhito Terui
- Hematology Oncology Department, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Kouto-ku, Tokyo 135-8550, Japan
| | - Kengo Takeuchi
- Pathology Department, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Kouto-ku, Tokyo 135-8550, Japan
| | - Masahiro Igarashi
- Endoscopy Department, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Kouto-ku, Tokyo 135-8550, Japan
| | - Takuyo Kozuka
- Radiation Oncology Department, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Kouto-ku, Tokyo 135-8550, Japan
| | - Ken Harada
- Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Takashi Uno
- Department of Radiation Oncology, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Kiyohiko Hatake
- Hematology Oncology Department, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Kouto-ku, Tokyo 135-8550, Japan
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24
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Moy BT, Wilmot J, Ballesteros E, Forouhar F, Vaziri H. Primary Follicular Lymphoma of the Gastrointestinal Tract: Case Report and Review. J Gastrointest Cancer 2016; 47:255-63. [PMID: 27277664 DOI: 10.1007/s12029-016-9847-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
PURPOSE Primary gastrointestinal follicular lymphoma (GI-FL) is considered a rare disease with fewer than 400 cases reported in the literature. It accounts for roughly 1-3 % of GI non-Hodgkins lymphomas (NHL). It originates in the GI tract and typically affects small bowel. The disease has an indolent course, and a prolonged survival can be expected in most cases. Due to its rarity, an optimal diagnostic work up and treatment plan has not been well established. METHODS Endoscopic evaluation of the entire gastrointestinal (GI) tract using esophagogastroduodenoscopy (EGD), wireless capsule endoscopy, double-balloon enteroscopy, colonoscopy, and whole body examination with fluorodeoxyglucose-positron emission tomography (FDG-PET) has been suggested to more accurately stage the disease and guide the treatment plan. RESULTS Treatment options for GI follicular lymphoma include watch and wait strategy, surgery, chemotherapy, radiation, immuno-radiotherapy, or a combination of these modalities. CONCLUSION In this article, we have summarized the existing information regarding clinical presentation, diagnostic evaluation, and treatment options for this rare entity after presenting a case of GI-FL who was diagnosed during an EGD for evaluation of belching, heartburn, and weight loss.
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Affiliation(s)
- Brian T Moy
- Department of Medicine, University of Connecticut Health Center, Farmington, CT, USA
| | - Jonathan Wilmot
- Division of Gastroenterology and Hepatology, University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT, 06030-8074, USA
| | - Enrique Ballesteros
- Department of Pathology, University of Connecticut Health Center, Farmington, CT, USA
| | - Faripour Forouhar
- Department of Pathology, University of Connecticut Health Center, Farmington, CT, USA
| | - Haleh Vaziri
- Division of Gastroenterology and Hepatology, University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT, 06030-8074, USA.
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25
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Gjeorgjievski M, Makki I, Khanal P, Amin MB, Blenc AM, Desai T, Cappell MS. Early, Isolated Duodenal Mucosa-Associated Lymphoid Tissue Lymphoma Presenting without Symptoms or Grossly Apparent Endoscopic Lesions and Diagnosed by Random Duodenal Biopsies. Case Rep Gastroenterol 2016; 10:323-331. [PMID: 27482191 PMCID: PMC4945810 DOI: 10.1159/000447293] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2016] [Accepted: 05/31/2016] [Indexed: 12/31/2022] Open
Abstract
Clinical data regarding mucosa-associated lymphoid tissue lymphoma (MALToma) solely involving the duodenum are sparse because of the relative rarity of the disease. A comprehensive literature review revealed only 17 cases reported until 2004, and only a moderate number of cases have been reported since. MALToma can be asymptomatic in its very early stages but frequently produces localized or nonspecific symptoms, including early satiety, abdominal pain, vomiting, and involuntary weight loss in later stages. While gastric MALToma is strongly associated with gastric Helicobactor pylori infection, duodenal MALToma is often unassociated with H. pylori infection. A 74-year-old female presented with only dysphagia (without symptoms referable to a duodenal lesion), without systemic 'B' symptoms, and with no evident duodenal lesions at esophagogastroduodenoscopy; however, she was diagnosed with duodenal MALToma by pathologic examination of random duodenal biopsies performed to exclude celiac disease. An important clinical feature of this case is that duodenal MALToma was diagnosed by pathologic analysis of duodenal biopsies despite (1) no endoscopically apparent duodenal lesions; (2) duodenal involvement without gastric involvement; (3) lack of symptoms attributable to duodenal MALToma, and (4) absence of evident H. pylori infection. This work shows that early duodenal MALToma can be difficult to diagnose because of absent symptoms, absence of gastric involvement, absence of endoscopic abnormalities, and absence of H. pylori infection; it may require random duodenal biopsies for diagnosis.
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Affiliation(s)
- Mihajlo Gjeorgjievski
- Division of Gastroenterology and Hepatology, Department of Medicine, William Beaumont Hospital, Royal Oak, Mich., USA
| | - Issa Makki
- Division of Gastroenterology and Hepatology, Department of Medicine, William Beaumont Hospital, Royal Oak, Mich., USA
| | - Pradeep Khanal
- Division of Gastroenterology and Hepatology, Department of Medicine, William Beaumont Hospital, Royal Oak, Mich., USA
| | - Mitual B. Amin
- Department of Pathology, William Beaumont Hospital, Royal Oak, Mich., USA
| | - Ann Marie Blenc
- Department of Pathology, Oakland University William Beaumont School of Medicine, Royal Oak, Mich., USA
| | - Tusar Desai
- Division of Gastroenterology and Hepatology, Oakland University William Beaumont Hospital, Royal Oak, Mich., USA
| | - Mitchell S. Cappell
- Division of Gastroenterology, Oakland University William Beaumont School of Medicine, Royal Oak, Mich., USA
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Iwamuro M, Okada H, Takata K, Takenaka R, Inaba T, Mizuno M, Kobashi H, Tanaka S, Yoshioka M, Kondo E, Yoshino T, Yamamoto K. Colorectal Manifestation of Follicular Lymphoma. Intern Med 2016; 55:1-8. [PMID: 26726078 DOI: 10.2169/internalmedicine.55.5393] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
OBJECTIVE Due to their rarity, the endoscopic features and clinical backgrounds of colorectal follicular lymphoma lesions have not yet been fully investigated. The aim of this study was to reveal the characteristics of this disease entity. METHODS A database search performed at the Department of Pathology of our institute identified 12 follicular lymphoma patients with involvement in the cecum, colon, and/or rectum. Data regarding the endoscopic, radiological, biological, and pathological examinations performed were retrospectively reviewed from their clinical records. RESULTS The mean age of the patients (5 men, 7 women) was 58.7 years. Five patients were classified as being Lugano system stage I, while the other seven patients were stage IV. In all of the patients, colorectal follicular lymphoma presented with papular (n=4), polypoid (n=4), and flat elevated lesions (n=4). No erosions or ulcers were seen in any of the lesions. The initial pathological diagnoses included extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (n=2) and colitis/proctitis with infiltration of inflammatory cells (n=3), in addition to the correct diagnosis of follicular lymphoma (n=7). CONCLUSION Colorectal involvement of follicular lymphoma shows no erosions or ulcers. These lesions could be macroscopically observed as papular, polypoid and flat elevated lesions. Making a correct diagnosis of this disease based on the findings of biopsied samples is sometimes challenging. In such cases, multiple biopsies and/or endoscopic mucosal resection is required, in addition to appropriate consultation with pathologists.
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Affiliation(s)
- Masaya Iwamuro
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Japan
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Abstract
A large variety of lymphoma types may develop as primary intestinal neoplasms in the small intestines or, less often, in the colorectum. Among these are a few entities such as enteropathy-associated T-cell lymphoma or immunoproliferative small intestinal disease that, essentially, do not arise elsewhere than in the gastrointestinal tract. In most instances the primary intestinal lymphomas belong to entities that also occur in lymph nodes or other mucosal sites, and may show some peculiar features. In the case of follicular lymphoma, important differences exist between the classical nodal cases and the intestinal cases, considered as a variant of the disease. It is likely that the local intestinal mucosal microenvironment is a determinant in influencing the pathobiological features of the disease. In this review we will present an update on the clinical, pathological and molecular features of the lymphoid neoplasms that most commonly involve the intestines, incorporating recent developments with respect to their pathobiology and classification. We will emphasize and discuss the major differential diagnostic problems encountered in practice, including the benign reactive or atypical lymphoid hyperplasias, indolent lymphoproliferative disorders of T or natural killer (NK) cells, and Epstein-Barr virus (EBV)-related lymphoproliferations.
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Affiliation(s)
- Periklis G Foukas
- Ludwig Cancer Research Center and Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Second Department of Pathology, University of Athens Medical School, Athens, Greece; Institute of Pathology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
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A subset of ocular adnexal marginal zone lymphomas may arise in association with IgG4-related disease. Sci Rep 2015; 5:13539. [PMID: 26311608 PMCID: PMC4550912 DOI: 10.1038/srep13539] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2015] [Accepted: 07/29/2015] [Indexed: 02/06/2023] Open
Abstract
We previously suggested a relationship between ocular immunoglobulin (Ig)G4-related disease (IgG4-RD) and marginal zone lymphomas (MZLs). However, the cytokine background associated with these disorders and whether it differs between ocular adnexal MZLs with (IgG4-associated MZL) and without (IgG4-negative MZL) numerous IgG4+ plasma cells are unknown. In this study, we identified the mRNA expression pattern of Th2 and regulatory T-cell (Treg) cytokines in IgG4-RD and in IgG4-associated MZL and IgG4-negative MZL using real-time polymerase chain reaction analysis. Ocular IgG4-RD and IgG4-associated MZL exhibited significantly higher expression ratios of interleukin (IL)-4/β-actin, IL-10/β-actin, IL-13/β-actin, transforming growth factor (TGF) β1/β-actin, and FOXP3/β-actin than did IgG4-negative MZL (p < 0.05). This finding further supports our prior observations that a significant subset of ocular MZLs arises in the setting of IgG4-RD. Furthermore, the presence of a different inflammatory background in IgG4-negative MZLs suggests that IgG4-associated MZLs may have a different pathogenesis.
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IWAMURO MASAYA, OKADA HIROYUKI, KAWANO SEIJI, SHIODE JUNJI, TAKENAKA RYUTA, IMAGAWA ATSUSHI, INABA TOMOKI, SUZUKI SEIYU, NISHIMURA MAMORU, MIZUNO MOTOWO, ARAKI MASASHI, MANNAMI TOMOHIKO, UEKI TORU, KOBASHI HARUHIKO, FUKATSU HARUKA, TANAKA SHOUICHI, OMOTO AKIYOSHI, KAWAI YOSHINARI, KITAGAWA TAKASHI, TOYOKAWA TATSUYA, TAKATA KATSUYOSHI, YOSHINO TADASHI, TAKAKI AKINOBU, YAMAMOTO KAZUHIDE. A multicenter survey of enteroscopy for the diagnosis of intestinal follicular lymphoma. Oncol Lett 2015; 10:131-136. [PMID: 26170988 PMCID: PMC4486797 DOI: 10.3892/ol.2015.3251] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2014] [Accepted: 04/27/2015] [Indexed: 12/19/2022] Open
Abstract
The importance of enteroscopy examinations to investigate the entire length of the small intestines has been emphasized in follicular lymphoma patients with intestinal involvement. The aim of the present study was to determine the current state of enteroscopy examinations, including the performance rate, and the prevalence of small intestinal lesions in a patient population in Japan. A retrospective multicenter survey of 17 institutions collected the case information of 110 follicular lymphoma patients with gastrointestinal involvement. The results of the enteroscopy examinations were reviewed, and in order to identify potential factors affecting the performance rate of enteroscopy, patient gender, age at lymphoma diagnosis, histopathological grade, clinical stage, the date of the initial diagnosis and the annual volume of enteroscopy at the institution were compared between the patients who underwent one or more enteroscopy procedures and the patients who did not undergo enteroscopy. A total of 34 patients (30.9%) underwent enteroscopy, and 24 of these (70.6%) presented with involvement in the jejunum and/or ileum. It was found that more patients diagnosed in recent years and more patients treated at an ultra-high volume institution (≥101 enteroscopy examinations/year) underwent an enteroscopy. In conclusion, although the prevalence of small intestinal lesions was high (70.6%) in the follicular lymphoma patients presenting with intestinal involvement, the performance rate of enteroscopy was only 30.9%, and thus the majority of the patients have not undergone enteroscopy examinations. Further investigation is required to define the clinical significance of enteroscopy at the initial diagnostic work-up and during the follow-up period of these patients.
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Affiliation(s)
- MASAYA IWAMURO
- Department of Molecular Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
| | - HIROYUKI OKADA
- Department of Endoscopy, Okayama University Hospital, Okayama 700-8558, Japan
| | - SEIJI KAWANO
- Department of Endoscopy, Okayama University Hospital, Okayama 700-8558, Japan
| | - JUNJI SHIODE
- Department of Internal Medicine, Okayama Saiseikai General Hospital, Okayama 700-8511, Japan
| | - RYUTA TAKENAKA
- Department of Internal Medicine, Tsuyama Chuo Hospital, Tsuyama 708-0841, Japan
| | - ATSUSHI IMAGAWA
- Department of Gastroenterology, Mitoyo General Hospital, Kanonji 769-1695, Japan
| | - TOMOKI INABA
- Department of Gastroenterology, Kagawa Prefectural Central Hospital, Takamatsu 760-8557, Japan
| | - SEIYU SUZUKI
- Department of Internal Medicine, Sumitomo Besshi Hospital, Niihama 792-8543, Japan
| | - MAMORU NISHIMURA
- Department of Internal Medicine, Okayama City Hospital, Okayama 700-8557, Japan
| | - MOTOWO MIZUNO
- Department of Internal Medicine, Hiroshima City Hospital, Hiroshima 730-8518, Japan
| | - MASASHI ARAKI
- Department of Internal Medicine, Kagawa Rosai Hospital, Marugame 763-8502, Japan
| | - TOMOHIKO MANNAMI
- Department of Internal Medicine, Chugoku Central Hospital, Fukuyama 720-0001, Japan
| | - TORU UEKI
- Department of Internal Medicine, Fukuyama City Hospital, Fukuyama 721-8511, Japan
| | - HARUHIKO KOBASHI
- Department of Hepatology, Japanese Red Cross Okayama Hospital, Okayama 700-8607, Japan
| | - HARUKA FUKATSU
- Department of Internal Medicine, St. Mary's Hospital, Himeji 670-0801, Japan
| | - SHOUICHI TANAKA
- Department of Gastroenterology, Iwakuni Clinical Center, Iwakuni 740-8510, Japan
| | - AKIYOSHI OMOTO
- Department of Internal Medicine, Ako Central Hospital, Ako 678-0241, Japan
| | - YOSHINARI KAWAI
- Department of Gastroenterology, Onomichi Municipal Hospital, Onomichi 722-8503, Japan
| | - TAKASHI KITAGAWA
- Department of Surgery, Kitagawa Hospital, Okayama 709-0497, Japan
| | - TATSUYA TOYOKAWA
- Department of Gastroenterology, Fukuyama Medical Center, Fukuyama 720-8520, Japan
| | - KATSUYOSHI TAKATA
- Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
| | - TADASHI YOSHINO
- Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
| | - AKINOBU TAKAKI
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
| | - KAZUHIDE YAMAMOTO
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
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Akiyama S, Izutsu K, Ota Y, Imamura T, Ogawa O, Wake A, Takeuchi K. A case report of the histologic transformation of primary follicular lymphoma of the duodenum. Medicine (Baltimore) 2014; 93:e165. [PMID: 25474429 PMCID: PMC4616394 DOI: 10.1097/md.0000000000000165] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2014] [Revised: 09/08/2014] [Accepted: 09/11/2014] [Indexed: 12/21/2022] Open
Abstract
A 46-year-old woman underwent upper endoscopy for evaluation of anemia, which revealed whitish granules at the duodenal papilla, diagnosed as duodenal follicular lymphoma (DFL) by biopsy. Computed tomography and abdominal ultrasonography revealed that follicular lymphoma was confined to the duodenum. Seven years after the diagnosis, fluorine-18 fluorodeoxyglucose positron emission tomography scanning revealed multiple lesions including in bone marrow and lymph nodes. Bone marrow biopsy of the right iliac bone revealed diffuse large B-cell lymphoma, indicating systemic dissemination and histologic transformation of the DFL. The patient responded to chemotherapy and has been progression-free for 2.5 years. Although DFL is usually indolent even without any treatment, systemic dissemination with histologic transformation can occur. This case suggests that the life-time follow-up that is usually done for patients with nodal follicular lymphoma should be provided to patients with DFL.
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Affiliation(s)
- Shintaro Akiyama
- From the Department of Hematology (KI, AW); Department of Gastroenterology (SA, TI, OO, KT); Department of Pathology, Tokyo(YO); and Department of Hematology, Toranomon Hospital Kajigaya, Kawasaki, Japan (AW)
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A rare collision tumor composed of follicular lymphoma and adenocarcinoma in the ampulla of vater: a case report. Case Rep Pathol 2014; 2014:530727. [PMID: 25002984 PMCID: PMC4066863 DOI: 10.1155/2014/530727] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2014] [Accepted: 04/12/2014] [Indexed: 11/18/2022] Open
Abstract
The duodenum is infrequently affected by malignant lymphoma, and follicular lymphomas of the duodenum are rare histological subtypes. There are no reported cases of collision of follicular lymphoma and other tumors in the ampulla of Vater. A 57-year-old Japanese man presented with jaundice, and abdominal computed tomography revealed a tumor of the ampulla of Vater invading the pancreatic head with biliary dilatation and a thickened duodenal wall. The patient underwent subtotal stomach-preserving pancreaticoduodenectomy. Histopathology of the resected specimen revealed lymphoid follicular formations with small-to-medium-sized centrocyte-like cells and some centroblast-like cells. The atypical lymphoid cells were immunohistochemically positive for CD10, CD20, and CD79a but negative for CD5 and cyclin D1. BCL2 protein was highly expressed in the follicle centers. The diagnosis was duodenal follicular lymphoma, Grade 1. The follicular lymphoma, 40 mm in diameter, involved duodenal submucosa and regional lymph nodes without distant metastasis. This duodenal follicular lymphoma was partially overlapped by adenocarcinoma of the ampulla of Vater, measuring 25 × 20 mm, which involved the lower common bile duct, pancreas, and duodenum. We report the first case of a surgically treated collision tumor composed of a rare mass-forming follicular lymphoma and adenocarcinoma of the ampulla of Vater.
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Iwamuro M, Okada H, Takata K, Nose S, Miyatani K, Yoshino T, Yamamoto K. Diagnostic accuracy of endoscopic biopsies for the diagnosis of gastrointestinal follicular lymphoma: a clinicopathologic study of 48 patients. Ann Diagn Pathol 2014; 18:99-103. [PMID: 24513028 DOI: 10.1016/j.anndiagpath.2013.12.006] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2013] [Revised: 12/27/2013] [Accepted: 12/27/2013] [Indexed: 12/11/2022]
Abstract
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.
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MESH Headings
- Adult
- Aged
- Aged, 80 and over
- Biopsy
- Diagnosis, Differential
- Duodenal Neoplasms/diagnosis
- Duodenal Neoplasms/pathology
- Female
- Gastrointestinal Neoplasms/diagnosis
- Gastrointestinal Neoplasms/pathology
- Humans
- Lymphoma, B-Cell/metabolism
- Lymphoma, B-Cell/pathology
- Lymphoma, B-Cell, Marginal Zone/diagnosis
- Lymphoma, B-Cell, Marginal Zone/pathology
- Lymphoma, Follicular/diagnosis
- Lymphoma, Follicular/pathology
- Male
- Middle Aged
- Retrospective Studies
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Affiliation(s)
- Masaya Iwamuro
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
| | - Hiroyuki Okada
- Department of Endoscopy, Okayama University Hospital, Okayama, Japan
| | - Katsuyoshi Takata
- Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Soichiro Nose
- Department of Anatomic Pathology, Okayama Saiseikai General Hospital, Okayama, Japan
| | - Katsuya Miyatani
- Department of Pathology, Mitoyo General Hospital, Kanonji, Japan
| | - Tadashi Yoshino
- Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Kazuhide Yamamoto
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
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Iwamuro M, Shinagawa K, Okada H, Takata K, Yoshino T, Yamamoto K. Elevated soluble IL-2 receptor levels correlate with tumor bulk of follicular lymphomas with intestinal involvement. Clin Biochem 2014; 47:191-195. [PMID: 24362271 DOI: 10.1016/j.clinbiochem.2013.11.026] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2013] [Revised: 11/12/2013] [Accepted: 11/27/2013] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Establish a correlation between serum soluble interleukin 2 receptor (sIL-2R) levels and clinical characteristics of follicular lymphoma patients with gastrointestinal involvement. DESIGN AND METHODS Patients (n=44) presenting with follicular lymphoma lesions in the gastrointestinal tract were enrolled into the study and divided into 2 groups based on sIL-2R levels (normal vs. elevated). Clinical characteristics were also analyzed between groups. RESULTS Patients with elevated sIL-2R levels likely had systemic follicular lymphoma involvement (Ann Arbor system staging IIIES/IV or Lugano system staging II-2/IV), involvement of 5 or more nodal areas, and presentation of bulky tumors in the gastrointestinal tract. These patients also presented a high Follicular Lymphoma International Prognostic Index (FLIPI) score, suggestive of poor prognosis. No differences were found among other clinical characteristics including sex, age at lymphoma diagnosis, histological grade, LDH levels, bone marrow involvement, hemoglobin levels, and identification of tracer accumulation in gastrointestinal lesions by positron-emission tomography scanning. CONCLUSIONS sIL-2R levels can be used as an independent prognostic index in follicular lymphoma patients based on the correlation with the FLIPI score. Moreover, since high sIL-2R levels were associated with a large tumor bulk, sIL-2R may serve as a good indicator for monitoring disease relapse or progression.
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Affiliation(s)
- Masaya Iwamuro
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-Cho, Kita-Ku, Okayama 700-8558, Japan.
| | - Katsuji Shinagawa
- Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-Cho, Kita-Ku, Okayama 700-8558, Japan
| | - Hiroyuki Okada
- Department of Endoscopy, Okayama University Hospital, 2-5-1 Shikata-Cho, Kita-Ku, Okayama 700-8558, Japan
| | - Katsuyoshi Takata
- Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-Cho, Kita-Ku, Okayama 700-8558, Japan
| | - Tadashi Yoshino
- Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-Cho, Kita-Ku, Okayama 700-8558, Japan
| | - Kazuhide Yamamoto
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-Cho, Kita-Ku, Okayama 700-8558, Japan
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Maeshima AM, Taniguchi H, Nomoto J, Miyamoto KI, Fukuhara S, Munakata W, Maruyama D, Kim SW, Watanabe T, Kobayashi Y, Tobinai K, Tsuda H. Prognostic implications of histologic grade and intensity of Bcl-2 expression in follicular lymphomas undergoing rituximab-containing therapy. Hum Pathol 2013; 44:2529-35. [DOI: 10.1016/j.humpath.2013.06.013] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2013] [Revised: 06/19/2013] [Accepted: 06/21/2013] [Indexed: 10/26/2022]
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35
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Hayashi E, Takata K, Sato Y, Tashiro Y, Tachiyama Y, Sawada-Kitamura S, Hiramatsu Y, Sugiguchi S, Nose S, Hirokawa M, Ando M, Alkader LA, Maeda Y, Tanimoto M, Yoshino T. Distinct morphologic, phenotypic, and clinical-course characteristics of indolent peripheral T-cell lymphoma. Hum Pathol 2013; 44:1927-36. [DOI: 10.1016/j.humpath.2013.03.002] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2012] [Revised: 02/28/2013] [Accepted: 03/14/2013] [Indexed: 10/26/2022]
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Iwamuro M, Imagawa A, Kobayashi N, Kubota Y, Miyatani K, Takata K, Okada H. Synchronous adenocarcinoma and follicular lymphoma of the stomach. Intern Med 2013; 52:907-912. [PMID: 23583995 DOI: 10.2169/internalmedicine.52.7948] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Abstract
A 73-year-old Japanese man with synchronous follicular lymphoma and adenocarcinoma of the stomach underwent curative surgical resection. The follicular lymphoma lesion was preoperatively diagnosed as extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) according to biopsy samples. However, postoperative pathological evaluations revealed components of CD10-positive and CD10-negative lymphoma cells within the lymphoma lesion. This case highlights the potential difficulty of diagnosing gastric follicular lymphoma. In such cases, conducting repeat pathological examinations of biopsy samples or resected specimens is required to obtain a correct diagnosis of follicular lymphoma.
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Affiliation(s)
- Masaya Iwamuro
- Department of Gastroenterology, Mitoyo General Hospital, Japan.
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Hayashi H, Onishi Y, Mitsuoka H, Ogura T, Maeda M, Nishigami T, Harada M. Regression of follicular lymphoma of the duodenum following eradication of H. pylori infection. Intern Med 2013; 52:2611-4. [PMID: 24292749 DOI: 10.2169/internalmedicine.52.0552] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Abstract
A 64-year-old woman was referred for an examination of the upper gastrointestinal (GI) tract. Endoscopy showed an elevated lesion in the duodenum with central depression and multiple white granules. Biopsy specimens revealed lymphoid follicles composed predominantly of centrocytes with scattered centroblasts. The tumor cells were positive for bcl-2. The patient was diagnosed with follicular lymphoma and underwent antibiotic therapy for Helicobacter pylori (H. pylori) infection. The regression of the lesion was obvious. After 5.5 years of follow-up, there has been no evidence of recurrence. This case suggests that H. pylori eradication therapy is effective for treating follicular lymphoma in the duodenum.
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Affiliation(s)
- Hiroki Hayashi
- Department of Internal Medicine, IHI Harima Hospital, Japan
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38
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Takata K, Sato Y, Nakamura N, Tokunaka M, Miki Y, Yukie Kikuti Y, Igarashi K, Ito E, Harigae H, Kato S, Hayashi E, Oka T, Hoshii Y, Tari A, Okada H, Al-Kader LA, Mohamad AAL, Maeda Y, Tanimoto M, Kinoshita T, Yoshino T. Duodenal follicular lymphoma lacks AID but expresses BACH2 and has memory B-cell characteristics. Mod Pathol 2013; 26:22-31. [PMID: 22899287 DOI: 10.1038/modpathol.2012.127] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
We have reported previously that duodenal follicular lymphoma (FL) is distinct from nodal FL and showed more resemblance to mucosa-associated lymphoid tissue lymphoma, and that FL frequently involved the duodenal second portion. In the present study, we examined duodenal FLs and gastric/colonic FLs to clarify the clinicopathological and immunological differences between the tumor types. We analyzed 8 samples of gastric FL, 17 of duodenal ones, and 5 of colonic/rectal ones, and characterized them by immunohistochemistry, immunogenotyping, and histology. Gastric and colonic FLs presented in submucosal to subserosal areas, whereas duodenal ones presented in the mucosal to submucosal layers. Immunohistochemical analysis revealed that duodenal FLs exhibited the following phenotypes: CD10 (+), B-cell lymphoma 2 (BCL-2) (+), BCL-6 (+), activation-induced cytidine deaminase (AID) (-), BACH2 (+), CD27 (+), MUM-1 (-), Blimp-1 (-), and loose CD21 network (duodenal pattern). Gastric/colonic FLs exhibited the following phenotypes: CD10 (+), BCL-2 (+), BCL-6 (+), AID (+), BACH2 (+), CD27 (-), MUM-1 (-), Blimp-1 (-), and a dense CD21 network (nodal pattern). Expression of AID and CD27 in lymphoma cells and the CD21 network pattern were considerably different between duodenal FLs and gastric/colonic ones. Moreover, in situ hybridization revealed that, in the duodenal FLs, BACH2 was expressed at the periphery of the tumor follicle and tumor villi. The number of immunoglobulin heavy-chain variable domains VH4 and VH5 were higher in duodenal follicular lymphomoas than in gastric FLs. The lymphoma cells of duodenal FLs are different from those of gastric/colonic FLs, and duodenal FL is distinct even within the gastrointestinal tract. Somatic hypermutation in immunoglobulin genes and CD27 expression are hallmarks of memory B cells. We suggest that duodenal FL cells are in the memory B-cell stage, and require BACH2 instead of AID for ongoing mutation.
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Affiliation(s)
- Katsuyoshi Takata
- Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
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Al-Kader LA, Sato Y, Takata K, Ohshima KI, Sogabe Y, Fujii K, Iwaki N, Yoshino T. A Case of Conjunctival Follicular Lymphoma Mimicking Mucosa-Associated Lymphoid Tissue Lymphoma. J Clin Exp Hematop 2013; 53:49-52. [DOI: 10.3960/jslrt.53.49] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
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Iwamuro M, Okada H, Takata K, Shinagawa K, Fujiki S, Shiode J, Imagawa A, Araki M, Morito T, Nishimura M, Mizuno M, Inaba T, Suzuki S, Kawai Y, Yoshino T, Kawahara Y, Takaki A, Yamamoto K. Diagnostic role of 18F-fluorodeoxyglucose positron emission tomography for follicular lymphoma with gastrointestinal involvement. World J Gastroenterol 2012; 18:6427-p.6434. [PMID: 23197888 PMCID: PMC3508637 DOI: 10.3748/wjg.v18.i44.6427] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2012] [Revised: 08/29/2012] [Accepted: 09/12/2012] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the capacity for 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) to evaluate patients with gastrointestinal lesions of follicular lymphoma. METHODS This retrospective case series consisted of 41 patients with follicular lymphoma and gastrointestinal involvement who underwent 18F-FDG-PET and endoscopic evaluations at ten different institutions between November 1996 and October 2011. Data for endoscopic, radiological, and biological examinations performed were retrospectively reviewed from clinical records. A semi-quantitative analysis of 18F-FDG uptake was performed for each involved area by calculating the maximum standardized uptake value (SUVmax). Based on the positivity of 18F-FDG uptake in the gastrointestinal lesions analyzed, patients were subdivided into two groups. To identify potential predictive factors for 18F-FDG positivity, these two groups were compared with respect to gender, age at diagnosis of lymphoma, histopathological grade, pattern of follicular dendritic cells, mitotic rate, clinical stage, soluble interleukin-2 receptor levels detected by 18F-FDG-PET, lactate dehydrogenase (LDH) levels, hemoglobin levels, bone marrow involvement, detectability of gastrointestinal lesions by computed tomography (CT) scanning, and follicular lymphoma international prognostic index (FLIPI) risk. RESULTS Involvement of follicular lymphoma in the stomach, duodenum, jejunum, ileum, cecum, colon, and rectum was identified in 1, 34, 6, 3, 2, 3, and 6 patients, respectively. No patient had esophageal involvement. In total, 19/41 (46.3%) patients exhibited true-positive 18F-FDG uptake in the lesions present in their gastrointestinal tract. In contrast, false-negative 18F-FDG uptake was detected in 24 patients (58.5%), while false-positive 18F-FDG uptake was detected in 5 patients (12.2%). In the former case, 2/19 patients had both 18F-FDG-positive lesions and 18F-FDG-negative lesions in the gastrointestinal tract. In patients with 18F-FDG avidity, the SUVmax value of the involved gastrointestinal tract ranged from 2.6 to 17.4 (median: 4.7). For the 18F-FDG-negative (n = 22) and -positive (n = 19) groups, there were no differences in the male to female ratios (10/12 vs 4/15, P = 0.186), patient age (63.6 ± 2.4 years vs 60.1 ± 2.6 years, P = 0.323), presence of histopathological grade 1 vs 2 (20/2 and 17/2, P = 1.000), follicular dendritic cell pattern (duodenal/nodal: 13/5 vs 10/3, P = 1.000), mitotic rate (low/partly high, 14/1 vs 10/3, P = 0.311), clinical stage according to the Ann Arbor system (stages IE and IIE/other, 15/7 vs 15/4, P = 0.499), clinical stage according to the Lugano system (stages I and II-1/other, 14/8 vs 14/5, P = 0.489), soluble interleukin-2 receptor levels (495 ± 78 vs 402 ± 83, P = 0.884), LDH levels (188 ± 7 vs 183 ± 8, P = 0.749), hemoglobin levels (13.5 ± 0.3 vs 12.8 ± 0.4, P = 0.197), bone marrow involvement (positive/negative, 1/8 vs 1/10, P = 1.000), detectability by CT scanning (positive/negative, 1/16 vs 4/13, P = 0.335), and FLIPI risk (low risk/other, 16/6 vs 13/6, P = 0.763), respectively in each case. CONCLUSION These findings indicate that it is not feasible to predict 18F-FDG-avidity. Therefore, 18F-FDG-PET scans represent a complementary modality for the detection of gastrointestinal involvements in follicular lymphoma patients, and surveillance of the entire gastrointestinal tract by endoscopic examinations is required.
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Hangai S, Nakamura F, Yamada A, Watabe H, Ichikawa M, Koike K, Kurokawa M. Usefulness of double-balloon enteroscopy for evaluation of duodenal follicular lymphoma. Ann Hematol 2012; 91:1819-20. [PMID: 22538440 DOI: 10.1007/s00277-012-1471-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2012] [Accepted: 04/02/2012] [Indexed: 10/28/2022]
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Cui W, Che L, Sato Y, Huang X, Takata K, Orita Y, Goto N, Maeda Y, Tanimoto M, Yoshino T. Nodal follicular lymphoma without complete follicular dendritic cell networks is related to localized clinical stage. Pathol Int 2011; 61:737-41. [DOI: 10.1111/j.1440-1827.2011.02736.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Ono Y, Aoki K, Kato A, Arima H, Takiuchi Y, Nagano S, Tabata S, Yanagita S, Matsushita A, Maruoka H, Imai Y, Ishikawa T, Takahashi T. Systemic follicular lymphoma with massive intestinal involvement with leukemic manifestation. J Clin Exp Hematop 2011; 51:135-40. [PMID: 22104313 DOI: 10.3960/jslrt.51.135] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/15/2022] Open
Abstract
A 30-year-old man was referred to our hospital with leukocytosis and fecal occult blood. His white blood cell count was 30.2 × 10(9)/L with 79% small- to medium-sized lymphocytes. Surface antigen analysis revealed that these lymphocytes were positive for CD19, CD20, CD10, and CD23, but negative for CD5. The lymphocytes infiltrated the bone marrow. On endoscopic examination of the duodenum and jejunum, many small polypoid lesions were observed. A histologic picture of a biopsied lesion showed diffuse infiltration of small- to medium-sized lymphocytes in the submucosal region. On immunohistochemistry, these lymphocytes were positive for CD20, BCL2, and CD10 (weakly). Polymerase chain reaction analysis of cells from peripheral blood, bone marrow, and intestinal lesion showed a fusion product of BCL2 and immunoglobulin heavy chain (IGH) genes. The fused BCL2/IGH gene was also demonstrated by fluorescence in situ hybridization in the same cell sources. Computed tomography scanning showed marked wall thickening throughout the small intestine and enlarged mesenteric lymph nodes. A diagnosis of follicular lymphoma with massive intestinal involvement in a leukemic state was made. After 6 courses of rituximab-combined CHOP chemotherapy, complete remission was obtained.
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Affiliation(s)
- Yuichiro Ono
- Department of Hematology, Kobe City Medical Center General Hospital, Japan
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Burke JS. Lymphoproliferative disorders of the gastrointestinal tract: a review and pragmatic guide to diagnosis. Arch Pathol Lab Med 2011; 135:1283-97. [PMID: 21970484 DOI: 10.5858/arpa.2011-0145-ra] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
CONTEXT The gastrointestinal tract is the most common site of extranodal lymphomas. Although all histologic categories of malignant lymphoma develop in the gastrointestinal tract, large B-cell lymphomas predominate, followed by extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT) type; the latter is especially prevalent in stomach. The acceptance of extranodal marginal zone lymphoma of MALT type as a clinicopathologic entity has reduced the number of cases that formerly were interpreted as florid lymphoid hyperplasia ("pseudolymphoma"). Nonetheless, the distinction of lymphoid hyperplasia from a lymphoma of MALT type in small biopsy specimens remains problematic. OBJECTIVE To assess the relevant morphologic, immunologic, molecular, and genetic properties of gastrointestinal lymphomas and to present a feasible tactic for diagnosis, expressly for small biopsy specimens. DATA SOURCES Case-derived material and literature review using PubMed (National Library of Medicine). CONCLUSIONS Most gastrointestinal lymphomas are readily amenable to an unqualified diagnosis, primarily those cases consisting of monomorphic large cells whether of B- or T-cell lineage, including cases associated with enteropathy. Diagnosis for infiltrates dominated by small lymphocytes remains taxing, as the differential diagnosis embraces not only MALT lymphoma and lymphoid hyperplasia but also mantle cell lymphoma, follicular lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma. Adherence to strict morphologic criteria is the standard for diagnosis, but these criteria should be augmented by immunologic studies together with judicious use of molecular techniques to determine clonality. In establishing a diagnosis of gastric marginal zone lymphoma of MALT type, determination of t(11;18)(q21;q21) status may be required since this translocation has clinical ramifications.
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Affiliation(s)
- Jerome S Burke
- Department of Pathology, Alta Bates Summit Medical Center, Berkeley, California 94705, USA.
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45
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Bennani-Baiti N, Daw HA, Cotta C, Martin P, Mitchell KW, Ambinder RF, Macklis R, Pollock R, Spiro T. Low-grade follicular lymphoma of the small intestine: a challenge for management. Semin Oncol 2011; 38:714-20. [PMID: 22082756 DOI: 10.1053/j.seminoncol.2011.08.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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46
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Takata K, Okada H, Ohmiya N, Nakamura S, Kitadai Y, Tari A, Akamatsu T, Kawai H, Tanaka S, Araki H, Yoshida T, Okumura H, Nishisaki H, Sagawa T, Watanabe N, Arima N, Takatsu N, Nakamura M, Yanai S, Kaya H, Morito T, Sato Y, Moriwaki H, Sakamoto C, Niwa Y, Goto H, Chiba T, Matsumoto T, Ennishi D, Kinoshita T, Yoshino T. Primary gastrointestinal follicular lymphoma involving the duodenal second portion is a distinct entity: a multicenter, retrospective analysis in Japan. Cancer Sci 2011; 102:1532-1536. [PMID: 21561531 DOI: 10.1111/j.1349-7006.2011.01980.x] [Citation(s) in RCA: 101] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
We conducted a multicenter, retrospective study to determine the anatomical distribution and prognostic factors of gastrointestinal (GI) follicular lymphoma (FL). This study included 125 patients with stage I and II(1) GI-FL. Of the 125 patients, the small intestine was examined in 70 patients, with double-balloon endoscopy and/or capsule endoscopy. The most frequently involved GI-FL site was the duodenal second portion (DSP) (81%), followed by the jejunum (40%); 85% of patients with involvement of the DSP also had jejunal or ileal lesions. The absence of abdominal symptoms and macroscopic appearance of multiple nodules were significantly present in the DSP-positive group. During a median follow up of 40 months, six patients showed disease progression. Patients with involvement of the DSP had better progression-free survival (PFS) than those without such involvement (P = 0.001). A multivariate analysis revealed that male sex, the presence of abdominal symptoms, and negative involvement of the DSP were independently associated with poor PFS. In conclusion, most patients with GI-FL have duodenal lesions associated with multiple jejunal or ileal lesions. Gastrointestinal follicular lymphomas involving the DSP might be a distinct entity showing a favorable clinical course.
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Affiliation(s)
- Katsuyoshi Takata
- Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
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Pileri SA, Agostinelli C, Sabattini E, Bacci F, Sagramoso C, Pileri A, Falini B, Piccaluga PP. Lymphoma classification: the quiet after the storm. Semin Diagn Pathol 2011; 28:113-123. [PMID: 21842697 DOI: 10.1053/j.semdp.2011.02.001] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
The classification of malignant lymphomas remained controversial for over 30 years. The first scheme was proposed by Rappaport in the '60th and was based on incorrect histogenetic concepts. To overcome these limitations, several groups formulated new proposals in '70th. Among these two merited attention: the Lukes and Collins and the Kiel Classifications. They were based on the assumption that each lymphoma category might be related to a precise differentiation step of the lymphoid system, thus excluding any correlation with histiocytes, present on the Rappaport scheme. The Kiel Classification became very popular in Europe, while the one of Luke and Collins did not meet success in the United States (U.S.). In 1978, the National Cancer Institute proposed an international trial to compare the classifications used in Europe and U.S. The result was the genesis of the Working formulation, the tool for lymphoma classification in the U.S. up to the early '90th, but which was conversely rejected in Europe. In order to get over this lack of transatlantic communication, in 1994 the Revised European-American Lymphoma (REAL) Classification was proposed by the International Lymphoma Study Group. Its goal was to list "real" entities, each defined by the presence of homogeneous morphologic, phenotypic, cytogenetic, molecular, and clinical criteria, along with the possible recognition of its normal counterpart. The REAL Classification became the model for the WHO Classification of all haematopoietic tumours published in 2001. The present review aims to analyse future perspectives after the fourth edition of the WHO Classification released in 2008.
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Affiliation(s)
- Stefano A Pileri
- Department of Haematology and Oncological Sciences L. and A. Seràgnoli, Bologna University School of Medicine, Bologna, Italy.
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Schmatz AI, Streubel B, Kretschmer-Chott E, Püspök A, Jäger U, Mannhalter C, Tiemann M, Ott G, Fischbach W, Herzog P, Seitz G, Stolte M, Raderer M, Chott A. Primary follicular lymphoma of the duodenum is a distinct mucosal/submucosal variant of follicular lymphoma: a retrospective study of 63 cases. J Clin Oncol 2011; 29:1445-51. [PMID: 21383289 DOI: 10.1200/jco.2010.32.9193] [Citation(s) in RCA: 145] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
PURPOSE Small series with limited follow-up have suggested primary follicular lymphoma of the duodenum (FL-D) to be an indolent disease. We report our experience on a large series of patients followed for a median time period of longer than 6 years. PATIENTS AND METHODS The study comprised 63 patients with primary FL-D defined as stage I disease. Endoscopy and detailed pathologic work-up was performed at diagnosis and at restaging to monitor the behavior of the neoplastic process. RESULTS Histologically, all 63 patients had FL, low grade (1 to 2). Duodenal endosonography demonstrated lesions confined to mucosa/submucosa in 19 of 20 patients. At an overall median follow-up of 77 months (range, 12 to 177 months), only two untreated patients had developed nodal disease, the remaining 61 patients never experienced extrasmall intestinal disease and large cell transformation did not occur at all. Among 24 patients followed by watch and wait strategy, seven showed spontaneous complete regression and 17 had stable disease; radiotherapy resulted in complete regression in all 19 patients; anti-CD20 antibody monotherapy achieved complete regression in four patients and stable disease in one patient. Various chemotherapy protocols in eight patients caused complete regression in all of them, but local relapses occurred in three. No patients required surgery or died of disease. CONCLUSION These findings characterize primary FL-D as a remarkably indolent FL variant, which, even left untreated, does not develop tumorous growth, very rarely disseminates (two of 63 patients) and does not transform to high grade disease. A watch and wait approach appears to be the most sensible strategy.
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Affiliation(s)
- Ana-Iris Schmatz
- Medical University Vienna, Vienna General Hospital, Vienna, Austria
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Ferry JA. Recent Advances in Follicular Lymphoma: Pediatric, Extranodal, and Follicular Lymphoma in Situ. Surg Pathol Clin 2010; 3:877-906. [PMID: 26839293 DOI: 10.1016/j.path.2010.08.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Follicular lymphoma is a relatively common B-cell lymphoma composed of follicle center B lymphocytes. Follicular lymphomas occurring in the pediatric population and in some extranodal sites exhibit particular clinicopathologic features and clinical behavior that are often distinct from adult nodal follicular lymphoma. A type of "in-situ" follicular lymphoma presents as intrafollicular neoplastic cells in a background of architecturally normal lymphoid tissue and may be difficult to recognize in routine sections. Accurate recognition of the morphologic variants and clinicopathologic subtypes of follicular lymphoma is important to avoid confusing them with other lymphomas and reactive processes; in addition, some of these subtypes of follicular lymphoma display unusually indolent clinical behavior that warrant their separation from "conventional" follicular lymphoma.
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Affiliation(s)
- Judith A Ferry
- Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA; James Homer Wright Pathology Laboratories of the Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
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Iwamuro M, Okada H, Kawahara Y, Shinagawa K, Morito T, Yoshino T, Yamamoto K. Endoscopic features and prognoses of mantle cell lymphoma with gastrointestinal involvement. World J Gastroenterol 2010; 16:4661-4669. [PMID: 20872966 PMCID: PMC2951516 DOI: 10.3748/wjg.v16.i37.4661] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2010] [Revised: 06/01/2010] [Accepted: 06/08/2010] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the endoscopic manifestations and prognoses of gastrointestinal (GI) mantle cell lymphoma (MCL). METHODS A database search at the Department of Pathology of Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences revealed 57 MCL patients with GI involvement. Clinical records were available for 35 of the 57 patients from 21 institutions, and those 35 patients were enrolled in this study. We summarized the gross types of endoscopic features, event-free survival (EFS), and overall survival (OS) of those patients. RESULTS Of the 35 patients, GI involvement in the esophagus, stomach, and duodenum was found in 2 (5.7%), 26 (74.3%), and 12 (34.3%) patients, respectively. Twenty-one of the 35 patients underwent colonoscopy; among them, GI involvement in the ileum, cecum, colon, and rectum was found in 10 (47.6%), 3 (14.3%), 12 (57.1%), and 10 (47.6%), respectively. Various lesions, such as superficial, protruded, fold thickening, or ulcerative, were found in the stomach, whereas multiple lymphomatous polyposis (MLP) was dominant from the duodenum to the rectum. Twelve patients were treated with a hyper-CVAD/MA regimen, and they had better OS (3-year rate, 88.3% vs 46.4%, P < 0.01) and better EFS (3-year rate, 66.7% vs 33.8%, P < 0.05) than the remaining 23 patients who were not treated with this regimen. CONCLUSION MLP was a representative form of intestinal involvement, whereas a variety of lesions were found in the stomach. The hyper-CVAD/MA regimen may improve survival in these patients.
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