Extranodal Follicular Lymphoma Research Articles

Abstract 3820: Impact of primary site in early-stage follicular lymphoma on patient outcomes: Analysis of a large national database

Abstract Introduction: Follicular lymphoma (FL) is the most common indolent Non-Hodgkin lymphoma and is associated with better outcomes compared to other types of lymphoma. Despite this, cure is usually elusive and most patients experience multiple relapses within their lifetime. Previous studies have identified risk factors associated with worse outcomes, but little is known about the role of primary disease site in FL. We sought to investigate the outcomes of patients with extranodal early-stage FL compared to nodal disease using a large national cancer database. Methods: The Surveillance, Epidemiology, and End Results (SEER) public database was used to identify and extract data for patients with FL. Early-stage disease was defined as stage I or II by the Ann Arbor staging system. Most patients in the database were diagnosed after 2000 so this was used as the diagnosis year cutoff and also to reflect the impact of recent management strategies on outcomes. Patients were divided into two groups based on their primary disease site. These two groups were nodal (includes spleen) and extranodal. Treatment effect (surgery, radiation, or chemotherapy) was analyzed when available. Survival was estimated using the Kaplan-Meier method and compared using log-rank tests. Cox proportional hazards models were used for adjusted survival analyses. Results: A total of 13,400 patients with FL of all histologic grades diagnosed between 2000 and 2015 were identified in the SEER database. The median age at diagnosis was 65 years (2-100). A majority of patients were Caucasian (81%), had stage I disease (62%), and belonged to the nodal FL group (79%). Median overall survival (OS) for patients with nodal FL was 181 months [95% CI (175-187)]. Median OS for extranodal FL was 189 months [95% CI (179-195)]. Extranodal FL was associated with better OS compared to the nodal group [HR=0.89, 95% CI (0.84-0.96); p-value =0.00012] even after adjusting for age and race [HR=0.84, 95% CI (0.79-0.90); p-value <0.0001]. Conclusions: In this analysis of a large national cancer database, early-stage FL presenting as extranodal disease can be seen in about 20% of patients and is associated with slightly better outcomes. Citation Format: Olivia Davis, Rana Kasht, Andrew Cohoon, Silas Day, Sami Ibrahimi, Adam Asch, Taha Al-Juhaishi. Impact of primary site in early-stage follicular lymphoma on patient outcomes: Analysis of a large national database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3820.

Pathogenesis of Gastrointestinal Follicular Lymphomas: Consideration Based on Histopathology and Endoscopic Findings.

Gastrointestinal (GI) follicular lymphoma (FL) is the most frequently diagnosed extranodal FL; however, its pathogenesis is debatable. We investigated the distribution, endoscopic, and histopathologic findings of 366 GI FL samples obtained from 298 patients. FLs were most frequently observed in the small intestine (71%), including the duodenum (52%), but were also commonly found in the stomach (15%) and colon (12%). The proportion of granular lesions in the duodenum, terminal ileum, colon, and stomach was 74%, 39%, 24%, and 0%, respectively. Submucosal or ulcerated tumors were frequently observed in the stomach (48%) and colon (52%). Most GI FL showed grade 1 to 2 histology (89%) as well as CD10 + (93%) and BCL2 + (98%) positivity. There were no significant differences in the endoscopic or histologic findings between primary and secondary GI FLs. As known, the mucosa of the small intestine is thin and villous, while the mucosa of the stomach and colon is thicker and has a smooth surface. Granular lesions corresponding to very small FL were detected in the former but rarely in the latter. Nine (7%) patients with primary GI FL developed histologic transformation to diffuse large B-cell lymphoma (n=8) or high-grade B-cell lymphoma (n=1) 10 months to 14 years after the diagnosis of FL. Two patients died of lymphoma. In conclusion, the incidence and endoscopic findings differed, but the histopathology was similar in FLs in each site. These differences might be attributed to variations in each GI site's mucosal structure and the neoplastic follicles' size. Due to its characteristic structure, very small classic FLs might be detectable mainly in the small intestine.

Follicle Center Lymphoma (FCL) of the Lower Female Genital Tract (LFGT): A Novel Variant of Primary Cutaneous Follicle Center Lymphoma (PCFCL).

Primary cutaneous follicle center lymphoma has been distinguished from nodal follicular lymphoma (FL) based on genomic and clinical features. The nature of other extranodal FLs is not well defined. We report 15 cases of follicle center lymphoma involving the lower female genital tract. Cases were evaluated using an immunohistochemical panel for B-cell lymphoma, B-cell clonality, fluorescence in situ hybridization for BCL2 gene rearrangement, and next-generation sequencing. All patients had localized disease with no evidence of bone marrow involvement. Most cases (12/15, 80%) had a follicular pattern, at least focally. Large centrocytes were a prominent feature leading to concern for diffuse large B-cell lymphoma by referring pathologists. Neoplastic cells were positive for CD20 and BCL-6, while BCL-2 was positive in 2/15 (13%) cases. Fluorescence in situ hybridization for BCL2 gene rearrangement was negative in 10/11 (91%) cases. Next-generation sequencing performed in 10 cases revealed TNFRSF14 as the most frequently mutated gene in 6/10 (60%) cases. No case had CREBBP or KMT2D mutations as seen in nodal FL. None of the patients had progressive disease with durable complete remission achieved in 10/12 (83%) cases. The median follow-up period was 7.8 years (range: 0.2 to 20.5y) with a 5-year overall survival of 100%. We conclude that follicle center lymphoma of the lower female genital tract is a novel variant of primary cutaneous follicle center lymphoma. Despite a frequent component of large cells, it is characterized by localized disease and low risk for dissemination. Awareness and recognition are important to distinguish these lesions from aggressive B-cell lymphomas.

Evaluating patterns of care for early-stage low-grade follicular lymphoma in the rituximab era

Radiotherapy (RT) utilization for early-stage, low-grade follicular lymphoma (FL) is low despite treatment guideline recommendations. We compare treatment trends for early-stage FL in the era of involved-site RT and rituximab. We identified 11,645 patients in the National Cancer Database (NCDB) with stage I–II, grade 1–2 nodal or extranodal FL diagnosed 2011–2017, with median follow-up of 44 months. From 2011 to 2017, RT utilization rates decreased from 33.4% to 22.4%, observation decreased from 65.3% to 49.7%, chemoimmunotherapy increased from 0.5% to 15.0%, immuno-monotherapy increased from 0.6% to 10.2%, and RT + systemic therapy increased from 0.6% to 2.5%. RT utilization remains low in the involved-site RT and rituximab era.

S3463 Primary Intestinal Follicular Lymphoma

Introduction: Follicular Lymphoma (FL) mostly presents as a nodal lymphoma, however primary extranodal involvement is rare. The gastrointestinal tract is the most common site of extranodal FL, and with rates of FL increasing it remains important to recognize the characteristic endoscopic features of the disease. It typically carries an indolent course that may not even require treatment. We present a case of primary intestinal FL that involved the entire small intestine. Case Description/Methods: A 53-year-old Hispanic male with a history of gastrointestinal reflux disease (GERD), presented with refractory GERD symptoms despite maximal PPI therapy. An upper endoscopy was performed and revealed an irregular Z line, gastritis and numerous, patchy, small (< 1cm), white nodules in the second and third portion of the duodenum. Multiple biopsies were taken from the nodules. Pathology revealed Grade I-II FL. Capsule endoscopy was performed and revealed numerous similar lesions throughout the entire small intestine. He was referred to Oncology and underwent PET-CT scan which revealed multiple FDG-avid abdominopelvic lymph nodes. After discussion with Oncology, the patient elected for a watch and wait approach. Repeat PET-CT scan 6 months later revealed multiple abdominopelvic lymph nodes that are no longer FDG-avid. He remains asymptomatic and will be monitored closely off therapy. (Figure) Discussion: The most common primary intestinal lymphomas are diffuse large B-cell lymphoma (DLBCL) and mucosa associated lymphoid tissue (MALT) Lymphoma. FL only comprises approximately 1-2% of primary intestinal lymphomas. The small intestine is the most common location, with the second portion of the duodenum as the most likely site of involvement. It is rarely seen in the colon and stomach and there are no reported cases of esophageal involvement. Rates of diagnosis are on the rise, thus highlighting the importance of endoscopic recognition as it may often be seen in the second portion of the duodenum on routine upper endoscopy. Given the indolent course of FL, a watch and wait approach may be reasonable. Other options for therapy include chemotherapy, Rituximab, or radiation.Figure 1.: White nodular mass in duodenum visualized on capsule endoscopy consistent with patient's known diagnosis of Follicular Lymphoma.

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

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

Validation of FLIPI1, FLIPI2, PRIMA and POD24 in Patients with Extranodal Follicular Lymphoma: A Cohort from Two Cancer Centers in Peru

BackgroundFollicular lymphoma (FL) is the second most common non-Hodgkin lymphoma subtype, being nodal involvement its main characteristic. However, data about Extranodal (EN) involvement is not reported in Latin American patients. Our aim was to evaluate the clinical features, treatment patterns outcomes of Peruvian patients with ENFL from two cancer centers and validate FLIPI1, FLIPI2, PRIMA and POD-24 prognostic index in our cohort.Methods:This is a retrospective study, including all patients with a pathological diagnosis of FL grade 1 to 3A treated at the National Institute of Neoplastic Diseases and Oncosalud, both in Lima, Peru from 2010 to 2019. All cases were reviewed by specialized pathologists. Baseline clinical and pathological data were collected. Responses were assessed based on the Lugano criteria. Overall survival (OS) was estimated using the Kaplan-Meier method. Differences were compared with the log-rank test.ResultsA total of 86 patients were evaluated. The median age was 61 years (30-91), 43% were male, 20% had bulky disease (≥6 cm in diameter), 51% had stage III/IV disease, 31% had hemoglobin <12 g/dl, 11% had serum albumin <3 g/dl, 25% had elevated serum LDH, 31% had B2-microglobulin ≥3,5 mg/l, 27% had bone marrow involvement and 19% had lymph node sites >4. The most frequent EN sites were gastrointestinal, bone marrow, cutaneous and breast with 22%, 21% and 9%, and 6%% respectively. Low, intermediate and high-risk FLIPI1 was seen in 56%, 23% and 21% of patients, respectively. Low, intermediate and high-risk FLIPI2 was seen in 28%, 58% and 14% of patients, respectively. Low, intermediate, and high PRIMA was seen in 57%, 10% and 33%, respectively. 55 patients (64%) received any treatment, 47% received CHOP ± rituximab (R), 16% CVP ± R, 22% radiotherapy alone, 9% CHOP, 15% other treatments. Response data were available in 44 patients with complete response in 45%, partial response in 43% and no response in 12%, for an overall response rate of 88%. From patients who received CHOP/CVP ± R, 13% patients had disease progression within 24 months of first treatment initiation (POD24). For the entire cohort (N=88) the median follow-up time was 2.1 years (interquartile range [IQR] 0.08-11.3), median overall survival was 8.25 years (IQR 4.4-not reached [NR]). 5y OS was71.7% (95% CI 55.3-82.9), figure 1. For the FLIPI group 5y OS for low, intermediate and high FLIPI were 86.9% (95% CI 64.7-95.6), 60.1% (95% CI 24.4-83.2) and 75.7% (95% CI 30.4-93.7), respectively (p=0.07; Figure 2). For the FLIPI2 group (N=58) 5y OS for low, intermediate and high FLIPI2 were 79.5% (95% CI 39.3-94.5), 77% (95% CI 55.3-89.2) and 86% (95% CI 33.4-97.8), respectively (p=0.86). For the PRIMA group (N=38) 5y OS for low, intermediate and high PRIMA was 86% (95%55.6-96.6), 100% (95% CI 100), and 80% (95% CI 42-95), respectively (p=0.80). Patients who had and did not have POD24 had median OS of NR (IQR 0.6-NR) and NR (IQR 2.69-NR), respectively. 5y OS for patients who had and did not have POD24 was 71.2 % (95% CI 48-85) and 75% (12.7-96), respectively (p<0.87).Conclusion:Peruvian patients with ENFL showed a higher rate of female patients. Gastrointestinal involvement was the most common primary site. The OS rates is similar to our nodal involvement cohort. Chemoimmunotherapy is the standard approach to FL patients, which is associated with high rates of overall response. In our study FLIPI, FLIPI2, PRIMA and POD24 were not predictors for OS, but larger cohorts and longer follow-up are needed to find more accurate predictors of survival in these patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Primary Extranodal Follicular T-Cell Lymphoma and Ductal Breast Carcinoma Diagnosed by a Magnetic Resonance Imaging-Guided Vacuum-Assisted Biopsy: A Case Report

Patient: Female, 62-year-oldFinal Diagnosis: Primary non-Hodgkin lymphoma and ductal carcinoma in-situSymptoms: No specific symptomsMedication:—Clinical Procedure: —Specialty: RadiologyObjective:Rare co-existance of disease or pathologyBackground:Extranodal non-Hodgkin’s lymphomas (NHLs) are most commonly low-grade B-cell lymphomas, and the breast is not an usual site for this condition. This case report describes a 62-year-old woman with a primary NHL and ductal carcinoma in situ (DCIS) of the left breast diagnosed by a magnetic resonance imaging (MRI)-guided vacuum-assisted breast biopsy. The simultaneous diagnosis of breast cancer and NHL is rare, with few cases described in the literature. Primary breast lymphomas account only for 0.04% to 0.5% of breast malignancies.Case Report:In November 2016, a 62-year-old woman was treated for a peripheral T-cell lymphoma (follicular helper T-cell phenotype) of the left upper central breast; later she underwent periodic breast imaging follow-ups. In October 2018, MRI revealed a focal 33-mm non-mass contrast enhancement (according to the Breast Imaging Reporting and Data System –MRI lexicon of the American College of Radiology) in the lower external quadrant of the left breast. Neither mammography nor ultrasonography demonstrated any suspicious features. The multidisciplinary medical team performed an MRI-guided vacuum-assisted breast biopsy and the histological analysis confirmed the diagnosis of a DCIS. Subsequently, she underwent surgery resulting in eradication of the disease and has had regular follow-ups, including mammography, ultrasonography, and MRI.Conclusions:This is a rare case of both a primary NHL of the breast and DCIS, which was detected only by MRI. It highlights the role of an MRI-guided vacuum-assisted breast biopsy, which allows an accurate and economic diagnosis in case of suspicious findings on MRI. We recommend the use of MRI in follow-ups for patients with previous breast lymphomas (high-risk patients).

Thyroid Lymphoma: A Rare Cause of Thyroid Malignancy

Background: Primary Thyroid Lymphoma is rare accounting for 2-5% of all thyroid malignancies and less than 2% of extranodal lymphomas. Data has suggested annual incidence to be 2 per 1 million. (1)Clinical Case: A 72-year-old female with coronary artery disease, hyperlipidemia and hypothyroidism was diagnosed with extranodal follicular cell lymphoma of the breast. FDG-PET showed evidence of diffuse avidity within her thyroid gland, with SUV of 13.8. She denied any drastic change in the size of her neck or any compressive symptoms. Thyroid ultrasound performed months before her diagnosis of lymphoma, showed a two-fold increase, most notable to the right lobe compared to prior imaging; her gland remained otherwise unchanged with heterogenous echotexture.Fine needle aspiration and flow cytometry were obtained on thyroid tissue that showed follicular cell lymphoma. She was started on single-therapy Rituxan regimen with oncology. Several months later appearance and examination of her neck had improved with decrease in size of thyroid gland.Repeat FDG-PET scans, with the most recent being 11 months after starting Rituxan therapy, showed reduction in the avidity within the thyroid gland and decreasing size; with SUV of 7.8.Repeat thyroid ultrasound continued to show heterogeneous echotexture with overall decrease in volume in gland size by nearly 50% within the right lobe and approximately 30% within the left lobe. Conclusion: Thyroid lymphoma should be suspected in a rapidly enlarging thyroid gland with or without pain or compressive symptoms. However, we propose that it should also be considered in the setting of FDG-PET avidity in thyroid tissue in setting of clinical suspicion.Diffuse FDG-PET scan avidity in the thyroid gland does not automatically equate to malignancy as prospective and retrospective information has shown that diffuse uptake can be seen incidentally, in cases of diffuse goiter, Graves disease or chronic lymphocytic thyroiditis and that the uptake has been seen to range between 5.6-16.8 SUV. (2) The American Thyroid Association 2015 thyroid cancer guidelines propose that if diffuse uptake is seen within the thyroid gland on PET imaging that thyroid ultrasound imaging and functional testing be undertaken. If imaging shows findings suggestive of only chronic lymphocytic thyroiditis (diffuse heterogeneous gland) that no further action is required. In this patient a different approach was taken with investigations pursued in the setting of enlarging thyroid gland on imaging and known extranodal lymphoma allowing for ultimate diagnosis.

Oncological outcome and recurrence pattern analysis after involved-field irradiation in combination with rituximab for early-stage nodal and extranodal follicular lymphoma

PurposeCombined radioimmunotherapy (RIT) in follicular lymphomas (FL) has shown promising treatment efficacy in the Mabthera® and Involved field Radiation (MIR) study. Aim of this study was to analyze treatment efficacy and recurrence patterns after RIT in early-stage nodal and extranodal FL.MethodsWe reviewed 107 patients who were treated with combined RIT in two centers. Treatment consisted of 4 × rituximab followed by RIT with 4 × rituximab and involved field (IF) radiotherapy with 30/40 Gy. Median follow-up period was 71 months. In contrast to the MIR study, extranodal involvement and grade 3A histology were included in the analysis.ResultsExtranodal involvement and grade 3A histology were present in 21.8% and 13.1%, respectively. Overall response rate (ORR) after 4 × rituximab, after completion of RIT, and after 6 months was 78.1%, 98.8%, and 98.8%, respectively, with increasing rates of complete remissions (CR). Predictive factors associated with superior PFS were tumor size, completely excised lymphomas, and response to first 4 × rituximab. 5‑year PFS rate was 87.3%, with mostly outfield recurrences (94.1%). Second-line treatment was effective, with 53.3% CR and 46.7% partial remissions (PR). 5‑year OS was 98.1%. RIT was tolerated well, with mainly grade 1–2 acute side effects.ConclusionThe real-world efficacy of RIT is comparable with the results of the MIR study. Additionally, this analysis shows that extranodal involvement and grade 3A histology are not associated with inferior PFS.

1584 A Rare Case of Follicular Lymphoma of Sigmoid Colon

INTRODUCTION: Follicular lymphoma is defined as a neoplasm of follicle B cells and is characterized immunohistochemically by a positive reaction to B-cell markers and Bcl-2. Follicular lymphomas of the colon are very rare. Within GI Lymphomas, colorectal lymphomas are very uncommon and account for only 3% of GI lymphomas and 0.3% of large intestinal malignancies. We describe an unusual presentation of extra-nodal follicular lymphoma within the sigmoid colon. CASE DESCRIPTION/METHODS: A 59-year-old Caucasian female with history of hypertension was referred by her primary care physician for an average risk screening colonoscopy. Prior to referral for screening colonoscopy, the patient was being screened for colon cancer with annual occult stool testing which had been negative. She underwent a colonoscopy which showed a sessile polyp in the hepatic flexure and two polypoid lesions in the sigmoid colon (Figure 1). The patient was referred for endoscopic mucosal resection of the polyps. A snare mucosal resection was performed for the hepatic flexure polyp (12 mm in size). The 2 sessile polyps in the sigmoid colon (8-12 mm in size) were also resected with a hot snare. Pathology from the sigmoid colon polyp was consistent with Grade IIIA Follicular Lymphoma and immunohistochemistry was positive for CD20, CD10, BCL6 and BCL2 (Figure 2). The polyp in the hepatic flexure was noted to be a benign sessile serrated polyp. Patient was referred to Oncology for further management. A bone marrow biopsy and PET/CT did not show any evidence of disease involvement elsewhere. DISCUSSION: Primary NHLs of the GI tract are rare, accounting for only 1 to 4 percent of malignancies arising in the stomach, small intestine, or colon. Colonoscopy with biopsy is the principal diagnostic modality. Colonoscopic findings of follicular lymphomas include mucosal ulcerations, diffuse mucosal nodularity or polypoid mass like lesions. However, due to its rarity, an optimal diagnostic work up and treatment plan has not been well established. Making a correct diagnosis of the disease based on findings of biopsied samples can be challenging and multiple biopsies or endoscopic mucosal resection may be required in addition to appropriate consultation with pathologists.

Early Stage Extranodal Follicular Lymphoma: Characteristics, Management, and Outcomes

IntroductionExtranodal follicular lymphoma (E-FL) is a rare entity that has distinct characteristics and outcomes compared with nodal follicular lymphoma. Patients and MethodsThis cohort comprised 37 patients with stages I/II E-FL, diagnosed from 2003 to 2013. Outcomes included progression-free survival (PFS), and overall survival (OS). Survival outcomes were calculated using Kaplan–Meier methods. ResultsMedian age was 60 years (range, 37-84 years). Disease was stage I in 29 (78.4%). The Follicular Lymphoma International Prognostic Index score was 0 to 1 in 31 (83.8%), 2 in 2 (5.4%), 3 in 1 (2.7%), and missing in 3 (8.1%). Sites of involvement included the gastrointestinal (GI) tract in 22 (59.5%), and non-GI sites in 15 (40.5%). Initial management consisted of chemotherapy (CHT) alone in 21 (56.8%), radiation therapy (RT) alone in 2 patients (5.4%), RT and rituximab in 1 (2.7%), CHT and RT in 7 (18.9%), and observation in 6 (16.2%). RT was to a median dose of 30.6 Gy (range, 23.4-44.0 Gy). At a median follow-up of 69 months (range, 8-157 months), 5-year PFS and OS were 70.4% and 94.4%, respectively. Although the 5-year PFS of those observed was worse than for those who received therapy (33.3% vs. 77.6%; P = .011), that did not translate into an OS difference. Patients who received RT as part of upfront management had a 100% local control (LC) rate and a trend toward improved 5-year PFS (90% vs. 62.2%; P = .067). ConclusionEarly stage E-FL is an indolent disease and is associated with excellent OS. Treatment strategies should be individualized with RT prioritized when LC is a significant goal.

Pediatric follicular lymphoma of the parotid gland.

Primary malignant lymphoma rarely presents as a mass in the salivary gland. It accounts for about 1% of salivary gland tumors. The lymphomas of the parotid gland are mainly non-Hodgkin’s lymphoma of B-cell follicular type. It usually occurs in male adults and is very rare in children. In contrast to the intractable disease course of adult parotid follicular lymphoma, when occurred in children or adolescent, its prognosis is very good when it is first treated with surgical excision. Thus, a solitary follicular lymphoma in an extranodal site that has occurred in children is termed separately as pediatric follicular lymphoma (PFL). We share our treatment experience of a 16-year-old PFL patient through surgical removal combined with superficial parotidectomy. In line with the few previous case reports of PFL, we suggest that active surgical removal should be undertaken for solitary, extranodal follicular lymphoma of the pediatric and adolescent population.

Gastrointestinal follicular lymphoma: Current knowledge and future challenges.

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.

Primary Extranodal Follicular Lymphoma: Characteristics, Management, and Outcomes

Primary Extranodal Follicular Lymphoma: Characteristics, Management, and Outcomes

Difference of Relapse Pattern Between Nodal and Gastrointestinal Follicular Lymphomas

The characteristics and treatment result of localized nodal follicular lymphoma (FL) is relatively well recognized, while those of extranodal follicular lymphomas have not been fully elucidated. The purpose of this study is to compare the relapse patterns between patients with localized nodal FL and extranodal FL, focusing on gastro-intestinal (GI) FL, treated with radiation therapy (RT) in modern era. We reviewed consecutive 70 patients with early stage FLs treated by RT with/without pharmaceutical therapy between 2005 and 2015 at single institution. All patients were histologically proven with low grade FL by expert hemato-pathologists. Information of patient characteristics, detailed RT, toxicities, relapses and salvages treatment, and outcomes were collected with chart review. The characteristics of all patients were following; median age 60 years (range, 33-79 years old), male/female: 32/38, clinical stage I: 50 II: 20, nodal 36 and extranodal 34 (Gastro-Intestinal tract 30, H&N 4). As an initial treatment, 65 patients with grade 1/2 FL were treated with radiation therapy alone and 5 patients with grade 3a FL + high tumor burden were treated with RC(H)OP+IFRT. The median radiation dose was 30.6 Gy (range, 24-40). The IFRT was delivered to the patients with nodal FL and ISRT was delivered to the patients with extranodal FL. The median follow-up time was 53 months (range 14-132). None of all patients died with FL, 2 died of other disorder, and 54 patients are alive without any evidence of relapse. The local control was achieved in 69/70 patients. One patient developed local gastric relapse. Of 36 nodal FL, 8 (22%) patients developed relapses (all of 8 relapse were systemic), while 34 extranodal FL, 6 (11%) patients developed relapse. Of extranodal FL, all relapse were patients with GI-FL, only 1 (4%) systemic relapse was recorded, and the other 5 cases were classified into local or regional relapse. The 5 loco-regional relapse sites were recognized as the organs presenting the homing receptor of GI-FL. No toxicities greater than grade 2 were observed during treatment and over follow-up time. The RT for localized follicular lymphomas provides excellent local control with low toxicities. The extranodal FL patient, especially GI-FL, has significantly lower incidence of systemic relapse than nodal FL. The RT plays more important role on the management of GI-FL than nodal FL, because of the relapse of GI-FL were few but limited within the homing sites.

Primary duodenal follicular lymphoma: a case report

<h3>Background</h3> Follicular lymphoma (FL) is a predominantly nodal disease and extranodal involvement can be seen in widespread nodal disease. Primary extra-nodal FLs are, however, reported in skin, ocular adenexa, Waldeyer's ring and intestine where the majority are mucosa-associated-lymphoid-tissue (MALT) lymphoma and diffuse large B-cell lymphoma. Primary duodenal follicular lymphoma (FL-D) is a distinct mucosal/submucosal variant of FL. <h3>Case presentation</h3> A 44-year-old man presented with vomiting and subsequent endoscopic examination revealed small bubbly appearances in the first part of the duodenum. Three superficial duodenal mucosal biopsies showed preservation of the normal villous architecture; however, there was a prominent lymphoid infiltrate with prominent follicle formation within the lamina propria of the villi. Whilst CD3/CD5 positive T lymphocytes were present, the majority of the lymphoid cells, and the lymphoid cells forming the lymphoid follicles were positive for CD20, bcl2, bcl6 and CD10 and negative for cyclinD1; CD21 highlighted the follicular dendritic networks. Only very occasional centroblasts were noted within the lymphoid follicles, consistent with Grade-1 FL. <h3>Disscussion</h3> FL-D, first described in 1997, is a rare disease accounting for 1–3.6% of primary GIT lymphomas. FL-Ds are typically low grade. Transformation to high grade disease or systemic dissemination appears extremely uncommon.

Littoral Cell Angiomatosis: Splenic Lesions in a Patient with Follicular Non Hodgkin Lymphoma

A 67 year old patient was diagnosed with grade I extranodal follicular lymphoma of the parotid gland. She suffered from a painless swelling of the right parotid gland. No other symptoms, especially no B-symptoms were present on admission. The physical examination as well as the laboratory study was all normal. Histological, immunhistochemical and molecular genetic workup of the parotid gland showed an infiltration by a population of small CD20and CD10-positive clonal B-cells, consistent with an extranodal follicular Non Hodgkin Lymphoma (FL), grade I. The staging examinations (CAT scan, bone marrow trephine) showed no further lymphoma involvement apart from multiple hypoattenuating lesions in the spleen suspicious of a splenic infiltration of the lymphoma (Figure 1, white arrow). Since the treatment approach for a limited stage IEA (FLIPI 1) FL is curative, whereas a more extensive Ann Arbor stage [1] IIIEA (FLIPI 2) with spleen involvement is palliative, splenectomy was performed to define the exact stage of the disease. The histological workup showed multiple anastomosing neovascular channels lined by cells which have endothelial and histocytic (CD 68) properties, indicative of a littoral cell angioma (LCA) of the spleen (Figure 2 white arrow) beneath physiological lymphoid follicles (Figure 2, black arrow). The LCA is a rare splenic vascular tumor that derives from littoral cells which cover the splenic sinus channels of the red pulp. It was first described in 1991, normally shows a benign behavior and can be associated with solid and haematological neoplasias. Characteristic, but not specific CAT-findings are multiple defects in the spleen with low contrast. To exclude malignant primary splenic entities such as an angiosarcoma, splenic metastases, or, as suspected here, a lymphoma infiltration, a splenectomy is advisable in most cases [2]. In our patient, a splenic involvement of the spleen could be ruled out, and she underwent an involved field radiation and is still in remission 5 years later.

Extranodal follicular lymphoma in the lung of a free-ranging red deer (Cervus elaphus)

A hunted free-ranging female red deer (Cervus elaphus) from a region near the Nahuel Huapi National Park, Northern Patagonia, Argentina, had a focally extensive peribronchial lymphoid proliferative lesion in the lung characterized by formation of multiple follicles, with prominent germinal centers lacking mantle zone cells and antigen-related polarity. On examination of immunohistochemically stained tissues, a predominance of B cells (cluster of differentiation [CD]20 positive) with only a few scattered T cells (CD3 positive) were present. The histologic and immunohistochemical characteristics are consistent with follicular lymphoma, which is frequently seen in human beings and less frequently in domestic animals.

Initial features and outcome of cutaneous and non‐cutaneous primary extranodal follicular lymphoma

Follicular lymphoma (FL), a typically nodal disease, can arise in extranodal sites in about 10% of cases. The present study aimed to analyse the main differential features of patients with primary extranodal FL. Thirty-nine patients with primary extranodal FL were identified from a series of 354 patients with FL diagnosed at a single institution and their main clinicobiological features were analysed. Twenty patients (5·6%) had a primary extranodal non-cutaneous FL, and 19 (5·4%) a cutaneous FL. BCL2(+) and CD10(+) expression and BCL2/IGHJ@ rearrangement were less frequently observed in cutaneous FL. Absence of 'B'-symptoms, early stage, absence of bone marrow involvement and low-risk Follicular Lymphoma International Prognostic Index (FLIPI) were more frequent in extranodal FL. Five-year overall survival (OS) was 100%, 83% and 78% for cutaneous, non-cutaneous and nodal FL, respectively. When stage I patients were analysed separately, no differences were seen in terms of OS. In multivariate analysis, FLIPI was the most important variable to predict outcome. In conclusion, extranodal FLs, particularly cutaneous, have particular clinico-biological features, which differentiate them from nodal cases. Nevertheless, primary site of the disease is not the main issue to predict outcome.