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Revista colombiana de Gastroenterología

Print version ISSN 0120-9957On-line version ISSN 2500-7440

Rev. colomb. Gastroenterol. vol.36 no.4 Bogotá Oct./Dec. 2021  Epub Apr 26, 2022

https://doi.org/10.22516/25007440.695 

Case report

Primary duodenal follicular lymphoma: Case report and literature review

Lázaro Antonio Arango-Molano,1 
http://orcid.org/0000-0001-5197-2326

Andrés Sánchez-Gil,2 
http://orcid.org/0000-0002-1159-5316

Ileana Rocío Bautista-Parada.3  * 
http://orcid.org/0000-0001-5785-4494

1Specialist in General Surgery, Clinical-Surgical Gastroenterologist. Clinical-Surgical Gastroenterology Program Coordinator, Universidad de Caldas. President of Asociación Colombiana para el Estudio del Dolor (ACED), 2020-2022. Manizales, Colombia.

2Specialist in General Surgery, Clinical-Surgical Gastroenterologist. Universidad de Caldas. Manizales, Colombia.

33 Specialist in General Surgery, resident of clinical-surgical gastroenterology, Universidad de Caldas. Manizales, Colombia.


Abstract

Primary gastric lymphomas are rare diseases; however, they are the most common extranodal presentation of non-Hodgkin lymphomas. 30% of non-Hodgkin lymphomas correspond to follicular lymphomas and at the same time, nearly 10% of follicular lymphomas are produced in the gastrointestinal tract. Risk factors for gastric lymphomas such as Helicobacter pylori infection, immunosuppression after solid organ transplantation, inflammatory bowel disease, and human immunodeficiency virus (HIV) infection were described. Follicular duodenal lymphoma was recognized as a variant of follicular lymphoma in 2016 according to the World Health Organization (WHO) classification, considering that it is a condition with special biological and clinical characteristics. Its diagnosis is usually incidental or mild and nonspecific symptoms may occur. The histological grade is usually low, and the clinical course is benign; Therefore, in most cases, expectant treatment has been adopted as an option. Other therapies with similar effectiveness are radiotherapy, the use of rituximab, and immunochemotherapy. There is not enough evidence to date to generate a single management protocol for this pathology.

Keywords: Folicular lymphoma; Duodenal lymphoma; Extraganglionar non-Hodgkin’s lymphoma

Resumen

Los linfomas primarios del tracto gastrointestinal son infrecuentes; sin embargo, son la presentación extranodal más común de los linfomas no Hodgkin. El 30 % de los linfomas no Hodgkin corresponde a linfomas foliculares y, a su vez, cerca del 10 % de los linfomas foliculares se origina en el tracto gastrointestinal. Se han descrito factores de riesgo para el desarrollo de linfomas gastrointestinales como infección por Helicobacter pylori, inmunosupresión posterior a trasplante de órganos sólidos, enfermedad inflamatoria intestinal e infección por virus de la inmunodeficiencia humana (VIH). El linfoma duodenal folicular se reconoció como una variante del linfoma folicular en 2016 según la clasificación de la Organización Mundial de la Salud (OMS), al considerar que se trata de una condición con características biológicas y clínicas particulares. Su diagnóstico suele ser incidental o se pueden presentar síntomas leves e inespecíficos. El grado histológico suele ser bajo y el curso clínico, benigno; por lo que en gran parte de los casos se ha adoptado el manejo expectante como una opción. Otras terapias con similar efectividad son la radioterapia, el uso de rituximab y la inmunoquimioterapia. No existe a la fecha suficiente evidencia para generar un protocolo único de manejo para esta patología.

Palabras clave: Linfoma folicular; linfoma duodenal; linfoma no Hodgkin extraganglionar

Introduction

The gastrointestinal tract is an important component of the immune system and contains lymphoid tissue in varying amounts and types. The esophagus and stomach have little mucous lymphoid tissue, unlike the intestine, in which it is abundant, predominantly in the mucosa and submucosa. This tissue is known as mucosal-associated lymphoid tissue (MALT). The monoclonal proliferation of MALT in response to chronic antigenic stimulation or inflammation may lead to the development of various forms of gastrointestinal lymphoma1. Primary lymphomas of the gastrointestinal tract are rare; however, they correspond to the most common extranodal location in which non-Hodgkin lymphomas (NHL) develop, as they correspond to 30% of cases2,3.

Duodenal-type Follicular Lymphoma (DFL) is a rare variant of follicular lymphoma (FL), recently recognized as a subtype of the latter in the World Health Organization (WHO) classification due to its distinctive nature4.

Case presentation

A 42-year-old female patient with no medical history consulted in December 2013 for long-standing dyspeptic symptoms and an endoscopic study that reported chronic atrophic gastropathy, adenomatous-looking major papilla, and elevated lesion in the third portion of the duodenum. Endoscopic ultrasound(EUS) was performed, which revealed mucosal thickening in the third portion of the duodenum without compromising other layers; a biopsy was taken and the report suggested a lymphomatous process. The immunohistochemistry study confirmed FL grade 1, and the thoracoabdominal tomography performed at that time showed no nodal involvement.

The patient abandoned the controls and reconsulted in February 2020. A new esophagogastroduodenoscopy was performed, in which a normal duodenal bulb and the second portion of the duodenum with nodular, whitish, and friable mucosa were identified. Biopsies showed low-grade LF, and immunohistochemistry with negative MUM markers, kappa, lambda and CD3 positive in companion lymphocytes compatible with low-grade DFL (Figure 1). A control tomography scan was performed in which no nodal or other organ involvement was found. Currently, the patient is under management and follow-up by medical oncology.

Figure 1 Endoscopic findings: Granular-looking nodular lesions in the second portion of the duodenum. 

Discussion

FL is one of the most common low-grade B-cell lymphomas, accounting for 30% of all NHL in Western countries4. The gastrointestinal tract is the most frequent location of extranodal presentations, and about 10% of all LFs are of gastrointestinal origin5. Several risk factors for the development of gastrointestinal lymphomas have been identified, such as Helicobacter pylori infection, post-solid organ transplant immunosuppression, inflammatory bowel disease (IBD), and human immunodeficiency virus (HIV) infection3. The distinctive genetic alteration of LFs is the t (14; 18) (q32; q21) translocation of immunoglobulin (Ig) heavy chain genes. In addition, certain similarities have been described in the genetic profile with MALT lymphoma. These similarities are associated with antigenic stimulation in chronic inflammation. It is suspected that DFL may follow a course similar to MALT lymphoma, which originates from preexisting inflammation6.

The first case of DFL was reported in 1997, and gastrointestinal FL was historically established as a disease in the decade of 2000. As it was recognized as an entity, case series were reported and, as a result, it was established that primary follicular intestinal lymphoma corresponds to a variant of the classification of follicular lymphomas according to the WHO classification. Within this, duodenal lymphoma is also recognized as a specific entity, which has the characteristics of a low-grade localized FL, but is distinct from another gastrointestinal FL7. Duodenum (65%), ileum, and jejunum (20%) are the sites of the gastrointestinal tract most frequently affected by FL, although cases have also been reported in the colon, rectum, and stomach5.

DFL occurs predominantly in middle-aged adults with similar distribution between men and women8. Most patients are asymptomatic, therefore, the diagnosis is usually incidental, usually during an endoscopic study indicated for unrelated reasons. When present, clinical manifestations are generally upper gastrointestinal symptoms such as pain, abdominal discomfort, vomiting, and, less frequently, gastrointestinal bleeding7,9. Endoscopic findings are in most cases described as single or multiple nodular whitish lesions of granular appearance and not submucosal appearance; in other cases, they are referred to as small polypoid nodules between 1 and 5 mm. Less frequently, they present as erosions or ulcers; in this case, it is important to take samples from the surrounding area for greater diagnostic performance. Some authors have reported the identification of opaque whitish spots, enlarged villi, and a pattern of vascular dilation in the villi as characteristic findings of this pathology when using electronic staining. The whitish coloring of intestinal lesions is attributed to the infiltration of lymphomatous cells into villi8-10. Most cases are presented as localized pathology, but when the small intestine study is completed, up to 85% of patients with DFL have jejunal or ileal involvement9.

Histologically, the neoplastic follicles are similar to those identified in nodal disease, composed of a uniform population of centrocytes, usually with nuclear clefts and some centroblasts. The histological grade is defined according to the number of centroblasts per 40 high power fields (CAP): grade 1: 5 or less centroblasts per CAP, grade 2: 6-15 centroblasts per CAP, and grade 3: More than 15 centroblasts per CAP. Grade 3 is subdivided into 3a: Centrocytes still present and 3b: Centroblast sheets11,12. More than 95% of cases of DFL are grade 1 to 2 (low grade)4,7. A typical histological finding is the “duodenal pattern” in which follicular dendritic cells are located on the periphery of neoplastic follicles, unlike nodal disease, in which they form a dense mesh within follicles5.

Lymphomatous cells show an immunophenotype similar to that of low-grade nodal disease, with CD20 and CD10 antigens expression, and B-cell lymphoma type 2 (BCL-2) and type 6 (BCL-6); the Ki-67 proliferation rate is low. Unlike a systemic disease, DFL does not express activation-induced cytidine deaminase (AID) and expresses positivity for immunoglobulin A (IgA), BACH2 and CD27 antigen2,5,8.

Once histologic confirmation is present, the staging process includes a complete physical examination, neck and thoracoabdominal tomographic study, as well as blood chemistry studies (blood count, lactate dehydrogenase [LDH], kidney function, liver enzymes), and bone marrow aspiration. Positron emission tomography (PET scan) may be considered, especially if radiation therapy is considered appropriate and the double-balloon enteroscopy study is completed to evaluate the entire small intestine. Some criteria have been proposed to determine whether this is a primary gastrointestinal lymphoma: Absence of palpable adenomegaly, absence of mediastinal adenomegaly, normal differential leukocyte count, disease limited to the intestine and adjacent nodes, without liver or spleen involvement13,14.

Depending on the single or multiple involvements in the gastrointestinal tract, degree of intestinal wall infiltration, secondary lymph node involvement of adjacent or distant organs, the disease can be staged from I to IV (Lugano Classification)(Table 1)15.

Table 1 Lugano classification for extranodal lymphomas15  

Classification Features
Stage I Involvement of a single lymph organ
Stage IE Unique extra lymphatic involvement with the absence of nodal involvement
Stage II Involvement of two or more nodal zones on the same side of the diaphragm
Stage III Nodal involvement on both sides of the diaphragm
Stage IV Disseminated commitment

DFL is considered a painless condition with an excellent prognosis and average survival rates of more than 12 years. Taking into account the usually asymptomatic course of this condition and the low frequency of histological progression or transformation, on the one hand, expectant management has been proposed as a valid option for these patients, as it has been shown to be an equally effective strategy even with spontaneous remissions in some cases. Furthermore, patients treated with radiation therapy as initial therapy have been reported to have 10-year survival rates of up to 80%; therefore, this therapy may be curative in some cases, considering that relapse after this time is unlikely. When relapse occurs, survival decreases to 22% at 10 years. Adjuvant chemotherapy has not shown any additional benefit after radiation therapy8,16. Rituximab monotherapy (humanized monoclonal antibody anti-CD20) has been a treatment option in FL, and its effectiveness has been demonstrated with prolonged remissions, even relapses, or as a second line of treatment. Expectant management has also been compared with immunochemotherapy at follow-ups of up to 149 months, and similar results were found9. All of these could then be valid treatment strategies, although there is no consensus so far on the best management option for DFL.

Conclusions

DFL is a rare condition with particular clinical presentation and biological behavior. It has been recently recognized as a variant of FL according to the WHO classification. It is usually asymptomatic and rarely presents a histological transformation or progression to nodal disease. There is not enough evidence in the literature to establish a management protocol; However, taking into account its particular benign behavior, expectant management can be considered in most cases. Other therapeutic options that have proven highly effective include the use of radiation therapy, rituximab, and immunochemotherapy.

Referencias

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Citation: Arango-Molano LA, Sánchez-Gil A, Bautista-Parada IR. Primary duodenal follicular lymphoma: Case report and literature review. Rev Colomb Gastroenterol. 2021;36(4):525-528. https://doi.org/10.22516/25007440.695

Received: November 15, 2020; Accepted: January 20, 2021

*Correspondence: Ileana Rocío Bautista-Parada. ibautista4@hotmail.com

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