Discussion
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL) and accounts for around 30%-40% of all NHL cases. It is a neoplasm of B lymphocytes and comprises a heterogeneous group of clinically and pathologically distinct entities that result in the proliferation of germinal or post-germinal malignant B cells. [1, 2] The neoplasm is typically composed of a diffuse infiltrate of large, transformed blasts that resemble germinal center centroblasts and/or immunoblasts. DLBCL usually develops de novo due to a variety of genetic alterations. The most common abnormality involves rearrangements and mutations of the BCL6 gene at the 3q27 locus. [3] In some cases, DLBCL may develop as a result of the transformation of other NHLs, such as chronic lymphocytic leukemia/small lymphocytic lymphoma. This is known as the Richter transformation. [4] Immunosuppression (for example, an acquired immunodeficiency syndrome (AIDS), autoimmune disorders, organ transplantation), pesticides, dyes, and ultraviolet radiation may also increase the risk of the development of DLBCL. [3]
DLBCL typically presents at an advanced stage and has a median age of 60 years. [5] It is an aggressive disease that typically presents with rapidly enlarging lymphadenopathy and constitutional symptoms, including fever, night sweats, and weight loss. However, extranodal involvement is common and may be seen in up to 50% of patients. The gastrointestinal (GI) tract is the most common extranodal site to be involved. [6] The majority of extranodal GI NHLs occur in the stomach, followed by the small bowel and colon. [7] In the small bowel, the ileum is most commonly affected (60%-65%); while the duodenum is an uncommon location for primary GI NHL (6%-8%). [8] Patients with small intestinal NHL may present with nonspecific symptoms, such as abdominal pain, diarrhea, gastrointestinal bleeding, and weight loss. [9]
Since the clinical features of small intestinal DLBCL are highly nonspecific, an endoscopy is usually performed to identify any suspicious lesions and to obtain biopsies. [10] The tumor may appear as a circumferential bulky mass in the intestinal wall and may ulcerate and perforate into the adjacent mesentery. [11] The diagnosis of DLBCL can be established based on an excisional lymph node biopsy or by analyzing samples obtained from an affected organ via an incisional biopsy. [12] Histology and immunophenotyping, as well as staining for B-cell markers, are required for diagnosis. Morphologically, DLBCL is characterized by sheets of atypical lymphoid cells with large nucleoli and abundant cytoplasm. The cells usually express pan-B cell antigens, such as CD19, CD20, CD22, CD45, and CD79a. The different genetic rearrangements in BCL6, BCL2, and/or c-MYC genes can be identified using fluorescence in situ hybridization (FISH). [13] Bone marrow cytogenetic studies can also be used to determine nonrandom chromosomal aberrations in patients with DLBCL and can assist in the prognostic stratification of this condition. For instance, total or partial trisomy 3 is a frequent chromosomal aberration observed in patients with diffuse large B cell lymphoma. Similarly, as was the case with our patient, loss of genetic material from the short arm of chromosome 17 may be seen in some patients with DLBCL and is considered to be an indicator of poor prognosis. This is because chromosome 17 contains the tumor suppressor gene TP53 (17p13). Inactivation of this gene leads to uncontrolled cell proliferation and has been associated with decreased overall survival and reduced progression-free survival in patients with DLBCL. [4] Once the diagnosis of DLBCL is established, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) can be used to stage the disease. [10]
Due to the low incidence of de novo duodenal DLBCL, there are no guidelines available for the treatment of small intestinal DLBCL and the optimal treatment remains unknown. Patients with advanced diseases require more aggressive treatment. Surgery is reserved for patients with complications such as small bowel perforation, small bowel obstruction, or intractable bleeding, for both limited-stage and advanced disease. Surgery followed by adjuvant chemotherapy was historically considered the preferred treatment modality. However, since the lymphomas are highly chemosensitive, surgical resection is now rarely used and is typically reserved for the management of complications, such as bowel perforation, small bowel obstruction, or severe bleeding. The most commonly used chemotherapy regimen is R-CHOP, which is a combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. [9, 10, 14] In patients with unfavorable prognostic factors, DA-EPOCH-R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) may also be a beneficial treatment option [10, 15]. Response to treatment is measured using data collected from the post-treatment history, physical, and imaging (PET/CT) scan results. After the chemotherapy is completed, restaging and evaluation of complete remission should be done. Patients should be followed up at periodic intervals to monitor for complications related to treatment and for assessment for possible relapse. [16]
Our patient who presented with dysphagia and melena had iron deficiency anemia, likely due to recurrent intestinal bleeding caused by duodenal DLBCL. The biopsy findings along with the FISH and cytogenetic results confirmed the diagnosis and the patient was started on systemic chemotherapy with R-CHOP. Despite having the poor prognostic indicator of chromosome 17 partial deletion, the patient responded well to this treatment regimen. This case report highlights the fact that small intestinal DLBCL is a rare yet aggressive disease that can present with nonspecific symptoms, which may hinder diagnosis and prompt treatment. However, timely initiation of chemotherapy can result in favorable patient outcomes. Therefore, available diagnostic modalities should be used for the early identification and initiation of appropriate treatment in these patients.