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.