Keywords
Esophageal neoplasm - lymphoma - non-Hodgkin's
Introduction
Non-Hodgkin's lymphoma (NHL) is most commonly a disease primarily involving lymph
nodes; however, it has a well-known tendency to involve extranodal organs as its primary
site. The gastrointestinal (GI) tract is the most common extranodal site of NHL, accounting
for 5%–20% of all cases,[1] with the stomach affected in approximately 50%, the small bowel or ileocecal valve
in approximately 33%, and the large bowel in approximately 10%. Esophageal lymphoma
accounts for <1% of all GI lymphomas and is usually secondary to local extension from
adjacent structures, such as mediastinal lymph nodes or from a gastric lymphoma. Primary
esophageal lymphoma in an immune competent patient is very rare.[2] In a study of 79 cases of isolated lymphomas of the GI tract in HIV-seronegative
patients, sites of involvement were the stomach (55%), small intestine (31%), large
intestine (11%), and esophagus (1%). Lymphomas account for <1% of all malignant tumors
of the esophagus.[3] We report a case of histopathologically confirmed primary esophageal NHL of diffuse
large B-cell type (DLBCL), describe its clinicoradiological features, and review the
literature.
Case Report
A 60-year-old man presented to us with recent onset progressive dysphagia for solids
over the past 6 months. There was no history suggestive of gastroesophageal reflux
or esophagitis before initiation of his present symptoms. His physical examination
was normal without enlarged lymph nodes or palpable hepatosplenomegaly. Routine hematological
and biochemical investigations were normal. Esophagogastroduodenoscopy showed a circumferential
ulceroproliferative friable tumor from 30 to 35 cm with luminal narrowing. The remaining
part of the esophagus, stomach, and duodenum were normal. The biopsy showed malignant
round cells arranged in a diffuse pattern, suggestive of a NHL [Figure 1]a and [Figure 1]b. This was further confirmed by immunohistochemistry which showed diffuse positivity
of tumor cells for leukocyte common antigen [Figure 1]c and CD20 [Figure 1]d and negativity for CD3 antigen. Mib-1/Ki-67 (proliferation marker) labeling index
highlighted 98% tumor cell nuclei. Cytokeratin, epithelial membrane antigen, and CD138
were negative. Positron emission tomography (PET) scan [Figure 2]a and [Figure 2]b revealed 18-F fluorodeoxyglucose-avid circumferential wall thickening
of the mid and lower third of the esophagus for a segment of 10 cm with hypermetabolic
pretracheal, precarinal, and bilateral hilar lymph nodes. A bone marrow biopsy was
done which did not show involvement by NHL. Based on a final diagnosis of isolated
esophageal NHL of DLBCL type, and the multidisciplinary tumor board decision, we treated
the patient with chemoradiation with six cycles of chemotherapy, including cyclophosphamide,
etoposide, vincristine, and prednisolone, along with involved field radiotherapy)
in view of the bulky primary disease. Posttreatment response assessment PET [Figure 2]c and [Figure 2]d revealed complete metabolic and morphological response of the primary and aortopulmonary
lymph nodes. Endoscopic mapping after completion of treatment showed only posttreatment
changes in the form of mucosal tags with scarring and pseudodiverticula. The patient
is symptom and disease free on a 3-year follow-up.
Figure 1: (a) Tumor underlying esophageal squamous mucosa.(b) Malignant tumor composed
of round cells arranged in a diffuse pattern. (c) Tumor cells diffusely expressing
leukocyte common antigen. (d) Diffuse CD20 positivity within tumor cells
Figure 2: Pre- and post treatment 18-F fluorodeoxyglucose positron emission tomography-contrast-enhanced
computed tomography study in a patient diagnosed of esophageal Non-Hodgkin’s Lymphoma.
Axial-fused positron emission tomography-computed tomography images show the bulky
18-F fluorodeoxyglucose avid esophageal mass (arrow in 2a) and aortopulmonary lymph
node (circle in 2b). Post treatment positron emission tomography-contrast-enhanced
computed tomography study showing complete metabolic and morphological response of
the circumferential thickening in the middle and lower third esophagus (arrow in 2c)
and also the aortopulmonary nodes (circle in 2d)
Discussion
Epithelial tumors, namely squamous cell carcinoma and adenocarcinoma, are the most
common types of esophageal cancer. Nonepithelial malignancies comprise only about
0.5% of all primary esophageal neoplasms. Primary lymphoma of the GI tract accounts
for about 5%–20% of all cases of lymphoma. Isolated NHL of the esophagus is an extremely
uncommon occurrence, accounting for <1% of patients with lymphoma and occurs more
often in the distal esophagus.[4] Furthermore, isolated primary lymphoma of the esophagus without an extraesophageal
location is extremely rare and only 20 such cases have been reported in literature
to date.[5],[6]
The etiology of the disease is unknown, with the role of Epstein–Barr virus being
controversial. It has been noticed that it is most common in immune compromised patients,
with HIV infection as a probable risk factor. Dysphagia is the most common symptom
at presentation with less common symptoms being odynophagia, fever, and weight loss.
The age at presentation of the disease is highly variable. Endoscopic and radiological
findings of esophageal lymphoma are nonspecific and nondiagnostic. The diverse spectrum
of endoscopic/radiological patterns that have been described for esophageal lymphoma
include stricture, ulcerated mass, multiple submucosal nodules, varicoid pattern,
achalasia-like pattern, progressive aneurysmal dilatation, and tracheoesophageal fistula
formation. Computed tomography (CT) scan is valuable for the evaluation of the extraluminal
component of an esophageal mass, its mediastinal extension, fistula formation, and
status of the lymph nodes; therefore, it has a role in disease staging, assisting
in stratification of various available treatments, evaluating treatment responses,
monitoring patient progress, as well as detection of any relapses. PET-CT scanning
has emerged as an indispensable tool in the staging and follow-up of patients with
extranodal involvement in lymphoma. PET-CT has also significantly increased the detection
of indolent lesions that were undetected by conventional cross-sectional imaging.[7]
Dawson's criteria [8] to identify primary GI lymphoma include nonpalpable superficial lymphadenopathy,
no splenic involvement, and no enlargement of mediastinal or hilar lymph nodes. Our
patient fit Dawson's criteria fully, except that he also had enlarged mediastinal
nodes. The application of Dawson's criteria for the diagnosis of primary GI lymphoma
may not hold true for the esophagus. Modifications as exclusion of mediastinal lymphadenopathy
in the criteria for primary esophageal lymphoma have been suggested, because the esophagus
is a mediastinal structure with an extensive lymphatic network which results in wide
lymph node basins. Therefore, based on the predominant lesion being in the esophagus
with no involvement of liver, spleen, and peripheral lymph nodes, we did not consider
the absence of mediastinal lymphadenopathy as strict criteria for a diagnosis of primary
esophageal lymphoma; the positive endoluminal biopsy in the absence of nodal disease
infiltrating the esophageal wall confirmed the primary origin in the esophagus.
Conclusion
Primary NHL of the esophagus is an extremely rare esophageal neoplasm. Imaging modalities
are nonspecific, thus posing a diagnostic dilemma. Endoscopic biopsy is the gold standard
to confirm the diagnosis. Accurate histopathological diagnosis supplemented with necessary
immunohistochemical stains helps in accurate diagnosis; complete staging work-up using
PET-CT scanning aids in treatment decision and prognostication. Appropriate chemotherapy
with radiotherapy may offer a significant chance of long-term survival.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms.
In the form the patient(s) has/have given his/her/their consent for his/her/their
images and other clinical information to be reported in the journal. The patients
understand that their names and initials will not be published and due efforts will
be made to conceal their identity, but anonymity cannot be guaranteed.
