Keywords
non-Hodgkin’s lymphoma - extra nodal - cecum - BCLU
Introduction
Non-Hodgkin’s lymphomas (NHLs) commonly present as lymphadenopathy. About 85% of all
malignant lymphomas are NHLs. Burkitt’s lymphoma and lymphoblastic lymphoma occurs
in younger patients. One-third of NHLs involve the extra nodal sites.[1] Primary NHL accounts for 0.1 to 0.5% of all colorectal malignant disease and the
most common histological subtype occurring in the colorectal lymphoma is diffuse large
B-cell type with 47 to 81% of occurrence.[2]
Case History
A 28-year-old male presented with diarrhea and weight loss of 5 kg over a period of
6 months and frequent episodes of abdominal pain since 2 months. Clinical examination
was normal. Routine hematology and biochemistry was normal. Serology for HBV and HIV
was negative.
Colonoscopy showed small discrete ulcers measuring less than 1 cm in the cecum ([Fig. 1]) with mucosal thickening at the distal portion of the ascending colon. Contrast-enhanced
computed tomography (CECT) abdomen showed asymmetrical thickening (maximum 11 mm)
of the cecal wall with moderate thickening of ileocecal valve. Other organs were normal.
Fig. 1 Ulcers seen (arrows) in the cecum on colonoscopy.
Microscopy with routine showed ulcerated cecal mucosa with sub mucosa and muscularis
propria showing diffuse infiltration of monomorphic neoplastic lymphoid cells which
were large, round with vesicular nuclei, and prominent nucleoli ([Figs. 2]
[3]
[4]). Immunohistochemistry with specific markers, CD20/CD3/CD5 showed positive results
and CD10/TdT/cyclineD1 having negative results confirmed the diagnosis of B-cell lymphoma.
(NHL).The diagnosis according to World Health Organization (WHO) classification was
B-cell lymphoma, unclassified. (BCLU)
Fig. 2 Photomicrograph of colonic biopsy fragments showing nodular lymphoma aggregates in
mucosa (thin arrow) and beneath the muscularis mucosa (thick arrow).
Fig. 3 Photomicrograph showing extensive neoplastic lymphoid infiltrate in the mucosa and
disrupting the muscularis mucosa (arrow).
Fig. 4 Photomicrograph showing lymphoid aggregates in the mucosa and submucosa show a striking
predominance of CD20 positive B-cells admixed with scattered CD3 and CD5 positive
T-cells. The aggregates are negative for CD10, TdT, terminal deoxynucleotidyl transferase,
and Cyclin D1.
CD20 is the most widely used pan–B-cell marker and is expressed from the naı̈ve B-cell
until the final stages of B-cell development just prior to plasmacytic differentiation.
Positron emission tomography (PET) scan performed with 7.5 mCi of F-18 2-deoxyglucose
(FDG) showed circumferential thickening of cecum. FDG uptake was seen in multiple
mesenteric nodes measuring 1.5 × 1.2 cm, subcentric aortocaval node, mildly enhancing
mesenteric thickening along the SMV (superior mesenteric vein). The conclusion was
the patient has metabolically active cecal wall thickening consistent with histology
diagnosis of lymphoma. The presence of metabolically active mesenteric and aortocaval,
cervical nodes were noted ([Fig. 5]).
Fig. 5 PET scan showing metabolically active lesions (cecum and nodes). PET, positron emission
tomography.
The staging of the index case in our report of BCLU was T3N3M0B0 according to Paris
Staging system which is specifically meant for primary gastrointestinal (GI) lymphomas.
Discussion
NHLs are tumors originating from lymphoid tissues, mainly of lymph nodes. About 85%
of all malignant lymphomas are NHLs. These tumors may result from chromosomal translocations,
infections, environmental factors, immunodeficiency states, and chronic inflammation.[2] Colon is an uncommon site of involvement in NHL. The most common symptoms of colonic
lymphoma are abdominal pain and weight loss, with a palpable abdominal mass.[3] The standard criteria for the diagnosis of primary intestinal lymphoma were established
in 1961 by Dawson et al.[4]
In the Ann Arbor classification, no distinction is made between primary nodal and
primary extra nodal lymphomas, clearly because primary extra nodal involvement is
extremely rare in patients with Hodgkin’s disease, for whom this classification was
originally designed. Strict criteria were proposed in 1961 by Dawson et al in a study
on patients included only if superficial lymph nodes were not palpable at first examination,
absence of significant enlargement of mediastinal lymph nodes on chest X-ray, and
the normal white blood cell count. Furthermore, upon laparotomy, the bowel lesion
had to be shown to be dominant and only involvement of lymph nodes in the immediate
vicinity of the primary lesion was acceptable. The National Cancer Database report
on NHL (1997) from hospitals in the United States used the site of tumor as the only
criterion for primary nodal or extra nodal disease.[5]
Tumors were considered to be primary if (1) no palpable superficial lymphadenopathy
at the first examination; (2) no obvious enlargement of the mediastinal nodes on chest
X-ray; (3) normal white blood cell counts, total and differential, normal bone marrow;
(4) no focal lesions in the liver, spleen, and bone on single-photon emission computed
tomography (SPECT) scan and only lymph nodes obviously affected in the immediate neighborhood;
and (5) no FDG uptake in liver and spleen.
Krol et al[5] described three alternative definitions of primary nodal and extra nodal NHL, exploring
their effect on the percentage of the patients considered to have primary extra nodal
disease, their treatment outcome and survival in a population-based cohort of NHL
patients.
In the modern era, these criteria have been expanded to the newer diagnostic tools.
The most common histological subtype occurring in the colon and rectum is diffuse
large B-cell lymphoma with frequency ranging from 47 to 81% depending on the geographical
location.[6]
[7]
Most of T-cell lymphomas of the gut present usually as ulcers or strictures in the
endoscopic examinations, while primary B-cell lymphomas commonly present as exophytic
lesions.[8]
Staging of Lymphoma
Histology
The Ann Arbor staging system is suboptimal for documentation of the specific features
of primary lymphoma in the GI tract. Several modifications and alternatives have been
proposed like the modified An Arbor, Lugano, and Paris staging. Tumor nodes metastasis
(TNM) staging for tumors of epithelial origin has also been proposed as an alternative
in GI lymphoma to describe localized disease.
Primary intestinal lymphoma is mostly seen in the ileocecal region, probably due to
presence of high lymphoid tissue. Involvement of regional lymph nodes has a bad prognosis[2]
[9] Clinical diagnosis of GI tract lymphoma is very difficult and often needs surgical
specimen for histological diagnosis of NHL; B-cell or T-cell type. B-cell type has
better prognosis as compared with T-cell lymphoma.[10] Immunohistochemistry is a useful adjunct in subclassification of NHL pan–B-cell
markers such as CD20, CD19, CD22, CD45, and CD79a are generally expressed in BCLU.
CD10 is expressed in 30 to 60% of cases. CD10 is a marker for follicular center B-cell
differentiation. Seki et al reported that the presence of CD10 expression was associated
with improved survival in patients with BCLU; hence, CD10 expression may be useful
for determining the prognosis of BCLU.[11]
PET for Risk Stratification of Pretreatment
PET-CT was recommended in updated international guidelines for staging/restaging of
B-cell lymphoma (BCLU) and follicular lymphoma (FL).
Whole body FDG PET scan has a role in the initial evaluation of patients with NHL;
however, it is of more value in posttreatment scenario to differentiate between early
recurrences or residual disease and fibrosis or necrosis. According to current data,
BCLU intermediate between diffuse large B-cell lymphoma and Burkitt’s lymphoma represents
a highly aggressive type of lymphoma with dramatically bad response for chemotherapy.
Our patient had B-lymphoma spread beyond the regional nodes and required chemotherapy.
Conclusion
The diagnosis of primary colonic lymphoma is rarely made on colonoscopy as a first
line investigation but certainly provides tissue from the lesions for confirmation
by histopathological methods. The histological type is important, since BCLU is curable
with surgery and or chemotherapy. Thus lymphoma should be considered as a differential
diagnosis in patients presenting with colonic ulcers.
