Mantle-Cell Lymphoma in Barrett Esophagus

Mantle-cell lymphoma (MCL), a distinct B-cell lymphoma subtype, affects mainly elderly men and is commonly characterized by early systemic dissemination, relatively aggressive clinical evolution, minimal response to conventional chemotherapeutic regimens, and poor prognosis.^1–3 Its pattern of extranodal involvement, especially of the liver, small bowel, and central nervous system, is rather unique and infrequent. This report describes a case of MCL initially manifesting in Barrett esophagus (BE), an association that heretofore has not been previously reported in the PubMed-indexed literature.¹

Case Report

A 66-year-old white man presented with sudden-onset gastrointestinal bleeding, vague abdominal discomfort, dizziness, and light-headedness. Bowel movement was regular and twice daily. Rectal examination showed occult blood-positive stool. The remainder of clinical history and physical findings were unremarkable, and laboratory data were within normal limits, except for hemoglobin, which measured 12.4 g/dL.

Esophagogastroduodenoscopy revealed a 1.5-cm duodenal ulcer, hiatal hernia, and irregular micronodular Z-line or squamocolumnar junction (Figure 1), suggesting short-segment BE. Four-quadrant biopsies of the distal esophagus were taken, and duodenal ulcer bleeding was controlled with an epinephrine injection.

Figure 1.

Distal esophagus that is irregular, focally micronodular, and suggestive of short-segment Barrett esophagus.

In the distal esophagus, squamous mucosa was replaced by cardiac-type glandular mucosa with fairly diffuse goblet cell change from BE (Figure 2). This is associated with diffuse lymphoid nodules, composed of a mixture of small to medium lymphoid cells (Figure 3). Proliferation centers were absent, and immunostain of the lymphoid cells tested positive for monoclonal B-cell markers including CD5 and cyclin D1 (BCL1).

Figure 2.

Squamous mucosa diffusely replaced by cardiac-type glandular tissue replete with goblet cell change, which is associated with separate small and large diffuse lymphoid nodules without germinal centers (Hematoxylin & eosin stain, 200x).

Figure 3.

Lymphoid nodules revealing diffuse mixed small and large lymphoid cells (Hematoxylin & eosin stain, 400x).

The diagnosis of diffuse MCL was supported by microscopic evaluation, immunohistochemistry, and flow cytometry analysis of small deep cervical lymph nodes that were excised and visualized on computed tomography scan. Flow cytometry analysis was similarly proved by the positive monoclonal B-cell markers CD5, cyclin D1, and surface kappa light-chain immunoglobulin. Bone marrow biopsy demonstrated scattered paratrabecular lymphomatous infiltration, and cytogenetic examination indicated an abnormal karyotype of 38–46,XY, t(11;14)(q13;q32), also affirming MCL.

Combined intravenous chemotherapeutic agents (vincristine, bleomycin, cyclophosphamide, and dexamethasone) failed to result in response. The patient was treated with supportive and symptomatic regimens and eventually lost to follow-up.

Discussion

MCL, also known as centrocytic lymphoma, comprises approximately 3–10% of non-Hodgkin lymphomas and is predominantly diagnosed as stage III or IV disease in men over the age of 60.^1–3

Common clinical manifestations of MCL include lymphadenopathy, bone marrow involvement (in two thirds of patients), leukemia (in 20–60% of cases at the time of diagnosis), and splenomegaly (50% of cases with prominent white pulp involvement). Less common extranodal presentations are periportal hepatic infiltration, central nervous system parenchyma lesions, and lymphomatoid polyposis of the small bowel (10%). MCL involves both the distal small intestine and colon. Involvement of the stomach and duodenum is also common. The tumor frequently manifests inside an isolated mass and/or a micronodular polypoid lesion. Mesenteric nodal infiltration is often present.^1–3

In a recent large series, MCL cases were classified into four types: classic MCL (87.5%), defined as monotonous small-to-medium cells with indented nuclei, scant cytoplasm, and moderately dispersed chromatin; small-cell MCL (3.6%), defined as small cells with round or slightly indented nuclei and dense chromatin, mimicking chronic lymphocytic leukemia/small lymphocytic lymphoma; pleomorphic MCL (5.9%), defined as medium to large cells with nuclei of different sizes and shapes and a moderate amount of cytoplasm, mimicking diffuse large B-cell lymphoma; and blastic MCL (2.6%), defined as monomorphic small to medium cells with dispersed chromatin, scant cytoplasm, and frequent apoptotic bodies, mimicking lymphoblastic lymphoma. Admixtures of these different cell types were also identified. There was no statistically significant difference in overall survival among the histologic groups, although the number of pleomorphic and blastic cases was small.¹

In 80.5% of cases, there was a diffuse growth pattern, whereas 19.5% of cases had a nodular or mantle zone pattern, which was associated with a slightly better prognosis (median overall survival 43 months for nodular or mantle zone pattern versus 29 months for diffuse pattern). A high proliferation rate by mitotic or Ki-67 indices was associated with shorter overall survival. Likewise, in a univariate analysis of all prognostic factors with respect to overall survival, Ki-67 and mitotic figures, growth pattern, age, bone marrow involvement, performance status, lactate dehydrogenase level, stage B symptoms, and extranodal involvement all resulted in significant differences in overall survival.¹

Malignancies arising in BE are usually either adenocarcinomas or squamous-cell carcinoma and, rarely, small-cell carcinoma. The relationship of MCL and BE is interpreted as coincidental, despite known occurrence of mucosa-associated lymphoid tissue (MALT) in BE. Even in the presence of concurrent esophageal and gastric Helicobacter pylori colonization, MALT lymphoma has not been reported in BE.³

Summary

A unique instance of MCL presenting in BE, heretofore not previously reported in the literature, has been briefly described. The initial diagnosis was indicated by positive immunostains with monoclonal B-cell markers including CD5 and cyclin D1 (BCL1) on lymphoid tissue nodules associated with intestinalized, cardiac-type, glandular mucosa obtained by endoscopic biopsy. The results were subsequently affirmed by flow cytometry analysis, repeated immunostains, and cytogenetic study of nonpalpable but radiologically imaged, deep cervical lymph nodes. The occurrence of MCL in BE is probably coincidental.