Abstract
This report describes a 60-year-old man with concurrent gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) and classical Hodgkin lymphoma (CHL). Atypical, medium-sized, lymphoid cells proliferated in the mucosa to muscular layer of the stomach showing a lymphoepithelial lesion; admixed with Hodgkin/Reed-Sternberg (HRS) cells and an inflammatory cell background. MALT lymphoma cells expressed CD20, CD79a, PAX5, and BOB.1, and HRS cells expressed CD30, CD15, Epstein–Barr virus–encoded RNA, and EBV-latent membrane protein 1. Only CHL invaded into the regional lymph nodes. Two possibilities of transformation of MALT lymphoma into CHL and de novo CHL within MALT lymphoma are discussed.
Keywords
Introduction
In oriental countries, 60% of classical Hodgkin lymphoma (HL) is associated with Epstein–Barr virus (EBV), suggesting a role for the virus in the genesis of classical HL (CHL).1,2 Primary gastric HL is extremely rare. Only 7 cases of primary gastric HL have been reported between 1988 and 2007. 3 Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) type (MALT lymphoma) arises in a background of chronic Helicobacter-associated gastritis and is infrequently associated with EBV. 4
Transformation of low-grade lymphoma into a high-grade lymphoma is often described as a Richter’s transformation, a term that originally described the transformation of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) into more aggressive diffuse large B-cell lymphomas as an end-stage event. Careful studies of high-grade MALT lymphomas with widespread sampling have identified a component with low-grade MALT lymphomas in more than 25% of cases. 5 Transformation of MALT lymphoma into CHL is extremely rare.
The coexistence of 2 or more types of lymphoma in the same or different organs is referred to as a composite lymphoma. The histologic patterns are well defined and clearly demarcated, and may represent 2 or even 3 different types of non-HL (NHL) or a combination of HL with NHL. 6
We report a patient who suffered from a gastric tumor consisted of concurrent MALT lymphoma and CHL. CHL developed in MALT lymphoma and only CHL invaded into the regional lymph nodes. Hodgkin-Reed-Sternberg (HRS) cells expressed Epstein–Barr virus–encoded RNA (EBER), not MALT lymphoma.
Clinical Findings
A 60-year-old man suffered from hiccups in June 1996. His past history was type B chronic hepatitis. Endoscopic gastric biopsy showed low-grade MALT lymphoma. He was treated with antibiotics for Helicobacter pylori infection. Gastric biopsy done 4 times showed poor response of antibiotics and total gastrectomy was performed in March 1998. Bone marrow aspiration revealed no lymphoma invasion; however, its chromosome analysis showed 47,XY, +der(17) t(1;17)(q21;q25). He underwent 3 course of a combination chemotherapy with CHOP therapy: cyclophosphamide, doxorubicin (hydroxydaunomycin), vincristine sulfate (Oncovin), and predonisolone. He suffered from ileus many times since 2000. In August 2006, computed tomography showed systemic lymph node swellings, especially around the abdominal aortic and common iliac arteries and of the inguinal regions. In May 2007, he died of pneumonia, hepatic failure, and lymphoma recurrence. Autopsy was not performed.
Pathological Findings
The resected stomach measured 25 × 21 cm in size. A gastric tumor measured 18 × 14cm in size and was located in the fundus to antrum, especially in the posterior wall and lesser and larger curvature (Figure 1A). Multiple, 2 to 20 mm in diameter, lesions were observed in 64 specimens examined. Atypical, medium-sized, lymphoid cells proliferated in the mucosa, submucosa, and muscular layer of the stomach, showing a lymphoepithelial lesion (Figure 1B) and did not invade into the regional lymph nodes. They expressed CD20, CD79a, and not EBER. HRS cells, atypical large lymphocytes, and an inflammatory cell background were observed (blue circle area in Figure 1A) within MALT lymphoma (red circle area in Figure 1A) in 13 of 64 specimens, especially in the posterior wall of the stomach. HRS cells expressed CD30 (Figures 1B and 2B) and CD15 in a membrane pattern with prominent accentuation in the Golgi area of their cytoplasm, EBER in their nuclei (Figure 2D), and EBV-latent membrane protein (LMP)1 in their cytoplasm, and not BOB.1, Oct-2, and anaplastic lymphoma kinase (ALK)1. Less than half of HRS cells were weakly positive or positive for CD20 (L26) on their cytoplasmic membrane and the CD20 positive intensity was weaker than that of MALT lymphoma cells, reactive lymphocytes, and immunoblasts, scattered in the background. More than two thirds of them were negative and the remainder weakly positive for CD79a in their nuclear membrane and cytoplasm. MALT lymphoma cells, reactive lymphocytes, and immunoblasts scattered in the background were strongly positive for CD79a in their nuclear membrane and cytoplasm. HRS cells and variants involved into 8 of 32 regional lymph nodes examined (Figures 2A, 2C, 2E, and 2F). There were heterogeneous cellular infiltrates of reactive lymphocytes, plasma cells, neutrophils, histiocytes, macrophages, epithelioid cells, and foamy cells and the proliferation of vessels in the background. Therefore, we diagnosed the gastric tumor as concurrent gastric MALT lymphoma and CHL. Table 1 shows a summary of immunohistochemical findings of MALT lymphoma cells and HRS cells in the present case.
A gastric tumor was located in the fundus to antrum, especially in the posterior wall and lesser and larger curvature (A). Red circle area shows MALT lymphoma (extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue). Blue circle area shows Hodgkin lymphoma proliferated in MALT lymphoma. Hodgkin/Reed-Sternberg cells positive for CD30 were observed in close to a lymphoepithelial lesion of MALT lymphoma in the stomach (B, immunostain, 200×)
Hodgkin/Reed-Sternberg cells proliferated in the stomach (B, D) and regional lymph nodes (A, C, E, F). They were positive for CD30 (B), CD15 (C), and Epstein–Barr virus–encoded RNA (D, in situ hybridization) and weakly or ambiguous positive for CD20 (E) and CD79a (F). Reactive lymphocytes and immunoblasts were positive for CD20 (E) and CD79a (F). (A): Hemtoxylin–eosin stain. (B), (C), (E), and (F): immunostain 400×
Summary of Immunohistochemical Findings of MALT Lymphoma Cells and Hodgkin/Reed-Sternberg Cells in the Present Case
Abbreviations: MALT lymphoma, extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue; HRS, Hodgkin/Reed-Sternberg; EBER, Epstein–Barr virus–encoded RNA; EBV-LMP1, Epstein–Barr virus–latent membrane protein 1; EMA, epithelial membrane antigen; ALK1, anaplastic lymphoma kinase 1.
Discussion
Table 2 shows a summary of the 7 reported composite lymphoma cases composed of MALT lymphoma and CHL,7-13 including the present case. Similar to the present patient, 3 cases that with concurrent MALT lymphoma and CHL developed in the same extranodal organ have been reported.7-9 Aguilera et al 7 reported an intestinal lymphoma case. Zettl et al 8 reported a gastric lymphoma case (case 6 in their article). Harada et al 9 reported a splenic lymphoma case with CHL involvement in the liver and bone marrow later. Two lymphomas of the present case arose from the stomach synchronously. On the other hand, Fung et al 10 reported a laryngeal lymphoma with Hodgkin-like transformation of MALT lymphoma, and absence of the inflammatory cell background of CHL. Two cases that composite MALT lymphoma and HL that developed in different anatomic sites and at the different times have also been reported. Rosenquist et al 11 reported a case that developed nodal HL 15 years after the diagnosis of splenic MALT lymphoma. Shimizu et al 12 reported a patient who developed HL in the cervical lymph node after an 11-year remission of MALT lymphoma arising from the submandibular lymph node. We reported the remaining one (case 7 in Table 2): a composite pulmonary CHL and gastric MALT lymphoma developed at the same time. 13
Summary of Reported Composite Lymphoma Cases Composed of MALT Lymphoma and Classical Hodgkin Lymphoma
Abbreviations: MALT, extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue; CHL, classical Hodgkin lymphoma; EBV, Epstein–Barr virus; EBER, Epstein–Barr virus–encoded RNA; LMP, latent membrane protein; LN, lymph node; AF, atrial fibrillation; nd, not done.
In general, CHL is associated with EBV; on the other hand, MALT lymphoma is infrequently associated with EBV. When CHL and NHL are present in the same anatomic site, there is a higher correlation with the presence of EBV in both lymphoma cells than when 2 lymphomas occur at the different times and/or at the different sites. 9 If the 2 components demonstrate positivity for EBV, it had been suggested that a commonly infected progenitor cell might be responsible for both lymphomas. 14 In the present case, 2 lymphomas occurred at the same anatomic organ; however, HRS cells were positive for EBER and MALT lymphoma cells were negative. Ultimately, we could not determine the alternative of CHL transformation from MALT lymphoma or de novo CHL within MALT lymphoma.
Footnotes
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
The author(s) received no financial support for the research, authorship, and/or publication of this article.