Japanese Journal of Clinical Oncology Advance Access originally published online on June 23, 2005
Japanese Journal of Clinical Oncology 2005 35(7):412-416; doi:10.1093/jjco/hyi105
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© 2005 Foundation for Promotion of Cancer Research
Case Report |
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue (MALT Lymphoma) in the Thymus: Report of Four Cases
1 Division of Thoracic Surgery, 2 Pathology Division and 3 Division of Oncology/Hematology, National Cancer Center Hospital East, Kashiwa, Chiba and 4 Pathology Division, Saitama General Medical Center Hospital, Kawagoe, Saitama, Japan
For reprints and all correspondence: Atsushi Ochiai, Pathology Division, National Cancer Center Research Institute East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan. E-mail: aochiai{at}east.ncc.go.jp
Received December 2, 2004; accepted March 8, 2005
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Abstract |
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 TOP Abstract INTRODUCTIONCASE REPORTDISCUSSIONReferences |
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Mucosa-associated lymphoid tissue (MALT) lymphoma in the thymus is extremely rare, and little is known about its clinicopathological features. In this study, we examined four cases of MALT lymphoma in the thymus at our institute in terms of clinicopathological features. Most patients had autoimmune disease or hyperglobulinemia, and they also had cysts in the tumors. Both elevated serum levels of autoantibodies and the polyclonal increase in serum Ig remained almost unchanged after total thymectomy in all patients. We recommend that MALT lymphoma in the thymus should be considered in the differential diagnosis when a cystic thymic mass is found and if the patient is Asian and/or has autoimmune disease or hyperglobulinemia.
Key Words: MALT lymphoma • thymus • autoimmune disease • hyperglobulinemia
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INTRODUCTION |
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TOPAbstractINTRODUCTIONCASE REPORTDISCUSSIONReferences |
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Mucosa-associated lymphoid tissue (MALT) lymphomas account for 7–8% of all B-cell lymphomas, and the gastrointestinal tract is the most common site, accounting for 50% of all cases. Other common sites include the lung (14%), head and neck (14%), ocular adnexae (12%), skin (11%), thyroid (4%) and breast (4%) (1). It is well known that Hodgkin's disease, lymphoblastic lymphoma and large cell lymphoma of B-cell origin arise in the thymus, but MALT lymphoma of the thymus is extremely rare (2).
Four cases of MALT lymphoma arising in the thymus were encountered at the National Cancer Center Hospitals East, and their clinicopathological and immunohistochemical features are reviewed in this report.
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CASE REPORT |
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TOPAbstractINTRODUCTIONCASE REPORTDISCUSSIONReferences |
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The clinical findings of these four patients are shown in Table 1. All patients were Japanese. Two (case 1 and case 2) of them were presented previously as case reports from our institute (3,4). Three patients were asymptomatic, and their tumors were detected incidentally on chest radiography at an annual health check-up or during follow-up study for other diseases. Case 1 had rheumatoid arthritis (RA). All patients underwent total thymectomy and received no additional therapy. To date, all patients are well without signs of recurrence.
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Laboratory findings before and after total thymectomy are shown in Table 2. Serum rheumatoid factor (RF) and antinuclear antibody (ANA) of the four patients were positive, except for RF in case 3 before thymectomy. The serum immunoglobulin G (IgG) level was elevated in three patients (cases 2, 3 and 4), and the serum immunoglobulin A (IgA) level was elevated in two patients (cases 2 and 3). The serum level of immunoglobulin M (IgM) was elevated in one patient (case 4). Anti-SS-A antibody was positive in three patients (cases 1, 2 and 4), and anti-SS-B antibody was positive in one patient (case 4). Interestingly, both elevated serum levels of autoantibodies and the polyclonal increase in serum Ig remained almost unchanged after total thymectomy in all patients. In case 2, serum Ig levels and serum autoantibodies remained elevated 3 years after thymectomy. Despite these immunological abnormalities, all the patients except the one with RA presented no symptoms relevant to autoimmune diseases, such as dry eyes and dry mouth. We did not perform further examination for autoimmune diseases in these cases.
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Computed tomography (CT) and magnetic resonance imaging (MRI) of the chest showed a cystic thymic mass in all three of our cases with macroscopic cysts. At MRI, all their cysts were of increased signal intensity compared with cerebrospinal fluid (CSF) on T1-weighted images and of markedly increased signal intensity (similar to that of CSF) on T2-weighted images (Fig. 1A and B).
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All tumors were confined to the thymus, and their greatest dimension ranged from 7.5 to 12.5 cm. The resected thymuses weighed from 50 to 270 g. Cross-sections revealed a solid tumor with gray-white to light tan cut surfaces. Three tumors exhibited a lobular structure and multiple macroscopic cysts (Fig. 1A and B).
Histologically, all tumors were separated from the thymic fatty tissue by a thin fibrous capsule. Multiple cysts and reactive lymph follicles with active germinal centers were scattered within the tumor (Fig. 2A). Multiple cysts whose walls were lined by flat epithelial cells were observed. Morphologically, the cysts were distinct from the perivascular space, which is characteristic of thymoma. Epithelium-lined macro/microscopic cysts were recognized in three patients (cases 2, 3 and 4), but only microscopic cysts were observed in case 1. All the tumors consisted mainly of dense centrocyte-like (CCL) cells and formed lobular structures (Fig. 2B). CCL cells had invaded the epithelium of the cyst wall (Fig. 2C) and Hassall's corpuscles (Fig. 2D), forming lymphoepithelial lesions (LELs).
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All samples were analyzed for expression of the API2–MALT1 chimeric transcipts by the multiple reverse transcription–polymerase chain reaction (RT–PCR) method described previously (5). Case 2 showed no ß-actin RT–PCR product, so we could not analyze the transcipts. The API2–MALT1 chimeric transcipts were not detected in the other three cases (Table 1).
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DISCUSSION |
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TOPAbstractINTRODUCTIONCASE REPORTDISCUSSIONReferences |
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MALT lymphoma of the thymus is extremely rare. Including the current series, 25 cases have been reported in the literature (6–11). It is noteworthy that at least 19 (76%) of these patients are Asians, and at least 17 (68%) of them had autoimmune diseases or hyperglobulinemia (6–11). In our cases, all four patients were Asians, and positive for RF and ANA. Three of them showed elevated serum Ig levels, which remained almost unchanged after total thymectomy. In case 2 in Table 2, Ig levels and antibody abnormality remained unchanged even 3 years after thymectomy. These data suggest that immunological disorders may be strongly associated with the genesis of MALT lymphoma and that they were not caused by MALT lymphoma itself.
Inagaki and colleagues investigated API2–MALT1 gene fusion in 15 thymic MALT lymphoma cases, and did not find it to be present in any of these cases (6), which was consistent with our results. These findings suggest that oncogenic events other than API2–MALT1 fusion are responsible for thymic MALT lymphoma development.
Three of our patients had macroscopic cysts in the tumor, and 13 (72%) of the previous 18 cases (macroscopic findings were not described in the remaining seven cases) also had macroscopic cysts. Even in cases with no cysts detected macroscopically, cystic spaces were recognized microscopically in all our cases. Epithelium-lined cysts appear to be a constant and distinctive feature of thymic MALT lymphoma. As Chan speculated, cyst formation may be related to the tendency for cystic transformation of medullary duct epithelium-derived structures (including Hassall's corpuscles) when the tumor grows in the thymic gland (6). Yi et al. (7) reported that MALT lymphoma should be considered in the differential diagnosis whenever a solid, cystic thymic mass is found. Our three cases with macroscopic cysts revealed a cystic thymic mass on CT and MRI. Cystic changes have been observed in neoplastic thymic lesions, including thymoma, non-Hodgikin's lymphoma, Hodgikin's disease, mediastinal seminoma and certain types of thymic carcinoma, or in non-neoplastic thymic lesions (12). Although cystic changes do not specify a specific histology, it is difficult to diagnose these lesions differentially based on radiological findings and/or a small amount of biopsy specimens. In thymic MALT lymphomas, however, prevalence in Asians and strong association with autoimmune disease or hyperglobulinemia were reported to be clinically distinctive and may be helpful in diagnosing the disease. Thus, we recommend that thymic MALT lymphoma should be considered in the differential diagnosis: (i) when a cystic thymic mass is found; and (ii) if the patient is Asian and/or has autoimmune disease or hyperglobulinemia.
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Acknowledgments |
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This work was supported in part by a Grant-in-Aid for cancer research from the Ministry of Health, Labour and Welfare, Japan.
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References |
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