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Primary Low-Grade Lymphomas of the Intestine

Taner Demirer, Harika Çelebi, Ender Akçalayan, Celalettin Üstün, Seher Demirer, Cemil Ekinci, Kadir Bahar, Haluk Koç

Department of Hematology/Oncology and Bone Marrow Transplant Unit, Ankara University Medical School, Ibn-i Sina Hospital, Sihhiye 06100, Ankara, Turkey

CASE 1: IMMUNOPROLIFERATIVE SMALL INTESTINAL DISEASE

A 23-year-old woman was admitted to the Department of Gastroenterology at Ibn-i Sina Hospital with diarrhea, abdominal pain, and weight loss of 5 kg over 3 months. On physical examination, the patient had pallor and clubbing of the fingers and toes (Fig 1). There was no organomegaly or lymphadenopathy. Laboratory examination showed a hemoglobin level of 8.2 g/dL, a 26.9% hematocrit level, a WBC count of 8.4 x 10⁹/L, and a platelet count of 620 x 10⁹/L. Protein electrophoresis revealed an increase in alpha-2 globulin to 22.5 g/dL (normal range, 9 to 14 g/dL). The immunoglobulin (Ig) A level was high while the other Ig fractions were low: IgA, 5.54 g/dL (normal range, 0.7 to 3.80 g/dL); IgM, 0.43 g/dL (0.60 to 2.60 g/dL); IgG, 11.7 g/dL (6.9 to 16.20 g/dL). Immunoproliferative small intestinal disease (IPSID) was diagnosed by duodenal biopsy, which showed infiltration of the glandular epithelium by neoplastic small lymphocytes (Fig 2A) with plasmacytoid differentiation (Fig 2B). After initial treatment with tetracycline, the patient's symptoms were alleviated. However, 2 months later increasing diarrhea and fatigue recurred. Therefore, the patient was admitted to the hospital for further treatment. Physical examination showed palpable intra-abdominal lymph nodes, but there was no hepatosplenomegaly. The patient achieved complete remission after six courses of cyclophosphamide, doxorubicin, vincristine, and prednisolone treatment. The patient relapsed 4 months later with abdominal distention caused by ascites. Ultrasonography examination showed ascites and hepatomegaly associated with patchy heterogeneous involvement of the liver parenchyma, suggestive of malignancy. Results of a liver biopsy were consistent with IPSID (Fig 3). Paracentesis showed numerous lymphoplasmacytoid cells (Fig 4). Cisplatin, cytarabine, and dexamethasone were administered as a salvage therapy. The patient's response was favorable, and she had a second remission after the second cycle of cisplatin, cytarabine, and dexamethasone.

View larger version (134K): [in this window] [in a new window]   Fig 1.

View larger version (134K): [in this window] [in a new window]   Fig 2.

View larger version (144K): [in this window] [in a new window]   Fig 3.

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IPSID is a special form of mucosa-associated lymphoid tissue low-grade lymphoma. Mesenteric and retroperitoneal lymph nodes are frequently involved, whereas the other intra-abdominal lymph nodes and organs are often spared. Hepatic and splenic involvement is unusual in patients with IPSID.^1-5 The presence of primary small intestinal lymphoma in the Mediterranean basin was first reported in 1962 and called Mediterranean lymphoma, although the term was later abandoned in favor of IPSID.^1-5 The anomalous (monoclonal) alpha–heavy-chain production is a specific laboratory marker of IPSID, and thus it is also referred to as alpha–heavy-chain disease.^3-5 The majority of reported cases have originated from Mediterranean countries, although sporadic cases of IPSID have also been reported from other parts of Europe, South America, and the United States.^6,7 Common demographic characteristics of IPSID are a lower socioeconomic status, poor personal hygiene, predominance of male sex, and a peak age between the first and third decades.^1-5 IPSID is caused by the proliferation of IgA-producing B lymphocytes. Histologically, it is usually a low-grade non-Hodgkin's lymphoma. Transformation into high-grade histology is rare, even in patients with progressive and ultimately fatal disease.^4,5,8 The disease represents a spectrum of histologic changes of the enteromesenteric system ranging from benign-appearing lymphoid infiltrates to high-grade lymphoma. Clinical manifestations include diarrhea, abdominal pain, malabsorption, weight loss, growth retardation, and clubbing of fingers and toes.^1-5 Extra-abdominal extension of disease is rare. Thus, most patients are considered to have stage I or II disease according to conventional clinical and pathologic staging, although invasive staging procedures are usually not done.^4,5,8 In general, the disease responds well to both radiotherapy and chemotherapy.^3-5 The clinical course is highly variable. Patients in the early phase of IPSID can be treated with indolent therapies such as antibiotics, including tetracycline. However, most patients will have progression and need combination chemotherapy. According to the flow cytometric evaluations, some patients with high S-phase and aneuploid DNA indices have a progressive course and chemotherapy-refractory disease with early death.⁹ Patients with normal S-phase and diploid DNA ploidy indices have a more benign course, and overall survival may range from 8 to 10 years.⁹ Although involvement of the liver and spleen with IPSID is rare, we were able to show hepatic spread in our case. Another rare and interesting clinical picture in this case was severe ascites containing abundant atypical lymphoplasmacytoid cells of IPSID.

REFERENCES

1. Azar HA: Cancer in Lebanon and Near East. Cancer15:66-78, 1962[Medline]

2. Khojaswteh A, Haghighi P: Immunoproliferative small intestinal disease: Portrait of a potentially preventable cancer from the third world. Am J Med89:483-490, 1990[Medline]

3. Rambaud JC, Galian A, Matuchansky C: Natural history of alpha-chain disease and the so-called Mediterranean lymphoma. Recent Results Cancer Res64:271-274, 1978[Medline]

4. Seligmann M: Immunochemical, clinical and pathological features of alpha-heavy chain disease. Arch Intern Med135:78-82, 1975[Abstract/Free Full Text]

5. Doe WF: Alpha chain disease: Clinicopathological features and relationship to so-called Mediterranean lymphoma. Br J Cancer31:350-355, 1975 (suppl 2)

6. Cohen HJ, Gonzalvo A, Krook J, et al: New presentation of alpha heavy chain and cellular studies. Cancer41:1161-1169, 1978[Medline]

7. Roth S, Riecken EO: Alpha-chain disease: Mediterranean lymphoma and primary intestinal lymphoma in Western countries—A review of the cases in the literature. Ergeb Inn Med Kinderheilkd39:79-116, 1977[Medline]

8. Rappaport H, Ramot B, Hulu N: The pathology of so-called Mediterranean abdominal lymphoma with malabsorption. Cancer29:1502-1511, 1987

9. Demirer T, Uzunalimoglu O, Anderson T, et al: Flow cytometric measurement of proliferation-associated antigen P105 and DNA content in immuno-proliferative small intestinal disease (IPSID). J Surg Oncol58:25-30, 1995[Medline]

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Demirer, T. Articles by Koç, H. Search for Related Content PubMed PubMed Citation Articles by Demirer, T. Articles by Koç, H. Social Bookmarking                            What's this?