Immunoproliferative small intestinal disease without alpha-chain disease: a pathological study

Biopsy specimens taken during exploratory laparotomy provided the material for a pathological study of 23 cases of nonsecreting immunoproliferative small intestinal disease (Mediterranean lymphomas without alpha-chain disease). The distinctive pathological feature of immunoproliferative small intestinal disease, i.e., a diffuse lymphoid infiltration, was present in the mucosa and submucosa of all or a major part of the small intestine. It was composed of a low- or intermediate-grade malignant lymphoid proliferation associated in 19 of 23 cases with benign-appearing follicular lymphoid structures. These follicular figures were surrounded and partially destroyed by the lymphoma cells. This association strongly resembles the newly described non-Hodgkin's lymphoma entities of perifollicular or parafollicular cell origin. Gross tumors of the small intestine were found in association with the diffuse lymphoid infiltration in 10 cases. They often constituted foci of lymphoma with a higher grade of malignancy. Mesenteric lymph node involvement was frequent and generally in direct ratio to the severity of intestinal involvement. A comprehensive study of the lesions observed in these cases led to the hypothesis that nonsecreting immunoproliferative small intestinal disease could result from the malignant change of perifollicular B cells; during an initial period the tumoral cells retain circulating and homing properties that explain their infiltrative and extensive method of spreading. The possible subsequent emergence of more aggressive subclones of noncirculating malignant cells could then explain the associated inconstant fungating tumor foci. Further studies using more sophisticated immunohistochemical techniques are necessary to establish the meaning of the hyperplastic lymphoid follicles, the possible etiologic role of benign nodular hyperplasia, the exact identification of the tumor cells, and the relationship of nonsecreting immunoproliferative small intestinal disease to closely related alpha-chain disease.     

Immunoproliferative small intestinal disease: portrait of a potentially preventable cancer from the Third World

PURPOSE: To review the recent progress in the understanding of clinical and laboratory characterization as well as management of immunoproliferative small intestinal disease (IPSID). DATA IDENTIFICATION: A literature search was conducted using Index Medicus, MEDLINE (1962 to 1989), and bibliographies of identified relevant articles. STUDY SELECTION: All international comprehensive reviews, reported epidemiologic or immunologic studies, and prospective clinical trials published or abstracted in English were selected. RESULTS OF DATA SYNTHESIS: A high incidence of lymphoma primarily in the gastro-intestinal tract in Third World countries has stimulated enormous epidemiologic and pathogenetic interests globally. IPSID, with a distinctive biologic marker (alpha heavy chain para-protein), affects the young underprivileged population of those countries. The initially benign-appearing antibiotic-responsive immunoproliferative lesions often evolve to fatal high-grade lymphomas. Roles of environmental and host factors in this evolutionary course are emerging. Recently demonstrated malignant potentials form the early onset of pathogenesis have given a new dimension to the traditional management strategy of IPSID. CONCLUSIONS: Epidemiologic, immunologic, and pathogenetic data that have emerged over the last 25-year study of IPSID have improved our understanding about the complexity of infection-immunity-cancer interrelationships, comparable to those that have arisen from the study of the acquired immunodeficiency syndrome. Early detection and institution of antimicrobial-based treatment regimens with judicious and consistent follow-up can save the lives of many young patients whose manpower is badly needed in Third World countries.     

Immunoproliferative small intestinal disease in South India: A clinical and immunomorphological study

Immunoproliferative small intestinal disease (IPSID), a proliferative disorder affecting the intestinal immune system, has only been reported sporadically in India. Fifteen patients with malabsorption syndrome who were diagnosed to have IPSID were included in this study. Mucosal biopsies from all patients, fall thickness surgical biopsies from 10 and autopsy material from four patients were examined by light microscopy and immunohistochemistry. The patients were predominantly young (aged 16–36 years) and male (13 of 15). Diarrhoea, weight loss, vomiting and abdominal pain were the major symptoms. The upper small bowel was involved in all cases. Involvement of large bowel was detected antemortem in three patients, but was found in all autopsied patients. Involvement of the stomach was noted in one patient at autopsy. Mesenteric lymph nodes were involved in all patients who underwent laparotomy. The plasmacytic infiltrate was uniformly positive for alpha-heavy chain, and either negative for light chain production or showed monotypic light chain production. Some of the blasts were also positive for alpha-heavy chain. Three patients died before therapy could be commenced. One patient with stage A disease is alive and clinically free of disease at 7 years. Of the remainder, there have been four long-term survivors with chemotherapy. Immunoproliferative small intestinal disease occurs in southern India and has characteristics similar to that in other parts of the world. Early diagnosis may improve outcome in this disease.     

Immunoproliferative small intestinal disease: prolonged 30-year course without development of lymphoma

Immunoproliferative small intestinal disease (IPSID) is mostly found in young adults of low socioeconomic class in developing countries. This condition is characterized by a dense lymphoplasmacytic infiltrate beneath the epithelium in the duodenal and proximal jejunal mucosa and in the mesenteric lymph nodes. In two thirds of cases, the involved lymphocytes elaborate an anomalous alpha-heavy chain protein. The etiology of this disease is unclear, although various parasitic, genetic, and toxic mechanisms have been proposed. Half of all IPSID patients will be found at diagnosis to have a concurrent intestinal B-cell lymphoma, and most of the remaining patients develop frank lymphoma within a few years. Although most reports of IPSID are from developing nations or indigent immigrant populations within Western countries, four cases of an IPSID-like condition have been documented in white women. Furthermore, although many IPSID patients progress to high grade indeterminate-type lymphoma within a few years of initial presentation, there have been occasional reports of long term survival without lymphomatous conversion. Here, we present an atypical case of IPSID--a California native who, though of Mexican heritage, had resided in the United States his entire life and did not belong to an indigent population. This patient had biopsy-proven IPSID that progressed over 30 yr but never exhibited lymphomatous conversion despite end stage intestinal stasis and recurrent obstruction, culminating in death. Our case calls into question some current assumptions about the prelymphomatous nature of this disease.     

Immunoproliferative small intestinal disease (IPSID): a model for mature B-cell neoplasms

Immunoproliferative small intestinal disease (IPSID) was recently added to the growing list of infectious pathogen-associated human lymphomas. Molecular and immunohistochemical studies demonstrated an association with Campylobacter jejuni. IPSID is a variant of the B-cell lymphoma of mucosa-associated lymphoid tissue (MALT), which involves mainly the proximal small intestine resulting in malabsorption, diarrhea, and abdominal pain. Geographically, IPSID is most prevalent in the Middle East and Africa. IPSID lymphomas reveal excessive plasma cell differentiation and produce truncated alpha heavy chain proteins lacking the light chains as well as the first constant domain. The corresponding mRNA lacks the variable heavy chain (V(H)) and the constant heavy chain 1 (C(H)1) sequences and contains deletions as well as insertions of unknown origin. The encoding gene sequence reveals a deletion of V region and parts of C(H)1 domain. Cytogenetic studies demonstrated clonal rearrangements involving predominantly the heavy and light chain genes, including t(9;14) translocation involving the PAX5 gene. Early-stage IPSID responds to antibiotics (30%-70% complete remission). Most untreated IPSID patients progress to lymphoplasmacytic and immunoblastic lymphoma invading the intestinal wall and mesenteric lymph nodes, and may metastasize to a distant organ. IPSID lymphoma shares clinical, morphologic, and molecular features with MALT lymphoma, lymphoplasmacytic lymphoma, and plasma cell neoplasms.     

Immunoproliferative small intestinal disease with protein loss complicated with duodenal T cell lymphoma during progression

A 52-year-old man was admitted to our hospital in October 2001 with abdominal pain. Abdominal X-ray indicated a diagnosis of ileus. Histopathological and immunological examination resulted in a diagnosis of immunoproliferative small intestinal disease (IPSID). He was treated with THP-COP therapy (pirarubicin, cyclophosphamide, vincristine, and prednisolone), which resulted in complete remission. Outpatient follow-up revealed hypoalbuminemia in May 2003 and upper gastrointestinal endoscopy showed duodenal mucosal nodularity. He was diagnosed with relapsed IPSID and salvage chemotherapy was started. Follow-up endoscopy confirmed that the therapy was effective, but uncovered another duodenal mucosal nodularity. Immunohistochemical staining revealed T-cell lymphoma. Chemotherapy was discontinued and the patient died in December 2004.     

Immunoproliferative small-intestinal disease: clinical features and outcome in 30 cases

Experience with 30 patients with immunoproliferative small intestinal disease followed prospectively between 1971 and 1986 is described. All presented with malabsorption or growth retardation and had similar clinical, biochemical, and radiological features, irrespective of the presence of lymphoma or immunological abnormality. Alpha-chain disease protein was detected in 4 of the 11 patients who had a non-lymphomatous, predominantly plasmacytic infiltration of the small bowel; and in 5 of the 19 cases with diffuse intestinal lymphoma. The importance of exploratory laparotomy to include full-thickness intestinal biopsy in patients who have a benign infiltrate on peroral biopsy is demonstrated by the finding of lymphoma in operative specimens in 9 of 15 patients with mature, lymphoplasmacytic cells, and 5 of 8 patients with atypical, lymphoplasmacytic cells. The majority of patients with fully established benign disease, even those elaborating alpha-chain disease protein, appeared to have a good prognosis. No patient with immunoproliferative small intestinal disease developed immunologically demonstrated alpha-chain disease or frank lymphoma, when this was not found initially at explorative laparotomy.     

Seven cases of Pompe disease from Greece

We present seven cases of Pompe disease (McKusick 232300; glycogen storage disease type II; acid maltase deficiency) from Greece. The onset of symptoms varied from early childhood to late adulthood, and the patients had quite variable duration of disease. All but one of them had muscle weakness and all had mildly to highly elevated serum creatine kinase. The diagnosis in all cases was confirmed by the finding of acid alpha-glucosidase (EC 3.2.1.3/20) deficiency in cultured skin fibroblasts. Thirteen mutant alleles were identified and nine different pathogenic mutations were encountered. Four were new: c.2071_2072insAGCCG leads to frameshift and total loss of function; c.1856G > A (p.Ser619Asn) leads to 90-95% loss of function; and the splice-site mutations c.1552-3C > G and c.2331+4A > G reduce the number of correct splicing events by more than 90%. The splice-site mutation c.-32-13T > G (IVS1-13T > G) was encountered four times and seems equally common among Greek and other caucasians. The other mutations: c.925G > A (p.Gly309Arg), c.[307T > G; 271G > A] (p.Cys103Gly; Asp91Asn), c.271del and c.1655T > C (p.Leu552Pro) have been reported earlier. Our study highlights the heterogeneity of Pompe disease in Greece and provides tools for diagnosis and carrier detection.     

以心脏症状为主要表现的线粒体病二例

例1 女性,19岁,进行性活动时心慌乏力17年.患者自2岁起行走约10 m即感心慌乏力,外出时需由家长背驮,有时尚伴胸闷与肌肉酸痛,休息可略缓解,无晨轻暮重现象.7岁时查心脏超声等未见异常,因心率增快,曾在多家医院长期以"心肌炎"和"早期心肌病"诊治.14岁时无明显诱因首次出现夜间抽搐,伴有意识丧失,全身强直,大小便失禁,持续约1 min,迄今已有类似发作6次.2009年首次来本院就诊.个人史:足月顺产,13岁月经来潮,中专毕业,学习成绩欠佳.家族史:家族中无类似疾病患者.     

Clinical analysis of primary small intestinal disease： A report of 309 cases

AIM: To evaluate the major clinical symptom, etiology, and diagnostic method in patients with primary small intestinal disease in order to improve the diagnosis. METHODS: A total of 309 cases with primary small intestinal disease were reviewed, and the major clinical symptoms, etiology, and diagnostic methods were analyzed. RESULTS: The major clinical symptoms included abdominal pain (71%), abdominal mass (14%), vomiting (10%), melaena (10%), and fever (9%). The most common disease were malignant tumor (40%). diverticulum (32%) and benign tumor (10%). Duodenal disease was involved in 36% of the patients with primary small intestinal diseases. The diagnostic rate for primary small intestinal diseases by double-contrast enteroclysis was 85.6%. CONCLUSION: Abdominal pain is the most common clinical symptom in patients with primary small intestinal disease. Malignant tumors are the most common diseases. Duodenum was the most common part involved in small intestine. Double-contrast enteroclysis was still the simplest and the most available examination method in diagnosis of primary small intestinal disease. However, more practical diagnostic method should be explored to improve the diagnostic accuracy.     

Colorectal GISTs: from presentation to survival. An analysis of 13 cases

This papers is a retrospective analysis of all cases of colorectal GIST treated at our institution. Considering the increased interest in this pathology, in 2008, we recently established a unit supported by Novartis in our department to research and treat GIST. Since then, there was a dramatic increase in the referral of this type of tumor to our center. Before initiating our research group, we had the permission of the ethics committee and the medical directors to study and publish the analysis of our cases. Now, we have a cohort of 98 patients treated during the last 10 years and from that, we selected all cases of Colorectal GIST's. They numbered 13 cases. We performed an analysis of these cases from the presentation to the results of treatment.     

肠结核误诊为克罗恩病2例

肠结核患者2例因反复腹泻1年入院, 被误诊为克罗恩病. 经病理、胸片及痰涂片确诊为肠结核. 本文提示肠结核与克罗恩病鉴别诊断困难, 暂时不能确诊时, 应首先考虑按结核病处理这一相对安全的原则.