Enteropathy-associated T-cell lymphoma in the West of Ireland: low-frequency of Epstein-Barr virus in these tumors

The Epstein-Barr virus has been implicated in the etiology of endemic Burkitt's lymphoma, post-transplant lymphoma, large-cell anaplastic CD30 (Ki-1)-positive lymphoma, and in many T-cell lymphomas. A recent report has found Epstein-Barr virus genome in association with 4 of 11 cases (36%) of enteropathy-associated T-cell lymphoma. In a retrospective study, we have characterized 22 consecutive cases of enteropathy-associated T-cell lymphoma from the West of Ireland where celiac disease is endemic. All cases were immunophenotyped with T- and B-cell markers including the anaplastic large-cell lymphoma marker CD30 or Ki-1. Nineteen cases were studied for latent membrane protein expression and 16 for Epstein-Barr virus small RNAs by in situ hybridization using EBER oligonucleotides on routinely processed sections. Only 1 of 16 cases (6%) showed Epstein-Barr virus in tumor cells and no cases stained with latent membrane protein. Eight of 22 cases (36%) including the EBER-positive case were positive for CD30. These results suggest that the Epstein-Barr virus does not commonly play a role in the pathogenesis of enteropathy-associated T-cell lymphoma from this area.     

Effects of maternal exercise on fetal activity in late gestation

Sixty malignant non-Hodgkin's lymphomas originating in the upper aerodigestive tract have been analyzed for their cytologic type, immunophenotype and association with the Epstein-Barr virus (EBV). The majority of these tumors were B-cell lymphomas of blastic cytology (78%) with the exception of lymphomas in the parotid gland. Large B-cell lymphomas were the most frequent encountered in the sinonasal region and Waldeyer's ring. Twelve lymphomas were of T- or T/NK (natural killer)-cell lineage. They were in the nasal cavity and the paranasal sinuses (4), the tonsil (5), and the oral cavity (3). Epstein-Barr sequences were detected in five angiocentric T/NK-lymphomas, one peripheral T-cell lymphoma, one lymphoma of lymphomatoid granulomatosis type, one large B-cell lymphoma, and in a lymphoroliferative disorder in an HIV-positive patient. These results suggest that EBV is not involved in lymphomagenesis of B-cell tumors, but is associated with angiocentric T/NK-cell lymphoma in the upper aerodigestive tract.     

Tumour progression in a patient with granulomatous mycosis fungoides

We report a patient with granulomatous mycosis fungoides whose disease transformed into a high grade blast lymphoma with angiocentric features within 12 months of the initial diagnosis. This repudiates previous claims that granulomatous inflammation is protective in cutaneous T-cell lymphoma.     

Primary cardiac lymphoma. No evidence for an etiologic association with Epstein-Barr virus

OBJECTIVES: To report two cases of primary cardiac lymphoma, a rare extranodal lymphoma with an unknown pathogenesis, and to compare them to secondary B-cell cardiac lymphoma. DESIGN: Clinicopathologic features are described, using histologic and immunophenotypic examinations. The Epstein-Barr virus genome is detected by in situ hybridization. PATIENTS: Of 80 autopsied cases of malignant lymphoma identified at Nagoya (Japan) University Hospital, two patients with primary cardiac lymphoma and five patients with secondary cardiac B-cell lymphoma were selected. RESULTS: None of the seven selected cases showed immunodeficiency, autoimmune disorders, or chronic inflammatory processes. Primary cardiac lymphomas had B-cell phenotypes with mu and lambda chain monoclonality. Immunostaining for Epstein-Barr virus (latent membrane protein-1) and Epstein-Barr virus-encoded RNA-1 in situ hybridization did not demonstrate an association of these lymphoma with Epstein-Barr virus infection. The majority of secondary cardiac B-cell lymphomas were extranodal lymphomas and extranodal or serosal involvement was more prominent than nodal involvement. CONCLUSION: These findings suggest that primary cardiac lymphoma, unlike pyothorax-associated pleural lymphoma, appears to have no association with chronic inflammation or Epstein-Barr virus infection.     

Primary cutaneous large B-cell lymphomas of the legs. A distinct type of cutaneous B-cell lymphoma with an intermediate prognosis. Dutch Cutaneous Lymphoma Working Group

BACKGROUND AND DESIGN: Primary cutaneous follicular center cell lymphomas represent a distinct type of cutaneous B-cell lymphoma, clinically characterized by localized skin lesions on the head or trunk and an excellent prognosis. Histologically similar lymphomas may occur on the legs. The clinical behavior of this group is still undefined, and controversy exists whether these lymphomas should be classified as follicular center cell lymphoma or B-immunoblastic lymphoma. We reviewed the clinical, histologic, and follow-up data of 18 patients with primary cutaneous large B-cell lymphoma of the legs. RESULTS: Primary cutaneous large B-cell lymphoma of the legs generally occurred in elderly patients (median age at diagnosis, 76 years), in particular women (male-female ratio, 7:2), and preferentially affected the lower legs (14 of 18 patients). Radiotherapy and/or systemic polychemotherapy resulted in complete remissions in 16 of 17 patients. Follow-up data demonstrated estimated 2- and 5-year survival rates of 77% and 58%, respectively. Histologic evaluation showed diffuse dermal infiltrates with variable proportions of centroblasts (large noncleaved cells), large centrocytes (large cleaved cells), and B immunoblasts. Seventeen of 18 patients were diagnosed as having primary cutaneous follicular center cell lymphoma; only 1 patient, whose histologic examination showed more than 30% immunoblasts, was diagnosed as having B-immunoblastic lymphoma. CONCLUSIONS: Primary cutaneous large B-cell lymphoma of the legs is a distinct clinicopathologic entity that mainly affects elderly patients and has an intermediate prognosis. Although most cases have a follicular center cell origin, primary cutaneous large B-cell lymphoma is proposed as the most appropriate term for this type of cutaneous lymphoma.     

Peripartum cardiomyopathy. Analysis of 3 cases and review of the literature

A patient with hypogammaglobulinemia is presented with a primary cutaneous B-cell lymphoma. Diagnosis requires clinical and histologic criteria as well as phenotyping and genotyping. The cause, differential diagnosis, staging criteria, and treatment of the cutaneous B-cell lymphoma are reviewed.     

Pyothorax-associated lymphoma. An unusual case with biphenotypic character of T and B cells

Pyothorax-associated lymphoma is known to develop in patients who received an artificial pneumothorax for pulmonary tuberculosis some 30 to 40 years previously. Such patients exhibit large, immunoblastic lymphoma cells and often have a B-cell phenotype. We present a patient with an artificial pneumothorax and such a late developing lymphoma but with the unique finding of aberrant T- and B-cell phenotypes. Southern blot hybridization using immunoglobulin gene JH and T-cell receptor beta chain receptors revealed germline configurations. Lymphomas developing in immunocompromised patients, such as those with acquired immunodeficiency syndrome, may show such unusual phenotypes. The unusual phenotypes found in this patient provide evidence that his pyothorax-associated lymphoma was related to an immunocompromised state.     

EBV-associated lymphoma

Several subtypes of human malignant lymphomas are known to be highly associated with the Epstein-Barr virus. These include the Burkitt's lymphoma, opportunistic (immune deficiency-associated) lymphoma, nasal T/NK lymphoma, Hodgkin's disease pyothorax-associated lymphoma, cutaneous panniculitis-type lymphoma, and mediastinal large B-cell lymphoma. Improvement of histopathological technology, the demonstration of EBV-encoded small RNAs(EBERs), as well as the molecular virological methods, contributed much in the progression of such EBV-associated lymphomas.     

Analysis of the ntp1+ gene, encoding neutral trehalase in the fission yeast Schizosaccharomyces pombe

We report a clinicopathologic feature of primary cutaneous T-cell lymphoma (CTCL) in a five-year-old boy with increasing swelling of his cheek since two years of age. Histologically, an infiltrate of atypical lymphoid cells with mature T-cell phenotype and clonality was prominent from the dermis to the subcutaneous tissue of the cheek. Although little effect was seen with aggressive multidrug-combined chemotherapy, therapy with interferon-alpha and steroids achieved a prolonged remission. This patient may provide important clues to understanding the clinicopathologic feature of rare primary CTCL in young children.     

Comparison of Ottawa ankle rules and current local guidelines for use of radiography in acute ankle injuries

INTRODUCTION: We report the occurrence of non-Hodgkin's lymphoma during the course of chronic hepatitis C treated with alpha-interferon. EXEGESIS: Specific viruses such as Epstein-Barr virus and human T-cell leukemia viruses I and II may be at the origin of various lymphomas in human. The presence of B cell lymphoma in the course of chronic hepatitis C has already been described and could be related to the lymphoid tropism of hepatitis C virus. CONCLUSION: This new report of an association between chronic hepatitis C and B cell lymphoma should lead physicians to search for signs of lymphoma in patients with chronic hepatitis C.     

Femur head necrosis and bone marrow edema syndrome in pregnancy

Patients with angioimmunoblastic lymphadenopathy (AILD)-type T-cell lymphoma may develop hypergammaglobulinemia. Among four cases of AILD-type T-cell lymphoma that we have studied, we detected a correlation between the number of plasma cells in tissue and the extent of interleukin-6 (IL-6) expression in lymphoma cells. We did not detect IL-6 in three patients who had no hypergammaglobulinemia and whose tissues showed only minimal plasma cell infiltration. In the fourth patient we observed an abundant IL-6 production by lymphoma cells, which accounted for a B-cell plasmacytic tissue response and for hypergammaglobulinemia. The pathogenic significance of IL-6 was substantiated by a concomitant decrease in the serum IL-6 level, measurable tumor mass, and immunoglobulin levels, as well as by a decline in the proportion of plasmacytoid cells in peripheral blood promptly on administration of chemotherapy. Plasmacytoid B cells could be maintained in culture in the presence of IL-6, but viability was lost on co-incubation with anti-IL-6. Interleukin-1 and tumor necrosis factor were not produced by T lymphoma cells and were incapable of sustaining plasmacytoid B-cell viability in vitro. Small amounts of IL-4 were noted in T lymphoma cells. Thus, in this case of AILD-type T-cell lymphoma, tumor cells with a T-cell phenotype produced IL-6 in large quantities, explaining the accompanying B-cell and plasmacytic histologic changes and humoral disease manifestations, including marked hypergammaglobulinemia. Although not all cases of AILD-type T-cell lymphoma have an accompanying plasma cell proliferation and hypergammaglobulinemia, and although the cytokine network in these patients may be more complex than has been recognized, this case with IL-6 expression serves to illustrate the utility of cytokine assays in the analysis of the histopathologic and clinical heterogeneities of peripheral T-cell lymphomas.     

Aggressive cutaneous T-cell lymphoma associated with the presence of Epstein-Barr virus. 2 cases

INTRODUCTION: The factors of prognosis of the cutaneous T-cell lymphomas are less well known as those of the B-cell lymphomas and the role of the Epstein-Barr virus (EBV) is not yet definitively evaluated. CASE REPORTS: Two male patients aged 62 and 82 years had a mycosis fungoides with a lethal outcome. The first patient had mutilating facial tumors; the RNA m of EBV and the genome of EBV were demonstrated in the diseased skin. The second patient had an erythrodermic course with enlarged peripheral lymph nodes and circulating Sézary's cells; the genome of EBV was demonstrated by PCR in the diseased skin. DISCUSSION: The role of the EBV has already been demonstrated in peripheral aggressive T-cell lymphomas. In the mycosis fungoides, the EBV is associated with the lesions in 0 to 32 p. cent according to the published series. EBV associated T-cell lymphomas have a poor survival rate and the EBV infection may be associated with the expression of the multidrug resistant gene-1 (MDR-1) and the risk of a terminal hemophagocytosis. In our both patients the presence of the EBV in the lymphocytes of the skin lesions is also an argument in favour of the pathogenic role of the virus.     

Clinicopathologic manifestations of Epstein-Barr virus-associated cutaneous lymphoproliferative disorders

OBJECTIVE: To elucidate clinicopathologic manifestations of cutaneous lymphoproliferative disorders associated with Epstein-Barr virus (EBV) infection. DESIGN: Retrospective survey of case series. SETTING: University hospital medical center. PATIENTS: Sixty-five patients with cutaneous lymphomas and related disorders. MAIN OUTCOME MEASURES: Detection of EBV genes and EBV-encoded small nuclear RNAs. RESULTS: Evidence of latent EBV infection was demonstrated in 15 patients: 3 had malignant lymphoma with clinical features mimicking cytophagic histiocytic panniculitis, 6 had facial vesiculopapular eruptions mimicking hydroa vacciniforme, 4 had angiocentric lymphoma, 1 had histiocytoid lymphoma associated with hemophagocytosis, and 1 had plasmacytoma. Hypersensitivity to mosquito bites was noted in a patient with hydroa vacciniforme-like eruptions and another with histiocytoid lymphoma. Angiocentric infiltration of atypical lymphoid cells was a common histological feature in the patients with hydroa vacciniforme-like eruptions and angiocentric lymphoma. No evidence of EBV infection was apparent in 19 patients with mycosis fungoides or Sézary syndrome, 7 with adult T-cell leukemia or lymphoma, 3 with lymphomatoid papulosis (type A), and 2 with lymphocytoma cutis. CONCLUSION: Patients with EBV-associated cutaneous lymphoproliferative disorders present with unique and diagnostic clinicopathologic features distinct from those of mycosis fungoides or Sézary syndrome.     

Erythromycin elicits opposite effects on antro-bulbar and duodenal motility: analysis in diabetics by cineradiography

Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) are infrequently associated with noninfectious granulomas in involved or noninvolved organs. Adult T-cell leukemia/lymphoma (ATLL) is an aggressive lymphoproliferative neoplasm associated with T-lymphotropic virus type 1 (HTLV-1). We describe a case of cutaneous type ATLL, affecting mainly the skin as a maculopapular eruption, in which some skin biopsies contained epithelioid cell granulomas in the lymphoma cutis (ATLL) lesion. These Lennert's-like epithelioid clusters were also present in lymph nodes, which showed some degree of invasion by the ATLL lymphocytes. Although prognosis of ATLL is generally poor, our patient has had a less aggressive course, with a survival time to date of 13 years. Our findings suggest that the presence of epithelioid granulomata in an ATLL patient may be a manifestation of a host response which confers some protection against the disease progression. To our knowledge, this is the first report of a case of ATLL with a noninfectious granuloma similar to a Lennert's lesion.     

Posttransplant T-cell lymphoproliferative disorders--an aggressive, late complication of solid-organ transplantation

T-cell non-Hodgkin's lymphomas are an uncommon occurrence after solid-organ transplantation. We describe a morphologically and immunophenotypically distinct group of T-cell lymphoproliferative disorders that occurred late in the course of six patients with solid-organ transplants. The patients ranged in age from 31 to 56 years (median, 43). Three were male; all were splenectomized. The interval from transplant to the diagnosis of lymphoma ranged from 4 to 26 years (median, 15). Symptoms at presentation were related to sites of involvement. Pulmonary, marrow, and CNS involvement were present in five, four, and one case, respectively. No patient had lymphadenopathy. Five patients had an elevated lactate dehydrogenase level (range, 226 to 4,880 IU/L; median, 1,220 IU/L). Five of six patients had a leukoerythroblastic reaction. All cases had large-cell histology and frequently contained cytoplasmic granules. Those cases tested expressed CD2, CD3, and CD8 and were negative for B-cell antigens. T-cell receptor beta- and gamma-chain genes were clonally rearranged in three of three and one of three cases, respectively. All T-cell posttransplant lymphoproliferative disorders (T-PTLDs) studied were negative for Epstein-Barr virus (EBV), human T-cell leukemia/lymphoma virus type 1 (HTLV-1), human T-cell leukemia/lymphoma virus type 2 (HTLV-2), and human herpes virus type 8 (HHV-8) genomes. Treatment with acyclovir (three patients) or chemotherapy (three patients) resulted in two responses. All patients had an aggressive course, with a median survival duration of 5 weeks. In conclusion, a clinically aggressive T-PTLD may be a late complication of solid-organ transplantation and does not appear to be related to EBV, HTLV-1, HTLV-2, or HHV-8 infection.     

Diffuse digestive tract B-cell lymphoma manifesting as exudative enteropathy

BACKGROUND: Early manifestations of primary lymphomas of the digestive tract generally include general signs and abdominal pain. Diarrhea is uncommon and may result from several mechanisms. We report a case of primary lymphoma of the digestive tract in a patient presenting exsudative enteropathy. CASE REPORT: A 68-year-old woman was hospitalized for profuse diarrhea of 15 days duration. Laboratory tests showed major hypoalbuminemia. Malabsorption could not be evidenced and no infectious foyer was found. Biopsies at different levels of the digestive tract showed mucosal invasion by MALT type B-cell lymphoma. The clinical course was initially favorable after chemotherapy. DISCUSSION: Classification of digestive tract lymphomas differentiates MALT type B-cell lymphoma (the most frequently encountered type in western countries), Mediterranean lymphomas, and T-cell lymphomas generally complicating coeliac disease. MALT type lymphomas may occur in association with Helicobacter pylori infection, usually in a gastric localization. Multiple localizations are uncommon and diffuse involvement of the digestive tract as in our observation appears exceptional. This extension would explain the exsudative enteropathy which regressed with chemotherapy.     

Prognosis of the skin UV-incidence increase in Poland

We studied the morphologic and immunohistochemical features of 10 peripheral T-cell lymphomas of a cytotoxic phenotype (CD3+/CD4-/CD8+), encountered among 98 peripheral T-cell lymphomas (PTCLs). Nine tumors were positive for both cytotoxic molecules, namely perforin (Pf) and granzyme B (GrB), and strong positivity was seen in the majority of the malignant cells. We also studied the expression of these molecules in 92 other cases of T-cell and natural killer (NK) cell neoplasms; 18 anaplastic large cell lymphomas (ALCLs); 63 CD4+ PTCLs; 10 CD56+ nasal lymphomas; and 1 NK-cell leukemia. Most of the CD4+ PTCLs (62 of 63) were negative for GrB, but all of the nasal lymphomas and the NK cell leukemia were positive for both Pf and GrB. Variable expression was seen among the 18 ALCLs. Within the 10 CD8+ PTCLs, 4 involved the skin, 3 of which were diagnosed as primary cutaneous lymphomas. Five patients died within 1 year of diagnosis. According to the Revised European-American Classification of Lymphoid Neoplasms, seven cases were categorized as "PTCL, unspecified," and three as "angioimmunoblastic T-cell lymphoma," "adult T-cell lymphoma/leukemia," or "small cell lymphoma," respectively. Three cases had characteristic morphologic features consisting of large lymphomatous cells with massive necrosis and nuclear fragmentation. Epstein-Barr virus mRNA was detected by in situ hybridization in three cases. Although the degree of apoptosis varied, apoptotic cells were detected in all cases by terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate-biotin nick end labeling. We conclude that CD8+ PTCLs are relatively rare, often involve extranodal sites, have an aggressive clinical course, and are often associated with Epstein-Barr virus. Compared with ALCLs, which have recently been considered as neoplasms of cytotoxic T-cells, we think that CD8+ PTCLs are more lineage-specific neoplasms of mature, cytotoxic, T lymphocytes.     

Secondary lymph node involvement from primary cutaneous large B-cell lymphoma of the leg: sentinel lymph nodectomy as a new strategy for staging circumscribed cutaneous lymphomas

BACKGROUND: Primary cutaneous large B-cell lymphoma of the leg (LBCLL) is a recently defined type of non-Hodgkin's lymphoma. It forms a separate category in the new classification of primary cutaneous lymphomas elaborated by the European Organization for Research and Treatment of Cancer. It is associated with a less favorable prognosis than the most frequently occurring types of primary cutaneous B-cell lymphoma. METHODS: The authors present four patients with the typical clinicopathologic constellation of LBCLL. Three of them died during the years 1993-1996. The authors reviewed their courses. The fourth patient was staged by sentinel lymph nodectomy (SLNE), i.e., the selective surgical removal and histologic examination of the first draining lymph node associated with the cutaneous tumor. RESULTS: The courses of the three previous patients were characterized by secondary involvement of regional lymph nodes followed by systemic dissemination of the lymphoma in a third step. Although the conventional staging of the fourth patient had been negative for any extracutaneous lymphoma manifestation, the SLNE revealed initial regional lymph node involvement, which had decisive implications for the choice of therapy. CONCLUSIONS: SLNE may gain a prominent role in the staging of circumscribed cutaneous lymphomas, in addition to its already established position in melanoma management. Further positive effects of SLNE are 1) better distinction of primary cutaneous lymphomas with secondary lymph node involvement from primary lymph node lymphomas with skin manifestation, and 2) better insight into the biology of different primary cutaneous lymphoma types.