Thaddäus Radaszkiewicz

Gastrointestinal malignant lymphomas of the mucosa-associated lymphoid tissue: factors relevant to prognosis.

Three hundred seven cases (244 gastric, 63 intestinal) of primary gastrointestinal non-Hodgkins lymphoma (NHL) in stages EI and EII, according to a modified Ann Arbor system, were examined retrospectively. The histological classification for mucosa-associated lymphoid tissue-derived lymphomas was applied. Gastric NHLs (male-female ratio, 0.97; mean age, 64.5 years) were stage EI in 51% and stage EII in 49% of cases. Histological grade of malignancy was low in 41% and high in 59% of cases; all NHLs were B-cell type. Tumors were radically resected in 87%, and overall 2-, 5-, and 10-year survival rates were 61%, 55%, and 46%, respectively. Early lymphomas (substage EI1) had best prognosis (5- and 10-year survival rates, 90% and 70%, respectively). Intestinal NHLs (male-female ratio, 1.1; mean age, 54.4 years) were stage EI in 30% and stage EII in 70% of cases. Histology was low grade in 21% and high grade in 79%, and all but 11 cases were B-cell type. In 58% of cases, radical tumor resection resulted in overall 2- and 5-year survival rates of 44% and 24%, respectively. Major prognosticators for survival in gastric location were low-grade histology, low depth of infiltration, and low stage and radical resectability of lymphoma; all factors were strictly intercorrelated. In intestinal site, radical tumor resectability was highly significant for survival. Cumulative proportion of relapses after 5 years was higher in intestinal than in gastric sites (44% vs. 22%). In conclusion, primary gastrointestinal tract NHLs may represent an entity with respect to characteristic histological features, focal tumor growth, and potential cure by radical resection. Because of late relapses, clinical follow-up is needed.

Primary gastrointestinal non-Hodgkin's lymphomas. A retrospective clinicopathologic study of 150 cases

The records of 150 primary gastrointestinal (GI) lymphomas in adults collected from 1974 to 1982 at the Department of Pathology, University of Vienna, were reviewed. One hundred thirty‐three cases of malignant lymphomas (ML) were analyzed with respect to histologic type, presenting tumor stage, and clinical course, as well as for factors influencing prognosis. The histologic type of ML as assessed by the Working Formulation and the Kiel, the Lukes and Collins, and the Rappaport classifications showed only a minor influence on prognosis. MLs of follicular center cell origin prevailed in the stomach and large cell, immunoblastic MLs prevailed in the bowel. Immunoperoxidase studies indicated a B‐cell nature of GI MLs and demonstrated intracytoplasmic IgM kappa or lambda in most of the MLs of the small lymphocytic, plasmacytoid, and immunoblastic type, respectively. The 105 cases of gastric MLs represented 3.6% of all malignancies of the stomach collected during the study period. Clinical symptoms preceded the diagnosis by 4.4 months on average, and endoscopic biopsy specimens indicated malignancy in 78%. Presenting tumor stages of gastric MLs according to the Ann Arbor staging system were Stage I in 20%, Stage II in 76.2%, and Stage IV in 3.8%. The 28 cases of intestinal ML localized in the small and large bowel without any site prevalence presented with Stage I in 14%, Stage II in 82%, and Stage III in 4%. Tumor resection was performed in 90% of all cases and was followed by multiagent therapy in 53%. Radical tumor resection was obtained in 58% of the gastric MLs and only 28.6% of the intestinal MLs and was closely related to tumor stage. Statistical analysis demonstrated a significant influence of the presenting tumor stage on prognosis as expressed by the overall 2‐year survival rate of 70% for Stage I versus 39% for Stage II ML. In addition, Stage II1 according to Musshoff et al. run a better course than II2 as shown by the disease‐free 2‐year survival rate of 49% versus 15%, respectively. Radical tumor resection was a major determinant of survival and cure of disease as exhibited by the disease‐free 2‐year survival rate of 57% after radical resection versus 8% after nonradical resection of ML. Finally, diffuse tumor growth and tumor penetration of the gastric wall beyond serosa decreased the survival rates.

Peripheral T cell lymphoma presenting primarily as lethal midline granuloma

This clinicopathologic study reports seven patients who primarily presented with ulcerative and destructive lesions of the upper aerodigestive tract and face, clinically consistent with so-called lethal midline granuloma (LMG). Histologically, the infiltrates were composed of atypical lymphoid cells that displayed angiocentricity and angiodestruction. In five patients, involvement of distant sites such as skin, lungs, lymph nodes, and bone marrow occurred, and in two cases, the disease remained localized. Immunomorphologic analysis, using monoclonal antibodies to frozen and paraffin sections, provided evidence for the diagnosis of peripheral T cell lymphoma (PTL) in all cases. The midline tumors were classified as diffuse mixed or diffuse large cell lymphoma occurred at distant sites. According to modern PTL classification systems, the lesions could be classified as pleomorphic T cell lymphomas. Those five patients who presented with or progressed to large cell lymphoma died within 18 months (mean, 7 months), whereas the two patients with localized disease are alive after 10 and 36 months, respectively. The size of the atypical lymphoid cells may be of prognostic significance since the large cell compartment seems to represent the major growth fraction in these PTLs.

Interferon-alfa corrects thrombocytosis in patients with myeloproliferative disorders

SummaryDuring previous therapeutic trials with interferon, decreased levels of peripheral platelet counts have been observed. Taking advantage of this effect, we investigated the efficacy of recombinant interferon (rec-IFN) in the treatment of thrombocytosis in myeloproliferative diseases. A total of 15 patients with polycythemia vera, essential thrombocytosis, or chronic myeloid leukemia received rec-IFN-alfa at initial doses of 25–70×106 units/week; maintenance therapy following week 8 of treatment consisted of 20–35×106 units/week rec-IFN. Observation periods ranged from 24 to 48 weeks. Significant reductions in the number of platelets were noted in all cases; 12/15 patients achieved platelet counts below 440×109/1 and maintained those normal values for at least 4 weeks. The number of bone marrow megakaryocytes, which had been increased prior to treatment, diminished during rec-IFN therapy, while the previously shortened platelet half-life further decreased with rec-IFN treatment. During rec-IFN-induced remission, the plasma levels of platelet factors, the activity of natural killer cells, and platelet aggregation showed changes between slight improvement and normal values. Severe side effects were only observed with the highest rec-IFN doses; dosage adjustments were effective in improving or eliminating all treatment-related symptoms. Rec-IFN may prove to be a valuable therapeutic alternative to cytostatic treatment of thrombocytosis in myeloproliferative disorders.

Variability of nm23-H1/NDPK-A expression in human lymphomas and its relation to tumour aggressiveness

The nm23-H1 gene is a putative metastasis-suppressor gene encoding a 17 kDa protein with nucleoside diphosphate kinase activity. Expression of nm23-H1/NDPK-A correlates inversely with the metastasising potential of some human tumours and experimental animal cells. No nm23 expression studies exist for human malignant lymphomas so far. In this study, we examined nm23-H1 expression by Northern and immunohistochemical analysis in 106 primary lymphoma samples from patients with Hodgkins disease (HD) (n = 15), high-grade non-Hodgkins lymphoma (NHL) from different lineages (n = 71) and low-grade NHL (n = 20). Both inter- and intra-subtype variations in nm23-H1/NDPK-A expression levels were demonstrated by all disease subtypes. Besides this heterogeneity, a general trend towards highly malignant samples expressing higher nm23-H1/NDPK-A, levels than the low-grade lymphomas was observed. Both adult and childhood HD and high-grade NHL samples exhibited significantly higher NDPK-A expression than the low-grade NHL found only in adults. High nm23-H1/NDPK-A levels in lymphoma samples did not always reflect proliferative activity of tumour cells as monitored by Ki-67 antigen staining. Fifty samples were further investigated for possible mutations in the nm23-H1 coding sequence by means of reverse transcriptase-polymerase chain reaction (RT-PCR) and single-strand conformation polymorphism (SSCP) analysis. No mutation was found by this screening. Our results suggest a role for nm23-H1 expression in the disease aggressiveness of lymphomas.

Spontaneous remission of acute myeloid leukemia after infection and blood transfusion associated with hypergammaglobulinaemia

Abstract Spontaneous remissions of acute myeloid leukemia (AML) have been documented in association with infection as well as blood transfusions. Activation of the immune system including an increased number of NK cells and cytokine release have been implicated in the mechanism of this phenomenon. We have observed spontaneous remissions in two patients with AML (one with a t(8;21)-positive M2, one with M5b), both occurring after infection and blood transfusions. The bone marrow showed a reduction of blast cells from 65% to 2% or 40% to 1%, respectively. Remission was accompanied by a marked polyclonal hypergammaglobulinemia in both cases (IgG values of 6420 and 2160 mg/dl, IgA of 802 and 811 mg/dl, respectively). A concomitant increase in bone marrow plasma cells was observed in both patients. Reduction of AML1/ETO PCR positivity from one-step to two-step PCR (approximately 100-fold) was documented in the patient with a t(8;21), while a regression of lymph node and skin leukemic infiltrations occurred in the patient with M5b. One patient relapsed after 4 months, at a time when his serum immunoglobulin levels had markedly decreased. The other patient is in continuous remission after 14 months. These cases suggest a potential role for a humoral immune response in the mechanism of spontaneous remission.

Expression of the mucosal homing receptor α4β7 in malignant lymphomatous polyposis of the intestine

Abstract Recent studies have identified the integrin α4β7 as a mucosal homing receptor that mediates lymphocyte migration to the intestinal mucosa by binding to MAdCAM-1, which is a vascular recognition molecule (adressin) selectively expressed on mucosal endothelium. The expression of the α4β7 mucosal homing receptor was studied in eight cases of malignant lymphomatous polyposis (MLP). This unusual presentation of non-Hodgkins lymphoma of mantle cell type is characterized by multifocal lymphomatous involvement of the gastrointestinal tract. Unlike nodal mantle cell lymphomas, cases of MLP showed expression of α4β7, suggesting that this homing receptor plays an important role in determining the characteristic mucosal dissemination pattern of MLP.

Primary peripheral T cell lymphoma in a kidney transplant under immunosuppression with cyclosporine A

A 56-year-old patient received a cadaveric renal allograft because of primary cystic kidney disease. The donor was a 28-year-old man who died from head trauma. No other major illnesses were present at the time of transplantation. Immunosuppression was performed with cyclosporine A and steroids. After 3 months, the patient presented with fever and abdominal pain which was located in the region of the allograft. Ultrasonography demonstrated a tumor mass at the renal transplant hilus that was suspected to be an infected hematoma. Kidney biopsy from the cortex revealed only severe morphologic signs of cyclosporine A toxicity which was due to high cyclosporine A levels during the first 2 months after transplantation. The patient died from pulmonary embolism 6 months posttransplant. Histologic evaluation of the tumor specimens obtained at autopsy showed an extensive infiltration of the renal hilus and the medulla by a peripheral T cell lymphoma of the large-cell type. The T cell origin was confirmed by immunohistochemistry using the T cell-associated monoclonal antibodies UCHL-1 and MT1.

Adhesion Molecules in the Dissemination of Non-Hodgkin’s Lymphomas

Most non-Hodgkins lymphomas (NHLs) express a number of different adhesion receptors. A large body of evidence indicates that these adhesion receptors not only regulate normal lymphocyte trafficking but also play a pivotal role in the dissemination of NHL. Thus, cutaneous lymphocyte antigen, alpha 4 beta 7, alpha E beta 7, and L-selectin, which mediate the tissue-specific positioning of normal lymphocytes in the skin, mucosa, epithelium and lymph nodes, respectively, are selectively expressed on lymphomas localized at these sites. Furthermore, expression of CD44, a family of adhesion receptors with pleiotropic effects on tumor behavior, is related to lymphoma aggressiveness and dissemination. Taken together, these findings offer a framework for the understanding of tumor dissemination in NHL. In view of the similarities between lymphocyte behavior and the metastatic behavior of solid tumors, these insights might contribute to the understanding of the basic mechanisms underlying tumor metastasis in non-lymphoid tumors.

Deficiency of pluripotent hemopoietic progenitor cells in myelodysplastic syndromes

SummaryPluripotent (CFU-MIX), erythroid (BFU-E) and granulocyte/macrophage (CFU-GM) progenitor cells were examined in bone marrow (BM) from 23 patients with myelodysplastic syndromes (MDS). Patients were grouped according to the FAB classification: Refractory anemia (RA), n=3; RA with ring sideroblasts (RARS), n=3; RA with excess of blasts (RAEB), n=8; RA with excess of blasts in transformation (RAEBt), n=7; chronic myelomonocytic leukemia (CMML), n=2. In FAB groups RA, RARS, RAEB and RAEBt CFU-GM concentrations were normal or decreased but both CMML-patients had increased CFU-GM values. Abnormal cluster growth was observed in 9 of 23 MDS-patients. BFU-E colony formation was subnormal in all cases. Mixed-colony assay values were at the lower limit of controls in one patient and decreased in the remaining 22 MDS-patients. A similar growth pattern of hemopoietic progenitor cells was observed in 19 patients with acute nonlymphocytic leukemia (ANLL), who were studied for comparison. These data suggest a quantitative or qualitative/functional defect of the pluripotent progenitor cell compartment as the major cause for the cytopenia in MDS-patients.