No evidence of HTLV-I proviral integration in lymphoproliferative disorders associated with cutaneous T-cell lymphoma

Several recent studies have reported detection of HTLV-I genetic sequences in patients with cutaneous T-cell lymphoma (CTCL) including mycosis fungoides and Sezary syndrome. The purpose of this study was to determine whether HTLV-I was detectable in lesional tissues of patients suffering from diseases known to be associated with CTCL. Thirty-five cases were obtained from diverse geographical locations including Ohio, California, Switzerland, and Japan. Six of them had concurrent CTCL. Cases were analyzed using a combination of genomic polymerase chain reaction (PCR)/ Southern blot, dot blot, and Southern blot analyses. All assays were specific for HTLV-I provirus. Sensitivity ranged from approximately 10(-6) for PCR-based studies to 10(-2) for unamplified genomic blotting. Lesional DNA from patients with lymphomatoid papulosis (fourteen cases), Hodgkin's disease (twelve cases), and CD30+ large-cell lymphoma (nine cases) was tested for the HTLV-I proviral pX region using a genomic PCR assay followed by confirmatory Southern blot analysis with a nested oligonucleotide pX probe. All cases were uniformly negative. All of the Hodgkin's disease cases, eight of the large-cell lymphoma cases, and six of the lymphomatoid papulosis cases were then subjected to dot blot analysis of genomic DNA using a full-length HTLV-I proviral DNA probe that spans all regions of the HTLV-I genome. Again, all cases were negative. Finally, eleven of the Hodgkin's disease cases were also subjected to Southern blot analysis of EcoRI-digested genomic DNA using the same full-length HTLV-I probe. Once again, all cases were negative. These findings indicated that, despite utilization of a variety of sensitive and specific molecular biological methods, HTLV-I genetic sequences were not detectable in patients with CTCL-associated lymphoproliferative disorders. These results strongly suggest that the HTLV-I retrovirus is not involved in the pathogenesis of these diseases.     

Hodgkin''s disease-like lymphoproliferative disorders in patients with different underlying immunodeficiency states

An actuarial life-table approach was used to study the mortality of 277 calves born alive in 16 traditionally managed herds in Bauchi, Nigeria from 1993 to 1995. The proportion of calves in the herds surviving for the first 12 months was 53.8%. The probability of dying was greatest during the first month of life and decreased with age. The proportion of calves surviving in the herds has been increasing for the last 2 years. We suspect that this is probably due to improvements in management practices. Septicaemia, malnutrition and injury were the common causes of calf mortality. We recommend that more attention be given to improving the management of calves early in life in order to reduce mortality of calves and hence reduce economic losses to the herd owner.     

Eosinophilia associated with clonal T-cell proliferation

Eosinophilia associated with the expansion of cloned T-cells is reviewed in relation to cytokine production. It has been proved that eosinophilopoiesis is caused by eosinophil-stimulating cytokines, including interleukin-5 (IL-5), granulocyte-macrophage colony-stimulating factor and interleukin-3, which are secreted from T-cells. Recently, we and other groups have reported several cases of eosinophilia including hypereosinophilic syndrome (HES) accompanied with proliferation of abnormal T-cells with an unusual phenotype CD3- CD4+ or CD3+ CD4- CD8- in the peripheral blood. The T-cells clonally proliferate, as confirmed by clonal rearrangements of the T-cell receptor (TCR) gene, and produce eosinophil-stimulating cytokines, especially IL-5, with or without stimulation in vitro. Although HES is defined by the combination of unexplained prolonged eosinophilia and evidence of organ involvement, these observations suggest that increased production of eosinophil-stimulating cytokines from the abnormal T-cells with phenotype CD3- CD4+ or CD3+ CD4- CD8- may cause eosinophilia, some of which have been diagnosed as HES.     

Lymphocytes with cerebriform nuclei in chronic B-cell lymphoproliferative diseases

Two patients with chronic lymphoproliferative diseases, a splenic marginal zone lymphoma and hairy cell leukaemia variant, were reported. In both diseases a B-immunophenotype was demonstrated but a variable percentage of lymphoid cells (30 and 52%) showed a highly irregular nuclear outline, sometimes mimicking the nuclei of Sézary cells.     

Splenic irradiation in the palliation of patients with lymphoproliferative and myeloproliferative disorders

INTRODUCTION: Splenic irradiation is an accepted mode of treatment for palliation of hypersplenism and splenic pain for patients with lymphoproliferative or myeloproliferative disorders. However, results are conflicting regarding the duration of palliation and the toxicity associated with this treatment. METHODS: Twenty-five patients with lymphoproliferative or myeloproliferative disorders were treated with splenic irradiation for palliation of splenomegaly and pain. The spleen was measured and pain and toxicity were assessed during radiation therapy. RESULTS: Splenomegaly and splenic pain decreased in 60 percent and 91 percent of patients, respectively. Radiation doses higher than 500 cGy appeared to be more effective than lower doses in reducing the spleen size in patients with chronic lymphocytic leukemia. Regression of splenomegaly and pain relief were maintained for less than one year and more than six months, respectively. Acute radiation toxicity resulted in the cessation of radiotherapy in two patients. CONCLUSION: Splenic irradiation is effective in the short-term palliation of splenomegaly and pain and may be most useful in the subset of patients with a life expectancy of less than one year. Terminally ill patients with splenomegaly secondary to lymphoproliferative or myeloproliferative disorders may benefit from splenic irradiation to minimize pain and pressure symptoms in addition to possible reduction of narcotic use.     

Decreased expression of bcl-2 (p26) in CD8(+) lymphocytes of patients with T-cell lymphoproliferative disorders of large granular lymphocytes

The objective of the present study was to identify the polychlorinated biphenyl congeners of Aroclor 1254 that are responsible for the induction of the cytosolic bioactivation of aromatic amines. Various chlorobiphenyls, ranging from di- to hexa-substituted, were administered to rats and the ability of the hepatic cytosol to bioactivate 2-aminoanthracene and 2-aminofluorene was investigated. These studies revealed that the induction of the cytosolic activation of aromatic amines increased with the increasing extent of chlorination; moreover, planar congeners were more effective inducers of this activity compared to their non-planar isomers. This observation prompted us to investigate whether the cytosolic activation of aromatic amines is associated with the Ah receptor. Treatment of mice with Aroclor 1254 stimulated the cytosolic activation of aromatic amines in C57BL6 mice, an Ah-responsive strain, whereas it had no effect in DBA2 mice, a non-responsive strain. These findings indicate that the bioactivation of aromatic amines by the liver cytosol is linked to the Ah receptor.     

Malignant lymphoproliferative disorders in liver cirrhosis

BACKGROUND: Lymphoproliferative disorders in patients with liver cirrhosis, although uncommon, have been reported in at least 49 cases. Some authors have suggested that the association between chronic liver disease and lymphoma is not coincidental, that immune mechanisms may be pathogenetically involved. PATIENTS AND METHODS: In the present study we calculated the incidence rate of lymphoproliferative disorders in 334 liver cirrhosis patients (201 males, mean age 59 +/- 12; 133 females, mean age 61 +/- 11) treated at the Gastroenterology Department of the Mauriziano Hospital in Turin from January 1987 to September 1990. RESULTS: We diagnosed 12 lymphoproliferative disorders, corresponding to an incidence of 9.56/1,000 person-years, a figure much higher than expected on the basis of the incidence rate registered in the Turin general population. Six of the 12 lymphoproliferative disorders were non-Hodgkin's lymphomas of the stomach, a proportion by far exceeding expectation. CONCLUSIONS: Our data support the hypothesis that the association between chronic liver disease and lymphoproliferative disorders is not just coincidental, and suggest that liver cirrhosis might be considered an immunological disturbance which entails an increased risk of developing lymphoproliferative disorders. Mechanisms causing lymphoproliferative disorders to develop in the course of chronic liver disease have been hypothesized.     

Simian-virus-40 footprints in human lymphoproliferative disorders of HIV- and HIV+ patients

BACKGROUND: In patients with spina bifida, traditional bowel management programs such as suppositories, retrograde enemas, and manual disimpaction have been largely unsatisfactory. The Malone antegrade continence enema (ACE) procedure has largely changed our approach to bowel management in this patient group. STUDY DESIGN: Over a 3-year period between January 1994 and January 1997, 27 patients with spina bifida underwent the Malone ACE procedure at our institutions. At the time of their ACE procedure, four patients underwent simultaneous continent urinary diversion and three had simultaneous small-bowel bladder augmentation. All the patients were evaluated for 9 months or more after their procedure, and 10 of the patients have been followed for more than 2 years. RESULTS: Postoperatively, predictable bowel control and continence were achieved in 19 of the 27 patients, but 6 had some rectal soiling requiring a sanitary pad. All patients were out of diapers and none reported stomal leakage. Eighteen of the 27 patients were able to manage independently and 9 required assistance. Two patients had stopped using their ACE stoma despite good technical results. The appendix was used as a catheterizable stoma in 15 of the 27 patients. The appendix was not available in 12 patients, so a tubularized cecal flap was used in 9 and a small-bowel neoappendix was created in 3. Complications included stomal stenosis in 5 patients, cecal-flap necrosis in 1, and stomal granulations in 3. CONCLUSIONS: We believe that the ACE procedure provides reliable colonic emptying and avoids fecal soiling in the majority of individuals, and we find it widely and enthusiastically accepted by patients with spina bifida.     

Primary lymphoproliferative disorders of the breast

Primary breast lymphoproliferative disorders are rare lesions and include both the malignant lymphomas and the benign pseudolymphomas. We reviewed 4,491 consecutive cases of breast cancer diagnosed and treated between 1973 and 1988. Patients with lymphoma in other sites and those with lymphomas limited to axillary nodes were excluded. RESULTS. Five patients (0.11%) presented with primary lymphoreticular lesions, of which three were primary non-Hodgkin's lymphoma and two were pseudolymphomas. Patients were followed clinically through to the present time or until death occurred. Surgical procedures included incisional or excisional biopsy in four patients and modified radical mastectomy in one. Two patients received chemo-therapy and one received radiotherapy. One patient with pseudolymphoma subsequently developed infiltrating ductal carcinoma of the same breast. Three patients with primary breast non-Hodgkin's lymphoma died within the follow-up period, with a mean survival of 33 months. CONCLUSIONS. We conclude that primary breast lymphoma is a rare and aggressive breast malignancy with a poor prognosis despite different treatment options.     

Clinicopathologic features of posttransplant lymphoproliferative disorders

Posttransplant lymphoproliferative disorders (PTLD) are primarily B lymphocyte tumors which are related to the Epstein-Barr virus. Recent studies have more clearly delineated neoplastic from hyperplastic forms of this disease. Factors associated with increased PTLD risk include recipient EBV seronegative status and heavy immunosuppression. The clinical presentation of PTLD is reviewed and lesser known features such as respiratory compromise or localization of tumors to skin are highlighted. The pathologic classifications of PTLD are surveyed and related to one another. Newer approaches to therapy, including the use of monoclonal antibodies and adoptive cellular immunotherapy are discussed.     

Management of lymphoproliferative disorders after cardiac transplantation

We conducted a retrospective study of 516 cardiac recipients who underwent transplantation between April 1983 and April 1992, 19 of whom had development of post-transplantation lymphoproliferative disorders (PTLDs). These 19 patients presented with involvement of lung (5), gastrointestinal tract (5), disseminated disease (6), and adenoids and lymph nodes (3). B-cell proliferations ranging from an atypical hyperplasia to malignant lymphoma developed in 18 patients, and mixed cellularity Hodgkin's disease developed in 1 patient. The 19 patients with PTLD displayed a predominance of both women and cardiomyopathy as the indication for transplantation when compared with two separate control populations. No correlation was found between demographic criteria analyzed and (1) early versus late diagnosis of PTLD after transplantation, (2) the site of PTLD involvement, or (3) the histopathologic category of the PTLD lesion. Patients with gastrointestinal tract and lung PTLD involvement enjoyed an improved survival after both transplantation and PTLD diagnosis when compared with patients with PTLD involvement of all other extranodal sites. We report a high incidence of PTLD involving the lung and gastrointestinal tract in our cohort study. These sites of involvement responded better to a reduction in immunosuppression than did the other extranodal sites of involvement.     

Demonstration of frequent occurrence of clonal T cells in the peripheral blood of patients with primary cutaneous T-cell lymphoma

Clonal T cells have been demonstrated in skin lesions of all stages of cutaneous T-cell lymphomas (CTCLs). However, there are conflicting data regarding the CTCL stage at which dissemination of clonal cells into peripheral blood occurs. Although the multifocal occurrence of cutaneous CTCL lesions and T-cell recirculation suggest an early appearance of neoplastic cells in the blood, circulating clonal T cells have only been detected in advanced stages. We investigated their occurrence by a highly sensitive polymerase chain reaction (PCR) assay amplifying T-cell receptor gamma rearrangements and subsequent heteroduplex temperature gradient gel electrophoresis (HD-TGGE) of the amplification products. Circulating clonal T cells were found in 26 of 45 patients with mycosis fungoides (MF), six of seven with Sezary's syndrome (SS), 10 of 13 pleomorphic CTCLs, and three of four unclassified CTCLs. Corresponding skin specimens carried clonal T cells in 29 of 40 MF, three of four SS, 12 of 12 pleomorphic, and two of two unclassified CTCL patients. Except for the blood specimen of a psoriatic patient, all samples of 60 controls (psoriasis vulgaris, atopic dermatitis, and healthy volunteers) revealed polyclonal amplification products. In 30 of 32 CTCL patients carrying a clonal rearrangement in blood and skin, identity of both clones was indicated by HD-TGGE and confirmed by sequencing six of these cases. We found an unexpected high frequency of identical clonal T cells in peripheral blood and skin of CTCL patients, including early stages of MF. This supports the concept of an early systemic disease in CTCL and raises new questions concerning the pathogenesis.     

The molecular genetics of post-transplantation lymphoproliferative disorders

The post-transplantation lymphoproliferative disorders represent a significant clinical and diagnostic problem. However, these disorders also represent an important biological model for studying the development and progression of lymphoid neoplasia in immune deficiency. Accurate diagnosis and classification of these disorders requires correlative multiparametric analysis of the clinical behavior of the patient with the histopathological features, immunophenotype, clonal composition, and genetic alterations of the lymphoproliferative disorder. Such analyses should also assist in furthering our understanding of the pathogenesis of these disorders.