Comparison of genetic probe with immunophenotype analysis in lymphoproliferative disorders: a study of 87 cases

We examined 91 specimens (from 87 patients) for the expression of B- cell- and T-cell-associated differentiation antigens and rearrangements of the Ig and beta-chain of the T-cell (beta-TCR) genes. Of these, 74 were representative of various histologic subtypes of non-Hodgkin's lymphoma and related disorders, 11 of Hodgkin's disease, and 6 of reactive lymphoid hyperplasia. An Ig gene clonal rearrangement correlated to a monotypic (kappa/lambda) phenotype in 32 of 33 histologically defined lymphoma samples. The genotypic analysis also confirmed clonality in six of seven malignant diffuse lymphomas that were nonmonotypic but expressed pan-B antigens; in four, more than one clone was detected within individual tumors. A beta-TCR clonal rearrangement was found in 19 of 19 tumor samples considered as malignant T-cell lymphoma on the basis of histopathology and of the CD3- positive phenotype of tumoral cells, and in two cases of CD3-positive lymphomatoid disorders. A loss of pan-T antigens (CD7, CD5, CD2, CD4/CD8) was observed in all but three of these CD3-positive samples. Such an incomplete T-cell phenotype always correlated to the presence of a monoclonal process as revealed by genotypic analysis. DNA analysis was the only way to demonstrate clonality in other samples with either a polymorphous (partial involvement, pseudolymphoma, angioimmunoblastic lymphodenopathy [AILD]) or an undifferentiated (large cell anaplastic) phenotype. It is concluded that although in the majority of cases immunophenotyping alone provides criteria adequate for the diagnosis of lymphoid malignancy, in some, particularly polymorphous or large cell anaplastic processes, genetic probe analysis was additionally discriminative.     

Auditory evoked phosphenes in optic nerve disease

Five patients with optic neuropathy, four vascular and one demyelinating, are described who each complained of an unusual symptom. Bright flashes of light (phosphenes) occurred in the affected eyes and were evoked by sudden unexpected sounds. Movement of the eye alone did not reproduce the symptom. In all patients the phenomenon was sufficiently prominent to interfere with sleep and was the main complaint of one patient. An anticonvulsant (phenytoin) greatly reduced the frequency and intensity of the phosphene in one patient.     

Natural killer-like T-cell lymphomas: aggressive lymphomas of T-large granular lymphocytes [see comments]

Natural killer (NK)-like T cells are major histocompatibility complex- unrestricted cytotoxic T cells that are surface CD3-positive, express NK-cell antigens, and rearrange their T-cell receptor. Most neoplasms arising from this T-cell subpopulation have been a chronic lymphoproliferative disease referred to as T-large granular lymphocyte (LGL) leukemia. Only 10 NK-like T-cell lymphomas have been described in detail previously; this study presents the clinicopathologic features of six others and distinguishes these lymphomas from T-LGL leukemia. All patients presented with B-symptoms and often had marked hepatosplenomegaly without significant peripheral lymphadenopathy. Four of the six patients were immunosuppressed. All had CD3, CD8, CD56- positive tumors, presumably of hepatosplenic (n = 3), intestinal (n = 1), pulmonary (n = 1), or nodal (n = 1) origin. Three patients had lymphomatous bone marrow infiltrates, and four had peripheral blood involvement by neoplastic large lymphocytes, some of which had a blastic appearance or resembled virocytes. Azurophilic granules, ultrastructurally corresponding to cytoplasmic dense core and/or double density granules, were seen in all cases. T-cell clonality was shown in five tumors by Southern blot analysis, and three had abnormal karyotypes. Two untreated patients died 20 days after presentation, and three patients who received combination chemotherapy died within 5 months of presentation. One patient remains in complete remission 22 months after treatment. These findings suggest NK-like T-cell lymphomas are aggressive, are clinicopathologically distinct from T-LGL leukemia, and should be in the differential diagnosis of extranodal T-cell lymphoproliferations, including those in immunosuppressed patients. Furthermore, the LGL morphology, phenotype, and tissue distribution of some NK-like T-cell lymphomas suggest they arise from thymic- independent T cells of the hepatic sinusoids and intestinal mucosa.     

High-dose intravenous gammaglobulin in alloimmunized platelet transfusion recipients

High-dose intravenous gammaglobulin (polyvalent immunoglobulin G) has been shown to be of benefit in some patients with immune thrombocytopenic purpura (ITP), possibly by producing reticuloendothelial system blockade. We studied this approach in patients refractory to random donor platelet transfusion using an IV IgG preparation manufactured by the Swiss Red Cross. Eleven adult patients with acute leukemia received either 0.4 g IgG/kg/d intravenously X five days (four patients) or 0.6 g/kg/d X five days (seven patients). All patients had high levels of lymphocytotoxic antibody and poor responses to random donor platelets. Except for mild headaches in two patients, there were no side effects related to the IgG infusions. All patients had significant elevations of serum IgG on the day after completion of treatment. Either random donor or partially HLA-matched platelet transfusions were administered the day after and, in some cases, during the IgG therapy. No patient had an improvement in one hour posttransfusion platelet count increments. Two additional patients received pooled platelet concentrates incubated for 30 minutes at 37 degrees C with IgG at a final concentration of 3 g% prior to transfusions. These results indicate that high-dose IgG, an extremely expensive treatment, cannot be recommended for alloimmunized adults with leukemia.     

Transfusion transmission of human T-lymphotropic virus types I and II: serologic and polymerase chain reaction results in recipients identified through look-back investigations

To determine the transmissibility of human T-lymphotropic virus types I and II (HTLV-I and HTLV-II) via transfusion, persons who, from 1983 to 1989, received blood components donated by persons who subsequently tested anti-HTLV-I-positive were evaluated. It was found that 16 (30%) of 54 evaluable recipients of transfused cellular components became infected with one of the HTLVs: 8 had HTLV-I and 8 had HTLV-II. Forty percent of platelet recipients and 28 percent of red cell recipients acquired infection. The rate of transmission of HTLV-I and HTLV-II was significantly correlated with storage age of red cell units prior to transfusion: 47 percent for red cells stored < or = 14 days and 0 for red cells stored > 14 days (p < 0.01). Multiple confirmatory serologic tests performed in 46 anti-HTLV-I enzyme immunoassay-negative recipients revealed that HTLV infection could not be excluded in 3 recipients of blood components from HTLV-II-infected donors. Polymerase chain reaction established HTLV-II infection in one recipient, and the other two recipients could not be classified with respect to HTLV infection status. It appears that some HTLV-II-infected transfusion recipients will not be detected by existing HTLV-I antigen-based reagents. If it is deemed necessary to initiate or continue look-back programs to detect transfusion transmission of HTLV-II infection, it is suggested that the current testing algorithm be modified in selected cases.     

Cryopreservation of all prezygotes in patients at risk of severe hyperstimulation does not eliminate the syndrome, but the chances of pregnancy are excellent with subsequent frozen-thaw transfers

In-vitro fertilization patients (n = 15) at risk of ovarian hyperstimulation syndrome (OHSS) (oestradiol > or =4500 pg/ml on the day of human chorionic gonadotrophin administration and 25 or more follicles of intermediate or large size) underwent aspiration of all follicles and cryopreservation of all fertilized oocytes at the pronuclear stage. Patients were monitored for up to 2 weeks post- retrieval. Subsequent transfer of cryopreserved-thawed embryos was performed in programmed cycles using exogenous oestrogen and progesterone for endometrial preparation. Two patients (13%) developed OHSS necessitating hospitalization and vaginal aspiration of ascitic fluid. Two other patients (13%) developed moderate OHSS requiring ascitic fluid vaginal aspiration in the office setting, with dramatic improvement of the condition. Subsequent transfer of cryopreserved- thawed embryos yielded a clinical pregnancy rate of 58% per transfer and ongoing or delivery rates of 42 and 67% per transfer and per patient respectively. By eliminating pregnancy potential with cryopreservation of all prezygotes and examining the pregnancy potential with subsequent cryopreserved-thawed transfers, it is concluded that OHSS is reduced, but not eliminated for patients at risk. Subsequent transfer of cryopreserved-thawed prezygotes in a programmed cycle with exogenous steroids yields an excellent pregnancy rate.      

Conceptual issues specifically related to health-related quality of life in critically ill patients

During recent years increasing attention has been given to the quality of survival in critical care. Health-related quality of life (HRQOL) is an important issue both for patients and their families. Furthermore, admission to the intensive care unit can have adverse psychological effects in critically ill patients. Recent studies conducted in critically ill patients have measured HRQOL. However, usually absent from such reports are evaluations of conceptual issues, addressing factors such as why HRQOL should be measured in critically ill patients, how to define and standardize domains of HRQOL, whether proxies can provide useful information about HRQOL in critically ill patients, whether response shift occurs in critically ill patients, and whether post-traumatic stress disorder (PTSD) occurs in critically ill patients. Some studies reported moderate agreement between patients and their proxies, although lower levels of agreement may be reported for psychosocial or physical functioning. Response shift (adaptation and change in perception) appears to be an important phenomenon and likely to be present, but it is seldom measured when estimating HRQOL in critically ill patients. Furthermore, vigilance for symptoms of PTSD and early interventions to prevent PTSD are needed.     

Liver metastasis of a mucinous colonic carcinoma mimicking a haemangioma in T2‐weighted sequences

We report the case of a patient with a single liver metastasis of a mucinous colonic carcinoma that mimics a haemangioma in T2‐weighted sequences. Although a very high T2 signal in non‐cystic lesions is highly specific for the diagnostic of haemangioma, the use of gadolinium‐enhancement MRI is recommended. In patients with a history of neoplasia, the diagnosis of benign liver nodules should be made with caution.