High-grade T-cell lymphoma complicating B-cell chronic lymphocytic leukemia: an unusual manifestation of "Richter's syndrome".

Approximately 3% of patients with B-cell chronic lymphocytic leukemia (CLL) develop a high-grade large-cell lymphoma consistent with Richter's Syndrome. In most cases, these lymphomas are of B-cell origin and are believed to arise by clonal evolution from the CLL cells. We present a case of a patient with a 10-year history of B-CLL who developed an aggressive large-cell lymphoma, confirmed by immunophenotype to be of T-cell origin. We suggest that in patients with CLL, immunodysregulation can result in the proliferation of T cells, which may mutate and result in the development of a new malignant clone.

Apoptotic index from fine needle aspiration cytology as a criterion to predict histologic grade of non-Hodgkin's lymphoma.

OBJECTIVE: To investigate whether the assessment of apoptotic index (AI) from fine needle aspiration (FNA) smears of non-Hodgkin's lymphomas (NHL) is reliable and has potential utility as a criterion to predict histologic grade. STUDY DESIGN: AI was independently determined by four cytopathologists as a percentage from routine FNA smears in 96 NHLs and 15 lymphoid hyperplasias. Working formulation (WF) grades from corresponding surgical biopsies were modified to include mantle zone-derived NHLs as intermediate grade and to make diffuse large cell NHL a separate category called "high" grade, whereas WF high grade NHLs were called "very high" grade. Histologic grades were also derived from the Revised European American Lymphoma (REAL) classification. AI was compared with histologic grade using the unpaired, two-tailed Student t test. These data were used to determine potential thresholds for AI that separate lower from higher grade NHLs. RESULTS: Measurements of AI strongly correlated between cytopathologists (median r = .93). Low and intermediate grade NHLs had indistinguishable AIs, whereas higher grade NHLs had significantly higher AIs. Appropriate potential AI thresholds between low or intermediate grade and higher grade NHLs were in the range of 1.5-2.5% (modified WF) and 1-2% (REAL). CONCLUSION: There is excellent interobserver reliability in the measurement of AI from FNAs of NHLs. Higher AIs distinguish higher from lower grade NHLs. Diffuse large cell NHLs had AIs that were similar to WF high grade NHLs.

Peripheral T cell lymphoma in a patient with common variable immunodeficiency disease: case report and literature review.

This report documents the occurrence of a peripheral T cell lymphoma arising in the bone marrow and liver of a patient with common variable immunodeficiency disease. The T cell origin of this lymphoma was demonstrated by immunohistochemical phenotyping and gene rearrangement studies and was not associated with EBV infection of the lymphoma cells. The frequency and characteristics of lymphomas complicating CVID are reviewed.

A paraneoplastic mixed bullous skin disease associated with anti-skin antibodies and a B-cell lymphoma.

BACKGROUND: The full spectrum of bullous diseases associated with underlying cancers remains to be fully defined. OBSERVATION: We describe a patient with a mixed bullous disease exhibiting combined features of cicatricial pemphigoid and pemphigus and associated with a B-cell lymphoma producing an IgM paraprotein to intercellular antigens in human skin. The patient had the clinical features of cicatricial pemphigoid and the histologic and immunofluorescence abnormalities of both cicatricial pemphigoid and pemphigus. These included oral and cutaneous erosions; ocular scarring; subbasal and acantholytic intraepidermal bullae; and circulating and tissue-fixed basement membrane zone and intercellular antibodies. The antibodies were directed to a 140-kd antigen in dermal extracts of skin split with 1 mol/L of sodium chloride and to antigens with approximate molecular weights of 150, 180, 230, and 285 kd in the dermal extract. In contrast to paraneoplastic pemphigus, the intercellular antibodies did not react to mammalian bladder. The intercellular antibodies were of the IgM class and were associated with the paraprotein produced by the malignant B cells. CONCLUSIONS: We believe that this condition represents a novel bullous disease, which we refer to as paraneoplastic mixed bullous disease. This condition illustrates that distinct bullous diseases are associated with paraneoplastic syndromes and that at least one possible mechanism for such eruptions is the production of anti-skin antibodies by malignant B cells.

The association of progressive, atrophying, chronic, granulomatous dermohypodermitis with Hodgkin's disease.

The case of a patient with an unusual skin disorder--progressive, atrophying, chronic, granulomatous dermohypodermitis (PACGD)--who developed Hodgkin's disease is reported. A review of the literature revealed only two other cases of PACGD, one of which affected a patient who also was found to have Hodgkin's disease. In an additional report, the diagnosis of Hodgkin's disease was made in a patient who may have had the same dermatologic disorder. The case is reported because the association of these two rare diseases is believed to be more than a chance event.

Simultaneous occurrence of mycosis fungoides and Hodgkin disease: clinical and histologic correlations in three cases with ultrastructural studies in two.

We present three patients who manifested both Hodgkin disease and mycosis fungoides. Ages ranged from 39 to 66 and two were male. Skin lesions were present from 3 to 40 years before the diagnosis of Hodgkin disease. In all cases, mycosis fungoides was confirmed histologically by skin biopsy; the clinical course of the mycosis fungoides was indolent in all cases. Hodgkin disease was confirmed histologically in three, and confirmed by electron microscopy in two. All three patients responded to appropriate treatment for Hodgkin disease and are alive and well at the present time.

Evolution of Sézary syndrome in the course of hairy cell leukemia.

A patient with a history of "leukemia" for 19 yr and documented hairy cell (HC) leukemia for 10 yr developed mycosis fungoides and the Sézary syndrome. The manifestations of both diseases were diagnostic on clinical and pathologic grounds. Ultrastructural, immunohistochemical, and surface marker techniques proved the HC to have phenotypic characteristics of the T-helper subset of lymphocytes to which the Sézary cells (SC) also belonged. Both types of cells contained tartrate-resistant acid phosphatase. HC did not infiltrate the skin. SC did not contain ribosome lamellar complexes. Because of otherwise overlapping morphology and the apparent replacement of HC by SC, it is likely that the Sézary cells constituted a genetic variant of the original neoplastic clone represented by the hairy cells. Since the biologic and therapeutic implications of such clonal evolution may be important, subtle phenotypic changes should be looked for repeatedly in patients with these diseases.

Procainamide-induced agranulocytosis and thrombocytopenia.

Procainamide therapy has frequently been reported as a cause of agranulocytosis, but severe thrombocytopenia associated with the use of this drug has been noted only once. We report a case of simultaneously occurring agranulocytosis and profound thrombocytopenia in a patient receiving procainamide hydrochloride. Different mechanisms appeared to be responsible for the two cytopenias.

In vivo lability of glucose-6-phosphate dehydrogenase in GdA- and GdMediterranean deficiency.

A decreased level of glucose-6-phosphate dehydrogenase might result from decreased rate of synthesis, synthesis of an enzyme of lower catalytic efficiency, increased lability, or a combined mechanism. To test the hypothesis of increased lability, the rate of decline of the enzyme in vivo was measured in three groups of individuals, controls, Gd(-),A-males, and Gd(-), Mediterranean males, by the slope of decline of activity in fractions containing erythrocytes of progressively increasing mean age. These fractions were obtained by ultracentrifugation on a discontinuous density gradient of erythrocyte suspensions free of contaminating platelets and leukocytes. The rate of in vivo decline of pyruvate kinase (another age-dependent enzyme) was also measured and found very similar in the three groups. The in vivo decline of glucose-6-phosphate dehydrogenase was found to follow an exponential rate, with a half-life of 62 days for controls and 13 days for Gd(-),A- erythrocytes. The activity in normal reticulocytes was estimated at 9.7 U and in Gd(-),A- reticulocytes at 8.8 U. These estimates were confirmed by direct measurements in reticulocytes isolated from patients with extreme reticulocytosis. In Gd(-),Mediterranean erythrocytes activity could be demonstrated only in reticulocytes, which were estimated to average 1.4 U. The rate of decline is so extreme that no activity could be detected in mature erythrocytes. These data suggest that the glucose-6-phosphate dehydrogenase deficiency of both the Gd(A-) and the GdMediterranean variant results from different degrees of in vivo instability of the abnormal enzyme.