Idiopathic pure red cell aplasia: first report on CD8 positive lymphocytosis in bone marrow biopsy sections.

There is no information in the literature regarding the lymphocyte content or type in bone marrow biopsies from patients with "idiopathic" pure red cell aplasia (PRCA). This report describes the bone marrow biopsy sections of a patient with PRCA. A diffuse CD3 positive (CD8 positive, granzyme B negative) lymphocytosis of approximately 1500/mm3 was revealed by immunohistochemical staining. The extent of the T cell increase was not evident from morphological examination of the bone marrow aspirate or biopsy, from flow cytometric analysis of the aspirate, or from the peripheral blood lymphocyte count. Therefore, immunohistochemical analysis should be performed routinely in this rare disease and the data acquired may help to inform the choice of treatment.

WHO reclassification of breast lymphomas.

Fourteen cases of breast lymphoma, identified from hospital records between 1990 and 2004, were reclassified according to the World Health Organisation criteria. Primary cases occurred more frequently and all cases were of B cell origin, predominantly involving the right breast. Most primary cases were diffuse large B cell lymphomas, whereas secondary cases were heterogeneous in type and most had a poor prognosis.

Quantitation of monoclonal plasma cells in bone marrow biopsies in plasma cell dyscrasia.

Direct measurement of monoclonal plasma cell mass in bone marrow biopsies may be a useful parameter to establish in plasma cell dyscrasia. In this study monoclonal plasma cells/mm in light chain immunoglobulin immunostained archival bone marrow sections from 22 patients in whom a diagnosis of multiple myeloma (MM) had been excluded but who had monoclonal proteins were counted by two observers at light microscopic level. There was good correlation between the counts of the two observers. The levels of monoclonal plasma cells/mm in biopsies were not related to the % counts in the aspirates taken at the same time as the biopsies. Three of seven patients with biopsy levels in excess of the polyclonal levels in patients without plasma cell dyscrasia developed progressive MM within the observation time. Monoclonal plasma cell levels/mm of bone marrow biopsies can be measured and they provide a useful parameter for the assessment of patients with low volume plasma cell dyscrasia.

Mantle cell lymphoma presenting as a breast mass.

Breast lymphoma accounts for less than 1% of all non-Hodgkin's lymphomas (NHLs) and approximately 0.1% of all breast neoplasms. Most breast lymphomas are classified as diffuse large B cell or mucosa associated lymphoid tissue (MALT) lymphomas. The case of a 53 year old woman presenting with a breast mass and found to have mantle cell lymphoma is described. Core biopsy of the breast lesion showed a B cell NHL, probably of large cell type and of high grade. Morphological and immunophenotypic analysis of peripheral blood and bone marrow samples suggested a mantle cell lymphoma (MCL). This was confirmed by the detection of a t(11;14) in the bone marrow aspirate and breast tissue by polymerase chain reaction analysis. There have been no previous reports of an MCL presenting as a breast lump. Because a diagnosis of MCL has prognostic and therapeutic implications, this case highlights the need for an awareness of MCL presenting in this way, and the requirement for specialised investigations in its detection.

Histiocytic lymphoma presenting as a testicular tumour and terminating in acute monoblastic leukaemia.

A 58 year old man presented in 1995 with a swollen testicle. After orchidectomy, a diagnosis of poorly differentiated lymphoma was made. Lymphoid, epithelial, and seminoma markers were all negative. Six months later he developed a buccal lesion, which was biopsied and reported as a high grade non-Hodgkin's lymphoma. It responded completely to chemotherapy but within a year he developed a forearm swelling, which was biopsied and imprints made before fixation of the material. Immunocytochemistry on the imprints showed positivity with antibodies to CD4, CD68, and muramidase, and the non-specific esterase cytochemical stain was strongly positive, leading to a diagnosis of true histiocytic lymphoma. Despite further treatment, the patient entered a terminal acute leukaemic phase, the blasts marking as monoblasts. Review of all the biopsies, including molecular investigations and further immunohistochemistry studies performed retrospectively on the original biopsy, demonstrated that this was the same malignant cell line throughout, and we conclude that this is a case of histiocytic lymphoma, initially presenting as a testicular tumour and terminating in acute monoblastic leukaemia. A diagnosis of histiocytic lymphoma should be considered when lymphoid markers are negative in an apparent lymphoma, but should not be made without recourse to appropriate immunophenotypic and molecular studies.

Quantitative deficiency of monocyte-specific esterase (MSE) mRNA in monocyte esterase deficiency (MED).

Cytochemical staining of monocyte-specific esterase (MSE) is widely used for identification of the monocytic lineage in leukaemias. Deficiency of this enzymatic activity occurs as a familial trait and the deficiency has been shown to occur with greater frequency in patients with lymphoproliferative or gastrointestinal malignant neoplastic diseases than in normal blood donors. Reverse transcriptase polymerase chain reaction (RT-PCR), sequencing and quantification by Northern blot analysis was conducted on the MSE mRNA of 12 subjects with monocyte esterase deficiency (MED) and seven MSE-positive subjects to examine whether mutations were present or whether the defect was quantitative. Mutations were not found in the mRNA sequences. However, MED subjects had significantly less MSE mRNA than MSE-positive subjects (P = 0.001). These findings show that deficiency of monocyte esterase activity in MED is not as a result of the presence of inactive isoenzymes and may be owing to an abnormality in the regulation of mRNA production.

Familiality of monocyte esterase deficiency in patients on continuous ambulatory peritoneal dialysis.

The purpose of this study was to determine whether or not peripheral blood monocyte esterase deficiency occurring in patients on CAPD was a familial characteristic. The peripheral blood monocyte esterase status of 74 patients on CAPD was determined by a naphthyl acetate esterase staining of cytospin preparations of their mononuclear cells following separation over ficoll. The peripheral blood of first degree relatives and spouses of monocyte esterase deficiency patients was similarly investigated for the deficiency. Three patients bad monocyte esterase deficiency and familiality of the defect was demonstrated in two of their families. The third family was incompletely investigated because of lack of consent. The monocyte esterase deficiency demonstrated in this cohort of patients did not result from their renal failure but was a familial characteristic.

Outcome in Hodgkin's disease: a 20-year cohort of patients.

We reviewed the long-term survival, treatment-related mortality and morbidity of a continuous cohort of patients with Hodgkin's disease diagnosed and staged at the Haematology unit of the Belfast City Hospital between January 1973 and October 1992. The analysis included a comparison of the survival of those patients who were entered into BNLI (British National Lymphoma Investigation) trials compared to those not entered during this 20 year period. In addition univariate and multivariate analysis of prognostic factors was performed. The complete remission rate (CR) was 79.6% with a 15 year survival of 55.3%. On multivariate analysis in which deaths due to active Hodgkin's disease only were considered age > 50 emerged as the most significant prognostic factor (P < 0.0007), the presence of B symptoms also having independent significance (P = 0.008). Trial status did not have any independent prognostic significance. Eighty one deaths occurred: active Hodgkin's disease (50), second malignancy (9), treatment-related (10), unrelated (9), unknown (3). This long-term follow up study provides useful information additional to the data produced by clinical trials which are biased by selection criteria. The occurrence of Haemophilus Influenzae meningitis in a patient 17 years following splenectomy highlights the need for appropriate vaccination of patients splenectomised for Hodgkin's disease.

Renal failure and esterase-negative monocytes.

Monocyte esterase deficiency (MED) has been found to be linked with autoimmune (1,2) and lymphoproliferative (2,3) disease. The incidence of MED where > 85% of peripheral blood monocytes are consistently negative in the cytochemical stain for monocyte esterase activity, was shown to be significantly raised in patients with renal failure (3.8%) as compared to the incidence in normal blood donors (0.8%) in a survey performed at the Belfast City Hospital in 1987 (2). The overall occurrence of any proportion of esterase-negative monocytes (ENMs) in patients with renal disease has not been previously studied. The aims of this study were to document this occurrence, and by examining the clinical and biochemical parameters associated with ENMs to identify possible reasons for their occurrence. The original survey data were reexamined and further information previously unreported regarding the occurrence of ENMs was extracted from the renal patient cohort data. Clinical and biochemical data were obtained from the hospital notes of the renal patients and associations sought between these parameters and the occurrence of ENMs. ENMs occurred in a significantly higher proportion (31%) of the renal patients than in the normal population (8%; p < 0.001 chi-sq.) or any other hospital population. A highly significant association between rising serum phosphate levels and increasing proportions of ENMs was identified (p < .001) and this association proved to be independent of serum creatinine levels and renal dialysis status. There is a marked increase in occurrence of esterase-negative monocytes in patients with renal failure. This increase was not caused by the degree of renal failure as reflected by serum creatinine levels, nor by renal transplantation or immunosuppressive therapy. A significant association between rising serum phosphate and increasing proportion of esterase-negative monocytes was identified. This new information, when considered with the previously described experimental and epidemiology evidence for malfunction of esterase negative monocytes, identifies a phenomenon which may contribute to the immunological difficulties of patients with chronic renal failure.

Organophosphates and monocyte esterase deficiency.

AIMS: To examine the possibility that monocyte esterase deficiency (MED) could be caused by exposure to organophosphates. METHODS: Pseudocholinesterase, paraoxonase and arylesterase activities were measured in the serum and acetylcholinesterase activity was measured in the red cells of a group of monocyte esterase deficient subjects and compared with the enzyme activities of a control group of monocyte esterase positive subjects. RESULTS: No significant difference was found between the enzyme activities of the monocyte esterase deficient group and the control group for any of the esterases investigated. CONCLUSION: Current or recent exposure to organophosphorus is not the cause of MED.

Bone marrow necrosis.

Bone marrow necrosis is most frequently diagnosed at postmortem examination. Antemortem diagnosis is still uncommon. In a recent review of world literature, we have found 133 cases of bone marrow necrosis diagnosed during life. It has been observed during the course of a wide variety of diseases, most commonly in association with acute and chronic leukemia, carcinoma, malignant lymphoma, infections, and sickle cell disease. We report two intravitally diagnosed cases of bone marrow necrosis occurring in two patients with high-grade B-cell lymphoproliferative disease. These cases are unusual in that both patients had a triad of bone marrow necrosis, high-grade B-cell lymphoproliferative disease, and hypercalcemia. Despite chemotherapy, both cases ultimately proved fatal, with progressive involvement of the central nervous system.

Monocyte esterase deficiency in gastrointestinal cancer.

AIM: To substantiate the high incidence of monocyte esterase deficiency (MED) in gastrointestinal carcinoma already reported in a small group of patients; to compare the clinical findings in esterase deficient and esterase positive patients. METHODS: Peripheral blood smears (n = 22) or cytocentrifuge preparations (n = 52) of mononuclear cells from the peripheral blood of patients with gastrointestinal carcinoma were stained by the non-specific esterase stain (pH 5.8) using a batch technique. Samples containing > or = 85% esterase negative monocytes were identified at light microscopic examination. RESULTS: Seven of 74 patients were identified as having MED. This correlated exactly with the proportion (five of 46) found before, using an automated method, and was significantly higher than the 0.8% incidence in normal blood donors shown in that study. Comparison of the clinical details of the 12 MED patients with those of 105 esterase positive patients showed a significantly longer disease free survival in the MED cohort and increased occurrence of benign neoplasms--largely colorectal polyps--in this group also. Three patients had a borderline degree of deficiency and were excluded from comparisons, although they showed the same clinical tendencies as the MED group. CONCLUSIONS: There is a strong degree of association between monocyte esterase deficiency and gastrointestinal carcinoma. Further evidence must be sought to prove that the deficiency precedes the disease and therefore may predispose to it, or at least may identify subjects with such a predisposition. This could lead to early diagnosis and effective treatment of gastrointestinal carcinoma in a sizeable proportion of patients.

Myeloma--results of treatment 1986-1990.

Sixty-nine patients with multiple myeloma diagnosed during a five year period at the Belfast City Hospital were followed until death or for a minimum of one year in a retrospective study of survival. Although the patients were unselected, survival data was found to be similar to results from trials in which patient selection had occurred. Overall median survival was thirty-two months. Median survival fell with advancing disease and was 47, 27 and 18 months for Durie-Salmon stages I, II and III respectively. Those patients presenting with a platelet count of < 100 x 10(9)/1 had a median survival of eight months in contrast to those with a platelet count > 100 x 10(9)/1 whose median survival was 36 months. Patients presenting in renal failure had a shorter median survival of 28 months compared to 46 months for those with normal renal function.

Myeloperoxidase deficiency in a patient with rheumatoid arthritis: oxygenation and radical activity by phagocytic cells.

Complete functional deficiency of the phagocytic cell enzyme, myeloperoxidase, is described in a patient with rheumatoid arthritis. Measurement of oxygenation and free radical activity by blood monocytes and polymorphonuclear leucocytes shows gross reduction in myeloperoxidase-dependent chemiluminescence. Implications of these data for theories linking reactive oxygen species to inflammatory tissue damage in rheumatoid arthritis are discussed.

Cell sizing in chronic lymphoproliferative disorders: an aid to differential diagnosis.

AIMS: To determine if leucocyte volume distribution analysis (LVDA), obtained using a Coulter Counter Model S Plus IV, can be used to aid differentiation of chronic lymphoproliferative disorder (CLPD) subtypes. METHODS: Mean lymphocyte volume and lymphocyte distribution width were measured on each patient (n = 90) using a hard copy of an amplified LVDA histogram. The mean lymphocyte volume was taken as the mean of the values on either side of the peak at half maximum height. The lymphocyte distribution width was taken as the range of cell values between the two values used to calibrate the mean lymphocyte volume. A template showing typical histograms from commonly occurring CLPD was also produced on an acetate sheet. This was used to examine the histogram from each new patient to evaluate its usefulness as an alternative to the calculation of mean lymphocyte volume and lymphocyte distribution width. RESULTS: Mean lymphocyte volume and lymphocyte distribution width were significantly higher in B cell lymphocytic leukaemia of mixed cell type (B CLL/PL), B cell non-Hodgkin's lymphoma with peripheral blood spill, hairy cell leukaemia and T cell prolymphocytic leukaemia than in B cell chronic lymphocytic leukaemia (B CLL). The mean lymphocyte volume, but not the lymphocyte distribution width, was also significantly higher in T cell chronic lymphocytic leukaemia than in B CLL. The template gave an immediate preliminary indication of possible subtype(s) of disorder and could be used as an alternative to measurement of mean lymphocyte volume and lymphocyte distribution width. CONCLUSIONS: Electronic haematology analysers producing an LVDA provide a useful, cost effective cell sizing analysis which can aid the differentiation of subtypes of CLPD.