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P G Isaacson

Publications and source records attributed to P G Isaacson.

At least 19 recordsLinked to original sources
PubMed1992

High incidence of primary gastric lymphoma in northeastern Italy.

We previously noted an extraordinarily high number of cases of primary gastric lymphoma (PGL) in northeastern Italy. We have now formally compared the incidence in Feltre, Italy, with that in three similar communities in the UK. Each community has a stable population served by a single endoscopy unit and histopathology laboratory. There were 13 times more cases of PGL in Feltre in 1986-91 than in the UK communities (66 vs 5 per 100,000 per 5 years). The incidence of gastric adenocarcinoma was also substantially higher in Feltre than in the UK (270 vs an average of 82 per 100,000 per 5 years), as was the prevalence of gastritis associated with Helicobacter pylori infection (87% of 1343 gastric biopsy samples in 1991).

Humans↗
PubMed1992

Epstein-Barr virus latent membrane protein expression by Hodgkin and Reed-Sternberg-like cells in acute infectious mononucleosis.

In the light of reports of latent membrane protein (LMP) expression by Hodgkin and Reed-Sternberg (HRS) cells, paraffin sections of tonsil (two cases), lymph nodes (eight cases; three cervical, one axillary, and four inguinal) and spleen (four cases) from 14 patients with acute infectious mononucleosis (IM) have been examined for the presence of HRS-like cells and immunostained with an antibody to LMP. Sections of the tonsils and one lymph node were also stained with a panel of antibodies which characterize HRS cells of Hodgkin's disease. The tonsils contained abundant HRS-like cells, mainly adjacent to the crypts, which were highlighted by strong LMP expression. The immunophenotype of these cells closely, but not completely, resembled that of HRS cells of Hodgkin's disease. The lymph nodes and spleens showed the typical changes of acute IM but only few LMP-positive HRS-like cells were present in the cervical lymph nodes and hardly any were present in the inguinal nodes and spleen. These findings suggest that tonsillar crypt squamous epithelium may play a role in the formation of LMP-positive HRS-like cells; these cells could be progenitors of Hodgkin's disease HRS cells and, if so, this might explain the restricted sites of presentation of Hodgkin's disease.

Acute Disease↗
PubMed1992

Proliferating cell nuclear antigen (PCNA) expression in Hodgkin's disease.

Previous studies of the proliferating cell fraction in Hodgkin's disease (HD) have been directed towards the classical Hodgkin and Reed-Sternberg cells (HRS) to the exclusion of the background population and have not included cases of nodular lymphocyte predominant Hodgkin's disease (NLPHD). Using an antibody to proliferating cell nuclear antigen (PCNA), we have determined the growth fraction of HRS cells and L&H cells in paraffin sections of 15 cases of classical HD [12 nodular sclerosis (NS), 3 mixed cellularity (MC)] and eight cases of NLPHD. By double staining with anti-PCNA and antibodies to B cells (CD20) and T cells (CD45RO), we also determined the growth fraction and immunophenotype of the background population in each case. In classical HD, 50.4 per cent of HRS cells were PCNA-positive and judged to be proliferating, which is comparable to previous studies, while in NLPHD 76.9 per cent of L&H cells were PCNA-positive. In both classical HD and NLPHD, the majority of PCNA-positive cells in the background were T cells, which showed a growth fraction of 57.8 and 68.5 per cent, respectively; in comparison, only 4 per cent of B cells were PCNA-positive in each type of HD. L&H cells are widely accepted to be B cells and there is growing evidence that HRS cells are also B cell-derived. Our results underline a relationship between classical HD and NLPHD and suggest that the characteristic histological features of both diseases may be caused by the production and release of cytokines from altered B cells.

Antigens, CD↗
PubMed1992

Cytogenetic study of B-cell lymphoma of mucosa-associated lymphoid tissue.

The recently described B-cell lymphomas arising in mucosa-associated lymphoid tissue (MALT) form a distinct clinico-pathologic group of non-Hodgkin's lymphoma, and therefore would be expected to be characterized by a recurrent chromosomal aberration. We have analyzed the cytogenetics of 23 cases of MALT lymphomas arising in the stomach, small intestine, lung, and lacrimal gland. In each case the presence of an abnormal clonal cell population was confirmed by the identification of rearranged bands when digested tumor DNA was hybridized with a probe to the joining region of the immunoglobulin heavy chain gene. Metaphase spreads were obtained in 14 cases, of which 9 cases showed an abnormal karyotype. Although no unifying aberration was detected, rearrangements of chromosome 1p, and numerical abnormalities of chromosomes 3 and 7, may play a role in the genesis of these tumors.

Chromosome Aberrations↗
PubMed1992

Splenic marginal zone cell lymphoma.

We describe four female patients with primary splenic low-grade non-Hodgkin's B-cell lymphomas with the morphology and immunophenotype of splenic marginal zone lymphocytes. The patients presented with splenomegaly, anemia, and weight loss. The bone marrow was involved in all four cases. Liver involvement was found in one patient; and in another, a CT scan revealed lymphadenopathy in the chest and abdomen. The histology of the spleen was characterized by broad concentric strands of monomorphic medium-sized lymphocytes around lymphoid follicles in one case and infiltrating follicles in two cases. Selective replacement of follicles was seen in one case. Tumor in splenic hilar lymph nodes (four cases) and liver (one case) was similar. Three patients remain well 4, 9, and 12 months, respectively, after splenectomy without further treatment. One patient who received chemotherapy died 1 year after splenectomy.

Adult↗
PubMed1992

Pathology of malignant lymphomas.

Although the subject is now seldom formally addressed, much of the pathologic research into malignant lymphoma is still tacitly directed at developing a rational and reproducible classification. Pure morphology, while remaining of critical importance in the diagnosis of malignant lymphomas, has been exhausted as a means of understanding the biology of these tumors, which must be the eventual basis of a firm, enduring and clinically relevant classification. Thus, histopathologists have turned first to immunohistochemistry and now to molecular genetics to make sense of their morphologic observations. Correlation of various genetic (including oncogenetic) rearrangements with morphology has preoccupied pathologists this past year and has led to important advances in the understanding of B- and T-cell lymphomas. Lymphomas occurring in a setting of immunodeficiency, whether therapeutically induced or acquired, have received special attention, and the possible role of the Epstein-Barr virus in their pathogenesis has induced pathologists to develop exciting in situ molecular hybridization techniques for its identification in tissues. The certainties underlying the diagnosis and classification of Hodgkin's disease (in which Epstein-Barr virus also appears to play a role), formally the only truly secure area for pathologists, have been disturbed, and the borderline between Hodgkin's disease and non-Hodgkin's lymphoma is now seriously blurred. The lymphoma pot has been well and truly stirred; we must now wait to see what the new sediment offers.

Humans↗
PubMed1992

The lymphoepithelial lesion of gastric low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT): an ultrastructural study.

Lymphoepithelial lesions are a characteristic feature of primary, gastric low-grade lymphomas of mucosa-associated lymphoid tissue (MALT). The lymphoepithelial lesions in 12 such lymphomas have been examined by electronmicroscopy and immunohistochemistry. The lymphocytes present in these lesions are neoplastic centrocyte-like (CCL) B-cells and are morphologically and immunophenotypically similar to those of the surrounding lymphoma. Once the CCL cells penetrate the gastric glands, there is marked structural distortion and disruption of the epithelial cells which leads to their ultimate death. The close association of the neoplastic CCL cells and epithelial cells suggests the presence of a factor, an antigen or other receptor, on the plasma membrane of the latter through which these effects are mediated.

Humans↗
PubMed1992

Low-grade gastric B-cell lymphoma of mucosa-associated lymphoid tissue (MALT): a multifocal disease.

Gastrectomy specimens from five patients following gastroscopic biopsies which showed low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) were examined by serially sectioning and paraffin wax embedding using a 'swiss roll' technique. This procedure allowed the construction of a map of the specimen on which the distribution of the lymphoma could be plotted. In each case confluent lymphoma was identified. In addition small foci of lymphoma consisting of 1-4 lymphoid follicles surrounded by neoplastic centrocyte-like cells were seen. The positions of these 'micro-lymphomas' were plotted on the gastrectomy maps, showing multiple foci distributed throughout the gastric mucosa. The identification of these microscopic lesions may explain the development of local relapse, often after a long disease-free interval, in patients with gastric MALT lymphoma treated by partial gastrectomy where excision appears to have been complete. Patients treated in this way should, therefore, be followed-up indefinitely, with regular endoscopy and gastric biopsy, in order to identify early local disease relapse.

Adult↗
PubMed1992

Primary central nervous system lymphoma.

Primary central nervous system lymphomas (PCNSL) are uncommon neoplasms accounting for less than 2% of brain tumours. Their incidence appears to be increasing across a wide age range, in both immunocompetent and immunosuppressed populations. Particular risk groups include those with congenital and acquired immunodeficiencies and transplant recipients. The spread of the AIDS epidemic has seen large numbers of complicating PCNSL develop. Epstein-Barr virus infection appears to play a role in the development of these lymphomas in the immunosuppressed population. The aetiology of these tumours in the immunocompetent is uncertain. Their tendency to remain within the nervous system is not well understood but may be a function of CNS binding molecules carried by lymphocytes. Clinically PCNSL may present with a wide variety of signs and symptoms and has a capacity to mimic many other neurological conditions. Radiologically they appear as hyperdense homogenous deposits in subcortical white matter. Although most lesions are intermediate or high grade B cell lymphomas, T cell lymphomas are being recognised with increasing frequency. Immunohistochemistry and genotypic analysis have an important role in accurately characterising PCNSL, particularly in stereotactic biopsies. Involvement of multiple areas of the neuraxis, the eye and multiple intracranial sites can occur in the absence of obvious systemic lymphoma. The role of surgery in their treatment is uncertain. A combination of radiotherapy and chemotherapy can increase the length of survival. The prognosis, however, remains poor in comparison with nodal lymphomas, and particularly so in those with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Extranodal lymphomas: the MALT concept.

Extranodal lymphomas account for as many as 40% of non-Hodgkin's lymphomas and most arise in the gastro-intestinal tract which is a major lymphoid organ in its own right. Gastrointestinal (gut) associated lymphoid tissue (GALT) and that of other mucosae (MALT), differs both structurally and functionally from nodal lymphoid tissue and low grade B cell lymphomas arising in the gastrointestinal tract and other mucosae have been found to recapitulate the structure and cytological features of MALT. Moreover, these lymphomas are clinically indolent which could be explained by the restricted homing patterns of MALT. Curiously, however, most MALT lymphomas arise in sites, such as the stomach, where MALT is not normally present. Several chronic inflammatory conditions, most of which have an autoimmune component, result in the acquisition of MALT-like lymphoid tissue, and have been identified as necessary precursors for the development of MALT lymphoma. These include Helicobacter pylori induced chronic gastritis, Sjögren's syndrome and Hashimoto's thyroiditis. Histologically, low grade MALT lymphomas are characterized by centrocyte-like (CCL) B cells which surround reactive follicles and form characteristic lympho-epithelial lesions with adjacent epithelium; they frequently show plasma cell differentiation. Specific colonization of reactive follicles by CCL cells often occurs and transformation into a high grade lymphoma may occur. The phenotype of MALT lymphoma CCL-cells is similar to that of marginal zone B cells; no characteristic genotypic features have yet been identified. When lymph nodes are involved by MALT lymphoma their appearance may be indistinguishable from those of so-called monocytid B cell lymphoma, a primary lymph node tumour which, unlike MALT lymphoma, shares the clinical features of other low grade nodal B cell lymphomas.

Gastric Mucosa↗
PubMed1992

[Proliferating cells in Hodgkin's disease].

We have studied the proliferation fraction of Hodgkin- and Reed-Sternberg (HRS) cells and L&H cells in paraffin sections of 15 cases of classical Hodgkin's disease (HD) (12 nodular sclerosis [NS], 3 mixed cellularity [MC]) and 8 cases of nodular lymphocyte predominant Hodgkin's disease (NLPHD) using an antibody to proliferating cell nuclear antigen (PCNA). By double staining with anti-PCNA and antibodies to B- and T-cells we also determined the growth fraction and immunophenotype of the background lymphocytes in each case. In classical HD 45.3% of HRS cells, and in NLPHD 76.9% of L&H cells were in cycle. In both classical HD and NLPHD the majority of proliferating cells in the background were T-cells with 57.8% respectively 68.5%, whereas only a few B-cells were proliferating in each type of HD.

Antigens, Neoplasm↗
PubMed1992

Properties of human thymic B cells.

B cells, distinct from those seen in myasthenia gravis, are present in normal human thymic medulla, concentrated around the Hassall's corpuscles. We have shown that they constitute 33 +/- 4.8% of the total cells in the thymic medulla. In tissue sections they were often seen to have rosettes of thymocytes around them, a relationship which was maintained when the cells were isolated from the thymus. Thymic B cells expressed cytoplasmic immunoglobulins IgD, IgM and IgG but only rarely IgA. Unlike murine thymic B cells, human thymic B cells were CD5-. Freshly isolated thymic B cells were activated cells, but they rapidly became quiescent and died in culture over a 10-day period unless stimulated with mitogens. Thymic B cells responded to polyclonal B-cell activators SAC and TPA and when stimulated, maintained their relationship with thymocytes. Electron microscopic studies showed that two morphologically different thymocyte populations associated with the B cells. The plasma membranes of larger thymocytes were juxtaposed to the B-cell membrane, but smaller thymocytes with darker cytoplasm were associated with the B cells via cytoplasmic strands. Studies in mice have suggested that B cells are involved in thymic negative selection. The close association between activated B cells and thymocytes observed in this study supports this hypothesis.

B-Lymphocytes↗
PubMed1992

Follicular colonization in thyroid lymphoma.

The presence of neoplastic (light chain restricted) B-cell follicles in low-grade B-cell gastrointestinal (GI) lymphoma of mucosa-associated lymphoid tissue (MALT) has been explained on the basis of specific colonization of reactive follicles by centrocyte-like (CCL) cells. Low-grade B-cell thyroid lymphomas have been included in the category of MALT lymphoma, but the frequent presence of a follicular pattern in these tumors has contributed to the view that they are follicle center cell (FCC) tumors. We have reviewed the histology and investigated the phenotype and genotype of nine cases of primary low-grade B-cell lymphoma of the thyroid, all of which were distinguished by a predominantly follicular pattern. All cases also demonstrated features of MALT lymphoma, including CCL cells and lymphoepithelial lesions. The appearances and immunohistology of the follicles were those of follicular colonization as described in GI MALT lymphoma rather than FCC follicular lymphoma. The predominant pattern of follicular colonization was replacement of the follicle center by slightly enlarged CCL cells that showed a strikingly high proliferation rate. No evidence of the t(14;18) translocation was found in any case, using the polymerase chain reaction (PCR) on DNA extracted from fresh (n = 1) or paraffin-embedded (n = 9) tissue. These findings argue against a FCC lineage for primary thyroid lymphomas and support their inclusion in the MALT category.

Base Sequence↗
PubMed1991

Helicobacter pylori-associated gastritis and primary B-cell gastric lymphoma.

Although lymphoid tissue is absent in normal gastric mucosa, primary lymphomas arise in the stomach and most of these recapitulate the features of mucosa-associated lymphoid tissue (MALT). Gastric lymphoid tissue is known to be acquired in response to local infection by Helicobacter pylori, and we have confirmed this in 450 patients with H pylori-associated gastritis of whom 125 showed mucosal lymphoid follicles. In 8 patients, B lymphocytes infiltrated epithelium, which is a feature characteristic of MALT. We also examined 110 cases of gastric MALT lymphoma and found H pylori infection in 101 of these (92%). We conclude that gastric MALT is acquired in H pylori infection and that this provides the necessary background in which MALT lymphoma might develop.

Gastric Mucosa↗