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Biomedical subjects

P Isaacson

Publications and source records attributed to P Isaacson.

At least 19 recordsLinked to original sources

Polymerase chain reaction for detection of dissemination in gastric lymphoma.

The polymerase chain reaction (PCR) was used to detect malignant lymphoma cells with the bcl-2 gene rearrangement in the peritoneal washings and bone marrow of a patient with an apparently localised gastric lymphoma. After four courses of cytotoxic drug treatment the cells could no longer be detected in either site. PCR is a useful addition to the staging investigations of non-Hodgkin lymphoma and can also be used to monitor response to treatment.

B-Lymphocytes

Rearrangement of the T-cell-receptor beta-chain gene in the diagnosis of lymphoproliferative disorders.

The arrangement of the T-cell-receptor and immunoglobulin genes has been analysed in 77 cases of lymphoproliferative disorder. All 6 T-cell leukaemias and 16 of 19 T-cell lymphomas showed rearrangement of the gene coding for the beta chain of the T-cell receptor, associated in all cases with a germline arrangement of the immunoglobulin genes. All 36 B-cell leukaemias and all 16 B-cell lymphomas showed rearrangement of immunoglobulin genes; the T-cell-receptor gene was in the germline configuration in most of these cases but showed a rearranged pattern in 3 cases (2 chronic lymphatic leukaemias and 1 immunoblastic lymphoma). The combined use of T-cell-receptor and immunoglobulin gene probes promises to be a valuable means of identifying and classifying T-cell neoplasms.

Autoradiography

Extranodal malignant lymphoma arising from mucosa-associated lymphoid tissue.

Four cases of extranodal malignant lymphoma, one each arising in the stomach, salivary gland, lung, and thyroid, are described. These cases have many clinical, histopathologic, and immunohistochemical features in common, and it is proposed that this is because they share a common pattern of histogenesis from mucosa-associated lymphoid tissue (MALT). Clinical features of MALT-derived lymphomas include a tendency to remain localized for prolonged periods, and, thus, to be responsive to locally directed therapy. Histologically, this group of tumors is characterized by a noninvasive lymphoplasmacytic infiltrate within which foci of follicle center cells (FCC) can be seen invading epithelial structures, forming lymphoplasmacytic infiltrate lesions. Immunohistochemistry reveals monotypic cytoplasmic immunoglobulin (CIg) in the plasma cells serving to highlight the CIg-negative lymphoepithelial lesions. The clinical and histopathologic features of these lymphomas can be understood in the context of the behavioral characteristics and morphology of MALT.

Adult

Malignant lymphoma of mucosa-associated lymphoid tissue. A distinctive type of B-cell lymphoma.

As illustrated in the two cases described in this paper close morphologic and immunohistochemical similarities exist between Mediterranean lymphoma (MTL) and primary gastrointestinal lymphoma of follicle center cell (FCC) origin as it occurs in Western countries. Similarities between the two conditions include a dense noninvasive monotypic lamina propria plasma cell infiltrate, present in all cases of MTL and in some cases of Western gastrointestinal FCC lymphoma, and an invasive infiltrate of FCCs morphologically distinct from the plasma cells. A distinctive lesion produced by individual gland invasion characterizes both types of lymphoma. A clonal relationship between the lamina propria plasma cells and the invasive FCCs, long suspected but never proved in MTL, can be demonstrated in Western cases. Many of the histologic and clinical features common to these lymphomas can be explained in the context of the normal maturation sequences of gut associated lymphoid tissue. It is suggested that MTL and Western cases of primary FCC gastrointestinal lymphoma share a common histogenesis from mucosa associated lymphoid tissue.

Adult

Malignant lymphoma of true histiocytic (monocyte/macrophage) origin.

Since the advent of the newer classifications of non-Hodgkin's lymphoma and the realization that the majority of tumors classified as histiocytic under the Rappaport classification were in fact of lymphocytic origin, there have been remarkably few reports of true histiocytic (monocyte/macrophage) tumors and it has been suggested by some that such tumors should not be considered as a variety of malignant lymphoma. This article describes five patients with malignant lymphoma of neither B- or T-lymphocyte origin in whom the malignant cells could be characterised immunologically, cytochemically, and immunohistochemically as of true histiocytic derivation. The cases showed considerable morphologic diversity but there were shared characteristics at both light microscopic and ultrastructural levels. Positive immunohistochemical staining for alpha 1-antitrypsin was the single most useful criterion in classifying these tumors. Without the use of special techniques there were no clinical or pathologic features that reliably distinguished these cases from non-Hodgkin's lymphomas of lymphocytic derivation. Tumors of histiocytic origin are, therefore, inevitably being included among the non-Hodgkin's lymphomas and are most appropriately classified as such. Identification of histiocytic lymphomas should be encouraged so prognosis and optimum treatment can be established.

Acid Phosphatase

Upper gastrointestinal endoscopy in systemic vasculitis presenting as an acute abdomen.

Three cases of upper gastrointestinal vasculitis presenting as acute abdominal emergencies highlight an uncommon but often fatal presentation of systemic vasculitis. Although abdominal symptoms are common in such diseases, there may be a doubt during assessment of the patient as to whether the gastrointestinal tract is the prime target organ. Radiology is often negative during the acute illness. Endoscopy was important in documenting early and more advanced bleeding lesions of polyarteritis nodosa (PAN) and Henoch-Schoenlein disease, both conditions in which upper gastrointestinal lesions are rare. The gastric and duodenal vasculitic lesions demonstrated by endoscopy in such a clinical setting were confirmed histologically. Endoscopic assessment and early aggressive medical therapy contributed significantly towards the overall successful outcome. Gastroduodenoscopy has not been used either routinely or as an emergency investigation for the assessment of patients with vasculitis who present with acute abdominal pain. Involvement of the stomach and duodenum by vasculitis is therefore poorly appreciated, but remains a serious complication of vasculitic disease when the gastrointestinal tract is the prime target organ, and the information gained by endoscopy in a difficult clinical situation might alter the overall outcome of the disease.

Abdomen, Acute

Merkel cell carcinoma: a report of three cases with neurone-specific enolase activity.

Three cases are described of a primary cutaneous neoplasm occurring in elderly patients, histological and immunohistochemical features of which support an origin from Merkel cells. Microscopically sheets of uniform small cells filled the dermis, often with a prominent trabecular pattern. Ultrastructurally the cells showed neurosecretory granules, tangles of microfilaments, scattered mitochondria and occasional intranuclear rodlets. Immunohistochemical staining for neurone-specific enolase was positive and for prekeratin was negative in each case. The definitive diagnosis of Merkel cell tumour can be made with a combination of electron microscopy and immunohistochemistry.

Adenocarcinoma

Changes in the mucosa of colon conduits with particular reference to the risk of malignant change.

Intestinal suction biopsies were obtained in 15 infants and children with cutaneous colo-ureterostomies. The patients were subdivided into groups according to the length of time the conduit had been established, i.e. less than 5 years, 5 to 10 years, 10 to 15 years and over 15 years. The histological changes found were chronic inflammation with a dense infiltration of plasma cells and eosinophils. The changes were progressive and correlated with the length of time the conduit had been established. As persistent chronic inflammation is a precursor of malignancy, it seems likely that there is a risk of malignant change in these conduits. Regular follow-up of such patients is recommended and should include flexible fibreoptic endoscopy of the conduit.

Adolescent

Middle Eastern intestinal lymphoma: a morphological and immunohistochemical study.

A total of 31 cases of Middle Eastern gastrointestinal lymphoma (from Mosul, Iraq) has been analysed by conventional histology, and also by immunoperoxidase staining of trypsinised paraffin sections with anti-Ig and anti-J chain antisera. Histologically these neoplasms fell into three categories: undifferentiated lymphoma of Burkitt type (8 cases); follicle centre cell (FCC) lymphoma, resembling European lymphomas of FCC origin (15 cases); and Mediterranean lymphoma (MTL) (3 cases). Immunohistological staining of the FCC neoplasms showed that these tumours resembled their European counterpart in that cytoplasmic Ig and J chain could be demonstrated in a proportion of cases. However there was a striking difference in that alpha chain alone, light chain alone, or J chain alone were detected in several cases (in contrast to the predominance of mu plus kappa or lambda light chains found in European cases). Furthermore, prominent intracellular inclusions of alpha chains were found in two cases. Staining of the MTL cases revealed that the characteristic mucosal plasma cell infiltrate was positive for alpha chain (weakly) and J chain (strongly) but that the invasive cells which morphologically resembled FCCs were negative for both constituents. It is argued that these three histological categories constitute the major types of gastrointestinal lymphoma in the Middle East; and that in MTL the invasive lymphoma is of FCC type.

Adolescent

Biopsy appearances easily mistaken for malignancy in gastrointestinal endoscopy.

A series of 10 cases is described which were characterized by the occurrence, in gastrointestinal endoscopic biopsies, of benign lesions which bore a close resemblance to malignancy. In three cases an erroneous diagnosis of carcinoma was made and major resections were performed unnecessarily. The lesions fall into two histological types, one of which is seen only in gastric biopsies and the other at any level of the gastrointestinal tract. The histopathology of these lesions is described in detail.

Adult

Immunoperoxidase study of the secretory immunoglobulin system and lysozyme in normal and diseased gastric mucosa.

Using an immunoperoxidase technique the distribution of secretory component, IgA, and lysozyme has been investigated in normal, inflamed, dysplastic, and carcinomatous gastric mucosa. Apart from pyloric glands which contain lysozyme, normal gastric mucosa stains negatively for all three antigens. In gastric mucosa neck cells appear to adapt by synthesising secretory component and lysozyme and transporting IgA. Intense staining for the three antigens is seen in dysplastic gastric epithelium and in well-differentiated intestinal type carcinomas. With progressive de-differentiation the tumours lose the ability to synthesise secretory component and lysozyme. Carcinomas of the diffuse type stain positively for secretory component and lysozyme and individual cells appear to take up IgA even in the absence of surrounding IgA containing plasma cells. These functional properties are retained in lymph node metastases. It is suggested that secretory component synthesising malignant cells might take up circulating dimeric IgA and that this could be a reflection of an important physiological mechanism.

Gastric Mucosa

Immunoperoxidase study of the secretory immunoglobulin system in colonic neoplasia.

The relation of the secretory immunoglobulin system in the colon to colorectal cancer and dysplasia has been examined by staining routine formalin-fixed, paraffin-embedded sections from cases of carcinoma, adenoma and ulcerative colitis for secretory component (SC), IgA and J chain. In carcinomas there was a close relation between SC synthesis and differentiation and a similar relation was apparent between SC synthesis and degrees of dysplasia in adenomas. In both morphological and functional (SC synthesis) terms degrees of dysplasia in adenomas resembled degrees of differentiation in carcinomas suggesting that the essential "switch" in the progression towards neoplasia may occur at the level of the adenoma and that invasive malignancy can arise from dysplastic mucosa of varying severity. Actively regenerating mucosa in ulcerative colitis (UC) showed intense staining for SC as opposed to foci of precancerous dysplasia where, with one exception, staining was markedly reduced or absent, suggesting staining for SC could be useful in identifying foci of precancerous dysplasia in UC. In the absence of severe chronic inflammation, as in UC, the number of IgA-containing plasma cells was closely related to SC staining of neoplastic mucosa suggesting that SC may be important in the mechanism by which IgA lymphocytes home to the lamina propria of the colon.

Adenoma

Malignant histiocytosis of the intestine: report of three cases with immunological and cytochemical analysis.

Tumour cells from three cases of malignant histiocytosis of the intestine (MHI) have been studied immunologically and cytochemically. The cells did not form E rosettes and showed weak Fc gamma surface receptors. They contained non-specific esterase and acid phosphatase in diffuse granular distribution. In one case tumour cells showed no staining by an immunoperoxidase technique with two monoclonal anti-T cell antibodies but positive staining with a monoclonal anti-Ia-like antibody. The malignant cells from all three cases could be shown to contain alpha-1-antitrypsin. These are the first cases of MHI to have been studied in this way and the results confirm the true histiocytic--that is, monocyte/macrophage, derivation of the tumour cells in this disease.

Aged

Toxic dilatation of colon in Crohn's disease.

12 cases of toxic dilatation of the colon in Crohn's disease were reviewed. In 11 this complication seemed to be the first manifestation of the disease and a considerable diagnostic delay may partly account for the strikingly high mortality (50%). On admission 83% had clinical features suggestive of Crohn's disease and 58% had experienced symptoms suggestive of preceding gastrointestinal disease. An iatrogenic precipitating factor was identifiable in all but the 1 patient with established disease and in 83% of cases antidiarrhoeals had been prescribed. Preoperative perforation occurred in 4 patients, 3 of whom had had a barium-enema examination, and thromboembolism was a common postoperative complication (50%). Fever, tachycardia, low serum calcium, and low serum albumin in a patient with diarrhoea, abdominal pain, and distension should alert the physician to the possibility of Crohn's disease even in the absence of preexisting symptoms. Sigmoidoscopy should be an early investigation with particular attention being paid to perianal disease.

Adult

Follicular center cell lymphoma of childhood: a report of three cases and a discussion of its relationship to Burkitt's lymphoma.

Three children with follicular center cell lymphomas are reported. The tumors were studied by light microscopy, electron microscopy, and the immunoperoxidase technique. All three tumors contained monotypic immunoglobulin; one had the morphology of a 'signet ring cell lymphoma,' and one had arisen in a child with Bloom's syndrome. Two tumors exhibited a nodular or partly nodular growth pattern. The tumors were compared with African cases of Burkitt's lymphoma and found to have marked differences in their morphologic and immunohistochemical characteristics. The authors believe that one should distinguish between Burkitt's lymphoma and follicular center cell lymphomas occurring in childhood.

Burkitt Lymphoma