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Biomedical subjects

R J Lukes

Publications and source records attributed to R J Lukes.

At least 73 records · Page 4Linked to original sources

The immunologic approach to the pathology of malignant lymphomas.

Presentations of malignant lymphomas in the past did not have the benefit of modern developments in immunology and do not bear any relationship to our modern understanding of immunology. The malignant lymphomas in our immunologic approach are regarded as neoplasms of the immune system and involve principally the T- and B-cell systems and alterations in lymphocyte transformation. The cytologic types of our new classification are an attempt to identify specific functional subtypes of the T- and B-cell systems as defective expressions of their normal counterparts. The results of our multiparameter studies on large case series of non-Hodgkin's lymphomas and those of others have demonstrated that the malignant lymphomas for the most part mark as T- or B-cell types, with the exception of a rare lymphoma of true histiocytic type and the unmarked portion of acute lymphocytic leukemia (ALL) of childhood. They have demonstrated the heterogeneity of the cytologic types of the past that possibly account for the diversity of their clinical manifestations and responses to therapy. The immunologic approach has permitted the identification of homogeneous cytologic types that are emerging as clinical morphologic immunologic entities.

B-Lymphocytes↗

An immunohistological study of immunoglobulin content of primary central nervous system lymphomas.

Paraffin sections of surgical and autopsy material from 24 cases of primary CNS lymphoma were examined for the presence of cytoplasmic immunoglobulin by an immunoperoxidase technique. Definite staining for cytoplasmic immunoglobulin was observed in 13 cases, and in eight of these the pattern of staining was consistent with current concepts of monoclonality. In every case the histological diagnosis of malignant lymphoma was confirmed, and cases were subclassified by both the Lukes-Collins and the Rappaport classifications. Morphologically 12 of the 24 cases resembled immunoblastic sarcoma occurring outside the CNS. Other cases showed features of follicular center cell lymphoma or plasmacytoid lymphocytic lymphoma. Of those cases with positive immunoglobulin staining of tumor cells, the majority showed some plasmacytoid features. It was concluded that the primary CNS lymphomas resemble their counterparts occurring outside the CNS, and that at least a proportion are derived from the B lymphocyte.

Adolescent↗

Immunoglobulin inclusions in non-Hodgkin's lymphomas.

The occurrence and characteristics of intracellular immunoglobulin inclusions in non-Hodgkin's lymphomas are described. Lymphoma cells from three patients with immunoblastic sarcoma contained classic cytoplasmic, periodic acid-Schiff (PAS)-positive Russell bodies. Immunoperoxidase staining revealed monoclonal IgG (k) in two cases and a polyclonal pattern in the third case, where the tumor evolved from a reactive lesion. Unusual cytoplasmic inclusions were observed in the neoplastic cells of two patients with follicular center cell lymphoma. In one case large globular structures lacking a distinct limiting membrane were seen, while the cells of the other patient contained "signet-ring-like" vacuoles filled with microvesicles. Both were PAS-negative and showed monoclonal immunglobulin staining. In two other cases PAS-positive intranuclear inclusions consisting of monoclonal immunoglobulin IgM(k) could be demonstrated. The possible significance of these findings in B-lymphocyte derived neoplasms is discussed.

Adult↗

Morphologic and cytochemical comparison of human lymphoblastoid T-cell and B-cell lines: light and electron microscopy.

Human lymphoblastoid cell lines characterized as T- or B-cells by various markers were compared morphologically and cytochemically by light and electron microscopy. Distinct differences in nuclear morphology, amount of cytoplasm, pyroninophilia, and periodic acid-Schiff (PAS) staining enabled us to discriminate between T- and B-cell lines. T-cells had nuclei with an irregular configuration, stippled heterochromatin, and small or absent nucleoli. The scanty cytoplasm of T-cells contained intensely stained, PAS-positive globules and was less pyroninophilic than the cytoplasm of B-cells. B-cells had more rounded, uniform, vesicular nuclei with prominent nucleoli and peripheral heterochromatin. The cytoplasm of B-cells was abundant and strongly pyroninophilic. Transmission electron microscopy generally confirmed these morphologic differences. These findings supported our contention that consistent cytologic features concordant with immunologic markers make it possible to identify certain lymphomas as being of B- or T-cell origin on purely morphologic grounds.

B-Lymphocytes↗

Convoluted lymphocytic lymphoma in adults: a clinicopathologic entity.

Twelve adults had a distinct clinicopathologic type of malignant lymphoma that closely resembles the mediastinal lymphomas of childhood. Nine patients presented with mediastinal masses, and seven had symptoms related to intrathoracic compression. Seven patients presented with or developed leukemia, and in four of these patients the central nervous system (CNS) became involved. Structurally, the tumor cells had a distinctive stippled chromatin pattern, in addition to the characteristic nuclear convolutions. Tumor cells from five patients were studied immunologically, and, in each case, the tumor cells formed rosettes with sheep erythrocytes. The response to combination chemotherapy was rapid and dramatic, but usually transient, with relapse in the CNS or previously involved sites. The above data strongly suggest that these cases represent a distinct clinicopathologic entity that should be treated similarly to childhood leukemia and lymphoma, with intensive multiple agent induction, CNS prophylaxis, possibly radiation therapy to initially involved sites, and prolonged maintenance.

Adult↗

A morphologic and immunologic surface marker study of 299 cases of non-Hodgkin lymphomas and related leukemias.

This study relateds the cytologic types of the classification of malignant lymphoma of Lukes and Collins to the results of immunologic surface marker studies as part of a systematic multiparameter study of 299 cases of non-Hodgkin lymphomas. The results support the hypothesis that malignant lymphomas are neoplasms of the immune system and involve the B- and T-cell systems and, rarely, histiocytes. The morphologic features of the cytologic types of Lukes and Collins are predictive of the subtypes of lymphoma and considerably more effective than the immunologic surface marker techniques in identifying homogeneous groups. There are considerable methodologic and interpretive problems that are evaluated in detail. The verification of the B- and T-cell subtypes of the Lukes and Collins classification indicates that the time has come to change from the terminology and classification of lymphomas of the past to a modern immunologic approach.

B-Lymphocytes↗

Staging laparotomy and splenectomy for Hodgkin's disease.

The major objective of diagnostic laparotomy in Hodgkin's disease is to define the extent of involvement not detectable by nonoperative means. Fifty patients in this institution had operative staging procedures; six for recurrent disease three to 11 years after initial therapy. Twenty-four patients had nodular sclerosis, 23 mixed cellularity, and three had other types. The clinical stages were advanced in 13 patients and decreased in seven patients. Two patients (both had mixed cellularity and systemic symptoms) had positive wedge biopsy of the liver, whereas direct needle biopsy was negative. Nineteen spleens contained Hodgkin's disease but only three could be palpated on physical examination. About half the patients with abnormal lymphangiograms had positive periaortic nodes; lymphangiogram had a false negative rate of 12%. Additional procedures performed included appendectomy, oophoropexy, and resection of Meckel's diverticulum. There was no mortality and only one case had severe postoperative Salmonella septicemia. Our findings are comparable with those reported in the literature.

Adolescent↗

Hodgkin's disease in siblings.

An incidence survey of Hodgkin's disease in Greater Boston during 1959-1973 detected five sibling pairs under the age of 45. The expected number is 0.7; thus, siblings of young adults with Hodgkin's disease have about a sevenfold excess risk of the disease (P = 0.0008). Eight sibling pairs, not in the incidence series, were also identified. Among all 13 pairs, 12 were sex concordant; the number expected is 6.8 (P = 0.01). The literature includes 46 sibling pairs under 45 of which 30 are sex concordant. The expected number is 23.9 (P = 0.05). Combining the present and the literature series suggests that siblings of the same sex as an affected person have a risk of Hodgkin's disease double that of siblings of the opposite sex. The sex concordance suggests that the excess Hodgkin's disease among siblings of affected persons is due either to inter-personal transmission of an etiologic agent by prolonged or intimate contact or to common-source exposures.

Adult↗

Lacunar cells of nodular sclerosing Hodgkin's disease: an ultrastructural and immunohistologic study.

Tissues from 22 cases of nodular sclerosing Hodgkin's disease were studied by light and electron microscopy in conjunction with immunohistologic and cytochemical staining. The presence of lipid in the cytoplasm of lacunar cells suggested that this was responsible for the distinctive "lacunar" appearance of the cells. Marked morphologic similarities between "blast cells" resulting from mitogen stimulation of lymphocytes in vi-ro, immunoblasts seen in reactive lymphoid tissues, and mononuclear "Hodgkin's" cells in Hodgkin's disease suggested that all three cell types may result from lymphocyte transformation. It also seemed apparent that there was a developmental sequence from lymphocyte to transformed lymphocyte to the abnormal mononuclear Hodgkin's cell, with further progression, through increasing size and nuclear lobulation, to the lacunar cell or, alternatively, to the diagnostic Reed-Sternberg cell. This proposed sequence was supported by immunoperoxidase studies in which cytoplasmic immunoglobulin was demonstrated in mononuclear Hodgkin's cells, lacunar cells and Reed-Sternberg cells. The proposed relationship between these cells was also supported by the findings of both kappa and lambda chains in the same cells, a pattern not seen in reactive transformed lymphocytes.

Cytoplasm↗

Human B lymphocytes in giemsa stained preparations.

A mixed antiglobulin procedure has been developed to provide simultaneous study of cell surface immunoglobulin and detailed cytological features in Giemsa stained preparations. The percentage of surface immunoglobulin bearing lymphocytes, monocytes and granulocytes changed dramatically when lymphocytes were incubated at 37 degrees C, or following sheep erythrocyte rosette enrichment procedures.

Animals↗

Surface immunoglobulin on leukemic, leukemoid, and normal granulocytes.

Using a new functional approach for the study of lymphomas and leukemias in which immunologic and cytochemical techniques were employed, we found a consistent surface immunoglobulin pattern of the gamma-, k-, lambda-type on cells from poorly differentiated (acute) and well-differentiated (chronic) granulocytic leukemias. This pattern was also found on nonneoplastic granulocytes from patients with leukemoid reactions as well as on granulocytes from normal individuals. These findings suggested that both leukemia cells and nonneoplastic granulocytes had IgG bound to the cell surface by an Fc receptor. This binding of IgG by granulocytes was not tumor-specific and appeared to correlate both with the degree of differentiation and possibly with the degree of activation of the granulocytes. In addition to raising the basic question of its functional significance, these findings offered an approach for distinction of poorly differentiated granulocytic leukemia from lymphomatous processes.

Adult↗

Immunoblastic lymphadenopathy. A hyperimmune entity resembling Hodgkin's disease.

Immunoblastic lymphadenopathy, although it resembles Hodgkin's disease, is a distinct, hyperimmune disorder apparently of the B-cell system. In 32 cases, it was characterized by a morphologic triad: proliferation of arborizing small vessels; prominent immunoblastic proliferations; and amorphous acidophilic interstitial material. Clinically, it is manifested by fever, sweats, weight loss, occasionally a rash, generalized lymphadenopathy and often hepatosplenomegaly. There is a consistent polyclonal hyperglobulinemia and often hemolytic anemia. The course of the disease is usually progressive, with a median survival of 15 months in 18 fatal cases. The cellular proliferation appears benign morphologically in the pretherapy biopsies and in 10 of 12 available autopsy cases. In three cases the process evolved into a lymphoma of immunoblasts, immunoblastic sarcoma. The basic process appears to be a non-neoplastic hyperimmune proliferation of the B-cell system involving an exaggeration of lymphocyte transformation to immunoblasts and plasma cells that may be triggered by a hypersensitivity reaction to therapeutic agents.

Adult↗