Morphologic and cytogenetic studies in vitro of surface-adherent lymphoreticular cells derived from Burkitt lymphoma tissue

A line of lymphoreticular cells (AL-1-G) that can adhere to glass surfaces has been derived from suspension cultures of Burkitt lymphoma cells (AL-1). By light microscopy, the predominant cell type in the AL-1-G cultures has features of a neoplastic histiocyte and ultrastructurally these cells have more elaborate development of cytoplasmic organelles, such as elements of the Golgi complex and mitochondria, than the predominant cell types in the suspension cultures of AL-1. Cytogenetically, the percentage of polyploid cells in the AL-1-G cultures increased progressively from 39% in 1967 to 100% in 1968 and 1969, while the percentage of polyploid cells in the suspension cultures remained between 12 and 24% during the same period. No herpesvirus or any other type of viral particle was found in the AL-1-G cultures on repeated electron microscopic examination.     

Initial and subsequent cytogenetic studies in malignant lymphoma

Two or more cytogenetic studies of lymph node biopsy specimens from 12 patients with non-Hodgkin's malignant lymphoma were performed. Each of the 12 patients had at least one clonal structural chromosome abnormality in their initial biopsy specimen. A comparison of the chromosome abnormalities in the initial lymph node biopsy specimens with those in subsequent biopsy specimens was made. Structural and numerical chromosome changes were not always accompanied by a change in the histologic type of the lymphoma. Similarly, a change in histologic type was not always associated with the appearance of new structural or numerical abnormalities. Serial cytogenetic studies from additional patients will further our understanding relevant to which chromosome changes are associated with lymphomagenesis and which are secondary or more of an evolutionary nature.     

乳腺恶性淋巴瘤形态学及免疫组织化学研究

目的:研究乳腺非霍奇金淋巴瘤(NHL)的组织形态特点及免疫表型.方法:对17例乳腺NHL作形态学分析,其中11例进行了免疫学标记.结果:13例为原发性,4例为继发性.8例(47.06%)见“淋巴上皮病变”,13例(76.47%)见肿瘤浸润脉管,4例(23.53%)伴有“淋巴细胞性乳腺病”,3例(17.65%)见局部瘤细胞呈靶环样排列.免疫组化示16例(94.12%)为B细胞NHL,其中2例(12.50%)KP1阳性,1例(6.25%)UCHL-1阳性.结论:(1)大多数乳腺原发性NHL为MALT型淋巴瘤;(2)淋巴细胞性乳腺病可能是一些乳腺NHL的前驱病变;(3)少数B细胞NHL能与KP1或UCHL-1发生交叉反应.     

Immunohistochemical and cytogenetic studies indicate that malignant angioendotheliomatosis is a primary intravascular (angiotropic) lymphoma

The authors performed immunohistochemical and cytogenetic studies in a 73-year old man with malignant angioendotheliomatosis. The patient was referred for evaluation of fever of unknown origin, hepatic failure, and neurologic deterioration. Examination of a muscle biopsy revealed numerous, noncohesive atypical mononuclear cells within small vessels. These cells stained positively with a pan-leukocyte marker CD45(PD7/26/16) and with a B-cell marker L26 but negatively with Factor VIII-related antigen, an endothelial cell marker. Peripheral blood obtained before chemotherapy was cultured and analyzed by the G-band method. A new translocation and numerous chromosomal aberrations were identified. The major cell line karyotype was 53,XY, +X, +5q?,-6, +i(6p), +7, -10, +11, -12, +12p-, +12p-, +18, +mar1, +mar2, t(1;3)(p22;p21),3q+,8p+. This is the first cytogenetic study performed in a case of malignant angioendotheliomatosis. Our findings demonstrate that the neoplastic cells in this disorder circulate in the peripheral blood and provide further evidence that malignant angioendotheliomatosis is a diffuse intravascular neoplasm of lymphoid origin. Furthermore, the authors conclude that this malignant lymphoproliferative disorder should be reclassified as a primary intravascular (angiotropic) lymphoma.     

Spontaneous regression of a small non-cleaved cell malignant lymphoma (non-Burkitt's lymphoblastic lymphoma). Morphologic, immunohistological, and immunoglobulin gene analysis

Complete spontaneous regression of high-grade malignant non-Hodgkin's lymphoma is extremely unusual. In this report the authors describe a complete spontaneous remission after surgical excisional biopsy of a small noncleaved cell malignant lymphoma (non-Burkitt's lymphoblastic lymphoma) of the tonsil in a 12-year-old boy. The diagnosis was confirmed by immunohistologic and immunoglobulin gene analysis. Similar studies were performed on the cervical lymph node excised 2 weeks later when spontaneous remission had occurred. The patient has remained in good health for over 3 years.     

Morphologic, immunologic and cytogenetic studies in acute myeloid leukemia following occupational exposure to pesticides and organic solvents.

In order to analyze the correlation between environmental exposure and the clinicopathological picture in acute myeloid leukemia (AML), cytogenetic, cyto-immunologic and clinical studies were performed in 70 newly diagnosed AML patients, 30 of which were anamnestically exposed to pesticides (21 cases) or to organic solvents (9 cases). Clonal chromosome aberrations, with involvement of chromosome 5 and/or 7 were more frequently encountered among exposed patients. While the classical t(15;17), t(8;21) and t(9;11) were detected more frequently among non-exposed patients, other recurring chromosome changes in the exposed group were: rearrangements leading to total or partial monosomy 17p (5 cases), structural aberrations involving the band 16q22 (4 cases), trisomy 11q (2 cases), breaks involving bands 6p23, 7p14, 11q13 (2 cases each). Cytologically, trilineage myelodysplasia was observed in 21 exposed patients, whereas morphologic aberrations of the non-blast cell population were confined to a minority of cells in most patients non-exposed. Immunologic studies revealed positivity for the CD34 stem cell marker in 80% exposed patients vs 22% in the non-exposed group. Conventional chemotherapy achieved complete remission in 3/21 patients exposed and in 16/32 patients non-exposed. Median survival was 2 months in the former group and 9 months in the latter group. These findings show that AML following occupational exposure to pesticides and organic solvents may represent a distinct cytogenetic and clinicopathological entity.     

Morphologic, immunologic and cytogenetic studies in children with acute lymphoblastic leukemia at diagnosis and relapse: a Pediatric Oncology Group study.

The morphologic, immunologic and cytogenetic features of leukemic cells obtained at the time of first bone marrow relapse were compared with those obtained at initial diagnosis in 287 children with acute lymphoblastic leukemia (ALL) who were entered consecutively in a laboratory classification study of the Pediatric Oncology Group (POG). L1 to L2 shifts in French-American-British morphologic subtype were more common than the reverse (81/178 versus 15/61, p less than 0.001). A small but marginally significant number of cases acquired cytoplasmic granules at relapse, and 50 cases underwent a shift in periodic acid-Schiff reactivity that slightly favoured positive to negative. Shifts in immunophenotype were relatively rare, although shifts in cases with a pre-B phenotype to early pre-B ALL or vice versa occurred in about a third of pre-B cases. Loss of HLA-DR or the common ALL antigen occurred in 20 and 11% of cases, respectively. Of the 116 cases with analyzable karyotypes at diagnosis and relapse, 36 (31%) showed a change in karyotypes at relapse, usually from normal to pseudodiploid or hyperdiploid. Cytogenetic evidence for the emergence of a new clone after initial diagnosis was found in only one case. Analysis of the correlation of clinical and lymphoblast biologic features with event-free survival after an initial marrow relapse failed to demonstrate any prognostic significance for the changes identified in this study. T-cell immunophenotype proved to be the only factor significantly related to the outcome of retrieval therapy.     

Morphologic, immunologic, and cytogenetic characteristics of secondary acute unclassifiable leukemia in Hodgkin's disease

Blast cells from five cases of secondary unclassifiable leukemia following therapy for Hodgkin's disease were studied by cytochemical, immunological and cytogenetic analyses. Cytochemical and immunological reactivity were in accordance with poorly differentiated, myeloid blasts. The four cases in which karyotype analysis was performed showed specific chromosomal abnormalities. No evidence of multiple lineage involvement was found. Problems in classifying these cases of secondary ANLL were due to the high grade of undifferentiation of the blast cells. Their low cytochemical reactivity with markers of myeloid differentiation was similar to what may be observed in patients with acute undifferentiated leukemia or with chronic myeloid leukemia in blast crisis.     

Immunophenotypic and molecular studies in the diagnosis and classification of malignant lymphoma

Immunophenotypic and molecular studies play an increasingly important role in the diagnosis and classification of lymphoid neoplasms. These studies are not yet a substitute for expert histopathologic evaluation, but are a valuable adjunct to the examination of the hematoxylin and eosin-stained slide. Major applications include determination of lineage, determination of B and T cell monoclonality, detection of oncoprotein expression, and detection of oncogene rearrangements and chromosomal translocations. The recognition of the lymphomas as distinct biologic entities with specific immunophenotypic and genotypic features, as embodied in the Revised European-American Lymphoma (REAL) and World Health Organization (WHO) classifications, is a key to the future development and application of targeted biologic and molecular therapies. In the future, application of gene expression array analysis to the lymphoid neoplasms will permit classification of the lymphomas at a molecular level.     

Primary pulmonary malignant lymphoma, clinical and pathological findings, immunocytochemical and ultrastructural studies in 15 cases

Fifteen cases of primary pulmonary malignant lymphoma (M.L.) were studied using strict criteria to distinguish them from secondary pulmonary manifestations. All were M.L.'s of the lymphoid B type. Diagnosis on the basis of non specific clinical, X-ray and endoscopic findings if often difficult but can be facilitated by the systematic use of immunocytochemical and ultrastructural techniques. Their evolution is in good agreement with the prognostic data given by the Kiel-Lennert histopathological classification. 14 of the patients had M.L. of low grade malignancy; the one case of high grade malignancy was quickly fatal. A few cases appeared as a complication of a preexisting dysimmune disease (Pigeon breeder's disease, Gougerot-Sjogren disease, Liebow's lymphomatoid granulomatosis).     

A case of malignant lymphoma, an anemone cell tumor of the leg, arising from osteomyelitis

An 80-year-old man, complaining of multiple fungating growth on his right leg, was hospitalized. A review of his previous history revealed that he had undergone three operations because of repeating osteomyelitis. A clinical examination showed that a tumor was localized on the right leg. Light microscopy revealed that tumor was composed of diffuse large round cell proliferations. Malignant lymphoma was suspected, but was difficult to distinguish in the undifferentiated carcinoma. Electron microscopically, extensive cytoplasmic processes resembling microvilli from the circumferential surface membrane were observed, but desmosomes, tonofilaments, secretory products or basal lamina were not seen. Immunohistochemically, IgG was demonstrated on the tumor cells. These findings led us to diagnoses an anemone cell tumor, originating from a malignant lymphoma and arising from osteomyelitis.     

Primary renal lymphoma and hypercalcemia in a child

Renal lymphoma is most frequently due to secondary lymphomatous infiltration of the kidneys in advanced stage disease. Rarely, are the kidneys the tissue of origin. We describe a 15-year-old male presenting with hypercalcemia and acute renal failure, due to a bilateral "primary B-cell lymphoma of the kidneys". The diagnosis was established by percutaneous needle biopsy of the right kidney. His disease was metastatic to multiple bones. His presenting features radiological findings and biopsy results are unique. We report his case, and review the pediatric literature.     

Secondary chromosome changes in mantle cell lymphoma: cytogenetic and fluorescence in situ hybridization studies.

To better define the incidence and nature of secondary chromosome anomalies in mantle cell lymphoma (MCL) carrying the t(11:14)/BCL1 rearrangement, cytogenetic and fluorescence in situ hybridization studies (FISH) were performed in 42 patients (39 classical histology, 3 blastoid variant), using 6q21, 9p21/p16, 13q14, 17p13/p53 and chromosome-12-specific probes. Karyotypes from 89 cases published in 5 recent series including patients diagnosed in a homogeneous fashion were reviewed. In our series, FISH confirmed the interpretation of the karyotype in all cases and disclosed cryptic chromosome deletions in a sizeable fraction of cases. One patient (2.4% of total) was found with a cryptic 9p21 deletion by FISH. Two cases (4.8%) had a 6q21 deletion at CCA and at FISH; +12 was found in three cases by CCA plus nine by FISH (28.6%); 13q14 deletion was found in six cases by CCA plus 16 by FISH (52.4%), 17p13 deletion in three cases by CCA plus 8 by FISH (26.2%). In 131 patients (42 present series plus 89 in the literature) secondary chromosome aberrations seen by conventional cytogenetic analysis in more than 5 cases included deletions/translocations (del/t) 6q15-23 [15 cases]; -13 [14 cases]; del/t 1p21-31 [12 cases]; +3q [11 cases]; del/t 17p [9 cases]; 8p translocations and del(Y) [8 cases each]; -20 [7 cases]; 13q14 deletion, del/t 11q22-23, del/t 9q, del(10)(q22q24), -20, -21, -22 and -X [6 cases each]. We arrived at the following conclusions: i) though no secondary anomaly is specific for MCL, there is a distinct profile of recurrent chromosome lesions in MCL with 1p21-31 deletions, 8p translocations, 11q22-23 anomalies having a strong association with CD5+ B-cell lymphomas of low-to-intermediate grade histology; ii) FISH enabled the detection of cryptic chromosome 12, 13q and 17p rearrangements in a sizeable fraction of cases; iii) 9p21/p16 deletions did not occur at a high incidence in this series, possibly because of the low number of cases with blastoid variant.     

CT and pathologic studies on detecting hepatic involvement of malignant lymphoma

In order to determine the value of CT in detecting lymphomatous involvement of the liver, 57 autopsied cases (48 cases of non-Hodgkin lymphoma and 9 of Hodgkin's disease) were analyzed in detail. Additionally, 90 recent cases of abdominal CT with liver study in the initial staging were reviewed and 6 cases in which the liver had been examined within 2 weeks before autopsy were compared for macroscopic and pathologic findings. The following results were obtained. Autopsy findings in 57 cases of malignant lymphoma. (1) Hepatic involvement was demonstrated in 56% of the patients with non-Hodgkin lymphoma and in 67% of those with Hodgkin's disease. Of these patients with hepatic involvement, intrahepatic nodular lesions over 1.0 cm in diameter were macroscopically identified in 22% of the cases of non-Hodgkin lymphoma and 33% of those with Hodgkin's disease. Lymphomatous involvements were seen in many organs in the cases of hepatic involvement. CT examinations of 90 cases for the initial staging showed no significant abnormality in the liver or spleen. Of the 6 cases in which the liver was examined by CT within about 2 weeks before autopsy, lymphomatous involvement was pathologically diagnosed in 5. Of these, only one having multiple nodules larger than the tip of a thumb was correctly diagnosed by CT. Hepatic involvement of lymphoma was thought to be the end stage, and minimal or early disease was detected in the region of Glisson's capsule. The above findings indicate that early hepatic involvement is not likely to be detected by CT at the present time.