Showing papers on "Large cell published in 1997"

The t(11;18)(q21;q21) chromosome translocation is a frequent and specific aberration in low-grade but not high-grade malignant non-Hodgkin's lymphomas of the mucosa-associated lymphoid tissue (MALT-) type

Abstract: Primary extranodal malignant non-Hodgkin's lymphoma arising from the mucosa-associated lymphoid tissue (MALT-type lymphoma) represents a subtype of B-cell lymphoid malignancies with distinct clinicopathological features and is often associated with a favorable prognosis. Unlike the situation in nodal non-Hodgkin's lymphoma of B-cell lineage, few data are still available concerning the chromosomal constitution of MALT-type lymphomas. Until now, cytogenetic data from 29 low-grade MALT lymphomas with karyotypic alterations have been reported from different institutions, and virtually no data were available for high-grade MALT-type lymphomas. We have analyzed the cytogenetics of 44 MALT lymphomas arising in the stomach, parotid gland, thyroid gland, lung, breast, and conjunctiva. Clonal chromosome aberrations have been detected in 13 of 20 (65%) low-grade and 20 of 24 (83%) high-grade tumors. More than half of the low-grade lymphomas with abnormal karyotypes (7 of 13 cases, 53%) displayed clonal t(11;18)(q21;q21), thus specifically associating this translocation with MALT-type lymphomas for the first time in a larger series. In contrast, t(11;18) was not found in a single case of 20 high-grade MALT-type lymphomas with abnormal karyotypes, nor were translocations t(14;18) or t(3;14), characterizing about 10-35% of primary nodal large cell lymphomas. Instead, these lymphomas were associated with t(8;14)(q24;q32) in three cases, frequent deletions in the long arm of chromosome 6, and partial or whole gains of chromosomes 3, 7, 17, 18, and 21.

Diffuse large cell lymphomas are derived from mature B cells carrying V region genes with a high load of somatic mutation and evidence of selection for antibody expression.

Abstract: In the Revised European American Lymphoma (REAL) classification, several subtypes of high-grade lymphomas were combined in the entity diffuse large cell lymphoma (DLL). In the present study, a total of 19 cases of DLL (10 cases of centroblastic lymphoma, 5 cases of mediastinal B cell lymphoma, 2 cases of immunoblastic lymphoma, 1 case of T cell-rich B lymphoma and one case of large cell anaplastic lymphoma) were analyzed for somatically mutated immunoglobulin V region genes. Somatic mutations are acquired in the course of the germinal center (GC) reaction and are thus found in GC B cells and their descendants, i.e. memory B cells. The V gene sequences revealed that the tumor cells of all five subtypes of DLL harbored mutated V region genes and are thus derived from antigen-experienced (post) GC B cells. This indicates that from the point of view of the stage of development of the tumor precursor, the combination of those five subtypes to one entity, i.e. DLL, seems reasonable. In some cases, an unusually high frequency of somatic mutations was detected. This may indicate that DLL are derived from GC B cells, which, due to transforming events, stayed in the GC for prolonged periods of time, thereby accumulating a high load of somatic mutation. An analysis of the mutation pattern suggests that the tumor clone or its precursor were selected for antibody expression while acquiring somatic mutations. The latter observation discriminates DLL from classical Hodgkin's disease, where we recently also observed a high load of somatic mutation within rearranged V region genes, but a frequent occurrence of crippling mutations.

Large cell neuroendocrine [corrected] carcinoma of the uterine cervix: a clinicopathologic study of 12 cases.

Abstract: Twelve cervical tumors showing morphologic evidence of neuroendocrine differentiation and lesional cells larger than those of typical small cell carcinoma are reported in women 21 to 62 (mean 34) years of age. The patients presented with an abnormal Papanicolaou smear or vaginal bleeding. Two tumors were stage Ia2, nine were stage Ib, and one was stage IIa. All patients were treated by radical hysterectomy, and most received adjuvant chemotherapy. Seven of 10 patients with > 1 year of follow-up died of tumor 6 to 24 months after hysterectomy. The tumors had insular, trabecular, glandular, and solid growth patterns and contained medium to large cells with moderate to abundant cytoplasm; eosinophilic cytoplasmic granules were present in nine cases. The tumors were mitotically active, and necrosis was present in 10 of them. Nine of 10 tumors were argyrophilic, and all 12 were immunoreactive for chromogranin. Individual cells containing somatostatin, serotonin, or glucagon were identified in four of eight cases. Adenocarcinoma in situ was present adjacent to the tumor in eight cases; invasive adenocarcinoma of non-neuroendocrine type was present in three of these tumors. Using diagnostic criteria established for pulmonary neuroendocrine tumors, the 12 tumors were classified as large cell neuroendocrine carcinomas. Cervical large cell neuroendocrine carcinomas are distinctive cervical carcinomas that are frequently misdiagnosed and have an unfavorable outcome, similar to that of small cell carcinoma.

Large cell calcifying Sertoli cell tumor of the testis: Contrasting features of six malignant and six benign tumors and a review of the literature

Abstract: We report six malignant and six benign large cell calcifying Sertoli cell tumors of the testis and compare the features of malignant and benign cases based on these cases and those in the literature All the tumors in this report consisted of sheets, nests, solid tubules, and cords of eosinophili

Malignant lymphoma of the bladder: evidence from 36 cases that low-grade lymphoma of the MALT-type is the most common primary bladder lymphoma.

Abstract: Patients with malignant lymphoma of the bladder were studied, and three clinical groups were defined: those with primary lymphoma localized in the bladder, lymphoma presenting in the bladder as the first sign of disseminated disease (nonlocalized lymphoma), and recurrent bladder involvement by lymphoma in patients with a history of malignant lymphoma (secondary lymphoma). The differences in these groups regarding lymphoma type, clinical presentation, and clinical outcome were studied. Mayo Clinic Tissue Registry records from 1940 to 1996 were searched to identify patients with lymphomas involving the bladder. The lymphomas were classified based on review of the histology and immunophenotype performed by immunoperoxidase methods. Clinical records were reviewed. Presenting symptoms included urinary frequency, dysuria, hematuria, and lower abdominal and back pain. Primary lymphoma was present in six patients. All were B-cell lineage low-grade lymphomas of the mucosa-associated lymphoid tissue (MALT) type. No patient had recurrent lymphoma or died of lymphoma. Nonlocalized bladder lymphoma occurred in 17 patients; one with low-grade lymphoma of the MALT type, four with follicle center lymphomas, and 12 with large cell lymphomas. Excluding two patients who died postoperatively, median survival was 9 years. Six patients died of lymphoma in the follow-up period. Secondary bladder lymphoma occurred in 13 patients: two with low-grade lymphoma of the MALT type, one with follicle center lymphoma, one with mantle cell lymphoma, and nine with diffuse large cell lymphomas. Median survival in this group was 0.6 years. Low-grade lymphoma of the MALT type was the most frequent type of primary bladder lymphoma and was associated with an excellent prognosis. The bladder can be the presenting site of lymphomatous involvement in patients with more widespread disease. Survival in this group is quite favorable and is presumably dependent on lymphoma histologic type, stage of disease, and other prognostic factors. Bladder involvement by recurrent lymphoma is a sign of widely disseminated disease and is associated with a very poor prognosis.

Extended operation for non-small cell lung cancer invading great vessels and left atrium.

Abstract: Objective: We analyzed the results of surgical treatment in patients with non-small cell lung cancer invading the great vessels (GV) and left atrium (LA) by direct extension and without distant metastases. Methods: From 1976 to 1993, 42 patients (37/male, 5/female) with lung cancer invading the GV and LA were treated surgically, 13 had invasion of the superior vena cava and innominate vein, 15 of the aorta and subclavian artery, and 14 of the left atrium. In all 42 the diagnosis was confirmed by pathological examination. Surgical resection included pneumonectomy (16 patients) and lobectomy (26 patients). The histologic type was squamous cell carcinoma in 27 patients, adenocarcinoma in 12, and large cell carcinoma in 3. Preoperatively, 13 patients were treated with radiation and chemotherapy. Postoperatively, further treatment was given to 22 patients. All were staged according to the international TNM staging system. Survival was calculated by the Kaplan-Meler method. Results: A total of 15 patients underwent complete resection. Reliability of clinical N factor was 80%. The overall survival was 17% at 3 years (median survival time (MST), 14 months). The operative mortality was 2.4%. Patients with lung cancer invading GV (MST, 19 months) had significantly longer survival than did those with cancer invading LA (MST, 10 months, P = 0.036). There were significant prognostic differences between N0-1 and N2-3 (MST,22 months; MST, 9 months, respectively, P = 0.0013). Cox regression analysis identified pathological N factor, completeness of resection, and pre- and postoperative radiotherapy as important in affecting survival. Conclusions: We conclude that patients with pathological N0-1 non-small cell lung cancer invading great vessels can achieve long-term survival with adequate surgical treatment.

Lymphomas associated with HIV infection.

Abstract: Lymphomagenesis in HIV positive patients is a complex phenomenon not yet completely understood (Karp and Broder, 1992). The great majority of NHL are of the B cell type. Burkitt lymphoma seems to develop early during the evolution of HIV infection in patients with a CD4 count above 200/microliter. MYC is rearranged in the majority of the cases. EBV latent infection is observed in 30-45%. EBV status is characterized by a negativity for EBNA2 and LMP1 The main sites of the tumour are the lymph node and the bone marrow. Diffuse large cell lymphomas, mostly represented by immunoblastic lymphomas with plasmacytoid differentiation and by centroblastic lymphomas rich in immunoblasts, are a late event in HIV infection, in patients with a low CD4 count (often below 50/microliter). The prognosis is worse than in Burkitt and Burkitt like lymphoma. MYC is rearranged in about 30-40% of the cases, whereas more than 70% are EBV positive. EBV status is characterized by a positivity for both EBNA2 and LMP1. B type ALC lymphomas are more frequently associated with EBV than in the general population and exhibit the same EBV status as diffuse large cell lymphomas. HD occurs at any stage of HIV infection. The majority of patients are in clinical stage III or IV at the time of diagnosis, and HIV associated HD shows a more aggressive course than non-HIV HD. Many cases remain difficult to classify; instead, the immunophenotype of neoplastic cells is similar to that in HD occurring in the general population. Histiocytes and epithelioid cells are even more numerous than T lymphocytes, and the CD4:CD8 ratio is low. Neoplastic cells are EBV positive in most or all cases, although they are consistently HIV negative by in situ hybridization. Lymphomagenesis seems to be very complex, with multiple agents acting together or successively. EBV, other viruses, rearrangement of various genes and production of cytokines all seem to have major roles in addition to immune deficiency.

Enhancement of tumor radio-response by irinotecan in human lung tumor xenografts.

Abstract: We investigated the ability of 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin (CPT-11) to increase tumor radio-response in vivo using human lung tumor xenografts. The xenografts were treated with (1) CPT-11 (10 mg/kg) intraperitoneally on days 1, 5 and 9, (2) single dose radiation (10 Gy/leg) on day 1, or (3) a combination regimen of both treatments in which radiation was given 1 h after the first dose of CPT-11. DNA flow cytometry studies were performed to define the cell cycle changes following treatment for 1 to 12 h with 0, 0.5, 2.0 or 8.0 ng/ml SN-38, the major active metabolite of CPT-11. In both small cell lung cancer (MS-1) and small cell/large cell carcinoma (LX-1) xenografts, combination treatment resulted in significant tumor regression compared with the use of CPT-11 (P = 0.0005, 0.0053) or radiation treatment (P = 0.00221, 0.0035) alone. Neither severe body weight loss nor enhanced skin reaction was observed following the combined treatment. In flow cytometry studies, the proportion of cells in G2/M-phase, the most radio-sensitive phase, increased after 1 h exposure to the lowest dose of SN-38 (0.5 ng/ml). These findings suggest that CPT-11 is a potent radiosensitizing agent, and that its activity is related to the cell cycle. This is the first report to indicate that CPT-11 serves as a radiosensitizer in vivo.

Nitric oxide synthase activity in human lung cancer

Abstract: Nitric oxide synthases (NOS) exist in human tumor cell lines and solid tumor tissues, and it has been suggested that NO may play important roles in growth, progression or metastasis of tumors. We investigated the activity and distribution of NOS in a series of human cancer and normal lung tissues. Seventy-two primary lung cancer samples (44 cases of adenocarcinoma, 18 of squamous cell carcinoma, 4 of large cell carcinoma, 2 of small cell carcinoma, 2 of adenosquamous carcinoma, and 2 of carcinoids) and corresponding normal lung samples were obtained from surgically treated patients. In normal lung tissues, little NOS activity was observed with no correlation between the patient's age and NOS activity. The total NOS activities in lung adenocarcinoma samples were significantly higher than those in other types of lung cancers of normal lung samples (P < 0.05). Analysis by tumor grade of the adenocarcinoma samples revealed no significant difference of NOS activity between grades. TNM classification showed that, although T stage did not correlate with NOS activity, cancer tissues from patients with N2 disease tended to have lower activity than those from patients with NO or N1 disease. Immunohistochemical studies revealed that the intensity of NOS immunoreactivity correlated with NOS activity. These results suggest that NO may play an important role in the metabolism and behavior of lung cancers, especially adenocarcinoma.

Cigarette smoking: CT and pathologic findings of associated pulmonary diseases.

Abstract: The health risks associated with cigarette smoking are well known. Cigarette smoking is the most important causative factor in the development of bronchogenic carcinoma. Pulmonary diseases such as chronic bronchitis, centrilobular and panacinar emphysema, respiratory bronchiolitis-associated interstitial lung disease (RB-ILD), and pulmonary Langerhans cell histiocytosis are also related to cigarette smoking. In adenocarcinoma and squamous cell carcinoma, the most common manifestation at computed tomography (CT) is a solitary pulmonary nodule; in small cell carcinoma, hilar and mediastinal adenopathy secondary to metastases; and in large cell carcinoma, a mass with central necrosis or cavitation in the lung periphery. For chronic bronchitis, the most common CT finding is bronchial wall thickening, but this finding is nonspecific. Emphysema, both centrilobular and panacinar associated with alpha-1-antitrypsin deficiency, usually manifests as areas of decreased attenuation and may involve bullous changes. Ho...

Malignant lymphoma of the kidney

Abstract: Background Primary renal lymphoma (PRL) is a rare disease, making information including etiologic factors for PRL extremely limited. Methods Clinical and pathologic findings of PRL in Japan are presented and compared with those from Western countries. The presence of Epstein-Barr virus (EBV) genomes in the tumor was also evaluated. Eight cases of PRL were collected from a review of the “Annual of the Pathological Autopsy Cases in Japan (1976–1992)”. These cases fullfilled the following criteria: (1) presence of renal mass without extrarenal lymphomatous involvement at admission and (2) absence of a leukemic blood picture. For histologic and immunohistochemical studies, 10% formalin-fixed and paraffin-embedded histologic specimens were used. Presence of Epstein-Barr virus (EBV) genome was examined by polymerase chain reaction (PRC) and in situ hybridization (ISH). Results There were five males and three females; age at admission ranged from 15 to 79 years (median 57 yr). Abdominal and/or flank pain were the most common presenting symptoms. No particular past history was present in any of the patients. Histologically, tumor cells in all cases showed a diffuse pattern of proliferation: large cell type in six cases, mixed cell type and small lymphocytic type in 1 each. Immunohistochemistry revealed B-cell nature of lymphoma cells in all cases. Neither PCR nor ISH showed the presence of EBV genome in any cases. Conclusions PRL is non-Hodgkin's lymphoma of predominantly large cell type with a B-cell immunophenotype. EBV etiology is unlikely in PRL. J. Surg. Oncol. 64:207–211, 1997 © 1997 Wiley-Liss, Inc.

Cathepsin B and cysteine proteinase inhibitors in human lung cancer cell lines.

Abstract: Cell lines derived from human squamous cell (EPCL), large cell (LCLC), and small cell lung cancer (SCLC) lines were investigated for the expression of cathepsin B (Cat B) and cysteine proteinase inhibitors (CPIs). The EPLC and LCLC lines expressed 5- to 50-fold more Cat B activity and contained more mature Cat B of M(r) 27-29 kDa (> 2.5 microg/mg total protein) than the SCLC lines ( or = 67 kDa). The LMM inhibitors of M(r) 10-15 kDa were cystatin C and stefins A and B, which were quantitated by ELISA: stefins A and B were present in cell extracts and medium in similar concentrations (5-200 ng/10(6) cells), while 80-99% of the cystatin C was released in the medium (10-195 ng/10(6) cells). Phorbol ester (PMA), which induces protein-kinase C mediated signal transduction and enhances cellular differentiation in many non-small cell lung cancer (NSCLC) cell lines, increased intracellular Cat B activity and Cat B protein as well as its secretion in some cell lines but not in others, regardless of their histological type. PMA significantly (P < 0.049) decreased intracellular stefin A concentrations in two EPLC lines and non-significantly in two LCLC lines. PMA decreased secretion of stefin A in all EPLC lines, but not in LCLC lines, while IGF-I significantly increased stefin B secretion in both SCLC lines. These data showed that lung tumor cells produce both cysteine proteinases and cystatins. As the antagonistic molecules are regulated differently in histologically different types of lung tumor cells, it is possible that an imbalance between the proteinases and their specific inhibitors plays a role in progression of certain types of lung tumors in vivo.

Ocular non-Hodgkin’s lymphoma: a clinical study of nine cases

Abstract: BACKGROUND Primary oculocerebral large cell malignant non-Hodgkin’s lymphoma, formerly called ocular reticulum cell sarcoma, runs a uniformly fatal course. Once the central nervous system (CNS) is involved, survival without treatment is very limited. Although treatment does not substantially improve the long term survival, it provides short term improvement in these patients. METHODS The charts of all patients with ocular involvement of non-Hodgkin’s lymphoma followed during the period 1984–93 were reviewed. The diagnosis of non-Hodgkin’s lymphoma was made by different diagnostic approaches: CNS biopsy, anterior chamber tap, vitrectomy, haematology, and necropsy. RESULTS Eight patients had oculocerebral large cell and one had small cell non-Hodgkin’s lymphoma. Five patients with pure ocular localisation had initially received steroid treatment for intermediate uveitis. First diagnosis was made on CNS biopsy in three, anterior chamber tap in one, vitreous aspirate in three, haematology in one, and necropsy in one case. CONCLUSION Ocular non-Hodgkin’s lymphoma is a difficult diagnosis. Vitrectomy allows cytological diagnosis in most but not all cases. When no treatment is given, patients survive for only a few weeks once the CNS is involved. Although the disease is eventually fatal, treatment by means of radiotherapy, steroid administration, and vitrectomy can allow these patients to lead a normal professional and social life during the years between recurrences.

CD56-positive cutaneous lymphoma: a poorly recognized entity in the spectrum of primary cutaneous disease.

Abstract: Summary CD56-positive (CD56+) lymphomas, characterized by the expression of the neural cell adhesion molecule on pathological lymphocytes, share a frequent extranodal involvement and a generally aggressive course. Five CD3- CD56+ lymphoma patients presenting with nodular lesions were identified among 180 immunophenotyped cutaneous lymphomas. All the patients were men, with ages ranging from 55 to 78 years. After staging, two patients were diagnosed as having primary cutaneous lymphomas: the remaining three had the secondary cutaneous type. The clinical course was aggressive and four patients died within 8 months from diagnosis. The remaining patient is still alive after a 17-month follow-up. The histological diagnosis was immunoblastic lymphoma in two patients, and medium and large cell pleomorphic lymphoma in three. The angiocentric infiltrate was located mainly in the dermis: azurophilic granules were present in three of the five patients. Immunogenotypic analyses suggested the natural killer cell origin of these neoplasias: all cases exhibited a CD56+ CD3- CD5- T-cell receptor (TCR) silent phenotype, and Southern blot analysis showed a germline configuration of the TCR β-chain gene.

CD30 ligand in lymphoma patients with CD30+ tumors.

Abstract: PURPOSECD30 ligand (CD30L), which is expressed on resting B and activated T lymphocytes, can induce cell death in several CD30+ cell lines. Patients with CD30+ tumors (Hodgkin's disease and Ki-1+ non-Hodgkin's lymphoma) frequently have elevated soluble CD30 (sCD30) levels in their serum, which correlates with a poor prognosis. The role of sCD30 in protecting tumor cells from CD30L-mediated cell death and the pattern of CD30L expression on human peripheral-blood lymphocytes (PBLs) of normal donors and patients with CD30+ tumors are investigated.MATERIALS AND METHODSCD30L surface protein expression was determined by two-color flow cytometry on PBLs of patients with CD30+ tumors and normal individuals. CD30L levels were determined on subsets of PBLs before and after stimulation with phytohemagglutinin (PHA), anti-CD3 antibody, or CD40L. sCD30 was measured by enzyme-linked immunosorbent assay (ELISA). The apoptotic activity of membrane-bound CD30L was tested in a CD30+ cell line by the annexin V-binding metho...

Intravascular lymphomatosis: a clinicopathological study of two cases presenting as an interstitial lung disease

Abstract: Aims: Intravascular lymphomatosis is an uncommon type of non-Hodgkin's lymphoma characterized by intravascular proliferation of neoplastic lymphoid cells. Although the tumour is basically a systemic disease, eventually involving multiple organs, primary presentation in the lung is rare. Methods and results: We describe the clinicopathological features of two patients with intravascular lymphomatosis presenting in the lung. One patient complained of fever, headache and chest pain; the other, of dyspnoea on exertion and headache. Both patients showed reticulonodular density on chest radiography and decreased diffusion capacity. Lung biopsy showed features characteristic of intravascular lymphomatosis. Malignant lymphoid cells were CD30 positive T-cells of anaplastic large cell type in one patient and B-cells of large cell type in the other. There was a poor response to chemotherapy and both patients died of the disease within 3 months of diagnosis. Conclusions: These cases and 10 previous reports illustrate the need to include intravascular lymphomatosis in the differential diagnosis of interstitial lung disease.

Angiogenesis correlates with vascular endothelial growth factor expression but not with Ki-ras oncogene activation in non-small cell lung carcinoma.

Abstract: A total of 195 non-small cell lung carcinoma (NSCLC) specimens were studied for the presence of mutations in their ras family genes, for tumor vascularity, and for their immunostaining pattern with an antibody to vascular endothelial growth factor (VEGF). ras mutation was found in 37 of 104 (34.6%) adenocarcinoma specimens, in 0 of 64 squamous cell carcinomas, and in 2 of 27 (7.4%) large cell undifferentiated carcinomas. All mutations were found on the Ki-ras gene, with 37 (95%) of them on codon 12 and the remaining 2 on codon 13. Thirty (77%) of the mutations were G to T transversions. There was a correlation between increasing tumor vascularity and VEGF immunostaining score, but there was no correlation between either of them with the activation of the ras oncogene. A study of VEGF mRNA expression in 14 NSCLC cell lines also demonstrated a lack of correlation between the constitutive expression levels of VEGF and the presence or absence of ras mutation in these cell lines. The results suggest that VEGF is a major angiogenesis factor in NSCLC but that other factors beside ras mutations may influence tumor vascularity in these tumors. The two parameters may potentially serve as independent prognostic factors in NSCLC.