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P van Heerde

Publications and source records attributed to P van Heerde.

At least 37 records · Page 2Linked to original sources

Noncutaneous T-cell lymphomas. Recognition of a lymphoma type (large cell anaplastic) with a relatively favorable prognosis.

BACKGROUND: The clinical relevance of the updated Kiel classification for T-cell lymphomas is discussed. Large series with long-term follow-up are needed to investigate the clinical relevance of a separation into high- and low-grade T-cell lymphomas, based on the Kiel classification. METHODS: The clinicopathologic data of 97 consecutive noncutaneous T-cell lymphomas, diagnosed in the Comprehensive Cancer Center Amsterdam, between July 1, 1985, and December 1, 1990, were reviewed and analyzed for their prognostic significance. RESULTS: Immunohistochemistry contributed substantially in the diagnosis of T-cell lymphoma. Using the updated Kiel classification, many difficulties occurred in classifying these lymphomas. Only large cell anaplastic lymphoma (LCAL) and lymphoblastic lymphoma (LBL) were classified with a high degree of confidence. Variables associated with prolonged survival were classified as LCAL and low stage of disease (Stage I and II) at clinical presentation. Multivariate survival analysis revealed that subtype (grouped as LCAL versus non-LCAL) was selected as the most significant variable, closely followed by stage of disease at clinical presentation (grouped as Stage I/II versus Stage III/IV). LCAL was associated with a significantly better survival than were all other types of high-grade T-cell lymphoma (P = 0.018) and tended to be associated with a better survival than low-grade T-cell lymphoma (P = 0.067). No significant differences in survival were found between the other types of T-cell lymphoma or between high- and low-grade T-cell lymphomas as classified according to the updated Kiel classification. Other variables, such as sex and age (younger than 60 years versus older than 60 years) had no significant influence on survival time. CONCLUSIONS: This study indicates that the clinical relevance of classifying primary noncutaneous T-cell lymphomas according to the updated Kiel classification is limited because only a diagnosis of LCAL has prognostic relevance in predicting survival.

Adolescent↗

The clinical spectrum and treatment of primary non-Hodgkin's lymphoma of the stomach.

BACKGROUND: Primary non-Hodgkin's lymphoma (NHL) of the stomach is a rare disease; diagnosis may be difficult and the method of treatment is at debate, especially the role of surgery. We therefore evaluated clinical findings, in particular endoscopic diagnosis and long-term results of various treatment strategies, especially the effect of the stomach-saving procedure with radiotherapy alone, in patients with stage I and II NHL of the stomach over a 20 year period (1970-91). PATIENTS AND METHODS: A series of 119 consecutive patients (71m + 48f, median age 62 years) were studied: 80 patients in stage I and 39 in stage II. Treatment schedules were: group A: standard radiotherapy alone, after clinical staging (n = 46); group B: gastric resection followed by standard radiotherapy (n = 28); group C: various combinations of resection, radiotherapy plus or minus chemotherapy (n = 45). Since 1978 surgery was no longer advocated: our resection rate dropped from 83% to 38%. RESULTS: Symptoms and signs were non-specific: epigastric pain (81%), nausea (33%), vomiting (24%) and weight loss (66%). Haemorrhage or perforation at presentation were unusual, in 14 (12%) and 5 (4%) cases, respectively. At endoscopy 3 main patterns were recognized: ulceration (34%); diffuse infiltration (18%) and a polypoid mass (37%). Endoscopic biopsies were diagnostic in 92%, including 11% after repeated endoscopy. Treatment results were excellent for stage I: local control in 93%, 5-year survival 70%; in stage II the results were less favorable: 57% and 37%, respectively. Recurrences were only seen in 17 cases, among which 10 cases were extra-abdominal. According to treatment schedule, results were similar in group A (n = 46), with radiotherapy alone, and group B (n = 28), with resection plus radiotherapy, leading to a 5-year overall survival of 71% and 82%, respectively (no significant difference). Severe complications of treatment were infrequent: one perforation, another with a fatal haemorrhage in group A. In group C (n = 45) various individualized schemes were applied, usually palliative either due to large tumour extent or patients of old age and poor condition, leading to a 5-year survival of only 31%. CONCLUSIONS: Clear patterns were recognized at endoscopy, and diagnosis on endoscopic biopsies was possible in the vast majority (92%); in clinical stage I radiotherapy alone is effective, safe and well tolerated.

Adult↗

Differences in clinical behaviour and immunophenotype between primary cutaneous and primary nodal anaplastic large cell lymphoma of T-cell or null cell phenotype.

The histological, immunophenotypic and clinical features of 19 primary cutaneous anaplastic large cell lymphomas (cutaneous ALCL) were compared with those of 18 primary nodal anaplastic large cell lymphomas (nodal ALCL) of T-cell or null cell type. Although cutaneous ALCL and nodal ALCL had identical morphological features, differences in surface marker expression and clinical behaviour were found. Immunophenotypical differences concerned the expression of epithelial membrane antigen (82% of the nodal ALCL were positive v. none of the cutaneous ALCL) and the cutaneous lymphocyte antigen (HECA-452), a possible skin-homing receptor on cutaneous T-lymphocytes (most tumour cells in 44% of cutaneous ALCL cases were positive, whereas nodal ALCL showed expression of HECA-452 on only few tumour cells (< 25%) in 18% of cases tested). Loss of T-cell markers was more pronounced for nodal ALCL. Patients with cutaneous ALCL were generally older (median 61 years) than patients with nodal ALCL (median 24 years) and, in contrast to the latter group, did not show bimodal age distribution. Survival after 4 years, using lymphoma-related death as an end-point, differed significantly between cutaneous ALCL and nodal ALCL; 92% for cutaneous ALCL and 65% for nodal ALCL (P = 0.04). The better survival of cutaneous ALCL patients could not be ascribed to differences in age, stage or initial mode of treatment. These data indicate that differences in immunophenotype and clinical behaviour exist between morphologically identical primary cutaneous and primary node-based ALCL. They indicate that the primary site is an important prognostic factor in predicting the clinical outcome of ALCL.

Adolescent↗

DNA ploidy and cell kinetic characteristics in canine non-Hodgkin's lymphoma.

Malignant lymphoma in the dog is frequently postulated and used as a therapeutic model for non-Hodgkin's lymphoma (NHL) in humans. In this study DNA ploidy and the cell kinetic characteristics of canine malignant lymphoma were studied by flow cytometric (FCM) nuclear DNA measurements on fresh frozen tumor tissue from 94 dogs with NHL and on material from non-neoplastic lymph nodes from 20 dogs. The results were correlated with histomorphology, immunophenotype and survival. All non-neoplastic tissues were diploid, whereas of the 94 lymphomas 74 were diploid or near-diploid and 20 aneuploid. Of the aneuploid lymphomas, 1 contained a hypoploid cell population. DNA-indices of the aneuploid peaks ranged from 0.87 to 1.21 (mean 1.11). The mean S-phase fraction (8.2%, SD 4.8) was significantly lower in the non-neoplastic tissues than in the lymphomas (11.4%, SD 5.1). A linear correlation was observed between FCM S-phase fractions and bromodeoxyuridine (BrdU) labeling indices (r = 0.78; p < 0.001) determined in paraffin-embedded tissue sections from 18 dogs with NHL after in vivo BrdU labeling. DNA ploidy status did not correlate to the S-phase fraction. There were no differences in S-phase fraction and DNA ploidy between B cell and T cell lymphomas or between different histological classes using the Working Formulation. No correlation was found between S-phase fraction or DNA ploidy and survival in a series of 59 dogs treated with a combination chemotherapy protocol. It is concluded that the frequency of DNA aneuploidy in canine malignant lymphoma is similar to that in human NHL. In contrast to findings in human NHL, however, no relationship was found between DNA ploidy or cell kinetic features and histomorphology or prognosis.

Animals↗

High incidence of EBV genome in CD30-positive non-Hodgkin's lymphomas.

In Hodgkin's disease, Epstein-Barr virus (EBV) is found in CD30-positive Reed-Sternberg cells. We therefore studied 60 CD30-positive non-Hodgkin's lymphomas (NHLs) for the presence of EBV by the polymerase chain reaction (PCR) and DNA in situ hybridization (DISH), and by immunohistochemistry for the latent EBV proteins LMP and EBNA-2. CD30-negative NHLs and reactive lymph nodes served as controls. The CD30-positive cases comprised 17 anaplastic large cell lymphomas (ALCLs) (> 75 per cent CD30-positive cells) and 43 non-ALCLs (with 5-35 per cent CD30-positive cells). By PCR, 40 of 60 CD30-positive NHLs (67 per cent) were EBV-positive; in CD30-negative cases, 6/29 (21 per cent) were EBV-positive, as were 12/50 (24 per cent) reactive lymph nodes. The DISH procedure demonstrated the EBV genome exclusively in the nuclei of tumour cells in 23 of the 37 PCR EBV-positive cases that were tested. PCR-negative cases were always DISH-negative, as were the PCR-positive reactive lymph nodes and CD30-negative NHLs. Immunohistochemistry demonstrated LMP in neoplastic cells of 7/47 (15 per cent) CD30-positive NHLs, both ALCL and non-ALCL always in PCR EBV-positive cases, but never in the two control groups. EBNA-2 staining could not be detected. It is concluded that EBV is present (and transcriptionally active) in a sizeable number of NHLs and an association between the presence of the EBV genome and CD30 expression seems likely.

Antigens, CD↗

Differential expression of the HECA-452 antigen (cutaneous lymphocyte associated antigen, CLA) in cutaneous and non-cutaneous T-cell lymphomas.

The monoclonal antibody HECA-452 identifies an antigen that is primarily expressed on high endothelial venules, the preferred site of lymphocyte extravasation in lymphoid tissues, and also on a subpopulation of myelomonocytic cells and some T-cells. We investigated the expression of the HECA-452 antigen, also called the cutaneous lymphocyte associated antigen, in primary cutaneous and primary non-cutaneous T-cell non-Hodgkin's lymphomas. The tumour cells of cutaneous T-cell non-Hodgkin's lymphomas were positive in 53% of cases, while only 5% of the non-cutaneous lymphomas were positive. These differences were also present in morphologically identical tumours. Thus, the tumour cells in six out of 10 primary cutaneous anaplastic large cell T-cell lymphomas were positive, while they were positive in none of 24 primary non-cutaneous anaplastic large cell T-cell lymphomas. In general, primary cutaneous and primary nasal T-cell non-Hodgkin's lymphomas were devoid of HECA-452 positive high endothelial venules, whereas most nodal T-cell non-Hodgkin's lymphomas contained HECA-452 positive high endothelial venules. These observations suggest that the HECA-452 antigen might be related to a skin-associated type of lymphoid tissue and to lymphomas originating in the skin. However, the results of HECA-452 expression in secondary sites, and the clinical data of the primary cutaneous large cell lymphomas did not support the concept that HECA-452 is functionally involved in homing to the skin, or that loss of the HECA-452 antigen is related to tumour progression of primary cutaneous T-cell lymphomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

Results of radiotherapy in patients with stage I orbital non-Hodgkin's lymphoma.

This paper describes the results of radiotherapy in early stage orbital non-Hodgkin's lymphoma. From 1970 to 1985, 33 orbital localizations in 30 patients were treated. The total dose applied ranged from 21 to 57 Gy (2 Gy per fraction), two-thirds of all patients received a dose of 40 Gy. The complete-response rate was 94% and the 10 years actuarial survival was 90%; no significant difference in survival was observed between patients with low grade or intermediate grade lymphoma. No local recurrence was detected during follow up and 20% of the patients developed generalized disease. Two optic nerve neuropathies and three retinopathies were observed in five patients, four of these occurred at a dose level of less than 43 Gy. Keratitis occurred in 58% of the patients treated, a sicca syndrome in 30% and cataract of different grades in 58% of the patients treated. Although local control was excellent, severe complications were observed in 13% of the patients who received a dose of less than 43 Gy.

Dose-Response Relationship, Radiation↗

Cerebrospinal fluid tumour markers in patients treated for meningeal malignancy.

The results of cerebrospinal fluid (CSF) biochemical markers were compared with conventional CSF cytology in patients treated for leptomeningeal metastases from extra cranial malignancies. For lumbar CSF, before treatment, no statistically significant difference of the probabilities of being positive was found between CSF cytology and a classification by linear discriminant analysis, based on patient's age, of beta-glucuronidase and beta 2-microglobulin. During treatment, classification by linear discriminant analysis was found more often positive than cytology. Possible mechanisms for this difference are discussed. For ventricular CSF a correlation was found between CSF cytology and beta-glucuronidase for solid tumours, and between CSF cytology and beta 2-microglobulin for haematological malignancies. Reference values for ventricular protein, CEA beta-glucuronidase and beta 2-microglobulin were obtained for cytological negative samples.

Adult↗

Polyethylene glycol-L-asparaginase versus native L-asparaginase in canine non-Hodgkin's lymphoma.

42 dogs with non-Hodgkin's lymphoma (NHL) were randomized for treatment with either PEG-L-asparaginase 10 IU/kg intramuscularly (n = 22) or L-asparaginase 400 IU/kg intraperitoneally (n = 20). Another 20 dogs were treated with either PEG-L-asparaginase 30 IU/kg (n = 10) or L-asparaginase 400 IU/kg (n = 10). Each treatment protocol consisted of two asparaginase treatments followed by a 10-week period of induction chemotherapy and then maintenance on asparaginase until progression occurred. No significant differences were found between treatments in the response rates after 2 weeks of asparaginase therapy or in the time to relapse, the time to treatment failure or the remission period. The reaction to asparaginase after the initial 2 weeks was a prognostic factor for the total duration of remission under asparaginase maintenance therapy. No side-effects were noted in the dogs treated with PEG-L-asparaginase, whereas 14 (48%) of the L-asparaginase treated dogs had side-effects related to this drug, including anaphylactic shock (9), anorexia or vomiting (4), hypersensitivity-related oedema (3), seizures (1) and acute pancreatitis (1). No abnormalities in clotting times, fibrinogen levels or antithrombin-III levels were found in any of the 62 dogs. PEG-L-asparaginase has the same anti-tumour activity as native L-asparaginase in dogs with NHL, but lacks side-effects.

Animals↗

Stage is a better prognostic indicator than morphologic subtype in primary noncutaneous T-cell lymphoma.

The authors reviewed 28 primary noncutaneous T-cell lymphomas, referred to the Comprehensive Cancer Center Amsterdam, using the updated Kiel classification. Clinical course was related with stage of disease, morphologic subtype, and immunophenotype of the tumor cells. The incidence of primary noncutaneous T-cell lymphomas was 4.1 cases per 1,000,000 people per year. Morphologic classification was difficult and arbitrary. Immunohistochemistry contributed considerably in diagnosis of this group of tumors. All primary noncutaneous T-cell lymphomas had a poor prognosis, with no significant difference between predominantly small cell (low-grade) and large cell (high-grade) tumors. The only parameter significantly correlating with survival was the stage of the disease at presentation. The results suggest that all types of primary noncutaneous T-cell lymphoma are to be considered high grade and that primary localization (cutaneous vs. noncutaneous) and stage of disease at presentation appear to be more important as predictors of clinical outcome than morphologic or immunophenotypic subtype.

Adolescent↗

Cytology of Ki-1 (CD-30) positive large cell lymphoma.

To study the cytomorphology of Ki-1 (CD-30) positive anaplastic large cell lymphoma, imprints and fine needle aspirates from a total of 20 of these tumours were collected. The results show that these tumours have a highly pleomorphic and variable picture, which can be easily confused with other poorly differentiated large cell tumours. Typical morphological differences between the B-cell and T-cell variety were found. B-cell tumours more often showed nuclear multilobation, a fine, hypochromatic chromatin pattern, and many lymphoglandular bodies. T-cell tumours more often displayed multinucleation, window nuclei, and a hyperchromatic coarse chromatin pattern. The diagnosis of anaplastic large cell Ki-1 positive lymphoma, B-cell type or T-cell type, should be included in the differential diagnosis of any large cell tumour of uncertain origin with mainly dissociated tumour cells. Immunocytochemistry is recommended to establish the correct diagnosis.

Antibodies, Monoclonal↗

Primary non-Hodgkin's lymphoma of the stomach: changing aspects and therapeutic choices.

Eighty-five consecutive patients, seen between 1970 and 1987, with primary gastric non-Hodgkin's lymphoma were studied to evaluate diagnostic findings and treatment results. At endoscopy three main patterns were recognized: ulceration (n = 21), diffuse infiltration (n = 16) and a polypoid mass (n = 26). Recently, the new technique of endoscopic ultrasonography was used to measure depth of infiltration and regional lymph nodes. Preoperative diagnosis altered the indication of surgery. Since 1978 surgical staging was performed in only 29% of the patients compared to 90% in the earlier period. In the later period stage II was more systematically treated with a combination of chemotherapy and radiotherapy. Over the whole period patients in stage I (n = 52) had a 5 year disease-free survival of 63%. In stage II 38% had a 5 year disease-free survival. Complications were one perforation and one haemorrhage after radiotherapy and two cases of haemorrhage after radiotherapy combined with chemotherapy. Intraabdominal recurrences were found in two cases. Recognition of endoscopic features may lead to early detection and ultimately improved survival.

Adult↗

Therapy-relevant discrepancies between diagnoses of institutional pathologists and experienced hematopathologists in the diagnosis of malignant lymphoma.

We have studied therapy-relevant discrepancies in the diagnoses of institutional pathologists and a panel of 4 experienced hematopathologists in 375 cases from patients with malignant lymphoma. Two hundred and fifty four cases (68%) were contributed by non-panel pathologists and 121 (32%) by individual panel pathologists. Overall, in 24% (91/375) of the cases, therapy-relevant discrepancies were present between institutional pathologists and panel diagnoses. Thirty-four percent (87/254) therapy-relevant discrepancies were present in cases contributed by non-panel pathologists, whereas in only 3% (4/121) discrepancies were found in cases forwarded by individual panel pathologists. The percentages erroneously diagnosed Hodgkin's disease by non-panel pathologists and individual panel pathologists were 8 and 0% respectively and faulty diagnosed Non-Hodgkin lymphomas 5 and 0%, whereas the number of consultation cases, in which the referring pathologist was not certain of his diagnosis, appeared to be 24 and 3% for non-panel and panel pathologists respectively. In addition, in 14% of panel confirmed NHL contributed by non-panel pathologists, therapy-relevant discrepancies in the degree of malignancy grading according to the Working Formulation were present, whereas no discrepancies in malignancy grading were noted between individual panel members and panel diagnoses. Apart from extensive hematopathological experience, a reason for the higher diagnostic accuracy of the panel pathologists could well be the frequency in which the diagnoses were supplemented by immunophenotyping: in 22% of the cases from non-panel pathologists and 63% of the cases from panel pathologists immunophenotyping on frozen sections was carried out.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnosis, Differential↗

Increased risk of lung cancer, non-Hodgkin's lymphoma, and leukemia following Hodgkin's disease.

The risk of second cancers (SCs) was assessed in 744 patients with Hodgkin's disease (HD) admitted to The Netherlands Cancer Institute from 1966 to 1983. Sixty-nine SCs were observed one month or more after start of first treatment. These included 14 cases of lung cancer, nine cases of non-Hodgkin's lymphoma (NHL), 16 cases of leukemia, and six cases of the myelodysplastic syndrome (MDS). The median interval between the diagnosis of HD and that of second lung cancer, NHL, and leukemia was 8.1, 13.3, and 5.7 years, respectively. The overall relative risks (RR) (observed/expected [O/E] ratios) of developing lung cancer, NHL, and leukemia were 4.9 (95% confidence limit [CL], 2.7 to 8.2), 31.0 (95% CL, 14.2 to 58.9) and 45.7 (95% CL, 26.1 to 74.2), respectively. At 15 years the cumulative risk of developing an SC amounted to 20.6% +/- 2.9%. The 15-year estimates of lung cancer, NHL, and leukemia were 6.2% +/- 1.9%, 5.9% +/- 2.1% and 6.3% +/- 1.7%, respectively. Increased lung cancer risk following HD has not frequently been clearly demonstrated before; that we were able to demonstrate such risk may be due to the completeness of follow-up over long periods that could be achieved in this study. Excess lung cancer risk was only noted in treatment regimens with radiotherapy (RT); also, all lung cancers arose in irradiation fields. Excess risk of leukemia was only found in treatment regimens involving chemotherapy (CT). For NHL, combined modality treatment was shown to be the most important risk factor. Risk of lung cancer and NHL increased with time since diagnosis. A time-dependent covariate analysis (Cox model) performed on leukemia and MDS showed an increasing risk with intensity of CT, age (greater than 40 years), and a splenectomy.

Adult↗

Atypia in fine-needle aspiration cytology of the breast: a histologic follow-up study of 301 cases.

A gray area of uncertainty exists in fine-needle aspiration (FNA) cytology of the breast in which common criteria to distinguish benign from malignant lesions overlap. Aims of this study were to define this area and to evaluate statistically cytomorphologic criteria in a semiquantitative analysis. In a test set of specimens from well-differentiated carcinomas and benign proliferative lesions, signs of malignancy were cell dissociation, arrangement in small clusters, nuclei greater than 16 microns, anisonucleosis, irregular nuclear borders, nucleoli, and necrosis. Features in favor of benignancy were large monolayers, nuclei less than 16 microns without variation in size, smooth nuclear borders, and bipolar nuclei in the monolayers. Originally the term "atypia" had been applied to 956 (12%) of all FNAs of the breast performed at our institute from 1974 to 1985. Using these criteria in a review of all 301 cases in which histologic follow-up and cellular smears were available, much better results were obtained than originally; specificity increased from 80% to 95%, and sensitivity increased from 60% to 90%. The number of overdiagnoses decreased from 24 to seven, and underdiagnoses decreased from 57 to nine. In this selected series, the area of uncertainty was restricted to 16% of the cases; the number of these cases that proved to be malignant and benign was equal. In such cases of indistinct cytomorphologic criteria, a surgical biopsy is indicated for histologic studies.

Biopsy, Needle↗

Treatment results of primary stage I and II non-Hodgkin's lymphoma of the stomach.

Gastric lymphoma in stage I or II was usually treated by partial gastrectomy and total abdominal irradiation in our institute since 1970. Since 1978, a number of patients were also treated without laparotomy, in clinical stage I with radiotherapy only and in clinical stage II with combined modality treatment. Treatment results of 58 patients are reported. A relapse-free survival rate of 85% was reached for 24 patients treated with resection and irradiation either in stage I or II, and for seven patients in stage I who did not undergo surgery. For these patients, survival in stage I was 85%, in stage II, however, survival dropped to 60% due to intercurrent deaths. Seven stage II2 patients received intensive chemotherapy and radiotherapy with 58% relapse-free survival. Twenty patients could not be treated according to the outlined treatment protocol. For the total group, survival in stage I is 65% and in stage II 35%. In the Addendum, an additional group of 17 patients is mentioned with the same result.

Actuarial Analysis↗

CSF cytology versus immunocytochemistry in meningeal carcinomatosis.

CSF immunocytochemistry with monoclonal antibodies was compared with conventional cytology to determine its sensitivity in detecting malignant cells in patients with meningeal carcinomatosis. One hundred and eighteen samples were investigated. Cytology was tumour positive in 83 samples and immunocytochemistry in 85. Dissimilar results between the two diagnostic methods were noted in 12 specimens, invariably occurring in samples with a low cell count and obtained from treated patients. Combined use of the two methods led to a 9% increase of sensitivity in detecting malignant cells compared with cytology alone. It is concluded that immunocytochemistry is of minor help in the problem of false-negative cytology in meningeal carcinomatosis.

Adenocarcinoma↗