To analyse incidence, risk factors, causes and prognostic significance of venous thromboembolism (VTE) in high‐grade non‐Hodgkin's lymphoma (HG‐NHL) a prospective clinical trial (N = 593), also undertaken to analyse other aspects of HG‐NHL, a study of haemostasis (N = 25) and a post‐mortem analysis (N = 70) were performed. Clinical analysis documented a 6.6% incidence of VTE, and 77% of all cases occurred before or within the first 3 months of chemotherapy. Ann Arbor stage IV and B‐mediastinal clear cell histology were risk factors for VTE, while rapid changes in tumour load or application of consolidation chemotherapy were not. Vessel compression by HG‐NHL was the leading cause of VTE, whereas a significant (paraneoplastic or chemotherapy‐induced) thrombophilic state was not disclosed by haemostatic tests. While VTE‐related fatality was found to be low in the clinical trial (1.7%) and at necropsy (8.5%), the occurrence of VTE was associated with an unsatisfactory response of HG‐NHL to chemotherapy and a high incidence of treatment‐related mortality due to diffuse alveolitis. Thus, fatal VTE in HG‐NHL is rare, but VTE is associated with an unfavourable clinical course of HG‐NHL.

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A 63-year-old woman presented with a history of increasing dysphagia of about two weeks duration. Laryngoscopy revealed a nonulcerated supraglottic epitheliomatous lesion that morphologically appeared well-differentiated and distinctly oncocytoid. Although the tumour lacked any criteria for malignancy such as cellular atypia, pleomorphism or necroses, it recurred twice after primary surgery and later gave rise to multiple painful skin metastases. The diagnosis of an oncocytoid differentiated neuroendocrine carcinoma of the larynx (laryngeal carcinoid) was made. Misinterpretation of laryngeal carcinoids is common, but can be avoided if one is familiar with this rare variant of laryngeal neoplasms

To evaluate treatment-related changes of the reticulin stain-measured fibrosis in Ph(1+)-CML, a clinicopathological study was performed on sequential trephine biopsies of the bone marrow following either interferon (IFN) or busulfan (BU) monotherapy. Using the monoclonal antibody CD61 for the identification of megakaryopoiesis and Gomori's silver impregnation method, number of megakaryocytes and density of argyrophilic (reticulin and collagen) fibers were determined by morphometry. We studied specimens from 26 patients with IFN-alpha 2b (including nine patients with additional IFN gamma) therapy and from 23 patients who had received BU. In both groups, repeated bone marrow biopsies (total 125) revealed a significant increase in the fiber content, as well as in the number of megakaryocytes during treatment. To assess the dynamics of myelofibrosis more precisely, computation of differences in the degree of fiber density between the first and last examination was carried out. Regarding the considerable variations in the biopsy intervals, a so-called myelofibrosis progression index (MPI) was calculated. Following this rationale, we were able to demonstrate that, in comparison to the BU-group, speed of progression of bone marrow fibrosis was significantly increased in CML patients treated with IFN. Preliminary statistical analysis indicated a relationship between myelofibrosis on admission, which was always associated with increased growth of megakaryocytes, and the MPI with survival. Even when these parameters were regarded, prognosis was significantly more favorable in the IFN-treated patients. The failure of IFN and BU to inhibit the evolution of myelofibrosis may be related to several conversely acting pathomechanisms. Among others, the inability of both therapeutic agents to reduce the number of megakaryocytes more effectively should be taken into consideration.

A comparative morphometric analysis was performed on smears and trephine biopsies of normal bone marrow and in chronic myelogenous leukaemia (CML) to assess the effects of therapy on apoptosis and cell proliferation. The in situ end‐labelling (ISEL) technique was used for the demonstration of programmed cell death, in combination with the monoclonal antibody PG‐M1 to identify macrophages. Cell proliferation was evaluated by employing the monoclonal antibody PC10 directed against proliferating cell nuclear antigen (PCNA). In CML (48 patients), significantly higher rates of apoptosis were observed than in normal bone marrow (smears, frozen sections, and paraffin‐embedded samples) of 15 patients. In contrast, the PCNA labelling index of CML was not different from controls. In bone marrow tissue derived from CML patients, about 36 per cent of apoptotic bodies were ingested with CD68‐positive macrophages. Study of the histotopographical distribution of labelled cells revealed that in CML, in contrast to the normal bone marrow, programmed cell death and PCNA activity were concentrated along the paratrabecular generation zone. In 28 patients with CML treated with interferon (IFN), sequential trephine biopsies displayed a significant enhancement of apoptosis which was associated with a decrease in PCNA reactivity. In contrast to this finding, no such alterations could be observed in 24 patients who received busulfan (BU) monotherapy. This study furthers the understanding of cell kinetics in CML. IFN therapy induces apoptosis and suppresses cell proliferation. The rate of programmed cell death prior to therapy and the extent of IFN‐triggered apoptosis exert a significant predictive impact on survival. In this study, ISEL‐positive (apoptotic) cells and bodies do not correspond to unscheduled cell repair as detected by PCNA immunoreactivity. © 1997 John Wiley & Sons, Ltd.