Occurrence of esophageal granular cell tumors in The Netherlands between 1988 and 1994.

Granular cell tumors (GCT) of the esophagus are rare. The tumor is generally beleived to be of neurogenic origin and shows a malignant course in 2-4% of cases. No unanimity has been reached regarding the management of this tumor. A national survey was conducted on the incidence of GCT of the esophagus, related symptoms, management, and follow-up. A national survey was performed on all newly registered esophageal GCTs in the PALGA system (Dutch register of all pathology diagnoses) for seven consecutive years (1988-1994). Fifty-two new cases (17 men, 35 women; median age 46 years, range 22-77 years) were registered. In 44 cases clinical data could be obtained (survey response 85%). The majority of the GCTs were solitary (42/44) and localized in the distal esophagus (33/44). At endoscopy the size of the tumor was estimated at <5 mm in 50%, 5-10 mm in 25%, and 10-30 mm in 18%. Most patients (40/44) presented with nonspecific gastrointestinal symptoms, only four had dysphagia (tumor size >1 cm). No malignancies were reported. Management of the tumor included excisional biopsy (1/44), endoscopic polypectomy (3/44), and surgical excision (1/44). Endoscopic follow up (1-60 months) in 16 out of 17 patients left untreated showed either a stable tumor size or regression of the tumor. In one case with multiple GCT's a slight tumor growth was seen after a follow-up period of 48 months. Esophageal GCTs in the Netherlands are rare, and mostly diagnosed incidentally. Most patients suffer from nonspecific symptoms; dysphagia occurs only with tumors >1 cm. The usual clinical course of esophageal GCTs is benign. Patients without dysphagia probably do not require routine endoscopic follow-up, provided they are instructed to contact their physician, once dysphagia develops.

Bronchoalveolar lavage fluid cytology in patients with Pneumocystis carinii pneumonia.

OBJECTIVE: To evaluate bronchoalveolar lavage (BAL) cytology and organism burden in patients with Pneumocystis carinii pneumonia (PCP) who were infected with the human immunodeficiency virus (HIV) and in those with other immunodeficiencies. STUDY DESIGN: BAL fluid samples from patients with PCP were selected (HIV-infected patients, n = 15; patients with other immunodeficiencies, n = 11). May-Grünwald-Giemsa-stained cytocentrifuge preparations were evaluated. Foamy alveolar casts (FACs) and P carinii clusters were counted. RESULTS: The numbers of FACs and P carinii clusters in BAL fluid samples of HIV-infected patients were significantly higher as compared to those in samples from patients with other immunodeficiencies. Striking cytologic findings observed in half the samples from both patient groups included the presence of foamy alveolar macrophages, activated lymphocytes, plasma cells and reactive type II pneumocytes. Furthermore, a peculiar cell type, "nonidentified cell" (NIC), was observed almost exclusively in BAL fluid samples from HIV-infected patients. CONCLUSION: BAL fluid samples from HIV-infected patients with PCP displayed higher organism burdens as compared to those from patients with other immunodeficiencies. Moreover, cytologic findings suggestive of noninfectious lung conditions were common in BAL fluid samples obtained from patients with PCP. Further study is required to elucidate the identity of the NIC cell type.

Cytocentrifugation conditions affecting the differential cell count in bronchoalveolar lavage fluid.

OBJECTIVE: To investigate variations in speed, duration and acceleration rate of the Cytospin 3 cytocentrifuge (Shandon Scientific Ltd., Astmoor, England) on the differential cell count of bronchoalveolar lavage (BAL) fluid samples. STUDY DESIGN: BAL fluid samples (n = 51) were cytocentrifuged at various combinations of speed (500, 1,200 and 2,000 rpm), acceleration rate (low, medium and high) and duration (5, 10, 15 and 20 minutes). The preparations were May-Grünwald-Giemsa stained and differentiated on 500 cells. Data were analyzed by mixed model repeated measurements ANOVA. RESULTS: The mean lymphocyte count was significantly higher at 1,200 rpm than at 500 rpm, whereas the macrophage count decreased. Between 1,200 and 2,000 rpm, the number of both cell types stabilized. Significantly higher numbers of lymphocytes were recorded at 10 and 15 minutes of cytocentrifugation than at 5 minutes. The acceleration rate did not influence the differential cell count. Seventeen BAL fluid samples were selected to test the diagnostic impact of cell damage using a validated computer program. In 1 of 17 samples the predicted diagnosis did not correspond between two different speeds (500 and 2,000 rpm). CONCLUSION: Variations in cytocentrifugation speed and duration affected the mean lymphocyte and macrophage counts of BAL fluid samples.

Differential cell analysis of cytocentrifuged bronchoalveolar fluid samples affected by the area counted.

OBJECTIVE: To investigate variations in the differential cell counts between the quadrants of cytocentrifuged bronchoalveolar lavage (BAL) fluid preparations and to evaluate the diagnostic impact of these differences in interstitial lung diseases (ILD). STUDY DESIGN: BAL fluid samples obtained from 30 patients suspected of having ILD or pneumonia were cytocentrifuged and additionally stained with May-Grünwald-Giemsa stain. Two observers differentiated 200 cells in each quadrant as well as in a circular pattern around the center of the cytocentrifuge spot. RESULTS: Lymphocytes and alveolar macrophages were not randomly distributed on the cytocentrifuge spot. Ten samples of patients with histologically confirmed ILD were selected to test the diagnostic impact using a validated computer program. The predicted diagnosis did not correspond to the histologic diagnosis for one quadrant from 1 of these 10 samples (sarcoidosis instead of idiopathic pulmonary fibrosis), whereas the differential cell counts performed around the center of the cytocentrifuge spot provided the correct diagnosis in all cases. CONCLUSION: BAL fluid differential cell counts varied between the quadrants of the cytocentrifuge spot. The center of the cytocentrifuge spot appeared to be the most reliable area. Therefore, cell counting is recommended in a circular pattern around the center of the cytocentrifuge spot.

Relationship between pernicious anaemia and gastric neuroendocrine cell disorders.

The incidence of gastric carcinoid tumours is increasing. This rise is probably due to the number of gastroscopies and improved histological techniques. The majority (65%) of these gastric tumours is associated with chronic atrophic gastritis and pernicious anaemia. In this article two patients are presented, one with pernicious anaemia and gastric neuroendocrine cell hyperplasia and one with pernicious anaemia and multiple gastric carcinoids. These neuroendocrine cell disorders have a relatively favourable prognosis. Therefore, a wait-and-see policy was preferred. The pathogenesis, clinical symptoms, diagnosis, prognosis and treatment of these different neuroendocrine cell manifestations are discussed. We recommend performing a gastroscopy at the time of diagnosis for young patients with pernicious anaemia, and whenever abdominal problems, unexplained weight loss or aggravation of the anaemia arise.

Detection of non-infectious conditions mimicking pneumonia in the intensive care setting: usefulness of bronchoalveolar fluid cytology.

The present study investigated the usefulness of bronchoalveolar (BAL) fluid cytology in the identification of non-infectious pulmonary conditions in patients hospitalized in the intensive care unit (ICU) and suspected of pneumonia. A total of 182 BAL fluid samples obtained during a 27-month period from 130 ICU patients with suspected pneumonia were quantitatively cultured and investigated for opportunistic pathogens. Cytocentrifuged preparations stained with the May-Grünwald Giemsa and Perls's methods were reviewed. A non-infectious aetiology was considered when cultures yielded micro-organisms in quantities < 10(3) colony-forming units (CFU) per ml, in the absence of any other pathogen and in conjunction with one or more of the following cytological findings: > 20% haemosiderin macrophages, > 10% lymphocytes, the presence of activated lymphocytes, plasma cells, > 5% eosinophils, a preponderance of foamy macrophages, reactive type II pneumocytes or malignant cells. Patients' clinical records were reviewed to identify a clinical diagnosis for these episodes. In thirty-five (19.2%) BAL fluid samples from 26 patients, the cytological findings pointed to a non-infectious origin. An alternative diagnosis was ascertained in 20 of 26 patients. Diagnoses included: drug-induced pneumonitis (n = 7), aspiration of gastric contents (n = 2), pulmonary emboli (n = 3), adult respiratory distress syndrome (n = 4), lung contusion (n = 1), cardiogenic pulmonary oedema (n = 1), and carcinomatous lymphangitis (n = 2). The BAL fluid cytological findings were readily discernable and proved to be useful in the diagnostic work-up of samples obtained from ICU patients with suspected pneumonia.

[Nonspecific symptoms due to gastrointestinal stromal tumors]. / Aspecifieke klachten bij gezwellen van de maag-darmwand.

Three patients, two women aged 64 and 52 years and one man aged 78 years, had non-specific symptoms and they had signs of a tumour at imaging examination. Immunohistochemical study of operation preparations led to the diagnosis of 'gastrointestinal stromal tumour' (GIST). It is important to consider the possibility of a GIST at surgery, because the potential malignancy requires a resection with free margins.

[New WHO-classification of lung and pleural tumors]. / Nieuwe WHO-classificatie voor long- en pleuratumoren.

A new classification of the World Health Organization (WHO) of lung and pleural tumours will be published presently. Compared with the previous edition of 1981 the changed parts more accurately reflect the available therapeutic choices and the prognostic characteristics of the different tumour types. The classification is based on conventional light-microscopical typing. Additional techniques (from histochemistry, immune histochemistry, electron microscopy and molecular biology) have not yet decisive influence on tumour typing. The dichotomy between small-cell and large-cell carcinomas is too simplistic, as the group of large-cell carcinomas is heterogeneous, and further differentiation leads to identification of tumour types with distinct therapeutic options and prognostic characteristics. There are new criteria for the classification of neuroendocrine tumours, such as the mitotic index. It is recommended to use the newly revised classification for diagnostic purposes, epidemiology and biologic studies.

Diagnosis of Pneumocystis carinii pneumonia in HIV-positive patients. Bronchoalveolar lavage vs. bronchial brushing.

OBJECTIVE: To evaluate the contribution of bronchoalveolar lavage (BAL) and bronchial brushing (BB) and the use of different tinctorial stains in the detection of Pneumocystis carinii (PC) in human immunodeficiency virus (HIV)-positive patients. STUDY DESIGN: In a retrospective study, 195 HIV-positive patients suspected of a pulmonary infection underwent bronchoscopy with BAL. In 143 cases subsequent BB was performed. On 135 BAL fluid cytocentrifuge preparations four staining techniques were applied simultaneously: May-Grünwald-Giemsa (MGG), toluidine blue-O (TOL), Papani-colaou (PAP) and Grocott methenamine silver (GRO). RESULTS: PC was recovered in 79 (40.5%) cases. The yields of MGG and TOL were identical (33.3%). PAP and GRO showed lower results, 31.1% and 29.6%, respectively. These differences were not statistically significant. The combination of BAL and BB revealed 64 cases of PC infection. BAL was positive in the vast majority of cases (63, 44.1%). BB was positive in 54 (37.8%). The combination of positive BB with negative BAL was present in one case. However, 10 cases of PC were found with the use of BAL and not detected by BB (P < .01). CONCLUSION: The results of this study indicate that to confirm a PC infection in HIV-positive patients, the use of bronchoalveolar lavage with a single staining technique is appropriate. Bronchial brushing seems to be of limited additional value.

[Diagnostic examination for causes of exudative pleurisy]. / Diagnostiek naar de oorzaak van exsudatieve pleuritis.

In two patients, men aged 65 and 57 years with complaints of exertional dyspnoea, dry cough, diminished appetite and weight loss, the cause of pleural fluid formation was not discovered despite several diagnostic procedures. In the first patient a diffuse mesothelioma was found at autopsy. The second patient had pleurisy secondary to an adenocarcinoma in the upper lobe of the right lung; he died from lung embolism after the second, diagnostic, thoracoscopy. It can be difficult to establish the diagnosis in patients with a pleural effusion. Specific reasons for this are abundant formation of connective tissue in cases of malignant pleural disease and subsequent risks of sampling errors.

Pulmonary infiltration associated with myelodysplasia.

Four case histories are reported in which the initial signs and symptoms were those of pulmonary infiltration and in which subsequently a diagnosis of myelodysplasia was made. The analysis of bronchoalveolar lavage fluid--demonstrating predominantly neutrophils and lymphocytes, and, occasionally blast cells as well as plasma cells--indicated that the pulmonary infiltration was related to the myelodysplastic process. As no other causes of pulmonary infiltration could be found, it seems that a pulmonary infiltrate can be the presenting symptom of a myelodysplastic syndrome. Although pleuropulmonary infiltrates most often are caused by infections, these cases illustrate that myelodysplasia related infiltrates should also be considered.

A comparison of NSP-reticulons with conventional neuroendocrine markers in immunophenotyping of lung cancers.

Neuroendocrine-specific protein (NSP)-reticulons are endoplasmic reticulum-associated protein complexes, which have been identified as markers for neuroendocrine differentiation. In this study, the expression of two members of the family of NSP-reticulons, NSP-A and NSP-C, have been investigated in different types of lung cancer and compared with the expression patterns of five conventional neuroendocrine markers, the neural cell adhesion molecule (NCAM), synaptophysin, chromogranin A, Leu-7, and neurofilament proteins. NSP-A and NSP-C antibodies were reactive with most carcinoid tumour and small cell lung carcinoma (SCLC) cases, while atypical carcinoid tumours showed a variable expression. In the total group of neuroendocrine tumours, a high concordance of expression was found between NSP-A and NSP-C, while their expression correlated well with NCAM and synaptophysin positivity. Chromogranin A, Leu-7, and neurofilament proteins were shown to be expressed to a limited extent in these neuroendocrine tumours. In a selected group of non-SCLCs known to exhibit neuroendocrine features, NSP-A expression was detected at much higher frequency than NSP-C. In virtually all NSP-A positive cases, this expression was associated with one or more of the other neuroendocrine markers. NSP-A expression showed a stronger correlation with conventional neuroendocrine markers than NCAM. In detecting neuroendocrine differentiation in non-SCLC, NSP-A is more sensitive than synaptophysin, chromogranin A, Leu-7, and neurofilament proteins. It is concluded that NSP-reticulons are valuable markers in the diagnosis of neuroendocrine differentiation in non-SCLC and should be used in conjunction with NCAM.

Serum LDH: a marker of disease activity and its response to therapy in idiopathic pulmonary fibrosis.

In the following case report the determination of serum lactate dehydrogenase (LDH)-a simple though non-specific test-reflects changes of disease activity and clinical improvement during treatment with cyclophosphamide and a tapered dose of prednisone from 100 to 0 mg daily in a 43-year-old woman with idiopathic pulmonary fibrosis. The trend observed in this case indicates that the serum LDH-activity may be directly proportional to the extent of this diffuse inflammatory pulmonary disease.

Cytomegalovirus induces interstitial lung disease in allogeneic bone marrow transplant recipient rats independent of acute graft-versus-host response.

Interstitial lung disease (ILD) after allogeneic bone marrow transplantation (BMTx) is an important clinical problem in terms of diagnosis, therapy, and pathogenesis. Graft-versus-host disease (GvHD) and cytomegalovirus (CMV) infection seem to be major risk factors for ILD, but their role in the pathogenesis is not well established. We previously reported CMV-induced ILD in allogeneic bone marrow recipient rats, which was prevented by antiviral drug treatment. In this paper, we describe the pathology of ILD in allogeneic bone marrow transplant recipient rats and the relation of ILD with CMV infection and GvHD. Brown Norway rats received an allogeneic (Lewis) BMTx and rat CMV infection, after an allogeneic (Lewis) lung transplantation and immunosuppression. CMV infection was recorded by the amount of infectious virus and viral antigens in the lung. ILD was monitored by the presence of diffuse histopathologic changes in the alveolar septal wall. GvHD was scored by the relative splenic weights and the presence of perivascular infiltrates in the lung. Cells expressing CMV antigens were more numerous in the alveolar septa of the allogeneic recipient lungs than in the syngeneic donor lungs (p < 0.05). The high viral load in the recipient lung of allogeneic BMTx recipient rats was accompanied by diffuse ILD, marked by extensive microvascular damage and congestion of the alveolar septa. ILD was observed neither in the syngeneic donor lung nor in both lungs of mock-infected animals. GvHD was not observed in rat-CMV-infected or in mock-infected animals. Our results indicate that CMV induces microvascular damage, resulting in ILD. This process is independent of GvHD.

Combinations of ganciclovir and antibody for experimental CMV infections.

The effect of combined treatment with ganciclovir and hyper immune serum (HIS) was evaluated in three animal models. It concerned a generalized CMV infection model, a meningo-encephalitis model and an interstitial lung disease (ILD) model in immunocompromised rats. In the generalized model, the ganciclovir and HIS had a moderate synergistic effect on survival and greatly decreased virus titers in internal organs. In contrast, in the meningoencephalitis model, combined treatment had no effect on the local virus titers and the histopathology. Combined treatment with ganciclovir and HIS, however, effectively abolished CMV-induced ILD.

Relationship between cells obtained by bronchoalveolar lavage and survival in idiopathic pulmonary fibrosis.

BACKGROUND: The relationship between cell types in bronchoalveolar lavage (BAL) fluid and the clinical course of patients with idiopathic pulmonary fibrosis (IPF) has been the subject of several studies. However, the results of these studies are not conclusive. The aim of this study was to investigate the relationship between the absolute and relative cell numbers in BAL fluid from patients with IPF and their survival. METHODS: Results obtained from the initial BAL fluid analyses of all histologically proven cases of IPF (n = 49) were selected retrospectively. Cox's proportional hazards survival analysis was used for estimating the relationship between absolute and relative cell numbers and survival. RESULTS: A negative relationship was found between both the absolute numbers and percentages of eosinophils in BAL fluid samples and survival. No such relationship was demonstrated for the absolute numbers or the percentages of any other cell type. CONCLUSIONS: Although this study has restrictions, these findings suggest a negative relationship between the absolute numbers and percentages of eosinophils in BAL fluid samples and survival in patients with IPF.

The choriocarcinoma syndrome: an emergency.

A 36-year-old male patient is described who presented with gynaecomastia, pulmonary nodules and a retroperitoneal mass in combination with a markedly elevated HCG level. A diagnosis of "choriocarcinoma syndrome" was made. Despite a clear response from the tumour to chemotherapy the patient died, at least partially due to delay in treatment. Prompt treatment even without cytological or histological proof is therefore stressed.