Tumour markers in the diagnosis of bronchial carcinoma: new options using fuzzy logic-based tumour marker profiles

The diagnosis of lung cancer and early knowledge of its histological type are very important; however, this is still a difficult subject for the physician. The aim of this study was to improve the diagnostic efficiency of tumour markers in the diagnosis of bronchial carcinoma by mathematical evaluation of a tumour marker profile employing fuzzy logic modeling. A panel of five tumour markers, including CYFRA 21-1, CEA, NSE, and five additional parameters was determined in 281 patients with confirmed primary diagnosis of bronchial carcinoma of different histology and stage. A further 131 persons, who had acute and chronic benign lung diseases, served as a control group. A classificator was developed using a fuzzy-logic rule-based system. The diagnostic value of the combined tumour markers was significantly better than that of the individual markers and of a combination of CYFRA 21-1, CEA, and NSE. The discrimination of malignant vs benign diseases was realized with a sensitivity of 87.5% and specificity of 85.5%. The rate of correct classification of small-cell vs non-small-cell lung carcinoma was 90.6% and 91.1%, respectively; for squamous cell carcinoma vs adenocarcinoma it was 76.8% and 78.8%, respectively. Our detailed analysis has shown that the fuzzy logic system improves diagnostic accuracy up to a rate of 20%, especially in early stages and in patients with all marker levels in the grey area. Our concept proved to be more powerful than measurement of single markers or the combination of CEA, CYFRA 21-1, and NSE. Its use may help in distinguishing between malignant and benign disease and make it possible to define different subgroups of patients earlier in the course of their disease.     

Laboratory detection of Dientamoeba fragilis

The authors report a case of a 25 years old woman in whom a coin lesion was fortuitously discovered. Initial investigations were negative and an exploratory thoracotomy was performed which enabled a benign clear cell tumour of the lung to be found (sugar tumour). This rare benign tumour whose cellular origin remains indeterminate is in general discovered in a fortuitous manner after a chest x-ray has been performed showing a round peripheral opacity. The diagnosis is confirmed following the excision of the tumour, complementary examinations are not helpful.     

Diffuse esophageal glycogenic acanthosis: an endoscopic marker of Cowden's disease

Cowden's disease is a rare autosomal dominant condition characterized by multiple hamartomas of ectodermal, endodermal, and mesodermal origin affecting many organ systems. Gastrointestinal manifestation includes the formation of multiple polyps of various benign histopathological types throughout the alimentary tract. Recent literature suggests that the frequency of gastrointestinal involvement is approximately 70-85%. The diagnosis of Cowden's disease, however, relies mainly on subtle dermatologic findings, which may not be obvious to the gastroenterologist. We describe a patient with Cowden's disease and review the English literature on the topic of gastrointestinal polyposis and Cowden's disease. These studies suggest that gastrointestinal polyposis is commonly found in this disease, and that diffuse esophageal glycogenic acanthosis is a characteristic feature of Cowden's disease. We propose that the finding of extensive glycogenic acanthosis in the presence of other benign gastrointestinal polyposis should be considered pathognomonic for the diagnosis of Cowden's disease.     

Independent segregation of von Hippel-Lindau disease and cerebral cavernomas

A probable diagnosis of von Hippel-Lindau disease was made in a two generation family in which the proband had a phaeochromocytoma, renal cysts, and multiple cerebral cavernomas. His sister had multiple similar cerebral vascular lesions and his father died from renal carcinoma aged 42. Although the family did not satisfy the conventional diagnostic criteria for von Hippel-Lindau disease, an underlying germline mutation in the von Hippel-Lindau disease tumour suppressor gene was identified in the proband. Molecular genetic analysis not only confirmed the putative diagnosis of the disease in the proband but also showed that the cerebral vascular lesions segregated independently from the von Hippel-Lindau disease mutation. This report exemplifies how molecular genetic investigations can enhance the diagnosis and management of families with suspected von Hippel-Lindau disease, particularly when the manifestations, as in this family, are not typical.     

Discrete synchronous multifocal osteoid osteoma of the humerus

A 24-year-old patient is described who had a 4-year history of pain in the right upper arm, with distinct night pain, that responded to salicylates. From the findings on conventional radiography, bone scintigraphy and MRI a multifocal osteoid osteoma was suspected, with one focus in the cancellous region of the greater tuberosity and a second cortical focus at the proximal humeral diaphysis. The resection "en bloc" of both tumors and histological examination confirmed the diagnosis. The patient was painfree after the curative resection of the two osteoid osteomas. Osteoid osteoma is a frequently found benign bone tumor, accounting for approximately 11% of cases. In rare cases a multicentric occurrence has been described. A possible occurrence of more than one osteoid osteoma in a single bone, not verified histologically, has been reported only three times in the literature. In patients with scintigraphic and radiographic findings of two foci, discrete synchronous multifocal osteoid osteomas should be suspected.     

PEDF (pigment epithelium-derived factor) promotes increase and maturation of pigment granules in pigment epithelial cells in neonatal albino rat retinal cultures

AIMS: To clarify the association of p53 and CD34 expression with development of malignant solitary fibrous tumour we have studied 10 cases of solitary fibrous tumour arising in the pleura, retroperitoneum and pelvic cavity with clinicopathological features of malignancy. METHODS AND RESULTS: Tumours were localized solid masses with or without necrosis in eight and they nearly totally occupied the pleural cavity in two. Basic histology of the tumours was the proliferation of spindle cells arranged in 'patternless' pattern or in interlacing bundles with nuclear atypia and mitotic activities of various degree. In two, high-grade foci were present within low or intermediate-grade tumours. Recurrent tumours also showed more atypical features than primary tumours in two. Immunohistochemical studies showed CD34 positivity in seven, but three of them showed marked diminution or complete loss of CD34 expression in high-grade foci or a recurrent tumour. Three high-grade cases showed totally negative staining for CD34. p53 was strongly expressed in cases with fatal outcome, clinical recurrence, nuclear atypia, high mitotic activity or local invasion, whereas almost negative in benign tumours. CONCLUSIONS: Malignant solitary fibrous tumours may occur de novo or by transformation within benign or low-grade tumours and may be associated with p53 mutation. Although CD34 is a useful marker in the diagnosis of solitary fibrous tumour, one should bear in mind that its expression can be lost in high-grade tumours.     

Renal oncocytoma

Authors review the case history of three patients with kidney tumours which had been surgically removed. In two of the cases radical nephrectomy while in one, organ-preserving surgery was performed. In all three cases histology revealed benign kidney tumours-oncocytomas. In light of the available literature authors indicate that preoperative diagnosis is almost impossible. Furthermore, it is their opinion that this benign kidney tumour has a less frequent occurrence than earlier thought.     

CYFRA 21-1, a sensitive and specific new tumour marker for squamous cell lung cancer. Report of the first European multicentre evaluation. CYFRA 21-1 Multicentre Study Group

The present study was designed to determine whether CYFRA 21-1, measuring cytokeratin 19, could be a specific and sensitive tumour marker for non-small cell lung cancer (NSCLC). Serum measurements were made at diagnosis in 2250 patient samples by an immunoradiometric "sandwich type" assay, using two cytokeratin 19 specific monoclonal antibodies. Among healthy individuals (n = 711) and patients with benign lung disease (n = 546), 95 percentiles were 1.2 and 2.95 ng/ml, respectively. Cumulative distribution analysis curves were established. From these data, 3.3 ng/ml gave 96% specificity. Using this cutoff, the sensitivity for small cell lung cancer was 16% (n = 74) compared to 41% for NSCLC (n = 547). In histological sub-groups, sensitivity was 57% for squamous cell lung cancer, 34% for undifferentiated large cell carcinoma and 27% for adenocarcinoma, the level of CYFRA 21-1 was correlated with tumour size and UICC stage. In squamous cell lung cancer, the sensitivity of the squamous cell carcinoma marker was 30%, 25% for carcinoembryonic antigen and 46% for tissue polypeptide antigen, using the same series of samples and cutoffs defined at 96% specificity. In conclusion, CYFRA 21-1 is a sensitive tumour marker for NSCLC, especially squamous cell lung cancer.     

Sensorimotor polyneuropathy and systemic amyloidosis as paraneoplastic symptoms of a carcinoid-like well differentiated carcinoma of the breast

HISTORY AND ADMISSION FINDINGS: A 75-year-old woman was admitted because of weakness and paraesthesias in both legs. 15 years earlier a chest radiogram had shown numerous round foci of uncertain cause. Physical examination confirmed muscular weakness in all limbs, especially the legs, as well as abnormal superficial and deep sensory perception. INVESTIGATIONS: Electromyography registered a patchy pattern of intentional muscular activity and marked denervation activity but largely normal nerve conduction. There was no evidence of inflammatory disease in the laboratory tests, including the CNS. DIAGNOSIS, COURSE AND TREATMENT: The neurological findings indicated progressive axonal sensorimotor polyneuropathy. A paraneoplastic cause was suspected, but search for a primary tumour was unsuccessful. The patient developed a urinary infection from which she died in septic shock. A carcinoid-like well-differentiated carcinoma of the breast with hematogenous metastases to liver, spleen and lung was discovered at autopsy. It also revealed severe systemic AA-type amyloidosis, involving liver, spleen heart and kidneys. In addition there was a severe progressive axonal neuropathy and marked neurogenic atrophy of the peripheral skeletal musculature. No amyloid deposition was seen. CONCLUSION: In case of amyloidosis and polyneuropathy of uncertain cause a paraneoplastic pathogenesis should be considered in the differential diagnosis, even in the absence of proven malignancy.     

Renal angiomyolipoma as cause of massive retroperitoneal haemorrhage

A previously healthy woman was admitted to the hospital because of sudden pain in the right flank. Massive retroperitoneal haemorrhage was found to be the cause, produced by spontaneous rupture of an angiomyolipoma in the right kidney. Both the tumour and the kidney were removed. Owing to the rare occurrence of angiomyolipoma, preoperative diagnosis is seldom arrived at. If the presence of the tumour could be suspected and its benign character confirmed, the kidney itself or its intact part could often be saved.     

Eosinophilic cystitis. Study of the clinical course in 6 new cases and review of the recent literature

Presentation of a series of 6 cases of eosinophilic cystitis diagnosed in our hospital and recorded in 1988-1993, with an average follow-up of 2 years from time of diagnosis. The actual trend with regard to this particular form of chronic cystitis is to abandon the idea of considering it a "benign" disease, basically due to its increasingly less uncommon association to bladder and/or prostate tumoral pathology (in the recent literature and most particular in the present series). Also, a relative increase in the frequency of occurrence of this disease is noted, because of chemoprophylaxis of surface bladder tumour with Mitomycin-C, an association which is increasingly frequent. Based on these 6 cases, a review of the most recent literature on this topic is made.     

Primary intraosseous meningiomas of the skull

The plain film, computed tomography (CT) and angiographic findings in 10 patients with primary intraosseous meningioma were reviewed and the differential diagnosis considered. In nine patients with benign primary intraosseous meningioma, the radiological findings revealed intraosseous expansile growth. In one patient with the malignant form of the tumour, osteolytic growth was evident on plain film and CT. In eight patients, the tumour tissue was hyperdense (65-85 HU) on the unenhanced CT images and striking enhancement was shown in seven. In five patients angiography showed that the external carotid artery fed the tumour, while in one the vasculature was normal. Benign primary intraosseous meningioma showed expansile growth and malignant tumour showed osteolytic growth. If a combination of the plain film, angiogram and CT findings is considered, a diagnosis of the benign tumour can be made and a diagnosis of benign meningioma can be suggested.     

Hereditary persistence of alpha-fetoprotein. Case report and review of the literature

BACKGROUND: The issue of performing simultaneous pulmonary resection and cardiac surgery in patients with coexisting lung carcinoma and ischaemic heart disease remains controversial. We report our experience and review the literature. METHODS: Thirteen patients (male ten, female three; mean age 65 years) underwent simultaneous cardiac surgery and pulmonary resection. Lung pathology consisted of primary lung carcinoma (n = 10), benign disease (n = 2) and carcinoid (n = 1). Lung resections included pneumonectomy (n = 3), lobectomy (n = 4), segmentectomy (n = 1) and local excision (n = 5). Cardiac procedures consisted of coronary artery bypass grafting (CABG) in 11, aortic valve replacement in one and mitral valve repair with CABG in one patient. In all but one case the lung resection was performed prior to heparinization and cardiopulmonary bypass (CPB). In two patients, with suitable coronary anatomy, myocardial revascularization without CPB was performed to reduce morbidity. RESULTS: There was no hospital mortality. Postoperative blood loss and ventilation requirements were reduced in the patients who were operated on without CPB. Prolonged ventilatory support was required in two cases. All patients with benign pathology are alive. In the lung cancer group there have been five late deaths: disseminated metastatic disease (n = 3), anticoagulant related haemorrhage (n = 1) and broncho-pleural fistula (n = 1). Of the remaining five patients four are alive and disease free 7-23 months post-operatively; one patient has recurrent disease 40 months post-operatively. CONCLUSIONS: Simultaneous pulmonary resection and cardiac surgery is associated with acceptable operative morbidity and mortality. In patients with lung carcinoma long-term survival was determined by tumour stage. The avoidance of CPB may be advantageous by decreasing blood loss and ventilation requirements.     

Endobronchial lipoma: two cases and review of the literature

Endobronchial lipoma is a benign tumour of the large bronchi occurring in middle-aged men. To the 38 successfully treated cases in the English literature a further 2 are added. The symptoms are those of obstructive pneumonitis mimicking bronchogenic carcinoma, and the result of delayed therapy may be bronchiectasis. Treatment includes local resection through a bronchoscope or a bronchotomy incision, or removal, if necessary, of the obstructed lobe or lung at thoracotomy. Smoking may be important in the pathogenesis of this tumour.     

Inflammatory pseudotumor--differential diagnosis in lung tumor in a child

A case of a twelve-year-old girl with a big solid tumour in the right lung is presented. As malignancy could not be excluded, she was operated. A lobectomy was performed. Frozen section showed no malignancy. Histology showed inflammatory pseudotumour, which is a rare but important benign lung tumour in childhood. The recommended treatment is conservative resection.     

Analysis of renal water excretion in full-term newborn infants

The clinicopathologic characteristics of two patients with Gorham's disease and bilateral recidivant pleural effusions are reported. The first case corresponded to a nine year-old girl with osteolysis in her right clavicle and ribs. The second case was a 55 year-old male with osteolytic lesions in ribs, cranium, pelvis and femurs; a thymic cyst was also documented. In both patients, biopsies were performed from ribs, which showed proliferating, benign, thin walled small vessels that extensively replaced the intertrabecular spaces. Thoracocentesis, instillation of talcum and radiation therapy were used in the former patient and no recidivant pleural effusions have developed after one year. The second patient was not treated with radiation therapy, persisted with pleural effusions and finally died two years after the diagnosis. Because Gorham's disease is rare, it was not immediately suspected in the cases described here. Its association with pleural effusion is even rarer and has been mentioned only occasionally in the literature. The utility of radiation therapy in Gorham's disease is commented.     

Ultrasonographically-guided fine-needle aspiration cytology in the diagnosis of colonic lesions

BACKGROUND: The use of fine-needle aspiration cytology (FNAC) in the diagnosis of colonic lesions was investigated. METHODS: Some 22 patients (median age 71 years) with a colonic lesion identified on abdominal ultrasonography underwent ultrasonographically-guided FNAC using a 21-G needle. The sample was checked immediately by a cytopathologist for adequacy. RESULTS: Eighteen patients had colonic carcinoma; aspiration cytology detected malignant epithelial cells consistent with colonic carcinoma in 17 patients and severely dysplastic cells in one patient. The sensitivity and specificity of ultrasonographically-guided FNAC in the diagnosis of colonic carcinoma was 94 and 100 per cent respectively. The remaining four patients had a diagnosis of ileocaecal tuberculosis, ileocaecal Crohn's disease, and metastatic adenocarcinoma in the liver with no identifiable primary (two patients). One demonstrated granulomata, grew acid-fast bacilli and the patient was treated for tuberculosis. One had inflammatory cells and the patient was found to have Crohn's disease on histology. The remaining two patients had confirmed metastatic adenocarcinoma in the liver on aspiration cytology but suspected colonic lesions were found to be benign on cytological examination and no primary lesion was subsequently demonstrated. There were no complications of FNAC and patients complained of minimal discomfort. There has been no evidence of tumour recurrence with a median follow-up of 12 (range 1-25) months. CONCLUSION: Ultrasonographically-guided FNAC is a valid method for the diagnosis of colonic tumours.     

Soluble intercellular adhesion molecule-1 in patients with lung cancer and benign lung diseases

Intercellular adhesion molecule-1 (ICAM-1) expression correlates with tumour progression in patients with malignant melanoma or renal cell carcinoma. To assess the value of soluble ICAM-1 (sICAM-1) for lung cancer patients, sICAM-1 was determined by means of an enzyme-linked immunosorbent assay. Sera from 147 patients with lung cancer, from 75 patients with benign lung diseases and from 108 healthy adults were investigated for sICAM-1 expression. Significant differences in sICAM-1 levels were detected in lung cancer patients (387 +/- 176 ng/ml) and patients with benign lung diseases (365 +/- 110 ng/ml) compared to the group of healthy adults (310 +/- 90 ng/ml). There was no difference in sICAM-1 level among the subtypes of lung cancer. Advanced tumour stages and patients with progressive disease tended to be associated with higher sICAM-1 levels, the site of metastasis being relevant for the level attained. Patients with liver metastasis had the highest sICAM-1 levels (547 +/- 295 ng/ml) compared to patients with cerebral metastasis (317.8 +/- 92.2 ng/ml). An increase of sICAM-1 expression during the progression of the disease coincided with a poorer survival prognosis for the patients compared to patients with stable or falling sICAM-1 levels.     

Prostatic leiomyosarcoma

The histopathological findings from the third prostate operation of a 63-year-old patient proved that his leiomysarcoma was malignant. Leiomyosarcoma is a disease of low incidence. Of 1000 cases of a carcinoma of prostate one proves to be this disease. Its clinical distinction from benign prostate disease meets difficulties. A survey of literature has shown that even multiple aggressive therapy fails when the process has overpassed the limits of the organ. Early diagnosis followed be radical pre- and postoperative X-irradiation may lead to long-term survival. Neither cytostatic nor hormonal therapy is successful. The course of the illness of our patients merits interest because of the rarity of the disease and the diagnostic difficulties.     

Cost effectiveness analysis of FDG-PET in the differential diagnosis and staging of lung cancer in Japan

Several studies have shown that FDG-PET is more accurate than CT for the differential diagnosis and for the staging of lung cancer. We have analyzed potential effect of FDG-PET on the medical cost for the management of patients suspected of lung cancer. In the differential diagnosis, chest CT plus FDG-PET protocol reduced the number of bronchofiberscope (BFS) and biopsy by one fourth of that in the conventional protocol using CT alone. PET protocol reduced unnecessary examinations for the patients of benign disease, however, it increased the total cost of examinations by 25% due to the higher cost of PET than that of BFS and biopsy in Japan. In the staging of lung cancer, PET protocol improved accuracy of staging, reduced unnecessary surgery by 67%, and showed a saving of the cost of examination by 5%, and the total medical cost by 2.5% compared to that in the conventional protocol using CT, brain MRI, and bone scan. Conclusion: Use of FDG-PET for the staging may contribute to the improvement of patient management of lung cancer patients also to the saving of the medical cost.