Diagnostic strategy in primary malignant bone tumors in children

Our experience concerning the diagnostic proceeding for primary malignant bone tumours in children and their often difficult differentiation from osteomyelitis are discussed. A retrospective evaluation of patient records of 66 children showed, that in 53 cases (41 with osteomyelitis, 12 malign tumours) diagnosis was immediately obtained from clinical and radiological results. For five more children osteomyelitis was proven by short term monitoring and paraclinical investigations, while in 8 cases final diagnosis required biopsy. CT was relevant for the evaluation of intraosseous and intramedullary extending tumours and mandatory for therapy planning. Conventional radiography, however, remains the most important method within the diagnostic strategy, but the need for close cooperation of radiologists and clinicians and a synoptic evaluation of clinical results, radiography and anamnestic data must be stressed.     

Localization of adrenal tumors

The application of newly developed methods to localization of adrenal tumours has improved diagnostic accuracy, yet the challenge still exists. The sensitivity of ultrasound is too low for imaging small adrenal tumours, thus reducing sonography to a screening method. Computed tomography is a fast and sensitive localizing method, even for small tumours, with a low radiation exposure. Endocrine-active tumours with high hormone-secreting activity or displaying a tendency to additional extra-adrenal presentation will generally be best localized by scintigraphic imaging. Sonography and computed tomography as non-invasive methods and invasive puncture of the tumour or of the cyst with consequent cytological examination of the obtained material are most important procedures in the diagnosis of endocrine-inactive adrenal masses.     

Detection and quantification of small numbers of circulating tumour cells in peripheral blood using laser scanning cytometer (LSC).

The detection of circulating tumour cells disseminated from solid tumours requires extremely sensitive methods. Molecular genetic methods, which are most sensitive, are not applicable to solid tumours because no tumour-specific genetic markers are available. Detection of disseminated tumour cells by immunocytochemistry is time-consuming, whereas fluorimetry is fast and quantitative. The laser scanning cytometer (LSC) provides an automated microscopic procedure for screening up to 5x10(4) cells in suitable time. Using this system together with an enrichment procedure which allows up to ten thousand-fold enrichment, we have quantified minimal numbers of tumour cells. In a model system, breast cancer cell line cells diluted into peripheral blood mimicked seeding of tumour cells into the periphery. After staining with fluorochrome-conjugated anti-epithelial antibody, slides were screened for positive events directly or after enrichment with antibody-coated magnetic beads. One positive cell was unequivocally detectable in 10(4) cells and 50 out of 60 tumour cells were reliably recovered from a 20 ml blood volume, equal to 1-2 cells per 10(7), after magnetic bead enrichment. This method allows quantitation of tumour cells in peripheral blood and bone marrow in reasonable time and will, for the first time, enable extensive investigation of the seeding behaviour of tumours.     

Splenic tumour: a clinicopathological study

Splenic tumours are occasionally found during routine physical check-ups or elective abdominal image studies. Histologically, most splenic tumours are of benign vascular origin. To avoid unnecessary surgery for asymptomatic patients with benign splenic tumours and clarify the clinicopathological features of spleen tumours, this study gathered 44 cases of primary or isolated metastatic spleen tumours confirmed by pathology from surgery specimens or biopsies. The differences in clinicopathological features and image presentations between benign and malignant spleen tumour were investigated. Thirty-two cases involved benign tumours while 12 cases were malignant. Among the benign tumours, vascular originating tumours were most common (with 14 cases of cavernous haemangiomas, 13 cases of lymphangioma, three cases of lymphangiohaemangioma and one case of Littoral cell angioma). Notably, one, case of inflammatory pseudotumour because of Schistosoma parasite infection was also noted. Among the malignant tumours, there were four cases of angiosarcomas with vascular endothelium origins, as well as lymphomas and six metastatic tumours. Image studies were non-specific. Image study alone is an inadequate basis for making differential diagnoses between benign and malignant tumours. Instead, pathological studies are required for a final diagnosis. Using previous studies and this investigation, fine needle aspiration biopsy of spleen tumours with the help of ultrasonic or computed tomography appears a safe and effective method for obtaining biopsy specimens. Splenectomy is recommended only for patients with malignancies or complications such as intractable abdominal pain, coagulopathy or tumour rupture with an unstable haemodynamic state.     

Mammography of non-palpable lesions (spot localisation) (author's transl)

Modern methods of mammary investigation currently enable the detection of tiny-tumours which are not clinically palpable and referral of these patients to surgery at an early stage. This poses a challenge to the surgeon, who cannot rely on palpation as a guide to accurate extirpation of the tumour, but has to rely wholly on the radiological report. A method was, thus, worked out in this department to provide accurate evaluation of the position of the suspect area of the breast to facilitate operative measures and, furthermore, act as safety measure between the time of tumor biopsy and receipt of the histological report. Preparation radiography proves that the suspect area on mammography is identical with removed specimen. The advantages of this procedure are obvious. The surgeon can rely fully on the radiodiagnostic findings and enlist the radiologist as essential member of the therapeutic team. As a result the operative procedure can be finely gauged by the surgeon and the tumour removed with maximum sparing of healthy breast tissue. This procedure has produced excellent results in 35 patients and can be recommended for application to patients with tiny tumours.     

子宫内膜间质肿瘤临床病理分析

目的 探讨子宫内膜问质肿瘤的临床、病理及其多成分分化特点、鉴别诊断和预后。方法 分析37例子宫内膜间质肿瘤(其中子宫内膜间质结节6例，低度恶性子宫内膜间质肉瘤22例，高度恶性子宫内膜间质肉瘤7例，子宫内膜间质平滑肌混合瘤2例)的临床、病理、合并症、鉴别诊断及预后。结果 不同类型肿瘤均有部分病例伴多成分分化(16例伴平滑肌分化，14例伴性索样分化，1例伴纤维分化)，其中8例同时伴2种分化成分；37例中有9例伴发子宫平滑肌瘤(其中1例同时伴发腺瘤样瘤，1例伴发高分化子宫内膜腺癌)。结论 不同类型子宫内膜间质肿瘤均可伴发多成分分化及其他类型肿瘤，具备多样性病理形态特征，其中以平滑肌分化及性索样分化最为常见；并发肿瘤以平滑肌瘤最为常见。组织化学及免疫组化染色对诊断及鉴别诊断有帮助；肿瘤预后与多成分分化的数量及类型关系不大；肿瘤有无浸润及瘤细胞异型程度、核分裂象数量是确定本瘤性质的必备条件。     

Histopathological classification of adrenal tumours

Tumours in the adrenals originate from the adrenal cortex, the adrenal medulla or as metastases from extra-adrenal primaries. Differentiating between these three groups is the first task a pathologist has to tackle when dealing with specimens from the adrenal region. Whereas this is possible in every case with total removal of the adrenal tumour it may be impossible in fine needle biopsies of such tumours. The second great problem is the dignity of adrenal tumours, which cannot be determined in many adrenomedullary and some adrenocortical tumours. Immunostainings are helpful but the basic method remains the histopathological examination of paraffin sections. This review gives an update of pathological findings in several adrenal tumour entities, and provides guidelines for the diagnosis of these tumours in the light of recently published data.     

Use of tumor markers in the diagnosis of salivary gland tumors

The group of tumour markers contain antigens and cell products which can be demonstrated in tumour cells by immunocytochemical methods (immunofluorescence, immunoperoxidase) and can, thus, be analysed for the classification of tumour. In human salivary gland tumours the distribution of cytoplasmatic antigens as components of the cytoskeleton, the occurrence of cell membrane antigens and of enzymatic cell products is demonstrated. Prekeratin, as an intermediate-sized filament protein, is a specific marker of epithelial tumours, whereas vimentin is a marker of mesenchymal cells. A special feature is the occurrence of prekeratin and vimentin in spindle-shaped cells of pleomorphic adenomas. The tumour-associated carcinoembryonic antigen (CEA) is found in glandular tumours and highly differentiated keratinized squamous cell carcinomas. With regard to enzymatic cell products, lactoferrin is present in glandular tumours and amylase in acinic cell tumours, but lysozyme is not detectable. The implementation of tumour markers contributes not only to an improvement in tumour diagnosis, but opens up new aspects in the cyto- and histogenesis of tumours.     

Perturbation of blood flow as a mechanism of anti-tumour action of direct current electrotherapy

Anti-tumour effects of direct current electrotherapy are attributed to different mechanisms depending on the electrode configuration and on the parameters of electric current. The effects mostly arise from the electrochemical products of electrolysis. Direct toxicity of these products to tumour tissue is, however, not a plausible explanation for the observed tumour growth retardation in the case when the electrodes are placed into healthy tissue surrounding the tumour and not into the tumour itself. The hypothesis that the anti-tumour effectiveness of electrotherapy could result from disturbed blood flow in tumours was tested by the measurement of changes in blood perfusion and oxygenation in tumours with three different methods (in vivo tissue staining with Patent Blue Violet dye, polarographic oximetry, near-infrared spectroscopy). The effects induced by electrotherapy were evaluated in two experimental tumour models: Sa-1 fibrosarcoma in A/J mice and LPB fibrosarcoma in C57B1/6 mice. We found that perfusion and oxygenation were significantly decreased after electrotherapy. Good agreement between the results of different methods was observed. The effect of electrotherapy on local perfusion of tumours is probably the prevalent mechanism of anti-tumour action for the particular type of electrotherapy used in the study. The importance of this effect should be considered for the optimization of electrotherapy protocols in experimental and clinical trials. The non-invasive technique of near-infrared spectroscopy proved to be a reliable method for detecting perfusion and oxygenation changes in small solid tumours.     

Studies in the diagnosis of breast disease (author's transl)]

The relative diagnostic accuracy of clinical examination, mammography, thermography and ultrasound was investigated in a comparative study. Mammography proved to be the most accurate diagnostic method, followed by clinical examination, thermography and ultrasound. Whereas in cases of advanced cancer (T2 to T4 tumour diameter greater than 2 cm) the correct diagnosis was made most reliably by clinical examination, mammography was superior to all other procedures in T1 tumours and in impalpable tumours. In our opinion thermography and ultrasound should be excluded for routine use or as a screening test because of the high false negative results. It is, however, noteworthy, that small intraparenchymal cysts can be detected and localized by ultrasound in a very high percentage of cases.     

Diagnosis and treatment of gastric neuroendocrine tumours

Gastric neuroendocrine tumours (NET) are rare. Clinically they are classified in tumours type 1 to 3. The histological classification is according to the WHO 2000 classification for endocrine tumours. NET type 1 occur in coincidence with chronic atrophic gastritis, as single or multiple small tumours. The prognosis of type 1 tumours is excellent, with no tumour related death reported during follow-up. NET type 2 are part of the MEN-1 syndrome. These tumours may be more aggressive and even develop metastasis. However, in most patients with MEN-1 the prognosis is due to other manifestations of the disease as duodenal or pancreatic neuroendocrine tumours. Gastric neuroendocrine tumours type 3 are sporadic tumours without relationship to other gastric pathology. They tend to occur earlier, without sex preference. These tumours may develop an aggressive course, with metastatic disease and an overall poor prognosis. Thus, aggressive surgical therapy is recommended.     

Ultrasound of adrenal gland tumours and indications for fine needle biopsy (uFNB)

The normal adrenal glands can be detected by high-resolution-sonography in a high percentage of cases. Sonography is also highly sensitive in the diagnosis of tumours of the adrenal glands. Only some of those tumours are hormonally active. Amongst the benign tumours, adenomas are the most frequent (up to 8%). Pheochromocytomas are less frequent (4.8% in uFNB statistics). Amongst the malignant tumours, metastases are more frequent than primary carcinomas (32.5% vs. 19.8% in uFNB-statistics). The adrenal glands are the fourth most common location of metastases. Bronchiogenic carcinomas, malignant melanomas, carcinomas of the breast and stomach as well as renal carcinomas metastasize into the adrenals most often. Much less frequent are infiltrates of lymphomas in adrenal glands tumours (3.4%). Incidentalomas are accidentally detected tumours of the adrenal glands without clinical symptoms. Malignant tumours only represent a very small part of incidentalomas (0.2%). They seldom show hormonal activity. In the case of an accidentally detected tumour, we propose a minimal laboratory profile (24-h-urinary-catecholamines, dexamethasone-test, electrolyte metabolism). The uFNB of the adrenal glands has a high sensitivity (90-95%). Complications are rare (pneumothorax, bleeding, pain; approximately 3%). Biopsy of pheochromocytomas (2-4% malignant) is dangerous because of the risk of provoking a hypertensive crisis. Case studies have been published about this problem. On the other hand, numerous cases of uncomplicated biopsies have also been published. Considering the excellent imaging methods and laparoscopic surgery methods on hand, the indication of FNP is restricted to the following cases: 1. the presence of a metastasis leading to therapeutical consequences; 2. suspected lymphoma 3. undefined lesion (3-5 cm), hormonally inactive, without typical signs of a tumour 4. patients refusing surgery. 5. uFNB in case of tumours of undefined dignity is only justified in specific cases. Recommendations for this procedure in accidentally detected tumours of the adrenal glands: < 3 cm and hormonally inactive --> US-follow up, > 5 cm + suspected tumour --> surgery, 3-5 cm uFNB after laboratory diagnostics.     

Gene therapy for malignant liver disease

For most patients with advanced or multifocal hepatocellular carcinoma (HCC) or with metastatic malignant liver disease treatment options are limited, resulting in a poor prognosis. Novel therapeutic strategies such as gene therapy are therefore urgently required. Gene therapeutic approaches use gene delivery systems (vectors) to introduce DNA constructs as therapeutic agents into living cells. Antitumour strategies include the reintroduction of tumour suppressor genes into tumour cells, the expression of foreign enzymes to render tumours susceptible to treatment with chemotherapeutic agents and the enhancement of tumour immunogenicity by expressing immunomodulatory genes or by genetic vaccination with tumour antigens. Furthermore, gene therapy may be also used for anti-angiogenesis to reduce tumour growth and metastatic potential. Other novel approaches aim at the development of genetically altered replication competent viruses, which selectively replicate in tumour cells inducing cell lysis. Although most clinical trials of antitumour gene therapy so far have failed to induce strong therapeutic effects, further improvement of antitumour gene therapy may finally result in potent clinical treatment options for patients with malignant liver tumours.     

Immunohistochemical analysis and biological behaviour of gastric glomus tumours: a case report and review of the literature

Gastric glomus tumours are rare and clinically recognized as benign. Nevertheless, some show biological behaviour similar to that of malignant lesions. During the last 40 years, we have encountered only one gastric glomus tumour. Analysis of frozen sections of this tumour suggested a mesenchymal tumour with malignant potential. Three mitoses per 50 high-power fields, with no cytological abnormalities, were observed. Tumour cells were positive for α-smooth muscle actin, vimentin and actin but negative for CD117, S-100 protein, creatine kinase, desmin, CD68, collagen type IV, CD34 and p53. The post-operative period was uneventful. During 37 months' follow-up, no recurrence or metastasis was detected and a benign course was considered likely. Literature on the immunohistochemistry and biological behaviour of gastric glomus tumours was also reviewed. Immunohistochemical studies are helpful in the differential diagnosis of gastric glomus tumours: although most are benign, malignancy cannot be excluded. Thus, long-term follow-up of the patient is necessary.     

Tumor markers in internal medicine hepatology

Primary liver tumour, i.e. hepatocellular carcinoma (HCC) is one of the world's most common malignancies. The age-standardized incidence rate varies widely from 6/100,000 (Austria) to 100 and more per 100,000 in Mozambique and Taiwan. In these high-risk areas, infection with hepatitis B virus is considered the main risk factor. In low-incidence areas as in Western Europe, main risk factors are older age, male sex and liver cirrhosis. The prognosis depends mainly on the size of the tumour. Alpha-fetoprotein is an ideal tumour marker for prospective screening in high-incidence areas. There is not much information, however, on the value of this marker for screening in low-incidence areas. There is some information that HCC-associated alkaline phosphatase could be a good tumour marker in non-viral liver tumours. Furthermore, des-gamma-carboxyprothrombin and vitamin B 12-binding protein could be specific markers for tumours in non-cirrhotic livers. But large clinical studies have not yet confirmed the value of these markers. Hormonal and haematological markers and some isoenzymes are tumour markers characterized by high sensitivity but low specificity. There are no specific tumour markers for metastatic liver disease.     

Pancreatic cancer stem cells – insights and perspectives

Background: Solid tumours are the most common cancers and represent a major therapeutic challenge. The cancer stem cell (CSC) hypothesis is an attractive model to explain the functional heterogeneity commonly observed in solid tumours. It proposes a hierarchical organization of tumours, in which a subpopulation of stem cell-like cells sustains tumour growth, metastasis and resistance to therapy. Objective: Here we review the most recent advances in the CSC field, with particular emphasis on pancreatic cancer as one of the deadliest human tumours, and highlight open questions and caveats to be addressed in future studies. Methods: This review focuses on the role of CSC in the promotion and metastasis of solid tumours and summarizes recent findings regarding the targeting of signalling pathways that are of particular importance for the maintenance and the elimination of CSC as the proposed root of the tumour. Results/conclusions: There is increasing evidence that solid tumours, including pancreatic cancer, are hierarchically organized and sustained by a distinct subpopulation of CSC. Direct evidence for the CSC hypothesis has emerged from mouse models only recently. While the clinical relevance of CSC remains a fundamental issue, current findings suggest that specific targeting of these cells is possible and therapeutically relevant.     

Tumour rejection antigens associated with carcinogen-induced tumours

Summary The most important immunological characteristic of tumours induced with chemical carcinogens is the expression of highly polymorphic tumour specific antigens. These cell surface components are primarily concerned with immune rejection reactions to these types of tumour, and current evidence strongly suggests that they are related to normal alloantigen.     

Radiofrequency ablation of brain tumours using MR guidance

Summary

MR-guided stereotactic thermal ablation was developed as a minimally invasive brain tumour treatment. Eighteen primary or metastatic brain tumours were treated in 15 patients. The entire procedure was performed under local anaesthesia in an MR suite. The outcome was analysed with 13-30 months of clinical follow-up. Local control was achieved in nine tumours in eight patients. Among them four patients with five tumours were disease-free for more than 22 months after the treatment. Four patients died from systemic disease or primary cancer while metastatic brain tumours were locally controlled. Local recurrence was seen in hypervascular metastatic tumours and a glioblastoma multiforme. For metastatic and primary brain tumours, MR provides not only accurate localization of brain tumour but also near real time thermal monitoring of acute tissue changes. This immediate imaging feedback facilitates safe and complete coagulation of the brain tumour. Based on our limited sample experiences, it is hoped that relatively long-term local control can be obtained in non-hypervascular metastases. MR-guided stereotactic RF thermal ablation is an attractive and promising technique, offering a potential treatment alternative for patients with previously treated brain tumour or systemic illness preventing other more conventional therapies.