[Pathology of primary tumours of the pleura]. / Pathologie der primären Pleuratumoren.

In the WHO classification, pleural tumours of mesothelial and mesenchymal origin as well as lymphoproliferative disorders are distinguished, with malignant mesotheliomas forming the most common primary pleural tumour. Histologically, a prognostically relevant differentiation between epitheloid (40-60 %), sarcomatoid (20-30 %), and biphasic mesotheliomas (20-30 %) is made. Besides other rare primary tumours of the pleura, the differential diagnoses of malignant mesotheliomas comprise carcinomatous pleuritis of intra- and extrapulmonary malignancies. Especially in early tumour stages, the differentiation from reactive pleural changes requires a close interdisciplinary cooperation with a careful correlation between histopathological findings and clinical presentation.

[Differential diagnosis of preneoplastic lesions of the pleura and of early mesothelioma: immunohistochemical and morphological findings]. / Praktische Differenzialdiagnose präneoplastischer Veränderungen der Pleura und früher mesothelialer Neoplasien Morphologische und immunhistochemische Befunde.

The morphological diagnosis of small mesothelial lesions in pleural biopsies is gaining importance in view of more aggressive, multimodal therapeutic options and of medicolegal aspects if a malignant mesothelioma is diagnosed. We present a light microscopically and immunohistochemically based morphological classification for the planning of further clinical follow-up procedures. A reactive mesothelial hyperplasia heals without scars. Mesothelial inclusions in pleuritic scars are common in recurrent pleuritis and must not be confused with an epithelioid component of a desmoplastic mesothelioma. In case of atypical mesothelial proliferations, further diagnostic procedures have to be performed to obtain a clear diagnosis of malignancy. Mesothelioma in situ is the first morphological step in neoplastic mesothelial changes, also with regard to medicolegal aspects for the unambiguous diagnosis of a mesothelioma. Early infiltrative growth is characteristic of so called early mesothelioma. A useful immunohistochemical panel for the differential diagnosis consists of anti-cytokeratin, Ck 5/6, calretinin, EMA and MiB-1, whereas the immunohistochemical detection of telomerase is not helpful.

[Mesotheliomas with leucocytic infiltration]. / Mesotheliome mit leukozytärem Infiltrat. Differenzialdiagnostische Aspekte.

Malignant mesotheliomas are rare tumors which can affect pleura, peritoneum, pericardium, or tunica vaginalis testis. Histomorphologically, predominant epitheloid, sarcomatoid and biphasic types can be distinguished. In some cases, leucocytic infiltrations can be observed adjacent to the tumor. Here, mesotheliomas presenting inflammatory reactions to tumor growth have to be differentiated from occasional cases with parasynchronic development of neoplastic lymphatic diseases. Moreover, so called lymphohistiocytoid mesotheliomas, a sporadically observed variant of malignant mesotheliomas, have been reported to imitate inflammatory patterns. These different forms of malignant mesotheliomas are difficult to distinguish and may lead to diagnostic misinterpretations and consequently therapeutic mismanagement. The purpose of this study was to differentiate morphological and immunohistochemical characteristics of the above mentioned diagnoses. We therefore studied two rare cases, a mesothelioma with parallel lymphoma and a lymphohistiocytoid mesothelioma, and compared them to a third more common case of mesothelioma with inflammatory tissue-reaction.

[CGH findings in neuroendocrine tumours of the lung]. / CGH-Befunde bei neuroendokrinen Tumoren der Lunge.

According to the 1999 World Health Organisation classification of lung tumors, the classification of neuroendocrine (NE) tumors is solely based on light-microscopic features. Typical and atypical carcinoid tumors are distinguished from large cell (LCNEC) and small cell neuroendocrine carcinomas (SCLC). We used comparative genomic hybridization (CGH) on 50 samples to investigate the cytogenetic relationships between NE tumors. On average, carcinoid tumors showed markedly fewer chromosomal imbalances (1.8/case, 23 cases) than LCNEC (13.3/case, 17 cases) or SCLC (17/case, 10 cases). The frequency of amplicons increased accordingly. Typical carcinoid tumors exhibited significant defects on chromosomes 11 and 13 only. Interestingly, only the frequency of losses on chromosome arm 11q was very similar for all three tumor entities (about 30%). In conclusion, the CGH results support the classification of typical carcinoid tumors as a separate entity in clear distinction from the NE carcinomas.

[Eccrine spiradenocarcinoma with unusual histiocytic giant cell components. Case report and review of the literature of a rare sweat gland tumor]. / Ekkrines Spiradenokarzinom mit ungewöhnlicher histiozytärer Riesenzellkomponente. Fallbericht und Literaturübersicht eines seltenen malignen Schweissdrüsentumors.

We report the case of a spiradenocarcinoma (malignant eccrine spiradenoma), a rare variant of a malignant sweat gland tumor, which occurred in the scalp of a 63-year-old woman. Some years before the current tumor occurred, a tumour of unknown histology had been excised from the same localization. The new tumor presented with rapid growth and exulceration. Malignant eccrine spiradenoma is characterized by the coincidence of a benign and a malignant portion within one specimen. We report case example 47 of this entity. The peculiarity of this case is the enormous heterogeneity with foci of atypical histiocytes like an atypical fibroxanthoma and an extensive foreign body reaction with cholesterol needles as in a xanthogranuloma. Static DNA cytophotometric analysis revealed different degrees of aneuploidy in the three tumor portions. The follow-up of 23 months is without recurrent tumor. A review of the literature is given.

Low malignant epithelioid peritoneal mesothelioma: successful treatment with surgical therapy alone.

A 31-year-old man presented with malignant peritoneal mesothelioma. His past medical history was uneventful, specifically there was no personal or environmental asbestos exposure. The patient was treated by complete tumor resection including peritonectomy. Because of the histologic diagnosis of a low malignant, unusual highly differentiated epithelioid tumor with very low proliferative activity a postoperative chemotherapy was not administered. After a follow-up of 20 months, the patient is in excellent clinical condition and there is no evidence of disease by computed tomography. The present paper reports a case of this rare variant of malignant peritoneal mesothelioma.

Inflammatory polyradiculoneuropathy with spinal cord involvement and lethal [correction of letal] outcome after hepatitis B vaccination.

We report on a 36-year-old man who developed an inflammatory polyradiculoneuropathy similar to Guillain-Barré syndrome 9 days after hepatitis B vaccination. Extensive immunotherapy including immunoglobulins, steroids, plasmapheresis, cyclophosphamide and methotrexate did not stop the progressive course of the disease and the patient died 4 months later due to multiorgan failure with septic shock symptoms and adult respiratory distress syndrome (ARDS).The neuropathological investigation showed severe axonal loss with mild demyelination of peripheral nerves and mononuclear cell infiltrates, predominantly T-lymphocytes, in nerve roots and spinal ganglia. In addition, there were unusual, perivascular and parenchymal lymphocytic cell infiltrates in the grey matter, especially the anterior horns of the spinal cord. The temporal relationship to hepatitis B vaccination, the strong increase of HBs-antibodies within 3 weeks after vaccination, and the presumptive immune mediated pathology of this disorder suggest a possible etiologic link with hepatitis B vaccine.

Prognostic significance of the presence of erythroblasts in blood after cardiothoracic surgery.

In patients suffering from a variety of severe diseases the detection of erythroblasts in peripheral blood is associated with poor prognosis. However, as yet the prognostic significance of erythroblasts in the blood of patients after cardiothoracic surgery has not been assessed. In a retrospective study we analyzed the database of 2074 patients, of whom 87 died in hospital during the postoperative period. All patients underwent cardiothoracic surgery using a heart-lung machine. Together with erythroblasts in blood, age, sex, body mass index, preoperative ejection fraction, smoking, diabetes mellitus, type of operation, emergency surgery, renal deficiency, pulmonary hypertension, and endocarditis were considered. The postoperative mortality of patients with erythroblasts in peripheral blood (n=57) was 45.6% (n=26), being significantly higher (p<0.001) than the mortality of patients without erythroblasts (3.0%). None of six patients with more than 2000 erythroblasts x 10(6)/l survived. The postoperative detection of erythroblasts is highly predictive of death, the odds ratio after adjustment for the other known prognostic factors being 7.2 (95% confidence interval 3.4-15.1). Erythroblasts were detected for the first time on average 11 +/- 2 days (median: 7 days; n=57) after surgery and 8 +/- 2 days (median: 6 days; n=26) before death. The detection of erythroblasts in blood after cardiothoracic surgery has a high prognostic significance in terms of in-hospital mortality, helping physicians to identify patients at high risk of death. This finding has to be confirmed by a prospective study with the use of a more sensitive and reliable technology and prospectively defined time intervals for counting blood cells.

[Malignant mesothelioma of the pleura, pericardium and peritoneum. 1: Etiology, pathogenesis, pathology]. / Malignes Mesotheliom der Pleura, des Perikards und des Peritoneums. Teil 1: Atiologie, Pathogenese, Pathologie.

The incidence of primary malignant neoplasms of the pleura, the pericardium and the peritoneum in Germany has been rising since about the mid-1980s. A continuing rise is expected until about 2020, predominantly due to the peak of asbestos processing in Germany between 1965 and 1980. About 90% of the mesotheliomas stored in the files of the German Mesothelioma Registry in Bochum are asbestos related and therefore possibly due to occupational exposure that may be compensated by the professional associations. More than 500 mesotheliomas annually can be diagnosed in the German Mesothelioma Registry. In this first part of the series on mesotheliomas, current concepts on etiology and pathogenesis as well as diagnostic procedures and standards are discussed. At the present, specific chromosomal or genetic defects that constantly give rise to a mesothelioma are not known. The initiation and progression of malignant mesotheliomas is a highly complex mechanism that is based on individual genetic alterations. A reliable diagnosis is the basis for therapeutic, prognostic and medicolegal consequences; in general, it can be achieved by thoracoscopic inspection with selected biopsy. Surgery may gain a more important role in the therapy of malignant tumors of serosal membranes not only in palliative, but also in potential curative approaches if the diagnosis can be made at earlier tumor stages.

Patterns of chromosomal imbalances in benign solitary fibrous tumours of the pleura.

Solitary fibrous tumours (SFTs) of the pleura, in contrast to malignant mesothelioma, occur independently of previous asbestos exposure. They are benign tumours, but may recur if the stalk to the adjacent pleural or lung tissue remains in situ during surgical removal. The molecular pathology of SFTs is largely unknown. We used comparative genomic hybridisation (CGH) to characterise 12 localised SFTs and 12 predominantly sarcomatoid mesotheliomas. Fifty-eight percent of the investigated SFTs did not show any chromosomal imbalances. The most frequent defects were losses on chromosome arms 13q (33%), 4q and 21q (17% each). Significant gains were seen at chromosome 8 and at 15q in two cases each. There was no correlation between tumour size and molecular pathology findings. In contrast, 75% of the mesotheliomas carried chromosomal defects. On average, the mesotheliomas showed over three times as many defects per tumour as the SFTs. Localisation of several frequent losses and gains were similar to those of the SFTs. Therefore, in individual cases, a clear distinction between SFTs and sarcomatoid mesotheliomas is not possible based on CGH analysis alone. Further molecular characterisation of this rare tumour entity will be necessary to elucidate possible genes involved in early tumorigenesis.

Primary myxoid sarcoma of the pleura: 5 years follow-up.

Primary sarcomas of the pleura are rare intrathoracic tumours. We describe a case of a recurring myxoid pleural sarcoma in a 51-year-old male patient with coronary heart disease, who initially was admitted for coronary revascularization surgery. Tumour diagnosis was based on pathological examination of a biopsy after radiological detection of a nodule in the right upper lobe. The nodule was excised. The first recurrence was diagnosed after 15 months. Pleuropneumonectomy was done. Four years after the first excision further tumour masses appeared above the diaphragm and were surgically removed and adjuvant irradiation carried out. A year later the patient is doing well.

[Angiomyolipoma of the lung]. / Angiomyolipom der Lunge.

We present a case of a 48 year old man who complained of progressive dyspnoea. Radiograph revealed a large tumor in the left lung. Biopsy was performed and revealed beneath a normal bronchial epithelium polymorph tumor cells admixed with some histiocytes. These tumor cells were strongly pigmented and expressed HMB-45 and protein S-100 immunohistochemically. Malignant melanoma of the bronchus was included in the differential diagnosis. A thoracotomy and left lower lobe resection was performed. Histology revealed an angiomyolipoma. The lung is an uncommon localisation of angiomyolipoma with so far three reported cases. Lipoma, leiomyoma and lymphangioleiomyomatosis have to be included in the differential diagnosis. The peculiarity of this case is the presence of multiple pigmented tumor cells that express HMB-45. This has not been reported yet.

[Pathology and molecular biology of lung cancer]. / Pathologie und Molekularbiologie bösartiger pulmonaler Tumoren.

Therapy and prognosis of lung cancer depend crucially on tumor size, tumor stage, and the histomorphological tumor type at the time of primary diagnosis. A tumor weighing only 1 g and barely detectable by clinical examination consists of about 1 x 10(9) tumor cells. The primary histological diagnosis is generally based on small biopsies 1-2 mm in diameter, which allow the assessment of only a few up to some hundred tumor cells in a section of 4 microns. Until 20 years ago light microscopic and histochemical investigations were the basis for sophisticated morphological tumor diagnosis. In recent years electron microscopy, immunohistochemistry, cytometry, and molecular biology have extended our knowledge of the complex tumor biology, with the range of phenotypes and genotypes indicating enormous tumor heterogeneity. The value, expressiveness, and prognostic importance of these laborious and expensive techniques must be examined in studies, keeping in mind new aspects of tumor classification. Histological and cytological findings are still the decisive basis for the primary diagnosis of the pathologist in any given case.

Benign solitary fibrous tumour of the thigh: morphological, chromosomal and differential diagnostic aspects.

Solitary fibrous tumours (SFTs) are rare and usually benign neoplasms of mesenchymal origin that are often found in the visceral pleura (fibrous pleural tumour, FPT) or other serosal surfaces. They have also been found in soft tissues. We report the case of an SFT localised in the thigh of an 86-year-old woman. The tumour specimen was examined morphologically, immunohistochemically and molecular genetically, using comparative genomic hybridisation (CGH). The latter detects unbalanced chromosomal alterations in human neoplasms by competitive nucleic acid hybridisation and consecutive computer image analysis. The tumour consists of fibroblast-like cells, arranged in a typical "patternless pattern". Immunohistochemically, the tumour stained positively for vimentin, CD34, CD99, and focally for actin and desmin. No reaction occurred with keratin or S100 protein antibodies. CGH detected a single loss on chromosome 13q.

Severe chromosomal aberrations in pleural mesotheliomas with unusual mesodermal features. Comparative genomic hybridization evidence for a mesothelioma subgroup.

Malignant mesotheliomas are tumors known for their extensive heterogeneity. Apart from the three classical patterns, predominantly epithelioid, sarcomatoid, and biphasic, some rare variants do exist. In some cases, one can find uncommon additional mesodermal tumor components. These tumors have previously been called "mesodermomas" and, like regular mesotheliomas, are usually associated with a previous asbestos exposure. We examined eight cases of mesodermomas by light microscopy, immunohistochemistry and comparative genomic hybridization (CGH). Besides biphasic and epithelioid areas, unusual epithelial, chondroid, osseous, or even angioblastic elements may be found to varying degrees. Immunohistochemical analysis shows similar staining results as with regular mesotheliomas. CGH reveals a high number of chromosomal imbalances (16.5 per case; range, 11-27). In 10 classical biphasic mesotheliomas that served as a control, defects of comparable number and severity could not be detected (8 per case; range, 2-16). The most frequent defects of mesodermomas (losses on 1p, 4pq, 9p, 13q, 14q, and gains on 1q and 15q), however, could also be found in mesotheliomas of the classical type. Thus, our results support the classification of the so-called mesodermomas as a separate tumor subgroup while maintaining the relationship to the classical mesotheliomas. Therefore, we propose to use the term mesodermoma for this subgroup.

[Pleural reaction pattern after talc pleurodesis]. / Pleurale Reaktionsmuster nach Talkum-Pleurodese.

Because of the rising importance of talcum pleurodesis in the therapeutic management of malignant and benign pleural effusions in Germany, pleural samples after talcum pleurodesis were compared to microscopic, immunohistochemical, and scanning electron microscopy findings after Tetracyclin and Novantron pleurodesis in 24 patients up to 18 months after intrapleural therapy. The histomorphological findings after talcum pleurodesis show an early phase of up to 4 weeks, characterized by the presence of talcum-containing granulation tissue with giant-cell foreign-body reaction, and a subsequent late phase with organization of the granulation tissue and connective tissue formation and obliteration of the pleura sheets. The resulting characteristic linear talcum zone in the pleural connective tissue is missing in cases with tumorous infiltration of the pleura. Continuous fibroblast activation, e.g., by macrophage or foreign-body giant-cell-released mediators, seems to be the decisive factor in the fibrosing process. No therapy-related tumor growth alterations could be demonstrated.

[Radical treatment by the surgeon and reality of the pathologist]. / Radikalitätsanspruch des Chirurgen und Realität des Pathologen.

The aim of the radical resection of lung tumors is curative treatment. However, in each lung tumor of more than 2 cm in diameter an angioinvasion of tumor cells could be proved by morphological means. Frequently, the existence of lymph nodes and especially hematogenic dissemination is underestimated at the time of resection. By pathological-anatomical means in 33% of T1/T2-N2 and 60% of T1/T2-N3 lung tumors, disseminated tumor cells or organoid metastasis in the bone marrow can be demonstrated. Therefore, the demand for radicalness of the surgeon does not agree with a curative tumor therapy in more advanced tumor stages. Actually, the course of the disease following a local radical resection is predominantly predetermined by the individual hematogenic metastatic spread.

Low specificity of cytokeratin 19 reverse transcriptase-polymerase chain reaction analyses for detection of hematogenous lung cancer dissemination.

PURPOSE: Sensitive detection of systemic tumor dissemination in lung cancer patients is important for selection of appropriate treatment modalities. Based on recent promising data that showed reverse transcriptase-polymerase chain reaction (RT-PCR) analyses for cytokeratin 19 (CK-19) expression in peripheral-blood or bone marrow samples to be a rapid and highly sensitive method for detection of hematogenous tumor dissemination in patients with breast and prostate cancer, we evaluated the specificity of this assay system in lung cancer patients and a large number of healthy controls. PATIENTS AND METHODS: We examined CK-19 mRNA expression by RT-PCR in 17 lung cancer cell lines and in peripheral-blood samples of 50 lung tumor patients and 65 healthy controls. RESULTS: Expression of CK-19 mRNA was observed in all lung cancer cell lines and in 50% of peripheral-blood samples from lung tumor patients. However, under the experimental conditions analyzed, at least 20% of the control samples were positive for CK-19 mRNA expression. CONCLUSION: Contrary to prior reports, RT-PCR may detect non-tissue-specific constitutive low-level (illegitimate) expression of CK-19 mRNA in peripheral-blood mononuclear (PBMN) cells in a significant number of healthy controls. This finding may not only hamper the use of this assay system in lung cancer patients, but also questions its proposed applicability in patients with other epithelial tumors such as breast and prostate cancer.

[Thoracic bilateral myelolipoma]. / Thorakales bilaterales Myelolipom.

Diagnostics, histogenetic derivatives and determination of the mediastinal neoplasms can still be problematic today despite the use of CT and MRT. Although the exact location and determination of neoplasmic density help to reduce the differential diagnostic spectrum in some cases, in the case of a 50-year old patient it was only via thoracoscopy and the taking of specimens that the diagnosis of a bilateral paravertebral crescent-shaped tumour of the posterior mediastinum as a rare myelolipoma could be obtained. Formal and causal pathogenesis of myelopomas are referred to in this paper with special reference to the clinical and pathologico-anatomical findings.