[Lymphocytic myocarditis in a patient with metastatic clear cell renal cell carcinoma treated with Nivolumab]. / Lymphozytäre Myokarditis unter Nivolumabtherapie bei metastasiertem klarzelligen Nierenzellkarzinom.

Immune checkpoint inhibitors against the PD-1 protein offer a new therapy option for many solid cancers. We report a patient with metastatic renal cell cancer treated with Nivolumab. As a rare immune-mediated adverse event, we describe a fatal lymphocytic myocarditis two weeks after starting immune therapy. The cause of death was first diagnosed at autopsy. This case report underlines the importance and need of clinical autopsies as an instrument of quality assurance and detection of rare therapy-induced adverse effects.

[Rare tumor of the epididymis]. / Seltene Raumforderung des Nebenhodens.

A 51-year-old man with known ethyl toxic chronic pancreatitis presented with a tumor of the left epididymis. Immunohistological examination disclosed it as a metastasis of a pancreatic carcinoma. Paratesticular metastases of a pancreatic carcinoma are very rare. Nevertheless a metastasis of a primary pancreatic carcinoma should be included in the differential diagnosis of a tumor of the paratesticular tissue. The epididymis should be integrated in the diagnostic procedures of pancreatic carcinoma.

Solitary plasmacytoma of thoracic vertebra in a woman with Lynch syndrome: A case report.

INTRODUCTION: One of the major disabling health conditions among elderly is back pain due to degenerative diseases. Less than 1% of spine disorders are caused by malignancies. Among the rare primary vertebral neoplasms the multiple myeloma and the plasmacytoma account for 26% of these cases. PRESENTATION OF CASE: We are reporting a case of 64 year-old woman, who suffered from progressive upper back pain and intermittent neurological symptoms including lower limb weakness and voiding disorder under axial loading. Her medical history includes a Lynch syndrome (LS). Computed tomography (CT) and magnetic resonance imaging (MRI) detected a single malignant osteolytic process of the spine involving T5. Urgent surgery with laminectomy intralesional tumor removal and posterior stabilization (Th4-Th6) due to unstable pathologic fracture with spinal cord compression was conducted after interdisciplinary decision. Histopathological examination of the tumor revealed a solitary plasmacytoma. DISCUSSION: To our knowledge this is the first case report of a solitary plasmacytoma of the bone (SPB) that arise in a patient who suffers from LS. Similar DNA mismatch repair malfunction is existent in LS and SPB. Hence, a hereditary correlation might be imaginable. CONCLUSION: When detecting a lytic spinal tumor in a patient who suffers from LS a SPB should be taken under consideration.

An experimental in vivo analysis of the resorption to ultrasound activated pins (Sonic weld) and standard biodegradable screws (ResorbX) in sheep.

We compared the healing and reaction in the mandibles of 11 sheep of a conventional bioresorbable screw osteosynthesis with the newly developed ultrasound-activated pin osteosynthesis. The thermal stress caused by insertion of the ultrasound-aided pins leads to no cellular reaction around the pin. There is neither clinical nor histological evidence of any initial inflammation that could have been induced by the insertion. Adequate attachment of fibrous tissue to the pin head and the absence of any inflammation are important preconditions for the introduction of this new method of osteosynthesis into clinical practice. Further advantageous characteristics are easy intraoperative handling and a reduction in operating time, because cutting the thread is not required. There must be sufficient interlinkage of the polymer and the trabecular structures to ensure stability.

The impact of nucleolar organizer regions for the lymph node spread and prognosis of invasive ductal mammary carcinoma.

In primary tumours of 40 patients with invasive ductal carcinomas the significance of nucleolar organizer regions (NORs) for metastatic spread to the axillary lymph nodes and for the prognosis was assessed. Silver-stained tissue sections were investigated by means of semiautomated image analysis. The nucleolar organizer regions of 100 tumour cell nuclei per specimen were measured. The number as well as the area of the NORs were evaluated together with morphometrical and DNA features, histopathological and clinical data. By means of multivariate discriminant analysis, significant differences between tumours of 20 node-negative and 20 node-positive patients could be found. The mean number of NORs was significantly higher in patients with lymph node metastases (p = 0.0059), whereas the mean area was significantly lower in node-positive patients. By using the NOR number as the only parameter both groups were classified with an overall efficiency of 95%. There was also a significant difference between long-term and short-term survivors by considering the mean number of NORs, but the Auer-type, the 2 cDl value, and the DNA-grade of malignancy were of better predictive value. Within the group of node-negative patients the NOR number was most suitable for distinguishing between good and poor prognosis, whereas within the group of node-positive patients once more the DNA parameters played the most decisive role for predicting prognosis. With regard to the small number of patients the results have to be considered as preliminary. Further investigations in a more extensive population are necessary.

Histological grading of breast cancer. Interobserver, reproducibility and prognostic significance.

A study was conducted to assess the reproducibility and prognostic significance of the histopathological grading by using the criteria of Bloom and Richardson. 166 breast carcinomas of the invasive ductal type (NOS - not otherwise specified) according to the WHO criteria, selected from the biopsy material of the years 1980 to 1988 were investigated. 85 of the patients presented axillary lymph node metastases in the mastectomy specimens. A satisfactory correlation of histopathological grades assessed by three pathologists was found in 72.3% of all cases. Fifteen cases (9%) were over- and 31 cases (18.7%) were underestimated compared with an expert's grade. A disagreement of two grades occurred in one case only. In comparison of grade 1 and grade 3 tumours as well as of grade 2 and grade 3 tumours significant differences in the overall survival could be found. Irrespective of statistically significant differences between the three grades in actuarial survival, the histopathological grading is of rather low value for the prediction of prognosis of individual patients.

Grading and prognosis of invasive ductal mammary carcinoma by nuclear image analysis in tissue sections.

In primary tumours of 84 patients with invasive ductal carcinomas the prognostic significance of the nuclear image was assessed. Feulgen stained tissue sections were investigated by image cytometry. At least 150 tumour cell nuclei as well as 50 lymphocytes or trout erythrocytes for diploid reference were measured in each specimen. 35 morphological features, including those of the chromatin pattern, were derived from the digitized nuclear images. By means of multivariate discriminant analysis, significant differences could be found between tumours of 41 node-negative and 43 node-positive patients. The differences were sufficiently large to distinguish subgroups with low and high risk of lymph node involvement. Irrespective of lymph node status, 66 patients with an adequate 5 year follow-up were divided into two groups according to their survival time. The classification results revealed a clear relationship between characteristics of the nuclear image and prognosis. By image cytometry it is thus possible to separate both node-positive and node-negative patients into subgroups with increasing risk of recurrence. The results indicate that nuclear image analysis provides prognostic information in addition to established prognostic factors, such as histological grade and tumour stage.

Expression of p53 and bcl-2 in correlation to clinicopathological parameters, hormone receptor status and DNA ploidy in breast cancers.

The expression of p53 and bcl-2 was immunohistochemically investigated in 61 formalin-fixed, paraffin-embedded invasive breast carcinomas. The study was aimed to elucidate the relationship between both markers and the correlation of p53 and bcl-2, respectively, to clinicopathological variables, to hormone receptor status and to DNA-ploidy. Twenty tumors showed a positive reaction with the monoclonal antibody DO-1 against p53 protein. Its immunohistochemical demonstration was significantly correlated with a tumor size larger than 2 cm, a low estrogen receptor status and DNA-aneuploidy. Bcl-2 was demonstrated in 51 breast cancers. Bcl-2 was preferably seen in low grade and hormone receptor positive tumors. We found a negative correlation between the immunoreactive scores of p53 and bcl-2, but in 17 carcinomas a coexpression of both proteins was seen. Cases with this coexpression did not differ significantly from the other tumors in clinicopathological parameters. In eight of these cases more than 10% of the cells were found to be positive for both markers. In four cases we could show many cells to exhibit both markers as it was assessed by an immunofluorescence double labeling technique.

[Concordance of the Gleason score in prostate multibiopsy and definitive histology]. / Die Ubereinstimmung des Gleason-Scores in Prostatabiopsie und definitiver Histologie.

BACKGROUND: Due to an insufficient mean agreement between the Gleason score (GS) revealed from multibiopsy and definitive histology after radical prostatectomy (RP) of merely about 45 %, a modification of the GS including an elimination of GS 2-4 was -accomplished in 2005. The aim of the present study was to evaluate the concordance of GS and WHO grading in biopsy and definitive histology and to -determine parameters influencing the diagnostic accuracy of the biopsy and the prognosis. MATERIALS AND METHODS: Within a 10-year-period before modification of the GS, radical prostatectomy was performed in 856 patients (study group, SG; mean age 64.2 years). The grade of agreement between GS and WHO grading in biopsy and definitive histology was calculated by kappa statistics (kappa) (for the complete and single time -periods). Furthermore, we assessed the univariable and multivariable influence of different preoperatively available parameters on disease-free survival (DFS). The mean follow-up period was 39 months (range: 10-139 months). RESULTS: Undergrading of GS and WHO grading decreased continuously within the three time -periods in favour of a higher agreement regarding the histological results revealed from biopsy and definitive histology. However, we found only a poor to moderate agreement in the complete time period (kappa values of 0.354 for GS and 0.404 for WHO grading) that - with regard to both parameters - was improved by an increased number of biopsy cores taken. PSA value, clinical -tumour stage, number of positive cores (dichotomised at 34 %), annual RP case load (dichotomised at 75), and GS revealed an independent significant influence on DFS. Patients with GS 2-4 in the biopsy exhibited an upgrade to GS > or = 7 in only 5.7 %, and -showed, -independent of the definitive histology, a significantly better prognosis in comparison with patients presenting with a higher GS. CONCLUSIONS: The results of the present study again suggest the independent prognostic impact of the GS revealed from biopsy. However, the concordance with the GS in the definitive histology remains deficient and is improvable by taking a higher number of biopsy cores. Although the elimination of GS 2-4 might be comprehensible for the pathologist's purpose, it results in a considerable loss of pretherapeutic prognostic information.

[Syringocystadenoma papilliferum of the outer ear canal]. / Syringocystadenoma papilliferum des äusseren Gehörganges.

Ceruminomata are tumours spreading from the ceruminous glands of the external auditory canal. Since 1894 190 cases have been described, but nomenclature is still confusing to some extent. Syringocystadenoma papilliferum is a special subgroup. 189 cases are reported in the literature; 11 tumours have been observed in the auditory canal. A further case is reported in this paper.

[Adult multilocular cystic nephroma simulating a kidney carcinoma]. / Adultes multilokuläres zystisches Nephrom unter dem klinischen Bild eines Nierenkarzinoms.

The multilocular cystic nephroma is a rare benign renal tumour which has its origin in the metanephrogenic blastema. As to the frequency it occurred in adults and children approximately share and share alike. It is reported on a 54-year-old woman with a right-sided multilocular cystic nephroma, who was operated on under the clinical suspicion of a renal carcinoma.

Nucleolar organizer regions in carcinomas of the oropharynx and hypopharynx.

It is supposed that the nucleolar organizer regions (NORs), genes on which ribosomal RNA is coded, may contain information on the structure of the nucleolus and on nucleolar activity which permits discrimination between normal and neoplastic cells and their proliferation activity. In the present study, the histological sections of 144 patients with carcinomas of the oropharynx and hypopharynx were studied in a retrospective approach to determine the absolute NOR counts per 100 nuclei and investigate their influence on the prognosis and extent of lymphogenic formation of metastases. An absolute NOR count of 681 per 100 nuclei was found to give reliable discrimination between stage N0 or N1 carcinomas and stage N2 or N3 disease.

[Rare late metastasis of a successfully treated advanced ovarian cancer]. / Seltene Spätmetastasierung eines kurativ behandelten fortgeschrittenen Ovarialkarzinoms.

A case of a 64 year old woman is reported suffering from bilateral inoperable ovarian carcinoma. Seven years before death the carcinoma was histologically confirmed by an explorative laparotomy. At this time even a diffuse peritoneal carcinosis was found. The polychemotherapy yielded to a reduction of tumor mass. This allowed a surgical radical operation two years later. During continued chemotherapy the patient was clinically and cytologically free of tumor. The death was caused by diffuse late metastases in the brain.

[Allogenic half-joint transplantations]. / Allogene Halbgelenkstransplantationen.

Reported in this paper are twelve cases of allogenic transplantation of half-joints and quarter-joints, following removal of locally delimited tumours. Three transplants were incorporated with functionally satisfactory result to three patients over a period of seven years. Infections and recurrence of tumours were the most frequent causes of failure of transplantations. These results are discussed together with possibilities of future allogenic half-joint transplantations.

Prognostic significance of image cytometry DNA parameters in tissue sections from breast and gastric cancers.

The ploidy patterns determined for several groups of mammary and gastric carcinomas were subjected to a set of statistical analyses. The DNA distribution patterns were derived from image cytometry measurements of each of at least 150 Feulgen-stained tumour cell nuclei from tissue sections from 84 invasive ductal carcinomas of the breast and from 30 tubular adenocarcinomas of the stomach. Widely used DNA parameters (mean value, standard error of the mean, DNA-malignancy grade, 2c deviation index and the exceeding rate according to Böcking, DNA-histogram types according to Auer, DNA-index according to Atkin) were analysed by univariate and multivariate statistics. The DNA histograms were also analysed multiparametrically. The results showed different prognostic groups of the breast tumours to be distinguishable on single parameters with a reliability of up to 66%. None of these parameters permitted the discrimination of gastric carcinomas. Although the DNA-histogram-analysis increased accuracy by nearly 10%, compared with the classification accuracy of the best single parameters, it is still far from being applicable in clinical diagnostics. The use of further image cytometry parameters will be required for such applications.

[Retroperitoneal ganglioneuroma as a cause of obstructed labor]. / Retroperitoneales Ganglioneurom als Geburtshindernis.

The case of a primigravida is reported who was operated on for a retroperitoneal ganglioneuroma at the age of 12. At that time the tumor surgically could not be completely removed because of its size and anatomical location in relation to the backbone and the large blood vessels. A renewed tumour growth was observed in the course of the years. At the end of pregnancy the tumour proved to be an obstruction to the labour process.

High resolution image analysis of cell nuclei in tissue sections of primary and metastatic carcinomas.

The present study examines whether certain histological tumour types can be differentiated on account of their nuclear image with the aid of automated image analysis. For karyometric investigations three tumour types (adenocarcinomas, squamous cell carcinomas and mammary carcinomas) were chosen, which occur frequently as occult primary tumours. From each type ten primary tumours with their corresponding lymph node metastases were examined. 100 cell nuclei were measured from each case using 4 micron thick paraffin sections stained with gallocyanin-chromalum. For each cell nucleus 21 contour and texture features were determined. Through the application of linear classifiers 41 out of 52 cases (25 primary tumours, 27 metastases) of these three tumour types were correctly classified. Eight cases could not be classified with certainty and only three cases were wrongly classified. In addition, within the group of adenocarcinomas differences due to localisation were detected which allow us to draw conclusions on the seat of the primary tumour.

Increase of precision and accuracy of DNA cytometry by correcting diffraction and glare errors.

In recent TV-based image cytometers considerable disproportionalities exist between the IOD values of reference cells, as well as diploid, tetraploid, and octoploid analysis cells compared with their theoretical IOD ratios. An important source of these deviations is the limited spatial resolution of the microscopic objectives, based on the effects of diffraction. Compared to these influences the glare is less important. A correcting method is given for reducing both effects on the DNA measurements, which considers a narrow region along the nuclear contour to be optically disturbed. The correction of this mean optical density (MOD)- and size-dependent geometric resolution error is applicable to any cell type. The method was tested on 25 rat liver imprints and 29 fine needle aspirates from breast cancers. The resulting stemline ratios are close to the theoretical ones. A further improvement was then reached by a glare correction. The slide-by-slide variations of stemline ratios, remaining after the corrections, were considered in a test statistic for defining the aneuploidy of a given stemline. Statistically based clear-cut decision rules were obtained for DNA histogram interpretation.

[Wilms' tumor in adults after curative treatment of Hodgkin's disease]. / Wilms-Tumor beim Erwachsenen nach kurativ behandeltem Morbus Hodgkin.

A fist-size Wilms tumour was recorded from a patient, 29 years of age, seven years after therapeutic irradiation for histologically secured Hodgkin's disease (nodular sclerosis, stage II with involvement of cervical and mediastinal lymph nodes). Nephrectomy was performed on the patient who died of bronchopneumonia on the 30th postoperative day. Autopsy did not reveal any residues of the lymphogranulomatosis or metastases of the nephroblastoma.