[Multiple bilateral pulmonary nodes following breast cancer]. / Multiple bilaterale Lungenrundherde nach Mammakarzinom.

HISTORY AND ADMISSION FINDINGS: Multiple new pulmonary nodules were demonstrated at chest radiography in a 69-year-old woman who had been treated for breast cancer ten years previously. INVESTIGATIONS: Laboratory tests suggested mild inflammation. Pulmonary function tests demonstrated small airways disease. But because of an atypical morphology at computed tomography (CT), metastases were considered unlikely. CT-guided percutaneous biopsy revealed cryptogenic organizing pneumonia (COP). TREATMENT AND COURSE: Oral medication with decreasing doses of steroids resulted in clinical and radiological improvement. CONCLUSIONS: Even in a patient with known malignancy the differential diagnosis of multiple bilateral pulmonary nodules includes a variety of conditions and is meticulous, if necessary invasive diagnostic procedures are required.

Whole-specimen histopathology: a method to produce whole-mount breast serial sections for 3-D digital histopathology imaging.

AIMS: To develop a method for preparing diagnostic-quality, whole-mount serial sections of breast specimens while preserving 3-D conformation. This required supporting the fresh specimen prior to breadloafing and refining the conventional tissue processing method. The overall goal is to use digital images of whole-specimen histopathology to improve the estimation of extent of disease. METHODS AND RESULTS: To maintain a 3-D conformation, the specimen is suspended in 3.5% agar at 55 degrees C. The block is sliced at 5-mm intervals. Sectioning is performed after extended fixation in 4% formaldehyde from paraformaldehyde in 0.1 m Millonig's buffer, followed by paraffin processing using a non-routine schedule and extended paraffin infiltration. Whole-mount serial breast sections are produced with features of equal or superior quality to that which can be achieved using conventional methods. The method is compatible with some immunohistochemical stains but requires further optimization for others. CONCLUSIONS: The technique is currently suitable for research applications. With the reduction in processing time achievable with microwave-assisted processing, there is the potential for its use as a routine clinical method. This tool may improve the accuracy of margin estimates and identification of multifocality in breast cancer; further evaluation is necessary.

Metastasis to the pancreas--an indication for pancreatic resection?

BACKGROUND AND AIMS: Isolated metastatic involvement of the pancreas is very rare. To evaluate the possible benefit of surgery, we retrospectively analyzed patients that underwent pancreatic resection for metastases into the pancreas. PATIENTS/METHODS: In 12 patients (8 men and 4 women), metastatic disease was treated by pancreatic resection (two total pancreatectomies, nine pylorus-sparing duodenopancreatectomies, and one left-side pancreatic resection) between 1993 and 2005 at our institution. Primary malignomas were renal cell carcinoma (RCC; n = 7), malignant melanoma (n = 4), and colon cancer (n = 1). All patients were followed-up until November 2006 or until death. RESULTS: Complications requiring relaparotomy were found in two patients (retroperitoneal abscess and bile fistula), whereas one patient with pancreatic fistula could be treated by conservative measures. There was no perioperative mortality. Median survival time was 51 months (5-105 months). At the end of follow-up, seven patients were alive at 12 to 86 months, whereas five died between 5 and 105 months: four died of the disease, and one patient died of cardiac failure without evidence of recurrent cancer. CONCLUSION: Patients with isolated pancreatic metastasis particularly of RCC benefit from surgery. Pancreatic resection may achieve long-term survival or good palliation in selected cases of other primaries as well.

Application of a single needle type for all image-guided biopsies: results of 100 consecutive core biopsies in various organs using a novel tri-axial, end-cut needle.

PURPOSE: To assess feasibility, results and complications in image-guided biopsies using a single needle design in various organs. MATERIALS AND METHODS: 100 consecutive percutaneous biopsies were performed in 54 females and 46 males aged 24-87 years (mean age/standard deviation: 64.5 +/- 12 years) using a full-core end-cut tri-axial full-automatic biopsy needle (18 gauge BioPince, InterV-MDTech, Gainesville, Florida) under CT (n = 45) or ultrasound (n = 55) guidance. In 63 biopsies a coaxial technique was used. RESULTS: Biopsies were obtained of liver (n = 32), lymph nodes (n = 17), thyroid (n = 11), lung (n = 9), adrenal (n = 9), pelvis (n = 6), chest wall/pleura (n = 6), mediastinum (n = 4), lytic bone lesions (n = 2), retroperitoneum (n = 1), muscle (n = 1), pancreas (n = 1), peritoneum (n = 1). Between 1 and 6 (mean/SD 2.83 +/- 0.92) needle passes were performed. In 77 cases a malignant (40 metastases, 37 primary tumours) and in 23 a benign lesion was diagnosed. Of the 23 benign lesions a specific diagnosis was possible in 22. In one case necrosis and haemorrhage was diagnosed. In this patient surgery and autopsy both revealed a mediastinal haematoma of unknown origin. Eight minor complications (mild pain/local haematoma requiring no therapy) and three major complications (three pneumothoraces in nine lung biopsies requiring two aspirations and one drainage) were observed. There was no mortality. CONCLUSION: Percutaneous image-guided biopsy using the described full-core end-cut needle resulted in a specific diagnosis in 99/100 consecutive biopsies in various organs with a low complication rate. We use this needle type for all CT- or US-guided biopsies in all organs except for solid bone.

Duodenal somatostatinoma: clinical and immunohistochemical patterns--difficult differential diagnosis in regard to gangliocytic paraganglioma: report of a case.

The authors report a large duodenal somatostatinoma, a very rare tumor entity. A 8.5 cm globular mass in the area of the unicate process of the pancreas was detected in a 45 year old caucasian female by computerized tomography. The patient had only mild complaints. Initial treatment consisted of right pancreatectomy with preservation of the pylorus. Histological evaluation rendered a diagnosis of low-grade malignant neuroendocrine carcinoma with expression of somatostatin, respectively of somatostatinoma arising in the duodenum and infiltrating into the pancreas. 26 months after the initial surgery liver and lymph node metastases were detected and surgically removed. This case confirms that duodenal somatostatinomas are very difficult to diagnose preoperatively because of unspecific symptoms. Most duodenal somatostatinomas are found incidentally. Treatment of choice is radical surgical resection with a possible cure in early stages of the disease. Even a large tumor as ours is resectable with negative surgical margins. Management of recurrent or metastatic disease is also surgical. Additional chemotherapy and supportive care may be beneficial for the patient.

Cyclin-dependent kinase-inhibitor 1 (CDKN1A) in the squamous epithelium of the oropharynx: possible implications of molecular biology and compartmentation.

The cdknlA gene encodes CDKN1A, a protein that regulates cell cycle progression, terminal differentiation, and apoptosis. Polymorphisms or loss of heterozygosity of this usually biallelically expressed gene have no major impact on carcinogenesis. The prevalence of somatic mutations in malignancies is low. Gene rearrangements involving cdknlA are scarce. CDKN1A is expressed in both premalignant and malignant lesions. While the prognostic value of nuclear CDKN1A expression is controversial, the prognostic value of its recently discovered cytoplasmic accumulation is simply unknown. CDKN1A translocates from the nucleus to the cytoplasm when cleaved by caspase-like activities during early apoptosis. The presence of cytoplasmic catabolites (e.g.: p14) might therefore indicate apoptosis. We found no correlation between nuclear and cytoplasmic anti-CDKN1A immunoreactivity in our samples of oropharyngeal squamous cell carcinoma. CDKN1A Cap20, CDKN1, CDKN1A, CDKNA1, Cip-1, Mda-6, P21, Pic1, Sdi-1, Waf-1.

[Extramedullary plasmocytoma of the bronchial system]. / Das extramedulläre Plasmocytom des Bronchialsystems.

We present a case of primary plasmocytoma of the left upper bronchus. Occlusion led to atelectasis of the left upper lobe and subsequent poststenotic pneumonia. Therapy consisted of local excision of the bronchus and postoperative radio-therapy. This type of lung-conserving therapy in a case of primary plasmocytoma has not been described before.

Molecular biology in diagnosis and epidemiology of Helicobacter pylori: PCR for the detection and AP-PCR for characterization of patient isolates.

Infection with Helicobacter pylori causes chronic active gastritis and has been associated with gastric and duodenal ulcer disease. In biopsy samples of 110 patients with clinical symptoms of active gastritis, H. pylori was detected by means of the polymerase chain reaction (PCR), using species-specific primers defining a 858 bp DNA fragment of H. pylori urease beta-subunit. Sensitivity and specificity of the PCR was compared with culture, histology and Warthin-Starry stain (WSs), detection of H. pylori urease antibodies in serum and urease testing with the Campylobacter-like organism (CLO) test. PCR yielded specific amplification products in 53 cases, whereas culture of the organisms was positive in a subset of 50 cases. Only direct detection in histological sections of biopsy specimens had a higher sensitivity, with 65 positive samples. In contrast, the CLO test was negative in eleven culture-positive and PCR-positive cases. Significant urease antibody titres were found in 39 patients with histologically confirmed diagnosis. These results placed the sensitivity of PCR between tat of the Warthin-Starry stain (WSs) and that of culture. Therefore, PCR can be proposed as a useful rapid and time-saving technique for the detection of H.pylori in gastritis. For epidemiological purposes, fingerprinting with arbitrarily chosen primers by AP-PCR was evaluated. Strain-specific patterns with up to 13 fragments were achieved with 10-nucleotide or longer primers (21-nt) with a G + C content > or = 55%. Thirty-five of 40 strains investigated by this method were distinguishable with a single primer. These results suggest a high level of DNA sequence diversity within this species with the possibility of confirming the clonality in consecutive isolates from a single individual. Alternatively, an increased in-vivo mutation rate could be responsible for DNA divergence, resulting in specific strains for each individual patient.

p53 expression in gastric cancer: clinicopathological correlation and prognostic significance.

For evaluation of the prognostic relevance of p53 expression in gastric cancer, the immunohistochemical tissue status of 133 primary gastric cancer patients was investigated for p53 expression and the association between p53 tissue status and clinicopathological parameters was analyzed. P53 immunoreactivity was detected in the nuclei of cancer cells in 35 cases (26.3%). The nuclear p53 immunoreaction was closely associated with tumor location, lymph node metastasis, and curability. Tumors with positive p53 stain reactions frequently metastasized to lymph nodes (metastatic rate: 91.4%) in contrast to tumors with negative p53 stain reactivity (71.4%, P = 0.021). Immunohistochemical analysis of primary gastric cancer appears to be an accurate and simple method of screening for p53 expression. In combination with common prognostic parameters, determination of p53 tissue status might help to detect prognostically unfavorable subgroups of gastric cancer patients.

Depth of infiltration of primary gastric B-cell lymphomas--correlations with proliferation, apoptosis and expression of p53 and bcl-2.

Local extension has been shown to be a major prognostic factor in primary gastric B-cell lymphoma. In order to evaluate whether this parameter might be correlated with cell proliferation or its regulation, a retrospective study was performed. Fifty-three surgical specimens with primary gastric B-cell lymphomas were analysed concerning histological grading, depth of infiltration and Ann-Arbor stage. In addition, immunohistochemistry (p53[Do7], bcl-2[bcl-2-124], Ki-67 [MiB1]) and in situ end-labeling (apoptotic bodies) were applied. The depth of infiltration was significantly correlated with Ann-Arbor stage (p < 0.001) and histological grading (p < 0.002). Furthermore, the semiquantitatively evaluated expressions of Ki-67, apoptotic bodies and p53 revealed that tumours limited to the mucosa and submucosa had lower numbers of stained cells than lymphomas infiltrating the muscularis propria or beyond (p < 0.001 in all cases). Analysis of bcl-2 expression showed an inverse picture (p < 0.05). The importance of local spread of gastric lymphomas is underscored by our findings: in gastric lymphomas infiltrating the muscularis propria or beyond, powerful proliferative stimuli have been acquired, e.g. associated with p53 mutations, that are independent of the known mucosa-associated stimuli, Helicobacter pylori and auto-immunity.

Atypical lymphoid infiltrations of the gastric mucosa--their interpretation and management by eradication of Helicobacter pylori.

Low-grade gastric lymphomas of mucosa-associated lymphoid tissue (MALT) may be extremely difficult to differentiate from atypical lymphoid infiltrations of the gastric mucosa caused by Helicobacter pylori (H. pylori) infection, especially if lympho-epithelial destructions are not detected. In order to clarify this diagnostic problem and to evaluate the potential benefit of clearing H. pylori-induced lymphoid infiltration a prospective study was performed. Our study included biopsy specimens from 61 patients, that showed excessive lymphoid infiltrations. Using histology and immunohistochemistry no definite diagnosis could be delivered. In 46 (76.4%) cases histological regression occurred 4 weeks after the end of therapy suggesting a reactive infiltrate. In 7 patients (11.5%) the histological picture remained unchanged, and in 8 (13.1%) the follow-up biopsies revealed lympho-epithelial destructions allowing the diagnosis of low-grade MALT lymphoma. On the basis of our data we conclude that eradication of H. pylori could provide an additional tool in the differential diagnosis between atypical lymphoid infiltrations of the gastric mucosa caused by H. pylori and an early primary gastric MALT lymphoma.

Heterotopic pancreas. A difficult diagnosis.

Heterotopic pancreas is seen in one of every 500 laparotomies or 0.55-13% of autopsies. Despite modern diagnostic procedures (endoscopy, endoscopic ultrasound) it is difficult to diagnose preoperatively. A 51-year-old patient with a 30-year history of recurrent gastric ulcers was diagnosed with a gastric wall tumor. Endoscopic biopsy sample showed normal gastric mucosa. Endoscopic ultrasound and contrast radiography were not able to specify the gastric wall tumor. The local excision and histologic preparation of the tumor showed heterotopic pancreatic tissue within the gastric submucosa without any signs of malignancy. Three years postoperatively the patient is without any complaints. There have been no further signs of gastric ulcers.

The histopathological spectrum of type A gastritis.

It has been recently shown that type A gastritis can be histologically diagnosed in the preatrophic stage. In order to evaluate whether parietal cell atrophy in AG might correlate with other histopathological findings in the antral and body mucosa, we retrospectively investigated 171 consecutive cases of histologically diagnosed preatrophic (active) or atrophic type A gastritis (H&E, Warthin-Starry). The prevalences of intestinal metaplasia (75% vs 44.4%) and micronodular hyperplasia (86.1% vs 52.4%) of endocrine cells in the oxyntic mucosa were significantly higher of parietal cell atrophy was present (p < 0.001 and p < 0.0001, respectively), whereas the prevalence of nodular lymphoid aggregates (77.8% vs 48.1%) and of Helicobacter pylori (14.3% vs 1.9%) in the oxyntic mucosa was significantly higher if parietal cell atrophy could not be detected (p < 0.001 and p < 0.01, respectively). In the antral mucosa, altered patterns of the inflammatory reaction could be demonstrated independent of the parietal cell mass possibly caused by impaired gastric acid production. Our data support the notion that the development of parietal cell atrophy in type A gastritis represents a stepwise process including initial pseudohypertrophy of these cells.

Helicobacter pylori and the evolution of gastritis.

Following the isolation of Helicobacter pylori from the stomachs of patients with peptic ulcer in 1982, intensive research has examined the relationship between this organism and gastritis. H. pylori affects the grade and activity of gastritis, the quality of surface epithelial cells, and the nature of mucus production. Gastritis results from a direct action, involving bacterial cytotoxins and enzymes, and also in an indirect way through the effect of monocyte and granulocyte infiltration. Eradication of H. pylori leads to the long-term healing of gastritis. H. pylori is also associated with intestinal metaplasia and the development of mucosa-associated lymphoid tissue (MALT). Regression of MALT lymphomas has been reported after H. pylori eradication treatment.

[Autoimmune gastritis in its various stages]. / Die Autoimmungastritis in ihren verschiedenen Stadien.

Based on 196 consecutively diagnosed cases of autoimmune gastritis the histological spectrum of this disease was examined with special regard to the so called active autoimmune gastritis. The analysis revealed statistically significant differences. The chronic atrophic type showed more often microglandular hyperplasia of endocrine cells (p < 0.005) and revealed less often colonisation of the body mucosa by Helicobacter pylori (p < 0.001) than the active form. The inflammatory reaction of the antral mucosa, however, showed no differences. In addition immunohistochemical stainings were performed in 25 patients in whom parietal cell antibodies had been detected. In cases with active autoimmune gastritis T cells were found not only in the lamina propria but as well within the oxyntic glands as contrasted with the atrophic form. Only in the former group of patients furthermore B cells could be identified in the lamina propria. We conclude that especially with respect to the active form further knowledge of the progression of the autoimmune process might be gained.

Tissue diagnosis of intestinal microsporidiosis using a fluorescent stain with Uvitex 2B.

AIMS: To detect intestinal microsporidiosis in paraffin wax embedded biopsy specimens using a fluorescence technique incorporating optical brighteners. METHODS: Eight HIV infected patients with confirmed intestinal microsporidiosis (six with Enterocytozoon bieneusi, one with Encephalitozoon intestinalis and one with Encephalitozoon cuniculi infection) and 10 without infection were studied. Tissue sections of paraffin wax embedded duodenal biopsy specimens were stained with 1% Uvitex 2B, coded and analysed independently by two investigators. RESULTS: In all eight cases with confirmed intestinal microsporidian infection, spores could be detected easily in tissue sections using the fluorescence technique. Spores or other elements consistent with microsporidiosis were not found in the 10 patients without infection. CONCLUSION: Staining of tissue sections from paraffin wax embedded intestinal biopsy specimens with stains incorporating Uvitex 2B is a rapid and easy technique for the diagnosis of intestinal microsporidiosis.

Analysis of antral biopsy specimens for evidence of acquired mucosa-associated lymphoid tissue in HIV1-seropositive and HIV1-negative patients.

BACKGROUND: There is conflicting evidence concerning the prevalence of Helicobacter pylori gastritis in HIV1-infected patients. Furthermore, a possible influence of immunodeficiency on the acquisition of mucosa-associated lymphoid tissue (MALT) in the antral mucosa remains to be elucidated. METHODS: Seventy-seven consecutive HIV1-infected patients (mean age, 40.2 years) were compared in a prospective study with 77 HIV1-negative age-matched patients, using immunohistochemical stainings. RESULTS: In HIV1-infected patients the prevalence of H. pylori gastritis was lower and the inflammatory reaction less pronounced than in controls. Lymphoid follicles and intraepithelial B cells were significantly more often detected in HIV1-negative patients. CONCLUSIONS: Evidence of acquired MALT is only rarely found in HIV1-infected patients. These findings might contribute to the explanation of why low-grade gastric MALT lymphomas have not been reported in HIV1-infected patients so far.