[Case report of granulomatous necrotizing sialadenitis. Rarity of first manifestation in submandibular gland]. / Fallbericht einer granulomatös-nekrotisierenden Sialadenitis. Rarität einer Erstmanifestation in der Glandula submandibularis.

This article presents the case of a 43-year-old male patient with recurrent painful swelling of the right submandibular gland. Submandibulectomy was performed. Histological investigations showed an intense granulomatous inflammation with severe destruction of the parenchyma. The inflammatory infiltrate consisted of abscesses with neutrophilic and eosinophilic granulocytes and ill-defined granulomas with multinucleated giant cells. Some of the blood vessels showed evidence of vasculitis. After further clinical and serological investigations with highly elevated levels of cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA) and antiproteinase-3 antibodies, a rare limited disease of granulomatous polyangiitis (Wegener granulomatosis) was finally diagnosed. Such a manifestation of the disease is exceedingly rare; therefore, only single case reports have so far been described. The certain establishment of the diagnosis seems to be challenging because of the lack of involvement of the respiratory tract and the kidneys. In this case a histological assessment and clinical findings are mandatory for the correct diagnosis.

Clinical significance of lymph vessel density in T3 colorectal carcinoma.

PURPOSE: The purpose of the present study is to characterise the lymphatic vessel density (LVD) in the T3 colorectal carcinoma and to correlate it with N status, grading and presence of tumour budding. METHODS: A total of 56 cases of T3 colorectal carcinoma were retrieved from the pathology's archive of Klinikum Augsburg. All slides were stained immunohistochemically with D2-40 (lymphatic endothelium) and with pancytokeratin to assess the tumour budding. Tumour budding and lymph vessel density were investigated independently by BM and CC. The highest density of lymphatic vessels was counted both in tumour centre (ILVD) and at the periphery of the tumour (PLVD) within an area of 0.24 mm(2). RESULTS: Due to the strong intra-observer (BM and CC) difference in ILVD and PLVD, all cases were re-evaluated establishing a consensus that has been used for the further analyses. There was a significant difference between PLVD and ILVD (12 ± 4 versus 6 ± 3; P < 0.001). Moreover, we found a non-significant trend towards high PLVD in the cases with nodal metastasis versus the negative one, 13 ± 5/hpf versus 11 ± 4 (P = 0.072). There was no association between tumour budding and ILVD and PLVD (P = 0.249 and 0.38). CONCLUSION: Colorectal carcinoma induces lymphangiogenesis. A higher PLVD could increase the capability of cancer cell to invade the lymphatic system. However, the obvious difficulties in immunohistochemical evaluation and the rather small differences between nodal positive and negative cases in T3 colorectal cancer seem to limit the clinical value of LVD evaluation.

[Lymph node staging in gastrointestinal cancer. Combination of methylene blue-assisted lymph node dissection and ex vivo sentinel lymph node mapping]. / Lymphknotenstaging bei gastrointestinalen Karzinomen. Methylenblauassistierte Lymphknotenpräparation in Kombination mit Ex-vivo-Sentinellymphknotenmarkierung.

The histopathological lymph node staging is of crucial importance for the prognosis estimation and therapy stratification in gastrointestinal cancer. However, the recommended numbers of lymph nodes that should be evaluated are often not reached in routine practice. Methylene blue assisted lymph node dissection was introduced as a new, simple and efficient technique to improve lymph node harvest in gastrointestinal cancer. This method is inexpensive, causes no delay and needs no toxic substances. All studies performed revealed a highly significantly improved lymph node harvest in comparison to the conventional technique. Moreover, this technique can be combined with a new ex vivo sentinel lymph node mapping that for the first time is based on histological sentinel lymph node detection. The success rate of this method is similar to conventional techniques and it enables an efficient application of extended investigation methods, such as immunohistochemistry or the polymerase chain reaction.

Neoadjuvant chemotherapy affects staging of colorectal liver metastasis--a comparison of PET, CT and intraoperative ultrasound.

PURPOSE: Surgery for colorectal liver metastasis facilitates long-term survival, and neoadjuvant chemotherapy improves resectability but may also alter staging accuracy. The aim of this study was to evaluate the effects of neoadjuvant chemotherapy on the efficacy of positron emission tomography (PET), PET-computed tomography (CT), CT and intraoperative ultrasound (IUS) in the detection of liver metastasis. METHODS: Between January 2007 and January 2010, 34 patients with resectable colorectal liver metastasis were included in this retrospective analysis. Seventeen patients had received neoadjuvant chemotherapy. PET or PET-CT, CT or magnetic resonance imaging (MRI) and IUS were performed in all patients. Sensitivity, specificity, positive predictive value and negative predictive value were analysed. Histopathological examination of the resected specimens served as standard reference. RESULTS: A total of 109 liver segments were resected, of which 50 showed no metastatic involvement (45.9%). For patients without systemic chemotherapy, sensitivities for PET, CT/MRI and IUS were 92%, 64% and 100% respectively as compared with 63%, 65% and 94% for patients after neoadjuvant chemotherapy in a segment-based analysis. For PET, standardised uptake values were decreased by 3.9 in 10 patients after chemotherapy whereas lesion diameters were similar (3.0 vs. 3.2 cm). Additional metastases were detected by IUS in seven patients resulting in a change of operative procedure in 20.6%. CONCLUSION: Staging accuracy of colorectal liver metastasis is influenced by neoadjuvant chemotherapy. For PET, decreased tumour metabolism rather than downsizing may account for a drop in sensitivity after neoadjuvant chemotherapy. IUS is critical to avoid incomplete resections.

Endoscopic submucosal dissection in gastric neoplasia - experience from a European center.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is a promising technique for the resection of early gastric neoplasia. There are only a few data from the Western world to date. METHODS: Over a 7-year-period, 104 gastric lesions were treated with ESD in a European referral center, of which 91 were included in this study. A total of 66 lesions were early gastric cancer (EGC) and 25 were adenomas. Of the EGCs, 11 lesions (16.7 %) fulfilled the guideline criteria (EGC-GC) and 55 lesions (83.3 %) fulfilled the expanded resection criteria (EGC-EC) of the Japanese guidelines for the treatment of gastric cancer. RESULTS: ESD was technically possible in 85 lesions (93.4 %). In six lesions ESD was not possible due to non-lifting. En bloc resection rates for all lesions, ECGs-GC, ECGs-EC, and adenomas were 87.1 %, 100 %, 88.2 %, and 79.2 %, respectively. R0 en bloc resection rates were 74.1 %, 90 %, 68.6 %, and 79.2 %, respectively. Complications were: one perforation during piecemeal endoscopic mucosal resection of a lesion in which ESD was judged to be impossible (1.2 %); three clinically relevant bleedings (3.5 %); one gastric ischemia (1.2 %); and four strictures (4.7 %). No mortality was observed. There were five recurrences after piecemeal resection (50 %) compared with only one after en bloc resection (1.5 %; P < 0.05). The rate of recurrence for EGCs was 5.6 %, and this were seen exclusively after piecemeal resection. CONCLUSIONS: Our data show that ESD is a feasible technique in Europe even in patients with EGC according to the extended criteria. Resection rates are promising and complication rates are acceptable. Results are worse compared with large studies from Japan but still excellent regarding the learning curve of the method. ESD should be offered as the treatment of choice for early gastric neoplasia especially when en bloc resection cannot be performed with other resection techniques.

Tumour budding, uPA and PAI-1 are associated with aggressive behaviour in colon cancer.

AIMS: The proteases PAI-1 and uPA play a major role in extracellular matrix degradation, which facilitates tumour progression. Tumour budding is a histomorphological expression of enhanced tumour cell migration. MATERIALS AND METHODS: To investigate their prognostic value for and correlation with colon cancer, a prospective study was performed. We analysed tissue levels of uPA and PAI-1 of 55 colon cancer tumours employing a commercially available enzyme-linked immunosorbent assay (ELISA). Tumour budding was analysed on cytokeratin-stained slides. RESULTS: There was a strong correlation between uPA and tumour budding (R = 0.440; P < 0.001). uPA levels were increased in high grade tumours, whereas PAI-1 was elevated in cases with venous invasion (P = 0.004 and P = 0.028). PAI-1 values and tumour budding are associated significantly with the occurrence of distant metastases (P < 0.001 and P = 0.034, respectively). Tumour budding was significantly associated with lymph node metastases (P = 0.034). Multivariate analysis revealed PAI-1 and lymph node metastases to be independently predictive of distant metastases (P = 0.007 and P = 0.004, respectively). CONCLUSIONS: The results of our study show that tumour budding and the plasmin/plasminogen system are related. PAI-1 was independently predictive for the occurrence of distant metastasis.

[Lymph node preparation in colorectal cancer. Ex vivo methylene blue injection as a novel technique to improve lymph node visualization]. / Lymphknotenpräparation bei kolorektalen Karzinomen. Ex-vivo-Methylenblau-Injektion als neue Technik zur Lymphknotendarstellung.

The UICC requires investigation of a minimum of 12 lymph nodes for adequate lymph node staging in colorectal cancer. Despite that, many authors recommend investigation of a larger number, and different techniques, such as fat clearance, have therefore been developed. In this study we introduce a novel technique involving ex vivo lymph node staining with intraarterial methylene blue injection in colon cancer. We compared 14 cases in which methylene injection was used with 14 cases from our records in which conventional investigation techniques were applied. The lymph node harvest differed highly significantly (p<0.001) between the two groups, with average numbers of 28+/-7 and 14+/-3 in the methylene blue group and the unstained group, respectively. The largest difference occurred in the size group 2-4 mm (191 vs 70 lymph nodes). In 6 cases in the unstained group additional embedding of fatty tissue was necessary to reach an adequate number of investigated lymph nodes. Methylene blue injection is a novel and highly effective method that will improve lymph node preparation in colorectal cancer.

Can an endocytoscope system (ECS) predict histology in neoplastic lesions?

BACKGROUND AND STUDY AIMS: An endocytoscope system (ECS) has recently been developed with the possibility of super-high magnification of gastrointestinal mucosa, thus allowing in vivo imaging of living cells. The aim of the present study was to assess the potential of ECS in the prediction of histology in both normal gastrointestinal mucosa and neoplastic lesions. PATIENTS AND METHODS: In total, 76 patients (57 men, 19 women; age range 37-86 years) with neoplastic lesions in the esophagus, stomach, or colon were enrolled into the study and underwent esophagogastroduodenoscopy or colonoscopy. After staining with 1% methylene blue, the mucosa was examined with the ECS probe (x 450 and x 1100 magnification), and video sequences were recorded on video disk. Biopsies from the examined areas were taken for histology and served as the gold standard. The endocytoscope video sequences were evaluated by two blinded pathologists. Finally the results were compared with those resulting from the evaluation of an experienced endoscopist who was aware of the macroscopic endoscopic pictures and the endocytoscope image results. RESULTS: A total of 25 patients with esophageal lesions, 28 patients with colonic lesions, and 23 patients with gastric lesions were examined. The sensitivity and specificity for the evaluation of the blinded pathologists was 81% and 100%, respectively, in the esophagus, 56% and 89% in the stomach, and 79% and 90% in the colon. If an endoscopist evaluated the endocytoscopic pictures in combination with the macroscopic endoscopic images sensitivity and specificity increased significantly. CONCLUSIONS: First experiences with ECS show good sensitivity rates even by blinded assessment for esophageal and colonic lesions. Sensitivity for neoplastic lesions in the stomach is lower because of gastric mucous secretion. Combining the endoscopic and cytoscopic appearance of the lesion may further enhance the diagnostic value of the method.

[Renal neurilemoma--a rare differential diagnosis of renal tumors]. / Das Schwannom der Niere - Eine seltene Differenzialdiagnose renaler Raumforderungen.

Neurilemomas originate from the Schwann cells of nerve sheaths. They can occur ubiquitously as benign or malign variants. Renal neurilemomas are extremely rare. Imaging does not allow a certain diagnosis. Complete tumor resectioning is the only curative therapy. Effective conservative treatment is not known. Histological criteria of renal neurilemoma are: mesenchymal, spindle cell, capsulated tumor intensely positive to S-100 antiserum. Epithelial markers do not react.

Galectin-3 and Cyclin D3 Immunohistochemistry and Tumor Dimensions Are Useful in Distinguishing Follicular Oncocytic Carcinomas from Oncocytic Adenomas of the Thyroid.

Aims. Oncocytic (Hurthle) follicular cell tumors (OTs) of the thyroid are both adenomas (OAs) and follicular carcinomas (OCs). The routine diagnosis of these tumors can be problematic even after an accurate sampling and histological examination. Beside preoperative evaluation due to the tumor's dimension several studies have been performed to find markers able to distinguish malignant from benign follicular tumors in the thyroid, with Galectin-3 being one of the most effective. Recently, some authors suggested cyclin D3 as adjunct to the diagnosis of the oncocytic lesions of the thyroid. Methods and Results. In this paper we assess the role of Galectin-3 and cyclin D3 in a well-selected group of follicular oncocytic tumors (14 OCs and 26 OAs). The diameter of each lesion was also evaluated. The combination of Galectin-3 and cyclin D3 has a good specificity (81%) and sensitivity (100%). Moreover, the maximum diameter (in cm) of OCs is greater than OAs (4.1 versus 2.3). Conclusions. We believe that the use of Galectin-3 and cyclin D3 in OTs of the thyroid can be a helpful panel in daily practice when histology is doubtful.

In situ hybridization of the mRNA for interferon-gamma, interferon-alpha E, interferon-beta, interleukin-1 beta and interleukin-6 and characterization of infiltrating cells in thyroid tissues.

Cytokine mRNA production in the thyroid tissues of patients with various thyroid diseases was analysed by in situ hybridization. In addition, infiltrating leukocytes were characterized by immunohistologic studies using the alkaline phosphatase anti-alkaline phosphatase (APAAP) staining technique. The following clinical material was investigated: two cases of Graves' disease, one with high and the other with a low amount of infiltrating leukocytes as well as two cases of non-toxic goitre also showing considerable quantities of infiltrating cells. The hybridization was performed on tissue sections with antisense probes for interferon-gamma (IFN-gamma), IFN-alpha E, IFN-beta, interleukin-6 (IL-6) and IL-1 beta. A small number of individual cells were found to express high levels of mRNA for IFN-gamma, IL-1 beta and measurable amounts of IL-6 throughout the tissue sections. However, IFN-alpha E or IFN-beta were not detected. Cytokine expressing cells were noted in the tissue of one patient with Graves' disease and in two cases with non-toxic goitre. In these samples a high amount of infiltrating leukocytes (CD45+) was detected, especially CD3+, CD8+, CD4+ and CD45RA+ T cells, in addition to B cells and macrophages. In one case an unusually large amount of T cell receptor gamma/delta+ (TcR gamma/delta+) cells was found. However, one sample of thyroid tissue derived from a patient with Graves' disease was poorly infiltrated and showed few cells expressing cytokines. In conclusion, using thyroid tissue as an example, our data suggest that the application of in situ hybridization with antisense RNA permits the study of cytokine production in tissues of both autoimmune and non-autoimmune origin.

Widespread aluminium deposition in extracerebral organ systems of patients with dialysis-associated encephalopathy.

We have described new silver-staining methods for the demonstration of lesions in senile dementia of the Alzheimer type. The same procedure was used to visualize characteristic aluminium (Al)-containing inclusions in choroid epithelium, glia and neurons of the central nervous system in dialysis-associated encephalopathy (DAE). Here we describe the patterns and degree of Al deposition in extracerebral tissues of 12 DAE autopsy cases. Light microscopy of silver-stained paraffin sections demonstrated autonomic ganglion cells filled with numerous intracytoplasmic black-stained fine granular inclusions, which were also seen in endocrine tissues (pituitary, parathyroid and adrenal) and in Leydig cells. Heart, liver cells and the testicular tubules were involved, but decalcified bones, haematopoetic elements, hyperplastic epithelium and one case of malignant epithelium lacked inclusions. Laser microprobe mass analysis revealed prominent Al-related mass signals within the en-bloc silver-stained inclusions which were seen at low intensity in adjacent non-stained structures. Electron microscopy demonstrated accumulations of small electron-dense granules intermingling with lipopigments.

Keratin, luminal epithelial antigen and carcinoembryonic antigen in human urinary bladder carcinomas. An immunohistochemical study.

14 urinary bladder carcinomas of all main types were investigated with antisera to "broad spectrum keratin" (aK), "luminal epithelial antigen" (aLEA) and carcinoembryonic antigen (aCEA), using an indirect immunoperoxidase method on formalin fixed paraffin embedded sections. Keratin and LEA were both present in normal transitional epithelium, papilloma and carcinoma in situ whereas CEA was absent. Transitional cell carcinomas reacted with both aK and aLEA whereas CEA was seen only in a few foci. In squamous metaplasia and squamous carcinoma reaction with aK was particularly strong, while LEA was almost lacking and CEA was present in necrotic centres. In adenocarcinomas aK and aLEA reacted equally while aCEA reacted only on the surface.

Improvement of nonradioactive DNA in situ hybridization.

With the introduction of microwave pretreatment, the quality of nonradioactive in situ hybridization (NISH) using DNA probes on formalin fixed tissue has significantly improved. Even after microwave treatment, however, there are cases where NISH results remain unsatisfactory. Therefore, we tried to improve NISH by testing other buffer systems as alternatives to the citrate buffer that is routinely applied during microwave pretreatment. By using buffer systems originally designed for immunohistochemistry, we significantly improved our NISH results. Difficult tissue samples were more accessible to NISH using these alternative buffer systems and made the quantitative evaluation easier. These results may also be of interest for combined applications of NISH and immunohistochemistry.

[Treatment of distal urethral cancer by laser coagulation]. / Behandlung des distalen Urethrakarzinoms durch Laserkoagulation.

Primary carcinoma of the urethra is a rare lesion, and there are no standard therapeutical modalities suggested in the literature. We report the case of a 65-year-old woman with transitional cell carcinoma of the distal urethra and metastasis to the inguinal lymph nodes (T2 N1 MO G2). Locally, the lesion was treated by Nd:YAG laser coagulation in four sessions. Ileoinguinal and pelvic lymph-node dissection was performed as a diagnostic and therapeutic procedure. Twenty-eight months after the initial treatment, no evidence of tumor recurrence has been found, although extensive biopsy specimens have been taken. Clinical staging showed no evidence of metastases.